C

CABG lean body tissue replaced by fat mass with little or no resulting weight loss. Cachexia occurs in ▶ Coronary Artery Bypass Graft (CABG) patients with chronic illnesses such as cancer, HIV/AIDS, chronic kidney disease, chronic heart failure, and chronic obstructive pulmonary disease.

Cachectin Description ▶ Tumor Necrosis Factor-Alpha (TNF-Alpha) Etiology The etiology of cachexia is multifactorial. Increased inflammatory processes in the form Cachexia (Wasting Syndrome) of cytokine production lead to metabolic dysregulation, such as increased resting energy Travis Lovejoy expenditure, and may contribute to heightened Mental Health & Clinical Neurosciences protein degradation accompanied by decreased Division, Portland Veterans Affairs Medical protein synthesis. Many patients with cachexia Center, Portland, OR, USA will also experience anorexia (i.e., a loss of appe- tite) and decreased nutrient absorption in the gastrointestinal tract, which accounts for con- Synonyms comitant weight loss. However, the overall loss of lean body tissue observed in patients with AIDS wasting; Cancer cachexia; Cardiac cachexia occurs independent of nutrient uptake. cachexia; HIV wasting; Slim disease Diagnosis The multifactorial etiology and absence of Definition a consensus definition for cachexia presents challenges to diagnostic uniformity. Most current Cachexia is a syndrome characterized by the loss of diagnostic systems for cachexia assess at least lean body tissue, often including involuntary some of the following: (1) percentage of weight loss, accompanied by increased metabolic unintentional body weight lost in a specific time and proinflammatory cytokine activity. It is distinct frame (e.g., the past 12 months); (2) proportion of from mere weight loss due to anorexia and from lean body mass to fat mass; (3) body mass index; sarcopenia, which is characterized by the loss of (4) the presence of clinical symptoms such as

M.D. Gellman & J.R. Turner (eds.), Encyclopedia of Behavioral Medicine, DOI 10.1007/978-1-4419-1005-9, # Springer Science+Business Media New York 2013 C 282 Caffeine decreased muscle strength, fatigue, and Cross-References decreased appetite; and (5) abnormal biochemis- try such as increased inflammatory markers. ▶ Body Composition ▶ Cytokines Treatment ▶ Sarcopenia Treatments for cachexia aim to restore lean body ▶ Tumor Necrosis Factor-Alpha (TNF-Alpha) mass and improve quality of life. Pharmacological treatments have focused on (1) increasing appetite References and Readings and caloric intake through the use of appetite stimulants; (2) maintaining and/or restoring lean Mantovani, G., Anker, S. D., Inui, A., Morley, J. E., body mass with testosterone, anabolic steroids, or Fanelli, F. R., Scevola, D., et al. (2006). Cachexia human growth hormone; and (3) downregulating and wasting: A modern approach. New York: cytokine activity through the use of systemic anti- Springer. Springer, J., von Haehling, S., & Anker, S. D. (2006). The inflammatory medications. Non-pharmacological need for a standardized definition for cachexia in treatments include resistance training for muscle chronic illness. Nature Clinical Practice Endocrinol- retention, nutritional counseling and supplementa- ogy & Metabolism, 2, 416–417. tion to ensure adequate macro- and micronutrient Wanke, C., Kohler, D., & HIV Wasting Collaborative Consensus Committee. (2004). Collaborative recom- intake, and targeted amelioration of conditions mendations: The approach to diagnosis and treatment that may exacerbate cachexia such as opportunis- of HIV wasting. Journal of Acquired Immune tic infections in those with compromised immune Deficiency Syndromes, 37, S284–S288. systems.

Psychosocial Impact of Wasting Caffeine Although cachexia has a gradual onset, its clinical manifestation occurs somewhat rapidly ▶ Coffee Drinking, Effects of Caffeine and often during advanced disease stages. Considerable reductions in physical activity, coupled with decreased appetite and metabolic changes, have a significant impact on patients’ Caloric Intake quality of life. Many patients with cachexia feel shame or embarrassment about their bodily Megan Roehrig1, Jennifer Duncan2 and changes and distance themselves from loved Alyson Sularz1 ones. Decreased libido may have deleterious 1Department of Preventive Medicine, Feinberg effects on individuals’ romantic partnerships. School of Medicine, Northwestern University, Chicago, IL, USA The Role of Behavioral Medicine 2Department of Preventive Medicine, Feinberg Behavioral medicine plays a key role in the treat- School of Medicine Northwestern University, ment of patients with cachexia. Behavioral med- Chicago, IL, USA icine professionals can provide patient education regarding cachexia treatment options, deliver Synonyms interventions to improve medication adherence, and offer counseling and instruction for tailored Energy In; Energy Intake nutrition and exercise programs. The provision of psychotherapy that addresses acute psychiatric conditions, adjustment to chronic illness, and Definition couples issues pertaining to sexuality can help to improve overall quality of life for persons Caloric intake is defined as the amount of energy diagnosed with cachexia. consumed via food and beverage. A calorie is Cancer and Diet 283 C a unit of energy that is defined as the amount of Cross-References heat energy required to raise 1 g of water by 1C. Calories are units that measure the energy in food ▶ Fat, Dietary Intake as well as the energy produced, stored, and uti- lized by living organisms. Daily caloric intake needs are determined by References and Readings a variety of factors such as age, gender, height, C weight, activity level, and genetics. Three well- Harris, J. A., & Benedict, F. G. (1919). A biometric documented formulas are used to calculate daily study of basal metabolism in man. Washington, DC: Carnegie Institution of Washington. caloric needs: the Harris-Benedict equation Mifflin, M., St Jeor, S., Hill, L., Scott, B., & Daugherty, S. (1919), the Mifflin-St Jeor equation (1990), and (1990). A new predictive equation for resting energy the Institute of Medicine’s Dietary Reference expenditure in healthy individuals. The American Intake equation (2002). These equations deter- Journal of Clinical Nutrition, 51(2), 241–247. Rolls, B., & Barnett, R. (2000). The volumetrics weight- mine the resting metabolic rate (RMR), which control plan. New York: Harper Collins. represents the minimum energy needed to Trumbo, P., Schlicker, S., Yates, A. A., Poos, M., & Food maintain vital body functions. While the terms and Nutrition Board of the Institute of Medicine, The RMR and basal metabolic rate (BMR) are often National Academies. (2002). Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, choles- used interchangeably, the BMR requires more terol, protein and amino acids. Journal of the American stringent testing conditions and factor in calories Dietetic Association, 102(11), 1621–1630. needed based on the individual’s activity level. U.S. Department of Health and Human Services and U.S. The HHS/USDA 2005 recommendations for Department of Agriculture. (2005). Dietary guidelines for Americans. Washington, DC: U.S. Government daily caloric intake requirements for healthy Printing Office. weight maintenance and prevention of obesity according to age, gender, and activity level are available at http://www.nhlbi.nih.gov/health/pub- lic/heart/obesity/wecan/downloads/calreqtips.pdf. Cancer and Cigarette Smoking Caloric intake can be measured using objec- tive and subjective methods. Common objective ▶ Cancer and Smoking methods are calorimetry and the doubly labeled water technique, while common subjective methods are 24-h dietary recall interviews and food diaries. Objective measurements are highly Cancer and Diet accurate but costly to implement, while subjec- tive measurements are less expensive but subject Akihiro Tokoro to greater error. In fact, subjective estimates can Department of Psychosomatic Medicine, be off by as many as 800 kcal (Beasly, Riley, & National Hospital Organization, Kinki-Chuo Jean-Mary, 2004). Chest Medical Center, Sakai Osaka, Japan One pound of body weight is equal to approx- imately 3,500 cal. When caloric intake is equal to caloric expenditure, an energy balance is Synonyms achieved and body weight is maintained. Weight loss occurs when caloric expenditure is greater Diet and cancer than caloric intake. Conversely, weight gain is the result of greater caloric intake than caloric expenditure. Caloric imbalances in either Definition extreme have multiple health risk implications, including obesity and eating disorders and their A field in which the relationship between cancer associated medical comorbidities. and diet is examined from the interdisciplinary C 284 Cancer and Physical Activity perspectives of basic medicine, clinical epidemi- 3. Consumption of a healthy diet, with an empha- ology, preventive medicine, and behavioral sis on plant sources medicine. 4. Limited consumption of alcoholic beverages Further research is required to examine the relationship between single dietary factors Description and development or progression of cancer and between health behaviors, including dietary life- The relationship between diet and cancer has style, and cancer. recently been recognized as an area of scientific interest. Dietary factors are thought to be involved in 30% of cases of cancer in developed Cross-References countries and in 20% in developing countries ▶ (Marian, 2010). Cancer Prevention In 2004, the American Society of Clinical Oncology (ASCO) announced a goal of achiev- References and Readings ing prophylactic intervention for cancer preven- tion, with a focus placed on reduction of tobacco American Cancer Society guidelines on use, control of obesity, cancer-causing infections, nutrition and physical activity for cancer prevention. and environmental carcinogens (Lippman & http://caonline.amcancersoc.org/content/vol56/issue5/ http://www.who.int/gho/en/ Bernard, 2004). International Agency for Research on Cancer (IARC). A WHO report (http://www.who.int/gho/en/) (2002). Weight control and physical activity. In H. showed that 35% of adults aged 20 years old Vanio & F. Biaciani (Eds.), IARC handbooks of cancer worldwide were overweight (body mass preventive effects. Lyons: IARC Press. Lippman, S. M., & Bernard, L. (2004). Cancer prevention index [BMI]: 25 kg/m2) and 12% were obese 2 and the American Society of Clinical Oncology. Jour- (BMI: 30 kg/m ) in 2008. The rate of obesity nal of Clinical Oncology, 22(19), 3848–3851. has more than doubled since 1980. Marian, L. (2010). Diet and cancer. In Psycho-Oncology Previous studies have suggested that (2nd ed., pp. 22–27). New York: Oxford University Press. unhealthy eating and lack of physical activity can affect the development and prognosis of some cancers, including breast cancer, colon can- cer, and prostate cancer. Cancer and Physical Activity Research into the details of the association of diet with development of cancer is limited. How- Akihiro Tokoro ever, a report by the International Agency for Department of Psychosomatic Medicine, Research on Cancer (IARC) in 2002 showed National Hospital Organization, Kinki-Chuo that being overweight or obese is associated Chest Medical Center, Sakai Osaka, Japan with an increased risk of cancer in both men and women (International Agency for Research on Cancer (IARC), 2002). Synonyms Based on these data, the American Cancer Soci- ety (ACS) guidelines (American Cancer Society Exercise and cancer; Physical activity and cancer guidelines on nutrition and physical activity for cancer prevention http://caonline.amcancersoc. org/content/vol56/issue5/) recommend: Definition 1. Maintenance of a healthy weight throughout life A field in which the relationship between cancer 2. Adoption of a physically active lifestyle and physical activity is examined from the Cancer and Smoking 285 C interdisciplinary perspectives of basic medicine, physical activity may improve the prognosis and clinical epidemiology, preventive medicine, quality of life of cancer patients and survivors rehabilitation, and behavioral medicine. (National Cancer Institute fact, sheet, physical activity and cancer).

Description Cross-References C The relationship between physical activity and ▶ Cancer and Diet cancer has recently been recognized as an area ▶ Cancer Prevention of scientific interest. The role of physical activity ▶ Exercise in preventing cancer has been examined in sev- ▶ Physical Fitness eral epidemiological studies and several reviews of publications. An appropriate physical activity may reduce cancer risk and improve the quality References and Readings of life of cancer patients (Marian, 2010). Epidemiological evidence suggests that phys- American Cancer Society guidelines on nutrition and physical activity for cancer prevention. http:// ical activity is associated with a reduced risk of www.cancer.org/acs/groups/cid/documents/webcontent/ colon and breast cancers. Some studies have also 002577 reported the link between physical activity and http://www.aicr.org/reduce-your-cancer-risk/recommendat- a reduced risk of endometrial (uterus), lung, and ions-for-cancer-prevention/recommendations_02_activity. html prostate cancers. More good news – physically Marian, L. (2010). Exercise and cancer. In Psycho-oncol- active lifestyle helps you reduce your risk of heart ogy (2nd ed., pp. 28–32). New York: Oxford Univer- disease, diabetes, and osteoporosis (American sity Press. Cancer Society guidelines on nutrition and physi- National Cancer Institute fact, sheet, physical activity and cancer. http://www.cancer.gov/cancertopics/factsheet/ cal activity for cancer prevention http://www. prevention/physicalactivity cancer.org/acs/groups/cid/documents/webcontent/ State indicator report on physical activity. 002577). (2010). http://www.cdc.gov/physicalactivity/downloads/ Based on several publications such as the PA_State_Indicator_Report_2010 American Cancer Society (ACS) guidelines (American Cancer Society guidelines on nutrition and physical activity for cancer prevention Cancer and Smoking http://www.cancer.org/acs/groups/cid/documents/ webcontent/002577), the Centers for Disease Con- Monica Webb Hooper trol and Prevention (CDC) (State indicator report Department of Psychology, University of Miami, on physical activity, 2010)andtheAmericanInsti- Coral Gables, FL, USA tute for Cancer Research (AICR) (http://www.aicr. org/reduce-your-cancer-risk/recommendations-for- cancer-prevention/recommendations_02_activity. Synonyms html) recommend at least 30 min of moderate to vigorous physical activity, above usual activities, Cancer and cigarette smoking; Cancer and 5 or more days a week, and they say 45–60 min of tobacco smoking; Lung cancer and smoking intentional physical activity is more beneficial. Further research is required to examine the role of physical activity in cancer survivorship Definition and its correlation with quality of life and reduced cancer risk. The National Cancer Institute (NCI)- A cancer diagnosis represents a heterogeneous funded studies are exploring the ways in which class of diseases characterized by uncontrolled C 286 Cancer and Smoking growth of malignant cells in the body. These cells to nonsmokers. In 1968, the Surgeon General’s form a tumor that starts in the epithelium, invades report concluded that smoking also caused lung organs of the body and nearby tissue, has the cancer in women (USDHEW, 1968). Lung capacity to metastasize to other sites through cancer remains the most common form of cancer the bloodstream or lymph nodes, and may recur among men and women. after surgical removal. The development of Cigarette smoking is responsible for the cancer may be influenced by hereditary and/or majority of deaths due to cancer. Between 1995 environmental factors. and 1999, over 70% of cancer deaths among Tobacco smoking is defined as the practice of US males were attributable to smoking burning and inhaling tobacco. The combustion (USDHHS, 2004). During the same years, over from the burning allows the nicotine, tar, and 50% of cancer deaths among women were due to other chemicals and toxins to be absorbed through smoking. This corresponds to almost 1.5 million the lungs. Cigarette smoking is the most prevalent years of potential life lost among men, and almost form of consuming tobacco. Most national surveys 1 million years among women (USDHHS). define a current smoker as having smoked at least Some have questioned how a causal relation- 100 (five packs) cigarettes in their lifetime and ship could be determined between cigarette currently smokes on at least some days. smoking and cancer. This is largely because random assignment and a control group are necessary preconditions to conclude that a cause- Description and-effect connection exists. However, the accu- mulation of robust associations over a long period Over 46 years of scientific research, including of time can also be used to establish causality. 29 reports from the US Surgeon General, has The criteria used by the Surgeon General’s report led to the unequivocal conclusion that cigarette included the following: (1) the consistency of asso- smoking causes cancer. But, Dr. John Hill, ciation; (2) the robustness of association; (3) the first deduced that snuff (smokeless tobacco) specificity of association; (4) the temporal nature might be cancerous in “Cautions Against the of association; (5) the rationality of association; Immoderate Use of Snuff,” written in 1761 and (6) experimental and clinical autopsy-based (U.S. Department of Health and Human Services evidence (USDHEW, 1967). Using these criteria, [USDHHS], 1982). The earliest scientific inves- there is no doubt that cancer is caused by smoking. tigations on the positive association between Since the finding that smoking definitively smoking and cancer were published in the 1920s causes cancer, the prevalence of cigarette and 1930s (USDHHS, 1982). In 1950, four retro- smoking has declined. In 1965, the overall spective studies examining the smoking histories smoking prevalence was 42%, which decreased of lung cancer patients compared to controls were to 33% by 1971 (USDHEW, 1971). The rates of published, all indicating a positive link between smoking sharply declined in the USA, although smoking and cancer. The first Surgeon General’s there was no change in the absolute number of report with sufficient evidence to declare that smokers (53 million) over the 20-year period smoking causes lung cancer was published between 1951 and 1971. Since 2004, smoking in 1964 (U.S. Department of Health, Education, rates have leveled off at about 20%. In 2010, and Welfare [USDEW], 1964). At that time, 19.3% of adults (45 million) were current smoking was causally linked to lung cancer smokers (Centers for Disease Control and among men, but there was insufficient evidence Prevention, 2011). The past decade witnessed among women. Early on, the most prevalent lung an overall decline in the prevalence of cancer in cancers, squamous cell and epidermoid, were the USA, which is directly related to declines specifically associated with smoking. It was also in smoking. found that the frequency of oat-cell and adeno- With each Surgeon General’s report, the evi- carcinoma was greater among smokers compared dence explicating the types of cancers caused by Cancer and Smoking 287 C

Cancer and Smoking, Table 1 List of cancers caused Cancer and Smoking, Table 2 Examples of known by smoking carcinogens in cigarette smoke (humans) Lung cancer Acute myeloid leukemia Category Name Esophageal Larynx Aldehydes Formaldehyde Stomach Oral cavity Aromatic amines 2-naphthylamine Pancreatic Pharynx 4-aminobiphenyl Bronchial Trachea Metals and inorganic compounds Arsenic C Kidney Renal pelvic Beryllium Uterine cervical Nasal cavity Nickel Urinary bladder Chromium (hexavalent) Cadmium Organic compounds Vinyl chloride Volatile hydrocarbons Benzene smoking have increased. It is now well National Toxicology Program (2011) established that smoking damages almost every organ in the human body and causes at least 15 types of cancer (Table 1). There is metabolize the carcinogens in cigarette smoke. a dose–response relationship between cancer Smokers with polymorphisms in the GSTM1 and mortality and the number of cigarettes smoked CYP1A1 genes appear to have greater frequen- per day (USDHHS, 1982). Smoking a greater cies of DNA adducts compared to those without number of daily cigarettes leads to increased these polymorphisms. These processes facilitate exposure to the 7,000 chemicals and toxins unconstrained cell increases and inhibit the contained in each cigarette (USDHHS, 2010). immune system’s ability to reduce their progres- Although addictive, the nicotine in cigarettes is sion and range. not the source of cancer development. Rather, it Cigarette smoking is the single most important likely results from the effects of the 69 carcino- avoidable cancer risk behavior. Smoking cessa- gens contained in cigarettes (USDHHS, 2010). tion is the only method for stopping the patho- There are several key chemicals in cigarettes genic processes that ultimately lead to cancer. that are known to be cancer causing in humans Thus, quitting smoking reduces the likelihood (Table 2). Among these dangerous chemicals are of a cancer diagnosis. A former smoker’s chance formaldehyde and arsenic. of developing cancer declines gradually over The mechanisms that explain the causal time and depends on the extent of exposure to relationship between smoking and cancer are cigarette smoke. With the increasing duration of complex. Genetic predisposition and polymor- cessation, the overall rate of cancer mortality phisms are related to cancer risk among smokers approaches that of nonsmokers (USDHHS, and nonsmokers (USDHHS, 2010). Inhalation of 1982). Ex-smokers of 15 years or more have the chemicals and toxins in cigarette smoke lung cancer rates only two times greater than initiates genetic and cellular processes that lead never-smokers. to malignant tumor development. To date, the The prevalence of smoking among people unique contribution of the carcinogens found in diagnosed with cancer approximates the national cigarettes to cancer is not fully known. But the average. Many people erroneously believe that evidence suggests that cigarette smoking leads to once a person has been diagnosed with cancer, DNA damage. Repeated exposure to cancer- the damage is already done; thus, there is no causing agents alters major cellular pathways benefit of smoking cessation (USDHHS, 1990). through genetic mutation and the growth of However, the evidence indicates that continued DNA adducts. DNA adducts (i.e., DNA pieces smoking among cancer patients negatively that are chemically bonded to a carcinogen) are affects their prognosis. Specifically, smoking is formed by cytochrome P-450 enzymes, which associated with increased risks of recurrence, C 288 Cancer and Tobacco Smoking a second cancer, and decreased efficacy of cancer U.S. Department of Health and Human Services. (2004). treatment. Thus, smoking cessation is also The health consequences of smoking: A report of the surgeon general. Atlanta, GA: U.S. Department of important for cancer patients and survivors. Health and Human Services, Centers for Disease Con- In summary, cigarette smoking causes cancer. trol and Prevention, National Center for Chronic Indeed, smoking is the leading preventable cause Disease Prevention and Health Promotion, Office on of multiple cancers, including lung cancer. There Smoking and Health. U.S. Department of Health and Human Services. (2010). is a dose–response relationship between daily How tobacco smoke causes disease: The biology and smoking intensity and cancer mortality, but behavioral basis for smoking-attributable disease: there is no safe level of smoking. The prevalence A report of the surgeon general. Atlanta, GA: U.S. of smoking has declined since the first Surgeon Department of Health and Human Services, Centers for Disease Control and Prevention, National Center General’s report directly linking smoking to for Chronic Disease Prevention and Health Promotion, cancer, but about 20% of the US population Office on Smoking and Health. continues to smoke. All of the biological mecha- U.S. Department of Health, Education, and Welfare. (1964). nisms by which smoking leads to cancer are not Smoking and health: Report of the advisory committee to the surgeon general of the public health service. yet elucidated; but it is known that smoking leads Washington, DC: U.S. Department of Health, Educa- to DNA damage and reduces the immune sys- tion, and Welfare, Public Health Service, Center for tem’s ability to rid the body of cell overgrowth. Disease Control. PHS Publication No. 1103. Smoking cessation is the best way to reduce the U.S. Department of Health, Education, and Welfare. (1967). The health consequences of smoking. A public health risk of cancer and is beneficial even after a cancer service review: 1967. Washington, DC: U.S. Depart- diagnosis. ment of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration. PHS Publication No. 1696. U.S. Department of Health, Education, and Welfare. (1968). Cross-References The health consequences of smoking. 1968 supplement to the 1967 public health service review. Washington, ▶ Smoking Cessation DC: U.S. Department of Health, Education, and Welfare, Public Health Service, 1. DHEW Publication No. 1696 (Suppl.). U.S. Department of Health, Education, and Welfare. (1971). The health consequences of smoking. A report of the References and Readings surgeon general: 1971. Washington, DC: U.S. Depart- ment of Health, Education, and Welfare, Public Health Centers for Disease Control and Prevention. (2011). Vital Service, Health Services and Mental Health Administra- signs: Current cigarette smoking among adults tion. DHEW Publication No. (HSM) 71-7513. aged 18 years – United States, 2005–2010. Morbidity and Mortality Weekly Report, 60, 1207–1212. National Toxicology Program. (2011). Report on carcinogens (12th ed., 499 pp.). Research Triangle Park, NC: U.S. Department of Health and Human Cancer and Tobacco Smoking Services, Public Health Service, National Toxicology Program. ▶ Cancer and Smoking U.S. Department of Health and Human Services. (1982). The health consequences of smoking: Cancer. A report of the surgeon general. Rockville, MD: U.S. Depart- ment of Health and Human Services, Public Health Cancer Cachexia Service, Office on Smoking and Health, DHHS Publication No. (PHS) 82-50179. U.S. Department of Health and Human Services. (1990). ▶ Cachexia (Wasting Syndrome) The health benefits of smoking cessation. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Cancer of the Uterine Cervix Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. DHHS Publication No. (CDC) 90-8416. ▶ Cancer, Cervical Cancer Risk Perceptions 289 C

cancer may accelerate the advance of cancer and Cancer Prevention result in early recurrence or shorter survival. Examples include negative effects of continued Toru Okuyama smoking after development of lung cancer on sur- Division of Psycho-oncology and Palliative Care, vival and high fat consumption in promoting breast Nagoya City University Hospital, Nagoya, cancer recurrence. This level also includes reha- Aichi, Japan bilitation programs and patient support programs. C

Synonyms Cross-References ▶ Cancer Screening/Detection/Surveillance Screening ▶ Prevention: Primary, Secondary, Tertiary

Definition References and Readings Despite the development of modern medicine, American Cancer Society Cancer Prevention & Early cancer is a leading cause of death and disability. Detection Facts & Figures. (2008). Retrieved March Since the development of cancer is associated 29, 2012, from http://www.cancer.org/Research/ with many genetic and environmental factors, CancerFactsFigures/CancerPreventionEarlyDetection efforts to prevent cancer by decreasing environ- FactsFigures/cancer-prevention-early-detection-facts- figures-2008 mental factors have been made. Smith, R. A., Cokkinides, V., Brooks, D., Saslow, D., Shah, There are three levels in the cancer prevention M., & Brawley, O. W. (2011). Cancer screening in the strategy. The primary prevention is to reduce United States, 2011: A review of current American exposures to risk factors contributing to develop Cancer Society guidelines and issues in cancer screen- ing. CA: A Cancer Journal for Clinicians, 61(1), 8–30. cancer. It includes smoking cessation, treatment U.S. Preventive Services Task Force. Retrieved March 29, of viral infections including papillomavirus, hep- 2012, from http://www.ahrq.gov/clinic/uspstfix.htm atitis B and C virus, diet, physical activity, reduc- ing exposures to sunshine, ionizing radiation, or some harmful material such as aniline dyes, ben- zenes, and asbestos. Currently, at least one-third Cancer Risk Perceptions of all cancer cases are thought to be preventable via avoiding these risk factors. Michael E. Stefanek The secondary prevention intends to promote Research and Collaborative Research, Indiana early detection and early treatment and, therefore, University, Bloomington, IN, USA reduces significant morbidity or mortality by can- cer. Screening cancers is the main attempt but has been proven effective for relatively few types of Synonyms cancer, with a few exceptions. The U.S. Preventive Services Task Force currently recommends cervi- Health risk; Likelihood judgments; Risk cal cytology testing for cervical cancer screening, perception mammography for screening breast cancer, and fecal occult blood testing, sigmoidoscopy, or colo- noscopy for screening colorectal cancer. Definition Tertiary prevention involves activities to mini- mize the negative impact or outcome of cancer and Risk is the likelihood that something will happen. maximizing the quality of life after developing Risk is a combined function of the probabil- cancer. Some risk factors for the development of ity of loss and the consequences of loss C 290 Cancer Risk Perceptions

(e.g., severity of loss in the physical, psycholog- environment, what might be causing such excess ical, social, and economic realms). cancers, and what is needed to fix the problem. Risk is a population-based measure, the At the policy level, risk perceptions may chance of something happening, as determined influence funding for cancer research and the by its occurrence among a large group of people development of guidelines for screening to over time. An individual’s risk varies consider- detect cancer early or genetic tests to identify ably within a given numerical boundary of individuals who may inherit a higher risk of a population’s risk, due to variations in personal, developing cancer. genetic, environmental, and behavioral factors. Risk communication is the communication Risk Perceptions and Health Behavior with individuals (not necessarily face to face) Arguably the most critical issue determining the which addresses knowledge, perceptions, importance of risk perceptions is determining if attitudes, and behavior related to risk. such perceptions promote healthy behavior. Out- Cancer risk perception is the judgment, based side of the cancer realm, a recent meta-analysis of on cognitive and affective factors, of the chances vaccination behaviors did indeed find a consistent that a given individual will develop cancer over relationship between risk perceptions and behav- a certain period of time. It can be significantly ior, supporting the role of risk perceptions as influenced by the way in which an individual’s a core concept in health behavior theories risk is communicated to him or her. Both “think- (Brewer et al., 2007). Reviewing the link between ing” and “feeling” are critical components of risk risk perception and behavior in cancer, the rela- perception in general and cancer risk perception tionship is present, but appears modest. A solid in particular. summary of this data is provided by McCaul, Magnan and Dillard (2009) and a systematic review by Edwards et al. (2006) focusing upon Description personalized risk communication for informed decision making related to screening tests. The issue of risk perception and communication These summaries note a generally positive rela- in the cancer arena has received increasing atten- tionship in areas such as mammography screen- tion over the past decade (Klein & Stefanek, ing and smoking cessation, but also report that 2007; Peters, McCaul, Stefanek, & Nelson, such relationships may have any number of 2006; Rothman and Kivniemi, 1999). This is mediators or moderators involved in this risk due in large part to the increasing awareness perception – health behavior link, including that the judgment that people make about their worry, barriers to change, or the presence of likelihood of developing cancer has important a family history of cancer. Given the modest implications. At the level of the individual, risk relationship between risk perceptions and health perceptions guide protective action, such as not behaviors linked to cancer prevention or early smoking, exercise and dieting behavior, and detection, it is not surprising that direct evidence undergoing screening tests for early detection that changing risk perceptions will cause subse- of cancer. If the perception of risk is quent changes in behavior is less available. underestimated, such protective action may not However, there is indirect evidence that such occur. If the perception exceeds the objective changes may occur. McClure (2002) reviewed risk, such perception may cause anxiety, depres- a series of studies of interventions that have pro- sion, stress, or may even result in excessive vided biomarker data (carbon monoxide feed- screening behaviors or indulgence in “alterna- back to smokers) and supported the role of tive” health practices that have no evidence changes in risk perception in smoking cessation. base. At the community level, risk perceptions There is also some evidence that using “teachable may guide responses by communities concerned moments” such as the diagnosis of cancer to about “cancer clusters” in their immediate support smoking cessation may be productive, Cancer Risk Perceptions 291 C linked perhaps to a new appreciation of one’s risk someone hears a story of celebrities developing of death (McBride & Ostroff, 2003). cancer, perhaps by repeated media exposure, he In sum, risk perception is but one of a number or she may overestimate the risk of developing of variables impacting health behaviors most crit- similar cancers. While such “heuristics” may ical to cancer control such as healthy eating, indeed be helpful and accurate, they hold the physical activity, tobacco use, excessive alcohol potential for very inaccurate estimates of risk. intake, excessive sun exposure, and appropriate In addition to cognitive influences, there is C utilization of cancer screening tests. a growing appreciation of the role of “affect” or Given the data to date that supports the role of emotion in risk perception (Slovic, 2010). It has risk perception in cancer control, it is important to become clearer that people process information have an understanding of the processes involved in through two distinct modes: deliberative and how people develop their perception of risk, how it experiential (Slovic, 2010), following what has is measured, and future research needed to develop become known as the “dual process” theory of our understanding of cancer risk perceptions. thinking, with the “deliberative” system being logical, analytical, slower, and the “experiential” Risk Perception: The Role of Affect and system being more affective, intuitive, and fast. Cognition While it is assumed that these systems interact in How do people think about risk? It is now recog- forming risk perceptions, much work is needed to nized that our perceptions of risk are influenced determine how this process plays out in forming by a host of cognitive and affective variables. risk perceptions. The role of the “experiential” In addition, “how” risk is communicated impacts system may be even more contributory in the area how our perception of the risk of cancer may be of cancer risk perception, given the fear and formed. These processes often lead to biases and anxiety that accompanies the image of cancer misperceptions that influence both laypeople development and treatment. and health-care providers. There are a host of Finally, how risk is presented may signifi- such processes to consider, many reviewed by cantly influence the perception of risk. Risk esti- Klein and Stefanek (2007), Peters et al. (2006), mates can be provided in ways that differ only in and McCaul et al. (2009) in the context of cancer format. For instance, relative risk (RR) is most control and well explained by Slovic (2010)in commonly used (e.g., the risk of cancer is 25% a more general overview of risk and risk commu- higher in group A than in group B) in medical nication. A number of such cognitive processes journals and the media. Another approach is to involve mental “shortcuts” or “heuristics.” Very provide the number needed to treat (NNT) (e.g., briefly, these heuristics can be thought of as 300 people need to take medicine A in order to “rules of thumb” that are used often automati- save 1 life). Finally, the information can be cally to influence the perception of risk. These presented as an absolute frequency (1,000 people include the availability heuristic, representative- took medicine A and 3 developed cancer; 1,000 ness heuristic, the anchoring heuristic, and the people did not take medicine A and 4 developed affect heuristic. As one example, the availability cancer). Formats for conveying risk are critical heuristic refers to the common practice of making since individuals are not mathematically fluent, judgments about the frequency of an event based nor do they have stable opinions about the mag- upon the information that is most readily avail- nitude of any given risk (Lipkus, 2007). This able. If such information is unrepresentative or issue of presentation format becomes key, given incomplete, the subsequent judgment will be the recognition over the past several years of the inaccurate. For instance, if someone is in the influence of numeracy in risk communication. process of scheduling a flight and is exposed to several stories of airline crashes, this may make Conveying Risk Estimates the person feel relatively more at risk than driving Whether perceptions of risk impact decisions to his or her destination. Likewise, when and behavior relies on how messages of risk C 292 Cancer Risk Perceptions magnitudes are conveyed. It is important to acknowledge the role of affect in the perception emphasize that communicating risk is not equiv- of risk. This includes not only incident affect alent to communicating numbers. In fact, there is (emotional state when risk information is some controversy in the field of risk perception communicated) but also “integral” affect (i.e., about the degree to which presenting risk in affect specifically related to the risk in question). numerical format is critical to an individual’s It is not in the too distant past that cancer was understanding of risk over time and links to viewed as a death sentence, with disfiguring and behavior change. That is, what may be key is toxic treatments. Thus, the image of or beliefs not specific numerical reasoning, but simply surrounding cancer can clearly “link” to negative whether an individual has an understanding of affect, which may then influence the perception the risk in a general fashion, whether she or he of risk. Another key issue is how best to convey understands the “gist” of the risk (Reyna, 2004). risk information. In addition, numeracy impacts Presenting risk verbally (e.g., “you have the perception of risk. Many people have prob- a somewhat higher than average risk”) provides lems dealing with frequencies, percentages, or an overall sense of risk, but may fail to commu- fractions, which impacts accurate risk represen- nicate the exact magnitude of risk, and is not tations, and the use of verbal labeling to transmit helpful in making direct comparisons of risk risk information risks being less than specific and across individuals. Numbers may be more precise perhaps quite different in meaning than the com- than verbal representations of risk and provide municator(s) of such risk meant to transmit. a bit of scientific credibility to the risk communi- Continuing research is needed to determine cation, and most people express a preference for how best to present risk while also utilizing numbers. However, they do not address “gut” what we do know about presenting such informa- reactions or intuition well and do not provide tion in as “transparent” a manner as possible clear information to individuals who may strug- (Kutz-Micke, Gigerenzer, & Martignon, 2008). gle with numerical competency. This latter issue We must also continue to explore cultural differ- of “innumeracy” is a critical one since increasing ences in risk perception and how such influences evidence indicates that a large proportion of indi- may impact both perceptions and risk communi- viduals, even highly educated ones, struggle with cation in order to intervene most effectively to numbers (Lipkus, Samsa, & Rimer, 2001; enhance cancer control behaviors. Schwartz, Woloshin, Black, & Welch, 1997). In fact, Schwartz et al. (1997) found that numeracy was strongly linked to being able to accurately References and Readings use information about the benefit of mammogra- Brewer, N. T., Chapman, G. B., Gibbons, F. X., Gerrard, phy and called for more effective formats to M., McCaul, K. D., & Weinstein, N. D. (2007). Meta- present risks and benefits of mammography. analysis of the relationship between risk perception and Overall, there are few “best practices” cleanly health behavior: The example of vaccination. Health established, although the call to present informa- Psychology, 26(2), 136–145. Edwards, A. G. K., Evans, R., Dundon, J., Haigh, S., tion both numerically and visually (graphs, Hood, K., & Elwyn, G. J. (2006). Personalised tables) has been proposed (Lipkus, 2007). risk communication for informed decision making about taking screening tests. Cochrane Database of Summary and Future Directions Systematic Reviews, 4, 1–66. doi:10.1002/14651858. CD001865.pub2. It is clear that cancer risk perceptions are but Klein, W. M., & Stefanek, M. (2007). Cancer risk elicita- one of many influences on health behavior related tion and communication: Lessons from the psychology to cancer control. However, there is growing of risk perception. CA: A Cancer Journal for Clinicians, evidence that risk perception generally and 57, 147–167. Kutz-Micke, E., Gigerenzer, G., & Martignon, L. (2008). cancer risk perception specifically can impact Transparency in risk communication: Graphical and health behavior. In addition to cognitive influ- analog tools. Annals of the New York Academy of ences on risk perception, it is essential to Sciences, 1128, 18–28. Cancer Screening/Detection/Surveillance 293 C

Lipkus, I. M. (2007). Numeric, verbal, and visual formats Definition of conveying health risks: Suggested best practices and future recommendations. Medical Decision Making, 27, 696–713. Cancer screening is the use of diagnostic tests Lipkus, I. M., Samsa, G., & Rimer, B. (2001). General and procedures to detect the presence of cancer- performance on a numeracy scale among highly ous tissue before it is symptomatic. There are educated samples. Medical Decision Making, 21, recommended routine screening tests for some 7–44. C McBride, C. M., & Ostroff, J. S. (2003). Teachable of the more prevalent cancers. The parameters moments for promoting smoking cessation: The context (such as age, time intervals) set for screening of cancer care and survivorship. Cancer Control, 10, recommendations increase the likelihood that 325–333. tests may detect the disease rather than the dis- McCaul, K. D., Magnan, R. E., & Dillard, A. (2009). Understanding and communicating about cancer risk. ease presenting itself symptomatically. In S. M. Miller, D. J. Bowen, R. T. Croyle, & J. H. Rowland (Eds.), Handbook of cancer control and behavioral science (pp. 133–150). Washington, DC: Description American Psychological Association Press. McClure, J. B. (2002). Are biomarkers useful treatment aids for promoting health behavior change? American According to the President’s Cancer Panel, 41% Journal of Preventive Medicine, 22, 200–207. of Americans will develop cancer in their lifetime Peters, E., McCaul, K., Stefanek, M., & Nelson, W. (Reuben, 2010); however, data from the National (2006). A heuristics approach to understanding cancer risk perception: Contributions from judgment and Health Interview Survey indicates that only 75% decision-making research. Annals of Behavioral of the US population adheres to recommended Medicine, 31(1), 45–52. routine colorectal, breast, cervical, and prostate Reyna, V. F. (2004). How people make decisions that cancer screenings (National Health Interview involve risk. Current Directions in Psychological Science, 13(2), 60–66. Survey [NHIS], 1997–2010). Screening is impor- Rothman, A. J., & Kiviniemi, M. T. (1999). Treating tant because it increases the probability of finding people with information: An analysis and review a cancerous growth in its early stage, despite the of communicating health risk information. Journal lack of any noticeable symptoms. Finding a can- of the National Cancer Institute Monographs, 25, 44–51. cerous growth in its earliest stage (i.e., during its Schwartz, L. M., Woloshin, S., Black, W. C., & Welch, period of sojourn), or in some cases before it G. H. (1997). The role of numeracy in understanding becomes palpable, increases the likelihood of the benefit of screening mammography. Annals of successfully treating the disease before it spreads. Internal Medicine, 127, 966–972. Slovic, P. (2010). The feeling of risk. Washington, DC: Additionally, there must be sufficient evidence Earthscan. that treatment initiated earlier as a result of screening will lead to an improved outcome (National Cancer Institute [NCI], 2011). Cancer screening may reveal no tumor or the presence of a cancerous growth, which is then Cancer Screening/Detection/ classified by stage. The concept of staging as Surveillance a general classification of localized, regional, and distant disease was developed in the 1940s Tainya C. Clarke and David J. Lee (NCI, 2011). Staging describes the severity of Department of Epidemiology and Public Health, a person’s cancer based on the extent of the Miller School of Medicine, University of Miami, primary tumor. One of the more detailed and Miami, FL, USA more widely used staging systems is the Tumor, Node, Metastasis (TNM) system. In the TNM system, the tumor size, the status of the lymph Synonyms nodes, as well as the status of distant metastases (spreading to other parts of the body) are also Cancer prevention categorized (NCI, 2011). The statuses of these C 294 Cancer Screening/Detection/Surveillance core elements are aggregated into stages their benefits. Screening tests may present unnec- 0 through 4 and are associated with the likelihood essary physical and psychological risks for per- of disease survival. Adherence to recommended sons being tested. Some screening procedures routine screenings usually leads to discovery of have been known to cause bleeding, while others tumors in their earliest stage. This includes in have resulted in perforation of the lining of sen- situ, where any abnormal cells present are only sitive organs (Morbidity and Mortality Weekly in the layer of cells in which they developed, or Report [MMWR], 2010) (see Table 1). The risks localized, wherein the cancer is limited to the of screening tests may be further increased as the organ in which it originated, and has not spread. test results may not always be valid (i.e., a test There are several recommended routine may fail to detect a cancerous growth, and this cancer screenings, most of which are age specific, kind of false-negative result can lead to a delay some of which are gender specific (Table 1). in treatment and/or removal of the cancer). Recommendations to patients are usually made Contrarily, sometimes a test may detect a cancer by primary care physicians, but most screening when there is none present. This false-positive tests are performed by physicians or technicians test result causes undue stress and anxiety and specializing in that particular field. Adherence to usually leads to the patient being submitted recommended routine cancer screening has led to to further tests, which may also have risks the discovery of early stage tumors and has (Levin et al., 2008). prevented the development of advance stage can- The ability of a screening test to detect cancer cers. This has in turn resulted in an increase in in a person who truly has the disease (sensitivity) quality adjusted life years and saves thousands of or failure to find cancer in a person who is truly dollars in medical expenditure. There are several negative for the disease (specificity) is of outmost cancer registries in the USA which maintain importance in determining the gold standard for records of reported tumors and that work closely screening tests. A reliable screening test should with hospitals, cancer research centers, and agen- have both high sensitivity and high specificity. cies responsible for cancer surveillance. The con- tinued surveillance of screening behavior within History of Screening the population, the chronicling of cancer staging While cancers were being surgically removed as in addition to monitoring associated morbidity early as the 1700s, screening for the disease did and mortality rates provide valuable information not begin until the late nineteenth century. This treatment and survival. was as a result of an insightful discovery by Cancer surveillance and screening are a mid-nineteenth century, German pathologist carried out by several agencies and responsible named Rudolf Virchow. Virchow discovered programs such as the Surveillance, Epidemiol- that cancerous tumors were the result of abnormal ogy, and End Results (SEER) Program of the growth of normal cells (McNeely, 2002), which National Cancer Institute (NCI), and the Center laid the foundation for early detection. for Disease Control’s National Program of Cancer screening has evolved since its institu- Cancer Registries-Cancer Surveillance System tion in the early 1900s, and advances in detection (NPCR-CSS). Cancer surveillance involves the techniques have resulted in the early discovery of measurement and monitoring of cancer inci- cancerous cell growth. This is attributed to the dence, survival, morbidity, and mortality for per- highly sophisticated screening tools used for var- sons with cancer. Surveillance also assesses of ious tests and procedures. The most common genetic predisposition of a population, environ- types of screening tests are imaging and labora- mental risks in addition to population cancer tory tests. Imagining tests include x-ray mammo- health and risk behavior (NCI, 2010a). grams for breast cancer screening and computed Cancer screening is not without controversy, tomography (CT) scans used to detect or confirm and there are ongoing debates regarding whether the presence of brain, lung, and bone cancers, the harms associated with some tests outweigh among others. Papanicolaou (Pap) tests for Cancer Screening/Detection/Surveillance 295 C

Cancer Screening/Detection/Surveillance, Table 1 Advantages and disadvantages of some common cancer screening tests Screening exam Current recommendations Benefits/advantages Risks/disadvantages Breast Mammography Women 40 years should Only proven reliable False positive- which may cancer (a digital or film have mammograms method of detection of lead to unnecessary screening x-ray picture of every 1–2 years small abnormal tissue additional testing the breast) growths confined to the milk ducts (ductal C carcinoma in situ) Women who are at higher Detects all types of breast Over diagnosis may lead to than average risk of cancers, including invasive the treatment of clinically breast cancer should talk ductal and lobular cancers insignificant cancers. This with their health care may result in breast providers regarding deformity, frequency of screening and thromboembolic events, age at which to start lymphedema, development of new cancers, or toxicities due to chemotherapy Clinical breast Every 3 years for women in Lead to a decrease in breast False-negatives lead to exam their 20s and 30s and every cancer cause specific a false sense of security and year for women 40 years mortality among women a delay in cancer diagnosis 50 –69 years Cervical Pap test Recommended for women Reduces mortality from Regular Pap tests lead to cancer at least 3 years after having cervical cancer by finding additional diagnostic screening first vaginal intercourse, cancers when they are most procedures (e.g., but no later than 21 years treatable colposcopy) and treatment old for low-grade squamous Regular Pap test every 1 intraepithelial lesions year or newer (LSIL), with long-term liquid-based Pap test every consequences for fertility 2 years and pregnancy Women 30 who have had 3 consecutive normal Pap test results may get screened every 2–3 years. Women 30 years may also get screened every 3 years with either the conventional or liquid- based Pap test, in addition to the human papilloma virus (HPV) test Women 70 years with 3 or more consecutive normal Pap tests in and no abnormal Pap test results in the last 10 years may choose to stop having Pap tests Women who have had a total hysterectomy for non-cancer related reasons may stop having Pap-tests (continued) C 296 Cancer Screening/Detection/Surveillance

Cancer Screening/Detection/Surveillance, Table 1 (continued) Screening exam Current recommendations Benefits/advantages Risks/disadvantages Colorectal Flexible Men and women 50 years Allows the doctor to view Examines only the rectum screening sigmoidoscopy the rectum and the entire and the lower part of the colon colon. Any polyps in the Every 5 yearsa, or Doctor can perform upper part of the colon will a biopsy and remove polyps be missed Colonoscopy Every 10 years, oror other abnormal tissue Requires thorough cleansing during the test, as needed of the colon before the test. Some form of sedation is used in most cases CT colonography Every 5 yearsa Risks tearing or perforation (virtual of the lining of the colon colonoscopy) Double-contrast Every 5 yearsa, or cannot perform a biopsy or barium enema remove polyps during the test Fecal occult Annuallyb, or Not an invasive procedure, Additional procedures are blood test hence complications are rare necessary if the test (gFOBT) indicates an abnormality Fecal Annuallyb, or No sedation is necessary Fecal tests fail to detect most immunochemical polyps and some cancers test (iFOBT/FIT) No cleansing of the colon is Dietary changes necessary recommended a few days prior to gFOBT but not iFOBT FOBT does not cause Colonoscopy required if bleeding, tearing or the test indicates an perforation of the lining of abnormality the colon Digital Annually Interval uncertain (possibly No cleansing of the colon is Only detects abnormalities rectal 3–5 years)b necessary in the lower part of the exam rectum (DRE) Stool Interval uncertain DNA test (possibly every (sDNA) 3–5 years) Prostate Prostate specific Discuss with physician the Detects the disease in its Detects small non life cancer antigen (PSA) pros and cons of receiving early stage among high risk threatening cancers that screening blood test a baseline PSA and if men leads to over diagnosis and conducted, when another complications from test would be necessary unnecessary treatment PSA velocity test Causes unnecessary anxiety (How PSA measures rise over time) PSA density test Men at higher than normal Elevated PSA levels may (Ratio of PSA risk (Blacks, men whose be due to other level to size of father, brother or son have noncancerous conditions prostate gland) been diagnosed with such as benign prostatic prostate cancer) hyperplasia and prostatitis Percent-free PSA Discuss screening with (Ratio of physician at 45 years unattached PSA in blood to total PSA) (continued) Cancer Screening/Detection/Surveillance 297 C

Cancer Screening/Detection/Surveillance, Table 1 (continued) Screening exam Current recommendations Benefits/advantages Risks/disadvantages Age-specific PSA Men 50 years discuss the range harms and benefits of PSA screening with physician Digital rectal Men with a previous PSA exam of 4 ng/ml in the blood, C should be retested if discussion with physician dictates a necessity aIf the test is positive, a colonoscopy should be done bThe multiple stool take-home tests should be used. One test done by the doctor in the office is not adequate for testing. A colonoscopy should be done if the test is positive

cervical cancer screening and prostate-specific (NCI). The ACS, the ACR, and the NCI issue antigen (PSA) tests for prostate cancer screening guidelines for all cancer types considered amena- are typically confirmed by laboratory tests. Other ble to screening, while the ACOG makes recom- screening tools include ultrasound, magnetic mendations for female gender–related cancers resonance imaging (MRI), and fine-needle such as breast and cervical cancer screening biopsy. Additionally, proteomics have been (American Cancer Society [ACS], 2011b; used to diagnose and identify the best treatment American College of Obstetrics and Gynecolo- for specific individuals, and genetic testing has gists [ACOG], 2009, 2011; NCI, 2011). The been used to confirm whether women tested may United States Preventive Services Task have an increased probability of developing Force (USPSTF) is another organization that a certain type of cancer (NCI, 2011). makes screening recommendations. They are The use of vaginal smears (Pap test) for cervi- a small independent panel of nongovernment cal cancer screening was established in the late medical experts who have a strong foundation 1930s by George Papanicolaou (Papanicolaou in preventive and evidence-based medicine and Traut, 1941). Colorectal screening began in (United States Preventive Services Task Force the 1940s and was conducted with a rigid [USPSTF], 2011). The panel usually comprises proctoscope until the introduction of the flexible of general doctors (such as family physicians, sigmoidoscope in the 1980s (Grossman, 1998). internists, physician specialists, pediatricians, Breast cancer screening was implemented in the nurses, and health behavior specialists). There is 1960s (Fletcher, 2011), while PSA serum test was some amount of disagreement regarding some approved for prostate cancer screening by the screening guidelines among these different Food and Drug Administration in the early groups, especially with reference to the recent 1990s (NCI, 2010b). controversial changes in breast cancer screening. The USPSTF assigns one of five letter grades Recommending Authorities to each of its recommendations; a level of cer- Several authorities on cancer issues periodically tainty regarding net benefits accompanies each update screening guidelines. Some of the more letter grade (USPSTF, 2011). The USPSTF also prominent agencies which make screening uses an I-statement/grade when there is insuffi- recommendations include the following: the cient evidence to assess the balance of benefits American Cancer Society (ACS), the American and harms of the recommended service. These College of Radiology (ACR), the American Col- recommendation processes and methods are lege of Obstetricians and Gynecologists outlined in a procedure manual and are based on (ACOG), and the National Cancer Institute evidence-based medicine (USPSTF). C 298 Cancer Screening/Detection/Surveillance

Controversial Recommendations screenings. In an effort to increase the number of In 2009, the USPSTF recommended changing the early detections and reduce the incidence of avoid- breast cancer screening guidelines for women able cancers within the population, it is important from annual mammograms beginning at age 40 to resolve existing controversies and reduce the to every other year beginning at age 50 after frequency of changes in recommendations. These determining that the benefits of annual mammo- inconsistencies may result in confusion, mistrust, grams beginning at age 40 did not outweigh the and a negative attitude and behavior toward potential risks (Pickert, 2011). They argued that recommended cancer screenings. increased mammography screenings would lead to a greater likelihood of false positives, psycho- Surveillance logical stress, depression, overexposure to radia- Public health officials often consider the propor- tion, and unnecessary surgery. tion of the population that must participate in a The scientific panel supporting the USPSTF’s screening program for one death to be prevented decision strongly believes that much of the abnor- within a defined time interval. This proportion is mal cell growth detected in women in their 40s dependent on the disease characteristics as well could be detected in their 50s with no adverse as other population parameters. Epidemiologists effects from the delay. However, there have been and population scientists often investigate the numerous studies, including that by Anders et al. measures of risks within a particular population; (2008), which show aggressive fast-growing can- this translates to the implementation of public cers in younger women, which would in fact health policy and screening guidelines as well contradict the USPSTF. The ACS, ACR, as helps dictate the actions taken by medical ACOG, and the NCI still recommend annual practitioners. screenings, beginning at age 40 (ACOG, 2011; Ongoing surveillance conducted by the afore- ACR, 2008; ACS, 2011a; NCI, 2011). mentioned recommending authorities has iden- Prostate cancer screening is equally conten- tified disproportionately lower screening tious and is notorious for detecting false positives behavior among certain subsets of the US popu- and false negatives. PSA testing does not distin- lation. African American and Hispanics are less guish tumors that would cause no harm from likely to seek recommended cancer screening clinically significant tumors, which results in compared to their non-Hispanic White counter- overdiagnosis and overtreatment (Pickert, parts(Vidaletal.,2009). Uninsured Americans 2011). In October 2011, the USPSTF issued and those living below the poverty income level a ‘D’ grade for PSA screening, thus recalling are less likely to report having a routine place of previous recommendations of annual screenings care and thus less likely to get recommended for men who do not have an increased risk of screening advice from a medical professional. getting the disease. The USPSTF has determined Blue-collar workers and workers in the service that there is a moderate or high certainty that PSA industry are less likely to adhere to recommended screening offers no net benefit and that the harms screenings when compared to persons employed from associated tests and exams outweigh the in the white-collar job sector (Vidal et al.). In the benefits of the screening. United States, this information (on the noninstitu- As agencies try to improve on screening rec- tionalized civilian population) is collected and ommendations and clinical practice, careful con- stored in several population health databases. As sideration must be made with regard to the public such, epidemiologists and behavioral scientists are health message being communicated to the gen- able to assess the adherence to screening in con- eral population. New scientific discoveries, fre- junction with some of the more common social quent changes in recommendations, and determinants of health and demographic informa- disagreements between recommending authori- tion. With this information, we are also able to ties cast doubts among the general public and correctly identify groups of persons that are at dissuade persons from adhering to recommended a higher risk and therefore require more frequent Cancer Survivor 299 C screening. These analyses lead to reports which Levin, B., Lieberman, D. A., McFarland, B., Smith R.A., further drive policies and influence research and Brooks D. Andrews K.S. et al. (2008). Screening and surveillance for the early detection of colorectal cancer investigations into current recommendations and and adenomatous polyps: A joint guideline from the screening practices. It is of utmost importance to American Cancer Society, the US Multi-Society Task not only recommend cancer screening but also Force on Colorectal Cancer, and the American College provide the public with information on the associ- of Radiology. CA: A Cancer Journal for Clinicians, 58, 130. C ated harms and benefits to early detection and McNeely, I. F. (2002). Medicine on a grand scale: Rudolf encourage persons to take a more active role in Virchow, liberalism, and the public health. London: managing cancer-related and other preventive Welcome Trust Centre for the History of Medicine at health behavior. University College. Morbidity and Mortality Weekly Report (MMWR). The information in the table below has been (2010). Surveillance of screening detected cancers adopted from the American Cancer Society and (colon and rectum, breast, and cervix)-United States, the National Cancer Institute. It provides an over- 2004–2006. Morbidity and Mortality Weekly Report. view of general screening recommendations and Surveillance Summaries, 59,1. National Cancer Institute (2010a). Cancer Trends Pro- their associated advantages and disadvantages. gress Report – 2009/2010. Retrieved August 23, 2011 from http://progressreport.cancer.gov. National Cancer Institute (2010b). Cancer Advances in Focus: Prostate Cancer. Retrieved August 23, from Cross-References http://www.cancer.gov/cancertopics/factsheet/cancer- advances-in-focus/prostate. ▶ National Cancer Institute. (2011). Cancer screening over- American Cancer Society view. Retrieved August 29, 2011, from http://www. ▶ National Cancer Institute cancer.gov National Health Interview Survey (NHIS). 1997–2010. Retrieved September 3, 2011, from http://www.cdc. gov/nchs/nhis/quest_data_related_1997_forward.htm References and Readings Papanicolaou, G. N., & Traut, H. F. (1941). The diagnostic value of vaginal smears in carcinoma of the uterus. American Journal of Obstetrics and Gynecology, 42, American Cancer Society. (2011a). Guidelines for early 193–206. the detection of cancer. Retrieved August 26, 2011, Pickert, K. (2011, June 2). The Screening Dilemma. from www.cancer.org Time Magazine on line. Retrieved August 26, 2011, American Cancer Society. (2011b). Cancer facts and fig- from http://www.time.com/time/specials/packages/ ures 2011. Atlanta, GA: American Cancer Society. article/0,28804,2075133_2075127_2075108-2,00.html Retrieved August 25, 2011, from www.cancer.org Reuben, S. H. (2010). Reducing environmental cancer American College of Obstetricians and Gynecologists. risk: What we can do now. President’s Cancer Panel. (2011). Breast cancer screening. Obstetrics and Gyne- U.S. Department of Health and Human Services cology, 118, 372. ACOG Practice Bulletin No. 122. 2008–2009 Annual Report. American College of Obstetrics and Gynecologists. United States Preventive Task Force. (2011). Recommen- (2009). ACOG announces new pap smear and cancer dations. Retrieved August 26, 2011, from http://www. screening guidelines. Retrieved August 26, 2011, from uspreventiveservicestaskforce.org www.acog.org Vidal L, LeBlanc WG, McCollister KE, Arheart KL, American College of Radiology. (2008). ACR practice Chung-Bridges K, Christ S, Caban-Martinez AJ, guideline for the performance of screening and diag- Lewis JE, Lee DJ, Clark J 3rd, Davila EP, nostic mammography. Retrieved August 26, 2011, Fleming LE. Cancer screening in US workers. from www.acr.org (2009). Cancer screening in US workers. American Anders, C. K., Hsu, D. S., Broadwater, G., Acharya C.R., Journal of Public Health, 99(1), 59–65. Foekens J.A., Zhang Y. et al. (2008). Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. Journal of Clinical Oncology, 26, 3324–3330. Fletcher, S. W. (2011). Breast cancer screening: A 35-year perspective. Epidemiologic Reviews, 133, 165–175. Cancer Survivor Grossman, S. (1998). A new era in colorectal screening and surveillance. The Permanente Journal, 2,1. ▶ Cancer Survivorship C 300 Cancer Survivorship

survivor from diagnosis throughout the remain- Cancer Survivorship der of his or her life and includes family, friends, and informal caregivers. Thus, survivorship was Steven C. Palmer broadly defined and inclusive of those with whom Abramson Cancer Center, University of the patient interacted intimately and from Pennsylvania, Philadelphia, PA, USA whom the patient received support. The impetus for this definition appears to be a desire to shift the focus away from the concept of the “cancer Synonyms victim” to one in which individuals were seen as actively coping with the range of physical, Cancer survivor psychological, and social sequelae that occur throughout the cancer experience from diagnosis to end of life. Definition Although this is the most common view of when cancer survivorship begins, other views Cancer survivorship, as a construct, is a recogni- exist, as well. Historically, the medical field has tion of the large number of individuals living endorsed a more circumscribed definition of with cancer and its aftermath. The term repre- a cancer survivor as an individual who has com- sents an expanded emphasis placing quality of pleted active cancer treatment and experienced life on a par with efforts to prolong and lengthen a period of at least 5 years of disease-free status. survival. Although there is general agreement Thus, survivorship is more or less equated with that “cancer survivorship” represents a distinct “cure” of primary disease, and the focus is clearly concept within the cancer experience trajectory, on the aftereffects of cancer and its treatment. the definition of who is a survivor and when one Others have defined a cancer survivor as transitions from patient to survivor status is less “someone who has completed initial treatment clear and depends more on sociological and polit- and has no apparent evidence of active disease, ical considerations than empirical data. The most or is living with progressive disease and may be common definition and that preferred by the receiving treatment but is not in the terminal Office of Cancer Survivorship at the National phase of illness, or someone who has had cancer Cancer Institute is that cancer survivorship starts in the past.” Again, this focuses away from the at “the time of diagnosis” and continues “through immediate effects of cancer and treatment and the balance of (the survivor’s) life. Family mem- toward issues of posttreatment well-being. bers, friends, and caregivers are also impacted by the survivorship experience and are therefore Characteristics of Cancer Survivors included in this definition.” As of 2008, there were approximately 11,900,000 cancer survivors in the United States, representing about 4% of the population. As can Description be seen in Table 1, cancer is disproportionately a disease of older adults, and almost 60% of Origin cancer survivors are aged 65 and older, although Cancer survivorship is a relatively new area of these individuals represent only about 12% of the study. Only since the 1970s could more than half total population, while less than 1% of cancer of those adults diagnosed with cancer expect to survivors are aged 19 or younger. Thus, issues live at least 5 years. “Cancer survivorship,” as of cancer survivorship occur most commonly in a construct, was introduced in the mid-1980s by the context of physical comorbidities that are the National Coalition for Cancer Survivorship. frequent among older adults. The definition introduced by the founder of that The number of cancer survivors is growing organization defines an individual as a cancer in the USA, due to earlier detection of breast, Cancer Survivorship 301 C

Cancer Survivorship, Table 1 Cancer survivorship in recurrence, increased mortality, and decreased USA by age group (2008) overall survival times. Age group Proportion of survivors Less than 19 years <1% Seasons of Cancer Survival 20–39 years 4% In 1985, Mullen described the “seasons” of sur- 40–64 years 36% vival, each of which is centered around a different +65 years 59% stage of disease and treatment, and each of which C focuses on a specific set of concerns. These sea- sons, acute, extended, and permanent survival, are described in Table 2. prostate, and colorectal cancer and, to a lesser extent, improved treatments. Currently, more Long-Term and Late Effects of Cancer and than 66% of adults diagnosed with cancer can Its Treatment expect to live at least 5 years and 75% of children As noted, long-term survival is now the norm for can expect to live at least 10 years following most cancer patients. This increased survival a cancer diagnosis. The total number of survivors time has come with a cost; cancer and its treat- is expected to increase at even a faster pace as the ment can and often do lead to decreased quality of number of individuals aged 60 and older life. Some of these effects are caused directly increases due to population growth and the by tumor burden itself, while others are related aging of the “baby boomer” population. Simulta- to treatment exposures. That is, they are the neously, the number of individuals who have unintended consequences of exposure to surgery, survived cancer for a long period of time is toxic chemotherapy, and ionizing radiation, expected to increase. Currently, more than 15% among other treatments. The side effects of of cancer survivors have lived 20 or more years cancer and its treatment can occur in physical, from initial diagnosis. psychological, or social domains and are often In terms of specific cancer sites, female breast conceptualized in terms of long-term or late cancer survivors represent the plurality of effects. survivors (22%), followed by prostate cancer sur- Long-term effects are those side effects that vivors (20%), colorectal cancer survivors (9%), arise during cancer treatment and persist follow- gynecological cancer survivors (8%), hematolog- ing the treatment period. These effects can last for ical cancer survivors (8%), urinary tract cancer months or years following cancer treatment, but survivors (7%), and melanoma survivors (7%). may resolve over time. For example, many peo- Racial and ethnic minorities are somewhat ple treated with certain chemotherapies develop underrepresented among cancer survivors, partic- peripheral nerve damage during treatment that ularly African Americans who represent approx- can affect hearing, balance, or touch for years imately 13% of the total population but only 8% afterward. Late effects on the other hand, are of cancer survivors. Considering all cancers, those symptoms or toxicities that are either African Americans are more likely than other undetected or absent during active treatment but racial groups to die following a cancer diagnosis arise only afterward. In many cases, late effects and less likely to survive for extended periods may not be recognized for years following cancer (e.g., 10 years). The precise reasons for this treatment. Research into the long-term and late disparity are presently unknown, but likely effects of cancer and its treatment is ongoing, include a complex interplay of social, cultural, better understood in cases of pediatric cancer and economic factors, with access to adequate than adult-onset cancer, and not well-developed medical care and poverty playing key roles. in terms of prevalence estimates or an under- What is clear is that following diagnosis, racial standing of when they might arise or how long and ethnic minorities experience relatively worse they might last before resolving. Although many outcomes including greater chance of cancer long-term and late effects of treatment are C 302 Cancer Survivorship

Cancer Survivorship, Table 2 Seasons of survival (Mullen 1985) Disease and Season treatment stage Physical concerns Psychosocial concerns Acute survival Diagnosis, primary Pain control, side effects Mortality issues, fear, distress, treatment coping with treatment Extended Remission, completion Physical limitations, treatment Fear of recurrence, body survival of primary treatment effects, loss of strength, fatigue image Permanent Cure of disease Long-term and late effects of treatment, Employment, insurance, survival second tumors, reproductive health coping with diminished health

specific to particular cancer sites or treatment extends along a continuum, ranging from regimens, there are a number of common symp- common normal feelings of vulnerability, sad- toms and experiences. ness, and fears to problems that can become dis- abling, such as depression, anxiety, panic, social Physical Effects of Cancer and Its Treatment isolation, and existential and spiritual crisis.” The most common physical symptom reported by Thus, distress encompasses a broad range of emo- cancer patients regardless of cancer site or treat- tional experiences that range from normative ment is fatigue, with more than 50% of cancer feelings of sadness and fear about the future to patients reporting fatigue at some point in the more chronic and interfering experiences such as survivorship trajectory. Pain is also a common depression and anxiety. long-term effect of cancer treatment, with more Psychosocial difficulties such as distress than 40% of cancer patients reporting pain at some appear to be fairly common among early cancer point and more than one-fifth reporting pain as survivors, although many of these difficulties are long as 2 years after diagnosis, most commonly mild in severity and tend to decrease over time resulting from surgical intervention. Other physi- from diagnosis. One exception to this appears to cal effects that can arise from cancer, surgery, be an increase in negative emotional experience radiation, chemotherapy, or hormonal exposures among individuals nearing end of life or entering include second cancers, bone difficulties such as into palliative care. osteoporosis, cardiovascular and coronary dys- function, fertility difficulties, hormonal deficien- Essentials of Survivorship Care cies, sexual dysfunction, hematological problems, To improve the outcomes achieved by the ever immunosuppression, lymphedema, pulmonary increasing number of cancer survivors, the Insti- difficulties, and problems with renal function. tute of Medicine has outlined four components essential to quality survivorship care. First, sur- Psychosocial Effects of Cancer and vivorship care should focus on prevention of new Its Treatment and recurrent cancers, as well as other late effects The term “distress” has been used to describe of treatment. Second, there should be an empha- the emotional experience of cancer survivors in sis on surveillance for new, recurrent, or spread a nonpathologizing and nonstigmatizing manner. of cancer as well as medical and psychosocial late The most commonly used conceptualization of effects. Third, there is a need for intervention to distress, from the National Comprehensive Can- assist survivors in dealing with the consequences cer Network, defines it as “a multifactorial of cancer and its treatment. Fourth, given the unpleasant emotional experience of a psycholog- complex medical environments in which cancer ical (cognitive, behavioral, emotional), social, survivors find themselves, coordination of care, and/or spiritual nature that may interfere with particularly between specialty and primary pro- the ability to cope effectively with cancer, its viders, is essential to ensuring that survivors’ physical symptoms and its treatment. Distress needs are met. Cancer Treatment and Management 303 C

References and Readings Description

Ganz, P. A. (2009). Survivorship: Adult cancer survivors. Cancer patients are at an increased risk for psy- Primary Care: Clinics in Office Practice, 36, 721–741. chological and physiological distress throughout Harrington, C. B., Hansen, J. A., Moskowitz, M., Todd, B. L., & Feuerstein, M. (2010). It’s not the treatment and management of their disease. over when it’s over: Long-term symptoms in cancer The most common types of treatment, as previ- survivors – A systematic review. International Journal ously discussed, impact the body physically, C of Psychiatry in Medicine, 40(2), 163–181. mentally, and emotionally. Behavioral and psy- Hewitt, M., Greenfield, S., & Stovall, E. (Eds.). (2006). From cancer patient to cancer survivor: Lost in transi- chosocial strategies can not only be used to sup- tion. Washington, DC: The National Academies Press. plement these medical treatments but also reduce Mullen, F. (1985). Seasons of survival: Reflections of the physical and psychological side effects of a physician with cancer. New England Journal of cancer treatment and management. The primary Medicine, 313, 270–273. symptom of concern and of focus in the psycho- social treatment of individuals with cancer is distress. The National Comprehensive Cancer Cancer Treatment and Management Network (NCCN), an organization that has com- posed widely used guidelines for distress man- Deidre Pereira and Megan R. Lipe agement, posits that the term “distress” is more Department of Clinical Health and Psychology, acceptable in its use because it carries a less stig- University of Florida, College of Public Health matizing connotation. NCCN defines distress in and Health Professions, Gainesville, FL, USA cancer as “A multifactorial unpleasant emotional experience of a psychological (cognitive, behav- ioral, emotional), social, and/or spiritual nature Synonyms that may interfere with the ability to cope effec- tively with cancer, its physical symptoms and its Chemotherapy; Radiation therapy; Surgery; treatment.” Surgical resection Patients are at an increased risk for distress if they have a history of a psychiatric disorder or substance abuse, are cognitively impaired, have Definition language, literacy, or physical barriers to com- munication, have severe comorbid illness, expe- Medical intervention in cancer commonly rience uncontrolled physical symptoms, have involves multiple modalities including surgery, spiritual/religious concerns, have inadequate systemic chemotherapy, and radiation therapy. social support, or have additional stressors For patients newly diagnosed with cancer, surgery including family conflict, financial stressors, is typically the first of these methods as it is com- dependent children, limited access to healthcare, monly used to confirm a diagnosis, determine the or have a history of abuse. Providers participating severity of the disease (i.e., stage and grade), and in in the care of cancer patients should assess for some cases, for “tumor debulking.” Radiation ther- these risks and also be aware of times associated apy is used in more than half of all patients with with increased vulnerability for distress. Periods cancer, either as a definitive treatment, or in of increased vulnerability are often marked by combination with surgical interventions and/or times of change or novelty in a patient’s cancer chemotherapy. Finally, chemotherapy involves experience or feelings of uncertainty. For exam- the use of drugs to target and destroy rapidly divid- ple, awaiting diagnosis and/or treatment, altering ing cancer cells. As a treatment, its effectiveness is treatment modality, transitioning into survivor- dependent upon the type and severity of disease, ship, recurrence, and end of life are often circum- but it can be used to shrink tumors, control the stances under which distress may be more likely spread of disease, or cure cancer (i.e., remission). to manifest. C 304 Cancer Treatment and Management

In addition, distress is associated with physical psychotherapy in individuals with moderate to side effects of disease and/or cancer treatment severe distress. Psychological interventions includ- including pain, fatigue, nausea, and insomnia. ing cognitive-behavioral therapy (CBT), support- These symptoms are very common in cancer ive psychotherapy, and family or couples therapy patients and often result from psychological have been shown to help cancer patients manage distress and physiological effects of cancer treat- distress and improve quality of life. Cognitive- ment. As such, there is a bidirectional relation- behavioral treatments in cancer often focus on ship among these symptoms and distress such increasing problem solving skills and addressing that unpleasant physical side effects may prompt maladaptive thought patterns that promote feelings distress while the experience of emotional dis- of depression, anxiety, and/or guilt. Behavioral tress may also exacerbate and maintain these management strategies are also used with cancer physical symptoms. patients to decrease the psychosomatic manifesta- Psychosocial cancer management and treat- tion of distress. Fatigue in cancer can be managed ment must first begin with a brief distress screen- through the practice of relaxation, distraction, ing. It is optimal that these be completed earlier in exercising to increase energy, improving sleep, a patient’s cancer experience (i.e., upon diagno- and emotional support. Individuals with insomnia sis). NCCN provides a brief, validated distress benefit from behavioral treatments that place focus screening tool that measures recent distress and on creating a comfortable sleep environment that the presence of factors (i.e., practical, family, promotes sleep (i.e., stimulus control), avoiding emotion, spiritual, or physical problems) that behaviors that contribute to poor sleep such as may contribute to distress. Patients who endorse drinking caffeine and napping, and addressing clinically significant levels of distress should any emotional concerns that may contribute to then be referred to the appropriate service(s), poor sleep. Behavioral techniques can also be depending on their individual needs. Cancer used in addition to anti-nausea/vomiting medica- patients experiencing distress may benefit from tions and analgesics to help patients relax and feel assistance from a mental health professional, more in control of nausea and/or pain following social worker, and/or chaplain. cancer treatment. Guided imagery allows the Patients referred to a mental health profes- patient to mentally transition to a more pleasant, sional should undergo a more comprehensive safe place, and to distract oneself from the nausea evaluation in order to further understand the dif- and/or pain. Likewise, cancer patients can utilize ficulties they are having and to inform treatment hypnosis or learn self-hypnosis in order to block decisions. These evaluations will commonly physical discomfort and pain during and after treat- assess for suicidality, mood or anxiety disorders, ment procedures. Lastly, progressive muscle relax- adjustment disorders, substance-abuse disorders, ation and biofeedback can also be used to help personality disorders, and cognitive impairments patients increase awareness of tension, anxiety, secondary to disease and/or cancer treatment. and other bodily changes in order to achieve relax- Sleep disorders are assessed through a thorough ation and prevent nausea, pain, or insomnia. sleep and medical history and objective evalua- The initial screening, comprehensive evalua- tions such as polysomnography. Results from tion, and treatment are essential to ensuring that these evaluations are disseminated to all other cancer patients navigate their experiences effec- providers involved in the patient’s care in order tively; however, it is also important to conduct to ensure that their comprehensive treatment plan assessments of distress at further points along the is tailored to their individual needs. cancer experience. As previously mentioned, Treatment for distress and its associated there are periods of time in which patients may symptoms secondary to cancer is multifaceted have an increased vulnerability to distress and it in nature. While psychotherapy is indicated in is during these transitional periods in which their patients with mild to severe distress, antidepres- distress should be reassessed and treated as sants and anxiolytics can be used to supplement necessary. Cancer, Bladder 305 C

Given its complex nature, physical and psy- chological distress throughout the process of can- Cancer, Bladder cer treatment should be assessed and managed through comprehensive involvement by all pro- Heather Honore´ Goltz1,2, Marc A. Kowalkouski1, viders in the patient’s healthcare team. This Stacey L. Hart3 and David Latini4 requires that the patient’s healthcare team func- 1HSR&D Center of Excellence, Michael E. tion in an environment in which interdisciplinary DeBakey VA Medical Center (MEDVAMC 152) C work is promoted and in which there is regular, Houston, TX, USA open communication among all providers 2Department of Social Sciences, University of involved in the patient’s care and management Houston-Downtown, Houston, TX, USA of their disease. 3Department of Psychology, Ryerson University, Toronto, ON, Canada 4Scott Department of Urology, Baylor College of Cross-References Medicine, Houston, TX, USA

▶ Cancer Prevention ▶ Cancer Survivorship Synonyms ▶ Cancer, Types of ▶ Cancer: Psychosocial Treatment Bladder carcinoma; Urothelial carcinoma of the bladder

References and Readings Definition Abeloff, M. D., Armitage, J. O., Niederhuber, J. E., Kastan, M. B., & Gillies McKenna, W. (2008). Clini- Bladder cancer research has almost exclusively cal oncology (4th ed.). Philadelphia: Churchill Livingstone. employed epidemiological or clinical research American Cancer Society. (2010). Fatigue in people with approaches, leaving it understudied from cancer. Retrieved May 26, 2011, from http://www. a behavioral medicine perspective. Yet, research cancer.org provides many opportunities for clinicians and American Cancer Society. (2010). Nausea and vomiting. Retrieved May 26, 2011, from http://www.cancer.org researchers to develop targeted bladder cancer American Cancer Society. (2010). Pain control: A guide prevention and survivorship interventions for for those with cancer and their loved ones. Retrieved mental health, diet and exercise, fatigue, smoking May 26, 2011, from http://www.cancer.org cessation, and other areas. National Cancer Institute. (2010). Nausea and vomiting PDQ. Retrieved May 26, 2011, from http://www.can- cer.gov National Cancer Institute. (2010). Pain PDQ. Retrieved May 26, 2011, from http://www.cancer.gov Description National Cancer Institute. (2010). Sleep disorders PDQ. Retrieved May 26, 2011, from http://www.cancer.gov National Comprehensive Cancer Network. (2011). The Bladder Anatomy and Histopathology NCCN clinical practice guidelines in oncology: Dis- Bladder cancer originates in the urinary bladder, tress management [Version 1.011]. Retrieved May 26, a hollow, muscular organ that collects urine from 2011, from http://www.nccn.org the kidneys via the ureters and excretes it via the urethra (Konety & Carroll, 2007; Pashos, Botteman, Laskin, & Redaelli, 2002). Before excretion, urine is stored in the lumen, which is Cancer Types surrounded by several cell layers comprising the bladder wall. The innermost layer, or urothelium ▶ Cancer, Types of (epithelium), directly contacts urine in the lumen. C 306 Cancer, Bladder

The second layer, or lamina propria, consists of 60 years and over. Race/ethnicity is also important. subepithelial connective tissue. The third layer, Caucasian Americans are twice as likely to develop the muscularis propria, contains smooth muscle. bladder cancer as African Americans. Despite The final layer contains perivesical fat tissue. lower incidence, African Americans are diagnosed Approximately 70–80% of newly diagnosed at advanced-stage disease and have higher mortal- US bladder cancers are confined to the ity rates, even after controlling for tumor charac- urothelium or lamina propria (i.e., Ta, Tis, T1; teristics (Konety & Carroll, 2007;Pashosetal., also called superficial or nonmuscle invasive 2002;Sextonetal.,2010). [NMIBC]; Sexton et al., 2010). Remaining diag- Environmental risk factors for developing noses are classified as muscle invasive (MIBC), bladder cancer include behavioral risk factors where the tumor has invaded the muscularis and occupational or chemical exposures (Pashos propria (i.e., T2, T3). Once a bladder tumor et al., 2002; Sexton et al., 2010). Less than 10% of begins invading surrounding organs, it becomes individuals diagnosed with bladder cancer report T4 (Jacobs, Lee, & Montie, 2010; Konety & a positive family health history. Smoking is the Carroll, 2007; Pashos et al., 2002). Most US primary environmental risk factor (Jacobs et al., bladder cancer patients (90%) have transitional 2010; Pashos et al., 2002; Sexton et al., 2010). cell carcinoma; the remaining have squamous Additional behavioral risk factors include diet/ cell carcinomas (5%), adenocarcinomas (1–2%), nutrition, specific herbal supplements, chronic primary small cell carcinoma, or other tumor urinary tract infection or inflammation, parasitic histologies (Sexton et al., 2010). infection, arsenic-contaminated water, and pelvic radiation. Chemicals linked to increased bladder Bladder Cancer Epidemiology and Risk cancer risk include aniline dyes, aromatic Factors amines, cyclophosphamide, and specific analge- Bladder cancer incidence, morbidity, and mortal- sics. At-risk occupations include autoworkers; ity vary by country (Botteman, Pashos, Redaelli, metalworkers; hairdressers; painters; and paper, Laskin, & Hauser, 2003). It is the fifth most leather, dye, and rubber plant workers (Jacobs common cancer in the United States and the et al., 2010; Sexton et al., 2010). second most commonly diagnosed urologic can- cer (Altekruse et al., 2010). From 1988 to 2008, Bladder Cancer Symptoms and Detection the number of US diagnoses increased by more Approximately 80–90% of patients diagnosed than 50% (Shariat et al., 2009). The United States with bladder cancer present with gross or micro- had an estimated 70,530 new bladder cancer scopic amounts of blood in the urine (hematuria; diagnoses and 14,680 deaths in 2010 (Jacobs Pashos et al., 2002). As there is a small latent et al., 2010). period between bladder cancer development and While many cases contain no explicit ties to symptom onset, hematuria is considered the most carcinogenic exposure, bladder cancer has several important symptom (Pashos et al.; Sexton et al., well-established biological, sociodemographic, 2010). Twenty percent of patients report other and environmental risk factors (Pashos et al., symptoms, including flank pain, painful urination 2002). Men are three to four times more likely to (dysuria), increased urgency or frequency of uri- receive a diagnosis than women. While men have nation, and inability to urinate (Pashos et al., higher lifetime risk for developing bladder cancer, 2002). Many bladder cancer symptoms, particu- women tend to present with later-stage disease and larly hematuria, are also symptomatic of urinary worse prognosis for 5-year survival, even control- tract infections, benign prostatic hyperplasia, and ling for tumor stage and grade (Jacobs et al., 2010; other benign conditions. Women may inadver- Pashos et al., 2002; Shariat et al., 2009). Bladder tently be misdiagnosed with gynecological con- cancer diagnoses among adolescents and young ditions or chronic urinary tract infections in lieu adults remain relatively rare (Sexton et al., 2010). of bladder cancer, contributing to delayed diag- Over three quarters of cases occur in individuals nosis (Jacobs et al., 2010). Cancer, Bladder 307 C

Physicians suspecting bladder cancer as prevent reimplantation or tumor formation, and a potential explanation for these symptoms per- reduce the chance of stage/grade progression form a physical exam and health-history assess- (Jacobs et al., 2010; Konety & Carroll, 2007; ment, including smoking history/status and Sexton et al., 2010). Common side effects of chemical/occupational exposures (Pashos et al., TURBT include bleeding and infection, whereas 2002). Clinicians may use intravenous or intravesical therapies are associated with dysuria, retrograde pyelography, ultrasound, computed fever, chills, and increased frequency of urination C tomography, positron emission tomography, or (Pashos et al., 2002; Shariat et al., 2009). BCG magnetic resonance imaging to check for urinary intravesical therapy is linked to erectile difficul- tract tumors (Sexton et al., 2010). More com- ties; there may also be treatment-related female monly, physicians rely on cystoscopy, involving sexual issues. Patients who have recurrent, high- insertion of a camera attached to flexible tubing grade NMIBC unresponsive to intravesical ther- into the bladder via the urethra while the patient is apy may eventually undergo partial or radical under local anesthetic (Pashos et al., 2002; Sex- cystectomy (Pashos et al., 2002; Sexton et al., ton et al., 2010). This procedure is considered the 2010; see below). “gold standard” for detecting bladder cancer and allows direct visualization of the urethra and Muscle-Invasive Bladder Cancer (MIBC) urothelium for tumors (Sexton et al.). Urine Treatment cytology, or a bladder wash, is often performed Individuals with MIBC may require more inten- adjunctive to cystoscopy to check for hematuria sive treatment. A “curative” treatment involves and bladder cancer cells pretreatment and during radical cystectomy, in which the entire bladder is posttreatment surveillance (Pashos et al., 2002; removed and some adjacent lymph nodes and Sexton et al., 2010; see below). Early detection of organs. Male patients may have the prostate and cancer recurrence is linked to reduced morbidity seminal vesicles removed, while women may and mortality, although only 40% of bladder can- have their uterus, fallopian tubes, ovaries, and cer survivors are adherent with surveillance anterior vagina wall removed (Konety & Carroll, (Schrag et al., 2003). Behavioral medicine inter- 2007). Patients then receive some form of urinary ventions are warranted in this particular area of diversion so that they can continue to collect and cancer control. excrete urine. Options include ileal conduit (i.e., urine is stored in a small portion of intestine and Nonmuscle-Invasive Bladder Cancer (NMIBC) drained through a stoma in the abdomen into an Treatment ostomy bag), neobladder (i.e., urine is collected in Transurethral resection of the bladder tumor a section of small intestine connected to the ure- (TURBT) is a first-line treatment for NMIBC. thra, allowing “normal” urination), and continent TURBT may be performed under anesthesia and cutaneous pouch (i.e., urine is stored in a small serves diagnostic, prognostic, and therapeutic portion of the intestine and drained through functions. Individuals with low risk for progres- a stoma via catheter; Jacobs et al., 2010; Konety sion (i.e., those with low-grade Ta tumors) may & Carroll, 2007; Pashos et al., 2002). be treated using TURBT alone. A repeat TURBT Postoperative complication rates and side may be performed to restage individuals with effects vary by diversion type. Daytime and high risk for progression (e.g., high-grade T1) nighttime incontinence, urinary retention, inter- within the first month of initial diagnosis (Jacobs nal bleeding, infection, wasting syndrome, diar- et al., 2010; Konety & Carroll, 2007; Sexton rhea, renal failure, and vitamin deficiencies are et al., 2010). Intravesical chemotherapies such some short- and long-term effects (Pashos et al., as mitomycin C and immunotherapies such as 2002). Additional side effects include sexual bacillus Calmette-Gue´rin (BCG) may be used dysfunction and infertility. While cystectomy is immediately post-TURBT or as maintenance considered the gold standard for MIBC treat- therapy to treat persistent microscopic tumors, ment, there are bladder-preservation alternatives C 308 Cancer, Bladder for poor surgical candidates due to age, health gender and race/ethnic disparities or psychoso- status, or other factors, or whose beliefs and cial factors (e.g., fear of recurrence, social con- values preclude surgery. Alternatives include straint and support, psychological distress, and TURBT alone or in combination with external- anxiety) (Botteman, Pashos, Hauser, Laskin, & beam radiation therapy and/or systemic chemo- Redaelli, 2003). Given the chronic nature of this therapy; however, survival rates are generally disease and related symptoms, bladder cancer lower than those from radical cystectomy survivors may benefit from targeted, culture- (Konety & Carroll, 2007). and literacy-appropriate patient health education interventions that impact lifestyle/behavior Bladder Cancer Surveillance change, symptom management, health-related The risk for bladder cancer recurrence is higher quality of life, and treatment/surveillance adher- than for any other cancer but varies by tumor ence. Limited patient education materials are grade. For example, the 3-year recurrence rates available from The American Cancer Society for Ta- and T1-stage tumors are 40–70% and (www.cancer.org), Bladder Cancer Advocacy 50–80%, respectively (Schrag et al., 2003). Network (www.bcan.org), and National Cancer Therefore, surveillance is an important disease- Institute (www.cancer.gov). There are few management strategy. research-tested bladder cancer interventions; Bladder cancer is also the most expensive however, interventions designed for prostate cancer in terms of cost per patient per year and cancer may be helpful to survivors. lifetime costs per patient. Current estimates place total patient costs at almost $3 billion US dollars per year, of which an estimated 60% goes Cross-References to monitoring and treatment of recurrence. NMIBC treatment and monitoring represents ▶ American Cancer Society a substantial portion of these costs (Botteman, ▶ Cancer and Smoking Pashos, Redaelli, et al., 2003). ▶ Health Disparities Physicians vary in terms of their surveillance ▶ National Cancer Institute protocols. American Urological Association ▶ Occupational Health guidelines recommend intensive follow-up ▶ Smoking and Health consisting of cystoscopy and cytology every 3 months in years 1 and 2, semiannual cystoscopy and cytology in years 3 and 4, and annual cystos- References and Readings copy and cytology in years 5–10 or for life (American Urological Association, 2007). Altekruse, S. F., Kosary, C. L., Krapcho, M., Neyman, N., Given that cystoscopic examinations are time- Aminou, R., Waldron, W., et al. (Eds.). (2010). SEER consuming and invasive, current adherence rates cancer statistics review, 1975–2007. Retrieved to bladder surveillance are estimated at about January 17, 2011, from http://seer.cancer.gov/csr/ 1975_2007 40% (Schrag et al., 2003). Individuals who are American Urological Association. (2007). American older, non-Caucasian, less-educated, and living Urological Association: Guideline for the manage- in urban geographic locales or low-income areas ment of nonmuscle invasive bladder cancer: (Stages are significantly more likely to be nonadherent Ta, T1, and Tis): 2007 update. Baltimore: Author. Botteman, M. F., Pashos, C. L., Hauser, R. S., Laskin, with surveillance (Schrag et al.). B. L., & Redaelli, A. (2003). Quality of life aspects of bladder cancer: A review of the literature. Quality of Issues in Bladder Cancer Survivorship Life Research, 12, 675–688. More than 500,000 bladder cancer survivors cur- Botteman, M. F., Pashos, C. L., Redaelli, A., Laskin, B. L., & Hauser, R. S. (2003). The health economics of rently live in the United States (Altekruse et al., bladder cancer: A comprehensive review of the 2010), yet little is known about their survivor- published literature. Pharmacoeconomics, 21, ship needs, particularly those stemming from 1315–1330. Cancer, Cervical 309 C

Jacobs, B. L., Lee, C. T., & Montie, J. E. (2010). Bladder exist in cervical cancer incidence rates, with cancer in 2010: How far have we come? CA: Cancer African American and Hispanic/Latino women Journal for Clinicians, 60, 244–272. Konety, B. R., & Carroll, P. R. (2007). Urothelial having elevated rates compared to White, Asian carcinoma: Cancers of the bladder, ureter, & renal American/Pacific Islander, and American Indian/ pelvis. In E. A. Tanagho & J. W. McAninch (Eds.), Alaska Native women (NCI, 2011). Smith’s general urology (17th ed.). New York: Cervical cancer typically begins as McGraw-Hill Professional. C Pashos, C. L., Botteman, M. F., Laskin, B. L., & a precancerous condition, known as cervical Redaelli, A. (2002). Bladder cancer epidemiology, diag- intraepithelial neoplasia (CIN; (ACS, 2011)). nosis, and management. Cancer Practice, 10(6), 311–322. Patients who do not undergo regular pelvic Schrag, D., Hsieh, L. J., Rabbani, F., Bach, P. B., Herr, H., exams and Pap tests are likely to develop one of & Begg, C. (2003). Adherence to surveillance among patients with superficial bladder cancer. Journal of the the two main types of cervical cancer: squamous National Cancer Institute, 95(8), 588–597. cell cervical carcinoma or cervical adenocarci- Sexton, W. J., Wiegand, L. R., Correa, J. J., Politis, C., noma. The majority of cases, approximately Dickinson, S. I., & Kang, L. C. (2010). Bladder cancer: 80–90%, are squamous cell carcinomas of the A review of non-muscle invasive disease. Cancer Control, 17(4), 256–268. cervix (ACS). Persistent infection with human Shariat, S. F., Sfakianos, J. P., Droller, M. J., papillomaviruses (HPVs) has been identified as Karakiewicz, P. I., Meryn, S., & Bochner, B. H. the cause of cervical cancer in the majority of (2009). The effect of age and gender on bladder can- cases. There are over 150 types of HPV, includ- cer: A critical review of the literature. British Journal of Urology International, 105, 300–308. ing 40 types that are transmitted sexually (NCI). HPV types 16 and 18 are considered to be carci- nogenic (cancer-causing) to humans and have been classified as Group 1 carcinogens by the Cancer, Cervical International Agency for Research on Cancer/ World Health Organization. Accordingly, cervi- Deidre Pereira1 and Stephanie L. Garey2 cal infection with HPV types 16 and 18 confers 1Department of Clinical and Health Psychology, high risk for the transformation of CIN to cervical College of Clinical Health and Health cancer and causes over 70% of all cervical can- Professions, University of Florida, Gainesville, cers (ACS). In contrast, HPV types 6 and 11 have FL, USA been classified as possibly carcinogenic to 2Department of Clinical and Health Psychology, humans (Class 2B carcinogens) and are mostly College of Public Health and Health Professions, implicated in the development of anogenital con- University of Florida, Gainesville, FL, USA dylomata (genital warts; (ACS)). Women who are sexually active at a young age or have many Synonyms sexually partners are at a greater risk for HPV infection. As of 2011, the Federal Drug Admin- Cancer of the uterine cervix; Cervical adenocar- istration (FDA) has approved the use of two vac- cinoma; Invasive cervical cancer; Squamous cell cines for the prevention of the most common carcinoma of the cervix (SCCC) types of HPV infection (ACS; NCI). One vaccine prevents four HPV types (6, 11, 16, and 18) and is Definition indicated for use in females and males 9–26 years of age. A second vaccine protects against two Cervical cancer is a slow-growing cancer that HPV types (16 and 18) and is indicated for develops in the lower portion of the uterus, use only in females 10–25 years of age (NCI). known as the cervix. Approximately 1 in every Additional risk factors for cervical cancer include 145 women will develop invasive cervical cancer smoking cigarettes and exposure to secondhand in her lifetime. In 2010, an estimated 12,200 smoke, a high number of full-term pregnancies, women were diagnosed with cervical cancer long-term use of oral contraceptives, and (ACS, 2010). Significant racial/ethnic disparities immunosuppression (ACS). C 310 Cancer, Colorectal

Screening for cervical cancer includes regular Cross-References pelvic exams and a Papanicolaou (Pap) test to screen for precancerous or malignant changes in ▶ Cancer Prevention cervical cells (ACS). If the Pap test detects abnor- ▶ Cancer Survivorship mal cells, an HPV DNA test is conducted to ▶ Cancer, Types of determine whether HPV infection is present ▶ Cancer: Psychosocial Treatment (NCI). Furthermore, a colposcopic examination ▶ Reproductive Health can be performed to identify abnormal areas on ▶ Women’s Health the cervix visually and allow for a biopsy of cervical tissue (ACS). If invasive cancer is iden- tified, additional imaging studies may be References and Readings conducted to determine if the cancer has metas- tasized (spread) to distant organs and facilitate American Cancer Society. (2010). Cancer facts & figures staging. Women who have early-stage cervical 2010. Atlanta, GA: Author. American Cancer Society. (2011). Cervical cancer. In Learn cancer often do not experience any symptoms; about cancer. Retrieved February 27, 2011, from http:// however, once the cancer has progressed and www.cancer.org/cancer/cervicalcancer/index spread to proximal tissues, women may experi- National Cancer Institute. (2011). Cervical cancer. In ence abnormal vaginal bleeding, unusual dis- Cancer topics. Retrieved February 27, 2011, from http://www.cancer.gov/cancertopics/types/cervical charge, and pain during intercourse (ACS). Treatment of cervical cancer can include surgery, chemotherapy, and radiation therapy. As with all cancers, the appropriate treatment choice depends largely on the stage of disease. Cancer, Colorectal Surgical methods for treating cervical cancer include cryosurgery, laser surgery, conization, Hiromichi Matsuoka hysterectomy, and trachelectomy (NCI). Pelvic Department of Psychocomatic Medicine, Kinki exenteration or lymph node dissection may be University Faculty of Medicine, Osakasayama, performed when there has been spread or recur- Osaka, Japan rence of cervical cancer (ACS; NCI). The most common types of chemotherapy that target cer- vical cancer include cisplatin, paclitaxel, Synonyms topotecan, ifosfamide, and 5-fluorouracil (5-FU; ACS)). Six to seven weeks of radiation treatment Colorectal cancer may also be used to treat cervical cancer (ACS). Certain stages of cervical cancer may require a combination of chemotherapy and radiation, Definition known as chemoradiation. The 5-year survival rate of cervical cancer is Colorectal cancer (CRC) is the third most fre- 71% (ACS). While the number of deaths due to quently diagnosed cancer in men and women in cervical cancer has decreased across the last sev- the United States. Patients with localized colon eral decades, mortality rates have remained cancer have a 90% five-year survival rate (Jemal steady since approximately 2003. African Amer- et al., 2009). ican women have the highest cervical cancer Colorectal cancer mortality can be reduced by mortality rates compared to all other racial/ethnic early diagnosis and by cancer prevention through groups, which may be partly due to the fact that polypectomy. Therefore, the goal of CRC screen- African American women are less likely to be ing (CRCS) is to detect cancer at an early, curable diagnosed with early-stage cervical cancer than stage as well as to detect and remove clinically White women (ACS). significant adenomas (Levin et al., 2008). Cancer, Colorectal 311 C

Screening tests that can detect both early with external authorities, unexpressive through cancer and adenomatous polyps are encouraged. suppression or denial of negative emotions, self- Current technology falls into two broad catego- sacrificing, and predisposed to experiencing ries: structural tests and stool/fecal-based hopelessness and depression. There is evidence tests. Regular screening with the fecal occult of connections among personality, stress and can- blood test (FOBT) or sigmoidoscopy facilitates cer, as well as among personality, stress, and the earlier detection of CRC and lowers mortality. autonomic, endocrinological, and immune sys- C Screening colonoscopy may decrease CRC inci- tems. These psychological characteristics can be dence through early detection and removal of considered as cancer risk factors. Nevertheless, precancerous polyps. Reported interventions to a type C or cancer-prone personality should be promote the FOBT have included patient understood in terms of its synergic interactions reminders through use of personal media, with genetic, biological, and environmental fac- approaches that reduce structural barriers such tors (Eysenck, 1994). as mailing of FOBT kits, and use of provider Significant barriers to advanced cancer assessment and feedback (Baron et al., 2008; patients receiving mental health treatment for Hardcastle et al., 1996; Kronborg, Fenger, distress have been reported in the literature. Olsen, Jorgensen, & Sondergaard, 1996; Mandel Monthly monitoring of distress in older patients et al., 1993; Selby, Friedman, Quesenberry, & using telephone monitoring and educational Weiss, 1992; Shapiro et al., 2008; Winawer materials, along with referral for appropriate et al., 1993). help, has been found to be efficient means of Other preventive health behaviors are posi- reducing anxiety and depression, compared with tively associated with CRCS, including a recent patients who received only educational materials mammogram or Pap test for women, a recent pros- (Kornblith et al., 2006). tate-specific antigen (PSA) test for men, a choles- Acupuncture, transcutaneous electrical nerve terol test, dental visit, seat belt use, fruit and stimulation, supportive group therapy, self-hyp- vegetable consumption, and physical activity nosis, and massage therapy may provide cancer (See ff et al., 2004). pain relief in dying patients (Pan, Morrison, Ness, CRC is predominantly a disease of Western- Fugh-Berman, & Leipzig, 2000). ized countries, indicating that components of the Western lifestyle may contribute to the risk. A large body of evidence has implicated Cross-References modifiable lifestyle factors as causes of colorectal cancer, including smoking, lack of physical activ- ▶ Aspirin ity, body composition, alcohol intake, and diet ▶ Colorectal Cancer (Shapiro, See ff, & Nadel, 2001). ▶ Lifestyle Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence References and Readings and mortality due to colorectal cancer. Benefit was greatest for cancers of the proximal colon, Baron, R. C., Rimer, B. K., Breslow, R. A., et al. (2008). which are not otherwise prevented effectively by Client-directed interventions to increase community screening with sigmoidoscopy or colonoscopy demand for breast, cervical, and colorectal cancer (Rothwell et al., 2010). screening. American Journal of Preventive Medicine, 35(1S), S34–S55. Type C has emerged as a behavioral pattern, Eysenck, H. J. (1994). Personality, stress and cancer pre- coping style, or personality type that predisposes diction and prophylaxis. Advances in Behavior people to or is a risk factor for the onset and Research and Therapy, 16, 167–215. progression of cancer. Type C has been described Hardcastle, J. D., Chamberlain, J. O., Robinson, M. H. E., et al. (1996). Randomized controlled trial of fecal- as a personality that is overcooperative, stoical, occult-blood screening for colorectal cancer. Lancet, unassertive, patient, avoiding conflict, compliant 348(9040), 1472–1477. C 312 Cancer, Lymphatic

Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009). Cancer statistics, 2009. CA: A Cancer Cancer, Lymphatic Journal for Clinicians, 59, 225–249. Kornblith, A. B., Dowell, J. M., Herndon, J. E., 2nd, Engelman, B. J., Bauer-Wu, S., Small, E. J., et al. Hiroe Kikuchi (2006). Telephone monitoring of distress in patients Department of Psychosomatic Research, aged 65 years or older with advanced stage cancer: National Institute of Mental Health, National A cancer and leukemia group B study. Cancer, 107(11), 2706–2714. Center of Neurology and Psychiatry, Kronborg, O., Fenger, C., Olsen, J., Jorgensen, O. D., & Tokyo, Japan Sondergaard, O. (1996). Randomized study of screen- ing for colorectal cancer with fecal-occult-blood test. Lancet, 348, 1467–1471. Levin, B., Lieberman, D. A., McFarland, B., et al. (2008). Synonyms Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: Lymphoma A joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Can- cer, and the American College of Radiology. CA: A Cancer Journal for Clinicians, 58, 130–160. Definition Mandel, J. S., Bond, J. H., Church, T. R., et al. (1993). Reducing mortality from colorectal cancer by screen- ing for fecal occult blood. Minnesota Colon Cancer Lymphatic cancer is a cancer of the lymphatic Control Study. The New England Journal of Medicine, system, which is a part of the immune system. It 328(19), 1365–1371. is also called lymphoma. Although lymphoma Pan, C. X., Morrison, R. S., Ness, J., Fugh-Berman, A., & Leipzig, R. M. (2000). Complementary and alternative commonly affects lymph node, it also affects medicine in the management of pain, dyspnea, and other organs such as spleen. nausea and vomiting near the end of life. The new World Health Organization classifi- A systematic review. Journal of Pain and Symptom cation (Swerdlow et al., 2008) is usually used to Management, 20(5), 374–387. Rothwell, P. M., Wilson, M., Elwin, C. E., Norrving, B., classify lymphoma, and lymphoma is divided Algra, A., Warlow, C. P., et al. (2010). Long-term into Hodgkin lymphoma and non-Hodgkin effect of aspirin on colorectal cancer incidence and lymphoma (B cell and T/NK cell). Staging is mortality: 20-year follow-up of five randomised trials. basically based on distribution of the lesions. Lancet, 376(9754), 1741–1750. Epub 2010 Oct 21. See ff, L. C., Nadel, M. R., Klabunde, C. N., et al. (2004). Non-Hodgkin lymphoma is clinically classified Patterns and predictors of colorectal cancer test use in into indolent, aggressive, and highly aggressive. the adult US population: Results from the 2000 Symptoms and signs of lymphoma are lymph- National Health Interview Survey. Cancer, 100(10), adenopathy which is without tenderness and 2093–2103. Selby, J. V., Friedman, G. D., Quesenberry, C. P., Jr., & mobile, fever, fatigue, nocturnal sweating, Weiss, N. S. (1992). A case–control study of screening weight loss, bloating sensation, etc. sigmoidoscopy and mortality from colorectal cancer. In Hodgkin lymphoma, radiotherapy with or The New England Journal of Medicine, 326(10), without chemotherapy is used for a limited stage 653–657. Shapiro, J. A., See ff, L. C., & Nadel, M. R. (2001). and chemotherapy is the first choice for an Colorectal cancer-screening tests and associated advanced stage. High-dose chemotherapy with health behaviors. American Journal of Preventive autologous hematopoietic stem cell transplanta- Medicine, 21(2), 132–137. tion is considered for recurrent or refractory cases. Shapiro, J. A., See ff, L. C., Thompson, T. D., Nadel, M. R., Klabunde, C. N., & Vernon, S. W. (2008). In non-Hodgkin lymphoma, treatment is Colorectal cancer test use from the 2005 National selected depending on the pathological classifi- Health Interview Survey. Cancer Epidemiology, Bio- cation and the grade of malignancy. In B cell markers & Prevention, 17(7), 1623–1630. indolent lymphoma, radiotherapy or surgical Winawer, S. J., Zauber, A. G., Ho, M. N., The National Polyp Study Workgroup, et al. (1993). Prevention of therapy is used for a limited stage and chemo- colorectal cancer by colonoscopic polypectomy. The therapy or careful follow-up without any therapy New England Journal of Medicine, 329, 1977–1981. is selected for an advanced stage. Monoclonal Cancer, Ovarian 313 C antibody called rituximab is also used. In aggres- an epithelial cell tumor, arising from cells on the sive B cell lymphoma, chemotherapy combined surface of the ovary, or a germ cell tumor, in with rituximab is generally used and radiotherapy which the cancer forms in the egg cells. Approx- is combined for a limited stage. High-dose che- imately 22,000 new cases of ovarian cancer were motherapy with autologous peripheral blood reported in the United States in 2010, and ovarian stem cell transplantation is conducted at first cancer ranks as the fifth most common cause of remission in a high-risk group. In highly aggres- death among women with cancer (American C sive B cell lymphoma, treatment which is used Cancer Society [ACS], 2010). Because ovarian for acute lymphoblastic leukemia is applied. cancer is difficult to detect during the early Although no standard therapy is established for stages, women are often diagnosed with T cell lymphoma, chemotherapy is often applied. advanced disease that has spread to the lymph Eradication of Helicobacter pylori is used for nodes or metastasized to other organs. The over- gastric mucosa-associated lymphoid tissue all 5-year survival rate for women diagnosed with (MALT) lymphoma. ovarian cancer is 46% (ACS, 2010). The course of treatment varies by tumor type and stage but Cross-References may include chemotherapy, radiation therapy, and/or surgery to remove the tumor and/or one ▶ Chemotherapy or both ovaries (oophorectomy).

References and Readings Description

Swerdlow, S. H., Campo, E., Harris, N. L., Jaffe, E. S., A diagnosis of ovarian cancer and its Pileri, S. A., Stein, J., et al. (Eds.). (2008). WHO classification of tumours of haematopoietic and lym- corresponding treatment has been associated phoid tissues. Lyon: IARC. with significant decrements in emotional, physi- cal, and functional quality of life (Arriba, Fader, Frasure, & von Gruenigen, 2010). Women with ovarian cancer often report pervasive fatigue, Cancer, Ovarian disrupted sleep, and limitations in their ability to be active. Moreover, younger women typically Ashley Nelson1 and Erin Costanzo2 experience loss of fertility, and many survivors 1Department of Psychiatry, School of Medicine report sexual concerns that persist well beyond and Public Health, University of Wisconsin- the period of physical recovery. Not surprisingly, Madison, Madison, WI, USA emotional distress is common, including symp- 2Department of Psychiatry, Carbone Cancer toms of depression and anxiety. Distress can per- Center, University of Wisconsin-Madison, sist well after treatment ends, with survivors Madison, WI, USA commonly reporting fear of a cancer recurrence and significant anxiety around follow-up clinic visits and diagnostic tests (Arriba et al., 2010). Synonyms Research is also beginning to delineate biobe- havioral mechanisms by which behavioral factors Ovarian carcinoma; Ovarian neoplasm may alter physiological pathways associated with ovarian tumor growth and development, includ- ing effects on immunosuppression, inflammation, Definition and angiogenesis (growth of new blood vessels to nourish the tumor) (Costanzo, Sood, & Ovarian cancer is a malignancy of the tissue of Lutgendorf, 2011). For example, ovarian cancer the ovary and most commonly consists of either patients who report greater distress and have C 314 Cancer, Prostate more limited social support show poorer NK cell in ovarian cancer. Journal of Clinical Oncology, 23, activity in peripheral blood and tumor infiltrating 7105–7113. Lutgendorf, S. K., Weinrib, A. Z., Penedo, F., Russell, D., lymphocytes as compared to women with lower DeGeest, K., Costanzo, E. S., et al. (2008). Interleukin- distress and better support (Lutgendorf et al., 6, cortisol, and depressive symptoms in ovarian 2005). Greater depressive symptoms and less cancer patients. Journal of Clinical Oncology, 26, social support have also been associated with 4820–4827. Sood, A. K., Bhatty, R., Kamat, A. A., Landen, C. N., Han, elevated levels of pro-angiogenic cytokines L., Thaker, P. H., et al. (2006). Stress hormone- including interleukin-6 and vascular endothelial mediated invasion of ovarian cancer cells. Clinical growth factor (VEGF) (Costanzo et al., 2011). Cancer Research, 12, 369–375. Moreover, ovarian cancer patients who report more depressive symptoms show higher and less variable levels of nocturnal cortisol (Lutgendorf et al., 2008). Stress hormones, including norepi- nephrine and epinephrine, have been shown to Cancer, Prostate increase VEGF production and the in vitro inva- siveness of ovarian tumor cells (Lutgendorf et al., Marc A. Kowalkouski1, Heather Honore´ Goltz1,2, 2003; Sood et al., 2006). These findings suggest Stacey L. Hart3 and David Latini4 that behavioral factors may play an important 1HSR&D Center of Excellence, Michael E. role not only in quality of life, but also in ovarian DeBakey VA Medical Center (MEDVAMC cancer outcomes. 152), Houston, TX, USA 2Department of Social Sciences, University of Houston-Downtown, Houston, TX, USA Cross-References 3Department of Psychology, Ryerson University, Toronto, ON, Canada ▶ Cortisol 4Scott Department of Urology, Baylor College of ▶ Epinephrine Medicine, Houston, TX, USA ▶ Natural Killer Cell Activity ▶ Norepinephrine/Noradrenaline ▶ Vascular Endothelial Growth Factor (VEGF) Synonyms

Carcinoma of the prostate; Neoplasm of the pros- tate; Prostatic adenocarcinoma References and Readings

American Cancer Society. (2010). Cancer facts & figures 2010. Atlanta, GA: Author. Definition Arriba, L. N., Fader, A. N., Frasure, H. E., & von Gruenigen, V. E. (2010). A review of issues surround- Prostate cancer originates in the prostate, ing quality of life among women with ovarian cancer. Gynecologic Oncology, 119, 390–396. a walnut-shaped gland in the male reproductive Costanzo, E. S., Sood, A. K., & Lutgendorf, S. K. (2011). system. Fluid secreted by the prostate nourishes Biobehavioral influences on cancer progression. and transports sperm. Over 95% of cancers of the Immunology and Allergy Clinics of North America, prostate are adenocarcinomas, originating in 31, 109–132. Lutgendorf, S. K., Cole, S., Costanzo, E., Bradley, S., glandular tissue. The prostate is made up of Coffin, J., Jabbari, S., et al. (2003). Stress-related three distinct zones of glandular tissue. Approx- mediators stimulate vascular endothelial growth factor imately 70% of cancers develop in the peripheral secretion by two ovarian cancer cell lines. Clinical zone, 10–20% in the transition zone, and 5–10% Cancer Research, 9, 4514–4521. Lutgendorf, S. K., Sood, A. K., Anderson, B., McGinn, S., in the central zone. Most prostate cancers are Maiseri, H., Dao, M., et al. (2005). Social support, slow growing, and survival rates are high, partic- psychological distress, and natural killer cell activity ularly for men with localized disease. Cancer, Prostate 315 C

Description cancer has spread to other parts of the body. A Gleason score (range: 2–10) is also calculated Prostate Cancer Epidemiology to evaluate the growth rate of the cancer, depen- Aside from skin cancer, prostate cancer is the dent on the appearance of tumor cells under most common malignancy and the second most microscope. A high Gleason score indicates common cause of cancer death among men in the advanced disease. Together, tumor stage and United States. Roughly 1 in 6 men will be diag- Gleason score are used to determine prognosis C nosed with prostate cancer in their lifetime. In and to direct treatment decisions. Today, nearly 2010, an estimated 220,000 incident cases of all prostate cancers are detected when tumors prostate cancer were diagnosed in America, are confined to the prostate (i.e., Gleason score mostly among men over age 70. Additionally, 6 or 7). more than 30,000 prostate cancer deaths were projected, second only to lung cancer for cancer Prostate Cancer Treatment deaths among American men. Many treatment options are available to men The etiology of prostate cancer is not well diagnosed with localized prostate cancer (e.g., understood. However, the male sex hormone tes- active surveillance, radiotherapy, and surgery). tosterone, particularly at high levels, can acceler- However, there is currently no consensus regard- ate the reproduction and growth of existing ing optimal treatment. Each treatment impacts cancer cells in the prostate. Increasing age is the quality of life differently – ranging from urinary, most important risk factor for prostate cancer. sexual, and bowel dysfunction to more systemic A positive family history is also associated with concerns, such as weight gain, bone loss, hot increased risk. Additionally, African American flashes, and depression. Therefore, individuals men have higher incidence and mortality rates must make decisions based upon their own than Whites. Since 1975, incidence rates in the personal preferences, clinical characteristics, United States have fluctuated, slightly decreasing and a variety of external factors, including pro- since 2000. Substantial changes can be traced to vider recommendations. Most men experience the introduction of the prostate-specific antigen decreased sexual potency, regardless of treat- (PSA) screening test in the 1980s. ment. However, men undergoing radical prosta- tectomy suffer most from urinary problems, Prostate Cancer Screening while radiotherapy is associated with poor Screening for prostate cancer includes serum bowel function. The physical side effects associ- PSA testing and digital rectal examination. Due ated with prostate cancer treatment can severely to the widespread implementation of PSA testing, affect a man’s quality of life. Additionally, the over 90% of prostate cancers are detected at early emotional and psychological distress associated stages, when the disease is localized to the pros- with symptoms, as well as complications in tate and easiest to treat. However, PSA testing is spouse or partner relationships, can further not without controversy, and guidelines for diminish quality of life. Given the slow-growing screening differ. Please see Prostate-Specific nature of most prostate cancers, some individuals Antigen for additional information. may consider deferring treatment to maintain better quality of life. Active surveillance involves Prostate Cancer Diagnosis routine monitoring of patients diagnosed with Prostate cancer may be suspected if the PSA level early-stage, low-grade prostate cancer, in lieu of is greater than 4 ng per mL. When prostate cancer definitive treatment. However, this option carries is suspected, a core needle biopsy is performed its own burden, primarily the uncertainty and for tissue analysis. If the tissue biopsy confirms anxiety associated with having an “untreated” the presence of cancer, further testing (e.g., com- cancer. For men with advanced stages of disease, puted tomography or magnetic resonance imag- additional treatment options are available (e.g., ing) may be completed to determine whether the hormonal therapy, chemotherapy). C 316 Cancer, Prostate

Current Medical Research and Interventions prostate cancer patients and survivors. Only one in Prostate Cancer intervention has been developed to provide psy- A major concentration in current prostate cancer chosocial support for men on active surveillance. research focuses on the evaluation of potential Little data exist on gay and bisexual men with factors affecting the observed racial disparity. Sev- prostate cancer. No interventions have focused eral projects are attempting to identify genetic and on the particular needs of single men, for whom other variants that may increase incidence and treating erectile dysfunction related to prostate mortality in African American men. Furthermore, cancer may be particularly challenging. there is an emphasis on identifying additional bio- markers to improve detection and prognostic accu- racy. Studies are also being conducted to compare Cross-References the effectiveness of active surveillance for disease management with immediate treatment. Finally, ▶ Prostate-Specific Antigen (PSA) for men with advanced hormone-refractory dis- ease, improved chemotherapy regimens are being evaluated (e.g., docetaxel and cabazitaxel). References and Readings

American Cancer Society. (2010). Current Behavioral Medicine Research and Cancer facts and figures 2010. Atlanta, GA: Author. Interventions in Prostate Cancer Bailey, D. E., Jr., Wallace, M., & Mishel, M. H. (2007). Given the array of treatment options available to Watching, waiting and uncertainty in prostate cancer. men and the lack of consensus concerning best Journal of Clinical Nursing, 16, 734–41. Eton, D. T., & Lepore, S. J. (2002). Prostate cancer and practices, decision-making tools are essential to HRQOL: A review of the literature. Psychooncology, assist in determining which treatment option is 11, 307–26. most in congruence with their values and lifestyle Gore, J. L., Gollapudi, K., Bergman, J., Kwan, L., preferences. In a review of treatment decision-aid Krupski, T. L., & Litwin, M. S. (2010). Correlates of bother following treatment for clinically localized studies, aids were found to decrease distress, prostate cancer. Journal of Urology, 184, 1309–15. increase knowledge, and support shared decision Green, G. L., Sands, L. P., Latini, D. M., Kaniu, P., Barker, making. J. C., Chren, M. M., et al. (2009). Values insight and Additionally, only a limited number of evi- balance scales (VIBES-PC): Psychometric character- istics in the prostate cancer clinical setting. Annals of dence-based behavioral medicine interventions Behavioral Medicine, 37, S37. have been developed to address quality-of-life Knight, S. J., & Latini, D. M. (2009). Sexual side effects and concerns in this population. The first of these prostate cancer treatment decisions: Patient information interventions was developed from work done in needs and preferences. Cancer Journal, 15,41–4. Latini, D. M., Elkin, E., Cooperberg, M. R., Sadetsky, N., breast cancer and shown to be effective in DuChane, J., Carroll, P. R., et al. (2006). Differences improving quality of life. Unfortunately, the in clinical characteristics and disease-free survival for results have been more mixed in interventions Latino, African-American, and non-Latino white men focusing on improving psychosocial distress. with localized prostate cancer: Data from CaPSURE™. Cancer, 106, 789–795. Reductions in distress have generally been mod- Latini, D. M., Hart, S. L., Coon, D. W., & Knight, S. J. est and of short duration. However, other research (2010). Sexual rehabilitation after prostate cancer: suggests that men adjust to changes in functional Current interventions and future directions. In V. T. status and symptom distress improves over time. DeVita, T. S. Lawrence, & S. A. Rosenberg (Eds.), Cancer: Principles & practice of oncology – Advances Developing these materials and programs in oncology (Vol. 1, pp. 22–28). Philadelphia: should be an immediate priority for behavioral Lippincott Williams & Wilkins. medicine researchers. Promising results have Lin, G. A., Aaronson, D. S., Knight, S. J., Carroll, P. R., & been shown in adapting cognitive behavioral Dudley, R. A. (2009). Patient decision aids for prostate cancer treatment: A systematic review of the literature. stress-management programs, peer-support, CA: A Cancer Journal for Clinicians, 59, 379–90. nurse-led, and telephone-based interventions. Litwin, M. S., Hays, R. D., Fink, A., Ganz, P. A., Leake, Less work has been done with subgroups among B., Leach, G. E., et al. (1995). QoL outcomes in men Cancer, Testicular 317 C

treated for localized prostate cancer. Journal of the estimated 8,290 new diagnoses and about 350 American Medical Association, 273, 129–135. deaths due to testicular cancer each year. It is Rottman, N., Dalton, S. O., Bidstrup, P. E., Wurtzen,€ H., Hoybye, M. T., Ross, L., et al. (2011). No improve- most common in young and middle-aged men ment in distress and quality of life following psycho- such that about 9 out of 10 testicular cancers social cancer rehabilitation. A randomised trial. occur in men between the ages of 20 and 54. Psychooncology, doi: 10.1002/pon.192. Accessed Treatment is very successful and the risk of 8 Feb 2011 [Epub ahead of print] C Tanagho, E. A., & McAninch, J. W. (Eds.). (2008). dying from testicular cancer is low. Smith’s general urology (17th ed.). New York: Factors that may increase the risk for develop- McGraw-Hill. ing testicular cancer include abnormal testicle development, such as Klinefelter’s syndrome, undescended testicle (cryptorchidism), personal or family history of testicular cancer, age, and ethnicity. Non-Hispanic white men are more likely Cancer, Testicular than African-American and Asian-American men to develop testicular cancer. The risk of Hispanic/ Catherine Benedict Latino men developing this type of cancer is Department of Psychology, University of Miami, between that of Asians and non-Hispanic whites. Coral Gables, FL, USA Signs and symptoms of testicular cancer include a lump or enlargement in either testicle; a feeling of heaviness in the scrotum; a sudden Synonyms collection of fluid in the scrotum; pain or discom- fort in a testicle, scrotum, abdomen, or lower Nonseminoma; Seminoma; Testicular neoplasms back; and enlargement or tenderness of the breasts. However, many men do not experience symptoms, even when the cancer has spread to Definition other organs.

Testicular cancer is a type of cancer that forms in the tissue of one or both testicles, the male Diagnosis and Treatment reproductive glands located in the scrotum. There are several different types of testicular Initial diagnosis generally involves an ultrasound cancer but most cases originate in germ cells or biopsy. To determine whether the cancer has (cells that make sperm) and are called testicular spread outside of the testicle, a computerized germ cell tumors. Testicular germ cell tumors tomography (CT) scan to look for signs of cancer may be further categorized into seminomas and in the abdominal lymph nodes or blood tests to nonseminomas. Seminoma tumors are a slower look for elevated tumor markers may be used. growing and less aggressive form of testicular The staging of the cancer will depend on the cancer. They are usually isolated to the testicle results of these tests. There are three stages of or testes and are particularly sensitive to radiation testicular cancer: Stage I cancer is limited to the treatment. Nonseminoma tumors are faster grow- testicle (localized); Stage II cancer has spread to ing and more aggressive. This form of testicular the lymph nodes in the abdomen (regional); and cancer tends to occur in younger men. Stage III cancer has spread to other parts of the body and most commonly includes the lungs, liver, bones, and/or brain (distant). Description Cross-References Testicular cancer is not common and accounts for only 1% of all cancers in men. There are an ▶ American Cancer Society C 318 Cancer, Types of

References and Readings Cancer includes many forms of disease, and there are more than 100 different types of cancer. Chung, P., Mayhew, L. A., Warde, P., Winquist, E., & Most cancers are named for the organ or type of Lukka, H. (2010). Management of stage I cell from which they originate. Cancer types can seminomatous testicular cancer: A systematic review. Clinical Oncology, 22(1), 6–16. also be grouped into broader categories. Feldman, D. R., Bosl, G. J., Sheinfeld, J., & The main categories of cancer include: Motzer, R. J. (2008). Medical treatment of advanced Carcinoma – cancer that begins in the skin or in testicular cancer. Journal of the American Medical tissue that lines or covers internal organs Association, 299(6), 672–684. Glendenning, J. L., Barbachano, Y., Norman, A. R., Sarcoma – cancer that arises from bone, cartilage, Dearnaley, D. P., Horwich, A., & Huddart, R. A. fat, muscle, blood vessels, or other connective (2010). Long-term nerologic and peripheral vascular or supportive tissue toxicity after chemotherapy treatment for testicular Leukemia – cancer that starts in blood-forming cancer. Cancer, 116(10), 2322–2331. Howlader, N., Noone, A. M., Krapcho, M., Neyman, N., tissue such as the bone marrow Aminou, R., Waldron, W., et al. (Eds.). (2011). SEER Lymphoma and myeloma – cancers that begin in cancer statistics review, 1975–2008. Bethesda, the cells of the immune system MD: National Cancer Institute. Retrieved from Central nervous system cancers – cancers that http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to the begin in the tissue of the brain or spinal cord SEER web site, 2011. The cancers that are diagnosed with the greatest Huyghe, E. (2008). Testicular cancer. In: Editor-in-Chief: frequency in the United States are bladder cancer, K. Heggenhougen, Editor(s)-in-Chief, International breast cancer, colorectal cancer, endometrial encyclopedia of public health (pp. 309–318). Oxford: Academic Press. cancer, kidney cancer, leukemia, lung cancer, mel- van den Belt-Dusebout, A. W., de Wit, R., Gietema, J. A., anoma, non-Hodgkin lymphoma, pancreatic can- Horenblas, S., Louwman, M. W., Ribot, J. G., cer, prostate cancer, and thyroid cancer. Hoekstra, H. J., Ouwens, G. M., Aleman, B. M., & Some behavioral factors have been reported to van Leeuwen, F. E. (2007). Treatment-specific risks of second malignancies and cardiovascular disease in have an association with the incidences of cancer, 5-year survivors of testicular cancer. Journal of Clin- cancer screening, cancer recurrence, and cancer ical Oncology, 25(28), 4370–4378. mortality. For example, cigarette smoking con- tributes significantly to mortality rates for lung cancer, oral cancer, and cancers of the esophagus, larynx, bladder, stomach, pancreas, kidney, and cervix. Cancer, Types of Each type of cancer has characteristic- associated behavioral factors (see the section on Yoshinobu Matsuda a particular cancer for more information). National Hospital Organization, Kinki-Chuo Chest Medical Center, Sakai shi, Osaka, Japan Cross-References

Synonyms ▶ Breast Cancer ▶ Cancer, Bladder Cancer types ▶ Cancer, Cervical ▶ Cancer, Colorectal ▶ Cancer, Lymphatic Definition ▶ Cancer, Ovarian ▶ Cancer, Prostate Cancer is a term used for a disease in which ▶ Cancer, Testicular abnormal cells divide uncontrollably and invade ▶ Carcinoma other tissues. ▶ Kaposi’s Sarcoma Cancer: Psychosocial Treatment 319 C

References and Readings administered in both individual and group set- tings at multiple points along the cancer contin- Holland, J. C. (2009). Psycho-oncology (2nd ed.). New uum, from before diagnosis among people at York: Oxford University Press. elevated risk for cancer, to many years after National Cancer Institute. www.cancer.gov active treatment has completed. Psychosocial therapies have been shown in numerous studies to improve not only psychological (e.g., reduce C Cancer: Psychosocial Treatment distress) and quality of life outcomes, but also physical outcomes (e.g., improve immune func- Frank J. Penedo1, Catherine Benedict2 and tion and physical functioning) among cancer sur- Bonnie McGregor3 vivors in need of therapy. 1Department of Medical Social Sciences & Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Description IL, USA 2Department of Psychology, University of Natural History Miami, Coral Gables, FL, USA A cancer diagnosis can be considered an existen- 3Fred Hutchinson Cancer Research Center, tial crisis in the lives of many of those affected and Seattle, WA, USA can result in increased distress, changes in emo- tional roles, social roles, physical functioning, and quality of life for most people who are diagnosed. Synonyms Cancer patients have higher rates of clinically significant psychological disorders than their Behavioral oncology; Psycho-oncology; Psycho- non-diagnosed age-matched peers. Several factors social intervention; Psychosocial oncology tend to influence the extent of psychological dis- tress in response to a cancer diagnosis. These include younger age at diagnosis, history of mental Definition illness and premorbid psychological functioning, stage at diagnosis and prognosis, and social Psychosocial treatment in oncology covers support or other resources available (e.g., health a broad range of effective therapies that have insurance). As they do with other major life events, yet to become the standard of care for most individuals with a cancer diagnosis rely on cancer patients. Psychosocial therapies help a variety of strategies to cope with the changes cancer patients and their families emotionally their diagnosis and treatment bring. Notably, adjust to diagnosis and treatment, cope with most patients do not experience clinically signifi- treatment-related side effects (e.g., fatigue, pain, cant symptoms of distress or dysfunction and, over nausea), improve adherence to chemotherapy time, typically 1–2 years, most patients will regimens, and improve health behaviors. weather the crisis and return to baseline levels of Therapies can include cognitive behavioral functioning. However, for a significant number of therapy, hypnosis and guided imagery, mindful- individuals, full emotional and physical recovery ness-based therapies, cognitive behavioral stress can take much longer. Psychosocial intervention management, couple- and family-based therapy, can facilitate emotional and physical adjustment to play therapy for children, and motivational and recovery from cancer diagnosis and treatment. interviewing for behavior change. Psychosocial therapy is typically administered by clinical psy- Indications and Assessment chologists, psychiatrists, social workers, nurses, Psychosocial intervention is indicated not only and more recently, via web-based interventions when the patient is reporting elevated levels of and telephone counseling. This therapy can be distress, depression, or anxiety (which should be C 320 Cancer: Psychosocial Treatment assessed regularly during cancer treatment and components in multimodal intervention efforts posttreatment follow-up visits, see below), but include techniques such as relaxation training also when a patient reports difficulty with pain (e.g., guided imagery) to lower arousal, disease management, fatigue, cognitive complaints, or information and management, an emotionally sup- problems with sexual functioning. Assessment portive environment where participants can and patient education regarding available address fears and anxieties, behavioral and cogni- psychosocial interventions is warranted at routine tive coping strategies, and social support skills intervals during cancer treatment and care, as training. Therapeutic processes by which partici- many patients who might benefit from interven- pants benefit from intervention include giving and tion may not be reporting symptoms at the time receiving information, sharing experiences, reduc- and early intervention can be effective prophy- ing social isolation, and providing patients with laxis against later symptom development. coping skills that facilitate self-efficacy and sense Commonly used instruments to assess psychoso- of control over the cancer experience. Some evi- cial and physical well-being include a distress dence suggests that cancer patients may benefit thermometer or validated measures of mood and more from structured interventions than purely affect, such as the Hospital Anxiety and Depres- supportive ones; this may be due to learning skills sion Scale (HADS). To address concerns with which they can more effectively cope with regarding changes in cognitive functioning, cancer-related changes after the intervention has neuropsychological testing may be warranted. ended (e.g., stress management). Interventions For those who experience severe levels of distress may also be couple or family based, depending and/or meet clinical criteria for a mental health on the goals of therapy and targeted outcomes, and disorder, evaluation for pharmacologic treatment may be administered at all phases of the cancer may be warranted. continuum, from post-diagnosis and treatment decision making to end of life or long-term survi- Psychosocial Treatment Modalities vorship time periods. Such interventions can be Several psychosocial intervention models in delivered via several modalities including face-to- cancer have shown success in reducing distress, face and technology-based individual and group- improving quality of life, and facilitating the based formats. overall posttreatment adjustment period. Psycho- The model in Fig. 1 proposes that cancer social treatment approaches have ranged from patients and survivors may benefit from psycho- open support groups and psychoeducational social interventions that target multiple programs that are based on information components. For example, teaching anxiety reduc- provision, to supportive group therapy approaches tion skills can provide a way to reduce anxiety, and individual treatments that are structured to tension, and other forms of stress responses and, provide a nurturing environment to express con- thus, help the survivor achieve a sense of mastery cerns over the multiple challenges associated with over disease-related and general stressors. The use cancer survivorship. Both individual and group- of cognitive restructuring techniques can help based interventions based on cognitive behavioral patients identify links between thoughts, emo- intervention models that blend a variety of thera- tions, and bodily changes, and increase their abil- peutic techniques (e.g., cognitive restructuring, ity to identify commonly used distorted thoughts relaxation training) have shown success in and understanding of how these thoughts can improving health-related quality of life across interfere with emotional well-being, effective multiple cancer populations. Other intervention management of the disease, and multiple domains approaches include mindfulness-based stress of quality of life. Participants in these interven- reduction, emotional expression, symptom man- tions can also benefit from techniques that chal- agement, health behavior change, and motiva- lenge cognitive, behavioral, and interpersonal tional interviewing. A significant amount of coping strategies by increasing awareness of the research has shown that effective therapy use of maladaptive coping strategies to deal with Cancer: Psychosocial Treatment 321 C

Psychosocial Treatment Targets

Psychosocial Treatment Provide Anxiety Reduction Skills Outcomes

Modify Negative Appraisals Improved Mood & Social Relations Quality of Life & Build Coping Skills & Self-Efficacy Health Outcomes C Reduced Arousal Facilitate Emotional Expression & Health Related Quality of Life Communication Skills Improved Treatment Compliance Cancer-Specific Reduce Social Isolation Quality of Life Improved Health Reduce Risk Behavior & Behaviors Health Outcomes Enhance Treatment Adherence

Disease Related Factors Treatment Moderators

Disease Severity & Status SES, Age, Ethnicity & Culture Treatment Side Effects Personality, Pre-Morbid Function Social Stressors Available Inter- & Intrapersonal Resources

Cancer: Psychosocial Treatment, Fig. 1 Conceptual model of psychosocial treatment interventions stress and disease-related challenges. Therefore, as greater levels of anxiety, depression, and attention is given to replacing inefficient and indi- interpersonal disruption, as well as existential rect ways of dealing with stressors and promotes concerns regarding the end of life. Similarly, both emotion and problem-focused strategies treatment type and timing within the cancer while increasing patients’ ability to adaptively survivorship continuum will pose varying psy- express both positive and negative emotions. chosocial and physical responses that need to be These intervention models also promote identify- considered. Some treatments are characterized by ing and utilizing beneficial sources of social sup- immediate functional limitations with a slow port, as well as providing self-management skills recovery that invariably does not reach baseline to engage in positive lifestyle changes and behav- functioning over 1–2 years posttreatment. In iors. Communication skills are also targeted, par- contrast, other treatments have a more insidious ticularly those specific to interacting with health side effect trajectory with the greatest conse- care professionals and communicating concerns quences surfacing up to 1 year posttreatment. about functional limitations and treatment-related Therefore, an awareness and knowledge of the side effects with the spouse/partner, family, and trajectories of treatment-related side effects must friends. be considered as these symptoms will vary by Within the intervention model, disease-related treatment type. It is also critical to understand factors provide several considerations for psy- ongoing stressors not specifically related to chosocial treatment approaches. Disease severity cancer such as financial burdens or other major (localized vs. advanced disease) and status life events that may be impacting quality of life (disease free survival vs. recurrent disease) as these will also influence the efficacy of psy- significantly influences the experience of the chosocial treatments. Furthermore, a series of cancer patient and survivor. For example, possible treatment moderators need to be consid- advanced and recurrent diseases are character- ered. Older patients will be more likely to have ized by greater psychosocial compromises such multiple comorbidities and functional limitations C 322 Cancer: Psychosocial Treatment that will impact health-related quality of life Biological Effects of Intervention outcomes. Socioeconomic status can play Psychological distress can influence tumor a significant role in treatment adjustment as it progression via many different pathways has been consistently associated with (e.g., genetic changes, immune surveillance, health-related quality of life outcomes via its pro-angiogenic processes). For example, there influence on treatment compliance and are data to suggest that psychological interven- follow-up. It is also critical to have a good tion can influence important neuroendocrine understanding of pretreatment psychological (e.g., cortisol) and immune function pathways, functioning. Cancer patients with prior histories especially lymphocyte proliferation and TH1 of psychological dysfunction such as depression, cytokine production. One landmark study anxiety, or interpersonal difficulties seem to have showed that women with metastatic breast cancer greater difficulties in adjusting to the multiple who participated in an expressive supportive challenges faced posttreatment. Similarly, low group therapy intervention lived about twice as levels of education and a lack of interpersonal long as women in the comparison condition. This resources have also been shown to significantly effect has been partially replicated in a subset of impact adjustment. Therefore, any intervention women with estrogen-receptor-negative tumors. approach needs to consider multiple disease- While some groups have attempted to replicate related characteristics and possible treatment survival findings, and with only limited success, moderators as these will likely interact with other teams conducted studies focusing on intervention efficacy and influence psychosocial neuroendocrine and immune mechanisms to treatment outcomes. explain the putative health effects of psychoso- cial intervention in breast cancer patients. One Psychosocial Effects of Intervention recent longitudinal study, which started with the There is a large literature documenting the intent of evaluating the intervention effect on not effectiveness of psychosocial intervention with only psychological distress, but also immune cancer patients. Interventions have demonstrated function and survival, did show a survival positive effects across a range of psychosocial advantage for intervention participants compared and physical outcomes, including symptoms to comparison group participants. There is of depression and anxiety, and cancer-related evidence now that psychological stress, via the fear, social functioning, and disease- and HPA axis and SNS, can influence the course of treatment-related symptoms (e.g., fatigue, nau- tumor progression at almost every phase of the sea, pain). Although findings have been mixed cancer continuum, from health behaviors to with reports of nonsignificant effects as well, metastases. However, more systematic studies several reviews of the literature have concluded with large sample sizes and long-term follow-up that the majority of psychotherapeutic interven- effects are needed to provide conclusive evidence tions among cancer patients demonstrate some of any survival effects of these interventions. improvement in psychosocial adjustment. Potential psychosocial effects on biological Notably, sociodemographic factors (e.g., age, mechanisms are depicted in Fig. 2. education, and socioeconomic status), premorbid psychological and physical functioning, social Stepped Care Model of Psychosocial support, coping styles, and certain personality Intervention traits (e.g., neuroticism, interpersonal sensitivity, Several psychosocial treatments among cancer and social inhibition) have been associated with patients have shown promise in improving increased risk of adjustment difficulties follow- emotional well-being, and both general and ing cancer diagnosis and treatment, suggesting disease-specific quality of life. Most intervention that there may also be considerable variability approaches involved group therapy interventions in baseline functioning and response to following cognitive behavioral, stress and intervention efforts. coping, stress management, and supportive Cancer: Psychosocial Treatment 323 C

Psychological Stress (SNS,HPA)

C

Potential Intervention Effects

Smoking DNA damage Immune system VEGF ETOH DNA repair Cellular & antibody production Fat con sumption Telomere length Exercise Telomerase BMI activity

cancer Tumor poor health DNA phenotype Metastases behaviors changes vascularization e.g. MUC1

Cancer: Psychosocial Treatment, Fig. 2 Development and progression of cancer and how/where psychological stress and interventions might influence the process group environment theories and models. Some but still likely to provide benefit and progress to work has also provided psychoeducational inter- more intensive interventions only if patients do ventions, engaged spouses/partners, or provided not demonstrate improvement from simpler phone-based delivery of the interventions. approaches or for those who can be reliably Regardless of the intervention approach, it is predicted to not likely benefit. An important important to consider the distress continuum feature of the stepped care model is that progress among cancer patients to determine the most and decisions regarding intervention efforts are optimal level of care based on their needs systematically monitored and changes in (see Fig. 3). outcomes of interest are carefully assessed. Psychosocial intervention is not necessary for A “step up” to a more comprehensive therapy is all patients and a stepped care model of interven- made only when there are no significant gains in tion delivery is recommended. This involves the targeted outcomes. Stepped care may involve a collaborative care approach to intervention increasing intensity of a single therapeutic efforts in which patients are involved in treatment approach, transition to a different therapeutic planning and therapeutic resources are utilized approach, or using several therapeutic based on systematic assessment and monitoring approaches additively. Likewise, different inter- of patients’ psychosocial well-being. Stepped ventions may be applied to address different care approaches require that treatments of aspects of a patient’s problem. Psychosocial different intensity are provided depending on needs also change as patients move from through the need of the individual. Treatments are ini- their cancer experience and either transition to tially implemented that are of minimal intensity survivorship or face advanced disease and C 324 Cancer: Psychosocial Treatment

Normal Adjustment - Transient feelings of distress Reactions such as fear & anxiety Psychoeducational Approaches, Open Support Groups & Information - Functional impairments limited Provision to disease-specific functioning

Adjustment Disorder - Mild symptoms of distress such as fear & anxiety Brief Individual & Group Psychotherapy - Impairment in several general & disease-specific functioning areas Subclinical Symptoms - Mild to severe symptoms of of Severe Distress distress that do not meet Individual & Group criteria for a mental disorder Psychotherapy, Full Psychiatric - Symptoms of distress are Evaluation debilitating and impact multiple functioning domains Severe Emotional Reactions & Mental - Diagnosed mental health Health Disorders disorder

Individual & Group - Symptoms are severe and Psychotherapy, significantly impact multiple Evaluation for Pharmacologic areas of functioning Treatment

Cancer: Psychosocial Treatment, Fig. 3 Psychological interventions’ stepped approaches as a function of emotional reactions across the cancer distress continuum end-of-life concerns. Utilizing a stepped care with treatment-related side effects (e.g., sexual approach to promote adjustment and well-being aids), and communication skills to effectively at all phases of the cancer continuum may navigate the medical system or voice concerns enhance intervention efficacy through more with the spouse/partner and family and friends. stringent assessment methods and appropriate- A minority but yet significant number of cancer ness of intervention techniques, while also using patients may experience emotional reactions that the least amount of therapeutic resources. warrant a more structured approach at psycholog- The model in Fig. 3. proposes that treatment ical care. Those lacking in social resources, planning and intervention efforts must consider presenting with high levels of perceived stress the distress continuum among cancer patients to and enduring longstanding interpersonal dysfunc- determine the most optimal level of care based on tion – likely driven by deficits in interpersonal their needs. Most cancer patients adjust relatively skills and personality traits – are more likely to well to the cancer diagnosis and treatment. The benefit from such interventions. Similarly, indi- majority of individuals experience some transient viduals with premorbid psychopathology and levels of distress characterized by mild symptoms physical limitations, greater treatment-related of anxiety and depression, fear, and interpersonal functioning limitations, and recurrent disease are disruption specific to disease-related functioning more likely to experience greater levels of distress (e.g., sexual dysfunction). Because their emo- and benefit the most from psychosocial interven- tional reactions are transient and significantly tions. Those who meet criteria for a mental health below clinical levels, these patients are likely to disorder are likely to be experiencing an adjust- benefit from information provision or psychoedu- ment disorder which is characterized by clinically cational approaches that offer information on significant symptoms of distress. In such cases, what to expect from prostate cancer treatment, brief individual and group psychotherapeutic the recovery process, available options for coping approaches can be useful in ameliorating Canonical Correlation 325 C persistent symptoms of distress that among pros- (2007). The effect of psychosocial factors on breast tate cancer survivors are commonly related to cancer outcome: A systematic review. Breast Cancer Research, 9(4), 1–23. treatment-related dysfunction. If untreated, these Institute of Medicine. (2007). Cancer care for the whole symptoms can interfere with multiple domains of patient: Meeting psychosocial health needs. health-related quality of life. Cancer patients who Washington, DC: National Academies Press. experience subclinical manifestations of mental Jacobsen, P. B. (2010). Improving psychosocial care in outpatient oncology settings. Journal of the National C health disorders such as anxiety, depression, and Comprehensive Cancer Network, 8, 368–370. PTSD (i.e., experience severe symptomatology Jacobsen, P. B., Donovan, K. A., Vadaparampil, S. T., & but not meeting diagnostic criteria) may benefit Small, B. J. (2007). Systematic review and meta- from a full psychiatric evaluation to determine analysis of psychological and activity-based interven- tions for cancer-related fatigue. Health Psychology, the most appropriate level of care. For these sur- 26, 660–667. vivors, individual and group psychotherapeutic Jacobsen, P. B., & Jim, H. S. (2008). Psychosocial inter- approaches can positively impact mental health ventions for anxiety and depression in adult cancer and health-related quality of life outcomes. patients: Achievements and challenges. CA: A Cancer Journal for Clinicians, 58(4), 214–230. Among the small number of patients who experi- Manne, S. L., & Andrykowski, M. A. (2006). Are psycho- ence severe emotional reactions and are diagnosed logical interventions effective and accepted by cancer with a mental health disorder, evaluation for patients? II. Using empirically supported therapy pharmacologic treatment, in addition to guidelines to decide. Annals of Behavioral Medicine, 21(2), 98–103. individual and group psychotherapeutic McGregor, B., & Antoni, M. H. (2009). Psychological approaches, is warranted. intervention and health outcomes among women treated for breast cancer: a review of stress pathways and biological mediators. Brain, Behavior and Immu- nity, 23, 159–166. Cross-References Meyer, T. J., & Mark, M. M. (1995). Effects of psychoso- cial interventions with adult cancer patients: ▶ A meta-analysis of randomized experiments. Health Intervention Theories Psychology, 14(2), 101–108. ▶ Psychosocial Adjustment Spiegel, D., Butler, L. D., & Giese-Davis, J. (2007). Effects of supportive-expressive group therapy on sur- vival of patients with metastatic breast cancer. Cancer, 110(5), 1130–1138. References and Readings Stanton, A. L. (2006). Psychosocial concerns and inter- ventions for cancer survivors. Journal of Clinical Anderson, B. L., Yang, H. C., Farrar, W. B., Golden- Oncology, 24(32), 5132–5137. Kreutz, D. M., Emery, C. F., Thornton, L. M., et al. Zabora, J., Brintzenhofeszoc, K., Curbow, B., Hooker, C., & (2008). Psychological intervention improves survival Piantadosi, S. (2001). The prevalence of psychological for breast cancer patients: A randomized clinical trial. distress by cancer site. Psycho-Oncology, 10, 19–28. Cancer, 113(12), 3450–3458. Andrykowski, M. A., & Manne, S. L. (2006). Are psycho- logical interventions effective and accepted by cancer patients? I. Standards and levels of evidence. Annals of Behavioral Medicine, 21(2), 93–97. Canonical Correlation Burish, T. G., & Jenkins, R. A. (1992). Effectiveness of biofeedback and relaxation training in reducing the side effects of cancer chemotherapy. Health Stephanie Ann Hooker Psychology, 11, 17–23. Department of Psychology, University of Dale, H. L., Adair, P. M., & Humphris, G. M. (2010). Colorado, Denver, CO, USA Systematic review of post-treatment psychosocial and behaviour change interventions for men with cancer. Psycho-oncology, 19(3), 227–237. Daniels, J., & Kissane, D. W. (2008). Psychosocial inter- Definition ventions for cancer patients. Current Opinion in Oncology, 20(4), 367–371. Falagas, M. E., Zarkadoulia, E. A., Ioannidou, E. N., Canonical correlation is a multivariate statistical Peppas, G., Christodoulou, C., & Rafailidis, P. I. technique that specifies relationships between C 326 Capacity Assessment two sets of variables. Researchers interested in variables may be redundant in the interpretation. understanding how two multidimensional con- Once the researcher determines which measured structs are related may find this technique useful. variables contribute to each latent variable, he or For example, someone interested in further she names the latent factor and interprets the understanding the relationships between the meaning of the canonical correlation. multidimensional constructs of personality and a healthy behavioral lifestyle might identify two sets of variables that measure those constructs. Cross-References In the personality set, one might include factors like conscientiousness, openness to experience, ▶ Latent Variable and neuroticism, whereas in the healthy behavior set, one might include physical activity, healthy eating, sleep, or dental hygiene. References and Readings To use this technique, the researcher should identify two sets of measured variables. The vari- Stevens, J. P. (2009). Canonical correlation. In Applied ables selected for a set should measure different multivariate statistics for the social sciences (pp. 395–411). New York: Routledge. dimensions of the same construct (e.g., conscien- tiousness, openness to experience, and neuroti- cism would all be different facets of personality). Similar to exploratory factor analysis, canonical correlation identifies latent variables within Capacity Assessment each set. The canonical correlation (Rc) is the statistic that identifies the strength and direction- ▶ Functional Versus Vocational Assessment ality of the relationship between two latent variables (one from each set). Only statistically significant canonical correlations should be interpreted. The Rc is interpreted like the Pearson Capsaicin correlation coefficient, ranging from 1.0 to 1.0. A positive Rc indicates a positive relationship Barbara Resnick between the two latent variables and a negative School of Nursing, University of Maryland, Rc indicates a negative relationship between Baltimore, MD, USA the two latent variables. Rc values closer to 1.0 (or 1.0) indicate stronger relationships. Latent variables are interpreted using two sta- Synonyms tistics: standardized coefficients and canonical variate-variable correlations. Standardized coef- Pepper ficients indicate the extent to which each mea- sured variable contributes to the latent variable. Canonical variate-variable correlations indicate Definition the strength and directionality of the relationship between the measured variable and the latent Capsaicin is the ingredient found in different variable. Stevens (2009) suggests examining types of hot peppers, such as cayenne peppers, both the standardized coefficients and the canon- that makes the peppers spicy hot. You can eat it ical variate-variable correlations to include the raw or as a dried powder placed in food. It is also measured variable in the interpretation of the available as a dietary supplement, topical cream, latent variable. Many of the measured variables or via a high dose dermal patch (trade name may correlate highly with the latent variable, but Qutenza). Capsaicin, in any of these forms, is the standardized coefficient identifies which used to relieve the pain of peripheral neuropathy Carbohydrates 327 C from postherpetic neuraligia caused by shingles References and Readings and for temporary musculoskeletal pain and has been used to treat psoriasis (to decrease itching Bode, A. M., & Dong, Z. (2011). The two faces of capsa- and inflammation). Capsaicin works by first stim- icin. Cancer Research, 71(8), 2809–2814. Fraenkel, L., Bogardus, S. T., Concato, J., & Wittink, D. R. ulating and then decreasing the intensity of pain (2004). Treatment options in knee osteoarthritis: The signals in the body. Capsaicin stimulates the patient’s perspective. Archives of Internal Medicine, release of a compound believed to be involved 164, 1299–1304. C in communicating pain between the nerves in the Johnson, W. (2007). Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit spinal cord and other parts of the body. To be extract, capsicum annuum resin, capsicum annuum effective, the cream needs to be used four to five fruit powder, capsicum frutescens fruit, capsicum times a day. At the time of use, the skin may burn frutescens fruit extract, capsicum frutescens resin, or itch, although these sensations decrease over and capsaicin. International Journal of Toxicology, 26(Suppl. 1), 3–106. time. It is important to wash your hands thor- oughly after each use and to avoid getting the cream in your eyes or places in which there are moist mucous membranes such as the mouth or vaginal or rectal areas. Contact with these areas Carbohydrates will cause burning. The cream should also not be used on areas of broken skin. James Turner Capsaicin has also be used as a supplement to School of Cancer Sciences, The University of improve digestion, eliminate infections, prevent Birmingham, Edgbaston, Birmingham, UK heart disease by lowering blood cholesterol levels and blood pressure, and prevent clotting and atherosclerosis. Theoretically, capsaicin acts Synonyms as an antioxidant and protects the cells of the body from the damage of free radicals. In so CHO; Saccharide doing, health benefits can be derived. Lastly, capsaicin makes mucus thinner and thus may improve pulmonary function among those with Definition chronic obstructive pulmonary disease or chronic bronchitis. A carbohydrate is an organic compound, or in Capsaicin is generally considered safe when other words, a compound containing a carbon taken orally or used as a cream. As noted, it can atom. In addition to carbon, all carbohydrates cause some unpleasant effects. If this occurs, the also comprise the atoms hydrogen and oxygen, best way to alleviate further pain is to remove the and share the common formula exposure via removing clothing if it has been contaminated and washing off the skin with CnH2nOn soap, shampoo, or other types of detergents. Water, vinegar, and bleach are all ineffective at where n is any whole number. removing capsaicin. Applications of cool com- The name “carbohydrate” is derived from the presses may help with the burning sensations bonding of a water molecule to a carbon atom, experienced with capsaicin. thus carbohydrates are hydrates of carbon. An allergic reaction to capsaicin is possible. If Carbohydrates can be classified into several you are just beginning to use capsaicin, either as categories. Monosaccharides are the most fresh or prepared food or in powder form, start basic units, and when two monosaccharides are with small amounts. If you use a topical cream, chemically bonded, a disaccharide carbohydrate you should first apply it to a small area of skin to is formed. Oligosaccharides are generally consid- test for an allergic reaction. ered to be carbohydrates with three to ten C 328 Carcinogens monosaccharides, and polysaccharides are environmental interactions (Pfeifer & Hainaut, carbohydrates with more than ten of these basic 2011). Completely genetically induced tumors units. In nutrition, carbohydrates are often are rare (Pfeifer & Hainaut, 2011). Most malig- categorized into “simple” and “complex” forms. nancies occur as a result of exposure to internal or Simple carbohydrates include monosaccharides environmental agents that cause genetic damage and disaccharides (sugars) whereas complex (Pfeifer & Hainaut, 2011). However, susceptibil- carbohydrates are oligosaccharides and polysac- ity to these environmentally induced mutations charides (starches). Carbohydrates, despite being can be inherited (Pfeifer & Hainaut, 2011). Envi- nonessential dietary constituents, function pri- ronmental factors in a very broad sense can marily as a source of energy, and are a particu- include physical and chemical agents, dietary larly important fuel for high-intensity exercise. factors, behavioral exposures such as tobacco and alcohol and microenvironmental factors Cross-References such as infection and inflammation. Any such factor that causes cancer is a carcinogen. ▶ Glucose Sir Percivall Pott was the first to report that ▶ Insulin a malignancy could be caused by an environmen- tal carcinogen when he described “the chimney- sweepers” cancer in 1775 (Cogliano, 2010; References and Readings Stone, 2003). This work concluded that scrotal cancer was caused by soot that became wedged in Bender, D. A. (2002). Introduction to nutrition and metab- the scrotum and also marks the first time that an olism (3rd ed.). London: Taylor & Francis. McArdle, W. D., Katch, F. I., & Katch, V. L. (2001). occupational cancer was linked to a specific Exercise physiology. Energy, nutrition and human cause (Cogliano, 2010; Stone, 2003). As a result performance (5th ed.). Baltimore: Lippincott Williams of this type of work, it is now understood that & Wilkins. tobacco, including that found in second-hand smoke, causes lung cancer (Stone, 2003). It is also known that mesothelioma, frequent in ship- Carcinogens yard workers, is due to asbestos exposure (Cogliano, 2010; Pfeifer & Hainaut, 2011; Elizabeth Franzmann Siemiatycki et al., 2004; Stone, 2003), and Department of Otolaryngology/Division of Head leukemia, frequent in the shoe-production indus- and Neck, Miller School of Medicine, University try, is related to benzene (Cogliano, 2010; of Miami, Miami, FL, USA Siemiatycki et al., 2004). Similarly nickel refin- ing, smelting, and welding are associated with Synonyms cancers of the lung, nasal cavity, and sinuses and ionizing radiation is associated with bone, Mutagen leukemia, lung, liver, and many other types of cancer (Siemiatycki et al., 2004). Certain viruses such as human papillomavirus (HPV) Definition and hepatitis C virus are also carcinogenic (Stone, 2003). Substances that cause cancer Following Pott’s example, public health agen- cies such as the United States National Toxicology Program and International Agency for Research Description on Cancer (IARC) have worked to identify and educate the public about additional It is well established that cancer initiation and carcinogens (Cogliano, 2010; Siemiatycki et al., progression occurs through complex genetic and 2004). In the case of the IARC, agents, mixtures, Carcinoma 329 C or exposure circumstances are selected for evalua- Pfeifer, G. P., & Hainaut, P. (2011). Next-generation tion if humans are known to be exposed and there is sequencing: Emerging lessons on the origins of human cancer. Current Opinion in Oncology, 23,62–68. reason to suspect they may cause cancer Siemiatycki, J., Richardson, L., Straif, K., Latreille, B., (Siemiatycki et al., 2004). At regular intervals, the Lakhani, R., Campbell, S., et al. (2004). Listing occu- IARC meets as a working group consisting of pational carcinogens. Environmental Health Perspec- 15–30 experts from related fields (Siemiatycki tives, 112, 1447–1459. Stone, M. J. (2003). History of the Baylor Charles A. C et al., 2004). These experts identify a concerning Sammons cancer center. Proceedings (Baylor Univer- agent and review the epidemiological, animal, and sity Medical Center), 16(1), 30–58. other laboratory studies to help determine whether a substance of interest is carcinogenic (Siemiatycki et al., 2004). Epidemiologic evidence is generally considered the most important determinant Carcinoma (Siemiatycki et al., 2004). This evidence stems from associations between suspected causal agents Elizabeth Franzmann and presence or absence of cancer in populations. Department of Otolaryngology/Division of Head The second most important determinant is the and Neck, Miller School of Medicine, University direct laboratory animal evidence of carcinogenic- of Miami, Miami, FL, USA ity (Siemiatycki et al., 2004). Other laboratory evidence such as genotoxicity, mutagenicity, metabolism, cytotoxicology, or mechanisms are Synonyms also considered important (Siemiatycki et al., 2004). Based on the combination of these different Malignant neoplastic disease types of data, the IARC develops a consensus and then classifies the substance as carcinogenic, prob- ably carcinogenic, possibly carcinogenic, not clas- Definition sifiable, or probably not carcinogenic (Siemiatycki et al., 2004). Results of the working group meetings Carcinoma includes malignancies that begin in are published in the IARC monographs which the lining or covering of organs. provide important information for determining research priorities and preventing cancer (Siemiatycki et al., 2004). Description Despite Pott’s work, incidence of scrotal can- cer in England did not decrease until the 1950s According to the National Cancer Institute when counteractive measures such as improved (National Cancer Institute [NCI], 2011), carci- chimney-cleaning, alternative heating methods, noma is the most common category of cancer and protective clothing were put in place and includes malignancies that begin in the lining (Cogliano, 2010). Even today, exposure to many or covering of organs. Other cancer categories of the hundreds of common and suspected car- include sarcomas that begin in connective or sup- cinogens occurs in industry (Cogliano, 2010). portive tissue such as muscle and bone, leuke- Further education and preventive measures are mias which start in blood-forming tissues, needed to fully educate and protect the public. lymphoma and myelomas which originate in the immune system, and central nervous system tumors which include malignancies that start in the brain and spinal cord (NCI, 2011). References and Readings Nonmelanoma skin cancer, including basal cell and squamous cell, are the most common carci- Cogliano, V. J. (2010). Identifying carcinogenic agents in the workplace and environment. The Lancet Oncology, nomas in the United States with more 1,000,000 11, 602. diagnosed annually (NCI, 2011). Other C 330 Carcinoma carcinomas involving the prostate, breast, lung, still some controversy whether risks outweigh and colon are the next most common (NCI, benefits (Smith et al.). The ACS recommends 2011). that men aged 50 or over and with at least Carcinoma, like any cancer, is characterized a 10-year life expectancy should have an oppor- by dysregulated growth and uncontrolled dissem- tunity to make an informed decision with their ination of abnormal cells which, left unchecked, health care provider about prostate cancer screen- can result in death (American Cancer Society ing after receiving counseling as to the risks, [ACS], 2011). Exposure to environmental factors benefits, and uncertainties associated with such such as tobacco, viruses, chemicals, and radiation screening (Smith et al.). can cause cancer and such agents are known as Prevention of carcinoma focuses on decreas- carcinogens (ACS, 2011; NCI, 2011). Internal ing tobacco use, increasing nutritional awareness, factors such as inherited mutations, immunodefi- and limiting exposure to known carcinogens. ciency, and mutations arising from metabolic Tobacco use is leading risk factor for carcinoma dysfunction can also give rise to cancer (ACS, and the most preventable cause of death world- 2011). Because most malignancies initiate and wide, responsible for the deaths of half of long- progress through a combination of environmental term users (ACS, 2011). Furthermore, it has also and internal factors, only about 5% of cancers are been estimated that one-third of cancer deaths felt to be familial (ACS, 2011). Decades can pass in the United States each year are due to poor between exposure to external factors and detect- nutrition, physical inactivity, and excess weight able cancer (ACS, 2011). Some individuals who (ACS). In addition, environmental exposures are exposed to known carcinogens, such as other than tobacco use can increase risk of tobacco, for many years may never develop can- carcinoma. These exposures include infectious cer (ACS, 2011). Individual factors such as abil- agents, excessive sun exposure, and exposures ity to repair DNA damage, remove carcinogens, to carcinogens that exist in air, food, water, and and destroy abnormal cells all play a role in soil (ACS). The United States’ National Toxicol- determining who will go on to develop cancer ogy Program and the International Agency for (NCI, 2011). Research on Cancer work to identify carcinogens Depending on site, stage, and specific and provide information to the public and other pathology of the carcinoma, treatment includes regulatory agencies in an effort to decrease the combinations of surgery, radiation, and chemo- burden of human cancer (ACS, 2011). therapy (ACS, 2011;NCI,2011). Other thera- pies such as hormone therapy, biological therapy, and targeted therapy may also be used Cross-References (NCI, 2011). Treatment can be very toxic, resulting in long-term morbidity especially for ▶ Carcinogens late stage disease which is primarily determined by its size and whether it has spread to lymph nodes or other areas of the body (NCI, 2011). References and Readings Even with the most aggressive therapy, some- times cure cannot be attained. For these rea- American Cancer Society. (2011). Cancer facts & figures sons, programs to prevent and detect cancers 2011. Atlanta, GA: Author. early are imperative. National Cancer Institute. (2011). What is cancer? Accessed July 17, 2011, from http://www.cancer.gov/ The American cancer Society (ACS) recom- cancertopics/cancerlibrary/what-is-cancer mends regular screening for breast, colorectal, Smith, R. A., Cokkinides, V., Brooks, D., Saslow, D., and cervical cancer as screening programs have Shah, M., & Brawley, O. W. (2011). Cancer screening resulted in decreased mortality for these cancers in the United States, 2011: A review of current American Cancer Society guidelines and issues in (Smith et al., 2011). Though evidence in favor of cancer screening. CA: A Cancer Journal for Clini- prostate cancer screening is increasing, there is cians, 61, 8–30. Cardiac Events 331 C

Carcinoma of the Prostate Cardiac Events

▶ Cancer, Prostate Siqin Ye Division of Cardiology, Columbia University Medical Center, New York, NY, USA Cardiac Arrhythmia C

▶ Arrhythmia Synonyms

Coronary event; Major adverse cardiac and Cardiac Cachexia cerebrovascular event (MACCE); Major adverse cardiac event (MACE); Major adverse ▶ Cachexia (Wasting Syndrome) cardiovascular event (MACE)

Cardiac Death Definition

Ana Victoria Soto1 and William Whang2 The term cardiac event is used to denote the 1Medicine – Residency Program, Columbia composite of a variety of adverse events related University Medical Center, New York, NY, USA to the cardiovascular system. 2Division of Cardiology, Columbia University Medical Center, New York, NY, USA Description

Synonyms The exact definition for cardiac events often varies depending on the specific study. At the Sudden cardiac death narrowest, it is synonymous with coronary event, which refers to adverse events caused by disease processes affecting the coronary arteries. Definition These may include what are termed “hard” events such as deaths that are attributed to coronary Cardiac death is defined as occurring when artery disease and nonfatal myocardial infarc- the rhythmic contractions of the heart cease tions but also occasionally “soft” events such as and do not return spontaneously. Generally speak- angina or revascularizations for progressive cor- ing, cardiac death may occur suddenly or onary artery disease (Kip, Hollabaugh, non-suddenly. Sudden cardiac death is defined by Marroquin, & Williams, 2008). More broadly, death within 1 h of the onset of symptoms, in the the term cardiac event is often used interchange- absence of preceding evidence of severe heart ably with another loosely defined term, major failure. This definition is usually used to capture adverse cardiac event or MACE. Common defi- death due to cardiac arrhythmia. Non-sudden nitions of MACE include death (either all-cause cardiac death generally encompasses death due or cardiac), nonfatal myocardial infarction, to pump failure (Hinkle & Thaler, 1982). and revascularization (with optional additional specification of target vessel or lesion, i.e., if References and Readings the revascularization occurred at the site of a previously identified diseased coronary vessel Hinkle, L. E., Jr., & Thaler, J. T. (1982). Clinical classifi- or atherosclerotic lesion, respectively); occasion- cation of cardiac deaths. Circulation, 65, 457–464. ally, stroke is also incorporated into MACE, and C 332 Cardiac Output the term is alternatively defined as major adverse Cross-References cardiovascular event or major adverse cardiac and cerebrovascular event (MAACE). Finally, in ▶ Coronary Event some circumstances, nonfatal heart failure events (i.e., hospitalization for heart failure) are also con- References and Readings sidered cardiac events, though this is infrequent and occurs mainly in studies that focus on the ACC Writing Committee for Acute Coronary Syndromes prognosis and treatment of heart failure (Skali, Clinical Data Standards & ACC Task Force on Pfeffer, Lubsen, & Solomon, 2006). Clinical Data Standards. (2001). American college of cardiology key data elements and definitions for Since cardiac events and the other related measuring the clinical management and outcomes of terms described above are composites of clinical patients with acute coronary syndromes. Journal of the events of varying significance, there remains con- American College of Cardiology, 38(7), 2114–2130. siderable debate on what should constitute the DeMets, D. L., & Califf, R. M. (2002). Lessons learned from recent cardiovascular clinical trials. Circulation, most appropriate component endpoints and how 2002(106), 746–751. to define them. Furthermore, it has been increas- Kip, K. E., Hollabaugh, K., Marroquin, O. C., & ingly recognized that the wide variability in these Williams, D. O. (2008). The problem with composite definitions may significantly influence the results end points in cardiovascular studies. Journal of the American College of Cardiology, 51(7), 701–707. and impact of clinical trials and other studies. For Lim, E., Brown, A., Helmy, A., Mussa, S., & instance, many have noted that less consequential Altman, D. G. (2008). Composite outcomes in but more frequently occurring endpoints such as cardiovascular research: A survey of randomized revascularizations or heart failure exacerbations trials. Annals of Internal Medicine, 149, 612–617. Skali, H., Pfeffer, M. A., Lubsen, J., & Solomon, S. D. are often what drive the statistical significance or (2006). Variable impact of combining fatal and the lack there of for the results of many trials nonfatal end points in heart failure trials. Circulation, (DeMets & Califf, 2002; Lim, Brown, Helmy, 2006(114), 2298–2304. Mussa, & Altman, 2008). Different component Thygesen, K., Alpert, J. S., White, H. D., on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the endpoints may also trend in opposing directions, Redefinition of Myocardial Infarction. (2007). rendering the interpretation and generalization of Universal definition of myocardial infarction. the primary result problematic (Wilcox, Kupfer, European Heart Journal, 28(20), 2525–2538. & Erdmann, 2008). These considerations have Wilcox, R., Kupfer, S., Erdmann, E., on behalf of the PROactive Study investigators (2008). Effects of induced recent attempts to standardize the pioglitazone on major adverse cardiovascular events in definitions of events that have the most clinical high-risk patients with type 2 diabetes: Results from relevance, and guidelines such as the 2001 ACC PROspective pioglitAzone clinical trial in macrovascular Clinical Data Standards and the 2007 Joint ESC/ events (PROactive 10). American Heart Journal, 155(4), 712–717. ACCF/AHA/WHF Task Force for the Redefini- tion of Myocardial Infarction Expert Consensus Document have outlined explicit definitions for terms such as cardiovascular death and myocar- Cardiac Output dial infarction, with emphasis placed on objective findings that include ECG changes and the typical Simon Bacon rise and fall of biomarkers such as cardiac tropo- Department of Exercise Science, Concordia nins. In addition, most contemporary studies have University, Montreal Behavioral Medicine begun routinely disclosing the results of individ- Centre, Montreal, QC, Canada ual endpoints as well as those of alternative composite measures. It is hoped that with these and other future efforts, the methodological chal- Definition lenges inherent in the use of composite endpoints such as cardiac events will finally be adequately Cardiac output (Q) is the volume of blood addressed. pumped out of the heart (specifically from the Cardiac Rehabilitation 333 C right and left ventricles) per minute. It is gener- ally calculated as a function of heart rate and Cardiac Rehabilitation stroke volume (cardiac output ¼ heart rate stroke volume). Average resting cardiac output Leah Rosenberg1 and Sarah Piper2 is about 5 L/min (normal range 4–8 L/min) and 1Department of Medicine, School of Medicine, tends to be slightly higher in men versus women. Duke University, Durham, NC, USA During acute exercise and mental stress, cardiac 2Institute of Metabolic Science, Addenbrookes C output increases. This increase can be as high as Hospital, Metabolic Research Laboratories, 35 L/min for exercise (in elite athletes) and University of Cambridge, Cambridge, UK 15 L/min for mental stress. There are many methods of measuring cardiac output, which range from intracardiac catheteri- Synonyms zation (invasive) to arterial pulse tonometry (non- invasive). The Fick principle, which uses Secondary prevention programs the measurement of oxygen consumption and the oxygen content of the arterial and venous blood, is considered the most accurate method Definition of assessing cardiac output, though it is an inva- sive technique, which limits its utility. Great Cardiac rehabilitation is a multidisciplinary effort has been placed into finding accurate reli- program of secondary prevention measures that able noninvasive methods of assessing cardiac assist cardiovascular disease patients in their output, such as, dye dilution, ultrasound-based comprehensive recovery to previous functioning. techniques, impedance cardiography, and, more recently, magnetic resonance imaging. Each Description one of these comes with both positives and neg- atives and the selection of one method over Introduction another needs to be made given the individual Cardiac rehabilitation is a comprehensive platform requirement for cardiac output measurement. of pharmacologic, psychosocial, and behavioral As cardiac output is driven by heart rate and secondary prevention measures that is typically stroke volume, the factors that control changes in provided to patients with a history of cardiovascu- these parameters also influence cardiac output. lar disease. Cardiac rehabilitation is designed Specifically, parasympathetic and sympathetic with a multidisciplinary approach to patient care activity and venous return influence cardiac and requires a cohesive plan of various therapies output. and practitioners. Cardiac rehabilitation has been shown to improve outcomes and initiate a type of “re-conditioning” process for many patients (Clark et al. 2005). Targeted patient populations Cross-References for cardiac rehabilitation include those individ- uals who have recently had an acute cardiovascu- ▶ Blood Pressure lar event (i.e., myocardial infarction or unstable ▶ Heart Rate angina), post-cardiac bypass patients, and those who have stable angina, heart failure, or other patients with cardiac disease who have become References and Readings deconditioned for any reason.

Berne, R. M., & Levy, M. N. (2001). Cardiovascular History of Cardiac Rehabilitation Programs physiology (8th ed.). St. Louis, MO: Mosby. Hall, J. E. (2011). Guyton and Hall textbook of medical In the 1930s, patients who had suffered physiology (12th ed.). New York: Elsevier. a myocardial infarction were instructed to C 334 Cardiac Rehabilitation observe strict bed rest, often up to 6 weeks in patients should undergo a thorough medical eval- duration. Gradually, increasing levels of physical uation prior to initiating any program of physical activity were added to the post-event regimen. exertion. This is particularly relevant for those In addition to the salutatory effects of cardiac who are survivors of an acute coronary syndrome rehabilitation for recovery of previous functional or symptomatic heart failure. While there used to status, it was eventually recognized that there be a prevalent belief in the medical community were significant benefits in avoiding the hazards that prolonged bed rest was the only safe activity of bed rest which included deconditioning, level after a cardiac event, numerous studies have deep venous thrombosis, and even limb atrophy demonstrated the safety of medically supervised and contractures. Today, post-acute coronary exercise programs (Franklin, 1998). These exer- syndrome patients are encouraged to return to cise programs not only improve the quality of life physical activity soon after the event. Early inter- for cardiac patients but have actually been shown vention with physical therapy is now a hallmark to increase life expectancy in some cases. Specif- of contemporary cardiovascular care. ically, most individualized exercise programs should encompass aerobic activities for at least Typical Components of Cardiac 2 days per week. Rehabilitation The United States Public Health Service Guidelines for Cardiac Rehabilitation (USPHS) defines cardiac rehabilitation programs The American Society of Cardiovascular and as comprehensive, multidisciplinary efforts with Pulmonary Rehabilitation have published guide- the following components (Hamm et al. 2011). lines outlining ten core competencies that practi- These are the broad categories that encompass tioners must have to provide the highest standard both short- and long-term goals. Newly admitted of evidence-based care for patients. Briefly, the cardiac rehabilitation patients must undergo risk ten areas are patient assessment, nutritional stratification to identify their needs for supervi- counseling, weight management, blood pressure sion and particular exercise plan. management, lipid management, diabetes man- 1. Medical evaluation agement, tobacco cessation, psychosocial man- 2. Exercise training agement, physical activity counseling, and 3. Secondary prevention efforts and risk factor exercise training evaluation. The guidelines reduction encompass an array of skills that transcend the 4. Patient education and counseling abilities of any single provider. Instead, they assume a collaborative and comprehensive Evidence Supporting Cardiac Rehabilitation approach to cardiac rehabilitation. The compe- There are several trials that have compared the tencies are divided into discrete “knowledge” efficacy of cardiac rehabilitation programs that points and then “skills” without specific reference focus primarily on risk factor reduction versus to the particular type of provider who will pro- an approach that favors increasing exercise vide the services. To coordinate the broad variety tolerance. An integrated approach is the most of necessary services, they suggest a case man- favorable for reducing morbidity and mortality agement model for individual patients. In the after a cardiovascular event. Modification of position statement enunciating the ten core com- depressive symptoms is an important target for petencies, the Society emphasizes the extent a cohesive rehabilitation program (Milani et al. to which individual providers need not be profi- 2007). Other less-quantifiable benefits include the cient in all facets of secondary prevention but socialization and support that comes from working rather be willing and able to identify particular with a variety of clinicians and peer groups. patient needs. The focus on multidisciplinary A growing body of evidence in the literature care involves the participation of physicians, supports exercise-training programs for cardiac nurses, physical therapists, clinical nutritionists, rehabilitation (Antman et al. 2008). All enrolled social workers, and psychologists. Cardiac Surgery 335 C

Of particular interest is the core competency prevention professionals: 2010 Update: Position state- of psychosocial management. The knowledge ment of the American Association of Cardiovascular and Pulmonary Rehabilitation. Journal of Cardiopul- piece requires cardiac rehabilitation providers monary Rehabilitation and Prevention, 31(1), 2–10. to become aware with the literature on the impact Milani, R. V., & Lavie, C. J. (2007). Impact of cardiac of psychological factors on the pathophysiology rehabilitation on depression and its associated mortal- of cardiovascular event onset and the impedi- ity. American Journal of Medicine, 120(9), 799–806. Prochanska, J. O., & DiClemente, C. C. (1983). Stages and C ments that can prevent recovery. In particular, processes of self-change of smoking: Toward an inte- the competency requires specific attention to grative model of change. Journal of Consulting and developing familiarity with the effect of major Clinical Psychology, 51, 390–395. depression on adverse cardiovascular outcomes and worse adherence to treatments (Prochanska & DiClemente, 1983). This references the current research question of whether poorer outcomes Cardiac Risk Factor among depressed post-heart attack patients are due to their non-adherence of rehabilitative thera- ▶ Heart Disease and Cardiovascular Reactivity pies or rather a distinct pathophysiologic state.

Cross-References Cardiac Stress Test

▶ Cardiovascular Disease ▶ Maximal Exercise Stress Test ▶ Physical Therapy ▶ Recovery ▶ Rehabilitation Cardiac Surgery

References and Readings Leah Rosenberg Department of Medicine, School of Medicine, Antman, E. M., Hand, M., Armstrong, P. W., Bates, E. R., Duke University, Durham, NC, USA Green, L. A., Halasyamani, L. K., et al. (2008). 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myo- cardial infarction: A report of the American College of Synonyms Cardiology/American Heart Association task force on practice guidelines: Developed in collaboration With Cardiothoracic surgery; Cardiovascular surgery the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to review new evidence and update the ACC/AHA 2004 guidelines for the management of Definition patients with ST-elevation myocardial infarction, writ- ing on behalf of the 2004 writing committee. Circula- tion, 117(2), 296–329. Cardiac surgery is the subset of operative proce- Clark, A. M., Hartling, L., Vandermeer, B., & dures focused on the heart and vasculature. Com- McAlister, F. A. (2005). Meta-analysis: Secondary mon examples of cardiac surgery include coronary prevention programs for patients with coronary artery artery bypass grafting (CABG), valvular repair, disease. Annals of Internal Medicine, 143(9), 659–672. Franklin, B. A., Bonzheim, K., Gordon, S., & Timmis, G. C. and the correction of congenital cardiac (1998). Safety of medically supervised outpatient car- malformations. Cardiac surgery is a subspecialty diac rehabilitation exercise therapy: A 16-year follow- of general surgery that requires additional training up. Chest, 114(3), 902–906. beyond a traditional 5-year residency. Advance- Hamm, L. F., Sanderson, B. K., Ades, P. A., Berra, K., Kaminsky, L. A., Roitman, J. L., et al. (2011). Core ments in anesthesiology have been critical to competencies for cardiac rehabilitation/secondary the development of cardiac surgery. For example, C 336 Cardiologist the widespread use of heart-lung bypass machines Definition since the 1990s have extended the possible dura- tion and complexity of these procedures. A cardiologist is a physician who has specialty Surgeries on the heart and great vessels training in the area of cardiology. Cardiologists (e.g., aorta and vena cavae) are generally are often MD trained, and typically had general performed on seriously ill patients who have training in internal medicine (or pediatrics if either tried or been deemed ineligible for less a pediatric cardiologist) prior to the completion invasive measures such as medication-based of cardiology fellowship. Cardiologists are often or percutaneous interventions (Lie, Bunch, confused with cardiac or cardiothoracic surgeons, Smeby, Arnesen, & Hamilton, 2012). Increased who primarily perform operations on the heart. rates of mood disorder such as depression or A “board-certified cardiologist” is a physician cognitive impairment have been noted in post- who trained in cardiology, met minimum training CABG patients, suggesting a possibly important requirements, and also passed the cardiology role for behavioral therapies (Katon, Ludman, & board exams. After cardiology fellowship, physi- Simon, 2008). To date, however, it is unknown cians can choose to undergo additional training in whether depression treatment in post-CABG a subspecialty of cardiology (e.g., echocardiog- patients improves cardiovascular outcomes. raphy, nuclear cardiology, intervention, etc).

Cross-References Cross-References

▶ Cardiovascular Disease ▶ Cardiology ▶ Coronary Artery Disease ▶ Coronary Heart Disease References and Readings

References and Readings Baughman, K. L., Duffy, F. D., Eagle, K. A., Faxon, D. P., Hillis, L. D., & Lange, R. A. (2008). Task force 1: Training in clinical cardiology. Journal of the Ameri- Katon, W., Ludman, E., & Simon, G. (2008). The depres- can College of Cardiology, 51(3), 339–348. sion helpbook (2nd ed.). Chicago: Bull Publishing. Lie, I., Bunch, E. H., Smeby, N. A., Arnesen, H., & Hamilton, G. (2012). Patients’ experiences with symp- toms and needs in the early rehabilitation phase after coronary artery bypass grafting. European journal of Cardiology cardiovascascular nursing, 11(1), 14–24. Daichi Shimbo Center for Behavioral Cardiovascular Health, Columbia University, New York, NY, USA Cardiologist

Daichi Shimbo Synonyms Center for Behavioral Cardiovascular Health, Columbia University, New York, NY, USA Cardiovascular medicine

Synonyms Definition

Cardiology expert; Cardiovascular medicine Cardiology is a medical specialty of the structure, expert; Heart doctor function, and disorders of the heart. Cardiovascular Disease Prevention 337 C

Traditionally, cardiology has mainly focused on the heart; however, more recently, the field of Cardiovascular Disease (CVD) cardiology has expanded into the study and dis- orders of the arteries and veins, as well as other ▶ Heart Disease and Smoking organs such as the brain (i.e., stroke or transient ischemia attack) or kidney (i.e., cardiorenal syn- drome). This is probably due to a common under- C lying pathophysiology of disease. As such, Cardiovascular Disease Prevention cardiology has recently involved areas of medi- cine typically associated with other specialties Stephanie Ann Hooker (such as neurologists, nephrologists, etc.). Department of Psychology, University of Colorado, Denver, CO, USA Cross-References Synonyms ▶ Cardiologist CVD prevention References and Readings

Fuster, V., O’Rourke, R., Walsh, R., & Poole-Wilson, P. Definition (2007). Hurst’s the heart (12th ed.). New York: McGraw-Hill Professional. Cardiovascular disease is a group of chronic dis- eases (e.g., myocardial infarction, chronic heart disease, stroke) of the heart and blood vessels. Cardiology Expert Cardiovascular disease prevention is composed of the various early actions taken to thwart the onset of cardiovascular disease. ▶ Cardiologist

Description Cardiothoracic Surgery Cardiovascular diseases (CVD) claim the lives of ▶ Cardiac Surgery thousands of individuals every year. In 2007, the top cause of death in the United States was heart disease (616,067 deaths), second was cancer (562,875 deaths), and third was stroke (or cere- Cardiovascular Disease brovascular disease, in many cases a form of cardiovascular illness; 135,952 deaths) (U.S. ▶ Acute Myocardial Infarction Centers for Disease Control and Prevention ▶ Angina Pectoris [CDC], 2010). Although there is a general inher- ▶ Cardiovascular Disease Prevention itability for CVD, the formation of these diseases ▶ Congestive Heart Failure is seen as largely preventable. In a unique ▶ Coronary Heart Disease interpretation of the causes of death in the year ▶ Heart 2000, Mokdad and colleagues (Mokdad, Marks, ▶ Heart Disease Stroup, & Gerberding, 2004) found that the top ▶ Heart Failure three actual causes of death were due to three ▶ Hypertension modifiable behavioral risk factors: (1) smoking ▶ Hypertrophy (435,000 deaths; 18.1% of total deaths in the year C 338 Cardiovascular Disease Prevention

2000); (2) poor diet and physical inactivity not smoke cigarettes or other forms of tobacco, (400,000 deaths; 16.6%); and (3) alcohol con- and those who do should quit. Exposure to sumption (85,000 deaths; 3.5%). All three of secondhand smoke should be limited as well these behaviors are risk factors for CVD and are (Pearson et al., 2002). Tobacco use accounted considered preventable. for 18.1% of all deaths in the United States in Primary prevention of CVD, like other the year 2000 and was the top behavioral risk chronic, noncommunicable diseases, is seen as factor for death (Mokdad et al., 2004). Cigarette more cost-effective than treatment of the disease, smoking is one of the main risk factors for which is usually long term and expensive (Probst- coronary heart disease, and women who smoke Hensch, Tanner, Kessler, Burri, & Kunzli,€ 2011). have a 25% greater risk of coronary heart disease Practitioners of behavioral medicine can encour- than men after controlling for other risk factors age their patients and the community at large to (Huxley & Woodward, 2011). make lifestyle modifications to prevent the onset of CVD. These can include behavioral changes Engage in Regular Physical Activity such as (1) getting regular health screenings; The American Heart Association recommends (2) limiting tobacco exposure; (3) engaging in that individuals engage in at least 30 min of regular physical activity; (4) eating a heart- moderate-intensity exercise most days of the healthy diet; (5) maintaining a healthy weight; week (Pearson et al., 2002). Exercise treats (6) limiting alcohol use; and (7) reducing stress many CVD risk factors, including elevated and negative emotionality. These seven behav- blood pressure, insulin resistance, glucose intol- ioral changes are described in detail below. erance, obesity, elevated triglycerides, and low HDL cholesterol (Thompson et al., 2003). Exer- Get Regular Health Screenings cise also has short-term effects of reducing serum Beginning at age 20, adults should get screenings triglycerides for up to 72 h, introducing a spike in for CVD risk factors at least every 2 years. These HDL, reducing systolic blood pressure for up to include blood pressure, body weight, waist cir- 12 h, and helping stabilize glucose levels cumference, and pulse (as a screen for atrial fibril- (Thompson et al., 2003). Physical activity might lation). At least every 5 years (or less if at higher also help individuals make other preferable risk), blood lipids (either fasting serum lipopro- behavior changes, including helping with teins or total and high-density lipoproteins [HDL] smoking cessation (Ussher, Taylor, & Faulkner, if fasting unavailable) and fasting blood glucose 2008). should be recorded to monitor risk for hyperlip- idemia and diabetes (Pearson et al., 2002). Eat a Heart-Healthy Diet Blood pressure should be maintained at a level Individuals should eat a “heart-healthy” diet. below 140/90 mmHg for the average individual This is a diet that is low in fat (saturated fat whereas those with diabetes should maintain their <10% of calories), cholesterol (<300 mg/day), blood pressure below 130/80 mmHg (Pearson and trans-fats (limit as much as possible), and salt et al., 2002). Individuals with hypertension can (<6 g/day) and that is rich in assorted fruits, make behavioral modifications (e.g., limit salt vegetables, whole grains, and low-fat dairy. intake, increase physical activity, and reduce Energy intake should match energy expenditure, alcohol intake). Blood pressure medications are i.e., intake should not exceed what is needed, and recommended for individuals who have if necessary, intake should be reduced for weight attempted lifestyle modifications but have not loss (Pearson et al., 2002). Although there has succeeded in controlling blood pressure. been a major focus on how much individuals consume, there is evidence that what individuals Limit Tobacco Exposure eat is important to reduce CVD risk. In a meta- Individuals should avoid exposure to tobacco analysis of randomized clinical trials of dietary smoke as much as possible. Thus, they should interventions in which patients were advised to Cardiovascular Disease Prevention 339 C either (1) reduce total fat intake, (2) reduce satu- emotions. There is evidence that negative emo- rated fat intake, (3) reduce dietary cholesterol, or tions (i.e., depression, anxiety, and anger) are (4) shift from saturated to unsaturated fat, modi- related to the development of CVD. Multiple fication in dietary fat intake reduced risk for pathways have been proposed to explain cardiovascular mortality by 9% and reduced risk the relation between negative affect and CVD for subsequent cardiac events by 16% (Hooper risk, and these include engagement in more et al., 2001). adverse health behaviors, greater stress expo- C sure, greater physiological reactivity, lower Maintain a Healthy Weight heart rate variability, and greater inflammation Body mass index (BMI; weight (kg)/height (m)2) (cf., Suls & Bunde, 2005,forareview). should be maintained in the normal range In particular, type D personality, a personality (18.5–24.9 kg/m2)(Pearsonetal.,2002). Waist type comprised of negative emotionality and circumference should be maintained at less than social inhibition, is positively related to cardiac 40 in. in diameter for men and less than 35 in. events. A recent meta-analysis by O’Dell, Mas- in diameter for women (Pearson et al., 2002). In ters, Spielmans, and Maisto (2011)revealed a meta-analysis of over 80,000 individuals, greater that patients with type D personalities were waist-to-hip ratio and waist circumference were three times more likely to experience myocar- associated with greater risk of CVD-related mor- dial infarction, coronary artery bypass grafting, tality, after controlling for other relevant CVD risk percutaneous cardiac intervention, or cardiac factors, over an average 98.7-month follow-up mortality than non-type D individuals. Con- (Czernichow, Kengne, Stamatakis, Hamer & versely, there is preliminary evidence that Batty 2011). However, BMI, the most commonly some psychosocial resources may provide used measure of obesity, was not related to CVD- a protective buffer against cardiovascular risk. related mortality after controlling for other risk Roepke and Grant (2011)reviewed32studies factors, suggesting that some (if not all) of the of personal mastery (i.e., the belief that one risk that higher BMI contributes to CVD mortality has some control over future life circumstances) is subsumed by the other related risk factors (e.g., and cardiometabolic health and revealed that blood pressure, cholesterol). the overwhelming majority of studies found that higher mastery was associated with Limit Alcohol Use a reduced risk for cardiovascular outcomes. Alcohol use should be limited to 2 drinks/day for men (14 drinks/week) and 1 drink a day for women (7 drinks/week) (Pearson et al., Conclusions 2002). In a meta-analysis of prospective cohort studies linking alcohol use to cardiovascular out- Cardiovascular disease is largely preventable comes, including mortality and cardiovascular when individuals practice a healthy lifestyle. event morbidity, moderate consumption of This includes practicing health-promoting alcohol (about 1 drink/day) was associated with behaviors like engaging in regular physical activ- a 14–25% reduced risk of all cardiovascular ity, eating a heart-healthy diet, maintaining outcomes when compared to abstainers (Ronksley, a healthy weight, and getting regular health Brien, Turner, Mukamal, & Ghali 2011). Con- screenings and avoiding health-compromising versely, consuming higher amounts of alcohol behaviors like risky alcohol use and tobacco (>1 drink/day) was associated with higher proba- use. Additionally, individuals can make attempts bility of CVD-specific mortality and cardiac events. to reduce their experiences of stress and negative emotions and promote positive emotional expe- Reduce Stress and Negative Emotionality riences. The combination of these behaviors Individuals should limit their exposure to stress will help reduce the risk of CVD and promote and promote positive rather than negative longer, healthier lives. C 340 Cardiovascular Medicine

Cross-References Thompson, P., Buchner, D., Pin˜a, I., Balady, G. J., Williams, M. A., Marcus, B. H., et al. (2003). Exercise ▶ and physical activity in the prevention and treatment of Cardiovascular Disease atherosclerotic cardiovascular disease: A statement from the Council on Clinical Cardiology (Subcommit- tee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabo- References and Readings lism (Subcommittee on Physical Activity). Arterioscle- rosis, Thrombosis, and Vascular Biology, 8, e42–e49. Czernichow, S., Kengne, A., Stamatakis, E., Hamer, M., & US Centers for Disease Control and Prevention. (2009). Batty, G. (2011). Body mass index, waist circumfer- Heart disease prevention. Retrieved August 28, 2011, ence and waist-hip ratio: Which is the better discrim- from http://www.cdc.gov/heartdisease/prevention.htm inator of cardiovascular disease and mortality risk? US Centers for Disease Control and Prevention. (2010). Evidence from an individual-participant meta-analysis Deaths: Final data for 2007. National Vital Statistics of 82 864 participants from nine cohort studies. Report, 58. Accessed March 21, 2011, from http:// Obesity Reviews, 12, 680–687. www.cdc.gov/NCHS/data/nvsr/nvsr58/nvsr58_19.pdf Hooper, L., Summerbell, C. D., Higgins, J. P. T., Ussher, M. H., Taylor, A., & Faulkner, G. (2008). Exercise Thompson, R. L., Capps, N. E., Smith, G. D., et al. interventions for smoking cessation (Review). (2001). Dietary fat intake and prevention of cardiovas- Cochrane Database of Systematic Reviews, 4, 1–37. cular disease: Systematic review. BMJ, 322, 757–763 (Clinical Research Editions). Huxley, R., & Woodward, M. (2011). Cigarette smoking as a risk factor for coronary heart disease in women Cardiovascular Medicine compared with men: A systematic review and meta- analysis of prospective cohort studies. Lancet, 6736, ▶ 1–9. Cardiology Mokdad, A., Marks, J., Stroup, D., & Gerberding, J. (2004). Actual causes of death in the United States, 2000. JAMA: The Journal of the American Medical Association, 291, 1238–1245. Cardiovascular Medicine Expert O’Dell, K., Masters, K. S., Spielmans, G. I., & Maisto, S. A. (2011). Does Type-D personality predict out- ▶ Cardiologist comes among patients with cardiovascular disease? A meta-analytic review. Journal of Psychosomatic Research, 71, 199–206. Pearson, T. A., Blair, S. N., Daniels, S. R., Eckel, R. H., Cardiovascular Psychophysiology: Fair, J. M., Fortmann, S. P., et al. (2002). AHA guide- Measures lines for primary prevention of cardiovascular disease and stroke: 2002 update: Consensus panel guide to comprehensive risk reduction for adult patients with- ▶ Cardiovascular Recovery out coronary or other atherosclerotic vascular diseases. ▶ Psychophysiology: Theory and Methods Circulation, 106, 388–391. Probst-Hensch, N., Tanner, M., Kessler, C., Burri, C., & Kunzli,€ N. (2011). Prevention: A cost-effective way to fight the non-communicable disease epidemic. Swiss Cardiovascular Recovery Medical Weekly, 141, 1–8. Roepke, S., & Grant, I. (2011). Toward a more complete William Gerin understanding of the effects of personal mastery on cardiometabolic health. Health Psychology, 30, The College of Health and Human Development, 615–632. University Park, PA, USA Ronksley, P., Brien, S., Turner, B., Mukamal, K., & Ghali, W. (2011). Association of alcohol consumption with selected cardiovascular disease outcomes: A systematic review and meta-analysis. BMJ, Definition 342, 1–13. Suls, J., & Bunde, J. (2005). Anger, anxiety, and depres- Cardiovascular recovery refers to the extent to sion as risk factors for cardiovascular disease: which elevations in blood pressure (BP) or heart The problems and implications of overlapping affective dispositions. Psychological Bulletin, 131, rate (HR) due to a stressor persist after the 260–300. stressor is no longer present. Cardiovascular Recovery 341 C

Description (1936) found that hypertensive subjects showed longer recovery times than normotensives. Recovery of cardiovascular prestress resting Finally, studies examining race have found that levels following a stressor has been of interest Black women and men had slower recovery rates to researchers for many years, going back to the than White women and men (Linden et al., 1997). original cardiovascular reactivity studies by Thus, several important risk factors for hyper- Hines and Brown (1936), who noted that not tension and CHD appear to influence BP and HR C only did hypertensive patients show greater return to prestress levels following a stressor. responses to the cold pressor than normotensive The recovery data are important, especially controls but also recovered more slowly. Since given findings showing that in a sample of bor- then, evidence from several studies suggests that derline hypertensives, a strong predictor of future recovery may provide prognostic information stable hypertension was the recovery of diastolic concerning the development of cardiovascular dis- BP following a mental arithmetic task (Borghi, eases, such as hypertension and coronary heart Costa, Bocshi, Mussi, & Ambrosioni, 1986). In disease (CHD) (Fredrickson & Matthews, 1990). fact, these researchers found recovery a more Cardiovascular reactivity (the magnitude of useful predictor than reactivity. the acute BP or HR response to a stressor) has There are in theory many reasons why recov- been implicated as a risk factor in the develop- ery should be poorer in one individual than in ment of cardiovascular-related diseases (i.e., the another. In general, the mechanisms could be “reactivity hypothesis”). However, this measure central or peripheral. An example of the former does not take into account the duration of the would be a persistence of the autonomic arousal, response (i.e., recovery; the time BP or HR or an inability to “unwind” following exposure takes to return to prestress baseline levels from to a stressor. A second mechanism could be an elevations due to a stressor that is no longer impairment of baroreflex sensitivity. The func- present). There is strong evidence that sustained tion of the baroreflex is to buffer acute changes elevation of BP is a cause of target organ damage, of blood pressure, and an insensitive reflex e.g., left ventricular hypertrophy, and, over time, would result in an enhanced and protracted of essential hypertension (HTN) (Fredrickson & pressor response to a stimulus. A third, and Matthews, 1990). To the extent that we may peripheral, mechanism is changes in the vascu- regard slow recovery periods, observed in the lature, such as hypertrophy and remodeling, laboratory, as analogous to sustained elevated which could result in delayed relaxation of BP in the natural environment, this measure pro- vascular smooth muscle following exposure to vides information over and above that of the mag- a vasoconstrictor stimulus. nitude of the response. However, there is not There is evidence that recovery and reactivity nearly the body of evidence examining the causes represent independent dimensions. For example, and effects of recovery as there is for reactivity. in one review paper, reactivity changes were Much of the evidence that does exist for weakly correlated with recovery scores (Linden recovery comes from cross-sectional compari- et al., 1997). In addition, Haynes, Gannon, sons, examining variables that are related to the Orimoto, O’Brien, and Brandt (1991) reported development of cardiovascular diseases and that, across a total of 65 studies, of the 81 statis- including comparisons based on normotensive- tical analyses (out of 180) that indicated nonsig- hypertensive status; family history of hyperten- nificant stressor effects (i.e., reactivity) for sion; and ethnicity. For example, children of a variable (e.g., between group, between phases), normotensive parents show more rapid recovery significant effects were found during the recovery than children of hypertensives (Linden, Earle, phase for 74% of the same variables. Conversely, Gerin, & Christenfeld, 1997). It is noteworthy of the 74 statistical analyses that indicated that in this review, differences in reactivity were significant stressor effects for a variable, nonsig- not observed among the groups. Hines & Brown nificant effects were found during the recovery C 342 Cardiovascular Recovery phase for 42% of those same variables. This is responding. The sympatho-adrenal axis reflects important because it suggests that the physiolog- activation due to motor and cognitive effort, ical mechanisms underlying the two processes of including rises in epinephrine, norepinephrine, reactivity and recovery must be considered sepa- muscle tension, plasma free fatty acid levels, rately and that the information contained in both and blood pressure due to cardiac output. This measures may provide greater insight into the activation when accompanied by adrenocortical cardiovascular mechanisms underlying the stress hormone suppression has also been described as response than either measure alone. These con- a “positive stress reaction” because it is short- siderations have led a number of researchers to lived and permits adaptive responding with suggest that causal explanations of biobehavioral maximal strength (De La Torre, 1994). In con- disorders and the design of clinical interventions trast, the hypothalamic-pituitary axis (HPA) is may be well served by studying psychophysio- thought to reflect affective distress and be the logical recovery. result of chronic, unresolved strain (De La Torre), and may be the most indicative bodily Early Theories of Stress and Recovery response during delayed recovery. HPA axis As early as the 1930s, the seminal theories of activity is associated with increased release of stress, and the optimal ways to respond to stress, free fatty acid into circulation, suppression of were proposed. For example, Seyle (1936) immune function, increased glucose and urea proposed that stress has three phases: activation, production, and increased blood pressure due to resistance, and exhaustion. When the body is vasoconstriction (i.e., total peripheral resistance); initially challenged by a stressor, it responds HPA activation is inferred from the measurement with physiological activation of a defense system of cortisol and its precursor adrenocorticotropic to deal with the immediate stressor, what is hormone (ACTH). often referred to as the fight-or-flight response. A resistance (or coping) phase follows during Cognitive-Affective Determinants of Poorer which the body begins to suffer from the effects Recovery of heightened activity, but continues to function A fundamental question that arises concerns how to ward off the stress-inducing stimuli. If the acute stressors can have lasting effects for some resolution of stress is unsuccessful the body but not others, or put another way, why some may experience exhaustion. Activation that individuals have poorer recovery than others. endures beyond the resistance stage (i.e., does Brosschot, Gerin, and Thayer (2005) have pro- not lead to swift resolution) is presumed to posed that the tendency to relive stressors in one’s contribute to disease. At about the same time, mind (i.e., ruminate and worry) causes repeated Freeman (1939) posited that psychological HPA activation and results in negative health recovery from experimental loads may be useful outcomes, such as sustained hypertension. In in estimating an individual’s ability to withstand other words, people do not need an external conflict in ordinary life situations. Such early stressor to be present to experience stress. Rather, suggestions that quick recovery from stress- stress can have longer durations and impacts on induced arousal reflects particularly effective the body, simply through thinking about and coping laid the foundation for later theories of remembering negative emotions and having per- the stress-disease linkage. sistent thoughts about the negative experiences. Subsequent work has thus refined these theo- Furthermore, it is those individuals who continu- ries, and posited biological mechanisms for how ally experience the mental representation of stress impacts the body and contributes to dis- stress that have poor recovery and ultimately ease. Important to refinement was the altering of poor health. This focus on the cognitive-affective Seyle’s notion from a ubiquitous, “whole-sys- determinants of poorer recovery has begun to be tem” response to challenge, to one that distin- seen as an important area of study, augmenting guished at least two axes of physiological reactivity models. Cardiovascular Risk Factors 343 C

Conclusion experimentally induced frustration. Journal of Psy- chology, 8, 247–252. Gerin, W. (2010). Laboratory stress testing methodology. In sum, the duration of time it takes for an indi- In A. Steptoe (Ed.), Handbook of behavioral medicine: vidual’s cardiovascular system to return to resting Methods and applications. New York: Springer. levels is a key determinant of that person’s health. Haynes, S. N., Gannon, L. R., Orimoto, L., O’Brien, W. H., Furthermore, the duration of experienced stress & Brandt, M. (1991). Psychophysiological assessment of poststerss recovery. Journal of Consulting and Clin- C (i.e., recovery) is an independent and often more ical Psychology, 3, 356–365. important predictor of future health than the Hines, E. A., & Brown, G. E. (1936). The cold pressor test magnitude of the stress response (i.e., reactivity). for measuring the reactibility of the blood pressure: Current models of hypertension and cardiovascu- Data concerning 571 normal and hypertensive subjects. American Heart Journal, 11, 1–9. lar disease are beginning to focus on delayed Linden, W., Earle, T. L., Gerin, W., & Christenfeld, N. recovery as an essential variable to consider. (1997). Physiological stress reactivity and recovery: This work, and future explorations, will need to Conceptual siblings separated at birth? Journal of consider the role that perseverative cognitions, Psychosomatic Research, 42, 117–135. Obrist, P. A. (1981). Cardiovascular psychophysiology: such as rumination, play in delaying cardiovascu- A perspective. New York: Plenum Press. lar recovery. While the effects of the arrangement Seyle, H. (1936). A syndrome produced by diverse nocu- of stress in one’s environment cannot be ignored, ous agents. Nature, 138, 32. how stress is arranged in one’s mind appears to be Turner, J. R. (1994). Cardiovascular reactivity and stress: Patterns of physiological response. New York: as important a factor to determining one’s health. Plenum Press.

Cross-References Cardiovascular Response/Reactivity ▶ Blood Pressure Reactivity or Responses ▶ Blood Pressure Reactivity or Responses ▶ Cardiovascular Disease ▶ Hypertension ▶ Perseverative Cognition ▶ Psychophysiologic Recovery Cardiovascular Risk Factors ▶ Rumination Rachel S. Rubinstein and Richard J. Contrada Department of Psychology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA References and Readings

Borghi, C., Costa, F. V., Bochi, S., Mussi, A., & Synonyms Ambrosioni, E. (1986). Predictors of stable hyperten- sion in young borderline subjects: A five year follow- up study. Journal of Cardiovascular Pharmacology, 8, Protective factors; Psychosocial factors S138–S141. Brosschot, J. F., Gerin, W., & Thayer, J. F. (2005). The perseverative cognition hypothesis: A review of Definition worry, prolonged stress-related physiological activa- tion, and health. Journal of Psychosomatic Research, 60, 113–124. A cardiovascular risk factor is a predictor of one De La Torre, B. (1994). Psychoendocrinologic mecha- or more diseases of the heart or circulation. nisms of life stress. Stress Medicine, 10, 107–114. Fredrickson, M., & Matthews, K. A. (1990). Cardiovas- cular responses to behavioral stress and hypertension: Description A meta-analytic review. Annals of Behavioral Medicine, 12, 30–39. Freeman, G. L. (1939). Toward a psychiatric Plimsoll A “risk factor” is a variable that bears an empirical mark: Physiological recovery quotients in association with one or more diseases or other C 344 Cardiovascular Risk Factors medical conditions. “Cardiovascular disease” and heart disease can promote other cardiovascular “heart disease” refer to a set of specific disorders disorders, such as when damage due to that affect the heart and circulation. Therefore, myocardial infarction leads to congestive heart a cardiovascular risk factor is a correlate of one failure, a condition in which the pumping action or more cardiovascular diseases. A distinction is of the heart cannot adequately meet the demands sometimes made between risk and protective of the body for oxygen and nutrition. Atrial fibril- factors as a way to capture the direction of the lation is one of several forms of CVD that involve relationship. For example, elevated cholesterol is a disturbance in heart rhythm and may be a risk factor, whereas social integration has been a consequence of MI or heart failure. studied for its possible protective effects. Clinical CHD is usually a consequence of cor- The identification of risk factors for medical onary atherosclerosis, or coronary artery disease conditions is a major goal of the field of epidemi- (CAD). Coronary atherosclerosis involves the ology. The term “risk factor” was introduced in accumulation of plaque, comprising fatty the context of cardiovascular epidemiology, substances and other materials, which forms on a field that underwent great expansion during the inner lining of the coronary arteries, the vessels the twentieth century. Certain acute infectious that supply oxygenated blood to heart muscle. The conditions that had been the major sources of buildup of atherosclerotic plaque, which reflects death in the early 1900s came under control as a number of metabolic, hemodynamic, inflamma- a result of advances in the fields of public health tory, and hematologic processes, culminates in and biomedicine. As a consequence, several mul- CHD when blood vessel openings become tiply determined chronic disorders became more narrowed to the point at which blood flow to the prevalent. Chronic illnesses, and diseases of the heart muscle is obstructed and can no longer meet heart and blood vessels in particular, became the its metabolic demands. The triggering event leading sources of death in the United States and in CHD is often thrombosis (clot formation) in other industrialized nations. This continues to leading to occlusion of an already narrowed be the case despite reductions in cardiovascular coronary artery. The atherosclerotic process also death over the past several decades. Many risk may affect blood vessels of the brain, leading factors for cardiovascular disorders have been to cerebrovascular incidents commonly referred identified. They may be categorized in a number to as “stroke.” of different ways, for example, in terms of Still another form of cardiovascular disease is the particular form(s) of cardiovascular disease essential hypertension, a condition defined with which they are related or on the basis of by sustained high blood pressure levels with no characteristics of the risk factors themselves. identifiable cause. Hypertension is often associated with vascular inelasticity, referred to Major Cardiovascular Disorders as arteriosclerosis. Hypertension increases risk Among the various forms of cardiovascular for CHD as well as for stroke, retinopathy, heart disease (CVD), coronary heart disease (CHD) is failure, and kidney disease. a major contributor to cardiovascular morbidity Risk factors differ somewhat for different and mortality. Also referred to as ischemic heart forms of CVD. For example, cigarette smoking disease, CHD occurs when the heart is inade- is a well-established risk factor for MI and other quately supplied with oxygenated blood. It has forms of CHD, but its role in the development of several clinical manifestations including angina essential hypertension is less clear. On the other pectoris (a syndrome involving chest pain hand, dietary intake of salt, a possible risk factor and other symptoms), myocardial infarction for essential hypertension in some segments (MI) or “heart attack” (death of a portion of the of the population, has a less well-established myocardium), and sudden cardiac death (death relationship with other types of heart disease. within minutes of symptom onset). Coronary Similarly, certain kinds of heart valve problems Cardiovascular Risk Factors 345 C more clearly operate as predisposing factors the risk factor are twice as likely (or, equiva- for heart rhythm disturbances than for other lently, 100% more likely) to develop the cardiovascular conditions. condition by comparison with those without the Taken together, the multifaceted nature of risk factor. Major risk factors for one or more cardiovascular diseases, complexities in interrela- cardiovascular conditions are those for which tionships among its various forms, and their a significant relative risk is well established. overlapping but nonidentical determinants Variables for which the evidence is less clear C complicate the description and classification of are sometimes referred to as contributing risk cardiovascular risk factors. However, clinical factors. The more risk factors that are present, manifestations of CHD and other major forms of and the higher the level of each one, the greater CVD reflect a common substrate, atherosclerosis the risk for CVD. and, in the aggregate, account for considerable In addition to its relative risk, attributes morbidity and mortality. This provides an of a cardiovascular risk factor that determine important focus for much research in this area. its overall importance from a public health stand- Moreover, although genetic and other biological point include its prevalence, the degree to which risk factors may be in play from the time of birth, it can be readily modified, and the impact of its much of the burden of cardiovascular diseases modification on CVD outcomes. Several risk reflects the operation of multiple aspects of factors, such as resting blood pressure and lifestyle, as will be discussed further below. This cholesterol level, can be modified, and their raises the possibility that programs of primary modification is associated with reductions in prevention may bring about significant reductions cardiovascular morbidity and mortality. In other in the burden of cardiovascular disease. cases, including that of many suspected psycho- social variables, there are questions either about Attributes of Risk Factors the effects of interventions on the risk factor or Risk factor status, by itself, does not imply cau- about the impact of risk factor modification on sality. The case for a causal role requires several CVD outcomes. Still other risk factors, such as forms of evidence. For example, there should be gender and age, are clearly not modifiable, an association with disease in well-designed stud- though it remains possible that some of the ies that is consistent, strong, prospective (rather pathways through which they exert their effects than merely cross-sectional), and independent of are amenable to intervention. other possible risk factors. The putative risk fac- tor also should show a dose–response relation- Risk Factor Categories ship with disease outcomes and should plausibly In addition to distinctions in terms of the CVD be related to disease etiology and pathophysiol- outcomes with which they are associated, CVD ogy, and its removal should reduce the risk of risk factors may be distinguished on the basis of disease. Although causal analysis often follows their intrinsic characteristics. One rather broad after a variable is identified empirically as a risk distinction is that between states or conditions factor, in other cases a variable is examined as of the person and those that describe the environ- a possible risk factor only after a role in disease ment. Person factors include variables such as causation is first suggested in mechanistic resting blood pressure, gender, and personality. research. Environmental factors may be defined geograph- The strength of the relationship between a risk ically, in terms of regions, such as the Southeast- factor and disease is often expressed in terms of ern United States (where CVD is highly relative risk. Relative risk is the ratio of the prob- prevalent), or with respect to variables such as ability of disease occurrence with and without the the average socioeconomic status of individuals risk factor in question. For example, a relative residing in a particular community (which is risk of 2.0 would indicate that individuals with inversely associated with CVD risk). C 346 Cardiovascular Risk Factors

Risk factors also may be categorized in terms thought to amplify those of others. In particular, of the time point and chronicity of their influence cigarette smoking has been examined for its pos- on the natural history of CVD. The hypothesized sibly interactive effects with other variables pathogenic effect may be to promote progression including genes, high blood pressure, and oral of CAD, as in the case of variables related to contraceptive use. blood cholesterol or sugar levels. Alternatively, a risk factor may be suspected of playing a role in Traditional and Psychosocial Risk Factors the manifestation of clinical CHD, as where an Historically, those risk factors that were identi- acute stressor triggers an ischemic event in the fied early on or that fit within the original para- context of previously asymptomatic CAD. digm for understanding cardiovascular diseases Within these major disease phases, risk factors have been referred to as “traditional” or “biomed- may exert their influence gradually, over the ical.” Variables that exemplify this tradition and course of months and years, or more rapidly, that are recognized by contemporary epidemiol- within days, hours, or even minutes. ogists include cigarette smoking, resting blood Risk factors also may be described at several pressure, cholesterol levels, diabetes, older age, levels of analysis. Many are biological, ranging male gender, specific genetic markers, and family from the molecular, for example, specific genetic history; also implicated are obesity, physical polymorphisms and proinflammatory factors, to inactivity, a high fat, high carbohydrate diet, systemic physiological conditions such as high low levels of high-density lipoprotein choles- resting blood pressure. Some risk factors are terol, high levels of triglycerides, and high levels behavioral, including cigarette smoking, physical of C-reactive protein and other inflammatory inactivity, and various dietary practices, and markers. some are psychological, including personality Beginning in the middle of the twentieth cen- attributes like cynical hostility and mood and tury and continuing today, a very large body of anxiety disorders like major depression and research has sought to identify additional types of posttraumatic stress disorder. Still others are risk factors for CVD, including a number of described at a social level of analysis, including social and psychological variables. These efforts social network characteristics and socioeconomic were stimulated by limitations in the predictive status. power of the more traditional risk factors, theo- retical and empirical work concerning the effects Risk Factor Interactions of psychological stress and emotion on cardio- Risk factors for CVD do not operate in isolation vascular physiology, and informal observations from one another. Individual variables may by clinicians and empirical research findings that share causal antecedents, influence one another were suggestive of psychosocial influences on directly, and exert additive or synergistic effects CVD. Many of the more recently identified risk in the etiology and pathogenesis of disease. For factors (some of which are discussed below) are example, CVD risk factors such as poor diet and characteristics of the person and social context exercise habits combine to promote obesity and that are referred to as “psychosocial.” Recogni- high cholesterol levels, which are themselves tion of the potential importance of psychosocial CVD risk factors. Functional relationships CVD risk factors contributed significantly to the among a set of multiple determinants of a single emergence and growth of the fields of health outcome suggest that it may be useful to consider psychology, behavioral medicine, and behavioral them in combination. A case in point is cardiology. cardiometabolic syndrome, a biological CVD risk factor defined as a cluster consisting of cen- Lifestyle as the Major Determinant of CVD tral obesity, hypertension, and dysregulation in The designation of many of the traditional CVD glucose and fat metabolism. The disease- risk factors as “biomedical” is something of promoting effects of certain risk factors are a misnomer. For example, four major Cardiovascular Risk Factors 347 C cardiovascular risk factors identified in early epi- counteract or exacerbate stressors and their demiological work, and still the target of consid- impact; and (c) biological responses, including erable research, are cigarette smoking, resting neuroendocrine, autonomic, cardiovascular, and blood pressure, cholesterol levels, and blood immunological/inflammatory perturbations that sugar problems including diabetes. Cigarette are potentially damaging to cardiovascular smoking is, of course, a behavior pattern, and health. Among stressors that have been linked although it is maintained, in part, by physiologi- empirically to CVD outcomes are major life C cal processes of nicotine addiction, its initiation events, occupational stress, and marital conflict. and natural history also reflect social and psycho- Psychosocial factors that in some way interact logical influences. Similarly, blood pressure, cho- with psychological stress also have received lesterol, and blood sugar are to some extent attention as possible CVD risk factors. One such regulated by specific behaviors such as diet and construct, the type A behavior pattern (TABP), exercise and also may reflect psychosocial influ- formed the foundation for contemporary work on ences such as stress and emotion. psychosocial factors in CVD. Type A refers to Given that most forms of CVD take decades to a set of behaviors that include competitiveness develop, recognition that many of the traditional and achievement striving, impatience and time risk factors reflect aspects of lifestyle has impor- urgency, hostility and anger, and vigorous speech tant public health implications. One is that efforts and motor characteristics (Friedman & to prevent CVD should begin early in life. Behav- Rosenman, 1974). Type B refers to a more ior patterns such as cigarette smoking and those relaxed, less impatient, and less irritable pattern involved in weight regulation and nutrition begin of behavior. Type A was conceptualized as the during or even before adolescence. Tobacco use outcome of a person-situation interaction in has a devastating effect on health, including can- which its defining features are displayed in cer and respiratory consequences as well as CVD, response to stressful and challenging events and and recent trends involving the earlier emergence conditions in susceptible individuals. The TABP of obesity and, relatedly, diabetes mellitus, are construct initially attracted considerable attention alarming in light of their projected impact on for a prospective association with CHD that was trends in the prevalence of heart disease. When independent of traditional risk factors such as combined with possible psychosocial determi- cholesterol levels, resting blood pressure, and nants of CVD, which in many cases also may cigarette smoking (Rosenman et al., 1975). Sub- begin to emerge in the earlier years of life, the sequent research did not fully confirm these find- need for a life span perspective on CVD risk ings, resulting in diminished interest in the TABP reduction becomes quite clear. The promotion (Matthews, 1988). and maintenance of a healthy lifestyle in young About this time, evidence began to emerge to people has the greatest potential for reducing the suggest that hostility and anger form the risk- lifetime burden of cardiovascular diseases. enhancing components of the TABP. Prospective studies of hostility and anger constructs and dif- Stress and Emotional Dispositions ferent forms of anger expression have yielded Several promising psychosocial risk factors for promising findings (Kent & Shapiro, 2009). CVD involve the concept of psychological stress. Much of this research has relied on the Ho Scale Psychological stress entails (a) stressors, or envi- first described by Cook and Medley (1954). It ronmental events and conditions that place appears that hostility, characterized by cynicism demands and constraints on a person’s adaptive and interpersonal mistrust, may be related to resources; (b) psychological responses to CAD-related outcomes, although negative find- stressors, including perceptual-evaluative ings have been reported as well (Kent & Shapiro, (appraisal) processes that initiate stress and emo- 2009). tion processes, and cognitive and behavioral More recently, depression has been identified responses, including coping activity, that may as a potentially potent independent predictor of C 348 Cardiovascular Risk Factors

CHD in healthy populations and as a factor that may reflect difficulty in assessing anxiety in the may contribute to both the manifestation and context of a medical condition and hospitaliza- worsening of CHD among coronary patients. In tion, and in differentiating a temporary state of addition, depression is associated with several anxiety from chronic anxiety (Suls & Bunde). As major cardiac risk factors (e.g., hypertension, with depression, anxiety has been examined both physical inactivity). Various forms, severity as a subclinical dimension of individual differ- levels, and symptoms of depression have been ences and in terms of clinical conditions such as examined in this regard. Findings indicate that posttraumatic stress disorder. depressive symptoms and major depression are Still another emotional disposition that may associated with increased cardiovascular morbid- operate as a CVD risk factor, neuroticism, refers ity and mortality, even after controlling for other to individual differences in irritability, anger, risk factors (Kent & Shapiro, 2009). Further, sadness, anxiety, worry, hostility, self-conscious- major depression is associated more strongly ness, and vulnerability in response to threat, frus- with adverse cardiac events than is the presence tration, or loss. Initially, neuroticism was not of subclinical depressive symptoms (Rozanski, thought to play a causal role in CVD. Instead, Blumenthal, Davidson, Saab, & Kubzansky, the association with CAD was thought to reflect 2005). effects on somatic complaints and health-care- In addition, depressed individuals are more seeking behaviors (Costa & McCrae, 1987). likely than nondepressed individuals to have However, an expanding body of evidence impli- more than one risk factor for CVD, which may cates neuroticism as a possible causal agent in indicate that the association between depression multiple mental and physical disorders, including and CVD is due, in part, to the combination of CVD (Lahey, 2009). Neuroticism is thought to risk factors rather than to each risk factor consid- contribute to health risk through the experience ered independently (Joynt, Whellan, & of more stressors, less social support, and greater O’Connor, 2003). As with hostility, there are likelihood to engage in risky behaviors. Given some inconsistencies in this research. Nonethe- that neuroticism incorporates anger, sadness, less, the sheer volume of findings that support and anxiety, and in light of positive associations depression as a CHD risk factor builds a strong among these emotional dispositions when mea- case in its favor (Kent & Shapiro, 2009). sured separately, questions have been raised A third emotional disposition that has been about the independence of these variables and implicated as a possible CVD risk factor is anx- their possible interactions, especially since few iety. Research has revealed a link between anxi- studies have examined two or more of them ety and the development of CVD in physically simultaneously (Suls & Bunde, 2005). healthy populations, but evidence for this associ- ation has been mixed (Suls & Bunde, 2005). Social Factors Studies of populations with known CHD have In addition to these dispositional constructs, also yielded inconsistent findings, with some some CVD risk factors are present in an individ- reporting null effects and others finding an ual’s social environment. One example is low inverse relationship (Suls & Bunde). To assess social support (Krantz & McCeney, 2002). Social anxiety, some researchers use diagnostic inter- support refers to the availability of a variety of views and clinical criteria, whereas others use social contacts from whom to derive benefits. self-report measures. Generally, results Such benefits include emotional support, tangible supporting anxiety as a CVD risk factor are aid, feelings of belonging, and informational more consistent in samples of initially healthy support. Social support is associated with individuals than in CVD patients. This may sig- other factors that are related to health such nify that negative emotions constitute a greater as socioeconomic status and medication compli- risk for the development of CVD than for its ance. Prospective studies have found an associa- progression. Inconsistencies in the findings also tion between low social support and risk of CVD. Cardiovascular Risk Factors 349 C

Particular emphasis has been placed on stress including alterations in neuroendocrine, as a mechanism underlying the association autonomic, hemodynamic, hematologic, and between low social support and CVD, although immunological/inflammatory processes. Begin- relevant investigations have yielded divergent ning with research on TABP, findings began to findings (Uchino, Cacioppo, & Kiecolt-Glaser, emerge in which emotional attributes and social- 1996). It appears social networks may be contextual factors moderated the effects of psy- cardioprotective as a result of their stress- chological stress on one or more physiological C buffering effects, but they also may operate response measures. In addition, accumulating independently of stress, for example, by evidence suggested that physiologic reactivity promoting healthy behaviors and discouraging represents a dimension of individual differences unhealthy ones. that is consistent across different psychological Another social contextual factor that has been stressors and stable over time. It appears related identified as a CVD risk factor is low socioeco- to or may even constitute a form of emotional nomic status (SES). SES has been defined in volatility that runs through emotion constructs terms of a person’s occupation, economic discussed above including anger/hostility, resources, social standing, and education. There depression, anxiety, and neuroticism. These find- is considerable support for the existence of an ings, in turn, have led to the hypothesis that SES health gradient that affects many diseases, physiological reactivity might operate as an inde- including CVD. Higher SES is associated with pendent CVD risk factor and to empirical obser- better general health, less chronic illness, and vations linking reactivity to CVD outcomes decreased mortality. That this association is evi- including the development of CHD and essential dent throughout the SES spectrum suggests that hypertension and the precipitation of acute epi- its effects cannot be completely explained by the sodes of myocardial ischemia and other cardiac effects of poverty on access to affordable health events. care. Relevant mechanisms may include cognitive and emotional processes, as well as psychosocial factors including social support Conclusion (Marmot et al., 1991). Identification of possible psychosocial risk Although the risk and protective factors factors for CVD gave rise to research on described above have received considerable explanatory mechanisms. These may be attention, they are not exhaustive of the con- described in terms of three major categories, structs that have been examined as potential namely, stress-related physiological activity; causes of CVD. Many other variables have behaviors that may promote CVD in initially been investigated, including macrosocial fac- healthy individuals, including other CVD risk tors such as culture, political systems, and factors such as cigarette smoking, sedentary life- migration; additional forms of stress, such as style, and poor diet; and cognitive and affective racism; emotional dispositions such as Type responses to illness and its treatment once CVD D behavior (negative emotions accompanied has developed, including processes culminating by social inhibition); social and personal forms in delay in health-care seeking and treatment of religion and spirituality; specific behaviors noncompliance. such as alcohol consumption; and various infec- Of the many theoretical and empirical contri- tious conditions and biomarkers. These efforts butions to emerge from mechanism-focused are fueled by the need to identify additional work on psychosocial CVD risk factors, risk factors to account more completely for perhaps the most significant development new cases of CVD and to improve the public was formulation of the reactivity hypothesis. health benefits of risk factor modification for Reactivity refers to changes in physiologic this multiply determined set of chronic lifestyle activity associated with psychological stress, disorders. C 350 Cardiovascular Stress Responses

Cross-References of behavioral cardiology. Journal of the American College of Cardiology, 45, 637–651. ▶ Suls, J., & Bunde, J. (2005). Anger, anxiety, and depres- Anxiety and Heart Disease sion as risk factors for cardiovascular disease: The ▶ Cardiovascular Disease Prevention problems and implications of overlapping affective ▶ Depression: Symptoms dispositions. Psychological Bulletin, 131, 260–300. ▶ Epidemiology Uchino, B. N., Cacioppo, J. T., & Kiecolt-Glaser, J. K. ▶ (1996). The relationship between social support and Fibrinogen physiological processes: A review with emphasis on ▶ Psychological Stress underlying mechanisms and implications for health. ▶ Social Inhibition Psychological Bulletin, 119, 486–531. ▶ Social Relationships ▶ Social Support ▶ Stress Vulnerability Models Cardiovascular Stress Responses

▶ Blood Pressure Reactivity or Responses

References and Readings

Contrada, R. J., & Baum, A. (2011). Handbook of stress Cardiovascular Surgery science: Biology, psychology, and health. New York: Springer. Cook, W. W., & Medley, D. M. (1954). Proposed hostility ▶ Cardiac Surgery and pharisaic-virtue scales for the MMPI. Journal of Applied Psychology, 38, 414–417. Costa, P. T., & McCrae, R. R. (1987). Neuroticism, somatic complaints, and disease: Is the bark worse than the bite? Journal of Personality, 55, 299–316. Care of Older Adults Friedman, M., & Rosenman, R. H. (1974). Type A behavior and your heart. New York: Knopf. ▶ Geriatric Medicine Joynt, K. E., Whellan, D. J., & O’Connor, C. M. (2003). Depression and cardiovascular disease: Mechanisms of interaction. Biological Psychiatry, 54, 248–261. Kent, L. M., & Shapiro, P. A. (2009). Depression and related psychological factors in heart disease. Harvard Care Recipients Review of Psychiatry, 17, 377–388. Krantz, D. S., & McCeney, M. K. (2002). Effects of psychological and social factors on organic disease: Maija Reblin A critical assessment of research on coronary heart College of Nursing, University of Utah, Salt Lake disease. Annual Review of Psychology, 53, 341–369. City, UT, USA Lahey, B. B. (2009). Public heath significance of neurot- icism. American Psychologist, 64, 241–256. Marmot, M. G., Stansfeld, S., Patel, C., North, F., Head, J., White, I., et al. (1991). Health Inequalities among Synonyms British civil servants: The Whitehall II study. Lancet, 337, 1387–1393. Matthews, K. A. (1988). Coronary heart disease and Patients Type A behaviors: Update on and alternative to the Booth-Kewley and Friedman (1987) quantitative review. Psychological Bulletin, 104, 373–381. Definition Rosenman, R. H., Brand, R. J., Jenkins, C. D., Friedman, M., Straus, R., & Wurm, M. (1975). Coronary heart disease in the Western Collaborative Group Study. Journal of One who receives care; an individual with the American Medical Association, 233, 872–877. a medical condition or who requires support with Rozanski, A., Blumenthal, J. A., Davidson, K. W., activities of daily living and is in a relationship Saab, P. G., & Kubzansky, L. (2005). The epidemiol- ogy, pathophysiology, and management of psychoso- with a caregiver, such as a doctor, nurse, friend, or cial risk factors in cardiac practice: The emerging field family member, who provides treatment, Caregiver/Caregiving and Stress 351 C assistance, or comfort (National Alliance for Caregiving & AARP. Caregiving in the U.S, Caregiver/Caregiving and Stress 2009). Care recipients are not necessarily passive; action often must be taken to access, secure, and Alyssa Parker personalize care. This may involve navigation of UTSW Health Systems, South western Medical the health-care and insurance system; decision Center, Dallas, TX, USA making based on personal, family, or cultural C values and beliefs; selecting, managing, and adher- ing to the treatment regime; emotional responses Synonyms to and coping with the potential stress of receiving care; and managing communication with care Caregiver burden providers (Holman & Lorig, 2000).

Definition References and Readings Caregiving affects the quality of life of millions Holman, H., & Lorig, K. (2000). Patients as partners in of individuals and is frequently associated with managing chronic disease. Partnership is a prerequisite physical and psychological distress. Caregiving for effective and efficient health care. BMJ, 320(7234), 526–527. burden has been linked to decreased preventative National Alliance for Caregiving and AARP. Caregiving health behaviors and perception of quality of life, in the U.S. (2009). Available at: http://www.caregiv- which ultimately negatively impacts the care ing.org/data/Caregiving_in_the_US_2009_full_report. recipient. Additionally, the chronic stress of care- pdf giving has been found to decrease immune func- tioning of the caregiver in general, including decrements in cellular immunity, higher risk for infectious disease, and slower wound healing. Caregiver Acts of Omission Multicomponent interventions have been helpful in coping both cognitively and behaviorally. ▶ Child Neglect

Description

Caregiver Burden Caregiving has become an issue of national pub- lic health. Due to advances in medicine and tech- ▶ Caregiver/Caregiving and Stress nology, a shortage of nurses and other health-care ▶ Stress, Caregiver workers, and a movement since the 1960s away from institutionalization, caregiving, especially family caregiving, has become a necessity that affects the quality of life of millions of individ- Caregiver Hassle uals (Family Caregiver Alliance, 2011). Caregiv- ing is a diverse endeavor because the demands of ▶ Stress, Caregiver caregiving differ with regard to age, developmen- tal level, mental health needs, and physical health needs of both the caregiver and the care recipient. Those in the caregiving role become Caregiver Strain a critical agent between the recipient and a multitude of environments, including biologi- ▶ Stress, Caregiver cal, psychological, social, cultural, physical, and C 352 Caregiver/Caregiving and Stress political (Perkins & Haley, 2010). Although the to which activities of daily living can be com- core of successful caregiving revolves around pleted independently, play an important role in the caregiver’s own physical and mental health, caregiver burden. Those in the care position with it is a situation that has been described as one the heaviest burden are more likely to report their filled with heartache, pain, and loss (George & health as fair or poor and are more likely to report Gwyther, 1986; Poulshock & Diemling, 1984). physical strain as well as significant emotional Thrust into a role devoid of formal training, strain (Caregiving in the US, 2004). Burden has choice, or compensation, many family caregivers also been linked to caregiver mood, caregiver’s suffer physical and psychological distress related perceptions of the degree of recipient disability, to their experiences. In an effort to provide care and negative affectivity. Negative affectivity is for their ill relatives, caregivers often neglect the extent to which a person experiences negative their own health. Some caregivers believe they mood states, including upset, anger, worry, guilt, are not entitled to time to themselves or time fear, and disgust. Caregivers who rate high in away from the recipient, which ultimately leaves negative affectivity often report distress, discom- them feeling fearful and guilty (Bedini & Guinan, fort, and dissatisfaction over time, regardless of 1996). Those who do participate in noncaring the situation (Blake et al., 2000). Higher negative activities, such as socializing or discovering affectivity has also been linked to less adaptive hobbies, may derive less positive experiences coping strategies and is a vulnerability factor due to the spillover effect of distress resulting in the development of anxiety and depression from care. As a result, subjective well-being, (Gunthert et al., 1999). Relationship with the including positive affect, life satisfaction, and recipient prior to illness or disability and avail- perceived quality of life, may be affected ability of social support also play important roles (Gilleard, et al., 1984; Kosberg & Cairl, 1986). in the extent to which the caregiver experiences Compared to matched controls, caregivers, espe- strain. cially spousal caregivers, have demonstrated uni- Research on the differences between male and formly negative changes in immune function due female caregivers has been mixed. Although men to chronic stress, including decrements in cellular and women do not differ greatly in aspects of immunity, higher vulnerability to infectious dis- providing care, male caregivers report experienc- ease, and slower wound healing. These immuno- ing less burden and demonstrate more problem- logical consequences often persist at measurable focused coping strategies than female caregivers levels even after cessation of caregiving tasks (Tiegs et al., 2006). One explanation is that and may be the cause of morbidity and mortality women’s involvement in the caregiving role in the elderly (Kiecolt-Glaser, Dura, Speicher, tends to be more intensive and affective in nature Trask & Glaser, 1991; Kiecolt-Glaser, 1999). than their male counterparts. Additionally, it has Additionally, individuals who report strain are been suggested that women are more likely to less likely to engage in preventative health carry out household tasks while caring for behaviors such as getting enough sleep, taking a family member (Miller & Cafasso, 1992; time to recuperate, exercising, eating regular Parks & Pilisuk, 1991). Other research has meals, and keeping medical appointments shown no gender differences when controlling (Burton et al., 1997; Talley & Crews, 2007). for protective factors, such as personality and Consequently, caregivers are at significant risk social support. for experiencing health problems, depression, Due to the associated risks, individuals caring anxiety, and social isolation. for loved ones benefit from the development of Risk for physical and mental health difficulties a repertoire of both cognitive and behavioral can be predicted to some extent by qualities pre- strategies that enable them to defend against dis- sent in both the caregiver and the care recipient. tress while continuing to provide effective care. The dependency needs of the recipient, such as Research to date on caregiver interventions has the number of hours of care needed or the degree focused primarily on reducing depression and Caregiver/Caregiving and Stress 353 C strain via an emphasis on the following six some symptom relief from depression and anxi- intervention approaches: psychoeducational, ety (Konstam et al., 2003). Finding meaning supportive, respite/adult care, psychotherapy, through caregiving allows the caregiver to improvements in care receiver competence, and hold positive beliefs about one’s self and one’s multicomponent interventions (Sorenson et al., caregiving experience. 2002). Intervention outcomes include the family caregiver’s well-being, psychologic morbidity C (stress, depression, perceived burden), beliefs Cross-References (self-efficacy, control), cognitive behaviors and positive psychological outcomes (rewards, ▶ Care Recipients gains), and care recipient’s function, behavior, ▶ Chronic Disease or Illness and ability to avoid institutionalization (Gitlin ▶ Daily Stress et al., 2003). The most effective caregiver inter- ▶ Dementia ventions to date have been multicomponent inter- ▶ Disability ventions that utilize a combination of cognitive ▶ Disease Burden behavioral approaches to reducing caregiver ▶ Elderly stress. Behaviorally, exercise and the utilization ▶ End-of-Life Care of social support have been the most valuable ▶ Family Assistance techniques in relieving stress associated with ▶ Family, Caregiver caregiving. Available social support and per- ▶ Home Health Care ceived social support can buffer caregiver vulner- ▶ Lifestyle Changes ability to stress and provide physical assistance ▶ Medical Decision-Making when needed (Dean & Lin, 1977; O’Brien, 1993). ▶ Stress, Caregiver Cognitively, the utilization of logical analysis ▶ Stress, Emotional and problem solving has been associated with higher levels of life satisfaction, better health, and lower depression in caregivers. A realistic References and Readings appraisal and acceptance of the difficult situation is healthy and allows the caregiver to live his or Bedini, L. A., & Guinan, D. M. (1996). If I could just be her own life while accommodating the needs of selfish. Caregivers’ perceptions of their entitlements to leisure. Leisure Sciences, 18, 227–239. the recipient. Less effective cognitive coping Blake, H., Lincoln, N. B., & Clarke, D. (2003). Caregiver styles include avoidant-evasive, regressive, and strain in spouses of stroke patients. Clinical Rehabili- an increased use of wishfulness and fantasizing tation, 17(3), 312–317. by the caregiver, all of which have been related to Burton, L. C., Newsom, J. T., Schulz, R., Hirsch, C. H., & German, P. S. (1997). Preventative health behaviors higher levels of care burden (Hayley et al., 1987; among spousal caregivers. Preventative Medicine, Quayhagen & Quayhagen, 1988). 26(2), 162–169. Despite the reality of care strain and its Connell, C. (1994). Impact of spouse caregiving on health resulting physical and mental health risks, many behavior and physical and mental health status. Amer- ican Journal of Alzheimer’s Care Related Disorders caregivers persist for years in their roles and are Research, 9, 26–37. able to report positive and reciprocal caregiving Dean, A., & Lin, N. (1977). The stress-buffering role of experiences (Pinquart & Sorenson, 2004). Long- social support. The Journal of Nervous and Mental term caregiving may result in the acquisition of Disease, 6, 403–417. Family Caregiving Alliance, (n.d.). National Center on skills and a sense of self-efficacy within the care Caregiving: Family caregiving and public policy, role. Some individuals found that caregiving pro- principles for change. Retrieved January 2011, from vided a sense of usefulness during a time in which http://www.caregiver.org/caregiver/jsp/content_node. they felt a loss of control. This sense of usefulness jsp?nodeid=788 George, K. L., & Gwyther, L. (1986). Families caring for and improved self-esteem based on perceived elders in residence: Issues in measurement of burden. abilities to handle difficult situation may provide Journal of Gerontology. C 354 Carpal Tunnel Syndrome

Gilleard, C. J., Gilleard, K., Gledhill, K., & Whittick, J. Talley, R. C., & Crews, J. E. (2007). Framing the public (1984). Caring for the mentally infirm at home: health of caregiving. American Journal of Public A survey of the supporters. Journal of Epidemiology Health, 97(2), 224–228. and Community Health, 38, 319–325. Tiegs, T. J., Heesacker, M., Ketterson, T. U., et al. (2006). Gitlin, L. N., Belle, S. H., Burgio, L. D., et al. (2003). Effect Coping by stroke caregivers: Sex similarities and of multicomponent intervention on caregiver burden and differences. Topics in Stroke Rehabilitation, 13(1), depression: The REACH multisite initiative at 6-month 52–62. follow-up. Psychology and Aging, 18(3), 371–374. Gunthert, K., Cohen, L., & Armeli, S. (1999). The role of neuroticism in daily stress and coping. Journal of Personality and Social Psychology, 77, 1087–1100. Hayley, W. E., Levine, E. G., Brown, S. L., Berry, J. W., & Carpal Tunnel Syndrome Hughes, G. H. (1987). Psychological, social, and health consequences of caring for a relative with senile demen- Daniel Gorrin tia. Journal of American Geriatrics Society, 35, 405–411. Department of Physical Therapy, University of Kiecolt-Glaser, J. K. (1999). Stress, personal relation- ships, and immune function: Health implications. Delaware, Newark, DE, USA Brain, Behavior, and Immunity, 13, 61–72. Kiecolt-Glaser, J. K., Dura, J. R., Speicher, C. E., Trask, O. J., & Glaser, R. (1991). Spousal caregivers of Definition dementia victims: Longitudinal changes in immunity and health. Psychosomatic Medicine, 53, 345–362. Konstam, V., Holmes, W., Wilczenski, F., Baliga, S., The carpal tunnel refers to the area of the wrist Lester, J., & Priest, R. (2003). Meaning in the lives between the carpal bones and the overlaying of caregivers of individuals with Parkinson’s disease. fibrous band of connective tissue called the trans- Journal of Clinical Psychology in Medical Settings, 10(1), 17–26. verse carpal ligament or the flexor retinaculum. Kosberg, J. I., & Cairl, R. E. (1986). The cost of The median nerve passes through the carpal care index: A case management tool for screening tunnel along with nine tendons of muscles pro- informal care providers. Gerontologist, 26, 273–285. viding finger and wrist flexion (flexor digitorum Miller, B., & Cafasso, L. (1992). Gender differences in caregiving: Fact or aritfact? Gerontologist, 32, 498–507. profundus, flexor digitorum superficialis, and Monahan, D. J., & Hooker, K. (1995). Health of spouse flexor pollicis longus). caregivers of dementia patients: the role of personality Carpal tunnel syndrome refers to an entrap- and social support. Social Network, 40(3), 305–314. ment or compression of the median nerve at the National Alliance for Caregiving/AARP. (2004). Caregiv- ing in the U.S. Washington, DC: Author. wrist. The median nerve can become compressed O’Brien, M. T. (1993). Multiple Sclerosis: Health- under the flexor retinaculum. The etiology is promoting behaviors of spousal caregivers. Journal unknown in most cases; however, carpal of Neuroscience Nursing, 25(2), 105–112. tunnel syndrome can result from a trauma such Parks, S. H., & Pilisuk, M. (1991). Caregiver burden: Gender and the psychological costs of caregiving. The American as a fracture or dislocation of the carpal bones at Journal of Orthopsychiatry, 61, 501–509. the wrist. Such trauma can lead to direct injury of Perkins, E. A., & Haley, W. E. (2010). Compound care- the nerve and increased pressure within the giving: When lifelong caregivers undertake additional carpal tunnel. Other potential causes of the roles. Rehabilitation Psychology, 55, 409–417. Pinquart, M., & Sorenson, S. (2004). Associations of condition include rheumatoid arthritis, renal caregiver stressors and uplifts with subjective well- disease, hypothyroidism, lupus, obesity, preg- being and depressed mood: a meta-analytic compari- nancy, alcoholism, diabetes, and certain collagen son. Aging & Mental Health, 8(5), 438–449. diseases. If the underlying cause of the condition Poulshock, S. W., & Diemling, G. (1984). Families caring for elders in residence: Issues in measurement of bur- can determined and treated, the median nerve den. Journal of Gerontology, 39, 230–239. dysfunction could be resolved. Quayhagen, M. P., & Quayhagen, M. (1988). Alzheimer’s Symptoms of carpal tunnel syndrome include stress: Coping with the caregiving role. Gerontologist, burning, numbness, and tingling in the region of 28, 391–396. Sorenson, S., Pinquart, M., & Duberstein, P. (2002). How the hand supplied by the median nerve (thumb, effective are interventions with caregivers? An updated index finger, middle finger, and medial side of the meta-analysis. Gerontologist, 42(3), 356–372. ring finger) which can be exacerbated at night. Case Reports 355 C

Increased symptoms at night can likely be attrib- Definition uted to the patient favoring wrist flexion during sleep. This position narrows the space within the A case report is a descriptive study that provides carpal tunnel causing increased pressure on the a detailed description of a case of a disease that nerve. In more severe cases, the patient may is unusual, and therefore noteworthy, for some experience weakness and atrophy of the muscu- particular reason. It is usually written by a doctor, lature controlling the thumb. or perhaps by a group of doctors who have all C Electrodiagnostic tests and electromyographic become familiar with the case with each having studies can be used in conjunction with patient something unique to contribute to the report. An history and physical examination in order to extension of the case report is a case series, where diagnose carpal tunnel syndrome. Initially, the first report sparks interest and leads to reports treatment is intended to control inflammation on similar cases. and decrease stress on the nerve. Conservative In the discipline of epidemiology, a more sub- treatment includes activity modification, stantive investigative process often begins with splinting to decrease wrist flexion and pressure a case report or case series (Webb, Bain, & on the median nerve, and steroid injections Pirozzo, 2005). These reports provide detailed to decrease inflammation within the tunnel. descriptions of an individual, or a small group If the patient does not respond to conservative of individuals, who share salient characteristics. management, a surgical decompression of the The disease might not have been seen before, median nerve may be indicated. been noted in the literature before, or rarely been seen in that form before. Also, it may be References and Readings noteworthy that a known disease occurred in a patient who would not normally be expected Drake, R. L., Wayne Vogl, A., & Mitchell, A. W. M. to have the disease, or in a geographic location (2010). Gray’s anatomy for students (2nd ed.). Phila- where the disease is particularly rare. delphia: Churchill Livingstone Elsevier. Magee, D. J. (2008). Orthopedic physical assessment Such reports are by nature selective: Doctors (5th ed.). St. Louis, MO: Saunders Elsevier. may or may not write a case report which may or Magee, D. J., Zachazewski, J. E., & Quillen, W. S. (2009). may not be published and reach a large readership Pathology and intervention in musculoskeletal reha- of other doctors. Additionally, they are not able to bilitation (1st ed.). St. Louis, MO: Saunders Elsevier. Standring, S. (2008). Gray’s anatomy (40th ed.). provide evidence of causality, and they cannot Philadelphia, PA: Churchill Livingstone Elsevier. provide much evidence on the patterns of disease occurrence. For these reasons, they tend to appear toward the bottom of the “Hierarchy of Evi- Case Fatality dence,” a tabular representation of the relative strengths of various investigational methodolo- ▶ Mortality gies. Nonetheless, they can be very informative as the starting point for more extensive investigation. Case Reports Provocative case reports can certainly lead to important findings. A report of a series of five J. Rick Turner cases of Pneumocystis carinii pneumonia that Cardiovascular Safety, Quintiles, Durham, occurred in young, previously healthy, homosex- NC, USA ual men in three Los Angeles hospitals in a 6-month period during 1980–1981 is notewor- thy (Webb et al., 2005). In this case, the disease Synonyms had been seen before, but virtually always in patient populations with different characteristics: Case studies the elderly, patients who were severely C 356 Case Studies malnourished (and hence compromised when Definition combating infection), and patients receiving che- motherapy for cancer who had developed A case-control study is a study in which subjects compromised immune systems. The clustering are selected based on their outcome status, such of cases in the population of young homosexual as with disease or disease-free. Investigators men suggested a different disease. While the case select cases (subjects with the outcome of inter- reports, as noted previously, were not able to est) and controls (subjects without the outcome of address causality or causal biological pathways, interest) and then compare the exposure (or risk they did suggest the possibility of a relationship factor) status in the two groups. with the patients’ sexual behavior. You may rec- ognize that this disease is now known as HIV/ AIDS (which is certainly not limited to young Description homosexual men). Case-control studies are a very common observa- tional study design within behavioral medicine Cross-References research. Because the participants are selected based on their outcome status (commonly disease ▶ Clusters status), this study design is well suited for an ▶ Hierarchy of Evidence outcome that is rare. For diseases with long latency periods (for example, melanoma or coro- nary heart disease), case-control studies can also References and Readings be time efficient because the outcome has already occurred at the initiation of the study. When the Webb, P., Bain, C., & Pirozzo, S. (2005). Essential epi- exposure (or risk factor) is rare, a case- control demiology: An introduction for students and health study is often not practical. professionals. New York: Cambridge University Case-control studies determine the subjects’ Press. exposure retrospectively, commonly through his- torical records or self-report conducted after the exposure has occurred. Limitations of using ret- rospective data contribute to results from case- Case Studies control studies being considered weaker than results from experimental designs that examine ▶ Case Reports similar associations. Recall bias can occur when case subjects remember exposure differentially compared to controls. For example, a mother whose infant was born with a birth defect may Case-Control Studies differentially recall her use of medication during pregnancy compared to a mother of an infant Jane Monaco without a birth defect (Rockenbauer, Olsen, Department of Biostatistics, The University of Czeizel, Pedersen, & Sørensen 2001). The use North Carolina at Chapel Hill, Chapel Hill, of retrospective data, however, may facilitate NC, USA study approval by ethical review boards, particu- larly, when the risk factor is illegal or known to be harmful, such as illicit drug use or tobacco use. Synonyms The selection of control subjects is critical in the design of a case-control study. Subjects cho- Observational designs; Observational studies; sen as controls should be as similar as possible to Observational study the case subjects except, potentially, with respect Case-Crossover Studies 357 C to the exposure. Specifically, cases and controls • Usually can only address a single outcome should have had equal chance to be exposed to (disease) the risk factor. For this reason, cases and controls • Susceptible to recall bias (since exposure and are often matched with respect to age, gender, outcome are determined retrospectively) and ethnicity, and other factors. selection bias (which can occur when the con- In many case-control studies, the groups are trols are selected in such a way that they did compared by evaluating the odds ratio which is not have same risk of exposure as the cases) C defined as the odds of exposure among the cases • Often considered weaker study design com- divided by the odds of exposure among the con- pared to cohort studies or randomized trials trols. In general, investigators cannot determine that study analogous associations incidence rates of the disease since the subjects are selected based on disease (outcome) status. Cross-References Thus, computing a relative risk directly is not possible. However, the relative risk can be ▶ Cohort Study approximated by the odds ratio when the outcome ▶ Odds Ratio of interest is relatively rare. ▶ Retrospective Study In a typical behavioral medicine case-control example, Brent et al. (1993) investigated the References and Readings association between adolescent suicide and mul- tiple psychiatric risk factors. Sixty-seven adoles- Brent, D. A., Perper, J. A., Moritz, G., Allman, C., cent suicide victims (cases) were matched to 67 Friend, A., Roth, C., et al. (1993). Psychiatric risk factors for adolescent suicide: A case-control study. controls with respect to age, gender, socioeco- Journal of the American Academy of Child and nomic status, and county of residence. Investiga- Adolescent Psychiatry, 32(3), 521–529. tors obtained information about the suicide Hennekens, C. H., Buring, J. E., & Mayrent, S. L. (1987). victims through a “psychological autopsy proto- Epidemiology in medicine. Boston, MA: Lippincott Williams & Wilkins. col” in which parents, siblings, and friends were Kleinbaum, D. G., Sullivan, K. M., & Barker, N. D. interviewed concerning the victim’s risk factors. (2007). A pocket guide to epidemiology. New York: The controls’ risk factor information was Springer. obtained from the participant and at least one Rockenbauer, M., Olsen, J., Czeizel, A. E., Pedersen, L., & Sørensen, H. T. (2001). Recall bias in a case-control parent. The study found that the suicide victims surveillance system on the use of medicine during had significantly higher odds of major depression pregnancy. Epidemiology, 12(4), 461–466. and substance abuse compared to the controls. Some characteristics of case-control studies: • Usually less expensive and less time consum- Case-Crossover Studies ing than cohort designs or experimental designs • Often used when the outcome of interest is J. Rick Turner rare or has a long latency period Cardiovascular Safety, Quintiles, Durham, • Not practical when exposure is rare NC, USA • Sample size requirement is usually smaller than cohort or experimental designs • Often used in initial investigations of an asso- Definition ciation due to logistical ease and relative lower cost The innovative case-crossover study design is • May be used when exposure of participants to a hybrid design. Hybrid designs are those that risk factor would be considered unethical in an combine the elements of two or more basic experimental design designs, or extend the strategy of one basic design • Appropriate when studying multiple risk through repetition (Kleinbaum, Sullivan, & factors Barker, 2007). C 358 Casual Sex

The case-crossover design represents an Rothman, K. J., Greenland, S., & Lash, T. L. (2008). Case- attempt to achieve the ideal, but unattainable, control studies. In K. J. Rothman, S. Greenland, & T. L. Lash (Eds.), Modern epidemiology (3rd ed., pp. 111– design of studying a group of subjects exposed 127). Philadelphia: Lippincott Williams & Wilkins. to a particular event, activity, or influence, and Webb, P., Bain, C., & Pirozzo, S. (2005). Essential epide- also studying exactly the same subjects during the miology: An introduction for students and health pro- same period when not exposed to it. The design fessionals. New York: Cambridge University Press. utilizes each subject as his or her own control. Exposure to the event in a defined (and likely fairly short) time period before the onset of Casual Sex disease is compared with typical exposure to it ▶ in a much longer period before disease onset, Sexual Hookup defined as the normal exposure. Only a limited set of research topics are ame- nable to the employment of the case-crossover CAT Scan design (Rothman, Greenland, & Lash, 2008). The exposure must vary over time within individuals, Mary Spiers rather than stay constant, and the exposure must Department of Psychology, Drexel University, have a short induction time and a transient effect. Philadelphia, PA, USA A classic example is the study reported by Maclure (1991), which used this design to study the effect of sexual activity on incident myocardial infarc- Synonyms tion. Several aspects make this design appropriate and informative in this case. First, the exposure to Computed transaxial tomography; Computerized the factor of interest, sexual activity, is intermittent axial tomography; CT scan; X-ray computed and presumed to have a short induction period for tomography the hypothesized effect. Second, any increase in risk for myocardial infarction caused by sexual activity is presumed to be confined to a short Definition time interval following the activity. Third, since myocardial infarctions are thought to be triggered A CAT scan is a structural imaging method based by events close in time, this outcome is well suited on the x-ray principle but is more sensitive to to this type of study (Rothman et al., 2008). bone, tissue, and fluid density differences and employs a narrower beam, allowing for the seg- mentation of the imaged area into multiple Cross-References transaxial images from many different angles. These images can be combined via computer ▶ Case-Control Studies technology to provide either 2D or 3D images. Enhanced CAT scans can reveal even greater References and Readings contrast through injection of an intravenous dye. CAT scans are useful for imaging bones, soft Kleinbaum, D. G., Sullivan, K. M., & Barker, N. D. tissue, blood vessels, and internal organs and (2007). A pocket guide to epidemiology. New York: particularly useful in imaging size and location Springer. Maclure, M. (1991). The case-crossover design: A method of tumors and their relationship to normal tissue. for studying transient effects on the risk of acute CAT scans are also useful in imaging injuries to events. American Journal of Epidemiology, 133, skeletal structures in relation to the surrounding 144–153. tissue and the detection of vascular disorders in Maclure, M., & Mittleman, M. A. (2000). Should we use a case-crossover design? Annual Review of Public the body and brain. CAT scans are particularly Health, 21, 193–221. useful in the identification of emboli (blood clots) Catecholamines 359 C and aneurysms. Scans of the brain cannot reveal or outcomes of an event. Catastrophizing is a microscopic brain changes (e.g., axonal injury) characteristic type of cognitive distortion or but are useful in identifying lesions, tumors, and error that may underlie a negative and inaccurate stroke (infarct) and particularly for differentiat- thought (Beck, Rush, Shaw, & Emery, 1979; ing hemorrhagic from nonhemorrhagic stroke. Clark, Beck, & Alford, 1999). It can have nega- CAT scans are generally cheaper than magnetic tive health consequences for individuals who are resonance imaging (MRI) but provide poorer res- managing a chronic illness. For example, a recent C olution. In relation to the brain, CAT scans also cancer survivor may interpret his fatigue as do not show the functioning of the brain as would meaning that he will never recover his usual be revealed with functional imaging methods energy level and that he will have to give up all such as (functional MRI (fMRI) or positron emis- of his meaningful activities. This type of thinking sion tomography (PET)). can maintain negative emotions such as depres- sion and lead to adverse or unhelpful behaviors Cross-References such as poor medical adherence.

▶ Cancer Screening/Detection/Surveillance Cross-References ▶ Computerized Axial Tomography (CAT) Scan ▶ Functional Magnetic Resonance Imaging ▶ Cognitive Distortions (FMRI) ▶ Negative Thoughts ▶ Magnetic Resonance Imaging (MRI) ▶ Neuroimaging References and Readings

References and Readings Beck, A. T., Rush, A. J., Shaw, B. F., & Emery, G. (1979). Cognitive therapy of depression. New York: Guilford Press. Weissleder, R., Wittenberg, J., & Harisinghani, M. G. Clark, D. A., Beck, A. T., & Alford, B. A. (1999). Scien- (2007). Primer of diagnostic imaging (4th ed.). St. tific foundations of cognitive theory and therapy of Louis: Mosby. depression. New York: Wiley. Zillmer, E. A., Spiers, M. V., & Culbertson, W. C. (2008). Principles of neuropsychology (2nd ed.). Belmont, CA: Wadsworth/Thompson Learning. Catecholamines

Catastrophizing/Catastrophic George J. Trachte Thinking Academic Health Center, School of Medicine-Duluth Campus, Lara Traeger University of Minnesota, Duluth, MN, USA Behavioral Medicine Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA Synonyms

Adrenaline; Epinephrine; Norepinephrine/ Synonyms Noradrenaline

Arbitrary inference Definition Definition Catecholamines are derivatives of the chemical Catastrophizing refers to the anticipation without dihroxyphenyl (catechol) ethylamine. They are evidence of extreme and terrible consequences found in the sympathetic nervous system, adrenal C 360 Causal Diagrams medulla, and selected brain regions. The promi- stimulation of dopamine receptors include addic- nent naturally occurring catecholamines in tion, schizophrenia, psychoses, and learning def- humans are dopamine, norepinephrine, and epi- icits. Norepinephrine also is a critical central nephrine. These agents are intrinsic neurotrans- neurotransmitter. Augmentation of norepineph- mitters of the sympathetic nervous system and rine concentrations in nerve synapses is mediate the “fight or flight” reactions to stressful a frequent mechanism of action of situations. Examples of sympathetic responses antidepressants. include tachycardia, hypertension, pupillary The synthesis of catecholamines is regulated dilation, sweating, and liberation of fuel sources. primarily at the tyrosine to DOPA step. The They also are prominent neurotransmitters in release of catecholamines is regulated by activity specific regions of the brain, typically being asso- of the sympathetic nervous system, involving ciated with pleasure, excitement, and movement. acetylcholine as a neurotransmitter, or by activa- Catecholamine synthesis involves conversion tion of specific brain regions. of the amino acid, tyrosine, to dihydroxypheny- Dopamine is recognized as a critical neuro- lalanine (DOPA) by adding a hydroxyl group. transmitter influencing movement, memory, cog- DOPA is converted to dopamine by removal nition, emotion, and reward. As such, it of a carboxyl group. Dopamine is a neurotrans- influences movement and its absence is most mitter in the brain and in peripheral nerves. Dopa- easily noted in the symptoms of Parkinson’s mine also is a precursor of norepinephrine, disease. Dopamine also is involved in a variety requiring a conversion by dopamine ß hydroxy- of psychological abnormalities such as addiction, lase. Norepinephrine is the major neurotransmit- schizophrenia, psychoses, and learning deficits. It ter of the sympathetic nervous system and also is also inhibits prolactin release, potentially indi- a major neurotransmitter in the central nervous rectly elevating mood. system. Norepinephrine can be converted to Norepinephrine has mood-elevating effects epinephrine by phenylethanolamine-N-methyl and a variety of antidepressants increase the transferase, primarily in the adrenal medulla but concentrations of norepinephrine in neuronal syn- also in the brain. Epinephrine is considered to be apses of the brain. The variety of antidepressants a neurotransmitter of the sympathetic nervous elevating norepinephrine concentrations includes system although it functions more as an endo- monamine oxidase inhibitors, tricyclic antidepres- crine agent, circulating in the blood to promote sants, and norepinephrine reuptake inhibitors. various stress-related effects. The physiological relevance of norepineph- Cross-References rine and epinephrine in the periphery is quite obvious because these agents mediate most of ▶ Central Nervous System the responses to stressful situations. They have ▶ Epinephrine the following effects: activation of ß1 receptors ▶ Norepinephrine/Noradrenaline on the heart to increase heart rate, force of contraction, and blood pressure; activation of a1 receptors on vascular smooth muscle, the eye, Causal Diagrams and sweat glands to raise blood pressure, dilate pupils, and promote sweating; and activation of J. Rick Turner a1, ß2, and ß3 receptors to liberate fuel stores for Cardiovascular Safety, Quintiles, Durham, energy. Central actions of dopamine and norepi- NC, USA nephrine are equally obvious. Dopamine is criti- cally involved in movement, reward, emotion, memory, and cognition. Conditions related Synonyms to dopamine deficiencies include Parkinson’s disease. Conditions related to excessive Causal pathway diagram; Causal pathway model Cellular Theory of Aging 361 C

Definition Causes A causal diagram is a more modern form of causal pathway models that have been used to ▶ Attribution Theory summarize visually hypothetical relationships between variables of interest to the researcher. They represent a merger of graphical probability C ® theory with path diagrams. This theory confers Celexa a powerful means of deducing the statistical asso- ciations implied by causal relations. ▶ Selective Serotonin Reuptake Inhibitors Once the rules for reading statistical associa- (SSRIs) tions from causal diagrams are mastered, they facilitate many tasks. These include understand- ing confounding and selection bias, choosing covariates for adjustment and for regression Cell Adhesion Molecule analyses, and understanding analyses of direct effects and instrumental-variable analyses ▶ Adhesion Molecules (Glymour & Greenland, 2008).

Cross-References Cellular Theory of Aging

▶ Bias Emil C. Toescu ▶ Regression Analysis Division of Medical Sciences, The University of Birmingham, Edgbaston, Birmingham, UK

References and Readings Definition Glymour, M. M., & Greenland, S. (2008). Causal Diagrams. In K. J. Rothman, S. Greenland, & T. L. Cellular theories explain the aging process as Lash (Eds.), Modern epidemiology (3rd ed., pp. 183–209). Philadelphia: Wolters Kluwer/ originating in individual cells, either at the level Lippincott Williams & Wilkins. of the genetic information or through changes in metabolism.

Causal Pathway Diagram Description ▶ Causal Diagrams The quest for understanding the process of aging is probably as long as human history, and its Causal Pathway Model resolution is still far from clear or even assured. A major factor for this state of affairs is that aging ▶ Causal Diagrams is a complex, multifactorial process that develops during ontogeny gradually, at multiple levels, involving a certain degree of stochastic random- ness. At a certain time (early 1990s), more than Cause Marketing 300 various hypotheses were circulating for explaining aging, and, responding to a need ▶ Social Marketing for organizing such a vast catalogue, these C 362 Cellular Theory of Aging hypotheses were classified as cellular theories breaks and oxidation of various bases. The other that explain the aging process as originating in category of damaging agents is exogenous, individual cells, either at the level of the genetic represented by chemical or physical (e.g., UV information or through changes in metabolism; and other types of ionizing radiations) factors. system theories, that propose that aging, while It has been shown that DNA mutations/alter- expressed at the level of individual cells, results ations and chromosomal abnormalities increase from dysfunction in one or another of the general with age both in animals (e.g., rodents) and system that maintain overall body homeostasis humans. In addition, the role of genetic mutation (e.g., the neuroendocrine theory of aging); and in inducing the aging phenotype is demonstrated evolutionary theories, that address the fundamen- by a number of syndromes of accelerated aging tal biological puzzle that aging, as a fundamen- (progeria). Amongst them, the best known is the tally deleterious process, should have been Werner’s syndrome which is determined by an gradually eliminated during evolution since evo- autosomal recessive mutation in a gene, WRN, lution aims to improve the adaptation of individ- that encodes for a protein with structural similar- uals and species to their environment. ities with a DNA helicase (enzyme catalyzing Within the group of cellular theories, the var- DNA unwinding). Loss of WRN function results ious hypotheses can be further separated into in a syndrome displaying the typical features those that invoke (a) changes in the genetic of aging, but starting as early as the second makeup (genome) of cells or (b) alterations and decade of life: bilateral cataracts, graying of dysfunction in various metabolic pathways (over- hair and alopecia, type 2 diabetes, atherosclerosis all, the “wear and tear” theories). and hyperlipidemia, osteoporosis, etc. Another The genome-related theories of aging start progeric manifestation is the Hutchinson- from the fundamental fact that the whole of the Gilford’s syndrome, with a rather similar clinical genetic information that controls the identity, manifestation but resulting from a point mutation development, and status of a cell is contained in the gene encoding for a nuclear protein: lamin within the DNA. Like anything else in nature, A/C (LMNA). Although the exact function of this molecule can be damaged either by random, either protein is not fully established, recent stochastic agents or by specific factors or pro- experimental evidence point to the fact that they cesses. Amongst other features, one of the unique are involved in the process of DNA repair. The properties of the DNA is that it is the only bio- importance of maintaining a robust genomic sta- logical molecule that relies for maintenance on bility led to the evolutionary development of the repair of the same existing molecule, without powerful and flexible DNA repair systems the possibility of remanufacture. Apart from the that include mechanisms for dealing with both implications for the importance and reliability of single-stand breaks (e.g., base excision repair the DNA repair mechanisms, this fact also leads and nucleotide excision repair) and double- to the conclusion that DNA molecules accumu- strand breaks (e.g., homologous recombination late damage over a lifetime since an error in DNA or nonhomologous end joining). Although there sequence information, once made during replica- are many reports of correlations between stability tion or recombination, becomes irreversible, due of DNA repair mechanisms and rate of aging in to the loss of the reference template. DNA integ- various animals (mammals) and, also, of an age- rity can be affected by several mechanisms. One dependent functional decline in one or another is endogenous, represented by the cellular metab- DNA repair mechanism, other studies found no olism; activity in all cells will generate continu- clear evidence for a drastic decline in DNA repair ously reactive oxygen and nitrogen species (free during aging, an observation taken simply to radicals) that either directly, or secondarily, reflect the central role of genome stability for through generation of lipid peroxidation prod- cell viability. In addition, accumulation of dam- ucts, alkylating agents or protein carbonyl spe- age with age does not necessarily imply a decline cies, will damage DNA by inducing single-strand in DNA repair – as any biological process, Cellular Theory of Aging 363 C genome maintenance systems are imperfect, and with time of metabolic dysfunction, that result in alterations can accumulate over time, particularly functional impairment of various cellular activi- in animals with longer life spans. ties, see below). It has been proposed that replica- A more recent line of investigation of the tive senescence ultimately results from the loss of relationships between DNA damage and aging telomeres, which are specific chains of a repeating stems from the fact that genome maintenance DNA sequences located at the ends of each linear involves not only the DNA repair systems but chromosome. With each cell division, a small C also the cellular responses triggered directly amount of DNA is necessarily lost on each chro- by the DNA damage. These responses include mosome end, resulting in ever-shorter telomeres, apoptosis, cellular senescence, and cell cycle altered telomere structure, and, when the telomere arrest, known to cause age-related impairments is under a critical length, a stop of replication and in various tissues. Thus, one of the most ubiqui- eventual replicative senescence. Activation of the tous response to unrepaired or improper repair telomerase enzyme will regenerate telomeres, pre- double-strand breaks involves the ataxia-telangi- vent replicative senescence, and immortalize ectasia-mutated (ATM) kinase. Activated ATM, human primary cell cultures. Importantly, in all in addition to modulation of several cell cycle cancer cells, there is an activation of telomerase or proteins DNA repair factors, targets p53, a central of an alternate pathway of telomere extension that protein at the crossroad of several cell viability avoids replicative senescence. pathways. While p53 suppresses the onset of Although there is a wealth of correlative data malignancy, having an indirect positive on (e.g., shorter telomeres in aged people or, more lifespan, it also triggers cellular senescence and specifically, in individuals with neurodegenera- apoptosis. A strong theoretical argument for the tive diseases, including Alzheimer’s; induction involvement of such a universal and general cel- of telomere shortening in condition of increased lular response in mediating the pro-aging effects metabolic stress), a causal involvement of telo- of DNA damage is that the phenotype of aging is mere reduction in aging is doubtful as telome- relatively constant from species to species and rase-deficient mice do not age more rapidly. also, in general lines, from individual to individ- Instead, as with the other genetic theories of ual whereas, with few exceptions, the exo- or aging discussed above, it is more likely that rep- endogenous induction of DNA damage is sto- licative senescence influences aging through the chastic and should result in highly variable func- various cellular responses it triggers. It has been tional outcomes. described that senescent cells produce and secrete An important cellular theory of aging is the various degradative enzymes and inflammatory cell senescence/telomere theory. The idea of cell factors that alter the microenvironment and lead senescence was formulated in 1965, describing to disturbed tissue structure and function. Also, the fact that normal cells can undergo only replicative senescence degrades and ultimately a limited number of cell divisions (Hayflick’s limits the regenerative potential of stem cell. limit), after which the cells enter replicative The intracellular mechanism triggered by telo- senescence, remain quiescent, and then, after mere shortening is the activation of the same a period of time, die. Since the number of cell tumor suppressor p53 protein. The type of p53- divisions varies from species to species (e.g., dependent cellular response (cell arrest, apopto- mouse cells divide roughly 15 times, while the sis, or senescence) is often cell type dependent cells for Galapagos tortoise divide 110 times), it and varies with the type of stimulus that triggers it has been proposed that this process of replicative and severity of stress that the cells are exposed to. senescence is an important regulator of life Being a tumor suppressor protein, it is not sur- span and thus a contributor to aging (NB this prising that mice mutated for p53 with loss of senescence process, dependent on the cell repli- function have a dramatically increased incidence cation, is different from the metabolic cellular of cancer, while p53 signaling is altered in the senescence, that results from the accumulation majority of human cancers. However, if cellular C 364 Cellular Theory of Aging senescence, linked with p53 activation, acts to instances, such redox changes result in suppress tumor formation, how can it be a modification of function of the target proteins, explained that cancer is more prevalent with age leading to loss of metabolic homeostasis and when senescence is also increased? There is cur- ensuing damage. If the free radicals attack is of rently no generally accepted explanation, and it is limited intensity or duration, the cellular damage likely that it results from subtle changes in the can be contained and either accumulate slowly balance between several processes and factors, over time or be repaired; more intense level of such that, due to its ample homeostatic and injury would result in cell death. The original functional reserve, in the adult organisms, the form of the Free Radical Theory of Aging functional and structural deleterious effects that (FRTA) envisaged aging as resulting from the senescent cells might cause to the tissues can be long-term accumulation of free radical–induced efficiently repaired by the normal tissue renewal damage, affecting mainly nuclear DNA, which is processes. Thus, in the main, in the mature very sensitive to the action of free radicals. An organisms, the main role of the p53-dependent important development of this hypothesis came senescence is to provide cancer protection. In con- with the discovery that the free radicals can result trast, in the aged organisms, the time-dependent not only from the effects of exogenous factors, accumulation of mutations (i.e., DNA damage), such as irradiation, but are also a natural output of together with the unfavorable metabolic environ- normal physiology. One of the reasons why this ment, and the decrease in the renewing capacity hypothesis of aging became so paradigmatic is generate conditions suitable for cancer growth. that it linked with several previous views, such One of the most widely acknowledged theo- that a higher rate of metabolism would generate ries of aging is the Mitochondrial Free Radical higher free radical loads and consequent damage, Theory of Aging (MFRTA), which has been and lead to a higher rate of aging. In the mid- presented in various guises, either as metabolic 1980s, the FRTA was complemented with the or as “wear and tear” theories, and linked to other mitochondrial perspective, with several observa- hypotheses, such as the “rate of living” theory. tions contributing to this development. (1) The The latter probably has the longest history, orig- mitochondria are the major source of free radicals inating at the beginning of last century with the since two of the protein complexes that form the empirical observation of a relationship between mitochondrial respiratory chain (aka, electron metabolic rate, body size, and longevity, such transport chain) generate stochastically, in an that long-lived animals are, on average, larger. unregulated fashion, reactive oxygen species Further metabolic studies led to the proposal that (i.e., oxygen free radicals). (2) Mitochondria pos- the faster the metabolic rate of an animal, sess specific mitochondrial DNA, that is, spa- a standby for biochemical activity and for the tially located very near to the source of free effect of temperature, the faster the organism radicals, in the mitochondrial matrix. (3) Mito- will age. In the mid-1950s, the mechanisms caus- chondrial DNA has limited repair capacity. ing cell damage and death in response to ionizing (4) Mitochondrial DNA codes for some of the radiation were becoming clearer: the production proteins in the respiratory complex, and DNA of free radicals, a highly reactive species of mol- mutation could generate dysfunctional proteins, ecules characterized by the existence of a single initiating a time (age)-dependent vicious circle of unpaired electron in the outer layers of the atom. increased free radical producing. Thus, the strong Due to their chemical properties, oxygen and formulation of the complete MFRTA flows along nitrogen are the molecules most prone to become the following functional axis: (a) oxygen free free radicals, and the instability of such radicals generated (mainly from mitochondria) a molecule renders them very reactive, generat- as a function of metabolic rate cause cumulative ing chain redox reactions of sequential oxidation oxidative damage, resulting in structural degen- (loss of electrons) and reduction (gain of elec- eration, functional decline, and age-related dis- trons) of a variety of cellular substrates. In many eases, leading to (b) oxidative stress that is the Cellular Theory of Aging 365 C predominant cause of age-associated degenera- oxidative stress. Alternatively, oxidative stress tive change, and thus (c) the mitochondrial free might result from the failure of one particular radicals are the cause of aging. maintenance system of the organism and thus In the last few decades, a huge amount of participate in causing aging, but only as a factor experimental evidence accumulated to show amongst others. This perspective on the role of that with age there is indeed an accumulation of oxidative stress in actually causing aging has also mitochondrial oxidative damage and a progres- practical implications, as it is still possible to C sive decline in mitochondrial function and per- advocate antioxidant therapies as being beneficial formance. In many tissues, including the brain to health in counteracting the effects of free (which has a special position since the neurons radicals, but not as a magic, blanket coverage are the only cell types in the body that are anti-aging cure. In addition, each intervention maintained in a postmitotic state, i.e., they do should be critically evaluated, both because not divide), there is an age-dependent accumula- some antioxidant supplementation trials provided tion of global oxidative damage to proteins, surprising results and because of an increasing DNA, and lipids. However, in the last few number of studies showing the crucial roles of years, the availability of very powerful experi- ROS in cellular signaling, and thus advocating mental models that allow genetic manipulations against a too strong suppression of free radicals (full or conditional knock-in of proteins or knock- production. down of proteins, use of interference RNA as silencers of specific protein synthesis, etc.) led to the expression of serious reservations about the Cross-References full validity of MFRTA. Thus, decreasing free radical levels with dietary antioxidants or by ▶ Neuroendocrine Theory of Aging genetically induced overexpression of protein antioxidants, such as superoxide dismutase (SOD), that metabolizes the oxygen superoxide References and Readings (a free radical) to hydrogen peroxide, or catalase, that metabolizes hydrogen peroxide to water and Bratic, I., & Trifunovic, A. (2010). Mitochondrial energy regenerates the gaseous oxygen, did not induce metabolism and ageing. Biochimica et Biophysica the expected significant increase in lifespan of the Acta, 1797(6–7), 961–967. Chen, J. H., Hales, C. N., & Ozanne, S. E. (2007). DNA test animals. In contrast, inactivation of antioxi- damage, cellular senescence and organismal ageing: dant activity while increasing the free radical Causal or correlative? Nucleic Acids Research, 35(22), levels did not determine a significant reduction 7417–7428. of lifespan and even increased, in some instances, Collado, M., Blasco, M. A., & Serrano, M. (2007). Cellular senescence in cancer and aging. Cell, the lifespan. 130(2), 223–233. It is worth assessing for a moment the reasons Garinis, G. A., van der Horst, G. T., Vijg, J., & of the discrepancy between the two sets of data. Hoeijmakers, J. H. (2008). DNA damage and ageing: The important point about most of earlier studies New-age ideas for an age-old problem. Nature Cell Biology, 10(11), 1241–1247. mentioned is that they were correlative, reporting Lapointe, J., & Hekimi, S. (2010). When a theory of aging that with age there is an increase in oxidative ages badly. Cellular and Molecular Life Sciences, damage. However, correlation is not necessarily 67(1), 1–8. causation and implies the possibility that both Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W. (2005). DNA repair, aging and increased oxidation can be caused, at genome stability, and aging. Cell, 120(4), 497–512. the same time, by another process(es), and, Mattson, M. P., Gleichmann, M., & Cheng, A. (2008). indeed, aging is viewed now as a multifactorial Mitochondria in neuroplasticity and neurological dis- process. It also can be that oxidative stress might orders. Neuron, 60(5), 748–766. Shawi, M., & Autexier, C. (2008). Telomerase, senes- be the consequence of aging, with aging having cence and ageing. Mechanisms of Ageing and Devel- some discrete cause, or causes, distinct from opment, 129(1–2), 3–10. C 366 Center for Epidemiologic Studies Depression Scale (CES-D)

Toescu, E. C. (2005). Normal brain ageing: Models and consistency of this measure is strong in both the mechanisms. Philosophical Transactions of the Royal general adult population (a ¼ 0.85) and among Society of London. Series B, Biological Sciences, a ¼ 360(1464), 2347–2354. clinically depressed adults ( 0.90; Radloff, Vin˜a, J., Borra´s, C., & Miquel, J. (2007). Theories of 1977). Further, reliability of the CES-D, as ageing. IUBMB Life, 59(4–5), 249–254. measured by test-retest correlations over periods ranging from 2 weeks to 12 months, has gener- ally been in the moderate range (0.45–0.67), indicating adequate stability (Radloff, 1977). With Center for Epidemiologic Studies regard to validity, the CES-D is capable of discrim- Depression Scale (CES-D) inating between the general adult population and psychiatric inpatients, as well as between severity Whitney M. Herge, Ryan R. Landoll and levels of clinical populations (Radloff, 1977). Annette M. La Greca Among clinical populations, it has also been Department of Psychology, University of Miami, shown to correlate positively with other measures Coral Gables, FL, USA of depression, including nurse-clinician ratings (0.56; Craig & Van Natta, 1976), and self-rating scales (0.44–0.75; Radloff, 1977). The CES-D pri- Definition marily has been used to screen for high levels of depressive symptoms in community populations The Center for Epidemiologic Studies Depres- (Radloff, 1977). Scores above 16 denote a level of sion Scale (CES-D Scale) is a 20-item self-report depressive symptoms which may require follow-up measure designed to assess depressive symptoms investigation (Zich, Attkisson, & Greenfield, 1990). over the previous week (Radloff, 1977). The Research regarding age, gender, and ethnic differ- CES-D assesses multiple symptom clusters, ences in the underlying factor structure and use of including depressed affect, lack of hope, feelings the CES-D is inconclusive to date, and as of guilt and shame, and somatic symptoms (e.g., such, a definitive statement cannot be made (e.g., disrupted sleep or appetite) with an emphasis on Callahan & Wolinsky, 1994; Hertzog, Van Alstine, negative affect (Radloff, 1977). Sample items Usala, Hultsch, & Dixon, 1990; Liang, Van Tran, include “During the past week, ...I felt that Krause, & Markides, 1989; Roberts, 1980). I could not shake off the blues even with help Recently, the CES-D has been used as from my family or friends,” and “...Ifeltthat a depression screening tool for adolescents as everything I did was an effort,” (Radloff, 1977). young as 14 years of age (e.g., Charbrol, Four items are worded positively and reverse Montovany, Chouicha, & Duconge, 2002; coded to (a) ensure the respondent is attending to Cuijpers, Boluijt, & van Straten, 2008; Sharp & each question and not answering carelessly and (b) Lipsky, 2002). The CES-D appears to be reliable measure the respondent’s positive affect (Radloff, for use with adolescents of high school age (M 1977). Each item is rated on a frequency scale age ¼ 17, SD ¼ 1.4; Chabrol et al., 2002). (0 ¼ Rarely or None of the Time, 1 ¼ Some or With a community sample of adolescents, the a Little of the Time, 2 ¼ Occasionally or reliability of the CES-D has been satisfactory aModerateAmountofTime,3¼ Most or All of (a ¼ 0.85; Chabrol et al., 2002). Further, the the Time; Radloff, 1977). Total scores can range factor structure of the CES-D appears to function from 0 to 60; higher scores represent more depres- similarly in adults and adolescents (four factors: sive symptoms (Radloff, 1977). depressed affect, positive affect, somatic and The CES-D is one of the most commonly used retarded activity, and interpersonal; Chabrol measures for assessing the presence of depressive et al., 2002; Radloff, 1977). Using a clinical symptoms in adults, as it has good psychometric cutoff score of 22, the CES-D has been shown properties (Sharp & Lipsky, 2002; Vahle, to have a specificity indicator of 74.31 and Andresen, & Hagglund, 2000). The internal a sensitivity indicator of 90.48 in adolescent Center for Scientific Review 367 C community samples (Cuijpers et al., 2008), although there is debate regarding the most appro- Center for Scientific Review priate cutoff score for use with adolescents (e.g., Roberts, Andrews, Lewinsohn, & Hops, 1990). Lee Ellington Department of Nursing, College of Nursing, References and Readings University of Utah, Salt Lake City, UT, USA C Callahan, C. M., & Wolinsky, F. D. (1994). The effect of gender and race on the measurement properties of the Basic Information CES-D in older adults. Medical Care, 32(4), 341–356. Chabrol, H., Montovany, A., Chouicha, K., & Duconge, E. (2002). Study of the CES-D on a sample of 1,953 The Center for Scientific Review (CSR) resides adolescent students. Encephale, 28, 429–432. within the National Institutes of Health (NIH) and Craig, T. J., & Van Natta, P. (1976). Recognition of is charged with the review of the scientific merit depressed affect in hospitalized psychiatric patients: of NIH grant applications. The mission of CSR is Staff and patient perceptions. Diseases of the Nervous System, 37(10), 561–566. to ensure that investigators’ applications receive Cuijpers, P., Boluijt, P., & van Straten, A. (2008). Screening fair, constructive, and timely feedback, resulting of depression in adolescents through the internet: Sen- in the goal of NIH to fund sound yet innovative sitivity and specificity of two screening questionnaires. research. A primary responsibility of CSR is to European Child & Adolescent Psychiatry, 17(1), 32–38. Hertzog, C., Van Alstine, J., Usala, P. D., Hultsch, D. F., & convene experts in the field to conduct peer Dixon, R. (1990). Measurement properties of the Cen- review of grant applications. The CSR receives ter for Epidemiological Studies Depression Scale all grant applications for NIH and some applica- (CES-D) in older populations. Psychological Assess- tions from the U.S. Department of Health and ment: A Journal of Consulting and Clinical Psychol- ogy, 2(1), 64–72. Human Services, resulting in well over 110,000 Liang, J., Van Tran, T., Krause, N., & Markides, K. S. applications per year. In 2009, CSR worked with (1989). Generational differences in the structure of the 25,000 peer reviewers. The CSR consists of the CES-D Scale in Mexican Americans. Journal of Ger- director, referral officers, integrated review group ontology, 44(3), S110–S120. Radloff, L. S. (1977). The CES-D scale: A self-report chiefs, scientific review officers, and related depression scale for research in the general population. administrative personnel. Applied Psychological Measurement, 1(3), 385–401. When an application arrives at NIH, a CSR Roberts, R. E. (1980). Reliability of the CES-D scale in referral officer examines the application and routes different ethnic contexts. Psychiatry Research, 2, 125–134. it to the integrated review group that best fits the Roberts, R. E., Andrews, J. A., Lewinsohn, P. M., & Hops, scope of the application. Within the integrated H. (1990). Assessment of depression in adolescents review group there are study sections, which are using the Center for Epidemiologic Studies Depres- essentially peer review groups. Each study section sion Scale. Psychological Assessment: A Journal of Consulting and Clinical Psychology, 2(2), 122–128. is managed by a scientific review officer (SRO) and Sharp, L. K., & Lipsky, M. S. (2002). Screening for typically includes 20 or more scientists. The SRO depression across the lifespan: A review of measures assigns two to four peer reviewers for each appli- for use in primary care settings. American Family cation. Reviewers provide written critiques and Physician, 66(6), 1001–1009. Vahle, V. J., Andresen, E. M., & Hagglund, K. J. (2000). provisional impact scores for each application and Depression measures in outcomes research. Archives then attend an in-person review meeting. Approx- of Physical Medicine and Rehabilitation, 81(12–2), imately half of the applications are discussed by the S53–S62. reviewers and other members of the study section Wiegman Dick, R., Beals, J., Keane, E. M., & Manson, S. M. (1994). Factorial structure of the CES-D among as a function of the provisional scoring process. American Indian adolescents. Journal of Adolescence, The assigned reviewers present their critiques and 17, 73–79. then the discussion is open to the entire review Zich, J. M., Atkisson, C. C., & Greenfield, T. K. (1990). group. After the general discussion, the assigned Screening for depression in primary care clinics: The CES-D and the BDI. International Journal of reviewers revisit initial overall impact scores and Psychiatry in Medicine, 20(3), 259–277. state their final score. The remainder of the study C 368 Centers for Disease Control and Prevention section members record their scores privately. References and Readings A few days after the review meeting, priority scores and percentile rankings are posted on NIH Com- http://cms.csr.nih.gov/ mons and can be accessed by the principal investi- http://nih.gov/icd/ gator for each application. Whether the application was discussed by the full group or not, there will be written critiques and scores. Centers for Disease Control and The CSR is independent from the NIH insti- Prevention tutes or centers (IC) that make funding decisions. That is, CSR is concerned with scientific merit ▶ Behavioral Sciences at the Centers for Disease outside the context of funding priorities at the Control and Prevention various institutes. After written critiques and scores are available, a second level of peer review is performed by the IC advisory councils. These councils consider the scientific merit of the appli- Central Adiposity cation from CSR in conjunction with their insti- tute’s funding priorities to determine which grant Simon Bacon applications will be funded. Applications that are Department of Exercise Science, Concordia not funded may be resubmitted a second time to University, Montreal Behavioral Medicine CSR for peer review. Centre, Montreal, QC, Canada

Major Impact on the Field Synonyms

Behavioral medicine research is often funded by Abdominal obesity; Apple shaped; Visceral the NIH, and a number of study sections review adiposity behavioral science research applications. These study sections include scientists from the multi- ple disciplines represented within the Society of Definition Behavioral Medicine and ensure that applications examining behavioral influences on health are Central adiposity is the accumulation of fat in the fairly evaluated. The CSR website provides lower torso around the abdominal area. Central review group descriptions. Some examples of adiposity is a function of both subcutaneous fat, study sections which are well suited for which sits under the skin, and visceral fat, which reviewing specific behavioral science applica- surrounds the internal organs in the peritoneal tions include behavioral and social consequences cavity. Currently, it would seem that the toxic of HIV/AIDS, psychosocial risk and disease pre- component of central adiposity is the visceral fat. vention, and social sciences and population stud- High levels of central adiposity have been ies. The SCR referral officer evaluates associated with an increased risk of a number of applications to find the most appropriate study diseases, including type 2 diabetes, hypertension, section. The assignment is posted on ERA Com- heart disease, and dementia. Of note, it would mons for the principal investigator to assess prior seem that central adiposity is independent of to review. body mass index (a proxy of total adiposity) as a predictor of disease (even though the two are highly correlated). This increased risk is thought Cross-References to be due to the hormonal action of visceral fat, which actively excretes adipokines, most of ▶ National Institutes of Health which impair glucose tolerance. Central Nervous System 369 C

Central adiposity is most often measured as Definition waist circumference (though the point of mea- surement varies across studies). However, there The vertebrate nervous system is divided into the are other measures such as waist-to-hip ratio, central nervous system (CNS) and the peripheral waist-to-height ratio, and CT- and MRI-based nervous system (PNS). The CNS consists of two visceral and subcutaneous fat. parts: the brain (located in the skull) and the While the causes of obesity and increased spinal cord (located in the spine). The PNS is C body weight are quite clear (an imbalance the division of the nervous system that is located between energy intake and expenditure), the outside the skull and spine consisting of two types exact causes of individual increases in central of neurons: afferent (sensory) neurons which adiposity are not known, i.e., why some people relay impulses toward the CNS and efferent can have high total adiposity but not central (motor) neurons which relay nerve impulses adiposity and vice versa. away from the CNS (Breedlove, Watson, & Rosenzweig, 2010; Pinel, 2006). The CNS integrates the sensory information Cross-References that it receives from the PNS (via the afferent nerves) and coordinates the behavior of the ▶ Obesity organism and the activity of all parts of the body (via the efferent nerves) (Pinel, 2006). Fur- thermore, the brain is processing not only simple References and Readings motor behaviors or physical actions like walking or digestion but also all the complex cognitive, Lee, C., Huxley, R., Wildman, R., & Woodward, M. (2008). motivational, and emotional processes like affect, Indices of abdominal obesity are better discriminators of learning and memory, and especially those cardiovascular risk factors than BMI: A meta-analysis. Journal of Clinical Endocrinology and Metabolism, actions that are believed to be quintessential to 61(7), 646–653. humans like thinking, speaking, or creativity Misra, A., & Vikram, N. K. (2003). Clinical and (Kandel, Schwartz, & Jessell, 2000). pathophysiological consequences of abdominal Research on CNS functioning – neuroscience – adiposity and abdominal adipose tissue depots. Nutrition, 19(5), 457–466. is a multidisciplinary field that analyzes the Rexrode, K. M., Carey, V. J., Hennekens, C. H., Walters, biological basis of behavior and psychological E. E., Colditz, G. A., Stampfer, M. J., Willett, W. C., & processes. The term “neuroscience” was intro- Manson, J. E. (1998). Abdominal adiposity and duced in the mid-1960s, signaling the beginning coronary heart disease in women. JAMA, 280(21), 1843–1848. of an era in which multiple disciplines – neuroanatomy, psychology, biology, medicine, pharmacology, and others – would work together cooperatively, sharing a common language, con- cepts, and goal, to understand the structure and Central Nervous System function of the normal and abnormal brain. Currently, neuroscience is still one of the most Moritz Thede Eckart rapidly growing areas of science (Squire et al., General and Biological Psychology, Department 2003). of Psychology, University of Marburg, Marburg, Germany Description

Synonyms Anatomy The CNS is the most protected organ of the Brain and spinal cord body: It is encased by bone and covered by C 370 Central Nervous System

of the limbs and trunk and controls movements of the limbs and the trunk. The spinal cord continues rostrally as the brain stem, which consists of the medulla oblongata, pons, and midbrain. The 12 cranial nerves are the only nerves of the PNS projecting directly into the brain rather than via the spinal cord. The medulla oblongata, which lies directly above the spinal cord, includes several centers responsible for vital autonomic functions (diges- tion, breathing, control of heart rate). The pons, which lies above the medulla Central Nervous System, Fig. 1 Sagittal MRI scan of oblongata, conveys information about movement a human brain with main structures: Cerebral hemispheres, from the cerebral hemispheres to the cerebellum. diencephalon, midbrain, pons, and cerbellum. Medulla The midbrain, which lies rostral to the pons, oblongata and spinal cord would continue ventrally from the Pons. (Courtesy of the working group “Brainimaging,” controls many sensory and motor functions like medicine department, Philipps-University of Marburg.) eye movement and coordination of visual and auditory reflexes. Medulla oblongata, pons, and midbrain are three protective membranes (1. dura mater, often summarized as the brain stem. The brain 2. arachnoid membrane/subarachnoid space, stem receives sensory information from the skin 3. pia mater). Also the cerebrospinal fluid has and muscles of the head and provides motor con- a protecting function: it supports and cushions trol of the head via the cranial nerves. It also the CNS. Additionally, the blood–brain barrier conveys information from the brain to the spinal protects the brain from toxins that could enter cord and vice versa. Furthermore, the brain stem the brain via the bloodstream. For instance, plays an important role in the regulation of the degree to which psychoactive drugs influence arousal and awareness. psychological processes depends on their ease of The cerebellum lies behind the pons and penetrating the blood–brain barrier (Pinel, 2006). is crucially involved in the modulation of the The CNS is a bilateral and essentially sym- force and range of movement, learning of motor metrical structure with seven main parts (see skills and movement patterns, coordination, and Fig. 1): (1) spinal cord, (2) medulla oblongata, tuning. (3) pons, (4) midbrain, (5) cerebellum, (6) dien- The diencephalon lies rostral to the midbrain cephalon, and (7) cerebral hemispheres and contains two structures: the thalamus, which (consisting of cerebral cortex, basal ganglia, processes most of the information reaching the hippocampus, and amygdaloid nuclei) (Kandel cerebral cortex from the rest of the nervous sys- et al., 2000). Other common nomenclatures for tem (and is thus often seen as the “gateway” to the the parts of the CNS are as follows: spinal cord, cortex), and the hypothalamus, which is involved myelencephalon (medulla), metencephalon (pons in the regulation of autonomic, endocrine, and and cerebellum), mesencephalon (midbrain), and visceral functions. diencephalon and telencephalon (cerebral hemi- The cerebral hemispheres consist of a heavily spheres) (Pinel, 2006, an integrated overview wrinkled outer layer – the cerebral cortex (syno- over both nomenclatures can be found in nym in mammals: neocortex or isocortex) – and Breedlove et al. (2010)). An integration of both three deep-lying structures: the basal ganglia, the nomenclatures is summarized in Table 1. hippocampus, and the amygdaloid nuclei. The The spinal cord is the most caudal part of the basal ganglia participate in regulating motor per- CNS. It receives and processes sensory informa- formance, the hippocampus plays a major role in tion from the PNS: the skin, joints, and muscles the consolidation of the declarative memory, and Central Nervous System 371 C

Central Nervous System, Table 1 A schematic view of the common nomenclatures of the brain, divided by main structures and substructures

Central Nervous System (CNS)

Spinal Cord Brain Myel- Met- Mes- Di- Tel- encephalon encephalon encephalon encephalon encephalon C (medulla (midbrain) (cerebral hemispheres) oblongata) Cerebellum Pons Thalamus Hypothalamus Cerebral cortex Basal ganglia Hippocampus Amygdaloid nuclei (PNS) Peripheral Nervous System Nervous Peripheral

the amygdaloid nuclei coordinate the autonomic morphologically defined regions: the cell body and endocrine response of emotional states. (soma), dendrites, the axon, and presynaptic ter- The cerebral cortex is divided into four ana- minals. The cell body is the metabolic center of tomical distinct lobes: frontal, parietal, temporal, the brain. Dendrites branch out in treelike fashion and occipital. The frontal lobe is involved in and are the main apparatus for receiving signals planning and executive functions, the parietal from other neurons. The axon extends away from lobe in somatic sensation, the occipital lobe in the cell body and is the main conducting unit for vision, and the temporal lobe in hearing (and carrying signals (action potentials: all or none speech in humans). impulses) to other neurons. Action potentials constitute the signals by which the brain receives, Cell Types analyzes, and conveys information. There are two main classes of cells in the nervous Near its end, the axon divides into fine system: nerve cells (neurons) and glial cells (from branches that form communication sites with Greek glia, meaning glue). Glial cells far out- other neurons – the synapses. The nerve cell number neurons – there are between 10 and 50 transmitting a signal is called the presynaptic times more glia than neurons in the vertebrate cell, the signal receiving cell the postsynaptic CNS (Breedlove et al., 2010; Kandel et al., 2000). cell. Between both cells lies the synaptic cleft. Glial cells are support cells that provide the When an action potential reaches a synaptic ter- brain with structure and sometimes insulate neu- minal, neurotransmitters are released into the ral groups and synaptic connections from each postsynaptic cleft as the neurons output signal. other. Also, they can communicate with each The number of released neurotransmitters is other and with neurons, and they directly affect determined by the number and frequency of the neuronal functioning by providing neurons with action potentials in the presynaptic terminals. raw materials and chemical signals that alter neu- The released neurotransmitters act on the recep- ronal structure and excitability. Further important tors of the postsynaptic neuron either in an functions (like the myelination of neurons) are excitatory (increasing the likelihood of an action summarized in Kandel et al. (2000), Chap. 2 or potential of the postsynaptic neuron) or in an Breedlove et al. (2010), Chap. 2. inhibitory (reducing the likelihood of an action Nerve cells are the main signaling units of the potential of the postsynaptic cell) manner. nervous system. A typical neuron has four Whether the effect is excitatory or inhibitory C 372 Central Nervous System does not depend on the type of released neuro- a degeneration of dopaminergic neurons in the transmitter but on the type of receptor in the substantia nigra. The major symptoms of postsynaptic neuron. One estimate puts the Parkinson’s disease involve movement – tremor, human brain at about 100 billion (1011) neurons rigidity, bradykinesia (poverty or slowing of and 100 trillion (1014) synapses. For details on movement) – and postural disturbances, but also nerve cell functioning see Kandel et al. (2000), cognitive dysfunctions. Chap. 2; Squire et al. (2003), Chap. 3; Pinel The mesolimbic and mesocortical pathways (2006), Chap. 4; or Breedlove et al. (2010), are involved in motivated behavior, reinforce- Chap. 2. ment of learning and emotional appetitive states (Alcaro, Huber, & Panksepp, 2007). That is why Neurotransmitter Systems the dopaminergic system also plays a crucial This section will focus on the main neurotrans- role in drug abuse addiction. Most dopaminergic mitter systems: ▶ dopamine (DA), norepineph- agonists, like amphetamine or cocaine, are addic- rine (NE), ▶ serotonin (5-HT), glutamate, and tive drugs because of their rewarding properties gamma-aminobutyric acid (GABA), their organi- and the induced positive affective states. Further- zation, function, and dysfunction (Meyer & more these pathways are closely related to the Quenzer, 2005). GABA and opioid system, which is important for understanding the highly addictive potential Dopamine of GABA agonists (like benzodiazepines and DA is metabolized from the precursor DOPA. most probably alcohol) and opioid agonists (like There are five main subtypes of DA receptors morphine or heroin). organized into D1-like (D1 and D5) and D2-like Also, a dysfunction of the dopaminergic sys- (D2,D3, and D4) families. The dopaminergic tem is observed in schizophrenia. The dopamine system can be divided into three major pathways: imbalance hypothesis suggests that schizo- 1. The nigrostriatal pathway, which originates in phrenic symptoms are due to reduced dopaminer- the substantia nigra (located in the midbrain) gic function in the mesocortical neurons, and innervates the striatum (part of the basal along with excess dopaminergic function in ganglia) mesolimbic dopaminergic neurons, resulting in 2. The mesolimbic pathway, which originates impaired prefrontal cortex function. Also, the in the ventral tegmental area (located in the reduction of schizophrenic symptoms by DA midbrain) and innervates various limbic struc- antagonists (like Haloperidol, a typical antipsy- tures, such as amygdala, nucleus accumbens, chotic, or Risperidone, an atypical antipsychotic, or hippocampus (all located in the deep lying see below) supports the hypothesis that dopamine structures of the cerebral hemispheres) is crucially involved in schizophrenic symptoms. 3. The mesocortical pathway, which also origi- But is has to be pointed out that not all symptoms nates in the ventral tegmental area and inner- occurring in schizophrenia can be explained by vates the cerebral cortex, particularly the dysfunctions of the DAergic system. For exam- prefrontal area ple, also dysfunctions and volume reductions of DA is also found in the hypothalamus, where it the hippocampus seem to play a crucial role. Also is involved in hormone secretion and in sensory 5-HT seems to be involved in the development of structures. schizophrenia (see below).

Function and Dysfunction of the Dopaminergic Norepinephrine System The central nervous noradrenergic system The nigrostriatal pathway plays a crucial role in originates in the locus coeruleus, a small area of voluntary control of movement. ▶ Parkinson’s the pons, which projects to almost all areas of the disease, first described by the physician James cerebral hemispheres, thalamus, hypothalamus, Parkinson in 1817 as the “shaking palsy” causes cerebellum, and spinal cord. Noradrenergic Central Nervous System 373 C neurons play an important role in vigilance, experiments” in Harvard in the working group arousal, and behavioral functions like hunger/ of Timothy Leary in the 1960s and 1970s eating, sexual behavior, fear and anxiety, and (Leary, Wilson, & Koopman, 1977). pain and sleep. Glutamate Serotonin Glutamate neurotransmitters have potent excit- 5-HT is synthesized from tryptophan, which atory effects on neurons throughout the CNS. C comes from proteins in our diet. Pharmacologists N-Methyl-D-aspartic acid or N-methyl-D- have identified at least 14 5-HT receptor subtypes aspartate (NMDA) receptors are the main target (Saulin, Savli, & Lanzenberger, 2011). The 5-HT site of glutamate. system originates from a cell cluster called Glutamate and, especially, NMDA receptors raphe nuclei (located in medulla, pons, and mid- are thought to play a crucial role in learning and brain) which projects to virtually all structures of memory, particularly long-term potentiation. the cerebral hemispheres, thalamus, and Especially the hippocampus has a very high hypothalamus. density of NMDA receptors. NMDA receptor agonists impair the acquisition of various learn- Function and Dysfunction of the 5-HT System ing tasks. The 5-HT system is involved in food intake, reproductive behavior, pain sensitivity, anxiety, Gamma-aminobutyric Acid learning and memory, and facilitation of motor GABA is synthesized from glutamate. Many output. In psychology, psychiatry, and pharma- main areas of the brain are rich in GABA, includ- cology, serotonergic drugs are commonly used in ing the cerebral cortex, hippocampus, basal treating depression. There are three major classes ganglia, and cerebellum. of antidepressants, which enhance the amount of 5-HT in the postsynaptic cleft in different ways: Function and Dysfunction of the GABAergic monoamine oxidase inhibitors, tricyclic antide- System pressants, and selective serotonin reuptake inhib- GABA is the main inhibitory neurotransmitter of itors (SSRIs). Although the pharmacological the brain. Because of GABA’s widespread inhib- mechanisms of these drugs are well known, it is itory effect on neural excitability, treatment with still not clear which of their neurochemical GABA antagonists leads to seizures. actions are responsible for their effectiveness in The effect of GABA on the GABA receptor is treating depression – especially regarding the fact enhanced by CNS-depressant drugs such as ben- that the pharmacological effects of the drugs zodiazepines, barbiturates, and ethanol (alcohol). occur within hours whereas antidepressant Due to their anxiolytic effects, benzodiazepines effects require weeks of chronic treatment. and barbiturates are often prescribed to treat Also, in pharmacological treatment of schizo- anxiety disorders, although these substances have phrenia, blockade of 5-HT receptors has become severe side effects. Among others, the sleep archi- a major topic of research in the past years, since tecture is altered (reduced REM sleep), they are the very effective atypical antipsychotics like highly addictive, and can cause coma and death by Risperidone act not exclusively on DA but also respiratory depression (especially at high doses or on 5-HT receptors. with combined alcohol consumption). Another Another class of drugs that act on the 5-HT medicinal use of benzodiazepines is as anticonvul- system are hallucinogens like LSD (the abbrevi- sants in the treatment of epilepsy. ation LSD comes from the German chemical name for the substance: lysergs€aurediethylamid; Brain Circuits English: lysergic acid diethylamide) or psilocy- Often, functionally related structures of the brain bin (found in “magic mushrooms”), which are integrated into one circuit such as the limbic became temporarily popular in “psychological system which is mainly associated with C 374 Central Nervous System emotional processes (Kandel et al., 2000, Chap. precisely the brain is investigated – by micro- 50) or the basal ganglia. In the following, the scope, imaging techniques, or in the future by basal ganglia will be described exemplarily even more exact methods – always the same The basal ganglia comprise of striatum (puta- physical objects will be found: neurons, synap- men and caudate nucleus), pallidum, substantia ses, neurotransmitters, ions, electrons, and pro- nigra, and the subthalamic nucleus. tons, but not mental processes. “Granted that The basal ganglia are – beside the cerebellum – a definite thought, and a definite molecular action one of the largest subcortical motor systems. in the brain occur simultaneously, we do not Cerebellum and basal ganglia appear to influence possess the intellectual organ, nor apparently (via thalamus) the same cortical motor systems. any rudiment of the organ, which would enable While the basal ganglia output is inhibitory, the us to pass by a process of reasoning from the one cerebellar output is excitatory. Discharge of phenomenon to the other. They appear together many basal ganglia neurons correlates with but we do not know why” (Mausfeld, 2010). movement and lesions or degenerations (like in Parkinson’s disease, chorea Huntington, obses- sive-compulsive disorder, or Tourette syndrome) Cross-References cause severe movement abnormalities: slow vol- untary movements or involuntary postures and ▶ Brain, Cortex movements. In order to distinguish the basal ▶ Brain, Regions ganglia from the “pyramidal” corticospinal ▶ Dopamine motor system, the basal ganglia are often termed ▶ Neurotransmitter “extrapyramidal” motor system. ▶ Norepinephrine/Noradrenaline However, beside motor control, the basal ▶ Parkinson’s Disease ganglia are also involved in nonmotor function ▶ Serotonin and cognitive aspects of movement (Squire et al., 2003, Chap. 31).

Chances and Limitations of Neuroscience References and Readings The new research methods of neuroscience enhanced the knowledge of how mental phenom- Alcaro, A., Huber, R., & Panksepp, J. (2007). Behavioral functions of the mesolimbic dopaminergic system: An ena are linked to processes in the brain, which affective neuroethological perspective. Brain Res Rev, allows, for instance, the mapping of mental pro- 56(2), 283–321 & Source. cesses to specific regions of the brain. Breedlove, S. M., Watson, N. V., & Rosenzweig, M. R. Nowadays it is possible to investigate by func- (2010). Biological psychology (Vol. 6). Sunderland, MA: Sinauer. tional magnetic resonance imaging (fMRI) which Kandel, E. R., Schwartz, J. H., & Jessell, T. M. (2000). brain regions are activated during the presenta- Principles of neural science (Vol. 4). New York: tion of emotionally salient stimuli or cognitive McGraw-Hill. tasks. However it has to be pointed out that Leary, T., Wilson, R. A., & Koopman, G. A. (1977). Neuropolitics: The sociobiology of human metamor- research on the biological bases of mental phe- phosis. Los Angeles: Starseed/Peace Press. nomena does not per se enhance the understand- Mausfeld, R. (2010). Psychologie, Biologie, kognitive ing of psychological processes: it is Neurowissenschaften: Zur gegenw€artigen Dominanz a misunderstanding that biological processes neuroreduktionistischer Positionen und zu ihren stillschweigenden Grundannahmen [Psychology, biol- can explain psychological phenomena. ogy, cognitive neurosciences. On the current predom- On the contrary, mainly neuroreductionist inance of neuroreductionist approaches and their tacit conceptions of psychological processes (often assumptions]. Psychologische Rundschau, 61(4), favoring investigations of input–output relations) 180–190. Meyer, J. S., & Quenzer, L. F. (2005). Psychopharmacol- may abridge the development of complex theo- ogy: Drugs, the brain and behavior. Sunderland: ries on mental phenomena. No matter how Sinauer. Cessation Intervention (Smoking or Tobacco) 375 C

Pinel, P. J. (2006). Biopsychology (6th ed.). Boston: clearly greater in the former group of hypotheti- Pearsons Education. cal numbers than in the latter group. Thus, the Saulin, A., Savli, M., & Lanzenberger, R. (2011). Serotonin and molecular neuroimaging in humans overall nature of the groups of numbers will differ using PET. Amino Acids. despite their means being identical. Squire, L. R., Bloom, F. E., McConnell, S. K., Roberts, J. L., Spitzer, N. C., & Zigmond, M. J. (2003). Funda- mental neuroscience (2nd ed.). San Diego: Elsevier Cross-References C Science. ▶ Dispersion ▶ Median ▶ Mode Central Tendency

J. Rick Turner CER Cardiovascular Safety, Quintiles, Durham, NC, USA ▶ Comparative Effectiveness Research

Definition Cerebrum Certain descriptive statistics provide concise yet meaningful summaries of large amounts of data. ▶ Brain, Cortex One category of such statistics is measures of central tendency. They provide a measure of a group’s central value. Three measures of central Cervical Adenocarcinoma tendency are the arithmetic mean, median, and mode, each of which has an entry in the ▶ Cancer, Cervical encyclopedia. Another way to conceptualize central ten- dency is to say that these measures provide an indication of the location of the data points. Cessation Intervention (Smoking or Imagine a set of data points ranging from 1 to Tobacco) 100. If the mean is 89, for example, this provides an indication that, overall, the data points are Mark Vander Weg located toward the top of the range rather than Department of Internal Medicine, The University toward the bottom. Conversely, if the mean is 27, of Iowa and Iowa City VA Health Care System, this indicates that, overall, the data points are Iowa City, IA, USA located toward the bottom of the range. Measures of central tendency (consider here the arithmetic mean) are often presented along Synonyms with measures of spread, or dispersion, of the individual values around the mean. It is possible Nicotine dependence and nicotine addiction to have a group of 100 numbers that range from 10 to 90, for example, and have a mean of 50. It is equally possible to have a group of 100 numbers Definition that range from 45 to 55 and that also have a mean of 50. While the measure of central tendency, the Cessation interventions refer to treatments mean, is the same in both cases, the dispersion is designed to assist individuals with stopping the C 376 Cessation Intervention (Smoking or Tobacco) use of a particular substance, in this case tobacco. undergraduate college degree and 5.6% for Cessation interventions may involve either those with a graduate degree. The prevalence of behavioral or pharmacological treatment smoking is also elevated among those who live approaches or some combination of the two. below the poverty line (31.1%) relative to those at or above the poverty level (19.4%). With regard to geographic variations in cigarette use, Description rates are lowest for those living in the West (18.8%) and highest for those residing in the Background Midwest (23.1%). Rates of cigarette smoking Tobacco use remains the single greatest prevent- are elevated among other subgroups as well. In able cause of morbidity and premature mortality particular, individuals with a history of psychi- in the United States (USA). Each year, cigarette atric disorders and nonnicotine substance abuse smoking is responsible for more than 440,000 tend to smoke at very high rates relative to the deaths, five million years of potential life lost, general population. and $190 million in excess health-care expendi- Although the onset of cigarette smoking con- tures and productivity losses in the USA alone. tinues through young adulthood, the vast major- Worldwide, tobacco use accounts for more than ity of regular tobacco users initiate smoking prior five million deaths annually, with the total to the age of 18. In the early stages of smoking, expected to increase to eight million by the year use tends to be episodic and is often isolated to 2030 (World Health Organization, 2008). specific social or environmental contexts In the USA, rates of cigarette smoking steadily (e.g., with friends, at a party). As tolerance to declined in the years following the publication of nicotine develops, however, the frequency and the first Surgeon General’s Report on Smoking intensity of use increase. Following a period of and Health in 1964. In fact, since the mid-1960s, regular use, many smokers become nicotine the prevalence of cigarette smoking has dropped dependent, which is characterized by tolerance by more than 50%. Rates of tobacco use have (the need for greater amounts of tobacco to stabilized in recent years, however, with levels achieve the same effect), compulsive use (diffi- remaining essentially unchanged since 2005. culty controlling cigarette use), and nicotine Currently, 20.6% of the adult population smokes withdrawal (a reversible and substance-specific cigarettes (Centers for Disease Control and syndrome of behavioral, cognitive, and physio- Prevention [CDC], 2010b). Among high school logical changes brought on by the cessation or students, the prevalence of current (past 30-day) reduction of tobacco use that causes distress or cigarette smoking is 17.2% (CDC, 2010a). As impairment in functioning) (American Psychiat- with adults, the rate of smoking has been rela- ric Association [APA], 2000). Signs of nicotine tively stable in recent years following a period of withdrawal include dysphoria or depressed significant decline during the 1990s. mood, insomnia, irritability, frustration, or A variety of sociodemographic factors are anger, anxiety, difficulty concentrating, restless- associated with cigarette use (CDC, 2010b). ness, decreased heart rate, and increased appetite Overall, men (23.5%) are more likely to smoke or weight gain (APA, 2000). Although it was cigarettes than women (17.9%). Adults aged once assumed that nearly all regular smokers 25–44 years of age are most likely be cigarette were nicotine dependent, it is now recognized smokers (24.0%), while those aged 65 and older that a sizeable proportion of cigarette smokers are the least likely to smoke (9.5%). The preva- do not meet formal criteria for nicotine depen- lence of cigarette smoking is also inversely asso- dence (Hughes, Helzer, & Lindberg, 2006). ciated with both educational attainment and Unfortunately, for those who do become nicotine income. Smoking rates among those with less dependent, cigarette use tends to follow a chronic than a high school education are 28.5% com- course lasting years or decades, often character- pared with 11.1% for those with an ized by multiple relapse episodes. Cessation Intervention (Smoking or Tobacco) 377 C

Treatment concerns they might have about quitting and A variety of effective behavioral and psychophar- experiences they encountered during prior quit macological approaches are available for the attempts. treatment of tobacco use and dependence. In addition to variability in content, behavioral The range of efficacious interventions for tobacco interventions also differ with regard to ways of use includes public health-based approaches such administering treatment. Evidence supports the as screening and brief advice and health policy use of several different formats for the delivery C initiatives. The present review, however, will of behavioral treatment for tobacco use. Both emphasize clinical approaches involving behav- individual and group counseling have been ioral and pharmacologic treatment strategies. shown to be effective strategies for treating nic- Behavioral treatments have long played an otine dependence. Proactive telephone counsel- important role in the treatment of tobacco use ing, in which an initial assessment is followed by and dependence. Behavioral approaches range a series of scheduled sessions initiated by the from brief advice lasting just a few minutes to clinician, is another empirically supported mode intensive group or behavioral counseling of delivery. Self-help materials, while advanta- conducted over a period of weeks. A variety of geous from cost and wide-scale dissemination different behavioral treatments have been applied perspectives, have demonstrated relatively mod- to smoking cessation including aversive therapies est success as a treatment strategy. Emerging data such as rapid smoking and smoke holding, nico- also suggest that of computer- and Internet-based tine fading, problem solving and skills training, cessation programs hold promise, although clear contingency management, relaxation training, evidence regarding the characteristics and con- and strategies emphasizing enhanced social sup- tent of programs that are most effective is port. Surprisingly, little is known, however, about currently lacking. the relative efficacy of the individual strategies or Recent trends in the delivery of behavioral components. This is due, in part, to the fact that treatment for smoking cessation have empha- most treatment programs combine a variety of sized the delivery of brief behavioral counseling different behavioral strategies and tend to be for purposes of widespread dissemination. Such evaluated as a whole rather than according to an approach is sound from a public health per- individual components. Nevertheless, sufficient spective in that it facilitates implementation and evidence is available to support the efficacy of increases potential reach. Nevertheless, evidence certain behavioral strategies. In the 2008 Update strongly supports a dose–response association to the Clinical Practice Guideline for Treating between treatment intensity and cessation out- Tobacco Use and Dependence, Fiore et al. iden- comes. The number of treatment sessions and tified two specific types of behavioral interven- total amount of contact time are both positively tions and counseling that have proven effective associated with cessation outcomes such that for promoting smoking cessation. These included more intensive interventions tend to be associated practical counseling and the provision of with a greater likelihood of cessation. intratreatment social support. Practical counsel- The most effective tobacco cessation interven- ing refers to general problem solving and behav- tions are those that combine behavioral and ioral skills training (e.g., setting a quit date, pharmacological treatment strategies. Indeed, identifying high-risk situations, developing cop- treatments involving medication and behavioral ing skills, and providing basic information about counseling are significantly more effective than smoking and successful quitting). Intratreatment those using only one strategy or the other. There social support simply involves providing encour- are currently seven medications considered to be agement to smokers during their quit attempt, first-line pharmacotherapies for smoking cessa- communicating caring and concern about the tion based on their demonstrated safety and effec- smoker, and encouraging them to talk about tiveness in the general population. Five of these issues related to the quitting process, such as agents are forms of nicotine replacement therapy C 378 Cessation Intervention (Smoking or Tobacco)

(NRT): transdermal nicotine patch, nicotine gum, & Gitchell, 2008; Zhu, Melcer, Sun, Rosbrook, nicotine lozenge, nicotine nasal spray, and nico- & Pierce, 2000). Behavioral interventions are tine inhaler. The patch, gum, and lozenge are all especially underutilized, with less than 10% of available over the counter in the USA, while the smokers using this form of treatment during any spray and inhaler require a prescription. The two single quit attempt (Shiffman et al., 2008; Zhu other first-line medications are bupropion hydro- et al., 2000). Furthermore, when smokers do chloride (trade name Zyban®), an atypical make use of nonpharmacological treatment antidepressant, and varenicline (trade name approaches, they tend to use self-help materials ® Chantix ), an a4b2 nicotinic acetylcholine rather than strategies with greater empirical sup- (ACh) receptor partial agonist. Each of these port such as individual, group, or telephone seven agents has strong empirical evidence to sup- counseling (Shiffman et al., 2008). A variety of port their efficacy, with no single medication dem- factors appear to contribute to the underutiliza- onstrating clear superiority over the others. All are tion of effective smoking cessation treatments associated with an approximate doubling of the including a lack of awareness of available treat- odds of successful quitting relative to placebo. ment options, a preference to quit smoking on Medication strategies combining bupropion with one’s own, perceived inconvenience, cost, and, the nicotine patch as well as the nicotine patch in the case of pharmacotherapy, concerns about with short-acting NRT (gum or nasal spray) have side effects. also been found to improve cessation rates relative to monotherapy comprised of either agent Relapse Prevention alone. Two other medications (the antihyperten- Nicotine dependence is becoming increasingly sive clonidine and the antidepressant nortriptyline) conceptualized as a chronic and refractory con- are considered to be second-line pharmacother- dition. Even among those who do receive apies for smoking cessation. Although there is evidence-based treatment for smoking cessation, considerable evidence to support their efficacy for most who attempt cessation eventually resume aiding smoking cessation, neither has yet been smoking following a given quit attempt. approved by the US Food and Drug Administration Although relapse can occur months or even (FDA) for treating tobacco use and dependence. years after an individual quits smoking, the vast In addition, these agents tend to have a less favor- majority occurs within the first 2 weeks. The able side effect profile than most of the first-line long-term cessation rates for even the most suc- agents. For that reason, it is recommended that they cessful interventions rarely exceed 30–35% (By be considered primarily among those for whom the comparison, for those who attempt to quit on their first-line agents are contraindicated or who have own without assistance, 1-year abstinence rates not been successful at quitting using those medica- tend to be less than 5%). Perhaps surprisingly in tions. To date, there is insufficient evidence to light of the variety of new (primarily pharmaco- support the efficacy of pharmacotherapy for use logical) treatments that have become available with pregnant women, light smokers, and adoles- over the past two decades, abstinence rates cents. For that reason, guidelines recommend that among participants in clinical trials have actually treatment focus on behavioral strategies and decreased over time (Inrvin & Brandon, 2000; counseling. Inrvin, Hendricks, & Brandon, 2003), leading to Despite the range of effective behavioral and the speculation that those who continue to smoke, pharmacological options for assisting with though fewer in number, are more likely to be tobacco cessation, the vast majority of smokers nicotine dependent and to have comorbid psychi- do not use an empirically supported treatment atric and substance use disorders that make it during a given quit attempt. An estimated more difficult for them to successfully quit 65–80% of smokers who attempt to quit smoking (Inrvin & Brandon, 2000). do so without the aid of behavioral or pharmaco- Given the high rates of relapse among once logical therapies (Shiffman, Brockwell, Pillitteri, abstinent smokers, much attention has been given Cessation Intervention (Smoking or Tobacco) 379 C to trying to prevent tobacco users from resuming continued smoking did so primarily due to tobacco use following a successful quit attempt. a lack of knowledge about the significant health Most of this work is based on the model origi- risks. However, while health education does play nally developed by Marlatt for the treatment of an important role in smoking cessation and alcohol use disorders (Marlatt & Donovan, advice to quit from one’s health or mental 2005). The approach focuses on helping individ- health-care provider is frequently cited as an uals to identify situations in which they may important factor in motivating a quit attempt, C be especially tempted to smoke cigarettes treatment strategies that rely on confrontation (e.g., when consuming alcohol, during situations and which solely emphasize the clinician’s role of elevated stress or dysphoria, when exposed to as the health expert who knows what is best for other smokers). Once these high-risk situations the client typically meet with little success. are identified, smokers can be taught to avoid One approach that has been particularly influ- them (at least in the short term) or to develop ential in the field of health behavior change, and alternative coping strategies to help them manage in the treatment of addictions in particular, is the situation without smoking. Although concep- motivational interviewing (MI) (Miller & tually appealing, relapse prevention interventions Rollnick, 2002). Motivational interviewing is based on enhancing coping skills have generally a directive, client-centered approach to counsel- not been shown to be effective for cigarette ing that seeks to promote behavior change by smoking. Other psychosocial and pharmacologi- helping people to explore and resolve ambiva- cal approaches have similarly failed to reduce lence. The MI approach recognizes that the relapse rates in most cases. Methodological lim- majority of smokers have mixed feelings about itations associated with this literature, however, their tobacco use. While nearly all tobacco users limit the conclusions that can be drawn regarding acknowledge the health risks and can identify the relative effectiveness (or ineffectiveness) of other negative consequences of smoking, most different intervention strategies. Given the high also perceive it as positively reinforcing and as rates of relapse, new strategies for helping to playing an important functional role in their lives maintain abstinence over the long term are (e.g., negative affect reduction, stress manage- clearly needed. ment). Helping clients to recognize and resolve their ambivalence about quitting smoking is cen- Addressing Smokers Who Are Not Interested tral to the MI approach. Rather than using direct in Quitting persuasion in an attempt to enforce change exter- The treatment approaches described above apply nally, MI takes the perspective that the individual primarily to those who express interest in quitting already possesses the motivation and skills nec- smoking. However, despite the fact that the vast essary to make a change. Instead of viewing majority of smokers indicate that they would like motivation as something an individual does or to quit, the proportion of tobacco users who does not have, it is seen as fluid and susceptible express readiness to quit smoking at any given to movement in either direction. The goal is to point in time is relatively small. Therefore, it is elicit and strengthen the motivation and commit- important to identify strategies for approaching ment through the use of “change talk,” in which the large number of smokers who indicate that the individual (rather than the clinician) makes they do not presently wish to make a quit attempt. his or her own argument for quitting smoking. Historically, approaches to address tobacco Four general principles help to guide the MI use among cigarette smokers who express reluc- approach. The first involves expressing empathy, tance to quit focused on providing education which entails making an attempt to view things about the harms of smoking and attempting to from the perspective of the client. The second persuade them to quit. Such strategies tended principle is to help the client to develop discrep- to be paternalistic and proscriptive in style and ancy between his or her values/goals and their based on the assumption that those who current behavior. For example, individuals who C 380 Cessation Intervention (Smoking or Tobacco) place being a good role model for their children significantly improve a smoker’s chances of quit- and being available to support their family and ting successfully. However, most smokers fail friends in high regard can be helped to see how to utilize effective interventions during any smoking is incongruent with these values. The given quit attempt. Even among those who do third principle involves rolling with resistance. receive empirically supported treatment, relapse It is very common for individuals faced with rates remain very high. In order to continue pro- decisions about modifying a health behavior gress in reducing rates of cigarette smoking, it is such as tobacco use to demonstrate resistance to important to identify and implement strategies change, particularly if they feel their autonomy is for increasing the use of evidence-based treat- being threatened. Rather than try to confront or ment for tobacco use and dependence, as well as fight the client’s resistance, the MI approach con- for helping to reduce high rates of relapse among tends that it can be much more productive to shift those who do attempt to quit. strategies and use this as an opportunity to further explore their views about the behavior. The final principle focuses on helping to support self- Cross-References efficacy. An individual’s belief that they are able to successfully make a change in their behavior is ▶ Motivational Interviewing strongly associated with their likelihood of doing ▶ Substance Use Disorders so. Therefore, fostering one’s sense of their own self-efficacy by eliciting examples of past suc- cesses or providing illustrative cases of others References and Readings who have made similar behavior changes can be very beneficial. In order to help facilitate these American Psychiatric Association. (2000). Diagnostic principles and resolve their ambivalence, MI uti- and statistical manual of mental disorders (4th ed., lizes interaction techniques such as open-ended text revision). Arlington, VA: American Psychiatric questions, reflective listening, and providing Association. Centers for Disease Control and Prevention. (2010a). positive affirmations. Tobacco use among middle and high school students – Considerable evidence now supports the use of United States, 2000–2009. Morbidity and Mortality MI for helping individuals to change their Weekly Report, 59, 1063–1068. smoking behavior. Although treatment effects Centers for Disease Control and Prevention. (2010b). Vital signs: Current cigarette smoking among adults tend to be modest, MI has been shown to success- aged 18 years – United States, 2009. Morbidity and fully increase the likelihood of smoking cessation. Mortality Weekly Report, 59, 1135–1140. The approach appears to be particularly effective Fiore, M. C., Jae´n, C. R., Baker, T. B., Bailey, W. C., for those expressing low motivation to quit. Due in Benowitz, N., Curry, S. J., et al. (2008). Treating tobacco use and dependence: 2008 update. Rockville, large part to its collaborative and nonconfron- MD: US DHHS, Public Health Service. tational style which respects an individual’s ability Hughes, J. R., Helzer, J. E., & Lindberg, S. A. (2006). to make their own decisions about when, how, and Prevalence of DSM/ICD-defined nicotine dependence. whether to change their behavior, MI also tends to Drug and Alcohol Dependence, 85, 91–102. Inrvin, J. E., & Brandon, T. H. (2000). The increasing be popular among both clinicians and clients. recalcitrance of smokers in clinical trials. Nicotine & Tobacco Research, 2, 79–84. Summary and Conclusions Inrvin, J. E., Hendricks, P. S., & Brandon, T. H. (2003). Although public health policy initiatives and The increasing recalcitrance of smokers in clinical tri- als II: Pharmacotherapy trials. Nicotine & Tobacco treatment advances have helped to reduce the Research, 5, 27–35. proportion of the population that smokes ciga- Marlatt, G. A., & Donovan, D. M. (2005). Relapse preven- rettes, tobacco use remains the leading cause tion: Maintenance strategies in the treatment of addic- of morbidity and premature mortality in our soci- tive behaviors (2nd ed.). New York: Guilford Press. Miller, W. R., & Rollnick, S. (2002). Motivational ety. Several evidence-based behavioral and phar- interviewing: Preparing people for change (2nd ed.). macologic treatments have been found to New York: Guilford Press. Character Traits 381 C

Shiffman, S., Brockwell, S. E., Pillitteri, J. L., & documented (Booth-Kewley & Vickers, 1994; Gitchell, J. G. (2008). Use of smoking-cessation treat- Ozer & Benet-Martinez, 2006). Hostility and ments in the United States. American Journal of Preventive Medicine, 34, 102–111. dominance, two components of the Type A behav- World Health Organization. (2008). WHO report on the ior pattern, have been related to asymptomatic global tobacco epidemic, 2008: The MPOWER atherosclerosis, incident coronary heart disease, package. Geneva, Switzerland: World Health and cardiac-specific and all-cause mortality Organization. C Zhu, S., Melcer, T., Sun, J., Rosbrook, B., & Pierce, J. P. (Smith, 2006). Each of the five character traits (2000). Smoking cessation with and without assis- that comprises the Five Factor Model, which has tance: A population-based analysis. American Journal been recommended as a culturally robust frame- of Preventive Medicine, 18, 305–311. work by which to guide investigations of the asso- ciation between personality and health outcomes (Taylor et al., 2009), has been linked to health CF behaviors, including wellness behaviors, accident control, traffic risk taking, and substance risk taking (Booth-Kewley & Vickers, 1994). ▶ Cystic Fibrosis These broad traits of the Five Factor Model include neuroticism (e.g., anxiety, hostility, and depression), extraversion (e.g., warmth, Changing assertiveness, and positive emotions), conscien- tiousness (e.g., self-discipline, order, and achieve- ▶ Aging ment striving), agreeableness (e.g., altruism, trust, and compliance), and openness to experience (e.g., fantasy, esthetics, and feelings). Neuroticism has additionally been linked to both distress- Character Traits relevant aspects of health (DeNeve & Cooper, 1998) and disease incidence (Friedman, Kern, & Jonathan A. Shaffer Reynolds, 2010). It has likewise been shown to Department of Medicine/Division of General predict, over more than four decades, Medicine, Columbia University Medical Center, subjective well-being, physical health, and lon- New York, NY, USA gevity (Friedman et al., 2010). Other research has shown that extraversion and conscientiousness predict longevity, low agreeableness (trait hostil- Synonyms ity) and negative affectivity predict poorer physical health and earlier mortality, and Personality; Psychosocial traits creativity predicts health and is associated with resiliency (Ozer & Benet-Martinez, 2006). Moreover, a meta-analytic review has identified Definition optimism as a significant predictor of positive physical health outcomes with regard to all-cause Character traits generally refer to the temporally mortality, survival, cardiovascular outcomes, stable and cross-situationally consistent individ- cancer outcomes, outcomes related to pregnancy, ual patterns in how people think, act, and feel. physical symptoms, immune functioning, and pain (Rasmussen, Scheier, & Greenhouse, 2009). Although researchers initially considered Description whether single diseases (such as coronary heart disease) were associated with single character Associations between character traits, health traits or personality types (such as hostility and behaviors, and health outcomes have been well Type A personality), Friedman and Booth-Kewley C 382 Characteristics

(1987) offered evidence in contradiction to this ▶ Neuroticism paradigm. In their meta-analysis of five emotional ▶ Personality facets of personality (including depression ▶ Trait Anger and anxiety) and five chronic diseases (including ▶ Trait Anxiety coronary heart disease) thought to be affected by ▶ Type A Behavior psychosomatic factors, they identified a pattern ▶ Type D Personality of associations between multiple predictors and multiple disease outcomes. Friedman and References and Readings Booth-Kewley’s research pointed to a broader “disease-prone personality,” and suggested the Booth-Kewley, S., & Vickers, R., Jr. (1994). Associations importance of assessing multiple character traits between major domains of personality and health behavior. Journal of Personality, 62(3), 281–298. and multiple health outcomes in the same DeNeve, K. M., & Cooper, H. (1998). The happy person- study (Friedman et al., 2010). Recent studies of ality: A meta-analysis of 137 personality traits and the associations of the five traits of the Five Factor subjective well-being. Psychological Bulletin, 124, Model with health outcomes reflect this paradigm 197–229. Friedman, H. S., & Booth-Kewley, S. (1987). The “dis- shift. For instance, Taylor and colleagues studied ease-prone personality:” A meta-analytic view of the whether character traits from the Five Factor construct. The American Psychologist, 42, 539–555. Model were associated with all-cause mortality Friedman, H. S., Kern, M. L., & Reynolds, C. A. (2010). in a general adult population in Scotland and Personality and health, subjective well-being, and lon- gevity. Journal of Personality, 78, 179–215. found that high conscientiousness and openness Ozer, D., & Benet-Martinez, V. (2006). Personality and were protective against all-cause mortality in men the prediction of consequential outcomes. Psychology, (Taylor et al., 2009). 57(1), 401–421. Current research on character traits and Rasmussen, H. N., Scheier, M. F., & Greenhouse, J. B. (2009). Optimism and physical health: A meta- physical health attempts to identify mechanisms analytic review. Annals of Behavioral Medicine, 37, by which personality gives rise to subsequent 239–256. health outcomes, and a variety of mechanistic Smith, T. (2006). Personality as risk and resilience in models have been proposed (Smith, 2006). physical health. Current Directions in Psychological Science, 15(5), 227–231. Health behavior models suggest that character Taylor, M. D., Whiteman, M. C., Fowkes, G. R., Lee, traits are associated with health behaviors, A. J., Allerhand, M., & Deary, I. J. (2009). Five factor which in turn elicit health outcomes. An interac- model personality traits and all-cause mortality in the tional stress moderation model posits that Edinburgh artery study cohort. Psychosomatic Medi- cine, 71, 631–641. character traits contribute to appraisal and coping, which in turn lead to physiological responses and health outcomes. A transactional stress moderation model expands the interac- Characteristics tional model by including the bidirectional effect of personality on exposure to stressful life ▶ Job Diagnostic Survey circumstances and availability of stress-reducing resources. Finally, the constitutional predisposi- tion model proposes that genetic or other psycho- biologic factors underlie both character traits and Chemical Dependency Treatment the development of health outcomes. ▶ Substance Abuse: Treatment

Cross-References Chemo, Cancer Chemotherapy ▶ Dispositional Optimism ▶ Heart Disease and Type A Behavior ▶ Chemotherapy Chemotherapy 383 C

needed for carcinogenesis and tumor growth. Chemokines Small-molecule tyrosine kinase inhibitors, like imatinib mesylate, and monoclonal antibodies, ▶ Cytokines like trastuzumab, are used in targeted therapy. Chemotherapy drugs can be administered orally, by injection, through a catheter or port, or topically. Chemotherapy drugs are most often C administered in combination, based on the known Chemotherapy biochemical actions of available anticancer drugs. To achieve superior outcome with com- Yu Yamada bined cancer chemotherapy, drugs which func- Department of Psychosomatic Medicine, Kyushu tion through separate cytotoxic mechanisms and University, Fukuoka, Japan have different dose-limiting adverse effects are administered together at full dosages. Patients may undergo chemotherapy at regular intervals, Synonyms i.e., once a week and once a month, depending on the type of cancer and drug therapy. Chemo, Cancer chemotherapy As most chemotherapy drugs are toxic to can- cer cells as well as normal healthy cells, they can cause a variety of side effects, including hair loss, Definition anemia, loss of appetite, nausea, and vomiting. Several behavioral medicine studies have also Chemotherapy is a treatment of diseases using suggested impairment of cognitive functions, chemical agents or drugs, particularly the treat- such as memory and attention, in some patients ment of cancer by cytotoxic and other drugs. In who receive chemotherapy, mostly as adjuvant a non-oncological setting, the term may also refer treatment for breast cancer. This impairment is to the administration of antibiotics against micro- referred to as “chemo-brain” or “chemo-fog.” organisms. Here, only cancer chemotherapy is Despite increasing research in this area, the discussed. mechanisms behind chemotherapy-induced cog- The main purpose of chemotherapy is to sys- nitive impairment remain largely unknown. temically kill cancer cells in the body. Most tra- Future studies are expected to shed light on both ditional drugs that are used in chemotherapy the prevention and treatment of “chemo-brain.” interfere with the ability of cells to grow and multiply. The variety of chemotherapy drugs are classified based on how they work. For exam- Cross-References ple, alkylating agents, like cyclophosphamide, kill cells by directly attacking DNA. Antimetab- ▶ Cancer Treatment and Management olites, like methotrexate, interfere with the ▶ Cancer, Types of production of DNA and the growth and multipli- cation of cells. Topoisomerase-interacting agents, antimicrotubule agents, and miscella- References and Readings neous chemotherapeutic agents are traditional chemotherapy drugs. These drugs target not Ahles, T. A., & Saykin, A. J. (2007). Candidate mecha- only cancer cells but also normal cells in the nisms for chemotherapy-induced cognitive changes. body. In contrast, there has been a recent emer- Nature Reviews Cancer, 7(3), 192–201. DeVita, V. T., & Lawrence, T. S. (2008). DeVita, Hell- gence of targeted therapy, which involves drugs man, and Rosenberg’s Cancer (Cancer: Principles that block the growth of only cancer cells by and Practice). Philadelphia: Lippincott Williams and interfering with specific targeted molecules Wilkins. C 384 Chesney, Margaret

Kennedy, B. J. (1999). Medical oncology: Its origin, evo- medicine perspectives to the prevention and treat- lution, current status, and future. Cancer, 85(1), 1–8. ment of HIV/AIDS. Tannock, I. F., Ahles, T. A., Ganz, P. A., et al. (2004). Cognitive impairment associated with chemotherapy From 2000 to 2003, while at UCSF, Chesney for cancer: Report of a workshop. Journal of Clinical pursued policy studies as a Senior Fellow at Oncology, 22(11), 2233–9. the Center for the Advancement of Health in Washington, DC, and served as a Scientific Advisor to the Office for Research on Women’s Health at the National Institutes of Health (NIH). In 2003, she became Deputy Director of the Chesney, Margaret National Center for Complementary and Alterna- tive Medicine (NCCAM) and a Senior Advisor to Margaret A. Chesney the Director of the Office of Behavioral and Department of Medicine & Center for Integrative Social Sciences Research at NIH. In 2010, Medicine, University of California, Margaret returned to UCSF as Professor in San Francisco, CA, USA Residence in the Department of Medicine, the Osher Foundation Distinguished Professor in Integrative Medicine, and Director of the Osher Biographical Information Center for Integrative Medicine at UCSF. Throughout her career, Chesney has chaired and served on numerous advisory groups for the NIH and the State of California, covering topics including health promotion and disease preven- tion, living with and beyond chronic illness, women’s health, and health-care policy. She is currently the Associate Editor of Psychology, Health and Medicine. Chesney has been President of the Academy of Behavioral Medicine Research, as well as President of the American Psychosomatic Society and President of the Division of Health Psychology of the American Psychological Association. She received the Distinguished Scientist Award from the Society of Behavioral Medicine in Margaret Chesney was born in Baltimore, 2011, the Director’s Award for work in Mind- Maryland. She graduated from Whitman College Body Medicine from the NIH in 2005, the in 1971 and received her PhD in Clinical and Charles C. Shepard Science Award, from the Counseling Psychology from Colorado State Centers for Disease Control and Prevention in University in 1975. She received postdoctoral 1999, and the President’s Award from the training in psychiatry from the Western Pennsyl- Academy of Behavioral Medicine Research in vania Psychiatric Institute where she studied 1987. In 2001, she was elected to the Institute of behavioral approaches to improving psychological Medicine. She received an honorary doctorate and physical health. In 1976, she joined Stanford from her alma mater, Whitman College, in 2008. Research Institute (SRI) to carry out research on stress and health. In 1978, she became Director of the new Department of Behavioral Medicine at Major Accomplishments SRI. In 1987, she moved her research to the Department of Medicine, University of California Chesney has been engaged in clinical practice San Francisco (UCSF), to contribute behavioral and research in the areas of stress, mind-body Chesney, Margaret 385 C interactions, and health. Her earliest studies Cross-References involved the use of relaxation-based exercises as an alternative to medication for managing ▶ Coping pain. Extending this approach to coronary heart ▶ Integrative Medicine disease, Chesney carried out a number of studies ▶ Stress Management to identify the coronary-prone features of the Type A behavior pattern. With colleagues at C SRI, she reported that hostility, competitiveness, References and Readings and depressed mood are characteristics associ- ated with increased risk of coronary events. Anderson, D. E., & Chesney, M. A. (2002). Gender- She followed this work with trials investigating specific association of perceived stress with inhibited lifestyle interventions designed to promote breathing pattern. International Journal of Behavioral health, prevent disease, and enhance well-being Medicine, 9, 216–277. Anderson, D. E., & Chesney, M. A. (2009). Gender in both women and men. differences in the role of stress and emotion in cardio- In the late 1980s, Chesney was invited to join vascular function and disease. In M. J. Legato (Ed.), the Center for AIDS Prevention Studies at UCSF Principles of gender-specific medicine (2nd ed., Vol. to develop behavioral interventions for persons 2, pp. 186–199). New York: Elsevier. Chesney, M. A. (2006). The elusive gold standard: Future living with HIV/AIDS. With Susan Folkman, perspectives for HIV adherence assessment and Chesney carried out research on stress and coping intervention. Journal of Acquired Immune Deficiency among caregivers of persons with HIV/AIDS and Syndrome, 43(Suppl. 1), S149–S155. developed a cognitive behavioral intervention, Chesney, M. A., Black, G. W., Swan, G. E., & Ward, M. M. (1987). Relaxation training for essential hypertension Coping Effectiveness Training (CET), for at the worksite. The untreated mild hypertensive. persons with HIV/AIDS, based on stress and Psychosomatic Medicine, 49, 250–263. coping theory. Shown to be effective with HIV, Chesney, M. A., Chambers, D. B., Taylor, J. M., Johnson, CET has been successfully applied to enhance L. M., & Folkman, S. (2003). Coping effectiveness training for men living with HIV: Results from coping with other chronic conditions including a randomized clinical trial testing a group-based inter- spinal cord injury and cancer. In addition, vention. Psychosomatic Medicine, 65, 1038–1046. Chesney developed measures of adherence and Chesney, M. A., Darbes, L., Hoerster, K., Taylor, J., led randomized trials of behavioral strategies to Chambers, D. C., & Anderson, D. E. (2005). Positive emotions: The other hemisphere of behavioral increase adherence to the complex treatment reg- medicine. International Journal of Behavioral imens for HIV/AIDS. She was also one of two Medicine, 12, 50–58. leaders of a San Francisco community-based Chesney, M. A., Hecker, M. H. L., & Black, G. W. (1988). study to encourage persons infected with HIV to Coronary-prone components of Type A behavior in the WCGS: A new methodology. In B. K. Houston & seek immediate treatment within the first days C. R. Snyder (Eds.), Type A behavior pattern: of infection, a study that led NIH to create Research, theory and intervention (pp. 168–188). a network investigating treatment of “primary New York: Wiley. HIV infection.” Chesney, M. A., Ickovics, J. R., Chambers, D. B., Gifford, A. L., Neidig, J., Zwickl, B., et al. (2000). Her interest in policy level interventions for Self-reported adherence to antiretroviral medications health promotion brought Chesney to Washington, among participants in HIV clinical trials: The DC, and NIH where she became familiar with the AACTG adherence instruments. AIDS Care, 12(3), emerging field of integrative medicine. Returning 255–266. Chesney, M. A., Koblin, B. A., Barresi, P. J., to UCSF, her current research is investigating Husnik, M. H., Celum, D. L., Colfax, G., et al. breathing, a core feature of many behavioral or (2003). An individually-tailored intervention for HIV integrative medicine interventions. With David prevention: Baseline data from the EXPLORE Study. Anderson, she is investigating whether breathing American Journal of Public Health, 93, 933–938. Chesney, M. A., Neilands, T. B., Chambers, D. B., Taylor, patterns may be a mechanism by which mind- J. M., & Folkman, S. (2006). A validity and reliability body interventions influence blood pressure, study of the coping self-efficacy scale. British Journal a major risk factor for cardiovascular disease. of Health Psychology, 11, 421–37. C 386 Chest Pain

rule out ST-elevation myocardial infarction, Chest Pain and other testing such as serial biomarkers (e.g., cardiac troponins or creatine kinase MB Siqin Ye isoenzyme), chest X-ray, and CT angiography Division of Cardiology, Columbia University of chest and thorax can be obtained based on the Medical Center, New York, NY, USA clinical suspicion (Cannon & Lee, 2008; Lee & Goldman, 2000). Despite the availability of these tests, however, the challenge remains to balance Synonyms the need to correctly diagnose patients with life-threatening conditions with avoidance of the Angina pectoris harm that can occur from unnecessary testing of those who are truly at low risk.

Definition Cross-References Acute chest pain is the common symptom of a multitude of medical conditions, ranging ▶ Angina Pectoris from the life threatening, such as myocardial infarction, pulmonary embolism, pneumothorax, and aortic dissection; to the less serious, such as References and Readings esophageal reflux, peptic ulcer disease, and gallbladder disease; to benign entities, such as Cannon, C. P., & Lee, T. H. (2008). Approach to the patient pericarditis, costochondritis, and panic attacks. with chest pain. In P. Libby, R. O. Bonow, D. L. Mann, D. P. Zipes, & E. Braunwald (Eds.), Braunwald’s heart As such, it is also one of the most frequent disease: A textbook of cardiovascular medicine causes for ER presentation in the United States, (pp. 1195–1205). Philadelphia: Saunders Elsevier. accounting for as many as seven million visits Lee, T. H., & Goldman, L. (2000). Evaluation of the annually. Rapid triage and accurate diagnostic patient with acute chest pain. The New England Journal of Medicine, 342(16), 1187–1195. workup are thus cornerstones of care for these Panju, A. A., Hemmelgarn, B. R., Guyatt, G. H., & Simel, patients (Cannon & Lee, 2008; Lee & Goldman, D. L. (1998). Is this patient having a myocardial infarc- 2000). tion? Journal of the American Medical Association, The evaluation of acute chest pain begins with 280(14), 1250–1263. a thorough history and physical that helps to distinguish the underlying etiology and guide testing. For instance, clinical features that are suggestive of myocardial infarction include prior history of coronary artery disease, pain or Child Abuse pressure radiating to the arm or jaw, and associ- ation with nausea, vomiting, or diaphoresis Melissa Merrick1 and Jason Jent2 (Panju, Hemmelgarn, Guyatt, & Simel, 1998). 1Division of Violence Prevention, Centers for Pain that is pleuritic (i.e., worse with deep inspi- Disease Control & Prevention, Atlanta, GA, USA ration) can be caused by pulmonary embolism, 2Department of Pediatrics, Mailman Center for while chest pain caused by aortic dissection is Child Development, University of Miami, typically described as excruciating and tearing Miami, FL, USA or ripping in quality, often radiating to the back. Pain that is worse with manual palpation, on the other hand, suggests a chest wall process such as Synonyms costochondritis and is often reassuring. Rapid ECG at time of presentation is recommended to Acts of commission Child Abuse 387 C

Definition penetration, however slight, between the mouth, penis, vulva, or anus of the child and another Child abuse is defined as acts of commission that individual. Sexual acts also include penetration, include the use of words or overt actions that however slight, of the anal or genital opening by cause harm, potential harm, or threat of harm to a hand, finger, or other object. Sexual acts can be a child (Leeb, Paulozzi, Melanson, Simon, & performed by the caregiver on the child or by the Arias, 2008). These are deliberate and intentional child on the caregiver. A caregiver might also C acts of commission by a caregiver, whether or not force or coerce a child to commit a sexual act harm to a child was the intended consequence. on another individual (child or adult). Abusive A caregiver is defined as a person who at the sexual contact involves intentional touching, time of the maltreatment is in a permanent (pri- either directly or through the clothing, of the mary caregiver) or temporary (substitute care- following: genitalia (penis or vulva), anus, giver) role. In a custodial role, the person is groin, breast, inner thigh, and/or buttocks. Abu- responsible for care and control of the child and sive sexual contact can be performed by the care- for the child’s overall health and welfare. giver on the child or by the child on the caregiver. A primary caregiver lives with the child at least Abusive sexual contact can also occur between part of the time and can include, but is not limited the child and another individual (adult or child) to, a relative or biological, adoptive, step-, or through force or coercion by a caregiver. Touch- foster parent(s); a legal guardian(s); or their inti- ing that is required for the normal care or atten- mate partner. A substitute caregiver may or may tion to the child’s daily needs does not constitute not live with the child and can include coaches, abusive sexual contact. clergy, teachers, relatives, babysitters, residential Noncontact sexual abuse can include any of facility staff, or others who are not the child’s the following: (a) exposing a child to sexual primary caregiver(s). activity (e.g., pornography, voyeurism of the Acts of omission, child neglect, are discussed child by an adult, intentional exposure of a child in a separate entry. to exhibitionism); (b) filming a child in a sexual manner (e.g., depiction, either photographic or Types cinematic, of a child in a sexual act); (c) sexually There are three different forms of child abuse that harassing a child (e.g., quid pro quo, creating involve acts of commission: physical abuse, sex- a hostile environment because of comments or ual abuse, and psychological/emotional abuse. attention of a sexual nature by a caregiver Physical abuse is defined as the intentional use to a child); and (d) prostituting a child of physical force against a child that results in, or (e.g., employing, using, persuading, inducing, has the potential to result in, physical injury enticing, encouraging, allowing, or permitting (Leeb et al., 2008). Physical abuse includes phys- a child to engage in or assist any other person to ical acts that range from those which do not leave engage in prostitution or sexual trafficking). a physical mark on the child to those which cause Psychological/emotional abuse includes permanent disability, disfigurement, or even intentional caregiver behavior that conveys to death. Examples of physical abuse can include a child that he/she is worthless, flawed, unloved, hitting, kicking, punching, beating, stabbing, bit- unwanted, endangered, or valued only in meeting ing, pushing, throwing, pulling, dragging, another’s needs (Leeb et al., 2008). Psychologi- dropping, shaking, choking, smothering, burning, cal/emotional abuse can be continual or episodic scalding, and poisoning. (e.g., triggered by a specific context or situation). Sexual abuse is defined as any completed or Psychologically/emotionally abusive behaviors attempted sexual act, sexual contact with, or often consist of blaming, belittling, degrading, exploitation (i.e., noncontact sexual interaction) intimidating, terrorizing, isolating, restraining, of a child by a caregiver (Leeb et al., 2008). confining, corrupting, exploiting, or otherwise Sexual acts include contact involving behaving in a manner that is harmful, potentially C 388 Child Abuse harmful, or insensitive to the child’s develop- increase a child’s vulnerability include child age mental needs or can potentially damage the younger than 4 years and those children with spe- child psychologically or emotionally. cial needs. Also, parents’ lack of understanding of child development and parenting skills; parents’ history of child abuse, substance abuse, and/or Description mental health issues; parental characteristics such as young age, low education, single parenthood, Prevalence large number of dependent children, and low In 2008, US state and local child protective ser- income; and nonbiological, transient caregivers vices (CPS) received 3.3 million reports of chil- in the home (e.g., mother’s male partner) all dren being abused and/or neglected. CPS seem to increase the risk of perpetration of estimated that 772,000 (10.3 per 1,000) of these child abuse in the home. Other risk factors for children had substantiated cases of child abuse perpetration include poor social connections and and/or child neglect. Approximately three quarters support, family violence (e.g., intimate partner of them had no history of prior victimization. violence), poor parent-child relationships, parent- Sixteen percent of the children were classified ing stress, community violence, and concentrated as victims of physical abuse, 9% as victims of neighborhood disadvantage (e.g., high poverty and sexual abuse, and 7% as victims of psychologi- residential instability, high unemployment rates). cal/emotional abuse (USDHHS, 2010). The Extensive research demonstrates that child remaining children were classified as victims of abuse can have devastating effects on physical child neglect. A recent national study estimated and mental health. Abuse during infancy or early that 1 in 5 US children has experienced some childhood can cause important regions of the form of child abuse or neglect in their lifetime, brain to form and function improperly with with a rate of 1 in 10 experiencing some form of long-term consequences on cognitive, language, child abuse or neglect in the past year (Finkelhor, and socioemotional development and mental Turner, Ormrod, & Hamby, 2009). In 2008, health. Children may experience severe or fatal a CPS-based study found that African-American head trauma as a result of abuse. Nonfatal conse- (16.6 per 1,000 children), American Indian or quences of abusive head trauma include varying Alaska Native (13.9 per 1,000 children), and mul- degrees of visual impairment (e.g., blindness), tiracial (13.8 per 1,000 children) children had motor impairment (e.g., cerebral palsy), and cog- higher rates of victimization than other racial nitive impairments (Christian, Block, & The groups, with slightly higher rates for girls Committee on Child Abuse & Neglect, 2009). (10.8 per 1,000 children) than boys (9.7 per 1,000 Also, the stress of chronic abuse may result in children) overall (USDHHS, 2010). Research has anxiety and may make children more vulnerable demonstrated similar negative sequelae for chil- to problems such as posttraumatic stress disorder, dren who have substantiated CPS reports of abuse conduct disorder, and learning, attention, and and for children who have alleged or suspected memory difficulties (Dallam, 2001; Perry, CPS reports of abuse (Hussey et al., 2005). 2001). Studies have found abused children are more likely to be arrested or become involved in Etiology and Sequelae delinquent and violent behavior in adolescence A combination of individual, relational, commu- and experience teen pregnancy, low academic nity, and societal factors contributes to the risk of achievement, and decreased high school gradua- child abuse. Although children are not responsi- tion rates (Langsford et al., 2007). Abused children ble for the harm inflicted upon them, certain are also at increased risk for adverse health behav- characteristics have been found to increase their iors, such as smoking, alcoholism, drug abuse, and risk of being abused (Berliner, 2011; Centers for engaging in high-risk sexual behaviors, which Disease Control and Prevention, 2009; Runyon & often lead to certain chronic diseases as adults, Urquiza, 2011). Individual child factors that including heart disease, cancer, chronic lung Child Development 389 C disease, liver disease, obesity, high blood pressure, Langsford, J. E., Miller-Johnson, S., Berlin, L. J., Dodge, and high cholesterol (Runyan, Wattam, Ikeda, K. A., Bates, J. E., & Pettit, G. S. (2007). Early phys- ical abuse and later violent delinquency: A prospective Hassan, & Ramiro, 2002). In one long-term longitudinal study. Child Maltreatment, 12, 233–245. study, as many as 80% of young adults who had Leeb, R. T., Paulozzi. L., Melanson, C., Simon, T., & been abused met the diagnostic criteria for at least Arias, I. (2008). Child maltreatment surveillance: Uni- one psychiatric disorder at age 21. These young form definitions for public health and recommended data elements, version 1.0. Atlanta, GA: Centers for C adults exhibited many problems, including depres- Disease Control and Prevention, National Center for sion, anxiety, eating disorders, and suicide Injury Prevention and Control. Retrieved July 20, attempts (Silverman, Reinherz, & Giaconia, 2011, from http://www.cdc.gov/violenceprevention/ 1996). Abuse can also increase the likelihood of pdf/CM_Surveillance-a.pdf Perry, B. D. (2001). The neurodevelopmental impact of adult criminal behavior and violent crime (Widom violence in childhood. In D. Schetky & E. Benedek &Maxfield,2001). Finally, early child abuse can (Eds.), Textbook of child and adolescent forensic have a negative effect on the ability of both men psychiatry (pp. 221–238). Washington, DC: American and women to establish and maintain healthy inti- Psychiatric Press. Runyan, D., Wattam, C., Ikeda, R., Hassan, F., & Ramiro, mate relationships in adulthood (Colman & L. (2002). Child abuse and neglect by parents and other Widom, 2004), which may also perpetuate the caregivers. In E. Krug, L. L. Dahlberg, J. A. Mercy, cycle of violence from one generation to the next. A. B. Zwi, & R. Lozano (Eds.), World report on violence and health (pp. 59–86). Geneva, Switzerland: World Health Organization. Runyon, M. K., & Urquiza, A. J. (2011). Child physical Cross-References abuse: Interventions for parents who engage in coer- cive parenting practices and their children. In E. John ▶ Family Violence & B. Myers (Eds.), The APSAC handbook on child maltreatment (3rd ed., pp. 195–214). Thousand Oaks, CA: Sage. Silverman, A. B., Reinherz, H. Z., & Giaconia, R. M. References and Readings (1996). The long-term sequelae of child and adoles- cent abuse: A longitudinal community study. Child Berliner, L. (2011). Child sexual abuse. In E. John & Abuse & Neglect, 20, 709–723. B. Myers (Eds.), The APSAC handbook on child mal- U.S. Department of Health and Human Services, Adminis- treatment (3rd ed., pp. 215–232). Thousand Oaks, CA: tration on Children, Youth and Families. Child Maltreat- Sage. ment 2008, Washington, DC: U.S. Government Printing Centers for Disease Control and Prevention. (2009). Child Office, 2010. Retrieved from http://www.acf.hhs.gov maltreatment: Risk and protective factors. Retrieved Widom, C. S., & Maxfield, M. G. (2001). An update on the July 20, 2011, from http://www.cdc.gov/Violence- “cycle of violence.” Washington, DC: National Insti- Prevention/childmaltreatment/riskprotectivefactors.html tute of Justice; 2001. Retrieved July 20, 2011, from Christian, C. W., Block, R., & The Committee on Child http://www.ncjrs.gov/pdffiles1/nij/184894.pdf Abuse & Neglect. (2009). American academy of pedi- atrics policy statement: Abusive head trauma in infants and children. Pediatrics, 123, 1409–1411. Colman, R., & Widom, C. (2004). Childhood abuse and neglect and adult intimate relationships: A prospective Child Development study. Child Abuse & Neglect, 28, 1133–1151. Dallam, S. J. (2001). The long-term medical consequences of childhood maltreatment. In K. Franey, R. Geffner, Debbie Palmer & R. Falconer (Eds.), The cost of child maltreatment: Department of Psychology, University of Who pays? We all do. San Diego, CA: Family Wisconsin-Stevens Point, Stevens Point, Violence & Sexual Assault Institute. WI, USA Finkelhor, D., Turner, H., Ormrod, R., & Hamby, S. (2009). Violence, abuse, and crime exposure in a national sample of children and youth. Pediatrics, 124, 1411–1423. Synonyms Hussey, J., Marshall, J., English, D., Knight, E., Lau, A., Dubowitz, H., et al. (2005). Defining maltreatment according to substantiation: Distinction without Adolescent psychology; Child psychology; a difference? Child Abuse & Neglect, 29, 479–492. Developmental psychology; Pediatric psychology C 390 Child Development

Definition developments, with an emphasis on how norma- tive functioning and processes either change The field of child development is concerned with or remain constant across time as a result of the scientific study of human growth and func- maturation and/or experience (Lerner, 2006). tioning across the early stages of development Biological processes in infancy and childhood (i.e., the prenatal period through adolescence) entail the growth and maturation of the internal and within the multitude of contexts of daily organ systems and observable increases in both life. Areas of interest include – though are not height and weight, and how these connect to the limited to – biological, cognitive, physical, development and refinement of advancing motor social, and emotional change across the early skills. Subsequent biological growth in adoles- portions of life. In all cases, an emphasis is placed cence is demonstrated by secondary sexual on understanding how normative functioning maturation through the process of pubertal devel- changes or remains constant across time as opment and the attainment of more adult-like a result of maturation and/or experience (Lerner, stature and weight. Cognitive growth in infancy 2006). Child development is one aspect of the and childhood includes rapid gains in language broader field of Developmental Psychology, processing, production, and comprehension. which examines human growth and functioning Memory capacity expands and more sophisti- across the entire lifespan. cated strategies for retention and recall are demonstrated. Also, individuals gain enhanced understanding of logic related to concrete Description concepts in childhood and to abstract concepts in adolescence. Social growth in infancy and The field of child development is concerned with childhood involves dependent interactions and the scientific study of human growth and attachments to caregivers and expands to include functioning throughout the early portions of life, peer and friendship relationships. Later in adoles- including the prenatal period through adoles- cence, social networks expand to include cliques cence. The entire human lifespan includes the and significant others as increasingly intimate prenatal period, infancy, childhood (early, relationships develop. Early emotional growth middle, and late), adolescence (early, middle, in infancy and childhood entails the presence and late), emerging adulthood, and adulthood of primary feelings and the development of self- (early, middle, and late) (Arnett, 2004; Santrock, conscious emotions. Subsequent growth in 2012; Steinberg, 2011). One way the earliest adolescence involves enhanced understanding of periods of human life may be contemplated is in societal rules for the display and regulation terms of chronological age. From this perspec- of emotions and coping with life’s challenges. tive, the prenatal period spans the time of These different domains of growth and devel- conception through birth and lasts approximately opment do not occur independently, but are 9 months for a typical pregnancy. Infancy encom- interrelated. That is, an infant who smiles at the passes from birth through 18 or 24 months of age. appearance of his or her father requires biological Early childhood includes from 18 or 24 months functioning (the sensation of seeing), cognitive through 5 or 6 years of age. Middle and late and social functioning (recognition of and feeling childhood runs from 5 or 6 years through approx- attached to a familiar caregiver), and emotional imately 11 years of age. Adolescence is from functioning (smiling) (Santrock, 2012). Child around 11 years of age through approximately development explores not only how these 18 years of age. different domains develop but also how their Child development considers the multitude of interrelated processes are manifested in mile- contexts of daily life that humans encounter. stones associated with each of the early periods Areas of interest include – though are not limited of human life. Prenatal development entails the to – biological, cognitive, social, and emotional development from a single fertilized egg to Child Development 391 C a fetus that is able to function outside the preschoolers may respond to the world in mother’s womb. The growth across the approxi- a manner very similar to how adults respond. mate 9-month period of time prepares the organ- That is, a child’s thinking may be just as logical ism for the life ahead of it. In early childhood, and well organized as that of an adult. He or she individuals are making rapid strides in autonomy may demonstrate the ability to successfully sort development and gaining self-control, which gets objects in to different categories (e.g., clothes are manifested in a variety of milestone achieve- separate from toys), show understanding when C ments, such as potty training and turn-taking there are different quantities or amounts present (Berk, 2003). Children are also being prepared (e.g., more cookies are in the jar than are on the to enter the formal education system at this time. plate), and retain information for long periods of In middle childhood, children typically enter the time (e.g., go straight to where the DVDs are formal educational system and attend elementary stored at grandma’s house after not visiting for school. Emphasis in milestone achievement weeks). However, a child’s thinking may be lim- is usually placed on academic ability, with ited by how little experience he or she has had in fundamentals such as reading, writing, and basic interacting with the world. From this perspective, mathematical skills attained and refined during a child possesses the same skills as an adult, but this time. The social world of children also has simply not acquired as much information or expands to include more peers and adults beyond been able to refine these skills compared to family members. Extracurricular activities such adults. An example of a discontinuous approach as those involving sports and other cultural to cognitive development includes the theoretical aspects of society (e.g., dance, music) are often work of Jean Piaget, who emphasized the impor- initiated during this time (Santrock, 2012). tance of adaptation to one’s environment and During adolescence, an emphasis is often placed increasing organization of knowledge across on the future, with preparation for later educa- development (Piaget, 1954). He stated that tion, careers, and relationships being stressed. cognition unfolded in an invariant manner, across Increased time is spent with peers away from four major stages: the sensorimotor period the family unit in less supervised settings. (experiencing the world through senses and Increasingly, and across numerous contexts, actions), the preoperational period (representing responsibility is gained, along with enhanced things with words and images but lacking logical expectations from others for self-reliant behavior reasoning), the concrete operational period and maturity. Rapid biological changes occur as (thinking logically about concrete events, analo- result of pubertal development, which enables gies), and the formal operational period (reason- the adolescent to become capable of reproduction ing abstractly). According to Piaget, cognitive and leads to changes in social relationships. development could be described as occurring Self-images become more complex to incorporate consistently across cultures and children were sexual and identity development. More influence active agents and not merely passive recipients is sought within family functioning, which neces- in their own development (Piaget, 1954). sitates adjustments in how parents and siblings Knowledge of child development is important relate to the adolescent (Steinberg, 2011). to the field of behavioral medicine in numerous Theoretical approaches in child development ways. Knowledge of normal child development can adhere to continuous or discontinuous can be extremely useful for parents, teachers, conceptualizations. Continuous approaches cast and health-care providers – as well as many others development as gradually changing across time – who may encounter and interact with those who and experience, while discontinuous approaches manifest diseases and/or deviations from normal cast development as being qualitatively distinct development. Knowledge of typical development across each life stage. A scenario that illustrates can aid in detecting and treating atypical develop- the continuous approach is offered by Berk ment, and enables researchers and clinicians to (2003), who suggested that babies and develop the most appropriate care for children C 392 Child Development with acute and chronic medical conditions, while (ages 18–25 years). This transition is risky par- also meeting children’s developmental needs. tially because it involves a transition from Programs crafted for adult patients to educate a pediatric to an adult health-care system or alter behaviors impacting health may not (i.e., pediatrician may treat an individual until he be appropriate for younger patients. Likewise, or she is 18; age limits on parents’ health insurance the effectiveness of health-care treatment of dis- policy), which generally needs to be addressed eases and disorders in childhood can be directly during the earlier adolescent years. Unfortunately, impacted by biological or other developmental the transition from adolescence to emerging adult- processes. For instance, changes in pubertal hood or young adulthood remains a significant hormones among adolescents with type 1 diabetes challenge for caregivers and their patients and can dysregulate glucose metabolism. By anticipat- the health-care system (Huang et al., 2011). ing these biological changes, clinicians may be There are numerous professional organiza- able to forewarn adolescent patients with type 1 tions that support practice and research at the diabetes and their parents and develop possible interface of child development and behavioral strategies to minimize deterioration in illness medicine. The Child and Family Health Special self-management during adolescence (Halvorson, Interest Group of the Society of Behavioral Med- Yasuda, Carpenter, & Kaiserman, 2005). icine is an interdisciplinary forum for researchers Child development research can also reveal and clinicians to promote child health and devel- periods of risk, when primary or secondary pre- opment, prevent childhood illness and injury, and vention efforts may be most effective. Health and foster family adjustment to chronic illnesses. health risk behaviors that affect morbidity and Other relevant organizations include the Society mortality in later life are established early in of Pediatric Psychology (Division 54 of the life. For instance, food selection choices (e.g., American Psychological Association), Society fast food versus more nutritionally balanced for Research on Child Development, Society for items) and decisions to be physically active may Research on Adolescence, and Eunice Kennedy become consistent behaviors during childhood Shriver National Institute of Child Health & and adolescence. Similarly, high-risk behaviors Human Development. (e.g., sexual experimentation, tobacco and alco- hol use) often become relevant concerns during adolescence (Williams, Holmbeck, & Greenley, Cross-References 2002). Thus, interventions to promote healthy behaviors and to prevent health risk behaviors ▶ Diabesity in Children may be most effective during childhood and ado- ▶ Family, Caregiver lescence. Other known periods of risk occur at ▶ Health Behaviors important developmental transitions such as ▶ Health Risk (Behavior) when rapid autonomy development among ado- ▶ National Children’s Study lescents with pediatric conditions may conflict ▶ Prevention: Primary, Secondary, Tertiary with the efforts of parental or family caregivers. ▶ Society of Behavioral Medicine Researchers in behavioral medicine/pediatric psychology have demonstrated the need to consider autonomy in the management of chronic References and Readings conditions such as spina bifida and type 1 diabe- tes (Buchbinder, 2009; Friedman, Holmbeck, Arnett, J. (2004). Emerging adulthood: The winding road DeLucia, Jandasek, & Zebracki, 2009). Another from the late teens through the twenties. New York: period of risk that has gained recent attention for Oxford University Press. youth with chronic conditions is that of emerging Berk, L. E. (2003). Child development (6th ed.). Boston: Allyn and Bacon. adulthood, the time between late adolescence and Buchbinder, M. (2009). The management of autonomy in the establishment of one’s identity as an adult type 1 diabetes: A case study of triadic medical Child Neglect 393 C

interaction. Health: An Interdisciplinary Journal for Definition the Social Study of Health, Illness and Medicine, 13(2), 175–196. doi:10.1177/1363459308099683. Friedman, D., Holmbeck, G., DeLucia, C., Jandasek, B., & Child neglect is defined as acts of omission by Zebracki, K. (2009). Trajectories of autonomy devel- a caregiver that include failure to provide for opment across the adolescent transition in children a child’s basic physical, emotional, or educational with spina bifida. Rehabilitation Psychology, 54(1), needs and/or failure to protect a child from harm 16–27. doi:10.1037/a0014279. C Halvorson, M., Yasuda, P., Carpenter, S., & Kaiserman, K. or potential harm (Leeb, Paulozzi, Melanson, (2005). Unique challenges for pediatric patients with Simon, & Arias, 2008). The resultant harm to diabetes. Diabetes Spectrum, 18(3), 167–173. a child may or may not be the intended conse- doi:10.2337/diaspect.18.3.167. quence of the act of omission, but still represents http://www.cfw.tufts.edu/ http://www.healthychildren.org/ neglect. Neglect typically consists of a chronic http://www.nlm.nih.gov/medlineplus/teendevelopment.html pattern of acts of omission by a caregiver that http://www.srcd.org/ result in actual or potential harm to a child. How- http://www.zerotothree.org/ ever, there are specific singular instances where Huang, J. S., Gottschalk, M., Pian, M., Dillon, L., Barajas, D., & Bartholomew, L. K. (2011). Transition to adult failure to supervise can result in significant harm care: Systematic assessment of adolescents with to a child (e.g., injury, death). chronic illnesses and their medical teams. Journal A caregiver is defined as a person who at the of Pediatrics, 159(6), 994–998. doi:10.1016/j. time of the maltreatment is in a permanent jpeds.2011.05.038. Lerner, R. M. (2006). Developmental science, develop- (primary caregiver) or temporary (substitute mental systems, and contemporary theories of human caregiver) role. In a custodial role, the person is development. In R. M. Lerner, W. Damon, & R. M. responsible for care and control of the child and Lerner (Eds.), Handbook of child psychology (Theo- for the child’s overall health and welfare. retical models of human development 6th ed., Vol. 1, pp. 1–17). Hoboken, NJ: Wiley. A primary caregiver lives with the child at least Piaget, J. (1954). The construction of reality in the child. part of the time and can include, but is not limited New York: Harcourt Brace Jovanovich. to, a relative or biological, adoptive, step-, or Santrock, J. W. (2012). A topical approach to life-span foster parent(s); a legal guardian(s); or their inti- development (6th ed.). New York: McGraw-Hill. Steinberg, L. (2011). Adolescence (9th ed.). New York: mate partner. A substitute caregiver may or may McGraw-Hill. not live with the child and can include coaches, Williams, P. G., Holmbeck, G. N., & Greenley, R. N. clergy, teachers, relatives, babysitters, residential (2002). Adolescent health psychology. Journal of facility staff, or others who are not the child’s Consulting and Clinical Psychology, 70(3), 828–842. doi:10.1037//0022-006X.70.3.828. primary caregiver(s). Acts of commission, child abuse, are discussed in a separate entry.

Types Child Neglect A caregiver’s failure to provide a child’s basic needs may result in specific types of neglect Jason Jent1 and Melissa Merrick2 including: physical neglect, emotional neglect, 1Department of Pediatrics, Mailman Center for medical neglect, and educational neglect Child Development, University of Miami, (Barnett, Manly, & Cicchetti, 1993). Miami, FL, USA Physical neglect is defined as a caregiver’s 2Division of Violence Prevention, Centers for failure to provide a child adequate nutrition, Disease Control & Prevention, Atlanta, GA, USA hygiene, or shelter; or caregiver fails to provide clothing that is adequately clean, appropriate size, or adequate for the weather (Leeb et al., 2008). Synonyms Emotional neglect occurs when a caregiver ignores the child or denies emotional responsive- Caregiver acts of omission ness or adequate access to mental health care C 394 Child Neglect

(e.g., pervasive failures by a caregiver to interact Exposure to violent environments includes with a child that include consistently not knowingly failing to take appropriate measures responding to infant cries or to an older child’s to protect a child from being exposed to pervasive attempts to interact with the caregiver) (Barnett violence (e.g., domestic violence) or dangerous et al., 1993). conditions (e.g., selling drugs out of the home) Medical neglect includes a failure by within the home, neighborhood, or community a caregiver to provide a child adequate access to (Leeb et al., 2008). Of course, such situations medical, vision, and/or dental care, when access are an ethical challenge for the child protection to care is available or when a caregiver fails to field because in many circumstances, if one par- seek timely medical attention for a child when ent is being battered, he or she may be ill needed (Leeb et al., 2008). Medical neglect is equipped and even unable to prevent his or her also indicated when a caregiver fails to follow children from witnessing violence in the home. through with medical recommendations and/or treatment regimens (e.g., not consistently admin- istering prescribed medications to a child), in Description which the caregiver’s failure to follow through may result in harm to the child. Prevalence Educational neglect refers to a caregiver’s The most recent estimates of the prevalence of failure to ensure that a child regularly attends child abuse and/or neglect indicate that approxi- school, which results in excessive absences mately 772,000 children (10.3 per 1,000 children (e.g., 25 or more days in 1 academic year) with in the population) are substantiated victims annu- no acceptable excuses (e.g., physician’s note; ally (USDHHS, 2010). Of the various forms of Leeb et al., 2008). Educational neglect is also child abuse and neglect, approximately 552,000 defined as the failure of a caregiver to enroll and children experience either neglect and/or medical maintain a child in school up until the age of 16. neglect annually. Neglect is the most prevalent With respect to a child’s emotional and devel- form of child maltreatment, with 71% of all sub- opmental level, failure to supervise a child’s stantiated cases of maltreatment being classified safety within and outside of the home is catego- as neglect (USDHHS, 2010). However, neglect is rized as specific types of neglect including inad- often the most difficult form of maltreatment to equate supervision and exposure to violent recognize because physical evidence is rare environments. unless a family’s home environment is physically Inadequate supervision refers to the failure of inspected or the neglect has resulted in an injury, a caregiver to ensure that the child engages in safe specific medical problem (e.g., failure to thrive), activities and uses appropriate safety devices so or an exacerbated chronic medical condition that the child is not exposed to unnecessary haz- (e.g., sickle cell disease). ards and/or that the child is being supervised by an adequate substitute caregiver when the pri- Etiology and Sequelae mary caregiver(s) is not available (Leeb et al., It is clear that no singular risk factor can ade- 2008). Inadequate supervision can also include quately explain why children are neglected. circumstances where a caregiver knowingly fails Rather, a combination of individual, relational, to protect a child from maltreatment perpetrated community, and societal factors contributes to by another caregiver. Under such conditions, the the risk of a child being neglected (Centers for primary caregiver’s behavior would be consid- Disease Control and Prevention, 2009;Cicchetti& ered neglectful only if the maltreatment was rec- Lynch, 1993; Erickson & Egeland, 2011). ognized and allowed to occur. Regardless of the Although children are not responsible for care- primary caregiver’s knowledge of the maltreat- givers’ neglectful behaviors, certain characteris- ment, the substitute caregiver’s behaviors would tics have been found to increase their risk of be considered maltreatment. being neglected (Centers for Disease Control Child Neglect 395 C and Prevention, 2009). Child factors that increase aggression, noncompliance, anxious attachment vulnerability for neglect include being to their caregivers, restricted positive views of younger than 4 years old and having special the self, and social withdrawal (Dubowitz, Papas, needs (e.g., developmental disabilities, chronic Black, & Starr, 2002;Hildyard&Wolfe,2002). medical conditions). A number of caregiver- Many of the problems observed in children specific risk factors contribute to an increased who are neglected in early childhood remain in risk for the perpetration of neglect, including care- school-aged children including continued cogni- C giver poor prenatal and postnatal medical tive problems (e.g., poor performance on academic care, a caregiver’s lack of understanding of child achievement tests and increased referrals for spe- development and parenting skills, lack of parental cial education services), negative mental represen- nurturance, substance abuse, caregiver mental tations of the self and others, avoidance of peer health issues, poor parent-child relationships, and interactions, limited social skills, and an increased parenting stress (Stith et al., 2009). Other caregiver prevalence of internalizing problems (e.g., depres- characteristics such as the caregiver’s own history sion, anxiety, peer rejection). of maltreatment as a child, young age, low educa- The effects of child neglect have also been tion, single caregiver household, and a large num- implicated in adult functioning. Adults who ber of dependent children all have been linked to have experienced neglect as a child are at increased risk of child neglect. Other risk factors increased risk for psychiatric disorders, substance include low family income, poor social connec- abuse, violent behaviors, and intimate partner tions and support, family conflict and violence violence (Erickson & Egeland, 2011; Horwitz, (e.g., intimate partner violence), community Widom, McLaughlin, & White, 2001; Mersky violence, and concentrated neighborhood disad- & Reynolds, 2007; White & Widom, 2003; vantage (e.g., high poverty and residential insta- Widom, Marmorstein, & White, 2006). bility, high unemployment rates). Child neglect has been found to have serious negative implications on children’s cognitive, Cross-References physical, and socioemotional development. How- ever, the consequences of individual cases of child ▶ Child Abuse neglect vary and are impacted by a combination of ▶ Family Violence factors, including the child’s age and developmen- tal status when neglected; the types of abuse and/or neglect experienced; the frequency, duration, and References and Readings severity of the neglect; and the relationship of the Barnett, D., Manly, J. T., & Cicchetti, D. (1993). Defining perpetrator to the victim child (English et al., 2005; child maltreatment: The interface between policy and Chalk, Gibbons, & Scarupa, 2002). If children’s research. In D. Cicchetti & S. Toth (Eds.), Child abuse, needs for physical touch, emotional attachment to child development, and social policy (pp. 7–73). a caregiver, and caregiver-child interactions are Norwood, NJ: Ablex. Centers for Disease Control and Prevention. (2009). neglected during infancy or early childhood, Child maltreatment: Risk and protective factors. long-term consequences have been found in chil- Retrieved on July 20, 2011 from http://www.cdc.gov/ dren’s cognitive and socioemotional development. ViolencePrevention/childmaltreatment/riskprotective Research on neglected infants has demonstrated factors.html Chalk, R., Gibbons, A., & Scarupa, H. J. (2002). The reduced brain wave activity and enlarged brain multiple dimensions of child abuse and neglect: New ventricles due to decreased brain growth (Perry, insights into an old problem. Washington, DC: Child 1997, 2002). Neglected infants and young children Trends. Retrieved on July 20, 2011 from www. are at increased risk for developmental delays, childtrends.org/Files/ChildAbuseRB.pdf Cicchetti, D., & Lynch, M. (1993). Toward an ecological/ expressive and receptive language problems, transactional model of community violence and child decreased positive affect, emotion regulation dif- maltreatment: Consequences for children’s develop- ficulties, impulse control problems, physical ment. Psychiatry, 56, 96–118. C 396 Child Psychology

Dubowitz, H., Papas, M. A., Black, M. M., & Starr, R. H., Jr. (2002). Child neglect: Outcomes in high-risk urban Child Psychology preschoolers. Pediatrics, 109, 1100–1107. English, D. J., Upadhyaya, M. P., Litrownik, A. J., Marshall, J. M., Runyan, D. K., Graham, J. C., et al. ▶ Child Development (2005). Maltreatment’s wake: The relationship of mal- treatment dimensions to child outcomes. Child Abuse & Neglect, 29, 597–619. Erickson, M. F., & Egeland, B. (2011). Child neglect. In E. John & B. Myers (Eds.), The APSAC handbook on Childhood Obesity child maltreatment (3rd ed., pp. 103–124). Thousand Oaks, CA: Sage. ▶ Diabesity in Children Hildyard, K. L., & Wolfe, D. A. (2002). Child neglect: Developmental issues and outcomes. Child Abuse & Neglect, 26, 679–695. Horwitz, A. V., Widom, C. S., McLaughlin, J., & White, H. R. (2001). The impact of childhood abuse and Childhood Origins of Cardiovascular neglect on adult mental health: A prospective study. Journal of Health and Social Behavior, 42, Disease 184–201. Leeb, R. T., Paulozzi, L., Melanson, C., Simon, T., & ▶ Bogalusa Heart Study Arias, I. (2008). Child maltreatment surveillance: Uni- form definitions for public health and recommended data elements, Version 1.0. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Retrieved on July 20, CHO 2011 from http://www.cdc.gov/violenceprevention/ pdf/CM_Surveillance-a.pdf ▶ Merksy, J. P., & Reynolds, A. J. (2007). Child maltreat- Carbohydrates ment and violent delinquency: Disentangling main effects and subgroup effects. Child Maltreatment, 12, 246–258. Perry, B. (1997). Incubated in terror: Neurodevelopmental factors in the “cycle of violence.” In J. D. Osofsky Cholesterol (Ed.), Children in a violent society (pp. 124–149). New York: Guilford Press. Barbara Smith Perry, B. (2002). Childhood experience and the expres- sion of genetic potential: What childhood neglect School of Nursing, University of Maryland, tells us about nature and nurture. Brain and Mind, 3, Baltimore, MD, USA 79–100. Stith, S. M., Liu, T., Davies, L. C., Boykin, E. L., Alder, M. C., Harris, J. M., et al. (2009). Risk factors in child maltreatment: A meta-analytic review of the literature. Synonyms Aggression and Violent Behavior, 14, 13–29. U.S. Department of Health and Human Services, Admin- Sterol istration for Children and Families, Administration on Children, Youth and Families, Children’s Bureau. (2010). Child maltreatment 2008. Retrieved on July 20, 2011 from http://www.acf.hhs.gov/programs/cb/ Definition stats_research/index.htm#can White, H., & Widom, C. (2003). Intimate partner violence Cholesterol is a steroid. It is essential to the among abused and neglected children in young adult- hood: The mediating effects of early aggression, anti- proper functioning of cell membranes and the social personality, hostility, and alcohol problems. synthesis of many hormones critical to normal Aggressive Behavior, 29, 332–345. physiologic processes and health. When choles- Widom, C., Marmorstein, N., & White, H. (2006). Child- terol is manufactured primarily by the liver, and hood victimization and illicit drug use in middle adult- hood. Psychology of Addictive Behaviors, 20, to a lesser degree by the intestines and other cells 394–403. in the body it is known as endogenous Chromosomes 397 C cholesterol. On the other hand, cholesterol which approach to primary prevention of coronary one consumes and is absorbed into the blood heart disease (CHD) in persons with high stream via the gastrointestinal tract is known as LDL (160 mg/dL) or borderline high LDL exogenous cholesterol. (130–159 mg/dL) and multiple risk factors. ATP II set a new optimal LDL level of 100 mg/dL for people with CHD. ATP III focuses on inten- Description sive LDL reduction in those with multiple risk C factors. Despite the essential role cholesterol plays in cell wall permeability and the synthesis of steroid hormones excessive amounts of circulating cho- Cross-References lesterol and the low-density lipoprotein (LDL) ▶ subfraction of total cholesterol have been associ- Lipoprotein ated with an increase in cardiovascular morbidity and mortality. This increase in morbidity and mortality is likely related to the development of References and Readings atherosclerosis, a disease of the large and inter- Expert Panel of Detection, Evaluation, and Treatment of mediate arteries where plaques form on the lining High Blood Cholesterol in Adults. (2001). Executive of the artery. At some point the plaques may summary of the third report of the National Cholesterol obstruct or at least impede the flow of blood Education Program (NCEP) expert panel on detection, through the vessel. High-density lipoprotein evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Journal of the (HDL) subfraction of total cholesterol protects American Medical Association, 285, 2486–2497. against the development of atherosclerosis by Hall, J. E. (2011). Guyton and hall textbook of medical a less well-understood mechanism. physiology (12th ed.). Philadelphia: Saunders Clinical trials support the hypothesis that (Elsevier). aggressive lowering of the LDL subfraction of cholesterol reduces CHD risk. Lifestyle modifi- cations that include losing weight, reducing sat- urated fats and the intake of exogenous Chromosomes cholesterol, and increased physical activity can reduce the LDL subfraction in healthy as well as Rany M. Salem1 and Laura Rodriguez-Murillo2 chronically ill populations; however, adherence 1Broad Institute, Cambridge, MA, USA to long-term dietary changes and increased phys- 2Department of Psychiatry, Columbia University ical activity can be difficult. If efforts to reduce Medical Center, New York, NY, USA LDL cholesterol using only lifestyle modification do not reduce LDL sufficiently, drug therapy should be considered. Efforts to reduce CHD Definition risk by raising the HDL subfraction are not as promising. Chromosomes are self-replicating structures The Executive Summary of the Third Report of found within cells, containing and organizing the National Cholesterol Education Program cellular DNA. The DNA contains the nucleotide (NCEP) Expert Panel of Detection, Evaluation, base sequence encoding the hereditary genetic and Treatment of High Blood Cholesterol in information. In most prokaryotes, the entire Adults (Adult Treatment Panel III or ATP III) genome is carried on a single circular strand of provides an update of the panel’s earlier clinical DNA comprising one chromosome. In eukaryotic guidelines (ATP I and ATP II) for cholesterol cells (cells with a nucleus), the genome is testing and measurement. ATP I presented an organized across multiple chromosomes. C 398 Chronic Bronchitis

Each eukaryotic organism has its own specific Lewis, R. (2005). Human genetics. Concepts and applica- number of chromosomes. Humans are diploid tions (7th ed.). Boston: McGraw-Hill Science/Engi- neering/Math. and have 23 pairs of chromosomes: one set Strachan, T., & Read, A. P. (2003). Human molecular of two sex chromosomes and 22 pairs of autoso- genetics (3rd ed.). London/New York: Garland Sci- mal chromosomes for a total of 46 chromosomes. ence/Taylor & Francis Group. Not surprisingly, given their name, sex chromo- somes determine sex. Females have two X chromosomes, and males an X and a Y chro- Chronic Bronchitis mosome. Humans are diploid, which means that they have two copies of each chromosome. Other ▶ Chronic Obstructive Pulmonary Disease species have different numbers. In humans, auto- ▶ Emphysema somal chromosomes are identified by the num- bers 1 through 22. Chromosomes can be seen under a light Chronic Care microscope and individual chromosomes can be differentiated using special stains to band the ▶ Disease Management chromosomes based on A/T vs. G/C content. The staining pattern results in a chromosome- specific karyotype, which was used in early Chronic Depression genetic studies to identify major chromosomal abnormalities (loss/extra chromosomes, translo- Kim Lavoie cations, deletions, and breaks) associated with Department of Psychology, University of Que´bec disease. For example, Down’s syndrome, at Montreal (UQAM); Montreal Behavioural a genetic condition that causes physical and Medicine Centre, Montre´al, QC, Canada cognitive impairment, can be diagnosed via Division of Chest Medicine, Hoˆpital du karyotyping to identify trisomy 21, the presence Sacre´-Coeur de Montre´al; Research Centre, of three copies of chromosome 21 (Korenberg Montreal Heart Institute, Montre´al, QC, Canada et al., 1994). However, most genetic variance occurs at a much smaller scale, at individual nucleotides such as in single nucleotide polymor- Definition phism (SNP) or groups of nucleotides, in microsatellites, and insertions-deletions. Depression is a negative mood state that is gener- ally characterized by feelings of sadness, discour- agement, and hopelessness (American Psychiatric Association, 2000). Brief or transient feelings of Cross-References depression (i.e., feelings lasting several minutes to several hours) are relatively common and ▶ DNA are likely to be experienced by just about everyone ▶ Gene at some point in their lives. However, more chronic forms of depression are less common and may be associated with significant interpersonal References and Readings difficulties and functional impairments. There now exist widely accepted, standard- Korenberg, J. R., Chen, X. N., Schipper, R., Sun, Z., ized diagnostic criteria that distinguish “normal” Gonsky, R., Gerwehr, S., et al. (1994). Down syn- from “abnormal” forms of depression, the drome phenotypes: the consequences of chromosomal latter of which have been classified as “mood imbalance. Proceedings of the National Academy of Sciences of the United States of America, 91(11), disorders” in the Diagnostic and Statistical Man- 4997–5001. ual of Mental Disorders-4th Edition Revised Chronic Depression 399 C

(DSM-IV-R) (American Psychiatric Association, The most common, widely accepted, and 2000). Although chronic depression has been clas- empirically validated treatments for chronic sified as a “mood disorder,” it is important to depression include pharmacotherapy (e.g., anti- recognize that mood disorders, which include depressant medications including selective such disorders as major and minor depressive dis- serotonin reuptake inhibitors [SSRIs] or selective order, dysthymia, cyclothymia, and bipolar disor- serotonin and norepinephrine reuptake inhibitors ders, actually represent syndromes, which are [SSNRIs]), psychotherapy (e.g., cognitive- C clusters of symptoms, only one of which is an behavioral therapy [CBT] and interpersonal ther- abnormality of mood. However, chronic forms of apy [IPT]), or some combination of the two depression also feature vegetative symptoms, (American Psychiatric Association, 2000; including sleep, appetite, weight, and libido Kessler, Demler et al., 2005). However, most disturbances; cognitive symptoms, including major depressive episodes resolve spontaneously decreased ability to concentrate, memory distur- over time, irrespective of whether or not they are bances, decreased frustration tolerance, low treated. The ▶ median duration of a major depres- self-esteem, and cognitive distortions; impulse sive episode has been estimated to be about control symptoms such as suicidal behavior; 23 weeks, with the highest rates of recovery occur- behavioral symptoms, including decreased ring within the first 3 months (Posternak, Solomon motivation and interest in engaging in pleasurable &Leo,2006; Fava, Park, & Sonino, 2006). activities, decreased ability to feel pleasure, and Research has shown that 80% of those suffering decreased energy; and somatic symptoms, includ- from their first major depressive episode will suf- ing increased psychomotor agitation, nonspecific fer from at least one more over the course of their aches and pains, and headaches. life, averaging four episodes over their lifetime. Chronic depression is a major cause of morbid- However, the morbidity associated with untreated ity worldwide and represents the 4th most impor- chronic depression has been compared to that of tant contributor to the global burden of disease, coronary artery disease, with mortality due to sui- accounting for 4.4% of all cases of premature cide affecting 30,000–35,000 individuals each mortality (Kastrup & Ramos, 2007). Lifetime year (Posternak et al., 2006). There are also enor- prevalence rates of chronic depression vary greatly mous personal and societal costs associated with according to geographical location, with the low- chronic depression, including higher rates of est rates found in Japan (3%) and the highest rates chronic illness (e.g., cardiovascular disease), found in the United States (17%) (Kessler, Chiu, decreased productivity, absenteeism and job loss, Demler, & Walters, 2005; Kessler, Demler, Frank substance abuse, family dysfunction, and reduced et al., 2005;WHO,2001;Andrade&Caraveo, overall quality of life (American Psychiatric Asso- 2003; Kessler, Beglund & Demler, 2003;Kessler, ciation, 2000; Posternak et al., 2006). Berglund, Demler, Jin, Merikangas, & Walters, 2005; Murphy, Laird, Monson, Sobol, & Leighton, 2000). On average, most countries report an aver- Cross-References age lifetime prevalence of about 10% (WHO, ▶ 2001; Andrade & Caraveo, 2003). Population Dysthymia studies have consistently shown major depressive disorder to be about twice as common among References and Readings women relative to men, though the reasons for this remain unclear. The peak age of onset of American Psychiatric Association. (2000). Diagnostic major depressive disorder is between 20 and and statistical manual of mental disorders: 40 years and is 1.5 to three times more prevalent (DSM-IV-R), (4th Rev. ed.). Arlington, VA: American Psychiatric Press. among individuals with first degree relatives with Andrade, L., & Caraveo, A. (2003). Epidemiology of a history of depression (American Psychiatric major depressive episodes: Results from the Interna- Association, 2000; Kessler et al., 2005). tional Consortium of Psychiatric Epidemiology C 400 Chronic Depressive Disorder

(ICPE) surveys. International Journal of Methods in Definition Psychiatric Research, 12(1), 3–21. Fava, G. A., Park, S. K., & Sonino, N. (2006). Treatment of recurrent depression. Expert Review of Neurother- Chronic disease management refers to a variety apeutics, 6(11), 1735–1740. of models to improve patient care for individuals Kastrup, M. C., & Ramos, A. B. (2007). Global mental affected by chronic disease. health. Danish Medical Bulletin, 54, 42–43. Kessler, R. C., Berglund, P., & Demler, O. (2003). The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication Description (NCS-R). JAMA: The Journal of the American Medi- cal Association, 289(203), 3095–3105. Chronic diseases typically require ongoing med- Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime ical care and may limit activities of daily living. prevalence and age-of-onset distributions of DSM-IV Examples include diabetes, hypertension, heart disorders in the National Comorbidity Survey Replica- diseases, mood disorders, and asthma. Chronic tion. Archives of General Psychiatry, 62(6), 617–627. diseases impact all countries, with increasing Kessler, R. C., Chiu, W. T., Demler, O., & Walters, E. E. (2005). Prevalence, severity, and comorbidity of prevalence due to several factors (e.g., increased 12-month DSM-IV disorders in the National Comor- life expectancy, treatment advances, and changes bidity Survey Replication. Archives of General in lifestyle behaviors; Singh, 2008). In the USA, Psychiatry, 62(6), 617–627. over 40% of the population is living with at least Kessler, R. C., Demler, O., Frank, R. G., et al. (2005). Prevalence and treatment of mental disorders, 1990 to one chronic disease (Centers for Disease Control 2003. The New England Journal of Medicine, 352(24), and Prevention [CDCP], 2010). Historically, pri- 2515–2523. mary care practices were designed for the provi- Murphy, J. M., Laird, N. M., Monson, R. R., Sobol, A. M., sion of acute care. In contrast, patients with & Leighton, A. H. (2000). A 40-year perspective on the prevalence of depression: The Stirling County Study. chronic diseases typically require long-term Archives of General Psychiatry, 57(3), 209–215. treatment planning, symptom management, and Posternak, M. A., Solomon, D. A., & Leon, A. C. (2006). regular follow-up with providers. The naturalistic course of unipolar major depression in the absence of somatic therapy. The Journal of Nervous and Mental Disease, 194(5), 324–329. Chronic Disease Management Models World Health Organization. (2001). The world health There is no single optimal approach to chronic report 2001 – Mental health: New understanding, disease management. Common components of New hope. Geneva: WHO. chronic disease management models include care coordination across medical disciplines; reg- ular monitoring and medication management; Chronic Depressive Disorder and tools to increase patients’ self-efficacy for managing the daily challenges of their disease(s). ▶ Dysthymia Several strategies have been suggested to be both effective and applicable in patient care settings, including those with limited resources. Examples Chronic Disease Management include tools for self-care (e.g., patient education), information collection (e.g., screening tools and Lara Traeger disease registries), and service provision in com- Behavioral Medicine Service, Massachusetts munity settings (Singh, 2008). A primary goal of General Hospital/Harvard Medical School, most models is to help individuals become Boston, MA, USA informed and active participants in their disease management, to reduce the duration and/or sever- ity of disease-related disability. Mental health care Synonyms is an important part of this process, as mental health problems such as depression can present Chronic disease prevention and management significant barriers to patient self-care. Chronic Disease or Illness 401 C

Current Approaches to Chronic Disease References and Readings Management Chronic disease management is an increasingly Centers for Disease Control and Prevention. (2010). populartermusedinhealthcarepolicyand Chronic diseases and health promotion. Accessed October 1, 2011, from http://www.cdc.gov/ industry communications as a reference point chronicdisease/index.htm for both cost containment and quality improve- Institute of Medicine. (2001). Crossing the quality chasm: ment. Current chronic disease management pro- A new health system for the 21st century. Washington, C grams include both targeted models which DC: National Academy Press. Singh, D. (2008). How can chronic disease management focus on case management for patients who programmes operate across care settings and pro- account for the most medical care utilization, viders? Copenhagen, Denmark: World Health and broader approaches which are based on Organization. assumptions that all chronically ill patients may benefit from regular assessment and tools for promoting self-care. Some programs are carved out to commercial vendors whereas Chronic Disease or Illness others are integrated within managed care insti- tutions. There are wide variations in program Tyler Clark quality, content, type of communication with School of Psychology, The University of Sydney, patients, and extent to which physician prac- Sydney, NSW, Australia tices are involved.

Challenges of Patient Care Definition Meeting the needs of chronically ill patients is one of the greatest challenges facing current Chronic disease or illness is any disease or illness healthcare systems. The 2001 Institute of Medi- which is both long lasting and permanent. cine report, “Crossing the Quality Chasm: Chronic diseases normally cannot be prevented A New Health System for the 21st Century,” through vaccination nor are they curable through emphasized that enduring improvements in dis- either medicine or time. For a disease to be clas- ease management require multi-level changes to sified as chronic, it must persist for a minimum of the environment in which healthcare organiza- 6 weeks. tions and providers function (Institute of Medi- cine [IOM], 2001). To date, healthcare delivery is complex and largely fragmented, with impli- Description cations for care quality, efficiency, and safety. Several factors have been suggested to facilitate Chronic diseases or illnesses are the leading chronic disease management practices within cause of mortality in the world and are estimated existing primary care systems. These include by the WHO to represent 60% of all deaths practice reorganization to support regular fol- (World Health Organization [WHO], 2010). low-up appointments; incorporation of empiri- Chronic diseases are mostly characterized by cally supported strategies for enhancing patient complex causality, multiple risk factors, long self-care; and provider education, provider latency periods, a prolonged course of illness, incentives, and information technology to sup- and functional impairment or disability port changes. (Pencheon, Guest, Melzer & Gray, 2006). While the term chronic disease technically incorporates all long-lasting, permanent diseases, classifica- Cross-References tion confusion may arise for diseases such as herpes zoster or seasonal asthma, which occur ▶ Disease Management intermittently throughout the lifespan and fulfill C 402 Chronic Disease or Illness the technical requirements of the definition, but Chronic Disease Management are typically categorized with those diseases Chronic diseases exist across the lifespan and which are not permanent, but fail to resolve and require long-term treatment and support. Treat- respond to treatment, such as chronic bronchitis ment therefore focuses on disease management, (Last, 2007). Ten major chronic diseases include: which serves to decrease the duration or severity • Coronary heart disease of impairment and disability associated with the • Stroke disease. This management manifests in a variety • Hypertension of forms including but not limited to occupational • Hypothyroidism or physical therapy and rehabilitation, psycholog- • Diabetes ical counseling and stress management, and self- • Mental health problems management strategies, depending on the type and • Chronic obstructive pulmonary disease severity of the chronic disease. Many governments • Asthma provide assistance or financial incentive programs • Epilepsy to individuals with qualifying disabilities. • Cancer Chronic disease may have psychological and The prevalence of chronic diseases increases emotional ramifications such as denial, anxiety, across the lifespan and is often comorbid with and depression following diagnosis not only for other chronic diseases, with the average person the affected individual, but for family and friends aged >65 years having more than one chronic as well, and these consequences may also affect disease. Chronic disease is prevalent in both prognosis. As a result, much effort in behavior wealthy and poor countries, but is correlated medicine has focused on developing adaptive with low socioeconomic status. The chronically strategies for coping with chronic diseases. ill constitutes an extremely large percent of home care visits, as much as 90% in the United States, as well as the majority of prescription drug use, Cross-References days spent in hospital, doctor visits, and hospital emergency room admittance. ▶ Coping As chronic diseases persevere throughout the ▶ Disease Management lifespan, they are accompanied by a high burden ▶ Lifestyle, Healthy of disease: a measure of potential years lost, ▶ Multiple Risk Factors quality of life lost, and disability attributed to ▶ Quality of Life a disease (Broemeling, Watson, & Black, 2005). ▶ Self-Management This burden of disease may include financial costs of chronic disease as well, such as the pri- mary and tertiary health care costs of disease References and Readings management and loss of workforce participation. Broemeling, A., Watson, D., & Black, C. (2005). Chronic Risk Factors conditions and co-morbidity among residents of British Comlumbia. Vancouver: Centre for Health Risk factors for chronic diseases such as coronary Services of British Columbia. Available at www. heart disease, stroke, and certain cancers include chspr.ubc.ca. Accessed January 8, 2011. high cholesterol, high blood pressure, and low Gidron, Y., Berger, R., Lugasi, B., & Ilia, R. (2002). fruit and vegetable intake (MedicineNet.com, Interactive effects of family history with psychological factors in relation to CAD. Coronary Artery Disease, 2004). Chronic disease development is also asso- 13, 205–208. ciated with physical inactivity, obesity, alcohol, Last, J. M. (2007). A dictionary of public health. Oxford/ and tobacco use. Risk factors often co-occur and New York: Oxford University Press. can operate synergistically, as well as with some MedicineNet.com (2004, June). Definition of Chronic Dis- ease. Available at: http://www.medterms.com/script/ psychosocial factors (e.g., hostility and family main/art.asp?articlekey=33490. Accessed December history; Gidron, Berger, Lugasi, & Ilia, 2002). 18, 2010. Chronic Fatigue Syndrome 403 C

Pencheon, D., Guest, C., Melzer, D., & Gray, J. A. M. problems. The first formal case definition of the (2006). Oxford handbook of public health practice illness was published in the USA in 1988 (2nd ed.). Oxford/New York: Oxford University Press. Taylor, S. E. (2009). Health psychology (7th ed.). New (Holmes et al., 1988). In 1994, an international York: McGraw Hill. International Edition. collaborative group published the current CFS World Health Organization. (2010). Available at http:// research case definition (Fukuda et al., 1994). www.who.int.com. Accessed January 2011. The 1994 case definition requires at least 6 months of persistent fatigue; this fatigue cannot be sub- C stantially alleviated by rest, is not the result of ongoing exertion, and is associated with substan- Chronic Disease Prevention and tial reductions in occupational, social, and per- Management sonal activities. In addition, at least four out of eight of the following symptoms must occur with ▶ Chronic Disease Management fatigue in a 6-month period: impaired memory or concentration, sore throat, tender glands, aching or stiff muscles, multijoint pain, new headaches, unrefreshing sleep, and postexertional fatigue. Chronic Fatigue Medical conditions that may explain the prolonged fatigue as well as a number of psychi- ▶ Fatigue atric diagnoses exclude a patient from the diagno- sis of chronic fatigue syndrome (Reeves et al., 2003). Consequently, a thorough medical history and physical assessment is required before the Chronic Fatigue Syndrome diagnosis can be formally established.

Urs M. Nater Comorbidity Department of Psychology, University of There is a considerable overlap between CFS and Marburg, Marburg, Germany psychiatric disorders. Recent data indicate that almost 60% of CFS cases in the population suffer from at least one comorbid psychiatric condition Definition (Nater et al., 2009). Consistent with the fact that fatigue is a common symptom in depressive dis- Chronic fatigue syndrome (CFS) is defined by orders, a substantial overlap in diagnoses of CFS unexplained disabling fatigue of at least 6 months and depression has been reported. However, there duration, accompanied by at least four out of are also distinct symptoms, such as suicidal ide- eight of the following symptoms: impaired ation, which are not more frequently present in memory or concentration, sore throat, tender CFS patients than in the general population. glands, aching or stiff muscles, multijoint pain, There are many patients with CFS who do not new headaches, unrefreshing sleep, and meet the current criteria for any other psychiatric postexertional fatigue. disorder, indicating that CFS is not merely a psychiatric epiphenomenon. Chronic fatigue syndrome often co-occurs Description with other medically unexplained syndromes such as fibromyalgia or irritable bowel syndrome. Chronic fatigue syndrome (CFS) is a complex These disorders have in common with CFS the illness defined by unexplained disabling fatigue fact that they are defined as disorders that, after as its core feature and a combination of other appropriate medical assessment, cannot be accompanying symptoms, such as diffuse pain, explained in terms of a conventionally defined subjective cognitive impairment, and sleep medical disease (Barsky & Borus, 1999). C 404 Chronic Fatigue Syndrome

Taken together, CFS co-occurs and shares 2009). Cytokines, such as IL-6 and TNF-alpha, core symptoms with a variety of conditions, have been implicated in the pathogenesis of suggesting that similar pathways may be fatigue and somnolence. Specifically, IL-6 par- involved in the etiology and development of ticipates in the pathogenesis of excessive daytime these pathological states. somnolence and post-exertional fatigue. In addi- tion, alterations in the gene expression involved Prevalence in immunity have been detected. Thus, immune Chronic fatigue syndrome is relatively common factors seem to play an important role in CFS, in the community, in primary care, and in hospital although the exact mechanisms have not been settings. The overall prevalence of CFS in the fully established yet. general population is reported to be between Patients with CFS also may have decreased 0.1% and 2.5%. Prevalence rates vary signifi- functioning of the hypothalamic-pituitary-adrenal cantly across studies, probably as a result of dif- (HPA) axis, one of the body’s primary stress ferences in diagnostic criteria and design. It is response systems, which is also contributing to estimated that 2.2 million Americans suffer with the peripheral and central causes of chronic pain CFS and that the disorder is more common in and fatigue. Several studies report decreased levels rural than urban populations (Bierl et al., 2004). of circulating cortisol and decreased adrenocorti- Rates for CFS in primary care are higher than cal reserve. This alteration may be associated with rates seen in the general population. Large com- several symptoms typical for CFS, including munity-based epidemiological studies in the fatigue, arthralgia, myalgia, exacerbation of aller- USA indicate that CFS is equally or more com- gic responses, feverishness, and changes in mood, mon in African Americans, Hispanics and Native cognition, and sleep. Cortisol exerts inhibitory Americans, and in individuals who make less effects on the secretion of cytokines, including than $40,000 per year. However, in all these IL-6, and helps return these cytokines to baseline groups women are two to four times more likely levels after stress. Thus, alterations in the immune than men to have CFS. system have an impact on the endocrine system, and vice versa. In addition to decreased function- Pathophysiology ing, the HPA axis has also been reported to lose its The pathophysiology of CFS is complex and normal diurnal rhythm in CFS patients (Nater far from being fully understood. Despite mixed et al., 2008). Clinical improvement has been asso- findings in the vast literature of potential ciated with the normalization of this diurnal pathophysiological processes in CFS, tentative rhythm. The overall picture may be summarized conclusions can be drawn concerning physio- as a relative hypoactivity of the HPA axis in CFS logical systems that may be abnormal in at patients (Cleare, 2003). least some patients. It is important to remember, It has been reported that abnormal autonomic however, that it remains unknown whether nervous system (ANS) functioning may be com- any given abnormality represents a cause or mon in patients with CFS, based on the fact that a consequence of CFS. CFS includes typical autonomic symptoms, such Early etiological theories of the disorder as disabling fatigue, dizziness, diminished con- focused on the immune system and infection centration, tremulousness, and nausea, and that at with Epstein Barr and other latent viruses. least some CFS patients demonstrate orthostatic Although cases of CFS may follow such infec- intolerance when subjected to tilt table testing. tions, most studies have shown that infections are Conversely, patients with postural orthostatic not a primary cause for the disorder. intolerance syndrome often manifest symptoms A variety of immune system abnormalities similar to those seen in CFS. Whereas there is have also been reported, including decreases in some evidence for involvement of altered ANS natural killer cell activity and increases in functioning, it needs to be noted that some CFS proinflammatory cytokines (Lorusso et al., symptoms, such as sore throat, myalgias, and Chronic Fatigue Syndrome 405 C cognitive alterations, cannot be attributed to replicated. Trials of antidepressants have yielded dysautonomia. an equally confusing mix of positive and negative Also, studies of the central nervous system results, but in general these agents appear to be (CNS) in CFS have examined both structural significantly less effective for CFS than for and functional alterations. Various studies have depression or anxiety disorders. pointed to subtle morphological changes in CFS, although these changes might not be specific for C CFS. Functional studies have found potential Cross-References explanations for some of the motor and cognitive dysfunctions typically described in CFS. ▶ Fatigue Finally, psychological and stress-related fac- tors have been associated with CFS. Some authors consider CFS as the consequence of dys- References and Readings functional cognitive styles and maladaptive cop- ing strategies. Many patients report an increase in Afari, N., & Buchwald, D. (2003). Chronic fatigue syn- life stress in the year prior to disease develop- drome: A review. The American Journal of Psychiatry, ment. Recent findings from a prospective study 160(2), 221–236. Barsky, A. J., & Borus, J. F. (1999). Functional somatic indicated that stress levels prior to manifestation syndromes. Annals of Internal Medicine, 130(11), of CFS predicted the risk for developing CFS 910–921. (Kato, Sullivan, Evengard, & Pedersen, 2006). Bierl, C., Nisenbaum, R., Hoaglin, D. C., Randall, B., In addition, adverse experiences early in life Jones, A. B., Unger, E. R., et al. (2004). Regional distribution of fatiguing illnesses in the United States: increased the risk of developing CFS in adult- A pilot study. Popululation Health Metrics, 2(1), 1. hood manifold and resulted in the above- Cleare, A. J. (2003). The neuroendocrinology of mentioned hypoactivity of the endocrine stress chronic fatigue syndrome. Endocrine Reviews, 24(2), system (Heim et al., 2009). Thus, stressful expe- 236–252. Fukuda, K., Straus, S. E., Hickie, I., Sharpe, M. C., riences seem to play an important role in trigger- Dobbins, J. G., & Komaroff, A. (1994). The chronic ing CFS symptoms. However, it is likely that fatigue syndrome: A comprehensive approach to its stress interacts with other vulnerability factors. definition and study. International Chronic Fatigue Ongoing or acute stressors might elicit physio- Syndrome Study Group. Annals of Internal Medicine, 121(12), 953–959. logical changes in the predisposed body, ulti- Heim, C., Nater, U. M., Maloney, E., Boneva, R., Jones, mately leading to pathophysiological changes J. F., & Reeves, W. C. (2009). Childhood trauma and associated with CFS. risk for chronic fatigue syndrome: Association with neuroendocrine dysfunction. Archives of General Psy- chiatry, 66(1), 72–80. Treatment Holmes, G. P., Kaplan, J. E., Gantz, N. M., Komaroff, Numerous treatments have been applied to CFS A. L., Schonberger, L. B., Straus, S. E., et al. (1988). patients with various results. Those with the best Chronic fatigue syndrome: A working case definition. experimental data to support efficacy include Annals of Internal Medicine, 108(3), 387–389. Kato, K., Sullivan, P. F., Evengard, B., & Pedersen, N. L. graded exercise training and cognitive behavioral (2006). Premorbid predictors of chronic fatigue. therapy (CBT) (White et al., 2011). CBT strate- Archives of General Psychiatry, 63(11), 1267–1272. gies for CFS typically involve organizing activity Lombardi, V. C., Ruscetti, F. W., Das Gupta, J., Pfost, and rest cycles, initiating graded increases in M. A., Hagen, K. S., Peterson, D. L., et al. (2009). Detection of an infectious retrovirus, XMRV, in blood activity, establishing a consistent sleep regimen, cells of patients with chronic fatigue syndrome. Sci- and attempting to restructure beliefs around self, ence, 326(5952), 585–589. as well as disease attributions (Malouff, Lorusso, L., Mikhaylova, S. V., Capelli, E., Ferrari, D., Thorsteinsson, Rooke, Bhullar, & Schutte, Ngonga, G. K., & Ricevuti, G. (2009). Immunological aspects of chronic fatigue syndrome. Autoimmunity 2008). Also, low dose corticosteroids have been Reviews, 8(4), 287–291. reported to improve symptoms in two studies. Malouff, J. M., Thorsteinsson, E. B., Rooke, S. E., However, these positive findings could not be Bhullar, N., & Schutte, N. S. (2008). Efficacy of C 406 Chronic Inflammatory Polyarthritis

cognitive behavioral therapy for chronic fatigue syn- Definition drome: A meta-analysis. Clinical Psychology Review, 28, 736–745. Nater, U. M., Lin, J. M., Maloney, E. M., Jones, J. F., Tian, Chronic obstructive pulmonary disease (COPD), H., Boneva, R. S., et al. (2009). Psychiatric comorbid- one of the leading causes of morbidity and mor- ity in persons with chronic fatigue syndrome identified tality worldwide, is a chronic disease of the lung from the Georgia population. Psychosomatic Medi- that is characterized by decreased air flow and cine, 71(5), 557–565. Nater, U. M., Youngblood, L. S., Jones, J. F., Unger, E. R., associated abnormal inflammation of the lungs. Miller, A. H., Reeves, W. C., et al. (2008). Alterations The disease results from interaction between in diurnal salivary cortisol rhythm in a population- individual risk factors (like alpha1-antitrypsin based sample of cases with chronic fatigue syndrome. deficiencies) and environmental exposures to Psychosomatic Medicine, 70, 298–305. Prins, J. B., van der Meer, J. W., & Bleijenberg, G. (2006). toxic agents (like cigarette smoking). The main Chronic fatigue syndrome. The Lancet, 367(9507), mechanisms that may contribute to airflow limi- 346–355. tation in COPD are fixed narrowing of small Reeves, W. C., Lloyd, A., Vernon, S. D., Klimas, N., Jason, airways, emphysema, and luminal obstruction L. A., Bleijenberg, G., et al. (2003). Identification of ambiguities in the 1994 chronic fatigue syndrome with mucus secretions (American Thoracic Soci- research case definition and recommendations for reso- ety, 1995; Global Initiative for Chronic Obstruc- lution. BMC Health Services Research, 3(1), 25. tive Lung Disease (GOLD), 2006; The COPD White, P., Goldsmith, K., Johnson, A., Potts, L., Walwyn, R., Guidelines Group of the Standards of Care Com- Decesare, J., et al. (2011). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded mittee of the BTS Thorax 1997; Petty & Nett, exercise therapy, and specialist medical care for chronic 2001). fatigue syndrome (PACE): A randomised trial. The Lan- The definition does not use the terms chronic cet, 377, 823–836. bronchitis and emphysema, although most patients with COPD have them. Chronic bronchi- tis is diagnosed based on the clinical presentation, such as a chronic cough and sputum production. Chronic Inflammatory Polyarthritis The diagnosis of emphysema, which is the term used to describe damage to the air sacs in the ▶ Degenerative Diseases: Joint lung, is made from a pathological and/or morpho- logical standpoint. The respiratory symptoms of COPD are dys- pnea, chronic cough, and sputum production. The Chronic Kidney Disease (CKD) dyspnea may initially be noticed only during exertion. Patients with a COPD exacerbation ▶ End-Stage Renal Disease complain of increased cough and sputum, wheez- ing, and dyspnea, with or without fever. Most patients with COPD have a history of cigarette smoking or other inhalant exposure. Chronic Obstructive Pulmonary Therefore, when a person with a history of expo- Disease sure to risk factors, especially smoke, has dys- pnea, chronic cough, and sputum production, Akihisa Mitani a diagnosis of COPD should be considered. Mea- Department of Respiratory Medicine, Mitsui surements of lung function are essential for the Memorial Hospital, Chiyoda-ku, Tokyo, Japan diagnosis of COPD. It is also used to determine the severity of the airflow obstruction and follow disease progression. Spirometry measures forced Synonyms vital capacity (FVC) and forced expiratory vol- ume in 1 s (FEV1.0). An FEV1.0/FVC ratio less Chronic bronchitis; Emphysema than 70% generally indicates airway obstruction. Chronic Pain Patients 407 C

The overall goals of treatment of COPD are to Global Initiative for Chronic Obstructive Lung Disease prevent further deterioration in respiratory func- (GOLD). (2011). Global strategy for the diagnosis, management, and prevention of chronic obstructive tion, relieve symptoms, improve quality of life, pulmonary disease: Revised 2011. Retrieved 10 April and reduce mortality (Global Initiative for Chronic 2012 from http://www.goldcopd.org. Obstructive Lung Disease (GOLD), 2006). Petty, R. L., & Nett, L. M. (2001). COPD: Prevention in First of all, reduction of risk factors is needed. the primary care setting. The National Lung Health Education Program. C All COPD patients with smoking habit should be The COPD Guidelines Group of the standards of care encouraged to quit smoking. Even a few minutes committee of the BTS. (1997). BTS guidelines for counseling could be effective. Pharmacotherapy, the management of chronic obstructive pulmonary such as nicotine replacement and varenicline, disease. Thorax, 52(Suppl. 5), S1. is also recommended. Preventive care is also very important, and all patients should be recommended to get an immunization, including influenza and pneumococcal vaccines. Chronic Pain The mainstay drugs of COPD are bronchodi- lators, and inhaled therapy is preferred. Beta ago- ▶ Arthritis: Psychosocial Aspects nists, anticholinergics, and methylxanthines are given alone or in combination depending upon the severity of disease and each patient’s individ- ual response to therapy. Inhaled glucocorticoids Chronic Pain Patients can reduce the frequency of the acute exacerba- tion, although it cannot improve lung function. Stuart Derbyshire Systemic glucocorticoids are not recommended School of Psychology, The University of for a long-time treatment. Mucolytic drugs might Birmingham, Edgbaston, Birmingham, UK be beneficial for selected patients. Non-pharmacological treatment is equally important for managing COPD. It includes pul- Synonyms monary rehabilitation and oxygen administration. Pulmonary rehabilitation has been shown to Persistent pain improve exercise capacity, decrease dyspnea, and improve quality of life and should be consid- ered as an addition to medication therapy for the Definition patients at all stages of disease. Long-term oxy- gen therapy improves survival and quality of life Chronic pain is typically defined as pain that in the patients with hypoxemia. continues in excess of 3–6 months regardless of the cause of the pain. Less commonly, chronic Cross-References pain is defined as pain that persists beyond the point of any possible healing or any other useful ▶ Lung Function function such as the enforcement of rest. ▶ Pulmonary Disorders, COPD: Psychosocial Aspects Description

References and Readings Major advances in the understanding of pain began with the observations of the physician American Thoracic Society. (1995). Standards for the diagnosis and care of patients with chronic obstructive Henry Beecher during World War 2. Beecher pulmonary disease. American Journal of Respiratory noted that seriously wounded soldiers brought and Critical Care Medicine, 152, S77. from the front line requested less-pain medicine C 408 Chronic Pain Patients and reported less pain than he was used to seeing experience of pain. Chronic, persistent pain is in his civilian patients. Beecher inferred that pain a distinct medical entity, syndrome, or disease is not simply a response to physical injury or in its own right, but it is not a disease that can disease but also includes a cognitive and emo- be defined by objective markers such as provided tional component. Twenty years later, Canadian by X-rays or histological tests; chronic pain is psychologist Ronald Melzack and British physi- a disease defined by the subjective experience ologist Patrick Wall published their gate control of pain. In short, chronic pain is a problem theory. Gate theory proposed that noxious and because it feels bad. non-noxious sensory information interact in the This understanding of chronic pain is further spinal cord with descending influence from the reflected in the international association for the brain. The theory explains pain experience as study of pain (IASP) definition of pain, which dependent upon that interaction rather than just states that pain is “an unpleasant sensory and the strength of a noxious stimulus. The precise emotional experience associated with actual or details of the theory are less important than the potential tissue damage, or described in terms of dramatic impact gate control had on the under- such damage... pain is always subjective. Each standing of pain. Gate control theory ended sim- individual learns the application of the word plistic ideas of pain based on an isolated through experiences related to injury in early dedicated pathway from the periphery to the life.” This definition recognizes a number of impor- brain. It provided the first plausible physiological tant facts about pain: (1) It is a multidimensional explanations for the influence of psychological experience. (2) It is subjective. (3) It may or may states on pain experience through a brain-spinal not be associated with tissue damage. cord loop. Most importantly, gate control theory The somewhat complex understanding of pain shifted attention away from the stimulus and provided by the IASP is perhaps not especially toward the spinal cord, brain, and the subjective important when considering acute pain. If some- experience of pain. After the gate it became one hits their hand with a hammer, it is patently increasingly apparent that pain cannot be reliably obvious that the pain was caused by the hammer judged based upon an objective measure of injury and it is reasonable to assume that the pain will or receptor activation and so assessment of pain subside once the injury heals. Although it may be requires subjective report – the “what it is like” to theoretically correct to point out that the pain is in be in pain. the patient’s mind, not their hand, and that the The shift in focus away from the noxious experience derives from psychology, and not the stimulus that triggers pain and toward the psy- hammer, such points would be overly chological experience of pain was particularly pedantic. When faced with an obvious injury it important for the understanding of chronic pain. is reasonable to depersonalize the experience as Chronic pain conditions are often characterized a consequence of external forces, which rapidly by the lack of a stimulus that can explain the pain. lose their influence with healing. For patients Patients with phantom limb pain, for example, with chronic pain, however, there is either no feel pain in a limb that has been amputated. external force to blame or the external force Patients with causalgia suffer severe burning never loses its influence. Either way, the experi- pain at a site of injury long after the injury has ence is deeply personal and subjective. healed. Even in diseases where there is an ongo- The personal and subjective nature of chronic ing trauma, such as patients with cancer or arthri- pain makes treatment difficult. Traditional treat- tis, the pain is typically difficult to predict based ment approaches involving periods of rest and on objective measures of disease activity and analgesic medication use are typically unsuccess- continues beyond any period when cessation of ful in resolving chronic pain. Physicians and activity and rest might facilitate healing. Thus, patients can easily become disillusioned when the understanding of chronic pain is not helped by multiple treatments, used sequentially or in com- a focus on injury or disease but by a focus on the bination, fail to provide pain relief. In many Chronic Pain, Types of (Cancer, Musculoskeletal, Pelvic), Management of 409 C cases, physicians are left frustrated and patients dissatisfied with chronic, unremitting symptoms. Chronic Pain, Types of (Cancer, Treatment approaches that focus on the patient’s Musculoskeletal, Pelvic), experience, what they feel and how they manage Management of their feelings, are usually more successful. Cog- nitive behavioral therapy, for example, aims to Michael J. L. Sullivan and Tsipora Mankovsky modify the reciprocal relationships between sen- Department of Psychology, McGill University, C sation, cognition, emotion, and behavior so as to Montreal, QC, Canada improve mood and decrease the disability asso- ciated with the pain. Cognitive behavioral ther- apy emphasizes the teaching of coping skills and Definition the active role patients have in modifying how they think, feel, and believe. The aim is to reduce Intervention approaches to improve function the negative impact of their pain even if the pain and promote successful adaptation to chronic itself is not directly reduced. pain. Among adults, the prevalence of chronic pain where an identifying cause is difficult to find ranges between 2% and 40% depending on the Description study. Unsurprisingly, chronic pain substantially reduces quality of life and also generates consid- This entry briefly reviews non-pharmacological erable costs. In the Netherlands, for example, the approaches to the management of pain-related cost of back pain alone equals 1.7% of the gross health conditions and pain-related disability. national product and in the UK, back pain results The review is selective as opposed to exhaustive, in the loss of over 150 million workdays annu- with emphasis on interventions that have been ally. There is also evidence that the problem may systematically evaluated. Where possible, refer- be increasing. In the USA, the rate of disability ences to clinical manuals are provided for claims associated with low back pain has readers who are interested in learning more increased over the rate of population growth by about the specific intervention techniques 1,400% since the early 1970s. Understanding described. chronic pain so as to address this increase and provide better treatments remains a considerable Psychological Treatment of Pain challenge. By the mid-1960s, mounting clinical and scien- tific evidence was calling for a model of pain that would consider both the physiological and psy- Cross-References chological mechanisms involved in pain percep- tion. The call was most compellingly answered ▶ Stress by Melzack and Wall’s gate control theory of pain. From an applied perspective, the work of Melzack and Wall evolved into behavioral conceptualizations of pain (Fordyce, Fowler, References and Readings Lehmann, & De Lateur, 1968), contributing ulti- Loeser, J. D. (2006). Pain as a disease. In F. Cervero & mately to the development of biopsychosocial T. J. Jensen (Eds.), Handbook of clinical neurology models of pain (Gatchel, Peng, Peters, Fuchs, & (pp. 11–20). Edinburgh: Elsevier. Turk, 2007). Biopsychosocial models propose McMahon, S., & Koltzenburg, M. (2005). Wall and that a complete understanding of pain experience melzack’s textbook of pain (5th ed.). Edinburgh: Chur- chill Livinstone. and pain-related outcomes requires consideration Melzack, R., & Wall, P. D. (1996). The challenge of pain. of physical, psychological, and social factors London: Penguin. (Gatchel et al., 2007). C 410 Chronic Pain, Types of (Cancer, Musculoskeletal, Pelvic), Management of

Behavioral/Operant Programs format compromised to some degree the control The first programs that specifically targeted the over environmental contingencies and required psychological aspects of pain-related disability greater reliance on self-monitoring and were based on the view that pain-related disabil- self-report measures (Sanders, 1996). ity was a form of “behavior” that was maintained by reinforcement contingencies. In the 1960s and Back Schools 1970s, Wilbert Fordyce and his colleagues Although back schools were first developed in the applied the concepts of learning theory to the late 1960s, the first published reports of the problem of chronic pain (Fordyce et al., 1968; benefits of “back schools” only appeared in Fordyce, 1976). The focus of Fordyce’s approach the literature in the early 1980s (Zachrisson- to treatment was not on reducing the experience Forsell, 1981). The structure and content of of pain but on reducing the overt display of pain. back schools reflected the prevailing view of The targets selected for treatment were pain the time that “information” or “knowledge” behaviors such as distress vocalizations, facial could be powerful tools to effect change in grimacing, limping, guarding, medication intake, behavior (e.g., pain-related disability) (Heymans, activity withdrawal, and activity avoidance. van Tulder, Esmail, Bombardier, & Koes, 2004). The first behavioral approaches to the manage- Back schools vary widely in terms of content, ment of pain and disability were conducted within duration, and the intervention disciplines used to inpatient settings that permitted systematic obser- administer the program. The duration of back vation of pain behaviors, as well control over school interventions has ranged from a single environmental contingencies influencing pain information session to a 2-month inpatient pro- behavior (Fordyce, 1976). Staff were trained to gram. Back school interventions have tended to monitor pain behavior and to selectively reinforce use group formats with a didactic format where “well behaviors” and selectively ignore “pain participants might be exposed to information behaviors.” Results of several studies revealed about biomechanics, posture, ergonomics, exer- that the manipulation of reinforcement contingen- cises, nutrition, weight loss, attitudes, beliefs, and cies could exert powerful influence on the fre- coping. As a function of the type of information quency of display of pain behaviors (Fordyce, being provided, the interventionist might Roberts, & Sternbach, 1985). The manipulation be a physician, physiotherapist, occupational of reinforcement contingencies was also applied therapist, nurse, or psychologist (Linton & to other domains of pain-related behavior and Kamwendo, 1987). shown to be effective in reducing medication A recent review of randomized clinical trials intake, reducing downtime and maximizing of back school programs concluded that (a) back participation in goal-directed activity. schools yielded benefit relative to treatment- A number of clinical trials on the efficacy of as-usual interventions, (b) the treatment effect behavioral treatments for the reduction of pain size was small, and (c) that back school programs and disability yielded positive findings (Sanders, implemented within occupational settings 1996). However, given the significant resources appeared to yield the most positive outcomes required to implement contingency management (Heymans, van Tulder, Esmail, Bombardier, & interventions, issues concerning the cost-efficacy Koes, 2005). of behavioral therapy for pain and disability were raised. Concern was also raised over the mainte- Cognitive-Behavioral Programs nance of treatment gains since reinforcement Cognitive-behavioral programs for the manage- contingencies outside the clinic setting could ment of pain and pain-related disability began to not be readily controlled. In order to increase appear in the 1980s (Turk, Meichenbaum, & access and reduce costs, behavioral treatments Genest, 1983). CBT programs incorporated con- were modified to permit their administration on cepts drawn from earlier behavioral approaches an outpatient basis. This change in delivery as well as information-based approaches used in Chronic Pain, Types of (Cancer, Musculoskeletal, Pelvic), Management of 411 C back schools. The objective of many CBT management programs have been used as preven- programs is to equip individuals with the psycho- tive interventions for individuals who are logical “tools” necessary to adequately meet experiencing symptoms of persistent pain but challenges of persistent pain (Turk et al., 1983). are still working. The primary focus of stress Cognitive-behavioral interventions are cur- management interventions might be on stresses rently considered the psychological treatment of within the workplace or the individual’s personal choice for individuals coping with chronic pain stresses (Feuerstein et al., 2004). C and disability, (Gatchel et al., 2007). A number of Problem-solving therapy is a variant of stress clinical trials have demonstrated that these management programs that has recently been types of interventions can lead to clinically sig- applied to individuals who are work-disabled nificant decreases in pain and emotional distress due to musculoskeletal pain conditions (Williams et al., 1996). (D’Zurilla, 1990; Smeets et al., 2008). Problem- It is important to note that the term cognitive solving therapy proceeds from the view that life behavioral does not refer to a specific interven- stresses can be minimized if the individual is able tion but, rather, to a class of intervention strate- to use appropriate problem-solving strategies to gies. The strategies included under the heading of deal with difficult situations that might be cognitive-behavioral interventions vary widely encountered at the work place or in daily life. and may include self-instruction (e.g., motiva- Problem-solving intervention programs will tional self-talk), relaxation or biofeedback, devel- typically span several weeks (8–10 weeks) and oping coping strategies (e.g., distraction, might involve didactic lectures, group discussion, imagery), increasing assertiveness, minimizing and homework assignments. The limited research negative or self-defeating thoughts, changing that has addressed the efficacy of this form maladaptive beliefs about pain, and goal setting of intervention indicates that the addition (Turk et al., 1983). A client referred for cogni- of problem-solving therapy to usual treatment tive-behavioral intervention may be exposed to might improve return to work outcomes in indi- varying selections of these strategies. The goals viduals with disabling musculoskeletal pain of CBT programs might also differ across settings (Smeets et al.). and may include pain reduction, distress reduc- tion, increased activity involvement, or return to Acceptance and Commitment Therapy work (Gatchel et al., 2007). Acceptance and commitment therapy, also referred to as contextually based cognitive- Stress Management Programs behavior therapy, is a type of cognitive therapy Stress management programs represent a special that has evolved from Stephen Hayes’ work on case of cognitive-behavioral intervention. Stress acceptance and adaptation (Hayes, Strosahl, & management programs proceed from the view Wilson, 1999; McCracken, 2005). Proponents of that, unless properly managed, chronic stresses ACT emphasize that they do use the term accep- can lead to a depletion of the individual’s physi- tance to refer to resignation but rather as a term to cal and psychological resources and, in turn, refer to the process of ceasing to struggle ineffec- increase the individual’s susceptibility to physi- tively against that which cannot be changed cal or psychological dysfunction (Lazarus & (Hayes et al., 1999). In the case of chronic pain, Folkman, 1984). Stress management approaches acceptance is viewed as a first step toward suc- are considered separately from cognitive- cessful adaptation (McCracken, 2005). Accep- behavioral pain management programs since the tance is said to occur when the individual with focus of stress management programs is not nec- chronic pain is willing to experience his or her essarily on managing pain symptoms or disabil- pain without attempting to control it. Through ity. Furthermore, while CBT programs are treatment, individuals with chronic pain are typically used for individuals who are work- taught to acknowledge their pain, observe it as disabled due to their pain condition, stress a sensation, and then accept it as part of their C 412 Chronic Pain, Types of (Cancer, Musculoskeletal, Pelvic), Management of reality without judgment. Through treatment, and contains the forms for various exercises that individuals are also encouraged to focus on their will be used through the treatment. Activity values and to commit to activities consistent with goals are established in order to promote resump- their values, in spite of ongoing pain. tion of family, social, and occupational roles. Several investigations have shown that ACT is Intervention techniques are invoked to target effective in reducing pain intensity and self- specific obstacles to rehabilitation progress (e.g., reported disability (Vowles & McCracken, catastrophic thinking, fear of movement, and 2008). To date, ACT has only been used with disability beliefs). In the final stages of the pro- individuals with long-standing chronic pain gram, the intervention focuses on activities that where the prospect of significant pain alleviation will facilitate reintegration into the workplace. is realistic low. When symptom-focused treat- PGAP has been shown to be effective in reduc- ment of the pain condition is unlikely to yield ing catastrophic thinking, fear of movement, and positive outcomes, acceptance-based interven- disability beliefs in individuals with whiplash inju- tions might represent a useful option for improv- ries and work-related musculoskeletal injuries ing the quality of life of individuals with chronic (Sullivan, Adams, Rhodenizer, & Stanish, et al., pain. It is not clear whether ACT would be 2006). Research has supported the view that effective or even appropriate for individuals reductions in catastrophizing are significant deter- with recent onset pain where a substantive pro- minants of treatment-related improvements in portion of individuals would be expected to show depressive symptoms, physical function, and significant recovery from their pain condition. return to work (Sullivan, Ward et al., 2005).

Risk-Factor-Targeted Interventions Graded Activity and Exposure Recent research on risk factors for prolonged pain The premise underlying graded activity or and disability has prompted the development of exposure interventions is that disability can be risk-factor-targeted intervention programs (Sulli- construed as a type of phobic orientation toward van, Feuerstein, Gatchel, Linton, & Pransky, activity (Vlaeyen & Linton, 2000). According to 2005; Vlaeyen & Linton, 2000). The Progressive the fear-avoidance model, individuals will differ Goal Attainment Program (PGAP) was designed in the degree to which they interpret their pain as a risk-factor-targeted intervention for individ- symptoms in a “catastrophic” or “alarmist” man- uals suffering from debilitating pain conditions ner. The model predicts that catastrophic thinking (Sullivan, Adams, Rhodenizer, & Stanish, 2006). following the onset of pain will contribute to The primary goals of the PGAP are to reduce heightened fears of movement. In turn, fear is catastrophic thinking and fear of movement in expected to lead to avoidance of activity that order to promote reintegration into life-role activ- might be associated with pain (Vlaeyen & Linton, ities, increase quality of life, and facilitate return 2000). Prolonged inactivity is expected to con- to work. The intervention is typically delivered tribute to depression and disability (Sullivan, by occupational therapists, physiotherapists, or Adams, Thibault et al., 2006). According to the psychologists. fear-avoidance model, reducing fear of move- Since the PGAP is a risk-factor-targeted inter- ment is a critical component of successful reha- vention, clients are only considered as potential bilitation of individuals with debilitating pain candidates for the intervention if they obtain scores conditions (Vlaeyen & Linton, 2000). Clients in the risk range on measures of catastrophic think- are typically only considered for exposure inter- ing, fear of movement, or disability beliefs. In the ventions if they obtain high scores on measures of initial weeks of the program, the focus is on the fear of movement. establishment of a strong therapeutic relationship Graded activity or exposure to feared activi- and the development of a structured activity sched- ties are treatment approaches that involve sys- ule. The client is provided with a client workbook tematic exposure or engagement in activities that serves as the platform for activity scheduling that individuals avoid due to fears that they Chronic Pain, Types of (Cancer, Musculoskeletal, Pelvic), Management of 413 C might experience an exacerbation of their symp- management of their condition. As such, infor- toms. Feared activities are initially identified mation-based approaches such as back schools and ranked hierarchically, from least to most might be an important element in the manage- feared activities. Beginning with the least feared ment of chronic pain. However, for most clients activities, clients are systematically exposed to with chronic pain conditions, information movements that comprise the activities that cli- alone is unlikely to yield clinically significant ents are currently avoiding. Clients are repeatedly improvements in mood, suffering, or disability. C exposed to specific movements until their fear of Information-based techniques might best be activity subsides. As clients overcome their fears viewed as important elements of a more compre- associated with the least feared activities in their hensive approach to treatment as opposed to feared activities hierarchy, the exposure tech- stand-alone interventions. niques are used on activities associated with For the greater part of the last two decades, higher levels of fear (Leeuw et al., 2007). psychosocial interventions were included primar- While graded exposure has been shown to be ily as part of tertiary care treatment for clients an effective intervention for reducing the fear of with long-standing chronic pain and disability. specific movements, its effects do not seem to With little expectancy of clinical improvement generalize to un-targeted activities (Goubert, of clients’ pain conditions, the focus of many Francken, Crombez, Vansteenwegen, & Lysens, treatment programs was primarily on the allevia- 2002). As such, the clinical significance of the tion of suffering. Cognitive-behavioral interven- intervention might depend on the degree to which tions that used distress reduction techniques important activities of daily living or occupational such as relaxation, reappraisal, and cognitive activities can be targeted. Graded activity and restructuring were ideally suited to achieve exposure interventions aimed at reducing fear of reductions in suffering in clients with long- movement have been shown to be effective in standing chronic pain (Morley, Eccleston, & reducing disability, reducing absenteeism, and Williams, 1999). facilitating return to work (Bailey, Carleton, As research accumulated showing that psy- Vlaeyen, & Asmundson, 2010). chological interventions yielded significant reductions in pain and emotional distress, there Choosing Among Different Psychological was greater interest in using psychological inter- Interventions ventions for clients who were at earlier stages of The intervention approaches described in this chronicity (Sullivan, 2003). The term secondary chapter differ in terms of their focus, structure, prevention is used to describe interventions that content, and objectives. With the range of poten- are implemented for individuals considered “at tial intervention avenues currently available, the risk” condition or chronic pain and disability clinician might reflect on the question of which but whose condition had not yet become intervention approach might be most suitable for chronic. With a less chronic population, treat- a particular client. Since little research has been ment objectives of psychological interventions conducting on matching client profiles to specific changed. Since many clients still had an employ- interventions, this question unfortunately cannot ment-relevant skill set, and some might also have be addressed from an empirical standpoint. There had a job to return to, there was an increased are, however, various points of consideration that focus on return to function as a central objective might assist the clinician in determining the most of treatment, as opposed to a primary focus on appropriate intervention for his or her client. reduction of suffering. Return to function is Few would question the importance of infor- a central objective of interventions such as mation provision in the management of chronic PGAP or graded exposure. pain and disability. The more that clients under- When treatment is initiated after a long period stand about the nature of their pain condition, the of chronicity, intervention strategies are more more they will be able to play an active role in the likely to address the consequences of pain and C 414 Chronic Pain, Types of (Cancer, Musculoskeletal, Pelvic), Management of disability (e.g., affective disorders, drug/alcohol clients with debilitating pain conditions. It is par- overuse, family dysfunction) as opposed to risk amount to consider the evidence base for psycho- factors for pain and disability. It is important for logical interventions for pain-related difficulties professionals working with clients with long- before offering them to clients with debilitating standing chronic pain and disability to have pain conditions. Offering interventions that are a background in mental health in order to be not evidence based increases the probability of able to intervene on psychological conditions treatment failure and is likely to contribute to that might be compounding the client’s pain further demoralization of a client already strug- condition. However, risk factors for chronicity gling with a heavy burden of distress and are not necessarily psychological disorders nor disability. would they necessarily be considered indices of dysfunction (in the absence of a pain condition). Nevertheless, their presence contributes to Cross-References a higher probability that a pain condition will persist or worsen over time. The challenge to ▶ Pain Management/Control effective secondary prevention lies not only in ▶ Pain, Psychosocial Aspects the development of risk-factor targeted interven- ▶ Pain-Related Fear tions but in developing mechanisms by which individuals at risk can be identified. Perhaps more so than is the case for psychological disor- References and Readings ders, risk factors for chronicity may be particu- Bailey, K., Carleton, N., Vlaeyen, J. W. S., & Asmundson, larly likely to go undetected during routine G. J. (2010). Treatments addressing pain-related fear primary care. Treating physicians often become and anxiety in patients with chronic musculoskeletal aware of psychological factors in pain and dis- pain: A preliminary review. Cognitive Behavior ability only once chronicity has developed and Therapy, 39, 46–63. D’Zurilla, T. (1990). Problem-solving training for effec- the client has become treatment resistant. tive stress management and prevention. Journal of Since psychological risk factors for chronic Cognitive Psychotherapy, 4, 327–355. pain and disability are not mental health condi- Feuerstein, M., Nicholas, R., Huang, G., Dimberg, L., tions, the development of secondary prevention Ali, D., & Rogers, H. (2004). Job stress management and ergonomic intervention for work-related upper interventions opened the door for using profes- extremity symptoms. Applied Ergonomics, 35, 565–574. sionals who were not mental health professionals Fordyce, W. (1976). Behavioral methods in chronic pain to deliver psychological interventions for pain. and illness. St. Louis: Mosby. Intervention programs like PGAP or graded Fordyce, W., Fowler, R., Lehmann, J., & De Lateur, B. (1968). Some implications of learning in problems exposure are more likely to use occupational of chronic pain. Journal of Chronic Diseases, 21, therapists, physiotherapists, or kinesiologists as 179–190. interventionists than psychologists. This should Fordyce, W. E., Roberts, A. H., & Sternbach, R. A. (1985). be viewed as a positive change since the shortage The behavioral management of chronic pain: A response to critics. Pain, 22(2), 113–125. of psychologists involved in the treatment of pain Gatchel, R., Peng, Y. B., Peters, M. L., Fuchs, P. N., & severely limits access to psychological services Turk, D. C. (2007). The biopsychosocial approach to for individuals with debilitating pain conditions. chronic pain: Scientific advances and future directions. Thus, chronicity and clinical complexity are Psychological Bulletin, 133, 581–624. Goubert, L.,Francken, G., Crombez, G., Vansteenwegen, D., two factors that will influence the type of psycho- & Lysens, R. (2002). Exposure to physical movement in logical intervention that will be considered, the chronic back pain patients: No evidence for generaliza- objectives of the intervention, and the training tion across different movements. Behaviour Research background of the professional that will be used and Therapy, 40(4), 415–429. Hayes, S. C., Strosahl, K. D., & Wilson, K. G. (1999). to deliver the intervention. Undoubtedly, other Acceptance and commitment therapy: An experiential psychological interventions will be added to the approach to behavior change. New York: Guilford repertoire of psychological services offered to Press. Chronobiology 415 C

Heymans, M. W., van Tulder, M. W., Esmail, R., Turk, D., Meichenbaum, D., & Genest, M. (1983). Pain Bombardier, C., & Koes, B. W. (2004). Back schools and behavioral medicine: A cognitive-behavioral for non-specific low-back pain. Cochrane Database of perspective. New York: Guilford. Systematic Reviews, 4, CD000261. Vlaeyen, J. W., & Linton, S. J. (2000). Fear-avoidance and Heymans, M. W., van Tulder, M. W., Esmail, R., its consequences in chronic musculoskeletal pain: Bombardier, C., & Koes, B. W. (2005). Back schools A state of the art. Pain, 85(3), 317–332. for nonspecific low back pain: A systematic review Vowles, K. E., & McCracken, L. M. (2008). Acceptance within the framework of the Cochrane Collaboration and values-based action in chronic pain: A study of C Back Review Group. Spine (Phila Pa 1976), 30(19), treatment effectiveness and process. Journal of 2153–2163. Consulting and Clinical Psychology, 76(3), 397–407. Lazarus, R., & Folkman, S. (1984). Stress, appraisal and Williams, A. C., Pither, C. E., Richardson, P. H., Nicholas, coping. New York: Springer. M. K., Justins, D. M., Morley, S., et al. (1996). The Leeuw, M., Goossens, M. E., Linton, S. J., Crombez, G., effects of cognitive-behavioural therapy in chronic Boersma, K., & Vlaeyen, J. W. (2007). The fear- pain. Pain, 65(2–3), 282–284. avoidance model of musculoskeletal pain: Current Zachrisson-Forsell, M. (1981). The back school. Spine state of scientific evidence. Journal of Behavioral (Phila Pa 1976), 6, 104–106. Medicine, 30(1), 77–94. Linton, S. J., & Kamwendo, K. (1987). Low back schools. Acriticalreview.Physical Therapy, 67(9), 1375–1383. McCracken, L. M. (2005). Contextual cognitive therapy Chronobiology for chronic pain. Seattle, WA: IASP Press. Morley, S., Eccleston, C., & Williams, A. (1999). System- Tanja Lange atic review and meta-analysis of randomized con- trolled trials of cognitive-behavior therapy and Department of Neuroendocrinology, behavior therapy for chronic pain in adults, excluding University of Luebeck, Lubeck,€ Germany headache. Pain, 80, 1–13. Sanders, S. H. (1996). Operant conditioning of chronic pain: Back to basics. In R. Gatchel & D. C. Turk (Eds.), Psychological approaches to pain manage- Definition ment. New York: Guilford. Smeets, R. J., Vlaeyen, J. W., Hidding, A., Kester, A. D., Chronobiology is the science of periodic van der Heijden, G. J., & Knottnerus, J. A. (2008). changes in physiology and behavior of living Chronic low back pain: physical training, graded activ- ity with problem solving training, or both? The one- organisms (Halberg, 1969). It describes these bio- year post-treatment results of a randomized controlled logical rhythms with statistical methods trial. Pain, 134(3), 263–276. (chronobiometry) and elucidates the underlying Sullivan, M. J. L. (2003). Emerging trends in secondary molecular/biochemical mechanisms at a cellular prevention of pain-related disability. The Clinical Journal of Pain, 19, 77–79. and systemic level, the entrainment of these Sullivan, M. J. L., Adams, H., Rhodenizer, T., & internal timing systems by external time cues, the Stanish, W. D. (2006). A psychosocial risk effects of timed light and drug therapy (chrono- factor–targeted intervention for the prevention of therapy, chronopharmacology, chronotoxicology), chronic pain and disability following whiplash injury. Physical Therapy, 86(1), 8–18. as well as disturbances of biological rhythms that Sullivan, M. J., Adams, H., Thibault, P., Corbiere, M., & may lead to pathology (Dunlap, Loros, & Stanish, W. D. (2006). Initial depression severity DeCoursey, 2004; Foster & Kreitzman, 2004; and the trajectory of recovery following cognitive- Koukkari & Sothern, 2006; Redfern & Lemmer, behavioral intervention for work disability. Journal of Occupational Rehabilitation, 16(1), 63–74. 2007). In behavioral medicine, the most relevant Sullivan, M., Feuerstein, M., Gatchel, R. J., Linton, S. J., biological rhythms show a period of about 24 h & Pransky, G. (2005). Integrating psychological and (circadian), 7 days (circaseptan), 30 days behavioral interventions to achieve optimal rehabilita- (circatrigintan), or 1 year (circannual). tion outcomes. Journal of Occupational Rehabilita- tion, 15, 475–489. Sullivan, M. J. L., Ward, L. C., Tripp, D., French, D. J., Description Adams, H., & Stanish, W. D. (2005). Secondary prevention of work disability: Community-based psychosocial intervention for musculoskeletal disorders. Life is adapted to rhythms that are generated by Journal of Occupational Rehabilitation, 15(3), 377–392. movements of the Earth, the Moon, and the Sun C 416 Chronobiology in relation to each other. Depending on the fea- organisms might have benefited also from the tures of its habitat, every living organism on separation of otherwise incompatible body and earth, including bacteria, plants, animals, and brain functions in time (e.g., encoding of new humans, shows rhythmic changes in physiology information during the active period and consol- and behavior with different periods like that of idation, i.e., the covert reactivation of “fresh” tidal rhythms (12 h, circahemidian), the daily memory traces that is incompatible with active light–dark cycle (24 h, circadian), the weekly stimulus processing during the resting period). cycle (presumably stemming from alternations To sum up, astronomically generated rhythms between spring- and neap-tides, 7 days, were evolutionary imprinted onto the genome of circaseptan), the lunar cycle (30 days, living organisms, creating anticipatory biological circatrigintan), and the seasons (1 year, clocks and the organization of physiology and circannual). Periods that are longer than 1 day behavior in time (see Fig. 1). The underlying are called infradian, those that are shorter than molecular machinery has been elucidated 1 day are termed ultradian. Ultradian oscillations mainly for the circadian rhythm in the 1970s show very different periods and, like the 90 min when the first clock gene was described in the of the non-REM-REM sleep cycle (REM: rapid fruit fly. By now many clock genes are discov- eye movement), often lack an environmental ered that are linked with their respective tran- counterpart. scripts in an interlocked feedback loop that takes Biological rhythms do not simply follow envi- about 24 h for a full cycle. Activity in this ronmental changes but rather appear to anticipate feedback loop represents the molecular pendu- them. They are still evident if an organism is lum of the clock (Panda, Hogenesch, & Kay, deprived of any external time cue (zeitgeber)or 2002). In mammalian brain and peripheral in isolated cells in culture (e.g., white blood organs, clock genes control basic cellular pro- cells). Under such free-running conditions, cesses and up to 10% of the transcriptome in a given rhythm period typically slightly deviates a tissue-specific manner. Though sophisticated, from the external cycle (e.g., 24.2 h instead of these self-sustained clocks are not precise – as it 24 h, hence the term “circa-dian”) and this becomes evident under free-running conditions unmasked endogenous rhythm represents a trait – and therefore have to be reset and synchro- with considerable interindividual differences nized (entrainment) by an external zeitgeber (Aschoff, 1965). This indicates that environmen- (synchronizer, entraining agent). The most tal rhythms are adopted by inheritable internal important zeitgeber is light. Photic entrainment time-keeping systems. It is assumed that endog- is provided by nonvisual retinal cells that enous timing mechanisms developed during convey the information about light and darkness evolution, with the goal of adapting the organism to the hypothalamic suprachiasmatic nuclei to relevant environmental changes (like the avail- (SCN), called the “master clock.” In a hierarchic ability of food, exposure to predators, changes in structure, the SCN signals to other brain centers ambient temperature, or periods of efficient (like sleep regulatory centers) and synchronizes reproduction) in an anticipatory manner. This clocks in peripheral tissues via the sympathetic anticipatory cycling is advantageous, e.g., with nervous system and the hypothalamic-pituitary- respect to energetic efficiency, and was therefore adrenal axis. Apart from light, further external preserved by natural selection. The adaptation of and internal synchronizers are ambient and core living matter to environmental changes reflects body temperature, sleep, physical activity, mel- a basic concept of physiology, i.e., homeostasis – atonin, food intake, and social cues. So, work- the maintenance of the “internal milieu” of the days and weekends are likely synchronizers for organisms at a constant level (setpoint) despite circaseptan rhythms, whereas circannual external challenges. Core body temperature, e.g., rhythms are assumed to be entrained by the is homeostatically regulated. In addition to length of the daily light span and changes in the advantage of adaptation, more complex environmental temperature. Chronobiology 417 C

C

Chronobiology, Fig. 1 Environmental rhythms like the to environmental rhythms and therefore serve to anticipate 24 h light–dark cycle were evolutionary imprinted onto external challenges (homeostasis). Two hormonal the genome of living matter. Clock genes and their tran- rhythms are depicted that can be statistically described scripts built up the molecular clock that ticks in the hypo- (chronobiometry). Experimental procedures in chronobi- thalamic suprachiasmatic nuclei (SCN), but also in many ology aim to dissect the effects of endogenous clocks from if not all cells of the human body. As these molecular entraining and masking influences. Apart from circadian clocks are not precise they are synchronized (entrained) rhythms, chronobiology also describes oscillations with by zeitgeber. Environmental zeitgebers reset the phase of periods that are shorter than 1 day (like the ultradian the SCN that itself signals to sleep regulatory centers and rhythm of rapid eye movement sleep) and with periods synchronizes peripheral clocks by intrinsic and activity- of about 7 days (circaseptan) and about 1 year related factors. This multi-oscillatory system induces (circannual). Important aspects of chronobiology in rhythms in physiology and behavior that are synchronized behavioral medicine are summarized in the grey box

In animals and humans, this complex time- that allow to dissect the endogenous component keeping system of clock genes and SCN regulates of these rhythms from masking environmental the sleep-wake cycle and induces rhythmic factors or behaviors. Experimental designs use changes in cognitive and physical performance, isolation procedures (cave or bunker experi- core body temperature, hormone levels, and ments) or constant lighting conditions in humans metabolism. Chronobiologists assess such and animals, respectively, to eliminate external rhythms with inferential statistical tools time cues. Emerging free-running rhythms may (chronobiometry) either under “natural,” i.e., then differ among parameters in terms of their entrained, conditions or in experimental settings period such that, e.g., the sleep-wake-cycle may C 418 Chronobiology desynchronize from the rhythm of core body disciplines of clinical medicine with respect to temperature (internal desynchronization) physiological functions, laboratory findings (Aschoff, 1965). The forced desynchrony proto- and the incidence of disease symptoms. In col intentionally induces such an effect. It addition, efficacy and potential side effects of exploits the fact that an endogenous rhythm can medical interventions show time dependency only be entrained to periods that differ not too (chronopharmacology, chronotoxicology). Dis- much from its own period (range of entrainment). ruption of biological rhythms, as evident in shift If, therefore, the sleep-wake cycle is experimen- workers, travels across time zones (jet lag), but tally scheduled to 28 h, the rhythm of core body also due to modern lifestyle, compromises mood, temperature runs out of phase with its own free- sleep, cognitive and physical performance, running period. Another elaborate approach used activates the stress axes, and may eventually to dissociate the circadian rhythm from masking lead to pathology and disorders like major influences in humans is the constant routine pro- depression, metabolic syndrome, obesity, immu- tocol. In this protocol, the participants stay awake nosuppression, low grade systemic inflammation, for more than 24 h under constant ambient light and cardiovascular diseases. Conversely, sleep and temperature, in a supine position in bed with curtailment, chronic stress, high fat diet, many hourly isocaloric snacks and beverages. All these infections, and autoimmune diseases are associ- methods aim to scrutinize the contribution of ated with circadian disruption thus feeding into multiple endogenous oscillators as well as a vicious circle (Phillips, 2009). These relation- entraining environmental, intrinsic, and activity- ships, however, also offer therapeutic options related factors to biological rhythms. In addition, of re-entraining biological rhythms by means of they address the bidirectional interactions zeitgebers (chronotherapy, chronobiotics), as it between the circadian system and sleep. is done with bright light therapy in mood To unravel molecular mechanisms of biologi- disorders and the administration of melatonin to cal rhythms chronobiologists study genetically prevent jet lag. The optimal timing of such inter- manipulated animals (knockouts or mutants of cer- ventions can be assessed by phase-response tain clock genes in the whole genome or in indi- curves representing an important research tool vidual organs), silence clock gene activity with of chronobiology. In addition, cognitive behav- RNA interference (RNA: ribonucleic acid) or cou- ioral therapy can alleviate circadian and sleep ple clock genes with luciferase to allow continuous disruption in psychiatric and neurologic diseases. long-term monitoring of gene activity in cell cul- As epidemiological data indicate that circadian tures as well as in vivo (Panda et al., 2002). Human disruption and associated sleep curtailments research focuses on twin studies and clock gene increase the incidence of metabolic and cardio- polymorphisms. Clock genotypes can then be set vascular diseases and the risk of cancer, it is into relation to the circadian preference of individ- the goal of future research to elucidate if uals (chronotype, i.e., whether one is a “lark” or an re-entrainment of biological rhythms can like- “owl”) that is assessed by investigating the phase wise be beneficial to prevent these diseases in of rhythms under “natural” entrained conditions by shift workers and the elderly. means of questionnaires, diaries, actigraphy, or dim light melatonin onset (DLMO). In this context, ontogenetic research elucidates the phase shifts Cross-References that occur during lifetime, i.e., the phase delay in adolescence and the phase advance in the elderly ▶ Cardiovascular Disease (Phillips, 2009). ▶ Central Nervous System Chronobiology is an interdisciplinary science ▶ Circadian Rhythm covering all fields of medical practice and ▶ Cognitive Behavioral Therapy (CBT) research. Circadian, circaseptan, circatrigintan, ▶ Cognitive Function and circannual rhythms are described in all ▶ Corticosteroids Church-Based Interventions 419 C

▶ Cortisol ▶ Diurnal Mood Variation Church Attendance ▶ Homeostasis ▶ Hypothalamus ▶ Religious Ritual ▶ Inflammation ▶ Life Span ▶ Lifestyle Changes C ▶ Metabolic Syndrome ▶ Metabolism Church-Based Interventions ▶ Mood ▶ Pathophysiology Marianne Shaughnessy ▶ Physical Functioning School of Nursing, University of Maryland, ▶ Polymorphism Baltimore, MD, USA ▶ Sleep ▶ Stress ▶ Sympathetic Nervous System (SNS) Synonyms

Faith community interventions; Faith-based References and Readings interventions

Aschoff, J. (1965). Circadian rhythms in man. Science, 148, 1427–1432. Definition Dunlap, J. C., Loros, J. J., & DeCoursey, P. J. (2004). Chronobiology: Biological timekeeping. Sunderland, MA: Sinauer. Refers to any research, clinical, public health, or Foster, R. G., & Kreitzman, L. (2004). Rhythms of life: The data collection initiative targeted to a faith-based biological clocks that control the daily lives of every organization or community. living thing. London: Yale University Press. Halberg, F. (1969). Chronobiology. Annual Review of Physiology, 31, 675–725. Koukkari, W. L., & Sothern, R. B. (2006). Introducing Description biological rhythms: A primer on the temporal organi- zation of life, with implications for health, society, reproduction, and the natural environment. Academicians, clinicians, and researchers have New York: Springer. partnered with church-based or faith-based orga- Panda, S., Hogenesch, J. B., & Kay, S. A. (2002). nizations for the purposes of descriptive and Circadian rhythms from flies to human. Nature, 417, interventional research, launching pilot programs 329–335. Phillips, M. L. (2009). Circadian rhythms: Of owls, larks and studying public health problems for years. and alarm clocks. Nature, 458, 142–144. There are multiple advantages to partnering Redfern, P. H., & Lemmer, B. (2007). Physiology and with such populations for these purposes. These pharmacology of biological rhythms (Vol. 125). groups tend to be established communities, with New York: Springer. an organized, recognized authority structure that provides a support network for all those within Websites the group. This infrastructure is well suited to Center for Chronobiology, University of California, San Diego. http://ccb.ucsd.edu allow investigation of social and public health Howard Hughes Medical Institute. Biological clocks, issues. Secondly, the groups share a common lecture series. http://www.hhmi.org/biointeractive/ belief and value system, allowing for an assess- clocks/lectures.html ment of how those beliefs affect behaviors. To the Society for Research on Biological Rhythms. http://www. srbr.org extent that health-related lifestyle behaviors Zivkovic, B. Clock tutorials. http://borazivkovic. are dictated by religious beliefs, studies of these blogspot.com/2005/01/clock-tutorials.html populations can address health outcomes, such as C 420 Church-Based Support those explored in the Nun’s study (University of communities in inner-cities in “It is Well with Minnesota), or the influence of genetics on My Soul: Churches and Institutions Collaborat- health, as in studies of the Old Order Amish ing for Public Health.” In this book, Rev. (Hsueh et al., 2000). Finally, depending on the Tuggle suggests the importance of approaching size of the faith community, it is possible to these collaborations as a true partnership and capture a large number of potential study subjects makes specific recommendations for ensuring within one faith community or a network of faith a successful collaboration. communities. Churches and faith communities can also Recognizing that church- and faith-based be starting points for interventions designed to organizations could be significant partners in be expanded to the community at large. By addressing social and health-related issues, Pres- introducing a program, initiative, or intervention ident George W. Bush established the White at a church, potential participants may observe House Office of Faith-Based and Community the enthusiasm of those already engaged and Initiatives in 2001 as a means to allow faith- create support for expansion of the project based organizations to apply for federal funding beyond the church group. With careful planning to implement social service programs. Under in advance and a thoughtful, respectful criticism from the Americans United for the approach, it is possible to create a true partner- Separation of Church and State and the Ameri- ship for research or clinical care projects to can Civil Liberties Union, safeguards were put improve public health. into place that prevent these groups from advancing their religious agendas while admin- References and Readings istering programs using federal funds. In 2009, President Barack Obama changed the name of Hsueh, W. C., Mitchell, B. D., Aburomia, R., Pollin, T., the organization to the White House Office of Sakul, H., Gelder Ehm, M., et al. (2000). Diabetes in Faith-based and Neighborhood Partnerships. The the old order Amish: Characterization and heritability Department of Health and Human Services now analysis of the Amish Family Diabetes Study. Diabe- tes Care, 23(5), 595–601. houses the Center for Faith-based and Neighbor- Tuggle, M. (2000). It is well with my soul: Churches and hood Partnerships. This center does not admin- institutions collaborating for public health. Washington, ister grants but provides information on building DC: American Public Health Association. and sustaining partnerships for community- University of Minnesota. The nun study. Accessed May 13, 2011, from https://www.healthstudies.umn.edu/ based programs. Several other US government nunstudy/ departments currently host initiatives for faith- US Department of Health and Human Services. Center for based and community partnerships, including the faith-based and neighborhood partnerships. http:// Substance Abuse and Mental Health Services www.hhs.gov/partnerships/ Administration and the US Department of Agriculture. Research interventions conducted within the context of church- or faith-based organizations can be effectively conducted only with careful Church-Based Support consideration in advance of the church and community challenges, selection of the right ▶ Religious Social Support faith community to meet the needs of the pro- ject, understanding of how to best implement the project without offense and skillful market- ing strategies. Rev. Melvin Tuggle (2000) Cigarette offers specific guidance on related principles and how to approach and interact with faith ▶ Nicotine Circadian Rhythm 421 C

Definition Cigarette Advertising A circadian rhythm is an approximately 24-h ▶ Tobacco Advertising cycle of a biochemical, physiological, or behav- ioral process that is generated by internal biolog- ical clocks. In most animals, the intrinsic rhythm of the clock (cycle length) is slightly longer than C Cigarette Smoking 24 h, but normally the clock is synchronized to the 24-h day (entrainment) by environmental ▶ Smoking Behavior time signals (zeitgebers), the primary one of which is solar light. In the absence of timing signals (temporal isolation), circadian rhythms free-run on a non-24-h cycle, expressing the Cigarette Smoking and Health intrinsic rhythm of the clock. The process of synchronization involves daily, stimulus-induced ▶ Smoking and Health adjustment (phase shifts) that compensate for the difference between the intrinsic period of the internal clock and the period of the environmen- Cigarette Smoking Behavior tal cycle. Light can induce phase shift that varies in magnitude and direction depending on the circadian phase of exposure. Light exposure in ▶ Smoking Behavior the subjective morning resets the internal clock to an earlier time, while light exposure in the early subjective night resets the clock to a later time. Cigarette Smoking Cessation Intensity of the light, duration of the light pulse, and the spectral characteristics of the light ▶ Smoking Cessation determine the magnitude of a phase shift at any specific circadian phase. Blue light is an efficient wavelength to shift the circadian rhythms. The suprachiasmatic nucleus (SCN), which is Circadian Clock situated bilaterally in the hypothalamus, just above the optic chiasm, is of central importance ▶ Circadian Rhythm in the generation and entrainment of mammalian circadian rhythms. Destruction of SCN disrupts a wide variety of circadian rhythms. Photic entrainment is thought to be largely mediated by retinal photoreceptors. Approximately one third Circadian Rhythm of SCN cells are photically responsive which is believed to result from glutamatergic stimula- Fumiharu Togo tion of N-methyl-D-aspartate receptors through Graduate School of Education, The University of the retinohypothalamic tract. Photic and Tokyo, Bunkyo-ku, Tokyo, Japan glutamatergic stimulation of SCN cells in the early subjective night causes phase delay, whereas such stimulation late in the subjective Synonyms night causes phase advance. Circadian rhythms in some species can also Circadian clock be shifted and entrained by stimuli other than C 422 Citalopram light, such as exercise, social stimuli, or feeding. These so-called nonphotic zeitgebers may in Classical Conditioning some cases engage a circadian pacemaker sys- tem separate from that affected by light. Annie T. Ginty Nonphotic influences on the clock phase appear School of Sport and Exercise Sciences, to be mediated by the geniculohypothalamic The University of Birmingham, Edgbaston, tract, neuropeptide Y, and serotonergic path- Birmingham, UK ways. Although the mechanism that constitutes exercise to promote phase shift in the human circadian clock is unclear, exercise during the Synonyms late subjective day has been shown to produce a phase advance of the rhythm, whereas exercise Pavlovian conditioning during most of the subjective night produces phase delays. Definition Cross-References Classical conditioning is learning by association ▶ Neuropeptide Y (NPY) and focuses on what happens before an individual responds. It is often used in behavioral training. References and Readings Perhaps, the most well-known example of classical conditioning is that of Pavlov’s dogs. Koukkari, W. L., & Sothern, R. B. (2006). Introducing Pavlov measured salivation responses in dogs. biological rhythms. New York: Springer. Before conditioning, he rang a bell and noted Refinetti, R. (2006). Circadian physiology (2nd ed.). Boca Raton, FL: CRC Press. that there was no increase in saliva from the dogs. Then, during conditioning, he rang a bell (unconditioned stimulus) and immediately put Citalopram meat powder (conditioned stimulus) on the dogs’ tongues which caused them to salivate ▶ Selective Serotonin Reuptake Inhibitors (unconditioned response); he continued this (SSRIs) several times. Finally, after conditioning, he rang the bell again but without food and the dogs salivated (conditioned response). Pavlov used classical conditioning so the dogs associated an unrelated stimulus (the bell) with food. Thus, Classic Migraine they eventually produced the same saliva response they would for food with the bell. For further ▶ Migraine Headache details, see Coon and Mitterer (2010)(Fig. 1).

Classical Conditioning, Fig. 1 Pavlovian conditioning Clinical Agreement 423 C

Cross-References Quantifying the extent to which clinical agree- ment exists in a given situation is therefore ▶ Operant Conditioning important. Consider the following hypothetical data presented by Jekel et al. (2007) concerning clinical agreement between two clinicians regarding their diagnosis of the presence or References and Readings absence of a cardiac murmur upon physical C examination of 100 patients: Coon, D., & Mitterer, J. O. (2010). Introduction to psychology: Gateways to mind and behavior Clinician number 1 (12th ed.). Wadsworth, CA: Wadsworth Cengage Learning. Murmur Murmur Clinician no. 2 present absent Total Murmur 30 7 37 present Murmur absent 3 60 63 Clinical Agreement Total 33 67 100

J. Rick Turner These data show the following: Cardiovascular Safety, Quintiles, Durham, 1. For 30 patients, the clinicians both determined NC, USA the presence of a murmur. 2. For 60 patients, the clinicians both determined the absence of a murmur. Synonyms 3. For 7 patients, Clinician number 2 determined the presence of a murmur while Clinician Medical agreement number 1 determined the absence of a murmur. 4. For 3 patients, Clinician number 1 determined Definition the presence of a murmur while Clinician num- ber 2 determined the absence of a murmur. It is important in both clinical medicine and The maximum possible degree of clinical research to assess the extent to which different agreement is equal to the total number of patients, individuals (e.g., clinicians, observers) observe i.e., 100. This would occur when the two clinicians and report the same phenomenon (Jekel, Katz, made the same determination for every patient. As Elmore, & Wild, 2007). Ideally, there would be already noted, this is an ideal but unlikely sce- perfect intraobserver agreement (the same person nario. (Actually, the operationalization of the would always observe and report the same phe- term “ideal” in this context has another aspect nomenon in an identical manner), and perfect when making clinical judgments: Ideally, both interobserver agreement (different people would clinicians make the same and CORRECT deter- observe and report the same phenomenon identi- mination; it is a theoretical possibility that they cally). However, these ideals are precisely that: could agree 100% of the time and also be wrong they describe an ideal scenario, and real-life sce- 100% of the time.) Various calculations can be narios are often quite different. Elmore, Wells, conducted to quantify the degree of agreement. Lee, Howard, and Feinstein (1994) studied both The actual degree of agreement is 90 out of intraobserver and interobserver agreement 100 cases. This value is typically presented as among radiologists’ interpretations of a specific a percentage, which is 90% (the numbers here mammogram, demonstrating that radiologists are deliberately chosen to facilitate straightfor- can differ, sometimes substantially, in their inter- ward calculations). However, purely by random pretations of mammograms and in their recom- chance, it is possible that the clinicians would mendations for management. agree sometimes. Imagine a scenario in which C 424 Clinical Decision-Making the two clinicians were asked simply to write a list of 100 terms, each time choosing between Clinical Decision-Making “murmur present” and “murmur absent.” Proba- bilistically, there would likely be some agree- J. Rick Turner ment. A key question therefore becomes: To Cardiovascular Safety, Quintiles, Durham, what extent does the degree of clinical agreement NC, USA between the two clinicians improve upon chance agreement alone? The kappa test ratio provides an answer to this Synonyms question. In this case, the mathematics (not presented here) lead to a kappa test ratio of Decision analysis; Medical decision-making 0.78, which is typically expressed in percentage terms, i.e., 78%. To put this in perspective, con- sider the arbitrary but useful divisions for the Definition interpretation of kappa scores as presented by Sacket, Haynes, Guyatt, and Tugwell (1991): Clinicians must make treatment decisions on 1. Less than 20% represents negligible improve- a daily basis, and these decisions, or recommen- ment in the degree of clinical agreement over dations (final decisions are best made by the chance alone. “health team” of a physician and his or her 2. 20–39% represents minimal improvement. patient) should be based on the best available 3. 40–59% represents fair improvement. evidence. The terms “evidence-based medicine” 4. 60–79% represents good improvement. and “evidence-based practice” have become part 5. 80% and above represents excellent of the health lexicon, and “evidence-based improvement. behavioral medicine” is also an established term These hypothetical data yielded a kappa score (see the ▶ Evidence-Based Behavioral Medicine of 78%, as noted already, meaning that this (EBBM) entry in this encyclopedia for a detailed degree of improvement would fall in the “good discussion). improvement” category. With regard to real data, While clinical decision-making relies on Jekel et al. (2007) stated that “the reliability of evidence, the evidence in the medical literature most tests in clinical medicine that require human (with the exception of case reports) typically judgment seems to fall in the fair or good range.” describes the experience of a population of patients rather than an individual patient. Cross-References Evidence-based clinical decision-making, therefore, requires “the application of popula- ▶ Clinical Decision-Making tion-based data to the care of an individual patient ▶ Probability whose experiences will be different, in ways both discernible and not, from the collective experi- ence reported in the literature” (Katz, 2001). References and Readings He also observed that “All of the art and all of the science of medicine depend on how artfully Elmore, J. G., Wells, C. K., Lee, C. H., Howard, D. H., & and scientifically we as practitioners reach our Feinstein, A. R. (1994). Variability in radiologistis’ interpretation of mamograms. The New England Jour- decisions. The art of clinical decision-making is nal of Medicine, 331, 1493–1499. judgment, an even more difficult concept to grap- Jekel, J. F., Katz, D. L., Elmore, J. G., & Wild, D. M. G. ple with than evidence.” (2007). Epidemiology, biostatistics, and preventive Decision analysis is a formalized approach to medicine (3rd ed.). Philadelphia: Saunders/Elsevier. Sacket, D. L., Haynes, R. B., Guyatt, G. H., & Tugwell, P. making complex clinical decisions that relies on (1991). Clinical epidemiology: A basic science for clin- plotting a “decision tree” containing the various ical medicine (2nd ed.). Boca Raton, FL: Little/Brown. options and then rating each in terms of Clinical Practice Guidelines 425 C probability and utility. In this way, the clinician attempts to make explicit the quantitative Clinical Practice Guidelines principles upon which a given clinical decision will be based. Once these principles have been Karina Davidson1 and Joan Duer-Hefele2 identified from the literature, both the clinician 1Department of Medicine, Columbia University and the patient can consider them, challenge them Medical Center, New York, NY, USA as appropriate, and systematically eliminate 2Columbia University, New York, NY, USA C treatment (or nontreatment) options until a clear preference emerges (Katz, 2001). Synonyms

Cross-References Clinical guideline; Consensus guideline; Guideline; Practice guideline ▶ Clinical Agreement ▶ Evidence-Based Behavioral Medicine (EBBM) Definition ▶ Generalizability Clinical practice guidelines “are systematically developed statements to assist practitioner and References and Readings patient decisions about appropriate health care for specific clinical circumstances” (Field & Katz, D. L. (2001). Clinical epidemiology and evidence- Lohr, 1990). Good practice guidelines should be based medicine: Fundamental principles of clinical specific, comprehensive, and yet flexible enough reasoning and research. Thousand Oaks, CA: Sage. to be useful (Field & Lohr, 1992).

Description Clinical Equipoise Clinical practice guidelines are needed because ▶ Principle of Equipoise early reports suggested that less than 5% of med- ical treatment decisions were based on strong research evidence; about half were based on shared clinician beliefs that had minimal scien- Clinical Ethics tific support and half were based on personal opinion (Field & Lohr, 1990). Well-constructed ▶ Ethical Issues clinical practice guidelines hold the promise of providing information to enable clinicians to choose the best treatments, diagnoses, or screen- ing practices available, and regulators to set Clinical Guideline policy based on the current state of scientific knowledge. Practice guidelines can assist ▶ Clinical Practice Guidelines policymakers and public health advocates to be able to better determine which behavioral medi- cine practices should be reimbursed (Davidson, Trudeau, Ockene, Orleans, & Kaplan, 2004). Clinical Health Psychology Risk management – that is, the effort to lower or curb the number of poor outcomes and potential ▶ Medical Psychology for malpractice litigation – is another possible C 426 Clinical Practice Guidelines reason for developing clinical practice guide- of evidence to support or refute the use of certain lines. They can also be used when considering interventions http://www.uspreventiveservices- accreditation and certification for education pro- taskforce.org/methods.htm. There are many grams and individual clinicians. However, the other bodies who create clinical practice primary reason for developing and then guidelines, such as the American Psychiatric implementing clinical practice guidelines is the Association http://www.psych.org/mainmenu/ expectation that they will improve the patient, the psychiatricpractice/practiceguidelines_1.aspx public, and the community’s health. and the CDC-sponsored Community Guide Each clinical practice guideline differs with (Briss et al., 2000) http://www.thecommu- respect to the practice it covers, the way in nityguide.org/about/index.html. which the evidence is collected, the rules used A examination of where to find clinical prac- to judge a practice as useful, and the way in tice guidelines revealed that most first look online which these guidelines are communicated to and prefer governmental agency guidelines over influence patient care. Essentially, some orga- others (Burgers, Cluzeau, Hanna, Hunt, & Grol, nization, whether a governmental body, a pro- 2003). There is an excellent resource to look for fessional society, or an empanelled group of any relevant clinical practice guidelines that is experts, reviews the evidence to support run by AHRQ – The National Guideline Clearing a specific screening, diagnostic, or treatment house – http://www.guideline.gov/. practice and then provides a guideline advising There are some excellent educational refer- on the usefulness of that practice. Evidence- ences that explain how to locate, evaluate, and based practice guidelines are often distin- then, if relevant, use the information in practice guished from consensus practice guidelines guidelines (Hayward, Wilson, Tunis, Bass, & that are informed by relevant research but not Guyatt, 1995; Wilson, Hayward, Tunis, Bass, & necessarily guided by systematic evidence Guyatt, 1995). For a systematic approach to reviews (Davidson et al., 2004). assessing guidelines, the AGREE instrument is American Heart Association (AHA), for available. http://www.agreecollaboration.org/ example, has set out an explicit and formal There is no formal accrediting body or review system for creating a guideline. The a professional society in behavioral medicine need for the guideline, the composition of the that regularly produces practice guidelines; loca- members of the writing group, and the approval tions of guidelines that may be useful for behav- process are all prespecified. Second, the criteria ioral medicine can be found in this citation for searching for the evidence, the grade that will (Davidson et al., 2004). be given the evidence, and the summary state- There is an optimistic assumption that the ment similarly must also follow the prespecified application of clinical practice guidelines results system. For example, evidence for benefit of in better patient outcomes (Spring et al., 2005). a drug or a preventive action is considered “A” However, rigorous program evaluation to support if there are multiple randomized controlled trials this assertion is only in its beginning stages. or meta-analyses from multiple populations that Grimshaw and others (Grimshaw & Russell, all show benefit to the patient or the community. 1993) conducted a systematic review to address The AHA methodology handbook for creating this question by examining evaluations of clinical systematic practice guidelines can be found guideline implementation for specific clinical as a pdf at: http://www.americanheart.org/pre- conditions and preventative services. Of 59 senter.jhtml?identifier=3039683. papers, all but 4 detected significant improve- Similarly, the United States Preventative ments in the process of care following the intro- Services Task Force has set up a system for duction of guidelines. They concluded that objectively obtaining and reviewing all evidence explicit guidelines do improve clinical practice, for preventative services and releases guidelines but careful evaluation is always required. As few advising practitioners and patients about the level explicit behavioral medicine clinical practice Clinical Predictors 427 C guidelines exist, little is known about the adop- Hayward, R. S., Wilson, M. C., Tunis, S. R., Bass, E. B., & tion of evidence-based guidelines and their use in Guyatt, G. (1995). Users’ guides to the medical literature. VIII. How to use clinical practice other fields, and certainly, this is uncharted within guidelines. A. Are the recommendations valid? The behavioral medicine (Spring et al.). Evidence-Based Medicine Working Group. JAMA: It is also by no means certain that using prac- The Journal of the American Medical Association, tices recommended by practice guidelines will 274, 570–574. Pincus, H. A. (1994). Dialogue: Treatment guidelines: C decrease health care costs; in medicine, it has What are the risks? Risks are outweighed by the sometimes increased them (Sackett, Rosenberg, benefits. Behavioral Healthcare Tomorrow, 3, 40–41. Gray, Haynes, & Richardson, 1996). However, in 44–45. the absence of evidence-based practice guide- Sackett, D. L., Rosenberg, W. M., Gray, J. A., Haynes, R. B., & Richardson, W. S. (1996). Evidence lines, managed care organizations and other based medicine: What it is and what it isn’t. British policymakers may reimburse the most economi- Medical Journal, 312, 71–72. cal treatment (Pincus, 1994), a measure that Spring, B., Pagoto, S., Kaufmann, P. G., Whitlock, E. P., would certainly restrict practice (Spring et al., Glasgow, R. E., Smith, T. W., et al. (2005). Invitation to a dialogue between researchers and clinicians about 2005). The value of clinical practice guidelines evidence-based behavioral medicine. Annals of for behavioral medicine is that, by making it Behavioral Medicine, 30, 125–137. possible to distinguish between effective and Wilson, M. C., Hayward, R. S., Tunis, S. R., Bass, E. B., & ineffective treatments, it encourages all of us to Guyatt, G. (1995). Users’ guides to the medical literature. VIII. How to use clinical practice guide- make informed decisions about training, about lines. B. what are the recommendations and will practice, and about reimbursement. they help you in caring for your patients? The Evi- dence-Based Medicine Working Group. JAMA: The Journal of the American Medical Association, 274, 1630–1632. References and Readings

Briss, P. A., Zaza, S., Pappaioanou, M., Fielding, J., Wright-De Aguero,€ L., Truman, B. I., et al. (2000). Developing an evidence-based Guide to Community Clinical Predictors Preventive Services – Methods. The Task Force on Community Preventive Services. American Journal Yori Gidron of Preventive Medicine, 18, 35–43. Faculty of Medicine and Pharmacy, Free Burgers, J. S., Cluzeau, F. A., Hanna, S. E., Hunt, C., & Grol, R. (2003). Characteristics of high-quality University of Brussels (VUB), Jette, Belgium guidelines: Evaluation of 86 clinical guidelines developed in ten European countries and Canada. International Journal of Technology Assessment in Definition Health Care, 19, 148–157. Davidson, K. W., Trudeau, K. J., Ockene, J. K., Orleans, C. T., & Kaplan, R. M. (2004). A primer on This term often refers to biomedical factors current evidence-based review systems and their known to influence or predict health out- implications for behavioral medicine. Annals of comes. These are taken into account in clinical Behavioral Medicine, 28, 226–238. Field, M. J., & Lohr, K. N. (1990). Clinical pratice practice, when estimating a patient’s prognosis. guidelines: Directions for a new program. Committee Additionally, clinical predictors are considered in to Advise the Public Health Service on clinical clinical research, when trying to test new etiolog- practice guidelines. Washington, DC: Institute of ical or prognostic factors, and there is a need to Medicine. Field, M. J., & Lohr, K. N. (1992). Guidelines for clinical statistically control for known or previously practice: From development to use. Washington, DC: established clinical predictors, which could Committee on Clinical Practice Guidelines, Division possibly explain the role of the new tested factors. of Health Care Services, Institute of Medicine. In behavior medicine, this is often the common Grimshaw, J. M., & Russell, I. T. (1993). Effect of clinical guidelines on medical practice: A systematic review of approach, when testing the effects of a psychoso- rigorous evaluations. Lancet, 342, 1317–1322. cial factor on health outcomes. Often, it is crucial C 428 Clinical Settings to control for the effects of clinical predictors in behavior medicine, as clinical risk factors are Clinical Settings either important in predicting prognosis, and since they may be associated with and partly Jeffrey Goodie explain the prognostic effects of psychosocial Department of Family Medicine, Uniformed factors. In coronary heart disease, clinical risk Services University of the Health Sciences, factors can include left ventricular ejection frac- Bethesda, MD, USA tion, number of occluded vessels, troponin levels, and comorbidities. In cancer, clinical risk factors can include performance level, tumor stage, Synonyms and treatments. In surgery, clinical risk factors can include age, severity of surgery, and Collaborative care; Integrated care; Primary care; comorbidities. Secondary care; Tertiary care Chida, Hamer, Wardle and Steptoe (2008), in their meta-analysis of over 160 studies, tested and found that psychosocial factors significantly Definition predicted incidence and prognosis in cancer, and this was maintained also when statistically con- Clinical settings include primary, secondary, ter- trolling for confounders, which included clinical tiary, and quaternary care settings. Primary care predictors. One example in heart disease is the clinical settings are typically the first point of study by Denollet et al. (1996) showing that type contact individuals have with the medical system. D personality (high distress and social inhibition) The majority of health care, including mental predicted mortality from coronary heart disease, health care, is provided in the primary care set- independent of clinical risk factors. Testing for ting. Family medicine (family practice), internal such factors provides important strength to the medicine, pediatric, and sometimes obstetrics claim that psychosocial factors affect health out- and gynecological clinics are classified as pri- comes, independent of biomedical factors. This mary care clinical settings. Primary care clinical then justifies the need to consider and intervene in settings are distinguished from other speciality modifying psychosocial factors beyond targeting care settings because no referral is needed for biomedical clinical predictors alone. care and it is the source of care continuity and advocacy for the patient. The full spectrum of health care from health promotion, disease pre- Cross-References vention, and assessment and treatment of acute and chronic medical conditions occurs in primary ▶ Confounding Influence care (American Academy of Family Physicians, ▶ Risk Factors and Their Management 2011; Shi & Singh, 2010). The remaining clinical care settings are distin- guished by the complexity of speciality care that References and Readings can be provided (Shi & Singh, 2010). Secondary clinical settings include referral treatment facili- Chida, Y., Hamer, M., Wardle, J., & Steptoe, A. (2008). ties and specialists who do not typically have Do stress-related psychosocial factors contribute to cancer incidence and survival? Nature Clinical Prac- first contact with patients, but are not as special- tice Oncology, 5, 466–475. ized as those in tertiary care. Cardiology, derma- Denollet, J., Sys, S. U., Stroobant, N., Rombouts, H., tology, oncology, pulmonology, and urology Gillebert, T. C., & Brutsaert, D. L. (1996). Personality clinics are examples of secondary clinical set- as independent predictor of long-term mortality in patients with coronary heart disease. Lancet, tings. Acute care provided in an emergency 347(8999), 417–421. room and mental health care provided by Clinical Settings 429 C specialists (e.g., psychologists, psychiatrists), behavioral medicine specialists may work with although they do not require referrals, are com- patients recovering from coronary artery bypass monly classified as secondary care. Tertiary clin- surgeries, patients diagnosed with cancer, or ical settings use highly specialized facilities and diabetes. Behavioral medicine specialists may providers to assess and treat referred patients. In conduct research, teach classes, or provide indi- tertiary clinical settings patients may receive vidual treatment related to managing the complex surgeries (e.g., coronary artery bypass biopsychosocial factors (e.g., improving medica- C grafts) or intensive care when they are critically tion adherence, increasing social support, ill (e.g., intensive care units). Quaternary clinical smoking cessation, stress management, weight settings offer unique, very highly specialized management) associated with effective disease care, typically associated with regional, national, management. Sometimes specialized clinics are and/or academic health centers. Organ transplan- formed, such as a chronic pain or sleep clinic, tation is one example of the care typically pro- where behavioral medicine specialists work with vided in a quaternary clinical setting. other secondary and tertiary providers to assess and treat the specific physiological, cognitive, and behavioral factors contributing to chronic Description pain and sleep disruption. To meet the complex, chronic healthcare In the United States, the fastest growing segment needs of the aging population, researchers and of the population is older adults (i.e., 65 years and providers are continuing to focus on behavioral older) and the majority of their medical care will medicine in secondary and tertiary care set- be provided in family and internal medicine pri- tings. Increasingly behavioral medicine spe- mary care clinics. Concurrently, the Patient cialists are also collaborating with and Centered Medical Home (PCMH) (American integrating into the primary care clinical set- Academy of Family Physicians (AAFP), Ameri- ting to assist the primary care team in meeting can Academy of Pediatrics (AAP), American the complex health care needs of the elderly in College of Physicians (ACP), & American Oste- a manner that brings evidence-based behav- opathic Association (AOA), 2007) concept and ioral medicine assessment intervention to the National Center for Quality Assurance’s where the bulk of the elderly receive care. accreditation process of the PCMH are reshaping There are a variety of ways to describe how the primary care clinical setting. The purpose of behavioral medicine services are integrated these efforts has been to facilitate the relationship into primary care including co-location and between patients and their personal physicians. embedding (American Academy of Family A key principle of the PCMH is the focus on the Physicians (AAFP), American Academy of “whole person” and the biopsychosocial preven- Pediatrics (AAP), American College of Physi- tive care, acute care, chronic care, and end of cians (ACP), & American Osteopathic Associ- life care needs of individuals at all stages ation (AOA), 2007). Co-location may simply of their lives. mean that the behavioral medicine services are Behavioral medicine is practiced across all offered in the same physical structure as the clinical settings. Specialists in behavioral medi- primary care clinic, but assessments and care cine commonly work in secondary (e.g., cardiol- are consistent with the standard of care typi- ogy, chronic pain, oncology, and sleep) and cally followed by the behavioral medicine spe- tertiary clinical settings. In these clinics the cialist (e.g., a psychologist seeing patients for behavioral medicine specialist works as part of 50-min hours) and maintaining separate a multidisciplinary, interdisciplinary, or transdis- records. An embedded behavioral medicine ciplinary team to research, assess, and/or treat the specialist is a primary care team member who biopsychosocial needs of patients. For example, follows the standard of care within primary C 430 Clinical Study Design care (e.g., 15–30 min appointments) and docu- ments all care within the primary care medical Clinical Trial record. The Primary Care Behavioral Health model (Hunter & Goodie, 2010; Robinson & Amy Jo Marcano-Reik Reiter, 2007) is one of the most widely used Department of Bioethics, Cleveland Clinic, examples of an embedded service. In contrast Cleveland, OH, USA to the Primary Care Behavioral Health model Center for Genetic Research Ethics and Law, is the Care Management model, which uses Case Western Reserve University, Cleveland, a specialist, often a nurse, to assist with the OH, USA education and coordination of care of patients. The care manager helps to ensure that patients are getting the services they need from the Synonyms medical system. Some clinics are blending Primary Care Behavioral Health and Care Clinical study design; Evidence-based medicine; Management models to optimize the benefits Observational designs; Observational studies; of both care models. Observational study; Randomized controlled trial

Definition Cross-References A clinical trial is a procedure in behavioral and ▶ Primary Care biomedical research that is conducted to investigate ▶ Primary Care Providers potential treatments and effects of medical inter- ventions. The public and US National Institutes of Health (NIH) service site, www.ClinicalTrials.gov, References and Readings provides updated information on clinical trials regarding background and history, availability, American Academy of Family Physicians. (2011). Pri- results and outcomes, and links to other useful mary care. Retrieved from http://www.aafp.org/ resources. Clinical trials may be designed to exam- online/en/home/policy/policies/p/primarycare.html# Parsys0002 ine the effects of certain medications (e.g., different American Academy of Family Physicians (AAFP), Amer- types of drugs or doses of drugs; Kahn et al., 2008, ican Academy of Pediatrics (AAP), American College The Lancet) or behavioral interventions (e.g., of Physicians (ACP), & American Osteopathic Asso- a smoking cessation program; Moller, Villebro, ciation (AOA). (2007). Joint principles of the patient centered medical home. Retrieved from http://www. Pedersen, & Tønnesen, 2002, The Lancet). There pcpcc.net/joint-principles are many protocols and regulatory measures in Hunter, C. L., & Goodie, J. L. (2010). Operational and place that must be adhered to for a clinical trial to clinical components for integrated-collaborative be established. Once the clinical trial has been behavioral healthcare in the patient-centered medical home. Family, Systems, and Health, 28, 308–321. approved, researchers recruit healthy volunteers Robinson, P., & Reiter, J. (2007). Behavioral consultation and/or patients to participate in the study. Patients and primary care: A guide to integrating services. may receive some benefit from the trial, such as New York: Springer. access to a new medication; however, there are Shi, L., & Singh, D. A. (2010). Essentials of the U.S. health care system. Sudbury, MA: Jones and Bartlett. clinical trials where the patient/volunteer does not gain direct benefit from participating, such as serv- ing in the control group (i.e., the placebo) or par- ticipating in a trial that includes a long-term design in which the treatments will not be available in the Clinical Study Design near/foreseeable future. These aspects will be dif- ferent across clinical trials as the type, size, pur- ▶ Clinical Trial pose, length, and location of trials will vary. Clusters 431 C

Cross-References must occur. Usual rates of the disease can be determined from the distribution of occurrences ▶ Clinical Decision-Making in the same location in other time periods, in one ▶ Clinical Practice Guidelines or more similar locations at the same time period, ▶ Clinical Settings or in larger areas than the specific locale of ▶ Medical Outcomes Study interest. ▶ Randomized Clinical Trial The theory of random sampling means that, at C ▶ Randomized Controlled Trial times, “chance clusters” will occur. Therefore, this possibility must be borne in mind when References and Readings starting to investigate a particular cluster phe- nomenon. Consider the example of clusters of Appel, L. J., Moore, T. J., Obarzanek, E., Vollmer, W. M., cancer in neighborhoods or small areas. It is of Svetkey, L. P., Sacks, F. M., et al. (1997). A clinical considerable importance to assess whether there trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. New England is likely to be a specific environmental influence Journal of Medicine, 336(16), 1117–1124. that is causing the cluster. If it is indeed likely, Figueiredo, J. C., Grau, M. V., Haile, R. W., Sandler, R. S., concerted efforts to identify the influence can be Summers, R. W., Bresalier, R. S., et al. (2009). Folic planned. However, if it appears particularly acid and risk of prostate cancer: Results from a randomized clinical trial. Journal of the National unlikely, such investigation (and the necessary Cancer Institute, 101(6), 432–435. resources to complete it) may not be advisable Kahn, R. S., Fleischhacker, W. W., Boter, H., Davidson, M., immediately. Vergouwe, Y., Keet, I. P., et al. (2008). Effectiveness of Jekel, Katz, Elmore, and Wild (2007) discussed antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: An open randomised an instructive example concerning cancer. If the clinical trial. The Lancet, 371(9618), 1085–1097. types of cancer in an identified cluster vary con- Moller, A. M., Villebro, N., Pedersen, T., & Tønnesen, H. siderably, and are of the more common types (e.g., (2002). Effect of preoperative smoking intervention on lung, breast, colon, prostate), it is probably the postoperative complications: A randomised clinical trial. The Lancet, 359(9301), 114–117. case that there is not a specific environmental Saposnik, G., Saposnik, G., Mamdani, M., Bayley, M., hazard in the immediate locale. In contrast, if Thorpe, K. E., Hall, J., et al. (2010). Effectiveness of most of the cases in the cluster are of only one or virtual reality exercises in stroke rehabilitation a small number of cancers (especially leukemia, or (EVREST): Rationale, design, and protocol of a pilot randomized clinical trial assessing the Wii Gaming brain or thyroid cancer), a more intensive investi- System. International Journal of Stroke, 5(1), 47–51. gation may be appropriate. www.clinicaltrials.gov Reports to local, state, and federal agencies of perceived clusters are made frequently by concerned individuals or groups, physicians, and Clusters other health-care professionals. A balanced approach must be taken that balances public J. Rick Turner well-being with the acknowledgment that Cardiovascular Safety, Quintiles, Durham, the majority of these reports do not lead to the NC, USA identification of a common causal exposure. It is typically difficult to draw a conclusion from a single cluster, even one in which the aggregation Definition of a disease seems particularly unusual.

A cluster is a term used in environmental epide- miology. A disease cluster can be defined as “an Cross-References unusual aggregation, in time or space or both, of occurrences of a disease” (Hertz-Picciotto, ▶ Cancer, Prostate 2008). This means that an assessment of “usual” ▶ Cancer, Testicular C 432 Coagulation of Blood

References and Readings 3. Blood coagulation: Clot formation occurs as a result of coagulation that is mediated by Hertz-Picciotto, I. (2008). Environmental epidemiology. blood-clotting factors. Blood-clotting factors In K. J. Rothman, S. Grenland, & T. L. Lash (Eds.), are inactive forms of proteolytic enzymes. Modern epidemiology (3rd ed., pp. 598–619). Phila- delphia: Wolters Kluwer/Lippincott Williams & When converted to active forms, they trigger Wilkins. a cascade of reactions that comprise the Jekel, J. F., Katz, D. L., Elmore, J. G., & Wild, D. M. G. clotting process. At the initiation of coagula- (2007). Epidemiology, biostatistics, and preventive tion, small amounts of thrombin are generated medicine (3rd ed.). Philadelphia: Saunders/Elsevier. via FXa formation by the TF:FVIIa complex (“extrinsic pathway”). Large amounts of thrombin generation (“burst”) follow; this process is dependent on FXa formation via FIXa- and FVIIIa-mediated complexes on an Coagulation of Blood activated platelet surface. Generated thrombin converts fibrinogen to insoluble fibrin, which Koji Miyazaki forms a meshwork cross-linked by factor Department of Hematology, Kitasato University XIIIa. The fibrin fibers subsequently enclose School of Medicine, Sagamihara, Kanagawa, platelets, erythrocytes, leukocytes, and other Japan plasma proteins to form blood clots (second- ary hemostasis). 4. Fibrinolysis: The blood clot is dissolved when Synonyms healing is complete, thereby assuring long- term vascular patency. Hemostasis; Thrombosis Disturbances of Blood Coagulation The human hemostatic system is dependent on Definition a delicate equilibrium between procoagulant and anticoagulant factors that interact with each Normal Hemostasis other to ensure effective hemostasis at the sites of Hemostasis is a complex and highly regulated vascular injury. The procoagulant forces include physiological process that maintains a balance platelet adhesion, aggregation, and fibrin clot for- between the liquid state of blood within the vas- mation, while the anticoagulant forces include the culature and the induction of blood clot formation natural inhibitors of coagulation and fibrinolysis. following injury. Any disruption in the balance between clot As such, it involves multisystem interactions formation and clot dissolution can result in either between components of the vessel wall, blood thrombosis (due to hypercoagulation) or hemor- cells (mainly platelets), and plasma proteins rhage (due to hypocoagulation) (Colman et al. (Colman et al., 2005; Kaushansky et al., 2010). 2005). The following events are involved in the Congenital disorders of coagulation include hemostatic process: those conditions in which there are deficiencies 1. Vasoconstriction: When the blood vessel rup- or excessive amounts of either procoagulant or tures, the wall of the vessel immediately con- anticoagulant factors, manifesting as excessive tracts to reduce blood flow and thereby clotting or bleeding. These disorders can have prevent blood loss. a profound effect on the overall health, well- 2. Platelet activation: Platelets adhere to the ves- being, and quality of life of affected children. sel injuries via von Willebrand factor and Further, thrombotic tendencies can be related to aggregate with fibrinogen to form platelet acquired risk factors, including obesity, immobi- plugs (primary hemostasis). lization, diabetes, and hypertension. Coffee Drinking, Effects of Caffeine 433 C

Cross-References Description

▶ Aspirin In this entry, we will summarize the main effects ▶ Fibrinogen known about coffee and caffeine consumption on ▶ Fibrinolysis health based on the numerous studies published ▶ Obesity: Causes and Consequences over the last 10 years. The recent studies have reported the beneficial effects of moderate doses C References and Readings of coffee (3–4 cups per day) on alertness, vigi- lance, and cognitive abilities. However, coffee/ Colman, R. W., Marder, V. J., Clowes, A. W., George, J. N., caffeine can disturb sleep and generate anxiety. Goldhaber, S. Z., et al. (2005). Hemostasis and throm- Its lifelong consumption slows down age-related bosis (5th ed.). Philadelphia: Lippincott Williams & Wilkins. cognitive decline and decreases the risk for Kaushansky,K.,Lichtman,M.A.,Beutler,E.,Kipps,T.J., developing Parkinson or Alzheimer’s disease, as Seligsohn, U., Prchal J. T., et al. (2010). Williams hema- well as type 2 diabetes and numerous cancers tology (8th ed.). Hightstown, NJ: McGraw-Hill (cancers of the digestive tract, breast, endome- Professional. trial, and skin in particular). Coffee has no negative influence on cardiovascular health. However, coffee/caffeine should be consumed Coding RNA in moderation during pregnancy. The data summarized here come from both animal ▶ RNA preclinical and human studies and in numerous cases originate in reviews and meta-analyses of the studies published in a given area. This large Coffee wealth of data allowed the evolution of the negative vision present in most minds that coffee ▶ Coffee Drinking, Effects of Caffeine was not good for health. Coffee is the drink most consumed by adults. Caffeine is the psychoactive substance contained Coffee Drinking, Effects of Caffeine in coffee, tea, soda, cocoa, and chocolate (Table 1). It is also found in analgesic medica- Astrid Nehlig tions, energetic drinks, and over-the-counter U666, INSERM, Faculty of Medicine, slimming creams. The mean world consumption University of Strasbourg, Strasbourg, France of caffeine, the major constituent of coffee (Table 2), is 1 mg/kg/day in adults from which about 80% come from coffee. It reaches Synonyms 2.4–4.0 mg/kg/day in the USA and Canada, up to 7.0 mg/kg/day in Scandinavia. In 7–10-year-old Age-related cognitive decline; Alertness; children, caffeine consumption ranges from Alzheimer’s disease; Anxiety; Attention; 0.5 to 1.8 mg/kg/day in developed countries, Caffeine; Coffee; Cognitive abilities; Concentra- mainly from sodas and chocolate. tion; Mood; Pregnancy; Sleep; Vigilance Low to moderate consumption of caffeine (50–250 mg, equivalent to a small to 2 large cups of coffee in one sitting) generates positive Definition effects: feelings of well-being, relaxation, good mood, energy, increased alertness, and better Coffee is the drink most consumed by adults after concentration. The consumption of high to water. Caffeine is the psychoactive substance very high doses (400–800 mg, or 5–10 large contained in coffee, tea, soda, cocoa, and chocolate. cups of coffee in one sitting) leads to negative C 434 Coffee Drinking, Effects of Caffeine

Coffee Drinking, Effects of Caffeine, Table 1 Caffeine Coffee Drinking, Effects of Caffeine, Table 2 Compo- content of foods and drinks (Adapted from Debry (1994)) sition of medium-roasted coffee (Adapted from Debry (1994)) Foods and Volume or Content of caffeine (mg) drinks weight mean (extreme values) Percentage of dry Percentage of Filtered coffee 150 mL 115 (60–180) matter extraction by Espresso 30 mL 40 (40–60) Constituents Arabica Robusta water at 100 C Instant soluble 150 mL 65 (40–120) Caffeine 1.3 2.4 75–100 coffee Trigonelline 1.0 0.7 85–100 Decaffeinated 150 mL 3 (2–5) Minerals 4.5 4.7 90 coffee Acids Tea (leaves or 150 mL 40 (30–45) Chlorogenic 2.5 3.8 100 bags) Quinic 0.8 1.0 100 Iced tea 330 mL 70 (65–75) Sugars Hot chocolate 150 mL 4 (2–7) Sucrose 0 0 100 Regular soda 330 mL 30–48 Reducing sugars 0.3 0.3 Sugar-free soda 330 mL 26–57 Polysaccharides 33 37 10 Chocolate bar 30 g 20 (5–36) Lignin 2.0 2.0 – Milk chocolate 30 g 6 (1–15) Pectins 3.0 3.0 – Dark chocolate 30 g 60 (20–120) Proteins 10 10 15–20 Lipids 17 11 1 Caramelized 23 22.5 20–25 products (e.g., melanoidins) effects: nervousness, anxiety, aggressiveness, Volatile substances 0.1 0.1 40–80 insomnia, tachycardia, and trembling. The Note that the content of caffeine in Robusta is twice as high moderate consumption of coffee and caffeine as in Arabica (3–4 cups/day) has no harmful effects on health (Table 3). Caffeine absorption by the gastrointestinal tract reaches 99% in 45 min. Caffeine crosses all bio- Coffee/Caffeine and the Central Nervous logical membranes, including the blood–brain bar- System rier and brain concentration is close to plasma Alertness and Sleep concentration. The half-life of caffeine ranges The consumption of 1–4 cups of coffee from 0.7 to 1.2 h in the rat and 2.5–4.5 h in (100–400 mg caffeine) daily increases alertness, humans. It is reduced by 30–50% in smokers, proportionally to the quantity absorbed. This effect increased twofold by oral contraception, and is particularly marked after sleep deprivation considerably prolonged during the third trimester and when alertness is decreased as during the of pregnancy, as well as in the newborn and infant post-lunch dip, night and shift work, and regular less than 6 months old. cold. Caffeine acts as an antagonist at adenosine A moderate consumption – 1–2 cups of coffee receptors. Adenosine is a neuromodulator that before bedtime – leads to difficulties and delays regulates the release of neurotransmitters, mainly in going to sleep up to 3 h post intake. It also excitatory. Among the four types of adenosine decreases the temporal organization of slow and receptors, A1, A2A, A2B, and A3, caffeine dis- REM sleep and the quality of deep sleep. The plays most of its biological effects by binding to consequences are night awakenings, nightmares, A1 and A2A receptors. The antagonism at these difficulties to stand up, and sleepiness during the receptors explains the stimulatory effects on caf- day. The effects vary and are more marked in feine on brain activity (Fredholm, B€attig, elderly and occasional consumers. Moreover, Holme´n, Nehlig, & Zvartau, 1999). the polymorphism of the gene coding for Coffee Drinking, Effects of Caffeine 435 C

Coffee Drinking, Effects of Caffeine, Table 3 Summary of the effects of coffee/caffeine on the cancer of different organs Type of Number of cancer studies Effects of coffee Doses Colorectal 5 cohort; 15 24–60% risk reduction except in 3 cohorts >3 cups/day case–control Liver 20 cohort; 11 30–55% risk reduction From 1 to 2 cups/day dose- C case–control dependent effect Stomach 23 studies No effect Pancreas 37 studies No effect Esophagus 17 studies No effect Risk increased in some studies because of the temperature of the drink Upper 9 studies 39% risk reduction 4 cups/day aerodigestive tract Breast 5 recent No effect after menopause; 40% risk reduction 4 cups/day studies before menopause even with increased genetic risk Ovary 11 studies No effect Endometrial 5 studies 60% risk reduction 3 cups/day Prostate 11 studies No effect Kidney 26 studies No effect Bladder 43 studies No effect <5 cups/day Increased risk >5 cups/day Link with tap water No dose-dependent effect Skin 5 studies Risk reduction if caffeine is applied topically

the A2A adenosine receptor determines the does not directly improve learning and memory interindividual sensitivity to the effects of abilities. These effects seem rather indirect and caffeine on sleep (Rogers et al., 2010). linked to better concentration and capacity to focus attention (Nehlig, 2010). Sensory and Intellectual Abilities A moderate consumption of coffee (1–4 cups per Anxiety and Pain day) facilitates cognitive functions, while higher Beyond 600 mg in one sitting, caffeine increases intake has rather negative effects on intellectual anxiety. The response largely differs between indi- function. These effects depend on sex, age, time viduals and there is a link between the state of of the day, and whether consumption is chronic or anxiety and two polymorphisms of the gene coding not. Low caffeine consumption increases sensory for A2A adenosine receptors (Rogers et al., 2010). and perceptive discrimination abilities. Attention Moderate caffeine consumption reduces ten- is increased even at low levels of intake, 100 mg sion headache, migraine, dental and abdominal caffeine (1 cup of coffee), markedly in pain through its analgesic effects, directly sleep-deprived subjects. via adenosine receptors and indirectly by the Up to 4 cups/day, coffee decreases reaction potentiation of the analgesic action of aspirin time. The effects are more prominent in and ibuprofen (Nehlig, 2004). suboptimal conditions, as at awakening, at night, in fatigued subjects, during long-lasting Caffeine and Dependence tasks, and in occasional consumers. The effects The abrupt cessation of caffeine intake may lead depend on dose and consumption habits. Caffeine to moderate withdrawal symptoms but only in C 436 Coffee Drinking, Effects of Caffeine about 10–20% of the population. These are mean estimated risk between coffee/caffeine con- mainly headaches, fatigue, lack of concentration, sumption and the development of AD is reduced anxiety, irritability, and occasionally, nauseas. by 23% for consumers compared to noncon- They start usually 12–24 h after abrupt caffeine sumers. The lowest risk to develop AD is found cessation and last 2–3 days. They do not occur if in consumers of 3–5 cups of coffee daily. The caffeine consumption is reduced progressively. confirmation of the reduction of the risk of AD by There is no tolerance to the central effects of coffee/caffeine consumption still needs prospec- caffeine. tive studies including more cases (Santos et al., Furthermore, caffeine does not activate the 2010). cerebral circuits of dependence, neither in In transgenic mice developing AD, the chronic humans after the consumption of 200 mg caffeine addition of caffeine to drinking water at a dose (2 cups of coffee) nor in rats at doses mimicking equivalent to 5 cups of coffee daily improves human levels of intake, i.e., 0.5–5.0 mg/kg (½ to learning and memory, and reduces the concentra- 5 cups of coffee). Caffeine has rather reinforcing tions of Ab peptide in hippocampus, the cerebral properties on its consumption. Doses of caffeine region that controls memory. Moreover, caffeine from tea or coffee (40–100 mg) appear sufficient drinking in aged mice with AD allows reversing to act as reinforcers (Nehlig, 2004). the working memory deficit and reducing cerebral Ab peptide concentration (Arendash & Coffee/Caffeine and Cognition: Normal and Cao, 2010). Pathological Aging Cognitive functions (reaction time, rate of per- Caffeine and Parkinson’s Disease ception, and treatment of information) remain The consumption of coffee and caffeine reduces stable until 60 and slow down between 60 and the relative risk (RR) to develop Parkinson’s dis- 80. Cognitive decline is accelerated by poor life- ease (PD). There is a global 25% decreased risk style, vascular diseases, genetic factors, oxidative of developing PD in coffee/caffeine consumers stress, and inflammation. versus nonconsumers with risk reductions up to 80% for the intake of 4 cups of coffee daily. The Normal Age-Related Cognitive Decline preventive effect is linked to caffeine since regu- Lifelong caffeine consumption allows improving lar coffee, tea, and caffeine decrease the risk cognitive functions (reaction time, verbal and while decaffeinated coffee does not (Costa, visuospatial memory) in elderly subjects. Some Lunet, Santos, Santos, & Vaz-Carneiro, 2010). studies reported positive effects in both sexes In women, data are less clear. In those not while others only observed an effect in women. taking hormonal therapy, coffee is as preventive The positive effect of coffee/caffeine is most as in men. In women taking hormones, caffeine is prominent in the oldest subjects, over 80. This preventive in low consumers while the risk is association is not found with decaffeinated coffee, increased fourfold in those drinking 6 cups of indicating the role of caffeine and is significant for coffee or more daily compared to nonconsumers consumptions as low as 2–3 cups of coffee/day. (Ascherio et al., 2003). These differences could Thus, the usual consumption of coffee/caffeine be linked to the polymorphism of the gene coding over lifetime could increase the cognitive reserve for one enzyme of caffeine metabolism (CYP1A2 of elderly subjects (Ritchie et al., 2007; Santos, rs762551) and to an interaction between caffeine Costa, Santos, Vaz-Carneiro, & Lunet, 2010). and some forms of estrogen receptors (Palacios et al., 2010). Coffee and Alzheimer’s Disease The mechanism involved in the preventive Alzheimer’s disease (AD) is the most frequent effect of caffeine in PD is its antagonism at cause of dementia, leading to progressive cogni- A2A adenosine receptors. Caffeine improves par- tive decline. AD is characterized by elevated kinsonian symptoms and potentiates the effects brain levels of b-amyloid peptide (Ab). The of L-dopa, the classical treatment of PD. Coffee Drinking, Effects of Caffeine 437 C

Coffee and the Cardiovascular System Coffee and Cancer Coffee has negative effects on some biological Cancers of the Digestive Tract markers of risk of coronary heart disease (CHD). Lifelong consumption of coffee reduces the risk Paradoxically, a high coffee consumption does of developing liver cancer by 38 a` 59% compared not increase the risk of CHD. A recent meta- to nonconsumers. The underlying mechanisms analysis of 21 prospective cohort studies showed remain to be clarified (Arab, 2010; Cadden, that compared to low consumption (<1 cup/day Partovi, & Yoshida, 2007; Nkondjock, 2009). C in the USA and <2 cups/day in Europe), the The risk of colorectal cancer is reduced by combined relative risk (RR) of CHD for moderate 17%incoffeeconsumersandupto30%in coffee consumption (3–5 cups daily) is signifi- highest consumers. This protection linked to cantly reduced by 18% in women and 13% in coffee seems to involve the anticarcinogenic men (Wu et al., 2009). properties of the diterpenes and antioxidants Likewise, in large populations with a long of coffee, the stimulation of the secretion of follow-up there is no influence of coffee (less than biliary acids and neutral sterols in the colon, 5 cups/day) on the risk of heart failure (RR 0.87 for and the stimulation of colon motility (Galeone 2 cups/day) and RR 0.89–0.94 for all other levels et al., 2010). (at least 3 cups/day) compared to men consuming There is no association between coffee con- less than 1 cup/day, confirming the lack of effect of sumption and the risk of developing stomach or moderate coffee consumption on heart failure pancreas cancer. There is no evidence to support (Ahmed, Levitan, Wolk, & Mittleman, 2009). a harmful effect of coffee consumption on pros- Furthermore, the consumption of coffee tate cancer risk. Caffeine intake does not change does not increase the risk of atrial fibrillation or the risk of esophagus or larynx cancer and flutter whatever be the dose. Even consumers reduces the risk of oral cavity or pharynx cancer of 1–3 cups or more than 4 cups of coffee by 39% for the consumption of 4 cups of coffee/ daily reduce their risk of arrhythmias by 7 or day (Turati et al., 2011). 18%, respectively, compared to nonconsumers (Klatsky et al., 2010). Breast, Ovary, and Endometrial Cancer Coffee intake increases systolic and diastolic In postmenopausal women, there is usually no blood pressure by 1.2 and 0.5 mmHg, respec- relation between caffeine/coffee intake and tively. At an equivalent dosage, caffeine intake breast cancer. During premenopause, the risk has a more marked hypertensive effect (4.2 and reduction reaches 50% in women consuming at 2.4 mmHg, respectively). However, coffee is not least 4 cups coffee daily compared to low con- considered a risk factor for arterial hypertension. sumers (1–2 cups/day). Also, in premenopausal Boiled coffee has the strongest effect, followed women that carry the BRCA1 or BRCA2 muta- by filtered and instant coffee; decaffeinated tion, which increases the risk of breast cancer, the coffee increases systolic blood pressure by risk is reduced by 25–70% by a consumption of 0.9 mmHg and decreases diastolic pressure by 4–6 cups of coffee daily. This beneficial effect is 0.15 mmHg (Noordzij et al., 2005). limited to caffeinated coffee (Arab, 2010). Filtered, instant coffee, and espresso do not While there is no relation between significantly modify lipid metabolism while unfil- coffee/caffeine intake and ovary cancer, coffee tered boiled coffee increases total cholesterol, consumption of at least 3 cups daily reduces the mainly the low-density lipoproteins and triglycer- risk of developing endometrial cancer by 60% ides, and should be avoided (Thelle, 2005). (Arab, 2010). In conclusion, there is no apparent cardiovas- cular risk linked to coffee consumption, except Prostate, Kidney, Bladder, and Skin Cancer possibly in some patients at risk that should also Prostate cancer and kidney cancer are not stop smoking, increase physical exercise, and influenced by the duration or quantity of coffee improve their diet. consumed (Arab, 2010; Park et al., 2010). C 438 Coffee Drinking, Effects of Caffeine

The most recent data on bladder cancer Caffeine, Fertility, Pregnancy, Fetal and report a lack of association in women and 26% Neonatal Growth increased risk in men consuming coffee. How- The effects of coffee ingestion on various param- ever, a critical risk factor is linked to the type of eters of reproduction, pregnancy, and fetal devel- waterusedtopreparecoffee.Chlorinatedtap opment were reviewed recently (Peck, Leviton, & water increases bladder cancer while mineral Cowan, 2010). water does not. The results of most epidemio- logical studies allow now excluding a strong Effects on Fertility relation between coffee and bladder cancer. In natural pregnancies, there is no link between The major risk factors are smoking and other caffeine consumption and reduction of fertility. dietary factors (Arab, 2010; Pelluci et al., Likewise, caffeine does not influence the number 2010). of ovocytes collected and fertilized, the number In mice, caffeine added to drinking water or of embryos transferred and successfully reaching topically destroys skin cells damaged by UVB term in in vitro fecundations. For male fertility, irradiation. Caffeine also doubles the mortality there is no association between caffeine intake of human skin cells damaged by UVB, and and the number, mobility, morphology, DNA hence could decrease the risk of skin cancer. status of spermatozoids, and the onset of preg- The underlying molecular mechanism is simi- nancy (Peck et al., 2010). lar in both species and leads to the hypothesis that caffeine applied topically could potentially Effects on the Course of Pregnancy protect human skin against the harmful effect Caffeine ingested by the mother is very rapidly ofUVB(Heffernanetal.,2009;Luetal., absorbed, crosses the placental barrier, and dis- 2008). tributes in all fetal tissues, including the central nervous system. The half-life of caffeine is dra- Coffee and Type 2 diabetes matically increased in the fetus (over 100 h) Since 2002, over 20 studies devoted to the rela- deprived of the enzymatic equipment necessary tion between coffee consumption and the risk of for caffeine catabolism. developing type 2 diabetes reported a largely Most studies did not find any association reduced risk linked to frequent coffee intake between a daily caffeine intake lower than across diverse populations. It is similar in men 300 mg (3 cups of coffee) and the risk of miscar- and women, obese and nonobese subjects. Most riage. Moreover, when accounting for the sever- studies suggest a dose–response curve with larger ity of nauseas that often lead to a reduction in risk reductions for high coffee intake. In general, coffee/caffeine consumption, the RR for miscar- the consumption of at least 4 cups daily is asso- riages drops from 1.5 to 1.7 for a daily caffeine ciated to a 30–40% decreased risk of type 2 consumption of 300–500 mg to 1.0–1.1. diabetes compared to nonconsumers. For lower Recently, a RR of 2.2 for miscarriages was intakes, the risk decreases by 7% for each addi- found at a caffeine intake higher than 200 mg/ tional coffee cup. This inverse association is day. However, this study did not carefully control observed with caffeinated and decaffeinated cof- for confounding factors such as degree of fee, with or without sugar but not with caffeine smoking and duration of the nausea period. By alone. caution, several associations advised women who Antioxidants from coffee, such as chlorogenic wish to start a pregnancy to limit their caffeine and quinic acids, are potential candidates for this intake to quantities lower than 200 mg/day, while preventive effect since they can act as regulators others maintained the earlier limit of 300 mg/day. of carbohydrate metabolism (Huxley et al., 2009; The vast majority of studies did not find any Pimentel, Zemdegs, Theodoro, & Mota, 2009; association between caffeine and fetal growth van Dam et al., 2008). whatever the dose. After adjustment for smoking Coffee Drinking, Effects of Caffeine 439 C and alcohol, a few studies observed fetal growth sensing pain or exertion is increased. Likewise, retardation for caffeine intake ranging from in team sports like rugby, soccer, and field hockey 300 to 800 mg/day. Fetal growth is more sensitive that alternate prolonged activity with bouts to caffeine during the first than during the third of intense activity, caffeine supplementation trimester of pregnancy and intrauterine growth provides beneficial effects. Caffeine is also retardation is only significant over 600 mg/day beneficial in long-distance swimming, rowing, caffeine. There is no consistent report of an asso- and middle and distance running races. In brief, C ciation between total exposure to caffeine and the physical exercise involving strength and power risk of early (34 gestational weeks) or late such as lifts, throws, and sprints the effects of premature delivery (35–37 weeks) (Peck et al., caffeine are less clear and variable. Women also 2010). benefit from caffeine in sports activities ranging Animal data showed dose-dependent terato- from recreational activities to rowing competi- genic effect of caffeine, only at very high doses, tions, mainly when trained and moderately active over 80 mg/kg (60–80 cups of coffee in one (Burke, 2008). sitting). In humans, no study reported any increase The effective dose of caffeine depends on the in the incidence of congenital malformations level of training, habituation to caffeine, and type in babies born from women consuming large of exercise. Usually, the efficacy of caffeine is quantities of caffeine (300–1,000 mg/day) during optimal at doses of 1.5–4.5 mg/kg in noncon- their whole pregnancy. sumers, 3–6 mg/kg in moderate consumers, and 6.5–9.5 mg/kg in high consumers. The ergogenic Effects on Postnatal Development effects of caffeine are more variable when caffeine Caffeine enters maternal milk but has no conse- is absorbed in a drink like coffee compared to the quence on its composition and stimulates its pro- anhydrous form (capsules or tablets) (Burke, duction. Hence, women are advised to consume 2008; Astorino & Robertson, 2010). their coffee after instead of before lactating. The effects of caffeine on muscle metabolism Studies on psychomotor development are are still unclear. Caffeine was suggested to mobi- reassuring. The prenatal consumption of caffeine lize fatty acids from adipose tissue to spare muscle does not influence the Apgar score, suction reflex, glycogen. In reality, it seems that caffeine has weight, height, or psychomotor behavior assessed rather a central effect central on fatigue or facili- during the first year. No effect could be shown on tates muscle function. Caffeine co-ingested with the intellectual quotient, motor skills, or vigilance carbohydrates can enhance their absorption and at 4 and 7 years (Nehlig & Debry, 1994). oxidation during exercise. In endurance cycling, In conclusion, a moderate caffeine consump- golf, and team sports, performance is more largely tion (lower than 200/300 mg/day), in all forms, improved by caffeine + carbohydrates than by does not seem to notably influence fertility and either constituent given alone. Caffeine reduces fetal growth. There is still some doubt for higher also pain in caffeine consumers as found in dosages and it is wise to recommend women that cycling, leg and arm muscle training, and other wish to start a pregnancy, or are pregnant, not to endurance activities (Goldstein et al., 2010). go over the reasonable limit of 200/300 mg/day caffeine. Conclusion The data presented here reflect a large number Caffeine and Sports Activity of studies performed over the last decade on Most studies reported positive effects of caffeine coffee and health. This wealth of data on performance in endurance tests; the distance allowed the evolution from the negative idea covered over a given time or speed in running and that coffee/caffeine could not be good for health cycling are increased, the efficacy in final because the consumer was enjoying these drinks sprinting is improved and the delay before too much. It is now widely accepted that C 440 Coffee Drinking, Effects of Caffeine the moderate consumption of caffeine (3–4 cups ▶ Reproductive Health coffee daily) in the context of a balanced diet has ▶ Risk Ratio no negative impact on human health. In fact, on ▶ Sex Differences the basis of the data on normal cognitive decline, ▶ Sleep Parkinson’s and Alzheimer’s disease, type 2 ▶ Sleep Quality diabetes, and cancer, the consumption of coffee ▶ Slow-Wave Sleep appears even beneficial for human health. ▶ Systolic Blood Pressure (SBP) ▶ Tachycardia ▶ Type 2 Diabetes mellitus Cross-References

▶ Aging ▶ Alzheimer’s Disease References and Readings ▶ Antioxidant ▶ Ahmed, H. N., Levitan, E. B., Wolk, A., & Anxiety Disorder Mittleman, M. A. (2009). Coffee consumption and ▶ Arrhythmia risk of heart failure in men: An analysis from the ▶ Aspirin Cohort of Swedish Men. American Heart Journal, ▶ Atrial Fibrillation 158, 667–672. ▶ Arab, L. (2010). Epidemiologic evidence on coffee and BRCA1 and BRCA2 cancer. Nutrition and Cancer, 62, 271–283. ▶ Breast Cancer Cadden, I. S., Partovi, N., & Yoshida, E. M. (2007). ▶ Cancer and Diet Review article: Possible beneficial effects of coffee ▶ Cancer, Bladder on liver disease and function. Alimentary Pharmacol- ▶ ogy & Therapeutics, 26, 1–8. Cancer, Colorectal Costa, J., Lunet, N., Santos, C., Santos, J., & Vaz- ▶ Cancer, Ovarian Carneiro, A. (2010). Caffeine exposure and the risk ▶ Cancer, Prostate of Parkinson’s disease: A systematic review and meta- ▶ Cancer, Types of analysis of observational studies. Journal of ▶ Alzheimer’s Disease, 20(Suppl. 1), S221–S238. Cardiovascular Disease Fredholm, B. B., B€attig, K., Holme´n, J., Nehlig, A., & ▶ Central Nervous System Zvartau, E. E. (1999). Actions of caffeine in the brain ▶ Cognitive Function with special reference to factors that contribute to its ▶ Cognitive Impairment widespread use. Pharmacological Reviews, 51, ▶ 83–133. Coronary Heart Disease Nehlig, A. (2010). Is caffeine a cognitive enhancer? Jour- ▶ Dementia nal of Alzheimer’s Disease, 20(Suppl. 1), S85–S94. ▶ Diabetes Nkondjock, A. (2009). Coffee consumption and the risk of ▶ Diastolic Blood Pressure (DBP) cancer: An overview. Cancer Letters, 277, 121–125. ▶ Noordzij, M., Uiterwaal, C. S., Arends, L. R., Kok, F. J., Elderly Grobbee, D. E., & Geleijnse, J. M. (2005). Blood ▶ Estrogen pressure response to chronic intake coffee and caf- ▶ Gender Differences feine: A meta-analysis of randomized controlled trials. ▶ Genetic Polymorphisms Journal of Hypertension, 23, 921–928. ▶ Palacios, N., Weisskopf, M., Simon, K., Gao, X., Heart Failure Schwarzschild, M., & Ascherio, A. (2010). Polymor- ▶ Hormone Treatment phisms of caffeine metabolism and estrogen receptor ▶ Hypertension genes and risk of Parkinson’s disease in men and ▶ Migraine Headache women. Parkinsonism & Related Disorders, 16, ▶ 370–375. Neurotransmitter Park, C. H., Myung, S. K., Kim, T. Y., Seo, H. G., Jeon, ▶ Pain Management/Control Y. J., Kim, Y., et al. (2010). Coffee consumption ▶ Parkinson’s Disease and risk of prostate cancer: A meta-analysis of epide- ▶ Physical Activity miological studies. BJU International, 106, 762–769. ▶ Peck, J. D., Leviton, A., & Cowan, L. D. (2010). A Relative Risk review of the epidemiologic evidence concerning ▶ REM Sleep the reproductive health effects of caffeine Cognitive Abilities 441 C

consumption: A 2000–2009 update. Food and Chem- As cognitions play a fundamental role in ical Toxicology, 48, 2549–2576. determining behavior, the study of cognitive fac- Pimentel, G. D., Zemdegs, J. C., Theodoro, J. A., & Mota, J. F. (2009). Does long-term coffee intake reduce type tors facilitates a better understanding of processes 2 diabetes mellitus risk? Diabetology and Metabolic and outcomes in health, health behavior, illness, Syndrome, 1,6. and disability. Examples of cognitions with par- Santos, C., Costa, J., Santos, J., Vaz-Carneiro, A., & ticular relevance for behavioral medicine include Lunet, N. (2010). Caffeine intake and dementia: Sys- C tematic review and meta-analysis. Journal of illness perceptions (Leventhal, Diefenbach, & Alzheimers Disease, 20(Suppl. 1), S187–S204. Leventhal, 1992); biases and distortions in Wu, J. N., Ho, S. C., Zhou, C., Ling, W. H., Chen, W. Q., decision making (Kahneman & Tversky, 1979); Wang, C. L., et al. (2009). Coffee consumption and attitudes, beliefs, and perceptions of control risk of coronary heart diseases: A meta-analysis of 21 prospective cohort studies. International Journal of (Ajzen, 1991); and the executive functions Cardiology, 137, 216–225. (Williams & Thayer, 2009).

Cross-References Cognition ▶ Beliefs ▶ Cognitive Factors ▶ Cognitive Factors ▶ Cognitive Function ▶ Cognitive Function ▶ Cognitive Impairment ▶ Cognitive Mediators Cognitions ▶ Cognitive Strategies

Julia Allan School of Medicine and Dentistry, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK References and Readings

Ajzen, I. (1991). The theory of planned behaviour. Organizational Behavior and Human Decision Synonyms Processes, 50, 179–211. Conner, M., & Norman, P. (2005). Predicting health behav- Ideas; Thoughts iour: Research and practice with social cognition models (2nd ed.). Buckingham: Open University Press. Eysenck, M. W., & Keane, M. T. (2010). Cognitive Psychology: A student’s handbook (6th ed.). London: Definition Psychology Press. Kahneman, D., & Tversky, A. (1979). Prospect theory: An Cognitions are internal mental representations analysis of decision under risk. Econometrica, 47, 263–292. best characterized as thoughts and ideas. Leventhal, H., Diefenbach, M., & Leventhal, E. A. (1992). Cognitions result from, and are involved in, mul- Illness cognitions: Using common sense to understand tiple mental processes and operations including treatment adherence and affect cognition interactions. perception, reasoning, memory, intuition, judg- Cognitive Therapy and Research, 16, 143–163. Williams, P. G., & Thayer, J. F. (2009). Executive func- ment, and decision making. tioning and health: An introduction to the special As internal mental states, cognitions are not series. Annals of Behavioral Medicine, 37, 101–105. directly observable but are still amenable to study using the scientific method. Cognitions can be subjectively elicited on questioning or experi- mentally measured using reaction times, psycho- Cognitive Abilities physical responses, or real-time neuroimaging techniques to infer internal processing. ▶ Coffee Drinking, Effects of Caffeine C 442 Cognitive Appraisal

make a secondary appraisal in regard to harm Cognitive Appraisal (harm-loss), threat, or challenge. • Secondary appraisal refers to the evaluation Tavis S. Campbell, Jillian A. Johnson and of an individual’s ability or resources to cope Kristin A. Zernicke with a specific situation. Secondary appraisal Department of Psychology, University of interacts with primary appraisal to determine Calgary, Calgary, AB, Canada emotional reaction to a situation. A harm (harm-loss) appraisal is the assessment that damage has occurred as a result of the situa- Synonyms tion and the necessary resources to effectively cope with the situation may not be available. Lazarus theory; Transactional model Threat appraisals occur when it is anticipated that the situation may result in loss or harm in the future and the resources to effectively cope Definition with the situation may not be available. A challenge is perceived when a situation is The concept of cognitive appraisal was advanced demanding but ultimately can be overcome, in 1966 by psychologist Richard Lazarus in the resulting in the individual benefiting from the book Psychological Stress and Coping Process. situation. Both harm and threat appraisals According to this theory, ▶ stress is perceived as result in the situation being deemed as stress- the imbalance between the demands placed on ful, whereas a challenge appraisal does not. the individual and the individual’s resources to • Reappraisal is the continuous reevaluation of cope (Lazarus & Folkman, 1984). Lazarus argued a situation based on the availability of new that the experience of stress differs significantly information. This step of reappraisal takes between individuals depending on how they place throughout the entire process and can interpret an event and the outcome of a specific change the way an individual perceives a sequence of thinking patterns, called appraisals situation. (Lazarus, 1991). Cognitive appraisal refers to the personal interpretation of a situation that ultimately influ- References and Readings ences the extent to which the situation is per- ceived as stressful. It is the process of assessing Folkman, S., Lazarus, R. S., Dunkel-Schetter, C., (a) whether a situation or event threatens our DeLongis, A., & Gruen, J. (1986). Dynamics of a stressful encounter: Cognitive appraisal, coping and well-being, (b) whether there are sufficient per- encounter outcomes. Journal of Personality and Social sonal resources available for coping with the Psychology, 50(5), 992–1003. demand of the situation, and (c) whether our Folkman, S., Lazarus, R. S., Gruen, J., & DeLongis, A. strategy for dealing with the situation is effective (1986). Appraisal, coping, health status, and psychological symptoms. Journal of Personality and (Lazarus, 1991). This process can then be further Social Psychology, 50(3), 571–579. subdivided into three categories: primary appraisal, Lazarus, R. S. (1991). Emotion and adaptation. secondary appraisal, and reappraisal: New York: Oxford University Press. • Primary appraisal refers to the initial evalua- Lazarus, R. S., & Folkman, S. (1984). Stress, appraisal, and coping. New York: Springer. tion of the situation, deemed as benign positive (positive), threatening (negative), or irrelevant (neutral). If the situation is appraised as being irrelevant or benign positive, no heightened physiological arousal occurs and the situation Cognitive Behavior Therapy will not be perceived as stressful. If the situation is appraised as negative, the individual will ▶ Cognitive Behavioral Therapy (CBT) Cognitive Behavioral Therapy (CBT) 443 C

first of the cognitive interventions to appear; it Cognitive Behavioral Therapy (CBT) introduced a novel, directive approach to chal- lenging patients’ irrational beliefs. Beck’s cogni- Lara Traeger tive therapy also emphasized a primary role of Behavioral Medicine Service, Massachusetts cognitions in psychiatric problems, and he for- General Hospital/Harvard Medical School, mally described the maladaptive cognitive biases Boston, MA, USA associated with depression as targets for thera- C peutic change. The coalescence of cognitive and behavioral Synonyms therapies over the past few decades has been due to several factors, including the challenges of Cognitive behavior therapy applying behavior theory to the complex range of human behaviors (for example, obsessional think- ing), the introduction of a formalized cognitive Definition therapy for depression, and the growing support for CBT interventions in both research and prac- Cognitive behavioral therapy is a classification of tice. Behaviorists view behavior change as the pri- psychotherapies which integrate cognitive and mary goal of therapy, whereas cognitive theorists behavioral theories and methods. CBT approaches view behavior strategies as means for affecting share fundamental assumptions that cognitions change. Yet both schools share a commitment to mediate situational responses and that changes in applying the scientific method to clinical problems cognitive activity can affect therapeutic changes and their treatments. Since the early works which in emotions and behaviors. focused primarily on depression and anxiety, CBT models have since been expanded to explain and treat a wide range of psychiatric disorders. Description A number of membership organizations sup- port CBT research and practice, and their histo- Brief History of CBT ries reflect the history of CBT itself. For instance, CBT interventions represent an integration of in 1966, the Association for Advancement of behavioral and cognitive theories and methods. Behavioral Therapies (AABT) was founded by Behavior therapy emerged in the 1950s and behaviorists due to their dissatisfaction with the 1960s through research on clinical applications psychoanalytic model. The name was formally of classical and operant conditioning theories changed to the Association for Behavioral and (e.g., systematic desensitization; Eysenck, 1966; Cognitive Therapies (ABCT) in 2005, to reflect Wolpe, 1958). Behavior therapy emphasizes the the increasing influence of cognitive theory primacy of behaviors, and radical behaviorists and methods. Similarly, the British Association view thoughts as a type of internal behavior. for Behavioural Psychotherapy (BABP) was The primacy of thoughts in shaping situational founded by behaviorists in 1972; its scope was responses appears in early philosophical tradi- broadened in 1992 when it became The British tions ranging from Stoicism to Buddhism Association for Behavioural and Cognitive (Wright et al., 2006). Formally, the cognitive Psychotherapies (BABCP). underpinnings of CBT emerged in the 1960s and 1970s, largely through developments by CBT Model of Clinical Symptoms Albert Ellis (rational emotive therapy; 1957) CBT emphasizes the role of individuals as active and Aaron T. Beck (cognitive therapy; 1963, information processors. The meaning we apply to 1964) and contributions from Alfred Adler, a situation shapes our emotional reactions to the George Kelly, and behaviorists described above. situation and what we may do to cope with our Rational emotive therapy has been considered the emotions. Our behaviors, in turn, affect our C 444 Cognitive Behavioral Therapy (CBT) thought patterns and emotional responses. In aspects of health promotion and disease manage- other words, cognitions, emotions, and behaviors ment. Research evidence strongly supports links are intimately linked. These relationships are between cognitions, feelings, and health behav- illustrated in the following scenario: iors. For instance, many chronic medical condi- A supervisor had begun to criticize two tions are associated with elevated risk for employees, J.F. and A.B., for minor errors at depression. Depressed individuals, in turn, have work. J.F. interpreted the situation to mean that difficulties with motivation, interest, and problem he was a poor performer and a liability to his solving, and are therefore less likely to practice department. This caused J.F. to feel dejected, self-care behaviors such as physical activity, which led him to increase his efforts to please healthy eating, and adherence to medical regi- the supervisor. J.F. began to work late at night; mens. The following scenario illustrates these drink more coffee to stay awake; and conse- relationships: quently experience fatigue and anxiety the next S.P. had been prescribed a daily HIV medica- day. This led him to make more errors at work, tion for the past year. She did not believe that the creating a self-fulfilling prophecy which medication did much to manage her condition. strengthened his anxiety and negative beliefs Every morning, she would dread looking at the about himself. Meanwhile, A.B. presumed that medication bottle. It was a reminder that she was the supervisor was simply singling her out for ill, and this reminder provoked other familiar criticism. This caused A.B. to feel irritated, thoughts that her life was over and that she which led her to act indifferently toward the would never find a romantic partner due to her supervisor while maintaining her current level HIV status. These thoughts, in turn, reminded her of work performance. Her relationship with the that she was profoundly alone. For S.P., it was supervisor deteriorated, reinforcing A.B.’s belief easier to ignore the sight of the bottle and skip her that people are generally disrespectful. medication dose, which she frequently did. How- This scenario highlights that two different ever, the thoughts remained and often provoked interpretations without clear evidence led to painful depressed moods which decreased her quite different emotional and behavioral conse- motivation and energy to answer phone calls quences. These interpretations also could rein- from her friends. S.P. spent most of her time at force longstanding negative beliefs about the home alone, which reinforced her beliefs about self (in the case of J.F.) or the world (in the case being undesirable to others. Most recently, she of A.B.). This is a key learning point for individ- missed her regular HIV primary care visit. It uals during therapy. In the long term, entrenched seemed too difficult to secure a ride to the clinic, patterns or styles of thinking and behaving can and she thought, “What’s the point anyway, this become associated with clinically significant dis- disease is not going away.” tress. Indeed, psychiatric disorders are distin- This scenario shows bidirectional relation- guished by distinct profiles of cognitive and ships between depression and poor HIV self- behavioral bias. In his original work, Aaron T. care. In practice, the CBT case formulation Beck described depression as the result of nega- would address how inaccurate cognitions, emo- tive thinking about the self, world, and future tional distress, and coping behaviors are influenc- (1963, 1964). Other examples include phobias ing each other in a perpetuating loop, which as the inaccurate perceptions of danger, and serves to maintain both depression and poor suicidality as the perception of hopelessness and self-care. The case formulation would also help deficits in problem-solving skills. to highlight key areas for CBT intervention to break this loop. In developing the CBT treatment Applications of the CBT Model in plan, a therapist may draw systematically from Behavioral Medicine CBT strategies, including: (1) providing psycho- The CBT model can be particularly useful in education about depression, HIV, and HIV med- behavioral medicine, to capture biopsychosocial ications; (2) increasing engagement in activities Cognitive Behavioral Therapy (CBT) 445 C which promote enjoyment and sense of mastery; a patient on long-acting pain medications may (3) challenging severe negative beliefs; and benefit from understanding the impact of missed (4) problem-solving medical adherence. This or delayed medication doses. approach highlights that all three domains (cog- Behavioral strategies are used to help patients nitions, emotions, and behaviors) are being break unhelpful behavior patterns such as fear addressed. Common CBT intervention elements avoidance or depressive inactivity. For example, are described further in the next section. exposure methods involve generating a hierarchy C of situations that induce fear and avoidance, and Common Elements of CBT Interventions conducting structured “experiments” which In CBT interventions, the therapist actively col- increase real-life or imaginal exposure to these laborates with the patient (i.e., “co-therapist”). situations. In behavioral activation, the patient is They work together to identify and alter problem- guided to increase activity level by generating atic patterns of thinking and behaving, and a list of activities that promote enjoyment and thereby help the patient manage negative emo- sense of mastery, and then setting and monitoring tions and improve quality of life. The therapist daily or weekly activity goals. first collects information about the patient’s Cognitive strategies are used to promote presenting problems, and then shares and revises optimal thinking about difficult situations. As the CBT case formulation with the patient. a primary example, cognitive restructuring is This formulation directly informs the therapy. a framework for recognizing negative, inaccurate The therapist and patient work together to set thoughts and replacing them with alternative ones a treatment plan and articulate goals at the that are more realistic and helpful. This may outset of therapy, and to set agendas at each involve several steps: write down the situation; therapy session. During the course of CBT, the list negative thoughts that occurred during the therapist may use Socratic questioning to guide situation; list emotions that arise when having patients in their own discovery of problematic these thoughts; identify cognitive distortions or patterns in their thinking and behaving. Sessions errors that may underlie each thought; challenge are problem oriented and typically focus on each thought; and generate rational responses. building skills which address these patterns. The rational responses are self-statements that “Homework” assignments encourage the patient are used to reduce distress and view situations to rehearse and problem-solve the skills in real- in a more helpful light. life situations. Throughout treatment, progress is monitored using symptom inventories (for exam- Considerations for CBT in Behavioral ple, the Beck Depression Inventory [BDI] or the Medicine Populations Hospital Anxiety and Depression Scale [HADS]) CBT interventions have been incorporated into as well as informal feedback. Most CBT inter- the American Psychiatric Association clinical ventions are intended to be time limited; the practice guidelines for a wide range of psychiat- ultimate goal is for patients to become increas- ric disorders. However, chronic medical condi- ingly independent in their use of the skills until tions introduce some unique aspects to consider the therapist is no longer needed. during CBT evaluation and delivery. Psychiatric The following is a sample of common CBT symptoms can overlap with or mask intervention strategies: disease symptoms and treatment side effects Psycho-education is used throughout CBT (for example, cancer-related fatigue, dyspnea, or interventions. A critical component of CBT is to uncontrolled pain), underscoring the importance engage patients in understanding the CBT model, of assessment and differential diagnosis for the rationale for treatment, and the therapeutic behavioral medicine patients. Also, health cogni- methods as applied to their clinical problems. In tions and emotional distress levels can be other examples, CBT for panic disorder includes dynamic, changing over time in response to information on physiologic activation, whereas disease-related events (for example, receiving C 446 Cognitive Behavioral Therapy (CBT) medical test results), uncertain disease courses, or CBT Applications in Behavioral Medicine certain disease progression. For many medical There is growing evidence to support CBT inter- conditions, disease symptoms fluctuate, influenc- ventions to improve health behaviors, enhance ing mobility, fatigue, and cognitive functioning. quality of life, and reduce psychological symptoms Adaptations to CBT protocols have been among individuals with medical comorbidities. For recommended to incorporate these factors. For instance, Safren, Gonzalez and Soroudi (2008) instance, behavioral activation and homework developed a CBT intervention for depression and assignments can be adapted so that patients mod- medical adherence (CBT-AD) in patients with ulate daily activities according to current level of chronic illness such as diabetes or HIV. Cognitive energy (activity pacing). Cognitive restructuring behavioral stress management (CBSM) is a group can be supplemented with acceptance-based or intervention developed by Antoni, Schneiderman problem-solving strategies when negative health and Ironson (2007) to improve quality of life in cognitions reflect both realistic and unrealistic HIV-infected adults, which has since been adapted elements, and both controllable and uncontrolla- for cancer survivors (Penedo, Antoni, & ble stressors. Schneiderman, 2008). CBT strategies have also For the sample scenario of S.P., described been adapted to treat or reduce disability associated above, a CBT intervention might proceed as with a range of specific medical concerns. Exam- follows: ples include nicotine dependence, obesity, chronic The therapist worked with S.P. to generate illness rehabilitation, hypertension, and various a CBT model of her depression and problems functional pain and fatigue conditions. For with HIV self-care. Socratic questioning was instance, CBT protocols for either nicotine depen- used to help S.P. discover links between her dence or obesity may include goal setting; psycho- thoughts (perceived impact of HIV on her value education; self-monitoring (recording number cig- as a person); feelings (sadness and loneliness); arettes or food intake per day); stimulus control and behaviors (medical non-adherence and self- (reducing contact with environmental cues that isolation). The therapist and S.P. used this model trigger smoking or overeating); and coping skills to develop a treatment plan and set goals. S.P.’s for relapse prevention. main goal was to repair some of the meaningful relationships in her life. The therapist provided psycho-education about depression and Cross-References HIV. S.P. began to internalize that self-care was a step toward improving relationships with others. ▶ Behavior Change Behavioral activation was introduced to help S.P. ▶ Behavioral Therapy increase engagement in activities that she used ▶ Cognitions to enjoy and that could give her opportunities to ▶ Cognitive Distortions challenge her belief that others would reject her. ▶ Cognitive Restructuring Activities were modified on days when S.P. expe- ▶ Cognitive Strategies rienced fatigue or medication side effects. Cogni- ▶ Problem Solving tive restructuring helped S.P. develop healthier ▶ Systematic Desensitization cognitions such as more neutral perceptions of HIV medications. Finally, problem solving was introduced to help S.P. organize her efforts toward References and Readings increasing her adherence and enhancing her social support. While S.P. experienced setbacks, Antoni, M. H., Schneiderman, N., & Ironson, G. (2007). she increasingly began to recognize her tendency Stress management for HIV: Clinical validation and intervention manual. Mahwah, NJ: Lawrence Erlbaum to make devaluing statements about herself during Associates. stressful situations, and she continued to work Beck, A. T. (1963). Thinking and depression. Archives of toward changing this pattern. General Psychiatry, 9, 324–333. Cognitive Factors 447 C

Beck, A. T. (1964). Thinking and depression, II: Theory and therapy. Archives of General Psychiatry, 10, Cognitive Evaluation Theory 561–571. Dobson, K. S. (Ed.). (2010). Handbook of cognitive- behavioral therapies (3rd ed.). New York: Guilford ▶ Self-determination Theory Press. Ellis, A. (1957). Rational psychotherapy and individual psychology. Journal of Individual Psychology, 13, C 38–44. Eysenck, H. J. (1966). The effects of psychotherapy. Cognitive Factors New York: International Science Press. Kelly, G. (1955). The psychology of personal constructs. Eric Roy New York: WW Norton. Moorey, S., & Greer, S. (2002). Cognitive behaviour Department of Kinesiology, University of therapy for people with cancer. Oxford/New York: Waterloo, Waterloo, ON, Canada Oxford University Press. Penedo, F. J., Antoni, M. H., & Schneiderman, N. (2008). Cognitive-behavioral stress management for prostate cancer recovery: Facilitator guide. Oxford/ Synonyms New York: Oxford University Press. Safren, S. A., Gonzalez, J. S., & Soroudi, N. (2008). Cognition; Cognitive strategy; Cognitive style; Coping with chronic illness: A cognitive-behavioral Mental ability; Mental function therapy approach for adherence and depression: Therapist guide. Oxford/New York: Oxford Univer- sity Press. Wolpe, J. (1958). Psychotherapy by reciprocal inhibition. Definition Stanford, CA: Stanford University Press. Wright, J. H., Basco, M. R., & Thase, M. E. (2006). Learning cognitive-behavioral therapy: an illustrated Cognitive factors refer to characteristics of the guide. London/Washington, DC: American Psychiat- person that affect performance and learning. ric Publishing, Inc. These factors serve to modulate performance such that it may improve or decline. These factors involve cognitive functions like attention, mem- Cognitive Control ory, and reasoning (Danili & Reid, 2006). Cognitive factors are internal to each person ▶ Behavioral Inhibition and serve to modulate behavior and behavioral responses to external stimuli like stress. Perfor- mance on various activities of daily living has been found to be affected by these factors. Exec- Cognitive Deficit utive functions, for example, have been shown to predict ability to live independently in older ▶ Cognitive Impairment adults such that those with poorer executive func- tioning are less able to live independently (Vaughn & Giovanello, 2010). Turning to behav- ioral responses to stress cognitive factors is known Cognitive Disorder to play a role in posttraumatic stress disorder. The nature of the memory of the trauma may play a role ▶ Cognitive Impairment in PTSD, that is, persistent PTSD is often associ- ated with memories of the trauma that are poorly elaborated and not well integrated into the person’s autobiographical memory (Dumore, Clark & Cognitive Distortions Ehlers, 2001). More generally cognitive style may serve as an important cognitive factor. ▶ Cognitive Behavioral Therapy (CBT) Messick (1994) refers to cognitive style as C 448 Cognitive Function characteristic modes of thinking, perceiving, prob- processes underlie how people perceive, remem- lem solving, and remembering that may influence ber, speak, think, make decisions, and solve prob- how a person approaches a problem or task. lems. Cognitive function is a general term used to describe many different functions such as mem- ory and attention thought to be components of the Cross-References mind (Benjafield, Smilek, & Kingstone, 2010).

▶ Cognitions ▶ Cognitive Function Description ▶ Cognitive Impairment ▶ Cognitive Strategy Cognitive functions are internal and are inferred from behavior using measures such as accuracy in performing a task like recalling a list of words or References and Readings the time taken to find some word on a page of text. The study of cognitive functions derives from the Danili, E., & Reid, N. (2006). Cognitive factors can information processing approach which argues potentially affect pupils’ test performance. Chemistry that these functions involve operations occurring Education Research and Practice, 7, 64–83. Dumore, E., Clark, D. M., & Ehlers, A. (2001). at various processing stages. The identification of A prospective investigation of the role of cognitive these processing stages is typically based on factors in persistent posttraumatic stress disorder a model of the cognitive function of interest. (PTSD) after physical or sexual assault. Behavioral Using this model, a task thought to reflect the Research and Therapy, 39, 1063–1084. Messick, S. (1994). The matter of style: Manifestations of cognitive function of interest is manipulated in personality in cognition, learning, and teaching. such a way as to place demands on the processing Educational Psychologist, 29, 121–136. stages identified. If we use memory as an example, Vaughn, L., & Giovanello, K. (2010). Executive function the task of recalling a list of words can be manip- in daily living: Age related influences of executive processes on instrumental activities of daily living. ulated to place demands on two processing stages: Psychology and Aging, 25, 343–355. encoding or putting words into memory or retrieval involving retrieving words from memory. The encoding stage is emphasized when demands are placed on just recognizing whether words Cognitive Function presented were in the list, while the retrieval stage is emphasized when demands are placed on Eric Roy recalling the words from the list. The study of Department of Kinesiology, University of cognitive functions then involves the use of exper- Waterloo, Waterloo, ON, Canada imentation through manipulation of task demands. This use of the scientific method spawned the development of another subdiscipline of psychol- Synonyms ogy termed cognitive science. The study of cognitive functions involves not Cognition; Mental ability; Mental function only identifying the processing stages but also the strategies used and the errors made. Turning again to memory function and word list recall as Definition an example, one strategy used involves semantic clustering where the person creates groupings of Cognitive function derives from the term cogni- words from the list based on the meaning cate- tion which refers to the internal mental processes gory such as clothes or fruit. This clustering studied in a subdiscipline of psychology termed serves to improve recall of the words. With cognitive psychology. These internal mental regard to errors, intrusions and false positive Cognitive Impairment 449 C errors in recalling words from the list provide neuroscience uses functional neuroimaging and insight into the integrity of memory. Intrusions correlates patterns of brain activity to the are errors where the person recalls a word not on processing stages in various cognitive functions. the list, while false positive errors occur when the The other approach called clinical neuropsychol- person is read a list of words some of which were ogy uses psychometrics alluded to above to iden- not on the recall list. A false positive error is one tify patterns of impairment in cognitive functions where the person endorses a word that was not on arising from some type of brain damage and C the list. Both of these errors indicate that the correlates these impairments with measures of ability to discriminate in memory between brain damage using structural (e.g., MRI) and words on the recall list from those not on the list functional (e.g., fMRI) brain imaging. is impaired. This information on cognitive functions has been used in the development of psychological Cross-References tests designed to examine cognitive functions (Hodges, 2007). These tests are administered to ▶ Assessment groups of people categorized based on factors such as age, sex, and years of education. Perfor- mance of these people is then used as normative References and Readings data against which to compare performance of people who take the tests in the future. These Benjafield, J. G., Smilek, D., & Kingstone, A. (2010). comparisons involve determining the average Cognition (4th ed.). New York: Oxford University Press. and the standard deviation for each group in the Hodges, J. (2007). Cognitive assessment for clinicians. normative sample. The mean and standard devi- New York: Oxford University Press. ation are reference points to determine where relative to the mean a person taking the test falls. The distance the person’s score falls relative Cognitive Impairment to the mean is measured in standard deviation units. The number of units above or below the Eric Roy mean reflects the percentage of people in the Department of Kinesiology, University of normative sample who are above or below the Waterloo, Waterloo, ON, Canada mean. Thus, if we use the memory test as an example, a person with a score at one standard deviation unit above the mean would be at a point Synonyms where 84% of people fall at or below this score. This approach to measurement termed psycho- Cognitive deficit; Cognitive disorder metrics reveals the relative strengths of a person on various cognitive functions. This pattern of strengths is used in the subdisciplines of psychol- Definition ogy called clinical psychology and educational psychology to direct people into education pro- Cognitive impairment refers to problems people grams and work placements. The alternative to have with cognitive functions such as thinking, patterns of strengths is patterns of weakness in reasoning, memory, or attention. cognitive functions. Such patterns are used in a subdiscipline of psychology called clinical neu- ropsychology to identify cognitive impairments. Description Another focus of study with regard to cogni- tive functions is the brain correlates of these Cognitive impairment can be present at any point functions. One approach called cognitive in a person’s lifespan (Kolb, & Whishaw, 2009). C 450 Cognitive Impairment

Early in life, cognitive impairment may arise standard deviation for each group in the norma- from, for example, genetic syndromes, prenatal tive sample. The mean and standard deviation are drug and alcohol exposure, trauma, or oxygen points of reference to determine where relative to deprivation during or after birth. the mean a person taking the test falls. The dis- Cognitive impairment in childhood and adoles- tance the person’s score falls relative to the mean cence may result from a number of conditions. is measured in standard deviation units. The num- Examples include malnutrition, heavy metal expo- ber of units above or below the mean reflects the sure, metabolic disorders, trauma to the brain, and percentage of people in the normative sample side effects of drug treatments for cancer or who are above or below the mean. Thus, if we Parkinson’s disease (Ogden, 2005). use the memory test as an example, a person with With age conditions such as traumatic brain a score at one standard deviation unit above the injury, neurodegenerative disorders such as mean would be at a point where 84% of people in Alzheimer disease, stroke, brain tumors, and the normative sample fall at or below this score. brain infections can cause cognitive impairment. This point is termed the 84th percentile. This In some cases, cognitive impairment is revers- approach to measurement reveals the relative ible if the cause is identified and treated. For strengths or weaknesses of a person on a cogni- example, cognitive impairment arising from tive function. A weakness is termed an impair- stroke due to a blockage of a blood vessel can ment or deficit and reflects performance at one be prevented if drugs designed to break up the standard deviation unit below the mean at the blood clots are administered within hours of the 16th percentile. At this point, 84% of the people formation of the clot. Similarly, cognitive impair- in the normative sample lie above this score. ments associated with metabolic disorders can be This psychometric approach to identifying a reversed with treatment of the disorder. cognitive impairment is often accompanied by a Cognitive impairment is defined as a disruption more qualitative approach where particular errors to some cognitive function such as memory or strategies in test performance are of interest. (Lezak, Howieson, & Loring, 2004). Identifying For example, in the context of a memory impair- a cognitive impairment requires a comparison of ment involving learning a list of words, the performance to some expected level of perfor- person may recall or recognize a word that was mance. In some cases, this expected performance not on the list. This error reflects an impairment is defined informally, for example, a person who is in discrimination in memory which provides unable to remember the name of a life-long friend is some insight into the nature of the memory thought to exhibit a cognitive impairment. In most impairment. cases, it is these cognitive impairments defined on the basis of informal expected level of performance which results in the person visiting a health-care Cross-References practitioner for a more thorough investigation. Such more thorough investigations identify ▶ Assessment cognitive impairments using more formal stan- ▶ Brain Imaging dards called norms which reflect expected perfor- ▶ Brain Injury mance on standardized tests of cognitive ▶ CAT Scan functions such as memory (Hebben, & Milberg, ▶ Cognitive Function 2009). These tests are administered to groups of ▶ Cognitive Strategies people categorized on factors such as gender, age, ▶ Dementia and years of education. Performance of these ▶ Depression: Symptoms people forms normative data against which is ▶ Disability compared performance of people who take the ▶ False-Negative Error tests in the future (Strauss, 2006). These compar- ▶ Neuroimaging isons require determining the average and the ▶ Neuropsychology Cognitive Mediators 451 C

▶ Psychometrics taking days or weeks. These processes are delin- ▶ Traumatic Brain Injury eated by mediation models of health experiences and behaviors which, in contrast to direct stimu- lus-response models, propose that events produce References and Readings an effect on individual responses indirectly via cognitive mediators. Cognitive mediators Hebben, N., & Milberg, W. (2009). Essentials of neuro- include interpretation of information, informa- C psychological assessment (2nd ed.). New York: Wiley. tion retrieval, judgments and evaluations, reason- Kolb, B., & Whishaw, I. (2009). Fundamentals of human neuropsychology (6th ed.). New York: Worth ing, and other mental processes. These processes Publishers. may be conscious or nonconscious (i.e., automat- Lezak, M., Howieson, D., & Loring, D. (2004). Neuropsy- ically elicited outside of one’s awareness), and chological assessment (4th ed.). New York: Oxford they can be distinguished from affective media- University Press. Ogden, J. A. (2005). Fractured minds: A case-study tors involving emotional processes. approach to clinical neuropsychology (2nd ed.). Mediational models have been used to better New York: Oxford University Press. understand the cognitive processes involved with Strauss, E. (2006). A compendium of neuropsychological a variety of health experiences, behaviors, and tests: Administration, norms and commentary (3rd ed.). New York: Oxford University Press. outcomes. Early behavioral medicine research on cognitive mediators examined their influence on pain perception and health status of individ- uals with medical conditions. More recently, Cognitive Impairment Tests research on cognitive mediators includes evaluations of their roles in the use of health- ▶ Screening, Cognitive promoting behaviors such as smoking cessation, physical activity, dietary behavior, and behaviors for reducing skin cancer risk.

Cognitive Mediators Cross-References Linda D. Cameron1 and Lana Jago2 1Psychological Sciences, University of ▶ Attitudes California, Merced, Merced, CA, USA ▶ Beliefs 2Department of Psychology, The University of ▶ Cognitions Auckland, Auckland, New Zealand ▶ Cognitive Factors ▶ Cognitive Strategies ▶ Health Behaviors Synonyms ▶ Health Outcomes Research ▶ Mediators Mediating cognitions ▶ Theory

Definition References and Readings

Cognitive mediators are mental processes or Baron, R. M., & Kenny, D. A. (1986). The moderator- activities that take place between the occurrence mediator variable distinction in social psychological of a stimulus and initiation of an associated research: Conceptual, strategic, and statistical consid- erations. Journal of Personality and Social Psychol- response. Such processes can occur immediately ogy, 51, 1173–1182. following the stimulus (i.e., within microsec- Gibbons, F. X., Gerrard, M., Lane, D. J., Mahler, H. I., & onds), or they may be a more delayed response, Kulik, J. A. (2005). Using UV photography to reduce C 452 Cognitive Reappraisal

use of tanning booths: A test of cognitive mediation. rational responses. The rational responses are Health Psychology, 24, 358–363. self-statements that are used to feel better about Preacher, K. J., & Hayes, A. F. (2004). SPSS and SAS procedures for estimating indirect effects in simple the situation. mediation models. Behavior Research Methods, Cognitive restructuring may help individuals Instruments, & Computers, 36, 717–731. with a chronic illness to manage how the illness Rucker, D. D., Preacher, K. J., Tormala, Z. L., & affects their perceptions of themselves, their rela- Petty, R. E. (2011). Mediation analysis in social psychology: Current practices and new recommenda- tionships, and their future. For example, an indi- tions. Social and Personality Psychology Compass, 5, vidual may be experiencing persistent anxiety 359–371. since his return to work following a myocardial infarction. The individual may be encouraged to identify a specific situation that is making him anxious (“My supervisor pointed out some errors in my work”); his negative thoughts (“I can’t do Cognitive Reappraisal anything right since I had my heart attack,” and “I’ll probably get fired”); and his resulting ▶ Cognitive Restructuring emotions (fear, despair). Through cognitive restructuring, the individual may work on chal- lenging his thoughts and generating alternative responses: “I don’t have any evidence that my supervisor is dissatisfied with my work in gen- Cognitive Restructuring eral. I have been taking care of myself since my heart attack. No one is perfect, and in the future, Lara Traeger I can leave more time to check my work.” The Behavioral Medicine Service, Massachusetts individual may then assess whether the rational General Hospital/Harvard Medical School, responses help him to reduce his distress and Boston, MA, USA view his situation in a more helpful light.

Synonyms Cross-References

Cognitive reappraisal ▶ Cognitive Behavioral Therapy (CBT) ▶ Cognitive Distortions ▶ Cognitive Strategies Definition

Cognitive restructuring is a strategy to recognize References and Readings negative, inaccurate thoughts and replace them with alternative ones that are more realistic and Beck, A. T., Rush, A. J., Shaw, B. F., & Emery, G. (1979). helpful. This cognitive strategy, a key part of Cognitive therapy of depression. New York: Guilford. Clark, D. A., Beck, A. T., & Alford, B. A. (1999). Scien- cognitive behavioral therapy, promotes optimal tific foundations of cognitive theory and therapy of thinking about a stressful or overwhelming situ- depression. New York: Wiley. ation to reduce emotional distress. Cognitive restructuring may involve several steps: write down the situation; list negative thoughts that occurred during the situation; list emotions that arise when having these thoughts; identify cogni- Cognitive Status Tests tive distortions or errors that may underlie each thought; challenge each thought; and generate ▶ Screening, Cognitive Cognitive-Behavioral Stress Management Training 453 C

Cross-References Cognitive Strategies ▶ Cognitive Appraisal Linda D. Cameron1 and Lana Jago2 ▶ Cognitive Behavioral Therapy (CBT) 1Psychological Sciences, University of ▶ Cognitive Factors California, Merced, Merced, CA, USA ▶ Cognitive Restructuring 2Department of Psychology, The University of ▶ Mindfulness C Auckland, Auckland, New Zealand ▶ Self-regulation Model

Synonyms References and Readings

Cognitive techniques; Mental strategies Chan, C. K. Y., & Cameron, L. D. (2011). Promoting physical activity with goal-oriented mental imagery: A randomized controlled trial. Journal of Behavioral Medicine. doi:10.1007/s10865-011-9360-6. Definition Hart, S. I., & Hart, T. A. (2010). The future of cognitive behavioral interventions within behavioral medicine. Cognitive strategies are sets of mental processes Journal of Cognitive Psychotherapy, 24, 344–353. Kamholz,B.W.,Hayes,A.M.,Carver,C.S., that are consciously implemented to regulate Gulliver, S. B., & Perlman, C. A. (2006). Identification thought processes and content in order to achieve and evaluation of cognitive affect-regulation strategies: goals or solve problems. Self-regulation theories of Development of a self-report measure. Cognitive Ther- behavior focus on cognitive strategies as playing apy and Research, 30, 227–262. McCracken, L. M. (Ed.). (2011). Mindfulness and accep- a critical role in guiding goal-directed behavior. tance in behavioral medicine: Current theory and Cognitive strategies are primary targets for numer- practice. Oakland, CA: Context Press/New Harbinger ous intervention approaches, including cognitive Publications. behavior therapy (CBT), mindfulness-based inter- ventions, and acceptance and commitment therapy (ACT). Cognitive strategies include those directing Cognitive Strategy attentional focus (e.g., attentional engagement or distraction), cognitive reframing or reinterpretation ▶ Cognitive Factors of distressing experiences, imagery techniques, and mental rehearsal of positive statements. Within the health setting, pain management is one area in which cognitive strategies may be Cognitive Style useful. Examples include distraction, where one diverts attention away from the painful stimulus ▶ Cognitive Factors and towards a non-painful alternative; imagery, such as imagining a favorite scene or other non-painful image; and redefinition, where pain Cognitive Techniques cognitions related to threat or fear are replaced with constructive or nonthreatening thoughts. ▶ Cognitive Strategies Cognitive strategies can also be of benefit to individuals with chronic illnesses who are experiencing psychological distress or difficulty managing their conditions. Within the context of Cognitive-Behavioral Stress health promotion, mental imagery techniques Management Training have been demonstrated to increase physical activity among sedentary adults. ▶ Williams LifeSkills Program C 454 Cohort Study

the outset of the study, this prospective design is Cohort Study less susceptible to many types of bias compared to other observational study designs, such as Jane Monaco case-control studies. Included in the prospective Department of Biostatistics, The University of cohort study design are large studies such as the North Carolina at Chapel Hill, Chapel Hill, Framingham Study in which participants were NC, USA selected for logistical reasons. By recruiting a large number of residents from the single com- munity of Framingham, Massachusetts, follow- Synonyms up was simplified, and investigators were able to study prospectively the associations between Follow-up study; Observational designs; multiple risk factors and outcomes among the Observational studies; Observational study participants (Dawber, Kannel, & Lyell, 1963). Not all cohort studies are conducted prospec- tively. In a retrospective cohort study, both the Definition exposure and outcome may have occurred at the time of the initiation of the study. These retro- A cohort study is an observational study design in spective, sometimes called historical, cohort which subjects are usually selected based on their studies are often conducted using data previously risk factor exposure and followed over time to collected for other purposes. For example, preg- evaluate whether they develop the outcome of nant women drivers involved in motor vehicle interest (usually disease). crashes were identified by linking Washington State Patrol records to birth and death certificates (Wolf et al., 1993). The exposure of interest, Description seatbelt use at the time of the crash, was deter- mined using the police reports. Investigators Cohort studies are commonly used in behavioral determined pregnancy outcomes (including low medicine research to investigate associations in birth weight and fetal death) based on the birth which experimental designs are unethical or too and fetal death certificate data. This retrospective costly. In a cohort design, participants who have cohort study found the risk of a low-birth-weight not experienced the outcome of interest are infant was higher among unrestrained female selected, usually based on whether or not they drivers compared to those wearing a seat belt at have been exposed to the risk factor of interest. the time of the crash. Therefore, a cohort study design is efficient when In a cohort study, investigators must follow the exposure is relatively rare but the outcome of both the exposed and unexposed subjects equally interest is common. For example, a cohort design carefully to avoid detection bias. If the exposed was used in a study of the association of prenatal subjects are followed more closely, then an polychlorinated biphenyl (PCB) exposure with excess number of outcomes may be detected behavior issues and cognitive disability (Lai within the exposed group resulting in an et al. 2002). A cohort design is also appropriate overestimate of the exposure effect. Also, loss when the exposure is common. to follow-up may result in biased results when The most common type of cohort study, that loss is associated with the exposure and a prospective cohort study, identifies subjects outcome. without the outcome of interest (such as disease- Some characteristics of cohort studies: free participants) at the outset of the study and • Usually more expensive and time consuming then follows them forward through time to assess than case-control designs; less expensive than their outcome (or disease) status. Because the an experimental design subjects have not experienced the outcome at • Often used when the exposure is rare Cold Pressor Test 455 C

• Not practical when outcome of interest (dis- ease) is rare or has a long-latency period Cold Pressor Test • Appropriate when studying multiple outcomes • Usually can only address a single risk factor Laura A. Mitchell • When information collected prospectively, Department of Psychology, School of Life reduces potential for bias Sciences, Glasgow Caledonian University, • Can be impacted by loss to follow-up Glasgow, Scotland, UK C • Can compute incidence and relative risk of outcome directly • Often considered stronger study design com- Synonyms pared with case-control studies, but weaker study design compared to randomized trials Cold pressor task that investigate analogous associations

Definition Cross-References The cold pressor test is a widely used experi- ▶ Bogalusa Heart Study mental technique for human pain or stress induc- ▶ Case-Control Studies tion, involving immersion of the hand or forearm ▶ Retrospective Study in cold water. First documented as a test of cardiovascular stress reactivity (Hines & Brown, 1936), its application in investigation of pain perception, mechanisms, and treatment is References and Readings due to a gradually mounting painful sensation of mild to moderate intensity. As water temper- Dawber, T. R., Kannel, W. B., & Lyell, L. P. (1963). An atures used are within the range considered nox- approach to longitudinal studies in a community: The ious (below 15C), nociceptors (pain receptors) Framingham study. Annals of the New York Academy of Sciences, 107(2), 539–556. are activated and transmit an aversive signal to Hennekens, C. H., Buring, J. E., & Mayrent, S. L. (1987). the CNS. While nociception-transduction ion Epidemiology in medicine. Philadelphia: Lippincott channels involved have been identified, the Williams & Wilkins. exact mechanisms of cold pain are not fully Kleinbaum, D. G., Sullivan, K. M., & Barker, N. D. (2007). A pocket guide to epidemiology. New York: elucidated (Basbaum, Bautista, Scherrer, & Springer. Julius, 2009). Lai, T. J., Liu, X., Guo, Y. L., Guo, N., Yu, M., Hsu, C., Like other pain inductions, the cold pressor et al. (2002). A cohort study of behavioral problems allows fast and precisely controlled evaluations and intelligence in children with high prenatal polychlorinated biphenyl exposure. Archives of Gen- not possible in a clinical context. Apparatus for eral Psychiatry, 59(11), 1061–1066. the task is a tank of circulating water of temper- Wolf, M. E., Alexander, B. H., Rivara, F. P., Hickok, ature most often between 0C and 5C, with D. E., Maier, R. V., & Starzyk, P. M. (1993). instruction to immerse the hand until too uncom- A retrospective cohort study of seatbelt use and preg- nancy outcome after a motor vehicle crash. The Jour- fortable to continue. A maximum time limit per nal of Trauma, 34(1), 116. immersion of 3–5 min is normally applied. Quan- titative measurement can then be made of pain threshold (point first perceived as painful), toler- ance time, and perceived intensity and unpleas- antness. The technique is regarded as safe for Cold Pressor Task pain evaluations in children, usually at a slightly higher water temperature (von Baeyer, Piira, ▶ Cold Pressor Test Chambers, Trapanotto, & Zeltzer, 2005). C 456 Colitis

Cross-References Colorectal Cancer ▶ Pain Threshold ▶ Cancer, Colorectal

References and Readings Common Cold Basbaum, A. I., Bautista, D. M., Scherrer, G., & Julius, D. (2009). Cellular and molecular mechanisms of pain. Denise Janicki-Deverts and Crista N. Crittenden Cell, 139, 267–284. Department of Psychology, Carnegie Mellon Hines, E. A., & Brown, G. E. (1936). The cold pressor test for measuring the reactibility of the blood pressure: University, Pittsburgh, PA, USA Data concerning 571 normal and hypertensive subjects. American Heart Journal, 11, 1–9. von Baeyer, C. L., Piira, T., Chambers, C. T., Trapanotto, Synonyms M., & Zeltzer, L. K. (2005). Guidelines for the cold pressor task as an experimental pain stimulus for use with children. The Journal of Pain, 6(4), 218–227. Upper respiratory infection (mild)

Definition Colitis The common cold is the familiar name for a mild upper respiratory infection (URI). Symptoms of ▶ Inflammatory Bowel Disease the common cold include nasal congestion, mucus production, sneezing, cough, and sore throat (Eccles, 2005). The common cold is caused by any of a number of viruses, most often one of Collaborative Care the rhinoviruses (see ▶ Common Cold: Cause). URIs are responsible for 50% of all acute ill- ▶ Clinical Settings nesses, with common colds accounting for most of that proportion. While symptoms are often mild, the common cold often confers a heavy burden on patients, healthcare providers, schools, and work- Collaborator places. Approximately 62 million cases of the com- mon cold occur each year in the United States. In ▶ Co-workers addition, 20 million school days are lost annually as well as 22 million work days due to the common cold (Adams, Hendershot, & Marano, 1999). The incubation period for the common cold Colleague largely depends on the virus that causes it. On average, symptoms begin 2–3 days after virus exposure and infection. From the onset of ▶ Co-workers the first symptoms, severity usually peaks within 2 days. Overall, the duration of the common cold is usually 7–10 days (Eccles, 2005). Because only a proportion of people who are College Students exposed to cold viruses actually develop symp- toms, the common cold has become a fertile ▶ Binge Drinking ground for studying psychosocial and behavioral Common Cold: Cause 457 C factors that influence vulnerability to infection. References and Readings Viral challenge studies expose healthy individ- uals to common cold viruses and then keep them Adams, P. F., Hendershot, G. E., & Marano, M. A. (1999). in quarantine over several days to assess who Current estimates from the national health interview survey 1996, National Center for Health Statistics. develops infection and symptoms and who does Vital Health Statistics, 10(200). not. Prior to virus exposure, a plethora of behav- Doyle, W. J., McBride, T. P., Swarts, J. D., Hayden, F. G., & ioral and psychological measures are performed Gwaltney, J. M. (1988). The response of the nasal C in order to assess the roles these factors may play airway, middle ear and Eustachian tube to provocative rhinovirus challenge. American Journal of Rhinology, 2, in illness susceptibility. 149–154. Within these experimental studies, individuals Eccles, R. (2005). Understanding the symptoms of the are determined to have a cold if they (1) are common cold and influenza. The Lancet Infectious infected with the challenge virus and (2) meet Diseases, 5, 718–725. a set of predetermined criteria based on subjective symptom reports and objective physiological mea- surements. Infection is determined by the presence of viral shedding (i.e., replication of the virus in the Common Cold: Cause host environment). Viral shedding is assessed by administering a nasal wash, which flushes the nasal Denise Janicki-Deverts and Crista N. Crittenden cavity and sinuses, and then culturing a sample of Department of Psychology, Carnegie Mellon the exposed wash solution for the presence of rep- University, Pittsburgh, PA, USA licating virus. Presence and severity of cold symp- toms, i.e., runny nose, sore throat, nasal congestion, etc., are assessed via observation and participant Synonyms report. Objective measures of cold severity include mucus production and mucociliary clearance func- Upper respiratory infection (mild): cause tion. Mucus production is assessed by collecting used tissues from participants and measuring their weight; nasal mucociliary clearance, or how effec- Definition tive the body is in clearing mucus from the nasal passage, is assessed as the time it takes for a dye The common cold is a mild upper respiratory administered in the nostrils to reach the illness that results from infection with any of nasopharyx (Doyle, McBride, Swarts, Hayden, & more than 200 viruses, most notably the rhinovi- Gwaltney, 1988). Additional measures, such as ruses. The rhinovirus family is comprised of over lung function, may also be taken. 100 different viruses, with the relative prevalence Through these common cold studies, several of each being dependent on a number of factors, behavioral and psychosocial factors have been from geographical area to time of year. Overall, found to greatly increase susceptibility to infec- rhinoviruses make up approximately 30–50% of tion, including sleep patterns, social integration all acute respiratory illnesses, but in the fall sea- and stress. These topics are discussed further in son this proportion jumps to about 80%. ▶ Common Cold: Cause and ▶ Common Cold: Coronaviruses comprise another family of The Stress Factor. viruses that cause the common cold. Infections with coronaviruses are estimated to account for 7–18% of adult colds, and in contrast to rhinovi- Cross-References rus infections, tend to be most prevalent during the winter and spring months. Additional cold ▶ Common Cold: Cause viruses include parainfluenza, respiratory syncy- ▶ Common Cold: The Stress Factor tial virus (RSV), the adenoviruses, and the ▶ Stress enteroviruses which collectively account for C 458 Common Cold: The Stress Factor a comparatively small percentage of infections. these factors remained associated with cold sus- In addition, 20–30% of common cold cases are of ceptibility even when controlling for age, sex, unknown origin (Heikkinen & Jarvinen, 2003). body weight, and season of exposure. Cold viruses are highly contagious, and inter- personal transmission of colds typically occurs in one of two ways: (1) inhaling viral particles that Cross-References are released into the air in tiny droplets when infected persons cough, sneeze, or blow their ▶ Common Cold nose; or (2) coming into contact with surfaces ▶ Common Cold: The Stress Factor that have been contaminated by infected secre- ▶ Stress tions (e.g., a doorknob that was touched by an infected person immediately after coughing into References and Readings his or her hand) and then touching one’s own eyes, nose, or mouth. Cohen, S., Doyle, W. J., Skoner, D. P., et al. (1997). Social Several factors have been found to influence ties and susceptibility to the common cold. Journal of whether individuals become infected following the American Medical Association, 277, 1940–1944. exposure to a cold virus and/or the severity of Cohen,S.,Doyle,W.J.,Turner,R.B.,Alper,C.M.,& Skoner, D. P. (2003a). Sociability and susceptibility to their symptoms once infected. Most of these find- the common cold. Psychological Science, 14, 389–395. ings have derived from viral challenge studies Cohen, S., Doyle, W. J., Turner, R. B., Alper, C. M., & wherein healthy individuals are exposed to cold Skoner, D. P. (2003b). Emotional style and suscepti- viruses (most often rhinoviruses), placed under bility to the common cold. Psychosomatic Medicine, 65, 652–657. quarantine, and monitored by trained medical Cohen, S., Tyrrell, D. A. J., Russell, M. A., Jarvis, M. J., & staff for objective signs and subjective symptoms Smith, A. P. (1993). Smoking, alcohol consumption, of a cold (see ▶ Common Cold). Of all potential and susceptibility to the common cold. American susceptibility factors, stress has been the most Journal of Public Health, 83, 1277–1283. Eccles, R. (2005). Understanding the symptoms of the explored. Accordingly, the role of stress in cold common cold and influenza. The Lancet Infectious susceptibility is discussed in a separate entry (see Diseases, 5, 718–725. ▶ Common Cold: The Stress Factor). Stress, Heikkinen, T., & Jarvinen, A. (2003). The common cold. however, is far from being the only factor that Lancet, 361, 51–59. has been found to influence who develops colds. For example, smokers are more likely than non- smokers to become infected with the cold virus Common Cold: The Stress Factor and, consequently, to develop illness symptoms (Cohen, Tyrrell, Russell, Jarvis, & Smith, 1993). Denise Janicki-Deverts and Crista N. Crittenden Social relationship factors have been found to Department of Psychology, Carnegie Mellon influence cold susceptibility as well. People who University, Pittsburgh, PA, USA are high in trait sociability (which is thought to be an important determinant of quantity and quality of social interaction) and those with more diverse Synonyms social networks are less susceptible to colds than their less sociable and less socially integrated Upper respiratory infection (mild): the stress counterparts (Cohen et al., 1997; Cohen, Doyle, factor Turner, Alper, & Skoner, 2003a). A third identi- fied susceptibility factor is affect. Specifically, greater positive affect is associated in a dose- Definition response manner with reduced likelihood of developing a cold (Cohen, Doyle, Turner, One of the most consistent findings from viral Alper, & Skoner, 2003b). Importantly, all of challenge studies (see ▶ Common Cold) is that Common Cold: The Stress Factor 459 C the experience of stress is positively associated age, general health, and past infection experi- with susceptibility to the common cold. Here ence. However, the repeated finding of greater stress is defined as a psychological state resulting stress being associated with increased risk for from outside factors or events placing demands colds independent of behavioral factors or health on an individual that exceed his or her resources practices suggests that stress may be influencing or ability to cope (Cohen, Kessler, & Gordon, the immune system, as well, by suppressing some 1995). Although stressful experiences such as resistance processes. For example, in influenza C bereavement and care giving have long been challenge studies, increased psychological stress believed to suppress host resistance, the common was associated with higher pro-inflammatory cold studies were the first to demonstrate the role cytokine concentrations, particularly interleukin of the stress factor under prospective, controlled (IL)-6 (Cohen, Doyle, & Skoner, 1999). In an conditions. experimental study in which stress was induced Cohen, Tyrrell, and Smith (1991)conducted in a laboratory setting, Marsland, Bachen, Cohen, one of the first studies to explore the role of stress Rabin, and Manuck (2002) found that being in susceptibility to the common cold. The authors exposed to a stressor was associated with assessed several stress factors, including life events increases in immune markers, such as circulating and perceived stress in a sample of healthy adults, natural killer cells and cytotoxic T cells. These and then experimentally exposed these individuals studies suggest that stress may be acting through to a cold virus or to a saline control. Despite con- major immunological pathways to increase trolling for several person and environmental fac- symptoms of infectious illnesses. tors, the researchers observed a dose-response association between stress and clinical colds: Cross-References more stress was associated with an increased like- lihood both of becoming infected and displaying ▶ Common Cold clinical symptoms. Furthermore, they also found ▶ Stress that long-lasting social stressors accounted for the greatest infection risk. These stress factor effects were all independent of potential mediators such as References and Readings smoking, diet, alcohol use, and sleep quality. Cohen, S., Kessler, R. C., & Underwood Gordon, L. (Eds.) Cohen et al. (1998) further explored several types (1995). Measuring stress: A guide for health and social of stressors linked to the common cold and found scientists. New York: Oxford. Strategies for measuring that severe, chronic stressors – especially work and stress in studies of psychiatric and physical disorders. interpersonal stressors, lasting 1 month or longer – Cohen, S., Doyle, W. J., & Skoner, D. P. (1999). Psycho- logical stress, cytokine production, and severity of conferred a substantial risk of developing a clinical upper respiratory illness. Psychosomatic Medicine, cold after virus exposure. Moreover, the longer the 61, 175–180. stress duration, the greater the relative risk of Cohen, S., Frank, E., Doyle, W. J., Skoner, D. P., Rabin, a cold. Again, these differences could not be B. S., & Gwaltney, J. M. (1998). Types of stressors that increase susceptibility to the common cold in healthy completely explained by environmental, person- adults. Health Psychology, 17(3), 214–223. related, or behavioral factors. Cohen, S., Tyrrell, D. A. J., & Smith, A. P. (1991). Psy- An important feature of the common cold is chological stress and susceptibility to the common that associated symptoms (sneezing, congestion, cold. The New England Journal of Medicine, 325, 606–612. etc.) are caused by the body’s immune response Cohen, S., Tyrrell, D. A. J., & Smith, A. P. (1993). Life to the virus, not the virus per se. Most symptoms events, perceived stress, negative affect and suscepti- result from the production of pro-inflammatory bility to the common cold. Journal of Personality and cytokines that recruit other immune cells to fight Social Psychology, 64, 131–140. Marsland, A. L., Bachen, E. A., Cohen, S., Rabin, B., & the infection. Several “host” factors influence the Manuck, S. B. (2002). Stress, immune reactivity and immune system’s response to infection and how susceptibility to infectious disease. Physiology and severe resulting symptoms will be. These include Behavior, 77, 711–716. C 460 Common Disease-Common Variant

Pritchard, J. K., & Cox, N. (2002). The allelic architecture Common Disease-Common Variant of human disease genes: common disease-common variant...or not? Human Molecular Genetics, 11, 2417–2423. Jennifer Wessel Reich, D. E., & Lander, E. S. (2001). On the allelic Public Health, School of Medicine, Indiana spectrum of dusease. Trends in Genetics, 17, 502–510. University, Indianapolis, IN, USA

Definition Common Migraine

The common disease-common variant (CDCV) ▶ Migraine Headache hypothesis predicts that for any given common disease, the genetic risk will be due to common variants with high frequency in the population (Pritchard & Cox, 2002; Reich & Common-Sense Model of Lander, 2001). Self-regulation The allelic spectrum, i.e., the frequency of the allele in the population and the number of Pablo A. Mora1 and Lisa M. McAndrew2 disease-predisposing alleles, of common diseases 1Department of Psychology, The University of is still not well understood. The number of com- Texas at Arlington, Arlington, TX, USA mon variants contributing to any given common 2Department of Veterans Affairs, NJ Healthcare disease will most likely vary from less than 100 to System, East Orange, NJ, USA several thousands, with many of these variants having a low effect on the disease (Padhukasahasram et al. 2010). Synonyms Genome-wide association studies (GWAS) have succeeded at identifying common Illness representation model; Mental models of variations, many with low effect sizes (odds ratio illness; Mental representations of illness 1.2–1.5). However, there are many more left to be identified. A number of reasons have been suggested as to why GWAS have not identified Definition more variations. These include rare variations con- tributing to common diseases, phenotypic hetero- The common-sense model of self-regulation geneity, sample size, or regions missed by single explains how individuals respond to and manage nucleotide polymorphism (SNP) microarrays. health threats. It proposes that people actively engage in problem-solving by developing mental Cross-References models of health threats, subjective and objective treatment goals, and practices and procedures most likely to achieve those goals. ▶ Allele ▶ Genome-Wide Association Study (GWAS) ▶ Single Nucleotide Polymorphism (SNP) Description

References and Readings Background The origins of the common-sense model of Padhukasahasram, B., Halperin, E., Wessel, J., Thomas, self-regulation (CSM) can be traced to the D. J., Silver, E., Trumbower, H., et al. (2010). Presymptomatic risk assessment for chronic non- parallel model proposed by Leventhal in the communicable diseases. PLoS One, 5, e14338. early 1970s to understand how individuals Common-Sense Model of Self-regulation 461 C

Identity Timeline Consequences Cause Control Days / Self / Label Physical / Social Labeled Years Expert Perceived Seen / Symptoms Imagined Felt Time Felt

Location Pattern C lllness Procedures and action plans Duration Representation for coping with threat Monitor Severity change Symptoms Evaluation Tools Somatic Interpretation Changes of experience Dysfunction Symptoms Affective function Response

Emotional Coping Reactions with Affect

Common-Sense Model of Self-regulation, representation consists of five bi-level domains. Cognitive Fig. 1 Individuals assess somatic changes based on the and emotional representations guide the selection of cop- features of the changes by using evaluation tools ing procedures and the criteria for assessing effectiveness (e.g., location, pattern, duration, or function) and compar- of these procedures (e.g., changes in symptom and/or ing these features against illness prototypes. If deemed to affectivity). Evidence of success or failure to achieve be a health threat, the individuals develops cognitive and desired changes will be used by the individual to re-assess emotional representations of the threat. The cognitive the illness representation respond to fear-arousing communications coping procedures) to reduce the discrepancy. (Leventhal, 1970). Similar to the parallel model, The illness representation developed during the the CSM posits that when a threat is perceived perceptual stage will help select the types of (e.g., physical symptoms or changes in function), coping procedures used by the individual during individuals develop two parallel, yet interrelated, the response stage. In the last stage, the appraisal representations of the stimulus: cognitive and stage, the results of the action(s) aimed at emotional (Leventhal et al., 1997). These repre- reducing or eliminating the discrepancy are sentations and their content specify the actions evaluated. If the actions are successful in dealing (i.e., behaviors) in which individuals engage to with the threat, the loop stops. If unsuccessful, the remove the health threat. The CSM proposes that individual may reassess the representation and the processes involved in the self-regulation of form a new illness representation, and/or select health threats are regulated by a TOTE and perform new corrective actions. This loop (Test-Operate-Test-Exit) system with both feed- will continue until the threat has been success- back and feed-forward loops (Miller, Galanter, & fully removed or controlled. Pribram, 1960). Common sense self-regulation is divided into Illness Representations three phases (Leventhal & Cameron, 1987). In The CSM assumes that people are active the first stage, the perceptual stage, a discrepancy problem-solvers who continuously assess the between a perceived input and a reference value meaning of somatic sensations and/or changes is detected (i.e., health threat). At this stage, the in function by forming cognitive and emotional individual develops a common sense illness illness representations (see Fig. 1). Illness representation of the potential health threat. In representations have a bi-level structure that the second stage (i.e., the response stage), the includes an abstract level (i.e., disease labels individual selects and performs actions (i.e., and chronological time) and a concrete level C 462 Common-Sense Model of Self-regulation

(i.e., symptoms and experienced time). Initially, coping actions. For instance, actions taken to the CSM identified five defining aspects of illness ameliorate a stomachache could involve drinking representation: identity, timeline, causes, conse- herbal tea or having a bland diet, whereas quences, and controllability. Abstract features of a headache might lead the person to take an identity include the label applied to the health over-the-counter pain reliever. The appraisal of threat (e.g., diagnosis or name of the condition). the effectiveness of these actions will also vary Concrete features of identity refer to how the depending on the specific content of the represen- threat is experienced (e.g., symptoms and/or tations. For example, the expected timeline for changes in function). Timeline refers to the ridding oneself of a stomachache is likely several objective (i.e., abstract: duration in minutes or hours to a day, while the expected timeline for hours) and perceived (i.e., concrete: perceived determining that a pain reliever is effective in duration) temporal features of the health threat. dealing with a headache could be to 1–2 h at Causes refer to the diagnosed (i.e., information most. conveyed by the doctor) and perceived (i.e., leav- Appraisal of Health Threats. When ing home with wet hair) factors that caused the a deviation from “normal function” is detected health threat. The causes of a threat can be (e.g., a health threat such as somatic symptoms or grouped into external agents (e.g., virus, bacteria, declines in physical function), the individual will or stress), internal susceptibilities (e.g., age, promptly engage in an automatic scanning genetics), and behaviors (e.g., smoking). Conse- process in which the properties of the health quences include both anticipated (i.e., abstract) threat are assessed (Leventhal, Breland, Mora & and perceived and experienced (i.e., concrete) Leventhal, 2010). These properties are compared physical, psychological, social, and economic against illness prototypes developed through effects that the health threat will produce. prior personal experience, observation of others, Controllability refers to whether the person and media exposure (cf. Fig. 1). Prototype checks expects and perceives the health threat to be are used evaluate somatic and/or functional susceptible to control by experts (e.g., physician) changes with respect to features such as their and/or the self. location (e.g., head, stomach, chest), duration The existence of a sixth domain, “illness (e.g., perceived and clock time), rates of coherence,” has been proposed by Weinman and change (e.g., sudden onset or insidious), conse- collaborators (Moss-Morris et al., 2002). Illness quences (e.g., disrupts breathing or impairs coherence is a metacognition that refers to the walking), causes (e.g., exposure to sick people extent to which an individual believes that the or perceived stress), and sensory properties various features of an illness hang together. For (e.g., sharp or dull). If the features of the somatic example, someone who suffers from a cold would or functional changes match an illness prototype, expect that symptoms such as a runny nose and then a preliminary illness representation will be a sore throat would last for a couple of weeks. formed and lead the individual to engage in However, if unusual symptoms are experienced actions to remove or control the threat (i.e., cop- or if the timeline of the symptoms is longer than ing procedures). A further appraisal of the threat expected, the individual will have trouble making will be conducted based on the perceived effects sense of the health threat. Low coherence has of these coping procedures. Feedback from been shown to have an impact on other dimen- coping procedures will provide critical sions of illness representations and on the information to either confirm or disconfirm the appraisal and enactment of coping procedures. preliminary illness representation. For instance, Illness representations and their content serve a headache and a runny nose may be the result of as guides for the selection, performance, and a cold or of seasonal allergies. If the symptoms evaluation of actions used to manage illness occur around spring, then the person may decide episodes. Feedback from these actions can to take an antihistamine pill to help clear the reshape the representations and alter subsequent symptoms. If after a few hours the symptoms Common-Sense Model of Self-regulation 463 C are not relieved, then the tentative “allergies” changes), causal factors (e.g., works by killing representation may be discarded, and a new bacteria), control (e.g., cure and control of health threat appraisal process will begin. disease symptoms), and consequences (e.g., Lack of experience with a specific condition or addiction or improved quality of life). Research unusual presentation of symptoms can create directly examining these dimensions of treatment confusion during the matching and appraisal pro- representations is limited. Several studies cess and result in negative consequences such as conducted by Leventhal and collaborators, how- C delayed care seeking or poor illness management. ever, have assessed some of these facets (e.g., For example, gastric pain caused by gallstones Halm, Mora, & Leventhal, 2006). These assess- could be attributed to indigestion or stomach flu if ments have focused on aspects such as triggers a person has never been exposed to gallstones and that initiate the use of medication (e.g., “I use the symptomatology associated with gallstones medications when I have symptoms”), control previously because the location is similar (i.e., (e.g., “My medicines protect me from becoming abdominal area). This could lead individuals to worse”), consequences (“My health in the future engage in watchful waiting which, in turn, could depends on my medications”), and emotional increase the risk of serious consequences such as reactions (“How worried are you about the side emergency hospitalization due to blockage of the effects of your medication?”). Evidence from pancreatic duct. Conditions that do not manifest these studies have shown that these aspects of according to the prototypes people have can treatment representations are strong predictors result in inadequate management or control of of illness self-management. the threat. For instance, the symptoms that people A different view of treatment representations with congestive heart failure usually experience has been put forth by Horne, Weinman, and (e.g., swollen legs, breathing and sleeping prob- Hankins (1999).Basedoncommonsense lems) are not the symptoms that a person with regulation principles, Horne and collaborators a “heart” condition is supposed to experience identified commonly held beliefs about medica- (e.g., palpitations). This mismatch can result in tions and medical treatments and grouped them poor adherence to medical treatment because into “general” and “specific” concerns about med- the heart condition does not represent an imme- ications. “General concerns” encompass beliefs diate threat. Similarly, depressive symptomatol- that medications, in general, are overprescribed ogy may not be properly identified and by practitioners (i.e., overuse) and beliefs that treated among older adults, because they are medicines can be harmful and addictive (i.e., less likely to experience symptoms of dysphoria harm). “Specific concerns” address the beliefs (i.e., depression without sadness, Gallo, Rabins, that a prescribed medication is necessary for and Gallo, & Rabins, 1999). Low negative affect will efficacious in controlling a particular condition make the matching processes difficult for both the and concerns about the harmful effects of individuals who experience depressive symptoms a medication prescribed for a specific illness. and mental health professionals because Despite the apparent differences, both views the symptoms do not fit with a “depression are conceptually consistent. Further, the CSM prototype.” could be used as a more general framework within which the two major domains (i.e., general Treatment Representations and specific concerns) can be organized. For From the CSM perspective, treatment represen- instance, specific beliefs include both cognitive tations are conceptualized using the same and emotional aspects of treatment representa- framework as illness representations (Leventhal tions. Similarly, some specific beliefs about the et al., 2010). That is, treatment beliefs are necessity of medications can be categorized as assumed to have an identity (e.g., “diuretic”), beliefs about the consequences of treatment timeline (e.g., for how long one should take the (e.g., my health in the future depends on medications or time for treatment to effect medicines). C 464 Common-Sense Model of Self-regulation

Measurement Questionnaire (IPQ) assesses the five original Because of their central role in the CSM, most domains of illness representations (i.e., identity, measurement efforts have focused on developing timeline, consequences, causes, and controllabil- instruments to assess the content of illness and ity), emotional representations, and illness coher- treatment representations. These efforts have ence (Moss-Morris et al., 2002). The items do been guided by two different approaches. In a good job of providing a snapshot of people’s the first approach (i.e., domain-based approach), illness representations. Two versions of the investigators develop measurement to assess IPQ are available: the IPQ-R which is the long content relevant to the specific illness condition version and consists of over 50 items and the brief under investigation. Researchers who use the IPQ which includes eleven questions (Broadbent, second approach (i.e., instrument-based Petrie, Main, & Weinman, 2006). The IPQ approach) prefer the use of basically the same questions are standard, though it is possible to instrument and items across domains. make modifications to the items’ wording and/or The domain-based approach requires close include a condition-specific symptom list, to familiarity with the health threat (i.e., illness reflect the illness condition being investigated. condition) to be studied. Although illness repre- The IPQ has been successfully used in a wide sentations of various conditions may share some range of studies examining various chronic features, they can be highly divergent in terms of conditions such as asthma, diabetes, cardiovascu- how they are experienced by individuals, their lar disease, and rheumatic conditions. consequences, and their management. Thus, to To date, the only instrument that assesses develop valid and relevant items, one needs to treatment representations is the Beliefs about rely on the use of theory, pilot interviews with Medications Questionnaire (BMQ) developed patients who suffer a given condition, and input by Horne et al. (1999). The BMQ is a multi-item from practitioners (Leventhal & Nerenz, 1985). instrument that comprises two scales that assess Items developed by using this approach usually general and specific concerns about medicines. focus on very specific aspects of illness and Similar to the IPQ, the wording of the items is treatment representations in order to gain standard but can be modified to reflect the differ- a more detailed understanding of underlying ent types of treatments. For example, pill can be psychological processes and mechanisms. The substituted for inhaler. Research has shown that resulting instrument may consist of single-item the aspects of treatment representations assessed subscales that may be unique for the illness by the BMQ predict self-management and condition being studied (e.g., Halm et al., 2006). medication adherence across various chronic The development of items to assess treatment rep- conditions (e.g., Horne & Weinman, 1999). resentations is conducted in a similar fashion. Both approaches present different limitations When developing items to assess treatment and offer unique advantages. The domain-based representations, one must pay special attention to approach has most often been criticized for issues such as the cues used by individuals for relying on single-item measures to assess the initiating and evaluating action (e.g., Do symp- various aspects of illness representations. The toms or objective information such as blood assumption underlying this criticism is that glucose monitoring initiate self-management?), single items have low reliability. However, the expected time for observing effects, and the there is no evidence to suggest that single items specific behaviors used to control or eliminate do not make reliable assessments (Wanous, the health threat (e.g., complementary medicine, Reichers, & Hudy, 1997). The main advantage rest, and distraction). of this approach is that the development of The instrument-based approach is best domain-specific items can facilitate the theoreti- represented by multi-item questionnaires devel- cal understanding about the precise pathways oped to assess both illness and treatment linking illness and treatment representations, representations. The Illness Perception behaviors, and health outcomes within each Common-Sense Model of Self-regulation 465 C illness conditions. The downside of domain- lifestyle changes) that target individuals who based measures is that the uniqueness of items feel healthy require that investigators understand makes it difficult to compare findings across ill- the factors that make them feel vulnerable to ness conditions. health threats (e.g., perceived risk based on age Because the IPQ-R and the BMQ include mul- or family history). Interventions with persons tiple items to assess each construct, the estima- suffering from chronic conditions require inves- tion of reliability is not an issue. However, tigators to have a detailed understanding of the C because there are several instances in each disease and its context. If the interventions are subscale where items are similarly worded, the aimed at improving self-management, for multi-item nature of the scales does not result instance, investigators need to know the cues necessarily in a more precise instrument. In that impede or facilitate behaviors (e.g., symp- addition, as indicated by Broadbent, Petrie, toms), beliefs about treatments (e.g., risk of addi- Main, and Weinman (2006), the large number of tion), and the complexity of the treatment. items makes it difficult to use when resources are The context in which the intervention is deliv- limited. Length of the instrument has been ered will also affect the foci and the delivery of addressed by the development and validation of interventions. For example, interventions to the brief IPQ. The main advantage of these instru- improve adherence to medical treatment may ments is that the wording of items is consistent have different targets for change depending on across studies and illness conditions, which facil- whether they are delivered in the office of itates comparisons. It is important to note, a primary care physician or in the community. however, that psychometric research is needed Primary care physicians can focus on eliciting to determine whether these instruments are illness and treatment representations and negoti- invariant across people with different illness ate with patients a representation that encourages conditions and across countries. adherence to medical treatment. For a condition Combining both approaches will most likely such as asthma, if patients hold an acute view of have the greatest impact from both a research and the condition and, therefore, use inhaled cortico- an applied perspective. A set of items such as steroids only when having symptoms, then the those from the brief IPQ would provide investi- primary care physician may provide them with gators with a core set of items that could be appraisal tools to disconfirm this inaccurate employed in all studies, thus enabling future belief. Such patients may be instructed to climb comparisons. The addition of domain-specific up one flight of stairs for a few days and take items to the brief IPQ would allow investigators notice of their breathing, before beginning their to delve into specific issues unique to the health daily regime of medications. This simple instruc- threat under investigation. tion should help patients realize that without their medication, their breathing becomes more diffi- Interventions and the CSM cult with minimal exercise, despite the absence of A basic corollary of the emphasis the CSM puts noticeable symptoms prior to the exercise. This on the content of illness and treatment represen- could provide experiential evidence for the tations and the actions specified by these patient that asthma is present even when representations is that successful interventions asymptomatic. To solidify this more accurate require an adequate model of the problem. This illness representation, these patients may then implies that interventions will vary depending on be instructed to repeat this exercise after follow- the health status of the target population ing the inhaled corticosteroid regime as pre- (e.g., well vs. not well) and on the type of illness scribed and notice improvements in their conditions individuals have if the target breathing after climbing up stairs. This second population for the intervention consists of people part of the intervention can allow patients to with chronic conditions. For instance, primary link improvements in breathing with the regular prevention interventions (e.g., screening or use of medications. Thereby, the reformulation of C 466 Common-Sense Model of Self-regulation their illness representation can be a life-saving to appraise coping procedures interact to tool. A community-based, population level inter- influence self-regulation. Not only is such knowl- vention, unlike the physician-patient dyad edge necessary for better understanding of interaction described above, is likely to deal psychological phenomena but also for the design with patients whose beliefs may differ widely. of more effective and potentially life-saving In this case, attempting to change each individ- interventions. Emotional aspects of illness and ual’s representations may not be feasible. A more treatment representations constitute another area effective and efficient approach would focus on that requires more research. Emotional represen- modifying management behaviors, such as how tations have been shown to play an important role to incorporate the use of inhaled corticosteroids in care seeking and self-management into one’s daily routine, by, for example, leaving (e.g., Mora, Robitaille, Leventhal, Swigar, & the inhaler on the kitchen or dining room table, Leventhal, 2002); however, their interaction the proper technique to use the inhaler, and incor- with illness representations in determining porating abstract information (e.g., peak flow behaviors is not yet fully understood. Progress meter readings) into the monitoring of asthma. in these areas will greatly benefit from basic An intervention focusing on patient-doctor behavioral medicine research conducted in con- interaction has provided important evidence that junction with intervention research. If properly physicians can successfully elicit patients’ illness designed and theoretically sound, intervention representations during medical visits (de Ridder, studies can provide strong evidence of causal Theunissen, & van Dulmen, 2007). Unfortu- relations. A comprehensive mapping of mecha- nately, this intervention did not test whether nisms, however, may require the use of discussion of illness representations results in nontraditional designs that focus on changing improved health outcomes. well-delimited processes in a sequential manner Despite the consistent and robust findings that (i.e., tailored, stepwise interventions). illness and treatment representations are powerful Theoretical progress should occur simulta- determinants of behaviors (Hagger & Orbell, 2003), neously with advances in measurement (Petersen, interventions using principles from the CSM are van den Berg, Janssens, & Van den Bergh, 2011). sparse. The results of these interventions, nonethe- Testing the full CSM will require that researchers less, are quite promising. Interventions with develop adequate measurement. Initiatives such patients suffering from chronic conditions have as the NIH PROMIS provide a good model to demonstrated that changing illness representations follow (Cella, Gershon, Lai, & Choi, 2007). The has an important effect on health outcomes (e.g., creation of item banks based on theoretical and Petrie, Cameron, Ellis, Buick, & Weinman, 2002). practical considerations would afford investiga- However, specific pathways through which tors both a common set of tools to allow changes in illness representations affect health are comparisons and flexibility to address issues not yet clearly understood. unique to the research problem. This will also require that researchers adopt current measure- Concluding Remarks ment strategies such as item response theory to Although the CSM is a sound and powerful examine the psychometric properties of their theoretical framework, there is still much to do instruments. to improve the understanding of the cognitive and emotional determinants of health-related behav- iors. Two key issues that need more research Cross-References attention can be highlighted. First, enormous pro- gress has been made in the study of illness and ▶ Coping treatment representations, but less is known ▶ Health Beliefs about how other aspects of the CSM such as ▶ Illness Perceptions Questionnaire (IPQ-R) appraisal tools, coping procedures, and criteria ▶ Self-regulation Communication Skills 467 C

References and Readings Leventhal, H., Leventhal, E. A., & Cameron, L. (2001). Representations, procedures, and affect in illness self- Broadbent, E., Petrie, K. J., Main, J., & Weinman, J. (2006). regulation: A perceptual-cognitive model. In A. The brief illness perception questionnaire (bipq). Jour- Baum, T. Revenson, & J. Singer (Eds.), Handbook of nal of Psychosomatic Research, 60(6), 631–637. Health Psychology. New York: Erlbaum. Cameron, L. D., & Leventhal, H. (2003). The Leventhal, H., & Nerenz, D. (1985). The assessment of self-regulation of health and illness behaviour. illness cognition. In P. Karoly (Ed.), Measurement New York: Routledge. strategies in health (pp. 517–554). New York: John C Cella, D., Gershon, R., Lai, J.-S., & Choi, S. (2007). The Wiley & Sons. future of outcomes measurement: Item banking, Miller, G. A., Galanter, E., & Pribram, K. H. (1960). Plans tailored short-forms, and computerized adaptive and the structure of behavior. New York: Holt. assessment. Quality of Life Research, 16, 133–141. Mora, P. A., Robitaille, C., Leventhal, H., Swigar, M., & doi:10.1007/s11136-007-9204-6. Leventhal, E. A. (2002). Trait negative affect relates to de Ridder, D. T., Theunissen, N. C., & van Dulmen, S. M. prior week symptoms, but not to reports of illness (2007). Does training general practitioners to elicit episodes, illness symptoms and care seeking among patients’ illness representations and action plans older people. Psychosomatic Medicine, 64(3), influence their communication as a whole? Patient 436–449. Education and Counseling, 66(3), 327–336. Moss-Morris, R., Weinman, J., Petrie, K. J., Horne, R., doi:http://dx.doi.org/10.1016/j.pec.2007.01.006. Cameron, L. D., & Buick, D. (2002). The revised Gallo, J. J., Rabins, P. V., Gallo, J. J., & Rabins, P. V. illness perception questionnaire (ipq-r). Psychology (1999). Depression without sadness: Alternative & Health, 17(1), 1–16. presentations of depression in late life. American Fam- Petersen, S., van den Berg, R. A., Janssens, T., & Van den ily Physician, 60(3), 820–826. Bergh, O. (2011). Illness and symptom perception: Hagger, M. S., & Orbell, S. (2003). A meta-analytic A theoretical approach towards an integrative mea- review of the common-sense model of illness repre- surement model.Clinical Psychology Review, 31(3), sentations. Psychology & Health, 18(2), 141–184. 428–439. doi:10.1016/j.cpr.2010.11.002. Halm, E. A., Mora, P., & Leventhal, H. (2006). No Petrie, K. J., Cameron, L., Ellis, C. J., Buick, D., & symptoms, no asthma: The acute episodic disease Weinman, J. (2002). Changing illness perceptions belief is associated with poor self-management after myocardial infarction: An early intervention ran- among inner city adults with persistent asthma. domized controlled trial. Psychosomatic Medicine, Chest, 129(3), 573–580. 64(4), 580–586. Horne, R., & Weinman, J. (1999). Patients’ beliefs about Petrie, K. J., & John, W. (1997). Perceptions of health and prescribed medicines and their role in adherence to illness: Current research and applications. treatment in chronic physical illness. Journal of Amsterdam: Harwood Academic Publishers. Psychosomatic Research, 47(6), 555–567. Skelton, J. A., & Croyle, R. T. (1991). Mental represen- Horne, R., Weinman, J., & Hankins, M. (1999). The tation in health and illness. New York: Springer. beliefs about medicines questionnaire: The develop- Wanous, J. P., Reichers, A. E., & Hudy, M. J. (1997). ment and evaluation of a new method for assessing the Overall job satisfaction: How good are single-item cognitive representation of medication. Psychology & measures? Journal of Applied Psychology, 82(2), Health, 14(1), 1–24. 247–252. Leventhal, H. (1970). Findings and theory in the study of fear communications. In L. Berkowitz (Ed.), Advances in experimental social psychology (Vol. 5, pp. 120–186). New York: Academic. Leventhal, H., Benyamini, Y., Brownlee, S., Communication Skills Diefenbach, M., Leventhal, E. A., Patrick-Miller, L., et al. (1997). Illness representations: Theoretical foun- dations. In K. J. Petrie & J. A. Weinman (Eds.), Per- Yori Gidron ceptions of health and illness: Current research and Faculty of Medicine and Pharmacy, Free applications (pp. 19–45). Singapore: Source Harwood University of Brussels (VUB), Jette, Belgium Academic Publishers. Leventhal, H., Breland, J. Y., Mora, P. A., & Leventhal, E. A. (2010). Lay representations of illness and treatment: A framework for action. In A. Steptoe Definition (Ed.), Handbook of behavioral medicine: Methods and applications (pp. 137–154). New York: Springer. Communication skills are an essential medium Leventhal, H., & Cameron, L. (1987). Behavioral theories and the problem of compliance. Patient Education & through which physicians interact with patients, Counseling, 10(2), 117–138. in order to diagnose and treat patients. According C 468 Communication, Nonverbal to Ong, de Haes, Hoos, and Lammes (1995), medical schools worldwide. Studies show that doctor-patient communication has three main such training positively influences patients’ roles: (1) to create a positive interpersonal rela- health outcomes including blood pressure and tionship, (2) exchange information, and (3) make glucose stability (Inui, Yourtee, & Williamson, treatment-related decisions. A positive interper- 1976). Interestingly, doctors’ communication sonal relationship includes facilitation of trust skills also influence patients’ decision making between the patient and a health professional (van den Brink-Muinen et al., 2006), an impor- that enables honest bidirectional expression of tant finding in an era where patients take a more concerns and report of behaviors (e.g., risky active role in their health care. behaviors, nonadherence). Exchange of informa- tion is the basis of the doctor-patient interaction, Cross-References where information from patient to doctor enables the latter to arrive at more accurate diagnoses ▶ Communication, Nonverbal and more suitable and effective treatments. ▶ Education, Patient Similarly, exchange of information from physi- ▶ Empathy cian to patient enables the doctor to inform ▶ Empowerment the patient about risks of unhealthy behaviors (e.g., smoking) and benefit of others (e.g., self-monitoring of glucose levels or of physical References and Readings activity). Finally, adequate communication helps physicians decide about patient-tailored treat- Beck, R. S., Daughtridge, R., & Sloane, P. D. (2002). ments, suitable to their age, culture, levels of Physician-patient communication in the primary care office: A systematic review. Journal of the American information-seeking, family history of an illness, Board of Family Practice, 15, 25–38. comorbidities, etc. Di Blasi, Z., Harkness, E., Ernst, E., Georgiou, A., & According to research (e.g., Di Blasi, Kleijnen, J. (2001). Influence of context effects on Harkness, Ernst, Georgiou, & Kleijnen, 2001; health outcomes: A systematic review. Lancet, 357, 757–762. Ong et al., 1995), doctor-patient communication Inui, T. S., Yourtee, E. L., & Williamson, J. W. (1976). skills (e.g., information giving, listening, Improved outcomes in hypertension after physician reassuring) affect patients’ satisfaction from tutorials. A controlled trial. Annals of Internal Medi- treatment, understanding and recall of the cine, 84, 646–651. Ong, L. M., de Haes, J. C., Hoos, A. M., & Lammes, F. B. interaction with doctors, adherence to medical (1995). Doctor-patient communication: A review of the regimes, and actual health outcomes. The influ- literature. Social Science & Medicine, 40, 903–918. ence of communication skills on patient recall van den Brink-Muinen, A., van Dulmen, S. M., is important given that patients can at times de Haes, H. C., Visser, A. P., Schellevis, F. G., & Bensing, J. M. (2006). Has patients’ involvement in recall very little of the information provided to the decision-making process changed over time? them during consultations. A review on this Health Expect, 9, 333–342. topic found 14 studies on verbal variables and patient outcomes and showed that factors such as empathy, reassurance, “psychosocial talk,” Communication, Nonverbal humor, and patient-centered talk correlated with positive health outcomes. The same review Ross Buck identified eight studies on nonverbal communi- Communication Sciences and Psychology, cation and patient outcomes and showed that University of Connecticut, Storrs, CT, USA factors such as head nodding, forward leaning, and less mutual gaze correlated with positive health outcomes (Beck, Daughtridge, & Sloane, Synonyms 2002). Communications skills can be, and are taught, as part of medical education in many Body language Community Coalitions 469 C

Definition what circumstances. Buck and van Lear (2002) termed this pseudospontaneous communication: Communication involves three elements: sender, it is symbolic on the part of the sender but spon- receiver, and message. In nonverbal communica- taneous on the part of the receiver. The ability to tion, the message does not involve words, but influence others’ emotions successfully is an rather employs body language. There are three importantaspectofcharisma. Ekman and Friesen major sorts of nonverbal communication. Sym- (1975) identified expression management tech- C bolic nonverbal communication is the intentional niques: a person might modulate the intensity of encoding of a message that is decoded by the the display, qualify a felt display by adding an receiver, the grammar and vocabulary of which additional display, and falsify the display in several must be learned by both sender and receiver. It is ways: neutralizing and showing no display, simu- propositional in that it is capable of logical anal- lating an unfelt display, or masking what one actu- ysis (e.g., it can be false). Symbolic nonverbal ally feels by showing a different, unfelt display. communication includes sign language, finger spelling, and pantomime, as well as facial expres- sions and gestures associated with language. In Cross-References Ekman and Friesen’s (1969) analysis, the latter include emblems with specific “dictionary” defi- ▶ Emotional Expression nitions, illustrators of what is said, and regula- tors of interaction flow. Left hemisphere damage produces deficits in both linguistic and symbolic- References and Readings nonverbal communication. Spontaneous communication involves the dis- Buck, R. (1984). The communication of emotion. New play of a motivational-emotional state by the York: Guilford Press. Buck, R., & Duffy, R. (1980). Nonverbal communication of sender and a pickup of that display by the affect in brain damaged patients. Cortex, 16, 351–362. receiver. It is non-intentional, based upon innate Buck, R., & van Lear, C. A. (2002). Verbal and nonverbal displays and preattunements that coevolved, that communication: Distinguishing symbolic, spontane- is, that evolved simultaneously with the function ous, and pseudo-spontaneous nonverbal behavior. Journal of Communication, 52, 522–541. of communication. Preattunements may be asso- Ekman, P., & Friesen, W. V. (1969). Nonverbal leakage ciated with mirror neuron systems that respond and cues to deception. Psychiatry, 32, 88–105. immediately and automatically to displays. The Ekman, P., & Friesen, W. V. (1975). Unmasking the face. elements of spontaneous communication are Englewood Cliffs, NJ: Prentice-Hall. Ross, E. (1981). The aprosodias: Functional-anatomic orga- signs, being inherent aspects of the referent (as nization of the affective components of language in the smoke is a sign of fire). If the sign is present, the right hemisphere. Archives of Neurology, 38, 561–569. referent must be present by definition so that spontaneous communication is nonpropositional. Spontaneous displays include facial expressions, affective vocal prosody or paralanguage, postures and gestures, eye behaviors, touch (haptics), spa- Community Coalitions tial behaviors (proxemics), and olfactory cues (e.g., pheromones). Right hemisphere damage Benjamin Hidalgo produces deficits in communication via facial Department of Psychiatry, Medical College of expression and affective prosody. Wisconsin, Milwaukee, WI, USA The third sort of nonverbal communication involves the intentional management of the dis- play by the sender to manipulate the receiver Synonyms (deception) or to follow display rules: learned rules about what displays are appropriate under Community collaboration; Community partnership C 470 Community Coalitions

Definition general stages (formation, maintenance, and institutionalization), but these stages recycle as The definition of community coalition can vary new members are recruited, plans change, or depending on the discipline of origin and different new issues are added. At each stage, specific variables of interest (Gentry, 1987). However, factors unique to that stage and to that coalition a common definition used in community health is enhance coalition function and progression to the “a group of individuals representing diverse orga- next stage. nizations, factions, or constituencies within the community who agree to work together to achieve Construct 2: Community Context a common goal” (Feighery & Rogers, 1990). Here it is proposed that contextual factors have a significant impact on the function and effective- ness of the coalition. These factors include but Description are not limited to geography, sociopolitical environment, social norms surrounding collabo- Types of Coalitions rative efforts, and timing. Historically, a diverse number of models have been conceptualized through which Construct 3: Lead Agency/Convener Group to understand the ways in which coalitions Coalitions form when a lead agency or convening function in their communities. These include organization responds to an opportunity, threat, collaboration approaches, empowerment, asset- or mandate. Through their review of the state of based approaches, constructions of risk and the field, the authors propose here that the protective factors for intervention development, formation of the coalition is more likely when citizenship models promoting citizen participa- the convener group provides support and tion, and promotion of community development resources during the formation stage (Francisco, Fawcett, Wolff, & Foster, 1996). (e.g., technical assistance, financial and material Other approaches to understanding coalitions support, credibility, and networks and contacts). focus, more specifically, on optimal They also argue that enlisting community internal functioning of these organizations gatekeepers to develop credibility and trust with (e.g., Allen, 2005 and Foster-Fishman, Berkowitz, others in the community is a way to increase the Lounsbury, Jacobson, & Allen, 2001). success of coalition formation.

Community Coalition Action Theory Construct 4: Coalition Membership While each of these emphasis and proposed mech- The authors propose, around membership, that anisms of action includes their own framework for coalitions begin by recruiting an initial core understanding the successful development of group of highly committed members. They also a coalition, the single most comprehensive frame- propose that effective coalitions eventually work is the Community Coalition Action Theory expand this established core group to include as proposed by Frances Butterfoss and Michelle a broader constituency of partners that represent Kegler (2009). This examination of the structure the more diverse needs, interests, and groups in and development of coalitions specifically in com- the community. munity change contexts was formulated through extensive research, practice, and review of the Construct 5: Operations and Process field. It is comprised of 14 major constructs each In order to ensure an effective internal process, five with its own set of theory propositions. necessary components are proposed: open and fre- quent communication among staff members, Construct 1: Stages of Development shared and formalized decision making, effective In this construct, it is proposed that coalition conflict management, positive relationships building is cyclical. Coalitions develop in three among members, and the perception by members Community Coalitions 471 C that the benefits of participation outweigh the costs Construct 14: Community Capacity of participation. The final construct in this model proposes that, as a result participating in a successful coalition, Construct 6: Leadership and Staffing organizations, and community members, achieve Here it is proposed that effective coalition func- increases in capacity and social capital that allow tioning, collaboration, and planning are improved them to address health and social issues in by strong leadership and skilled, paid, staff. the future. C

Construct 7: Structure Coalition Evaluation The proposition in this construct is that having Historically, there have been a wide variety of formalized rules, roles, structures, and proce- approaches to evaluating the effectiveness of coa- dures leads to routinized operations being better litions. These evaluations have employed quali- sustained and to overall coalition effectiveness. tative, quantitative, and mixed methodologies and typically have examined coalitions at one or Construct 8: Pooled Member and External more of the following levels: process and infra- Resources structure, specific programs and interventions, Here it is proposed that that synergistic pooling of health status or community change outcome, resources from members and from the commu- and extent of community capacity building nity leads to effective assessment, planning, and (Butterfoss, 2007; Granner & Sharpe, 2004). implementation strategies. Given the wide variety of coalitions, their reasons for existing, and the mechanism by which they Construct 9: Member Engagement propose to act on their communities, The authors propose that satisfied and committed Berkowitz (2001) argues that this diverse set of members will participate more fully in the work evaluation strategies is necessary if evaluators are of the organization. to effectively understand the degree to which coalitions are successful. Construct 10: Assessment and Planning While acknowledging the necessary The proposition here points to evidence that diversity of coalition evaluation strategies, shows that successful implementation of coali- Butterfoss (2007) proposes ten overall principles tion efforts is more likely when comprehensive to guide coalition evaluation: assessment and planning occur. 1. The evaluation should involve a process of partnership between coalition and evaluator. Construct 11: Implementation of Strategies 2. The evaluation design should be informed by The proposition here is that community change is research, previous evaluations, and commu- more likely to occur of coalitions direct their nity wisdom. efforts at multiple levels. 3. The evaluation should actively include the participation of all stakeholders. Construct 12: Community Change Outcomes 4. The evaluation process should be used to This proposition highlights the fact that coalitions assess, reflect, improve, and inform. that can change community policies, practices, 5. Expectations for the evaluation should be and environments are more likely to achieve made clear for all stakeholders. long-term success and increases in community 6. Issues of power and privilege should be capacity to address future issues. explicitly identified and addressed at the start. Construct 13: Health and Social Outcomes 7. The evaluation should constantly seek to Here the authors propose that the ultimate indi- foster positive relationships and trust among cator of coalition effectiveness is improvement in evaluators, community participants, practi- health and social outcomes. tioners, and funders. C 472 Community Coalitions

8. The process of evaluation should be closely Butterfoss,F.D.,Kegler,M.C.,&Francisco,V.T. integrated into ongoing functions and (2008). Mobilizing organizations for health promo- tion: Theories of organizational change. In K. Glanz, activities. B. K. Rimer, & K. Viswanath (Eds.), Health behav- 9. The evaluation process, itself, should be peri- ior and health education: Theory, research, and odically reevaluated to ensure that it practice (4th ed., pp. 335–361). San Francisco: continues to meet the coalition’s needs and Jossey-Bass. Cramer, M. E., Atwood, J. R., & Stoner, J. A. (2006). in order to apply findings to ongoing decision Measuring community coalition effectiveness using the making and learning. ICE# instrument. Public Health Nursing, 23(1), 74–87. 10. Findings should be shared frequently with all Downey, L. M., Ireson, C. L., Slavova, S., & McKee, G. stakeholders in a format that is accessible to (2008). Defining elements of success: A critical path- way of coalition development. Health Promotion them. Practice, 9(2), 130–139. Evaluations the follow these principles can Butterfoss, F. D., & Kegler, M. C. (2009). The community help coalitions in a number of ways (Butterfoss, coalition action theory. In R. J. DiClemente, R. A. 2007; Butterfoss & Francisco, 2004): providing Crosby, M. C. Kegler, R. J. DiClemente, R. A. Crosby, & M. C. Kegler (Eds.), Emerging theories in health accountability to the community and funders for promotion practice and research (2nd ed., the actions of the coalition, determining whether pp. 237–276). San Francisco: Jossey-Bass. coalition objectives are met, improving program Foster-Fishman, P. G., Berkowitz, S. L., Lounsbury, implementation, increasing awareness and support D. W., Jacobson, S., & Allen, N. A. (2001). Building collaborative capacity in community coalitions: of the coalition in the community, informing pol- A review and integrative framework. American Jour- icy decisions, and contributing the empirical liter- nal of Community Psychology, 29(2), 241–261. ature on best practices. Feighery, E., & Rogers, T. (1990). Building and maintaining effective coalitions. Palo Alto, CA: Health Promotion Resource Center, Stanford Center for Research in Disease Prevention. Cross-References Francisco, V. T., Fawcett, S. B., Wolff, T. J., & Foster, D. L. (1996). Coalition typology: Toward a research- ▶ Community-Based Health Programs based typology of health and human service coalitions. ▶ AHEC/Community Partners. Retrieved August 17, Community-Based Participatory Research 2011, from Community Partners website: http:// ▶ Health Promotion and Disease Prevention www.compartners.org/stacks/archive/hcm/coalition_ typology.pdf Gentry, M. E. (1987). Coalition formation and processes. References and Readings Social Work with Groups: A Journal of Community and Clinical Practice, 10, 39–54. Allen, N. E. (2005). A multi-level analysis of community Granner, M. L., & Sharpe, P. A. (2004). Evaluating com- coordinating councils. American Journal of Commu- munity coalition characteristics and functioning: nity Psychology, 35(1–2), 49–63. A summary of measurement tools. Health Education Berkowitz, B., & Wolff, T. (1999). The spirit of the coa- Research, 19(5), 514–532. lition. Washington, DC: American Public Health Kramer, J. S., Philliber, S., Brindis, C. D., Kamin, S. L., Association. Chadwick, A. E., & Revels, M. L. (2005). Coalition Berkowitz, B. (2001). Studying the outcomes of commu- models: Lessons learned from the CDC’s community nity-based coalitions. American Journal of Community coalition partnership programs for the prevention of Psychology, 29(2), 213–227. teen pregnancy. Journal of Adolescent Health, 37(S3), Butterfoss, F., & Francisco, V. T. (2004). Evaluating S20–S30. community partnerships and coalitions with Lentz, B. E., Imm, P. S., Yost, J. B., Johnson, N. P., practitioners in mind. Health Promotion Practice, 5, Barron, C., Lindberg, M. S., et al. (2005). Empowerment 108–114. evaluation and organizational learning: A case study of Butterfoss, F. D., Goodman, R. M., & Wandersman, A. a community coalition designed to prevent child abuse (1996). Community coalitions for prevention and and neglect. In D. M. Fetterman & A. Wandersman health promotion: Factors predicting satisfaction, (Eds.), Empowerment evaluation principles in practice participation, and planning. Health Education Quar- (pp. 155–182). New York: Guilford Press. terly, 23(1), 65–79. Wolff, T. (2001). The future of community coalition Butterfoss, F. D. (2007). Coalitions and partnerships in building. American Journal of Community Psychol- community health. San Francisco: Jossey-Bass. ogy, 29, 263–268. Community-Based Health Programs 473 C

to drinking water. Realistically, a study investigat- Community Collaboration ing the influence of fluoridation would need large community samples. A classic study was reported ▶ Community Coalitions by Ast and Schlesinger (1956)inwhichthedrink- ing water for one town in New York State was fluorinated and the water for a second town in the state was not. The towns were chosen to be as C Community Health Advisors similar as possible so that any difference in dental health could reasonably be attributed to the influ- ▶ Promotoras ence of interest, i.e., presence or absence of fluo- ride in the water. The study provided compelling evidence that fluoridation is both effective in reducing dental caries and a safe public health Community Health Representatives practice. Exposure status in community trials, there- ▶ Promotoras fore, is assigned to an entire community rather than to individuals. Typical outcomes of interest include the risk of disease or the frequency of a health behavior (Hartge & Cahill, 2008). Since Community Health Workers (CHW) the unit of observation is the community, the assessment of potential confounders can also ▶ Promotoras occur at the community level, and thus appropri- ate care in that regard is needed.

Community Partnership Cross-References ▶ Community Coalitions ▶ Bias ▶ Clinical Trial ▶ Randomization Community Sample

J. Rick Turner References and Readings Cardiovascular Safety, Quintiles, Durham, NC, USA Ast, D. B., & Schlesinger, E. R. (1956). The conclusion of a ten-year study of water fluoridation. American Jour- nal of Public Health, 46, 265–271. Hartge, P., & Cahill, J. (2008). Field methods in epidemi- Definition ology. In K. J. Rothman, S. Greenland, & T. L. Lash (Eds.), Modern epidemiology (3rd ed., pp. 492–510). Community samples are used in community Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. trials, or community intervention trials, i.e., trials in which the intervention is implemented at the community level. This contrasts with clinical trials, where intervention is implemented at the level of the individual subject. Community-Based Health Programs Consider the example of testing the dental health advantages of adding fluoride (fluoridation) ▶ Community-Based Participatory Research C 474 Community-Based Participatory Research

studies, cohort studies, and randomized con- Community-Based Participatory trolled trials. CBPR distinguishes itself, how- Research ever, by involving community members (through needs assessments, iterative commu- Lee Sanders nity-based meetings, and other opportunities Center for Health Policy and Primary Care forcomment)ineverystageoftheresearch Outcomes Research, Stanford University, process. Beginning with the research question, Stanford, CA, USA community members help define the health out- comes, behaviors, and environmental factors to be addressed by the research proposal. Synonyms A community advisory committee, normally chaired by a community-based stakeholder, is Community-based research often an integral part of the research process. In the spirit of mutual expertise and collabora- tion, CBPR research protocols often employ Definition community residents as members of the research team, and they may include support for research Community-based participatory research facilities and research materials housed inside (CBPR) is a set of principles and techniques a community-based facility (Stratford et al., designed to involve community members as col- 2003; Vander Stoep, Williams, Jones, Green, & laborators in every aspect of the research process, Trupin, 1999). All study interventions, research including design, funding, implementation, and trainings, survey materials, informed-consent dissemination (Higgins, Maciak, & Metzler, documents, and other materials include input 2001; Israel et al., 1998). Fully realized, CBPR and guidance from community members. Mea- includes shared expertise between researcher and sures employed in CBPR usually include social community, shared decision making, and mutual determinants of health and cost-effectiveness ownership of the research enterprise and its variables from the community perspective. results. Effective CBPR normally results from Study results are normally shared with the com- a long-standing, trusting relationship between munity advisory committee or other community an academic research team and a community- members for feedback and interpretation before based organization (CBO) (Israel et al., 1998; they are shared with outside audiences. With Viswanathan et al., 2004). CBPR is of particular attention to community standards and research value to health researchers, public health profes- ethics, results are also disseminated across the sionals, and community leaders attempting to community. In the case of interventions deter- address health disparities influenced by social mined to be effective, sustainability planning determinants (e.g., socioeconomic status, race, that includes community leaders is a critical ele- ethnicity, literacy, nutrition, environmental ment of the CBPR process. health). CBPR also holds relevance for policymakers attempting to turn community- Health Behavior Change needs assessments into evidence-based action or CBPR enables researchers to be sensitive and to translate basic and clinical research findings responsive to the cultural, political, and social into population-wide practice. context of health behaviors. This includes chal- lenges and opportunities for influencing sensitive Research Process health behaviors (e.g., smoking, drug use, sexual CBPR adheres to the same high-quality research practices, domestic violence, obtaining screening standards that apply to health and behavioral tests that involve pelvic or rectal exams) and research designs, including observational other health behaviors that can only effectively Comorbidity 475 C be addressed at the community level (e.g., nutri- Stratford, D., Chamblee, S., Ellerbrock, T. V., et al. tion, physical activity). (2003). Integration of a participatory research strategy into a rural health survey. Journal of General Internal Medicine, 18(7), 586–588. Vander Stoep, A., Williams, M., Jones, R., Green, L., & Ethical Considerations Trupin, E. (1999). Families as full research partners: What’s in it for us? Journal of Behavioral Health Services and Research, 26(3), 329–344. C CBPR may also present constraints for the conduct Viswanathan, M., Ammerman, A., Eng, E., Gartlehner, of ethical research. In choosing the primary G., Lohr, K. N., Griffith, D., Rhodes, S., Samuel- research topic or question, a community-driven Hodge, C., Maty, S., Lux, L., Webb, L., Sutton, S. F., process may not yield a result that meets the aca- Swinson, T., Jackman, A., Whitener, L. (2004, July). Community-based participatory research: Assessing demic considerations of relevance, novelty, and the evidence. Evidence Report/Technology Assess- generalizability. Similarly, community members ment No. 99 (Prepared by RTI-University of North may object to the publication of study findings or Carolina Evidence-based Practice Center under Con- interpretations, even if “objective” research tract No. 290-02-0016). AHRQ Publication 04-E022- 2. Rockville, MD: Agency for Healthcare Research methods were applied. Funding and other rewards and Quality. for CBPR also may introduce ethical dilemmas. In optimal circumstances, community representa- tives and organizations should be reimbursed fairly for their participation. If addressed early and forthrightly, many of these ethical concerns Community-Based Research may be mitigated. Effective should include gaining insight and assent from all available com- ▶ Community-Based Participatory Research munity leaders, providing appropriate training if appropriate to participants, ensuring financial and nonfinancial recognition for participants, and clar- ifying rules for ownership and use of study data, Comorbidity analyses, and publications. Amy Wachholtz Department of Psychiatry, University of Cross-References Massachusetts Medical School, Worcester, MA, USA ▶ Cost-Effectiveness Analysis (CEA) ▶ Health Behaviors ▶ Participatory Research Synonyms

References and Readings Co-occuring

Higgins, D. L., Maciak, B., & Metzler, M. (2001). CDC Urban Research C. CDC Urban Research Centers: Definition Community-based participatory research to improve the health of urban communities. Journal of Women’s Health & Gender-Based Medicine, 10(1), 9–15. Comorbidity occurs when an individual experi- Israel, B. A., Schulz, A. J., Parker, E. A., et al. (1998). ences two or more disorders at the same time Review of community-based research: Assessing part- (Eaton, 2006). Comorbidities can occur sequen- nership approaches to improve public health. Annual tially, or they can become symptomatic sim- Review of Public Health, 19, 173–202. Minkler, M., & Wallerstein, N. (2003). Community based ultaneously. Disorders that are considered participatory research for health. San Francisco: comorbidities can be either physical or psycho- Jossey-Bass. logical in nature. It is a common occurrence C 476 Comparative Effectiveness Methodology that a disorder in one domain (e.g., a physical disorder of spinal cord injury) will trigger or Comparative Effectiveness Research exacerbate a disorder in another domain (e.g., a psychological disorder of depression). Two dis- J. Rick Turner orders within the same domain are also consid- Cardiovascular Safety, Quintiles, Durham, ered comorbidities (e.g., depression and anxiety, NC, USA or chronic obstructive pulmonary disorder and ischemic heart disease). There are some disorders that are such frequent comorbidities that they Synonyms may eventually be combined under a single label and treated as a single syndrome (e.g., met- CER; Comparative effectiveness methodology abolic syndrome which often includes high blood pressure, Type 2 diabetes, obesity, hypercholes- terolemia, and dyslipidemia). Definition Treatment providers will often assess for comorbidities in order to tailor the best treatment The definition of Comparative Effectiveness approach to that individual. Being aware of Research (CER) for the Federal Coordinating a patient’s comorbidities allows a treatment pro- Council reads as follows (HHS.gov): vider to educate the patient, consider additional Comparative effectiveness research is the con- treatment options, and potentially begin treat- duct and synthesis of systematic research com- ment for the comorbidity. paring different interventions and strategies to prevent, diagnose, treat, and monitor health con- ditions. The purpose of this research is to inform Cross-References patients, providers, and decision-makers, responding to their expressed needs, about ▶ Anxiety which interventions are most effective for which ▶ Anxiety and Heart Disease patients under specific circumstances. To provide ▶ Cancer and Smoking this information, comparative effectiveness ▶ Heart Disease and Cardiovascular Reactivity research must assess a comprehensive array of ▶ Heart Disease and Smoking health-related outcomes for diverse patient ▶ Heart Disease and Stress populations. Defined interventions compared ▶ Insulin Resistance (IR) Syndrome may include medications, procedures, medical ▶ Metabolic Syndrome and assistive devices and technologies, behav- ▶ Obesity: Causes and Consequences ioral change strategies, and delivery system inter- ▶ Sleep and Health ventions. This research necessitates the ▶ Unipolar Depression development, expansion, and use of a variety of data sources and methods to assess comparative References and Readings effectiveness. The inclusion of “behavioral change strate- Eaton, W. W. (2006). Medical and psychiatric comorbid- gies” makes CER of immediate interest in the ity over the course of life. Arlington, VA: American field of behavioral medicine. Psychiatric Publishing.

Description Comparative Effectiveness Methodology Sox and Greenfield (2009) discussed various important steps in the development and formali- ▶ Comparative Effectiveness Research zation of CER. A seminal article was published Comparative Effectiveness Research 477 C by Wilensky (2006), and an Institute of Medicine conducting observational studies; (3) reviewing (IOM) report called for a national initiative of selected observational studies from the Veterans research that would support better decision mak- Health Administration; and (4) appreciating the ing about interventions in health care (IOM, importance of fundamental methodological prin- 2008). A major step occurred when President ciples when conducting or evaluating individual Obama signed into law the American Recovery studies. and Reinvestment Act of 2009 (ARRA), which Bonham and Solomon (2010) observed that C allotted US$1.1 billion to CER. The legislation the success of the federal investment in CER created a Federal Council on CER, and asked the will hinge on using the power of science to IOM to elicit input from a broad array of stake- guide reforms in health-care delivery and holders on which research topics should have the improve patient-centered outcomes (as will be highest priority for funding through the ARRA true for other sources of investment in this and to then develop a list of the highest-priority area). They noted that “Translating the results of topics for the Secretary of Health and Human comparative effectiveness research into practice Services to consider. The IOM committee formu- calls for the rigors of implementation science to lated a more succinct definition of CER: “CER is ensure the efficient and systematic uptake, dis- the generation and synthesis of evidence that semination, and endurance of these innovations.” compares the benefits and harms of alternative Academic medicine is in a strong position to help methods to prevent, diagnose, treat and monitor in various ways: thoroughly integrating its a clinical condition, or to improve the delivery of research and training missions with clinical care care. The purpose of CER is to assist consumers, that is focused on patient-centered outcomes; clinicians, purchasers, and policy makers to make building multidisciplinary teams that include informed decisions that will improve health care a wide range of experts such as clinicians, clinical at both the individual and population levels.” and implementation scientists, systems engi- As Kupersmith and Ommaya (2010) noted, neers, behavioral economists, and social scien- The US Department of Veterans Affairs (VA) tists; and training future care providers, scientists, has a long history of conducting CER. Along and educators to carry innovations forward with pharmaceutical interventions, they have (Bonham and Solomon, 2010). had a large focus on behavioral interventions. An informative discussion was recently pro- The success of their CER program has been facil- vided by Blumenthal (2011) in a paper entitled itated by several important aspects of scientific “New frontiers in cardiovascular behavioral med- infrastructure related to (1) research question icine: Comparative effectiveness of exercise and refinement, (2) study design, planning, and coor- medication in treating depression.” As noted, dination, (3) evidence synthesis, and (4) imple- Blumenthal and his colleagues began investiga- mentation research. In publications that had VA tions into cardiac rehabilitation, which they con- coauthors in two major medical journals, 25% of sidered to be a “new frontier for behavioral the published studies were classified as CER. medicine.” That field of investigation laid In the future, the CER enterprise will move groundwork that has now provided the opportu- toward increased input from clinicians in the nity to compare exercise therapy, an established choice of research topics and enhanced consider- component of cardiac rehabilitation, with antide- ation of other methodologies besides the random- pressant pharmacotherapy as a treatment for ized controlled trial. Concato et al. (2010) depression in cardiac disease patients. Two ran- reviewed and discussed the use of observational domized clinical trials have now been conducted, studies in CER, focusing on the following: and, following a detailed discussion of their (1) understanding how observational studies can findings, the author commented as follows: provide accurate results, comparable to those “While these results are preliminary and should from randomized clinical trials; (2) recognizing be interpreted with caution, it appears that exer- strategies used in selected newer methods for cise may be comparable with conventional C 478 Comparator Group antidepressant medication in reducing depressive Rich, E. C., Bonham, A. C., & Kirch, D. G. (2011). The symptoms, at least for patients who are willing to implications of comparative effectiveness research for academic medicine. Academic Medicine, 86, 684–688. try it, and maintenance of exercise reduces the Sox, H. C., & Greenfield, S. (2009). Comparative effec- risk of relapse” (Blumenthal, 2011). tiveness research: A report from the institute of med- icine. Annals of Internal Medicine, 151, 203–205. United States Health and Human Services. HHS.gov. Cross-References Accessed December 14th, 2011, from http://www. hhs.gov/recovery/programs/cer/draftdefinition.html. Wilensky, G. R. (2006). Developing a center for compar- ▶ Behavioral Medicine ative effectiveness information. Health Affairs ▶ Cardiac Rehabilitation (Millwood), 25, w572–w585. ▶ Depression: Treatment ▶ Institute of Medicine ▶ Randomized Clinical Trial Comparator Group

References and Readings ▶ Control Group

Blumenthal, J. A. (2011). New frontiers in cardiovascular behavioral medicine: comparative effectiveness of exercise and medication in treating depression. Cleveland Clinical Journal of Medicine, 78(Suppl. 1), Complementary and Alternative S35–S43. Medicine Bonham, A. C., & Solomon, M. Z. (2010). Moving comparative effectiveness research into practice: ▶ Alternative Medicine Implementation science and the role of academic ▶ medicine. Health Affairs (Millwood), 29, 1901–1905. Integrative Medicine Blumenthal, J. A., Califf, R., Williams, R. S., & Hindman, M. (1983). Cardiac rehabilitation: A new frontier for behavioral medicine. Journal of Cardiac Rehabilitation, 3, 637–656. Concato, J., Lawler, E. V., Lew, R. A., Gaziano, J. M., Complex Traits Aslan, M., & Huang, G. D. (2010). Observational methods in comparative effectiveness research. Amer- Abanish Singh ican Journal of Medicine, 123(12 Suppl. 1), e16–e23. Hoffman, B., Babyak, M., Craighead, W. E., Sherwood, Duke University Medical Center, Durham, A., Doraiswamy, P. M., Coons, M. J., et al. (2010). NC, USA Exercise and pharmacotherapy in patients with major depression: One-year follow-up of the SMILE study. Psychosomatic Medicine, 73, 127–133. Huang, G. D., Ferguson, R. E., Peduzzi, P. N., & O’Leary, Definition T. J. (2010). Scientific and organizational collabora- tion in comparative effectiveness research: The VA Mendelian genetics put forward the concept cooperative studies program model. American Journal of dominant and recessive traits, where the of Medicine, 123(12 Suppl. 1), e24–e31. Institute of Medicine (Eden, J., Wheatley, B., McNeil, B., phenotypes are controlled by single genes. Sox, H., eds.). (2008). Knowing what works in health These traits are known as monogenic or Mende- care: A roadmap for the nation. Washington, DC: lian traits. Though there are many genes that National Academies Press. control Mendelian traits, in contrast, there are Kupersmith, J., & Ommaya, A. K. (2010). The past, pre- sent, and future of comparative effectiveness research features or traits in human genetics which are in the US Department of Veterans Affairs. American controlled by multiple genes and whose inheri- Journal of Medicine, 123(12 Suppl 1), e3–e7. tance does not follow the rules of Mendelian O’Connell, J. M., & Griffin, S. (2011). Overview of genetics. Such traits are known as complex traits. methods in economic analyses of behavioral interven- tions to promote oral health. Journal of Public Health Examples of complex traits include disorders Dentistry, 71(Suppl. 1), S101–S118. such as autism, cardiac disease, cancer, Computerized Axial Tomography (CAT) Scan 479 C diabetes, Alzheimer’s disease, and asthma. Complex traits are believed to result from Computed Axial Tomography gene-gene and gene-environment interactions, genetic heterogeneity, and potentially other yet ▶ Computerized Axial Tomography (CAT) Scan unknown reasons.

Computed Tomography C Cross-References ▶ Computerized Axial Tomography (CAT) Scan ▶ Gene-Environment Interaction ▶ Gene-Gene Interaction Computed Transaxial Tomography References and Readings ▶ CAT Scan Frazer, K. A., Murray, S. S., Schork, N. J., & Topol, E. J. (2009). Human genetic variation and its contribution to complex traits. Nature Reviews Genetics, 10, 241–251. Computer Cartography Glazier, A. M., Nadeau, J. H., & Aitman, T. J. (2002). Finding genes that underlie complex traits. Science, ▶ Geographic Information System (GIS) 298, 2345–2350. Technology

Compliance Computer-Based Patient Record ▶ Electronic Health Record ▶ Adherence ▶ Medical Utilization

Computerized Axial Tomography

Complications of Atherosclerosis ▶ Computerized Axial Tomography (CAT) Scan ▶ CAT Scan ▶ Peripheral Arterial Disease (PAD)/Vascular Disease Computerized Axial Tomography (CAT) Scan

Complimentary and Alternative Siqin Ye Medicine Division of Cardiology, Columbia University Medical Center, New York, NY, USA ▶ Alternative Medicine

Synonyms

Composition CAT scan; Computed axial tomography; Com- puted tomography; Computerized axial tomogra- ▶ Family, Structure phy; CT scan; X-ray computed tomography C 480 Computerized Tomography (CT)

Definition to developing better protocols with lower radia- tion doses, the decision to obtain a CAT scan for Computed axial tomography, or CAT scan, uti- an individual patient should be made judiciously, lizes computer algorithms to combine series of taking into careful consideration the trade-off two-dimensional X-ray images (tomographs) to between clinical benefit and potential harm, so produce three-dimensional representations of the as to avoid excess testing and radiation exposure. insides of objects. It is used in clinical medicine to noninvasively visualize potential pathologies Cross-References inside the human body. By eliminating the superimposition of adjacent structures and ▶ CAT Scan distinguishing different tissue types based on their densities, CAT scans are able to generate References and Readings high-resolution images of particular anatomic regions. Intravenous and oral contrast agents Achenbach, S., & Daniel, W. G. (2008). Computed tomog- can also be used to further enhance image quality, raphy of the heart. In P. Libby, R. O. Bonow, D. L. Mann, D. P. Zipes, & E. Braunwald (Eds.), Braunwald’s helping to distinguish vasculature and bowel heart disease: A textbook of cardiovascular medicine lumen from the surrounding tissue, respectively. (pp. 415–438). Philadelphia: Saunders Elsevier. Common uses of CAT scan include scanning of Brenner, D. J., & Hall, E. J. (2007). Computed tomogra- the head/brain, to assess strokes, intracranial phy-an increasing source of radiation exposure. The New England Journal of Medicine, 357, 2277–2284. bleeding, or tumors; of the chest, to assess lung Buzug, T. (2008). Computed tomography: From photon- parenchyma, pulmonary embolism, or diseases of statistics to modern cone-beam CT. Berlin, Germany: the great vessels such as thoracic aortic aneurysm Springer. or dissection; of the abdomen and pelvis, to assess pathologies such as kidney stones, appendicitis, pancreatitis, diverticulitis, intra-abdominal Computerized Tomography (CT) abscesses, and various visceral malignancies; and of the bones, to identify osteoporosis and delineate ▶ Brain, Imaging complex fractures (Buzug, 2008). In recent years, ▶ Neuroimaging there has also been ongoing development of multidetector computed tomography (MDCT) scanners, allowing for further enhanced spatial Concentration and temporal resolution. These technological advances have made possible new modalities of ▶ Coffee Drinking, Effects of Caffeine CT imaging, such as virtual colonoscopy for colon ▶ Meditation cancer screening or cardiac CT to visualize coro- ▶ Transcendental Meditation nary arteries as well as other structures of the beating heart (Achenbach & Daniel, 2008). The popularity of CAT scans has also led to Concordance concerns with regard to their potential adverse effects. In addition to the risk of renal injury Jennifer Wessel associated with the use of iodinated intravenous Public Health, School of Medicine, Indiana contrast, there has been recognition that the wide- University, Indianapolis, IN, USA spread use of CAT scans has led to increased radiation exposure for the general population, with recent estimates showing they may contrib- Definition ute to 1.5–2.0% of all cancers in the United States (Brenner & Hall, 2007). Due to these consider- Among a pair of twins, the twin pair exhibits ations, it has been recommended that in addition an identical phenotype. Within the twin pair, both Condom Use 481 C individuals share or lack the trait or disease under Definition investigation. Measuring concordance can also be done among siblings or other family members. Condom use implies that an FDA-approved latex Greater concordance in MZs versus DZs is sug- condom covered the entire head and shaft of the gestive evidence for a genetic contribution penis from the start of sex (initial penetration) to a disease. Concordance is measured as the num- until sex ended (no more penetration). The term ber of pairs that both exhibit (or not) the trait also implies that the condom was used properly, C divided by the total and presented as a percentage. thereby avoiding breakage, spillage, leaking, and slipping off the penis. The term applies to penile- References and Readings vaginal penetration, penile-oral penetration, and penile-anal penetration. In research studies, when Nussbaum, R. L., Mc Innes, R. R., & Willard, H. F. a person uses condoms consistently and correctly, (2001). Genetics in medicine (6th ed.). Philadelphia: he is classified as “having no risk exposure,” W.B. Saunders. Spector, T. D., Snieder, H., & MacGregor, A. J. (2000). meaning that he has not engaged in unprotected Advances in twin and sib-pair analysis (1st ed.). vaginal sex (UVS), unprotected oral sex (UOS), London: Greenwich Medical Media. or unprotected anal sex (UAS). The same classi- fication applies to females who are the recipients of penetrative sex that is 100% condom Concurrent Control protected. In addition, condom use can also imply the consistent and correct use of ▶ Control Group a polyurethane sheath that is closed at one end (intended to cover the cervix) and open at the other end (for penile penetration). Known as the Concussion “female condom,” this device is also worn by males who will be receptive partners in the act ▶ Traumatic Brain Injury of penile-anal sex.

Conditioned Response Description

▶ Placebo and Placebo Effect Condom use is currently the single best method of reducing the global AIDS pandemic and the ever- expanding pandemic of sexually transmitted Condom Protected Sex infections such as Chlamydia, gonorrhea, syphi- lis, trichomoniasis, genital herpes, and chancroid. ▶ Condom Use The degree of protection conferred by condom use varies as a function of the infection. Evidence is strongest relative to protection against the Condom Use transmission and the acquisition of the human immunodeficiency virus (HIV). Emerging evi- Rick Crosby dence suggests that condoms can be highly pro- University of Kentucky, Lexington, KY, USA tective against the male insertive partner’s acquisition of gonorrhea, Chlamydia, and syphi- lis. Evidence also supports the protective value of Synonyms condoms against these same infections for the receptive partner. However, for infections such Barrier method of protection; Condom protected as human papillomavirus (HPV) and genital her- sex; Prophylactic use; Protected sex pes (HSV), the protective value of condoms is not C 482 Condom Use nearly as good simply because these infections that people will “switch” from one sexual act to spread by skin-to-skin contact of genital areas another without changing condoms in between that condoms do not cover. Nonetheless, it is acts, thereby creating issues with disease transfer. indeed correct to say that condom use does offer The sheer volume of condom use errors and partial protection against HPV and HSV. problems reported by men and women strongly Despite the tremendous public health value of suggests that all too often condoms fail because condom use, prevailing sociopolitical climates the users lacked proper education. These forms of have frequently precluded efforts to educate condom failure are also an unfortunate omission men and women about condoms and their correct in studies of condom effectiveness, thereby cre- use. This lack of education has proven to be ating a bias toward the null hypothesis (i.e., that problematic in that a large number of studies condoms do not work). show that men and women experience multiple A broad range of behavioral and social issues errors and problems when using condoms. The inextricably surround condom use. For example, most common error, reported by both men and a robust finding has been that people are more women, is known as incomplete use. This means likely to use condoms with new or “casual” sex that the condom was put on after penetrative sex partners and far less likely to do so with established had begun and/or it was taken off before penetra- partners. Thus, a challenge in behavioral medicine tive sex had ended. Both behaviors have been is promoting condom use among at-risk, linked to arousal and erection issues as well as established, couples. Also, condom use and the ill-fitting condoms. In addition, condoms that use of hormonal contraceptives tend to be lose their lubrication during sex may be removed inversely correlated, meaning that condom use is prematurely (rather than simply adding lubri- reduced or abandoned when a couple begins using cant). Breakage is the next most common prob- highly reliable contraception methods. Here, the lem with condom use. Rather than being challenge in behavioral medicine is to promote the a problem inherent in the production of condoms, dual use of condoms and contraception. A similar breakage occurs as a consequence of user errors dynamic may exist in relation to vaccines for HPV such as applying oil-based lubrication, not leav- and microbicidal agents designed to prevent HIV ing an air space in the reservoir tip upon applica- infection – as people perceive less risk as tion, using condoms that are too small for the a consequence of the vaccine or microbicide they penis, letting condoms contact sharp objects may reduce or abandon condom use. Condom use (including teeth and jewelry) and failure to add will also be problematic in cultures (or among adequate amounts of water-based lubricants dur- couples) that value reproduction – an inherent ing prolonged sex. The next most common prob- downside of condom use for disease prevention lem is having condoms slip off the penis, either is that the behavior precludes desired conception. during penetrative sex or during the act of with- Low arousability and erection loss are also issues drawing the condomized penis after male ejacu- that greatly affect condom use, with several studies lation occurs. Loose-fitting condoms, not indicating incomplete use or lack of use to increase unrolling condoms all the way to the base of the arousability and help maintain erection. The chal- penis, erection issues, use of erection enhancing lenge here to behavioral medicine is integrating drugs, and poorly lubricated condoms have all sex therapy with STI prevention. been associated with slippage during sex. Mis- takes that people make when using condoms include putting the unrolled condom on the References and Readings penis upside down and then “flipping” it over so it will unroll (thereby introducing per-cum Crosby, R. A., Milhausen, R., Yarber, W. L., Sanders, S. A., & Graham, C. A. (2008). Condom “Turn Offs” [semen] into the outside tip of the condom thus among adults: An exploratory study. International compromising protection). Studies have shown Journal of STD and AIDS, 19, 590–594. Confidentiality 483 C

Crosby, R. A., Sanders, S. A., Yarber, W. L., & Graham, providing medical care. Traditionally, medical C. A. (2003). Condom use errors and problems: ethics has viewed the duty of confidentiality as A neglected aspect of studies assessing condom effec- tiveness. American Journal of Preventive Medicine, a relatively nonnegotiable tenet of medical practice. 24, 367–370. Issues regarding the confidentiality of health infor- Crosby, R. A., Yarber, W. L., Sanders, S. A., et al. (2007). mation passed between patients, providers, and Men with broken condoms: Who and why? Sexually insurersledtotheevolutionofregulatorylanguage Transmitted Infections, 83, 71–75. C Holmes, K. K., Levine, R., & Weaver, M. (2004). to protect patient privacy. Effectiveness of condoms in preventing sexually trans- The Health Insurance Portability and mitted infections. Bulletin of the World Health Orga- Accountability Act of 1996 (HIPAA) includes nization, 82, 454–461. in its language specific direction for the manage- Misovich, S. J., Fisher, J. D., & Fisher, W. A. (1997). Close relationships and elevated HIV risk behavior: ment of protected health information (PHI) in Evidence and possible underlying psychological both clinical and research arenas. The Privacy processes. Review of General Psychology, 1(1), Rule protects all “individually identifiable health 72–107. information” held or transmitted by a covered Sheeran, P., Abraham, C., & Orbell, S. (1999). Psychoso- cial correlates of heterosexual condom use: a meta- entity or its business associate, in any form or analysis. Psychological Bulletin, 125(1), 90–132. media, whether electronic, paper, or oral. The Privacy Rule calls this information “protected health information (PHI).” “Individually identifiable health information” Confidentiality is information, including demographic data, that relates to the individual’s past, present, or future Marianne Shaughnessy physical or mental health or condition; the provi- School of Nursing, University of Maryland, sion of health care to the individual; or the past, Baltimore, MD, USA present, or future payment for the provision of health care to the individual, and that identifies the individual or for which there is a reasonable Synonyms basis to believe it can be used to identify the individual. Individually identifiable health HIPAA; Patient privacy; Privacy information includes many common identifiers (e.g., name, address, birth date, social security number). There are no restrictions on the use or Definition disclosure of de-identified health information. De-identified health information neither iden- Ethical principle that dictates communications tifies nor provides a reasonable basis to identify are “privileged” and may not be discussed or an individual. divulged to third parties. Privacy rules apply only to covered entities. Covered entities are defined as a healthcare provider (physicians, nurse practitioners, psychol- Description ogists, dentists, clinics, nursing homes, pharma- cies, etc.), health plans (insurance companies, Confidentiality is a term that commonly applies to Health Maintenance Organization (HMOs), etc.), conversations between health care providers and or a healthcare clearinghouse (entities that process patients. Legal protections are available to prevent nonstandard health information they receive from physicians from revealing certain discussions with another entity into a standard format). Individuals, patients, even under oath in court. However, the organizations, and agencies that meet the definition rule only applies to information shared between of a covered entity under HIPAA must comply physician and patient during the course of with the rules’ requirements to protect the privacy C 484 Confounding Influence and security of health information and must provide individuals with information regarding Confounding Influence their rights with respect to their health information. If an entity is not a covered entity, it does not have J. Rick Turner to comply with the Privacy Rule. Cardiovascular Safety, Quintiles, Durham, Researchers are also bound by the rules NC, USA regarding confidentiality of protected health information. Generally speaking, researchers are required to safeguard the privacy of all health Definition information obtained in the course of screening or enrollment in a study to the extent permitted When investigating the influence of a factor of by law. In certain types of research, there interest, it is critically important to keep all other may be a high risk of identifying information potentially relevant influences as constant as that if disclosed, could have adverse conse- possible. That is, the only reasons for differences quences for subjects or damage their financial in how subjects respond to the treatments in standing, employability, insurability, or reputa- a research study should be the nature of the treat- tion. Certificates of confidentiality are issued by ments (interventions) themselves. Extraneous the National Institutes of Health (NIH) to protect influences are called confounding influences: identifiable research information from forced They make it harder to isolate and hence evaluate disclosure. They allow the investigator and the degree of influence of the factor of interest. others who have access to research records to The list of potential confounding influences refuse to disclose identifying information on for a given study can be extensive and vary research participants in any civil, criminal, from study to study. It is therefore the responsi- administrative, legislative, or other proceeding, bility of the researcher to design the study and whether at the federal, state, or local level. By structure the study’s research methodology such protecting researchers and institutions from that confounding influences are controlled to the being compelled to disclose information that greatest degree possible. would identify research subjects, certificates of One example from other entries can be found confidentiality help achieve the research objec- in the entry titled “▶ Crossover Design.” In these tives and promote participation in studies by study designs, each subject receives all of the assuring confidentiality and privacy to interventions in the study. Because of the poten- participants. tial confounding influence of the order in which the interventions are completed (e.g., subjects may tend to respond better to the first intervention Cross-References rather than the last, regardless of the nature of the intervention), this factor needs to be controlled ▶ Protection of Human Subjects for. This potential issue is elegantly solved by ▶ Research Participation, Risks and Benefits Of counterbalancing the order in which the subjects receive the treatments. In a two-treatment study, for example, half of the subjects would receive References and Readings Treatment A first and Treatment B second, and the other half would receive the treatments in the U.S. Department of Health & Human Services Health reverse order. Information Privacy. Accessed May 9, 2011 from Using different but comparable nomenclature, http://www.hhs.gov/ocr/privacy/ the goal of a research study is to identify one U.S. Department of Health & Human Services National Institutes of Health Office of Extramural Research source of systematic influence, the influence that Certificates of Confidentiality Kiosk. Accessed May is systematically provided by the factor of inter- 12, 2011 from http://grants.nih.gov/grants/policy/coc/ est in the study. It is essential to remove all other Congestive Heart Failure 485 C identifiable sources of systematic influence, such myocarditis; alcohol toxicity; or genetic as the order in which treatments are administered. mutations. Other simple examples include not administering One way to classify heart failure is according Treatment A only to males and Treatment B only to left ventricular ejection fraction, a measure of to females, and not administering Treatment contractile function. “Systolic heart failure” is A only to relatively young subjects and Treat- defined by the presence of reduced left ventricu- ment B to relatively old subjects. lar ejection fraction, usually <40%. About half of C The process of randomization is a powerful patients with heart failure may still have pre- tool used to disperse influences that cannot served left ventricular ejection fraction, so-called readily be controlled equally (randomly) across heart failure with normal ejection fraction the subjects in a study, thereby removing (HFNEF) (Maeder & Kaye, 2009). This is often unwanted systematic influences. thought to be due to impaired left ventricular relaxation, or “diastolic dysfunction,” but can also occur in the setting of other conditions such Cross-References as anemia or renal dysfunction. Symptoms of this condition can include short- ▶ Crossover Design ness of breath, peripheral edema, and fatigue. ▶ Randomization Worse symptomatology has been associated with ▶ Research Methodology greater mortality risk. New York Heart Associa- tion class is one way to indicate the symptom severity of someone with heart failure (Mann, 2008): Congestive Heart Failure Class I – no symptoms and no limitation in ordi- nary physical activity William Whang Class II – slight limitation during ordinary Division of Cardiology, Columbia University activity Medical Center, New York, NY, USA Class III – marked limitation in activity due to symptoms, even during less-than-ordinary activity Synonyms Class IV – symptoms even while at rest, mostly bedbound patients Heart failure The prevailing view of pathogenesis of sys- tolic heart failure involves a neurohormonal hypothesis. After an initial insult that results in Description damage to heart muscle, a number of compensa- tory systems are activated, mainly involving Congestive heart failure is a condition in which overactivity of the sympathetic nervous system. the heart cannot provide enough cardiac output Activation of the renin-angiotensin-aldosterone for the metabolic demands of the body. The prev- system results in salt and water retention, as alence of heart failure has been estimated at 2% well as constriction of peripheral blood vessels. and is expected to grow due to improved survival This short-term adaptation leads to detrimental of people with cardiac conditions (Mann, 2008). increases in left ventricular size and wall thin- The lifetime risk of developing heart failure has ning, also referred to as remodeling. been estimated at 20%. Coronary artery disease is The overall prognosis in patients with heart the most frequent cause of heart failure (60–75%) failure is poor, with 1-year mortality as high as (Lloyd-Jones et al., 2002). Etiologies for heart 30–40% without treatment (Mann, 2008). Depres- failure aside from coronary artery disease include sion has been estimated by a meta-analysis to occur viral inflammation of the heart, also known as in about 21% of heart failure patients, and its C 486 Conjecture presence is associated with worse cardiovascular trial. Journal of the American Medical Association, outcomes and higher overall mortality (Rutledge, 301(14), 1439–1450. Rutledge, T., Reis, V. A., Linke, S. E., Greenberg, B. H., & Reis, Linke, Greenberg, & Mills, 2006). Mills, P. J. (2006). Depression in heart failure a meta- The hallmark of pharmacologic therapy for analytic review of prevalence, intervention effects, and heart failure involves treatment with angiotensin associations with clinical outcomes. Journal of the converting-enzyme (ACE) inhibitors and beta American College of Cardiology, 48(8), 1527–1537. blockers, which are known to improve long- term mortality. Of note, there is a relative lack of evidence for therapies for treatment of heart failure with normal ejection fraction, although Conjecture blood pressure control is thought to play an important role in treatment. ▶ Theory Behavioral interventions for heart failure may include cessation of tobacco/alcohol use, reduc- tion in salt intake, and exercise in selected patients. The Heart Failure: AControlled Trial Consensus Guideline Investigating Outcomes of Exercise TraiNing (HF-ACTION) trial was performed in 2,331 ▶ Clinical Practice Guidelines ambulatory patients with heart failure and reduced left ventricular ejection fraction (average 0.25) (O’Connor et al., 2009). The intervention consisted of a group-based, supervised exercise CONSORT Guidelines program for 3 months with transition to home exercise. During a median follow-up duration of Lisa A. Eaton 30 months, a nonsignificant reduction in the pri- Center for Health, Intervention, and Prevention, mary endpoint of all-cause mortality or hospitali- University of Connecticut, New Haven, CT, USA zation was achieved (HR 0.93, 95% CI 0.84–1.02. p ¼ 0.13). Exercise training was also found to be relatively safe in the intervention group. Synonyms

Guidelines for reporting randomized controlled trials References and Readings

Lloyd-Jones, D. M., Larson, M. G., Leip, E. P., Beiser, A., D’Agostino, R. B., Kannel, W. B., et al. (2002). Definition Lifetime risk for developing congestive heart failure: The Framingham heart study. Circulation, 106(24), Many studies employ a randomized controlled 3068–3072. Maeder, M. T., & Kaye, D. M. (2009). Heart failure trial (RCT) design to test the efficacy of products with normal left ventricular ejection fraction. Journal or services. However, inconsistencies in of the American College of Cardiology, 53(11), reporting trial information and outcomes of 905–918. RCTs have stymied the usefulness of these trials Mann, D. L. (2008). Heart failure and cor pulmonale (chap. 227). In A. S. Fauci, E. Braunwald, D. L. in regards to providing readily available data Kasper, S. L. Hauser, D. L. Longo, J. L. Jameson, & from trial findings. These shortcomings led to J. Loscalzo (Eds.), Harrison’s principles of internal the development of Consolidated Standards of medicine, 17e. New York: McGraw-Hill. Reporting Trials (CONSORT). CONSORT dic- O’Connor, C. M., Whellan, D. J., Lee, K. L., Keteyian, S. J., Cooper, L. S., Ellis, S. J., et al. (2009). Efficacy tates that trial authors answer a series of checklist and safety of exercise training in patients with chronic questions and provide a flowchart representing heart failure: HF-ACTION randomized controlled the trial when reporting outcomes. Construct Validity 487 C

The CONSORT Statement seeks to improve guidelines for reporting parallel group randomised reporting information from RCTs, including trial. BMJ, 340, c869. for the CONSORT Group. Moher, D., Schulz, K. F., Altman, D. G., & Lepage, L. increasing transparency of trial procedures and out- (2001). The CONSORT statement: Revised recommen- comes. As of 2010, there are 25 checklist items that dations for improving the quality of reports of parallel- cover what information should be included in the group randomised trials. The Lancet, 357, 1191–1194. title/abstract, introduction, methods, results, dis- cussion, and other (registration, protocol, and C funding). In addition, authors adhering to CON- Construct Validity SORT Statement guidelines should include a flow chart that depicts, in part, number of participants Annie T. Ginty screened, excluded and why, randomized, received School of Sport and Exercise Sciences, product or service, lost to follow-up and why, The University of Birmingham, Edgbaston, assessed, and included in data analysis. Birmingham, UK CONSORT was originally developed in the 1990s and has since been amended multiple times. Individuals from varied backgrounds have Definition taken part in forming the specifics of the guide- lines. A committee representing the purpose of the Construct validity is the extent to which the mea- CONSORT Statement meets regularly to review, surements used, often questionnaires, actually assess, and change as needed statement guidelines. test the hypothesis or theory they are measuring. Thus, making this document one that is continually Construct validity should demonstrate that scores evolving to best represent the reporting of the on a particular test do predict the theoretical trait scientific methods of an RCT. Multiple peer- it says it does. reviewed, scholarly journals follow the reporting There are two subsets of construct validity: guidelines set forth by the CONSORT Statement convergent construct validity and discriminant which has led to consistency across journals in construct validity. Convergent construct validity terms of reporting style. Evaluations have been tests the relationship between the construct completed to assess the impact of implementing and a similar measure; this shows that constructs the CONSORT Statement. Analyses of trial which are meant to be related are related. reporting before and after the time period of guide- Discriminant construct validity tests the relation- line availability have demonstrated a substantial ships between the construct and an unrelated mea- improvement in transparency of procedures and sure; this shows that the constructs are not related outcomes as a result of the CONSORT Statement. to something unexpected. In order to have good construct validity one must have a strong relation- Cross-References ship with convergent construct validity and no relationship for discriminant construct validity. ▶ Randomized Clinical Trial Cross-References

References and Readings ▶ Psychometric Properties ▶ Reliability and Validity Begg, C., Cho, M., Eastwood, S., Horton, R., Moher, D., ▶ Validity et al. (1996). Improving the quality of reporting of randomized controlled trials. The CONSORT state- ment. Journal of the American Medical Association, References and Readings 276, 637–639. http://www.consort-statement.org/ Bruce, N., Pope, D., & Stanistreet, D. (2008). Quantitative Moher, D., Hopewell, S., Schulz, K. F., Montori, V., methods for health research: A practical interactive Gøtzsche, P. C., Devereaux, P. J., et al. (2010). CON- guide to epidemiology and statistics. West Sussex: SORT 2010 explanation and elaboration: Updated Wiley. C 488 Constructive Coping

coordination and continuity of health care as Constructive Coping patients move through different settings. Organi- zational approaches that facilitate transitions ▶ Active Coping between settings are the use of transitions coach to educate the patient and family, and coordinate among the health professionals involved in the transition (Coleman, Parry, Chalmers, & Min, Contemplation 2006) and the transitional care nurse (Naylor et al., 2004) who coordinates the discharge plan and ▶ Meditation coordinates the plan in the home. ▶ Transcendental Meditation Chronological or longitudinal continuity of care describes health care interactions that occur in the same place, with the same medical record, and with the same professionals, so that there is Context Effect consistent knowledge of the patient by those pro- viding the care (Saultz, 2003). Interdisciplinary ▶ Nocebo and Nocebo Effect or team-based continuity implies allows previous ▶ Placebo and Placebo Effect knowledge of the patient to be present even when the patient requires a wide range of services. Given that healthcare needs can rarely be met by a single professional or a single provider set- Continuity of Care ting, a multidimensional model of continuity of care is a logical choice, (Gulliford, Naithani, & Marie Boltz Morgan, 2006) one that provides a longitudinal College of Nursing, New York University, and interdisciplinary approach, while providing New York, NY, USA the dependability and relational aspects of inter- personal continuity. This model relies on integra- tion, coordination, and the sharing of information Definition between different, but stable providers. Evalua- tion of continuity of care can be conducted from Continuity of care refers to the seamless provi- the patient perspective, i.e., the experience of sion of health care between settings and over time care, or satisfaction with the coordination of (Gulliford, Naithani, & Morgan, 2006). care and its interpersonal aspects. It also includes Traditionally, patients have viewed care con- the provider’s evaluation of outcomes and care tinuity as a permanent relationship with a processes (team functioning and case manage- dependable, caring health care professional. ment effectiveness). This view, defined as interpersonal continuity of care, implies that the identified professional is the sole source of care and information for the References and Readings patient. To health care providers, care continuity has historically implied the exchange of informa- Coleman, E. A., Parry, C., Chalmers, S., & Min, S. J. tion, e.g., between shifts of nurses, between units (2006). The care transitions intervention: results of a randomized controlled trial. Archives of Internal of a healthcare facility, and between providers Medicine, 166, 1822–1828. such as acute care and a nursing home. Coleman Gulliford, M., Naithani, S., & Morgan, M. (2006). What is and colleagues (2006) define the flow of informa- “continuity of care?”. Journal of Health Services tion between different locations or different Research and Policy, 11(4), 248–250. Naylor, M. D., Brooten, D. A., Campell, R. L, Maislin, G., levels of care within the same location as “tran- McCauley, K. M., & Schwartz, J.S. (2004). Transitional sitional care” necessary to ensure the care of older adults hospitalized with heart Contraception 489 C

failure: a randomized, controlled trial. Journal of the Contraceptive failure rates are most often American Geriatrics Society, 52, 675–684. reported as two numbers, the theoretical failure Saultz, J. W. (2003). Defining and measuring interpersonal continuity of care. Annals of Family Medicine, 1, rate or the rate of contraceptive failure when the 134–143. method is used correctly during every act of intercourse. The actual failure rate takes into account the actual variation in consistency of contraceptive usage (see Table 1). C Continuous Subcutaneous Insulin Infusion Description ▶ Insulin Pumps The various methods of contraception include barrier methods, natural methods, hormonal methods, intrauterine devices (IUDs), emergency Contraception contraception, and surgical sterilization. The barrier method provides a mechanical or Linda C. Baumann and Alyssa Karel chemical barrier to the sperm from reaching the School of Nursing, University of Wisconsin- egg. The most common form of the barrier Madison, Madison, WI, USA method is the male condom, which is usually made of thin latex. New materials have been developed and include polyurethane and styrene Abbreviations and styrene ethylene butylenes styrene. These materials have a longer shelf life and can be STI Sexually transmitted infections used with oil-based lubricants without increasing the risk of condom breakage. Male condoms are relatively inexpensive, easily accessible, and carry few health risks. Health risks include hyper- sensitivity to the latex or lubricant inside the Synonyms condom. If used correctly every time, male con- doms are very effective and carry only a 2% Birth control, family planning theoretical failure rate; actual failure rates are around 15%. Female condoms are soft plastic film linings Definition with flexible rings at both ends (see Fig. 1). When used correctly and consistently, this type of con- Contraception, or birth control, is any method, traception carries a slightly higher theoretical and action, device, or medication used to prevent actual failure rate than male condoms at 5% and pregnancy. Various methods of contraception 21%, respectively. Female condoms are more include blockage of the sperm from reaching the expensive than male condoms due to the polyure- egg, killing or damaging sperm, preventing the thane material they are made from. Both male release of an egg from the ovaries, or changing and female condoms are a beneficial form of the uterine lining so a fertilized egg will not contraception because they not only protect attach. Many factors can help couples choose against pregnancy, but also provide protection the most appropriate contraception based on against sexually transmitted infections (STI). frequency of sex, plans for pregnancy, age and Spermicides are another barrier method and overall health, side effects, number of sexual come in the form of foams, jells, suppositories, partners, protection against sexually transmitted creams, films, and tablets. The most widely used infections (STIs), and contraceptive failure rates. types contain nonoxynol-9 and octoxynol-9. C 490

Contraception, Table 1 Overview of contraceptive methods Failure rate (%) Method Theoretical/actual Benefits Health risks/side effects and disadvantages Barrier 2.0 15.0 Provides STI protection Occasional hypersensitivity to latex or Condom 5.0 21.0 Male condoms are relatively cheap and widely available lubricant inside condom Male condom May provide protection against conditions caused by STIs May lead to decreased sensitivity Female condom Female condoms are costly and bulky Spermicide 18.0 29.0 Widely available in many forms and relatively inexpensive Can cause vaginal or penile irritation Risk of urinary tract infection Frequent use of nonoxynol-9 may increase risk of HIV One of the least effective methods when used alone Diaphragm 6.0 16.0 May help protect against certain STIs Can cause vaginal or penile irritation Cervical cap 20.0 32.0 May help protect against cervical cancer May lead to the development of Toxic Shock Parous women 9.0 16.0 Syndrome if left in place for too long Nuliparous women Risk of bladder irritations that can lead to urinary tract infections Natural – 25.0 Completely natural Requires motivation and a commitment to Fertility awareness 4.0 27.0 LAM helps encourage healthy breast-feeding patterns, which benefits both learning Coitus interruptus 1.0 2.0 mother and child High failure rates Lactational LAM can only be used a maximum of 6 months amenorrhea after delivery (LAM) Hormonal methods 0.3 8.0 Available in many forms Can cause dizziness, headache, nausea, weight Combination 0.5 3.0 Provides many non-contraceptive health benefits including reduced risk of: changes, mood changes, and breast pain estrogen and 0.3 0.8 Ovarian and endometrial cancer, PID, ovarian cysts, osteoporosis, Cary risk of cardiovascular complications such progesterone 0.3 0.8 iron-deficiency anemia and dysmenorrhea as deep vein thrombosis and pulmonary Contraception Pill embolism Injection Risk of heart attack and stroke is present Patch but rare Vaginal ring Progesterone only 0.5 8.0 Can be used by women who are nursing and for whom estrogen is May cause irregular bleeding, mood changes, Contraception Pill 0.3 3.0 contraindicated weight gain, dizziness, headaches, and nausea Injections Intrauterine 0.6 0.8 May help protect against endometrial cancer Side effects such as bleeding, pain, perforation, devices 0.2 0.2 After initial insertion requires little maintenance and infection are rare but can be serious Copper T IUD Copper IUDs can remain in uterine and work effectively for up to 10 years May increase the risk of pelvic inflammatory Levonorgestrel Levonorgestrel can be effective for up to 5 years disease if gonorrhea or Chlamydia is present IUD Levonorgestrel IUD has been used to help treat menorrhagia and dysmenorrhea before the insertion Copper IUD can be used as emergency contraception if placed within 5–8 days If pregnancy does occur, the risk of of unprotected sex and is the most effective form of emergency contraception spontaneous abortion is increased by up to 50% May change bleeding patterns causing increased bleeding and menstrual pain in first few months Levonorgestrel IUD can cause headaches, nausea, dizziness, and weight gain Surgical 0.5 0.5 Very few side effects Complications of surgery and anesthesia are sterilization 0.2 0.2 Permanent form of contraception and therefore requires no other possible Female contraceptive efforts 3 months post operation Requires a back-up method of contraception sterilization Helps protect against pelvic inflammatory disease for first 3 months post operation Male sterilization 491 C C C 492 Contraception

calendar. Symptom-based methods include mon- itoring cervical mucus changes around the time of ovulation. These changes include the mucus becoming thin and watery. The symptothermal method includes taking regular basal body tem- peratures to recognize a decrease, which occurs prior to ovulation, and monitoring other cues such as abdominal cramps, breast tenderness, Contraception, Fig. 1 Female condom and changes in cervical position to predict ovu- lation. Calendar methods of fertility awareness include the standard day method and the calendar Spermicides are inserted deep in the vagina at least rhythm method. The standard day method tracks 30 min prior to sexual intercourse and create the menstrual cycle counting from the first day of a chemical barrier by killing or inactivating bleeding as day 1; days 9 through 18 are consid- sperm by causing the membrane of the sperm cell ered fertile days. The calendar rhythm method to break. Research has shown that frequent use of requires a record of the number of days in nonoxynol-9 can damage lower genital tract epi- a menstrual cycle for 6 months, with estimates thelial surfaces and may increase the risk of HIV of the fertile period calculated by subtracting 18 infection. New spermicides are being developed from the length of the shortest cycle – this day is to replace nonoxynol-9. When used alone, spermi- the estimated first day of the fertile period. To cides are one of the least effective forms of con- estimate the end of the fertile period, subtract 11 traception and it is recommended that they be used from the length of the longest cycle – this is the in conjunction with other forms of contraception. estimated last day of the fertile period. These Spermicides do not protect against STIs and carry calculations should be updated monthly using risks of local tissue irritation. the most recent cycles. Fertility awareness is con- A diaphragm is a latex rubber cup with sidered one of the least effective forms of contra- a flexible rim that covers the cervix. It is placed ception, especially in women with irregular in the vagina before intercourse and remains menstrual cycles. The theoretical failure rate for there for 6–8 h after intercourse. It is most fertility awareness is 10%, while the actual fail- often used in conjunction with a spermicide. ure rate is about 25%. Diaphragms are relatively effective with a 6% A second natural method of contraception is theoretical failure rate and actual failure rate of coitus interruptus, or withdrawal of the penis 16%. However, diaphragms must be prescribed from the vagina before ejaculation. The theoret- and fitted by a healthcare provider and carry risk ical failure rate is quite low at about 4%, but the of vaginal or penile irritation, urinary tract infec- actual failure rate is around 27%, which makes tion, and in rare cases toxic shock syndrome. this form one of the least effective methods. A cervical cap is a small, soft cup that fits Pre-ejaculate can be deposited into the vaginal snugly over the cervix and is used in conjunction canal prior to ejaculation and contributes to the with a spermicide. It is a more effective form high failure rate. A male who has recently ejacu- of contraception in nulliparous women. Like lated prior to sex should first urinate and clean the diaphragms, cervical caps must be fitted by tip of the penis to remove any sperm from the a healthcare provider and carry many of the previous ejaculation. same health risks. The last natural method of contraception is Natural methods of contraception used to lactational amenorrhea. This method can be control pregnancy include fertility awareness, used by nursing mothers after delivery because coitus interruptus, and lactational amenorrhea. frequent breast-feeding suppresses hormones that Women using fertility awareness identify cause ovulation. Because the suppression of ovu- ovulation based on body symptoms or the lation is variable, this type of contraception Contraception 493 C should not be used longer than 6 months after a long-term contraceptive plan with little mainte- delivery. nance required after the initial insertion. They are Hormonal methods of birth control suppress highly effective with theoretical and actual failure ovulation to prevent pregnancy and are the most rates below 1%. widely used form of reversible contraception in Emergency contraception is a form of contra- the United States. Combined estrogen and pro- ception that can be utilized after unprotected sex or gesterone and progesterone-only methods are the after a contraceptive failure. Emergency contra- C two available forms of hormonal birth control. ception comes in two forms, pills and an emer- Combined birth control methods come in many gency copper IUD insertion, and prevents forms including oral pills, transdermal patches, pregnancy by inhibiting ovulation, fertilization or monthly injections, and vaginal rings. Depending implantation based on the form used. Emergency on the form being used, failure rates for combined contraceptive pills are high doses of either a com- hormonal contraception vary. Theoretical failure bined estrogen and progesterone pill or a proges- rates for all forms are below 1%; however, some terone-only pill. To be most effective, emergency actual rates can be as high as 8%. contraception should be taken as soon as possible The second form of hormonal contraception after unprotected sex, but can also be effective if is progesterone-only contraception. Because taken within 5 days of unprotected intercourse. this contraception does not contain estrogen, it Emergency insertion of a copper IUD within is advantageous for women who are breast- 5–8 days of unprotected sex is a very effective feeding and for women in whom estrogen is form of emergency contraception. contraindicated. Progesterone-only contracep- Sterilization is a form of permanent contracep- tion comes in the form of oral pills and injections tion and can be done in both men and women. that work by thickening the cervical mucus, In females, tubal ligation involves a surgical inhibiting sperm movement, and disrupting the occlusion of both fallopian tubes preventing an menstrual cycle to prevent ovulation. Generally egg from entering the uterus. Vasectomy is progesterone-only contraception is not as effec- a male sterilization procedure that involves liga- tive as combination contraception and carries tion of the vas deferens. Because these proce- actual failure rates of 8–10%. dures are meant to be permanent, reversal Intrauterine devices (IUDs) are the most widely surgery is rare, and when done, rarely successful. used form of reversible contraception globally. An Unlike tubal ligation, a vasectomy is not imme- IUD is a small plastic or metal device that is diately effective and another contraceptive inserted by a healthcare provider into the uterus. method should be used for the first 3 months The two most common forms are the copper- post operation. In the past 30 years, the rate of bearing IUD and the levonorgestrel IUD. The cop- sterilization as a form of contraception has per IUD is a plastic frame (or “7”) with copper increased dramatically and is currently one of sleeves around it. The levonorgestrel IUD is the most widely used forms of contraception. a plastic T-shaped device that releases small Failure rates are extremely low with both the amounts of levonorgestrel, a form of progesterone. theoretical and actual rates below 1%. The IUD causes a sterile inflammatory response in Globally, many social determinants influence which sperms are destroyed or immobilized by the choice of contraceptive and include gender inflammatory cells. In addition to this inflamma- and the role of women in a culture, age, socio- tory response, the levonorgestrel further provides economic status, marital status, education level, contraceptive effect by thickening cervical mucus and religion. For example, in the United States, and causing atrophy of the endometrium. The women aged 22–44 who are less educated copper in copper IUDs adds to the contraceptive are more likely to use sterilization as a contra- effect by hampering sperm motility, making it ceptive method while college-educated women difficult to reach the fallopian tubes. Most IUDs of the same age range more often use pills as can be left in place for 5–10 years and are therefore the preferred method of contraception. Some C 494 Control religious beliefs sanction natural methods of con- traception to space pregnancies as opposed to Control Group using hormonal or barrier methods that prevent pregnancy from occurring. Surgical sterilization J. Rick Turner is most often used by an older population while Cardiovascular Safety, Quintiles, Durham, the pill is the preferred form in the population NC, USA below the age of 30. The percentages of contra- ceptive users and the most widely used forms vary by country. Synonyms

Comparator group; Concurrent control (which Cross-References applies only in some settings)

▶ Abstinence ▶ Family Planning Definition

References and Readings A control group is a group of subjects against whose information the information gathered Callahan, T. L., & Caughey, A. B. (2007). Contraception from an investigational group is compared. and sterilization. In N. A. Duffy & K. Horvath (Eds.), To judge the effectiveness of a therapeutic Obstetrics & Gynecology (pp. 248–266). Baltimore: Lippincott Williams & Wilkins. behavioral intervention, or the harm done by Medline Plus. (2010). Birth control. Retrieved August 24, engaging in behavioral activities such as 2010, from http://www.nlm.nih.gov/medlineplus/ smoking, it is necessary to have a reference birthcontrol.html. point. This is provided by data collected from Mosher, W. D., & Jones, J. (2010). Use of contraception in the United States: 1982–2008. National Center for individuals who are deliberately similar to those Health Statistics. Vital and Health Statistics 23(29), in the investigational group in as many ways as 1–44. possible with the single exception of receiving Rowlands, S. (2009). New Technologies in contraception. the therapeutic intervention or having engaged BJOG: An International Journal of Obstetrics & Gynaecology, 116(2), 230–239. in the behavior of concern. The American Congress of Obstetricians and Gynecolo- Control groups can be used in experimental gist. (2007). Birth control. Retrieved August 24, studies and nonexperimental (often called obser- 2010, from http://www.acog.org/publications/patient_ vational) studies. Testing the effectiveness of education/ab020.cfm Wong, D., Hockenberry, M., Wilson, D., Perry, S., & a therapeutic behavioral intervention in a group Lowdermilk, D. (2006). Maternal child nursing care of individuals who have not previously received (3rd ed.). St. Louis, MO: Mosby Elsevier. it would fall into the category of an experimental World Health Organization, Department of Reproductive study: The researchers administer an experimen- Health and Research (WHO/RHR), & John Hopkins Bloomberg School of Public Health/Center for tal treatment. To control for the fact that simply Communication Programs (CCP). (2008). Family participating in the study may have a sizeable planning: A global handbook for providers. therapeutic benefit (caused by a variety of poten- Baltimore/Geneva: CCP and WHO. tial factors, including the extra medical attention given to these subjects), it is necessary to have a control group that experiences all of the circumstances experienced by those in the Control investigational group with the exception of the intervention of interest. This can be a difficult ▶ Hyperglycemia challenge for those developing the experimental ▶ Interpersonal Circumplex methodology to be used in the study. Cook-Medley Hostility Scale 495 C

Cross-References predictive of coronary artery disease and all- cause mortality even after controlling for other ▶ Case-Control Studies health risk factors (Miller, Smith, Turner, ▶ Randomized Clinical Trial Guijarro, & Hallet, 1996). In contrast to the extensive evidence for its predictive validity, the exact construct(s) measured by the scale References and Readings have been the subject of some debate. A variety C of competing measurement models have been Rothman, K. J., Greenland, S., & Lash, T. L. (Eds.). proposed, with no clear favorite based on psycho- (2008). Modern epidemiology (3rd ed.). Philadelphia: metric criteria (Contrada & Jussim, 1992). Lippincott Williams & Wilkins. Turner, J. R. (2012). Key statistical concepts in clinical Although groups of items relating to constructs trials for pharma. New York: Springer. ranging from hypersensitivity to aggressive responding have been identified, the core factor of the Ho Scale may be best described as reflecting cynicism. A unidimensional index of that primary factor can be derived from the over- Control Group of a Randomized Trial all scale and was found in at least one study to maintain the predictive ability of the entire scale ▶ Usual Care (Strong, Kahler, Greene, & Schinka, 2005).

Cross-References

Co-occuring ▶ Cynical Hostility

▶ Comorbidity References and Readings

Bunde, J., & Suls, J. (2006). A quantitative analysis of the Cook-Medley Hostility Scale relationship between the cook-medley hostility scale and traditional coronary artery disease risk factors. Matthew Calamia Health Psychology, 25, 493–500. Department of Psychology, University of Iowa, Contrada, R. J., & Jussim, L. (1992). What does the Cook- Medley hostility scale measure? In search of an Iowa City, IA, USA adequate measurement Model1. Journal of Applied Social Psychology, 22, 615–627. Cook, W. W., & Medley, D. M. (1954). Proposed hostility Definition and pharisaic-virtue scales for the MMPI. Journal of Applied Psychology, 38(6), 414–418. Han, K., Weed, N. C., Calhoun, R. F., & Butcher, J. N. The Cook-Medley Hostility Scale (Ho Scale) (1995). Psychometric characteristics of the MMPI-2 (Cook & Medley, 1954) is a 50-item scale cook-medley hostility scale. Journal of Personality derived from the Minnesota Multiphasic Person- Assessment, 65, 567–585. Miller, T. Q., Smith, T. W., Turner, C. W., Guijarro, M. L., & ality Inventory. The creators viewed it as Hallet, A. J. (1996). A meta-analytic review of research a measure of “chronic hate and anger.” Scores on hostility and physical health. Psychological Bulletin, on the Ho Scale are related to a variety of health- 119, 322–348. relevant variables, including alcohol consump- Strong, D. R., Kahler, C. W., Greene, R. L., & Schinka, J. (2005). Isolating a primary dimension within the cook- tion, insulin resistance, and waist-to-hip ratio medley hostility scale: A rasch analysis. Personality (Bunde & Suls, 2006). Scores on the Ho are and Individual Differences, 39, 21–33. C 496 Coping

stress. Furthermore, responses that are inten- Coping tional and effortful when first used may become automatic with repetition. Some discussions of Charles Carver coping also include unconscious defensive reac- Department of Psychology, University tions as aspects of coping. This entry is limited, of Miami, Coral Gables, FL, USA however, to responses that are recognized by the person who is engaging in them.

Definition Distinctions and Groupings Among Coping is efforts to prevent or diminish threat, Coping Responses harm, and loss, or to reduce the distress that is often associated with those experiences. Coping is a very broad concept with a long and complex history (Compas et al., 2001; Folkman & Moskowitz, 2004). A great many Description distinctions have been made within the broad domain (Skinner, Edge, Altman, & Sherwood, The concept of coping presumes the existence of 2003). Some of the more important distinctions a condition of adversity or stress. A person who are described in the sections that follow. must deal with adversity is engaged in coping. Thus, coping is inextricably linked to stress. It is Problem-Focused Versus Emotion-Focused often said that stress exists whenever people Coping confront situations that tax or exceed their The first distinction made in modern examination ability to manage them (Lazarus, 1966; Lazarus of coping was that made between problem- & Folkman, 1984). Whenever a person is hard- focused and emotion-focused coping (Lazarus & pressed to deal with an obstacle or impediment Folkman, 1984). Problem-focused coping is or looming threat, the experience is stressful. directed at the stressor itself: taking steps to Adversity takes several forms. Threat refers to remove or to evade it, or to somehow diminish the impending occurrence of an event that is its impact if it cannot be evaded. For example, feared will have bad consequences. Harm refers if the arrival of a hurricane is forecast, to the perception that bad consequences a homeowner’s problem-focused coping might have already come to pass. Loss refers to the include bringing all potted plants indoors, putting perception that something of value has been up storm shutters, and buying batteries for use in taken away. flashlights. As another example, if layoffs People respond to perceptions of threat, harm, are expected at one’s place of employment, and loss in a wide variety of ways, many of problem-focused coping might include saving which are labeled coping. Coping is generally money, applying for other jobs, obtaining training defined as efforts to prevent or diminish threat, to enhance hiring prospects, or working harder harm, and loss, or to reduce the distress that is at the current job to reduce the likelihood of often associated with those experiences. Some being let go. theorists prefer to limit the concept of coping to Emotion-focused coping, in contrast, is aimed voluntary responses (Compas, Connor-Smith, at minimizing the emotional distress that is trig- Saltzman, Thomsen, & Wadsworth, 2001). gered by stressful events. Because there are many Others include automatic and involuntary ways to reduce distress, emotion-focused coping responses as well (Eisenberg, Fabes, & Guthrie, includes a very wide range of responses, ranging 1997; Skinner & Zimmer-Gembeck, 2007). from self-soothing (e.g., relaxation, seeking emo- It should be noted that it is not easy to distinguish tional support), to expression of negative emotion between voluntary and involuntary responses to (e.g., yelling, crying), to a focus on negative Coping 497 C thoughts (e.g., rumination), to attempts to escape is almost literally an effort to act as though the cognitively from the stressful situation (e.g., avoid- threat does not exist, so that no reaction is needed, ance, denial, wishful thinking). behaviorally or emotionally. Wishful thinking and Problem-focused and emotion-focused coping fantasy can distance the person from the stressor, have different initial or focal goals. The focal at least temporarily, and denial creates a boundary goal determines which category a particular between reality and the person’s experience. response is assigned to. Some behaviors can Although disengagement coping has the aim of C serve either a problem-focused or an emotion- escaping distress, it is generally ineffective in focused function, depending on the goal behind reducing distress over the long term, because it their use. For example, seeking support is emo- does nothing about the threat’s existence and its tion focused if the goal is to obtain emotional eventual impact. If you are experiencing a real support and reassurance; on the other hand, seek- threat in your life and you respond to it by going ing support is problem focused if the goal is to to the movies, the threat will generally remain obtain advice or instrumental help. when the movie is over. Eventually, it must be Although it is easy to distinguish between dealt with. Indeed, for many types of stress, the them in principle, problem-focused coping and longer a person avoids dealing with the problem, emotion-focused coping also tend to facilitate the more difficult or complex it becomes, and the one another. Effective problem-focused coping less time is available to deal with it when one does diminishes the threat or harm, but by doing so, finally turn to it. Finally, some kinds of disengage- it also diminishes the distress generated by that ment coping can create problems of their own. threat. Effective emotion-focused coping dimin- Excessive use of alcohol or drugs can create social ishes negative emotions, making it possible to andhealthproblems,andshoppingorgamblingas consider the problem more calmly. This often an escape can create financial problems. leads to better problem-focused coping. This Some have extended the concept of disen- interwoven relationship between problem- and gagement coping to include giving up on goals emotion-focused coping makes it more useful to that are threatened by the stressor (Carver & think of the two as complementary coping func- Connor-Smith, 2010). This differs from other tions, rather than as two fully distinct and inde- disengagement responses, in that it addresses pendent coping categories. both the stressor’s existence and its emotional impact by abandoning an investment in some- Engagement Versus Disengagement thing else. Disengaging from the threatened goal What turns out to be a particularly important dis- may allow the person to avoid negative feelings tinction is the distinction between engagement or associated with the threat. Depending on the approach coping and disengagement or avoidance nature of the goal being abandoned, however, coping (e.g., Skinner et al., 2003). Engagement this sort of disengagement can also have adverse coping is aimed at actively dealing with the secondary consequences. stressor or stress-related emotions. Disengage- ment coping is aimed at avoiding confrontation Accommodative Coping and with the threat or avoiding the stress-related emo- Meaning-Focused Coping tions. Engagement coping includes problem- Most adaptive coping is one or another form of focused coping and forms of emotion-focused engagement coping. Within engagement coping, coping such as support seeking, emotion regula- distinctions also have been made between tion, acceptance, and cognitive restructuring. Dis- attempts to control the stressor itself, called pri- engagement coping includes responses such as mary control coping, and attempts to adapt or avoidance, denial, and wishful thinking. Disen- adjust to the stressor, termed accommodative or gagement coping is often emotion focused, sometimes secondary control coping (Morling & because it typically involves an attempt to escape Evered, 2006; Skinner et al., 2003). The term feelings of distress. Some disengagement coping accommodative is perhaps to be preferred C 498 Coping because it does not carry connotations of exerting ways to group and organize coping responses. control, or of being secondary to other coping Further, it should be clear that these distinctions efforts. do not form a neat matrix into which all coping The concept of accommodative coping is reactions can be sorted. A given response typi- rooted in analyses of the process of successful cally fits several places. For example, seeking aging (Brandtst€adter & Renner, 1990). It refers emotional support is engagement, emotion- to adjustments within the self, which are focused, and accommodative coping. Each dis- made in response to constraints inherent in tinction that has been introduced can be useful for one’s life situation. In the realm of coping, answering certain questions about responses to accommodation applies to responses such as stress. No one distinction fully conveys the struc- acceptance, cognitive restructuring, and scaling ture of coping. The distinction that appears to be back of one’s goals in the face of insurmountable the most important is that made between engage- interference. Another kind of accommodation is ment and disengagement. Interestingly enough, self-distraction. Self-distraction is somewhat con- this is a distinction which also maps well onto troversial. Self-distraction is often thought of as goal-based models of personality functioning and disengagement coping. However, there is also evi- social behavior (e.g., Carver & Scheier, 1998). dence suggesting that intentionally engaging in positive activities is a useful means of adapting to uncontrollable events (Skinner et al., 2003). Relations Between Coping and Well- A concept that is related to accommodation is being what has been called meaning-focused coping. In meaning-focused coping, people draw on their In some respects, the question that everyone beliefs and values to find benefits in stressful wants answered is not “what are the ways in experiences or remind themselves of positive which people cope?” but “how do coping aspects of their lives (Tennen & Affleck, 2002). responses affect well-being?” Behind this ques- Meaning-focused coping may include reordering tion lie a number of thorny methodological issues one’s life priorities and focusing on the positive (Carver, 2007). Among them are issues of how meaning of ordinary events. The concept of often coping should be measured, what time lag meaning-focused coping has roots in evidence should be assumed and thus investigated between that positive as well as negative emotions are coping efforts and eventual outcomes, and common during stressful experiences, that those whether coping should be viewed as a cluster of positive feelings influence people’s outcomes, responses or a sequence of responses. and particularly the fact that people try to find In meta-analyses of relations between coping benefit and meaning in adversity (Helgeson, and well-being, effect sizes are typically small to Reynolds, & Tomich, 2006; Park, Lechner, moderate. Coping generally has been linked more Antoni, & Stanton, 2009). Although this concept strongly to psychological outcomes than to phys- emphasizes the positive changes a stressor brings ical health (Clarke, 2006; Penley, Tomaka, & to a person’s life, it is worth pointing out that Wiebe, 2002). Nonetheless, most kinds of meaning-focused coping also represents an engagement coping relate to better physical and accommodation to the constraints of one’s life mental health in samples coping with stressors as situation. Meaning-focused coping involves diverse as traumatic events, social stress, HIV, reappraisal of the situation. It appears to be and prostate cancer (Clarke, 2006; Littleton, most likely when stressful experiences are uncon- Horsley, John, & Nelson, 2007; Moskowitz, trollable or are going badly. Hult, Bussolari, & Acree, 2009; Penley et al., 2002; Roesch et al., 2005). However, some Stepping Back other less volitional responses that might be This brief review is far from exhaustive. None- seen as reflecting engagement, including rumina- theless, it should make clear that there are many tion, self-blame, and venting, predict poorer Coping 499 C emotional and physical outcomes (Austenfeld & which the question is whether the person changes Stanton, 2004; Moskowitz et al., 2009). Higher from one sort of coping to another across succes- levels of disengagement coping typically predict sive assessments as a function of lack of effec- poorer outcomes, such as more anxiety, depres- tiveness of the first response used. sion, and disruptive behavior, less positive affect, The impact of a given coping strategy may be and poorer physical health, across an array of quite brief. For this reason, laboratory and daily stressors (Littleton et al., 2007; Moskowitz report studies are essential to understanding the C et al., 2009; Roesch et al., 2005). Acceptance effects of situational coping strategies (Bolger, coping seems to be a double-edged sword. Davis, & Rafaeli, 2003). The small number of Acceptance that occurs in the context of other daily report studies of coping make it clear that accommodative strategies is helpful, but accep- the impact of coping changes over time, with tance that reflects resignation and abandonment responses that are useful one day sometimes hav- predicts distress (Morling & Evered, 2006). ing a negative impact on next-day mood or long- Relations between coping and adjustment also term adjustment (DeLongis & Holtzman, 2005). vary with the nature, duration, context, and con- Laboratory research also is useful in disentangling trollability of the stressor. In meta-analyses of stressor severity from individual differences in both children and adults, it appears to be impor- stress appraisals by using standardized stressors. tant to match one’s coping to the stressor’s con- Lab studies also make it easier to supplement trollability and to the resources that are available. self-reports with observations of coping and assess- Active attempts to solve problems help when ment of physiological responses. dealing with controllable stressors, but the same responses are potentially harmful when dealing with uncontrollable stressors (Aldridge & Cross-References Roesch, 2007; Clarke, 2006). Similarly, taking responsibility for uncontrollable stressors pre- ▶ Stress dicts distress, but taking responsibility is unrelated to adjustment in the context of control- lable stressors (Penley et al., 2002). In contrast, References and Readings emotional approach coping (e.g., self-regulation and controlled expression of emotion) appears to Aldridge, A. A., & Roesch, S. C. (2007). Coping and adjustment in children with cancer: A meta-analytic be most useful in the context of uncontrollable study. Journal of Behavioral Medicine, 30, 115–129. stressors (Austenfeld & Stanton, 2004). Austenfeld, J. L., & Stanton, A. L. (2004). Coping through One caveat must be applied to all of these emotional approach: A new look at emotion, coping, conclusions about the effects of coping. Although and health-related outcomes. Journal of Personality, 72, 1335–1363. coping is almost universally viewed as an ever- Bolger, N., Davis, A., & Rafaeli, E. (2003). Diary changing response to evolving situational methods: Capturing life as it is lived. Annual Review demands, most coping research fails to reflect of Psychology, 54, 579–616. € this view. Many studies assess only dispositional Brandtstadter, J., & Renner, G. (1990). Tenacious goal pursuit and flexible goal adjustment: Explication coping (overall coping styles), or one-time retro- and age-related analysis of assimilative and accommo- spective reports of overall coping with some dative strategies of coping. Psychology and Aging, stressor. Those studies tell virtually nothing 5, 58–67. about how timing, order, combination, or dura- Carver, C. S. (2007). Stress, coping, and health. In H. S. Friedman & R. C. Silver (Eds.), Foundations of health tion of coping affects outcomes. In contrast, psychology (pp. 117–144). New York: Oxford Univer- Tennen, Affleck, Armeli, and Carney (2000) pro- sity Press. posed that people typically use emotion-focused Carver, C. S., & Connor-Smith, J. (2010). Personality and coping largely after they have tried problem- coping. Annual Review of Psychology, 61, 679–704. Carver, C. S., & Scheier, M. F. (1998). On the self- focused coping and found it ineffective. This regulation of behavior. New York: Cambridge suggests an approach to studying coping in University Press. C 500 Coping Skills Training

Clarke, A. T. (2006). Coping with interpersonal stress and Skinner, E. A., & Zimmer-Gembeck, M. J. (2007). The psychosocial health among children and adolescents: development of coping. Annual Review of Psychology, A meta-analysis. Journal of Youth and Adolescence, 58, 119–144. 35, 11–24. Tennen, H., & Affleck, G. (2002). Benefit-finding and Compas, B. E., Connor-Smith, J. K., Saltzman, H., benefit-reminding. In C. R. Snyder & S. J. Lopez Thomsen, A. H., & Wadsworth, M. E. (2001). Coping (Eds.), Handbook of positive psychology (pp. 584– with stress during childhood and adolescence: Prob- 597). New York: Oxford University Press. lems, progress, and potential in theory and research. Tennen, H., Affleck, G., Armeli, S., & Carney, M. A. Psychological Bulletin, 127, 87–127. (2000). A daily process approach to coping: Linking DeLongis, A., & Holtzman, S. (2005). Coping in context: theory, research, and practice. American Psychologist, The role of stress, social support, and personality in 55, 626–636. coping. Journal of Personality, 73, 1–24. Duangdao, K. M., & Roesch, S. C. (2008). Coping with diabetes in adulthood: A meta-analysis. Journal of Behavioral Medicine, 31, 291–300. Eisenberg, N., Fabes, R. A., & Guthrie, I. (1997). Coping Coping Skills Training with stress: The roles of regulation and development. In J. N. Sandler & S. A. Wolchik (Eds.), Handbook of ▶ Williams LifeSkills Program children’s coping with common stressors: Linking theory, research, and intervention (pp. 41–70). New York: Plenum. Folkman, S., & Moskowitz, J. T. (2004). Coping: Pitfalls and promise. Annual Review of Psychology, 55, Coping Strategies 745–774. Helgeson, V. S., Reynolds, K. A., & Tomich, P. L. (2006). ▶ A meta-analytic approach to benefit finding and health. Coping Journal of Consulting and Clinical Psychology, 74, ▶ Denial 797–816. Lazarus, R. S. (1966). Psychological stress and the coping process. New York: McGraw-Hill. Lazarus, R. S., & Folkman, S. (1984). Stress, appraisal, and coping. New York: Springer. Coping Styles Littleton, H., Horsley, S., John, S., & Nelson, D. V. (2007). Trauma coping strategies and psychological ▶ Coping distress: A meta-analysis. Journal of Traumatic Stress, 20, 977–988. Morling, B., & Evered, S. (2006). Secondary control reviewed and defined. Psychological Bulletin, 132, 269–296. Coping with Stress Moskowitz, J. T., Hult, J. R., Bussolari, C., & Acree, M. (2009). What works in coping with HIV? A meta- ▶ Stress Management analysis with implications for coping with serious ill- ness. Psychological Bulletin, 135, 121–141. Park, C. L., Lechner, S. C., Antoni, M. H., & Stanton, A. L. (Eds.). (2009). Medical illness and positive life change: Can crisis lead to personal transformation? Washing- Copy Number Variant (CNV) ton, DC: American Psychological Association. Penley, J. A., Tomaka, J., & Wiebe, J. S. (2002). The 1 2 association of coping to physical and psychological Rany M. Salem and Laura Rodriguez-Murillo health outcomes: A meta-analytic review. Journal of 1Broad Institute, Cambridge, MA, USA Behavioral Medicine, 25, 551–603. 2Department of Psychiatry, Columbia University Roesch, S. C., Adams, L., Hines, A., Palmores, A., Vyas, P., Tran, C., et al. (2005). Coping with prostate Medical Center, New York, NY, USA cancer: A meta-analytic review. Journal of Behavioral Medicine, 28, 281–293. Skinner, E. A., Edge, K., Altman, J., & Sherwood, H. Synonyms (2003). Searching for the structure of coping: A review and critique of category systems for classifying ways of coping. Psychological Bulletin, 129, 216–269. Structural variant Coronary Artery Bypass Graft (CABG) 501 C

Definition in copy number in the human genome. Nature, 444(7118), 444–454. doi:10.1038/nature05329. Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., A copy number variant (CNV) is a type of genetic Lese-Martin, C., Walsh, T., et al. (2007). Strong variation in which a sequence of nucleotides is Association of De Novo copy number mutations with repeated in tandem multiple times in an individ- autism. Science, 316(5823), 445–449. ual’s genome. The variability arises from the The Wellcome Trust Case Control Consortium. (2010). Genome-wide association study of CNVs in 16,000 C gain and/or loss of genetic material, causing the cases of eight common diseases and 3,000 shared number of repeat copies to vary in a population. controls. Nature, 464(7289), 713–720. doi:10.1038/ In contrast to single nucleotide polymorphisms nature08979. (SNPs), which affect only one nucleotide, CNVs Xu, B., Roos, J. L., Levy, S., van Rensburg, E. J., Gogos, J. A., & Karayiorgou, M. (2008). Strong association are much larger, ranging from one kilobase to of de novo copy number mutations with sporadic several megabases in size (Conrad et al., 2010). schizophrenia. Nature Genetics, 40(7), 880–885. Large CNVs may contain genes, resulting in gene doi:10.1038/ng.162. duplication or deletion. CNVs are inherited, but can also arise de novo (although a rare event) via genomic rearrangements such as deletions, duplications, Coronary Artery Bypass Graft (CABG) inversions, translocations, and transposons activity. It is estimated that the human genome Siqin Ye contains 20,000 CNVs (Mills et al., 2011) Division of Cardiology, Columbia University and covers up 12% of the human genome Medical Center, New York, NY, USA (Redon et al., 2006). CNVs have been associated with several diseases, including schizophrenia (Xu et al., 2008), autism (Sebat et al., 2007), and others Synonyms (The Wellcome Trust Case Control Consortium, 2010). The full extent to which they contribute to CABG human disease is not known (Conrad et al., 2010).

Definition Cross-References Coronary artery bypass graft, or CABG, is ▶ DNA a surgical procedure performed to treat advanced ▶ Human Genome Project coronary atherosclerotic disease. ▶ Polymorphism ▶ Single Nucleotide Polymorphism (SNP) Description References and Readings By using segments of other arteries and veins as Conrad, D. F., Pinto, D., Redon, R., Feuk, L., Gokcumen, conduits to bypass diseased portions of the coro- O., Zhang, Y., et al. (2010). Origins and functional nary arteries, CABG can improve cardiac func- impact of copy number variation in the human tion by restoring blood flow to areas of the heart genome. Nature, 464(7289), 704–712. doi:10.1038/ that were inadequately perfused. The most com- nature08516. Mills, R. E., Walter, K., Stewart, C., Handsaker, R. E., monly used grafts include saphenous vein grafts, Chen, K., Alkan, C., et al. (2011). Mapping copy harvested either openly or endoscopically from number variation by population-scale genome the lower extremities; free radial grafts, which sequencing. Nature, 470(7332), 59–65. doi:10.1038/ are segments of the radial arteries from either nature09708. Redon, R., Ishikawa, S., Fitch, K. R., Feuk, L., Perry, wrists; and left or right internal mammary arteries G. H., Andrews, T. D., et al. (2006). Global variation (LIMA or RIMA), which arise from the C 502 Coronary Artery Bypass Graft (CABG) subclavian arteries and are anastomosed distally cardiovascular events as CABG (Seung et al., to the target coronary vessels. Currently, the 2008). The landmark Synergy between PCI with LIMA is most frequently used to bypass the left Taxus and Cardiac Surgery (SYNTAX) trial anterior descending artery (LAD) due its excel- published in 2009 randomized patients with lent long-term results, while vein grafts, which three-vessel or left main coronary artery disease have much higher rates of graft failure, are used to PCI or CABG and showed that while patients to bypass the other coronary vessels (Morrow & who underwent PCI had higher rate of repeat Gersh, 2008). revascularization, the rates of death and myocar- Despite the advent of percutaneous coronary dial infarction were similar between the two intervention (PCI), CABG remains one of the arms. In particular, for patients with less compli- most commonly performed surgical procedures cated lesions, the choice of revascularization in the United States. The main indications for strategy did not lead to a significant difference CABG are based on high-risk anatomical features in outcomes (Serruys et al., 2009). On the other and include significant left main disease or its hand, new surgical techniques such as off-pump equivalent (i.e., concomitant proximal LAD and CABG or minimally invasive CABG with hybrid proximal left circumflex artery stenosis), PCI may also significantly alter the risk-benefit multivessel coronary artery disease that involve balance. With these advances, it is likely that the the proximal LAD, and triple vessel disease optimal strategy for revascularization will con- (Eagle et al., 2004). Studies have also demon- tinue to evolve in the coming years and become strated that patients with left ventricular dysfunc- increasingly individualized. tion, and especially those with significant amount of viable myocardium on noninvasive imaging, may derive greater benefit from surgical revascu- Cross-References larization. In these selected patient populations, CABG has been shown to markedly improve ▶ Bypass Surgery survival compared with medical therapy (Yusuf ▶ Coronary Artery Disease et al., 1994). However, there are also significant risks associated with CABG. Registries maintained by the Society of Thoracic Surgeons References and Readings have consistently shown operative mortality of 2–3%. In addition, there are other known periop- Eagle, K. A., Guyton, R. A., Davidoff, R., Edwards, F. H., erative complications, including myocardial Ewy, G. A., Gardner, T. J., et al. (2004). ACC/AHA infarction, stroke, renal failure, bleeding, and 2004 guideline update for coronary artery bypass graft surgery: Summary article: A report of the American wound infections. Various scoring systems College of Cardiology/American Heart Association have been derived to predict the risk of these task force on practice guidelines (committee to update perioperative events and to aid in informed deci- the 1999 guidelines on coronary artery bypass graft sion making for individual patients. The careful surgery). Circulation, 110, 1168–1176. Morrow, D. A., & Gersh, B. J. (2008). Chronic coronary consideration of the benefits and risks of surgery artery disease. In P. Libby, R. O. Bonow, D. L. Mann, is especially important for those patients with D. P. Zipes, & E. Braunwald (Eds.), Braunwald’s heart a high-risk profile, such as the frail elderly or disease: A textbook of cardiovascular medicine those with many comorbidities (Eagle et al., (pp. 1353–1417). Philadelphia: Saunders Elsevier. Serruys, P. W., Morice, M., Kappetein, A. P., Colombo, A., 2004). Holmes, D. R., Mack, M. J., et al. (2009). Percutaneous There has also been ongoing debate on coronary intervention versus coronary-artery bypass whether a subset of patients with surgical disease grafting for severe coronary artery disease. The New may be treated with PCI rather than CABG. For England Journal of Medicine, 360, 961–972. Seung, K. B., Park, D., Kim, Y., Lee, S., Lee, C. W., instance, recent registries have suggested that in Hong, M., et al. (2008). Stent versus coronary-artery patients with uncomplicated left main disease, bypass grafting for left main coronary artery disease. PCI may yield comparable rates of major adverse The New England Journal of Medicine, 358, 1781–1792. Coronary Heart Disease 503 C

Yusuf,S.,Zucker,D.,Passamani,E.,Peduzzi,P.,Takaro,T., Force for the Redefinition of Myocardial Infarc- Fisher, L. D., et al. (1994). Effect of coronary artery tion Expert Consensus Document have been bypass graft surgery on survival: Overview of 10-year results from randomised trials by the coronary artery released to standardize the definitions of the bypass graft surgery trialists collaboration. Lancet, most important clinical events such as cardiovas- 344(8922), 563–570. cular death and myocardial infarction.

C Cross-References Coronary Artery Disease ▶ Acute Myocardial Infarction ▶ Coronary Heart Disease ▶ Angina Pectoris ▶ Cardiac Events ▶ Coronary Artery Bypass Graft (CABG)

Coronary Event References and Readings Siqin Ye Division of Cardiology, Columbia University ACC Writing Committee for Acute Coronary Syndromes Medical Center, New York, NY, USA Clinical Data Standards & ACC Task Force on Clini- cal Data Standards. (2001). American College of Car- diology key data elements and definitions for measuring the clinical management and outcomes of Synonyms patients with acute coronary syndromes. Journal of the American College of Cardiology, 38(7), 2114–2130. Kip, K. E., Hollabaugh, K., Marroquin, O. C., & Williams, Cardiac events D. O. (2008). The problem with composite end points in cardiovascular studies. Journal of the American College of Cardiology, 51(7), 701–707. Definition Thygesen, K., Alpert J. S., White H. D., on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. (2007). Univer- Although no standard definition exists, the term sal definition of myocardial infarction. European coronary event is used in clinical research to refer Heart Journal, 28(20), 2525–2538. to adverse events caused by disease processes affecting the coronary arteries. These may include what are termed “hard” events such as Coronary Heart Disease deaths that are attributed to coronary artery dis- ease and nonfatal myocardial infarctions, but also William Whang occasionally “soft” events such as angina or Division of Cardiology, Columbia University revascularizations for worsening coronary artery Medical Center, New York, NY, USA stenosis. Because coronary event is often such a composite of clinical events of varying signifi- cance, there remains considerable debate on what Synonyms should constitute the most appropriate compo- nent endpoints and how to define them, with the Coronary artery disease recognition that these choices may significantly influence the results and impact of clinical trials and other studies (Kip, Hollabaugh, Marroquin, Definition & Williams, 2008). To address this, guidelines such as the 2001 ACC Clinical Data Standards Coronary heart disease (CHD) is a condition in and the 2007 Joint ESC/ACCF/AHA/WHF Task which the arteries that supply the cardiac muscle, C 504 Coronary Heart Disease the coronary arteries, develop reduced luminal activation of the clotting cascade and develop- size due to the presence of atherosclerosis. ment of occlusive clot. Treatment of individuals with coronary heart disease involves primary or secondary prevention Description of myocardial infarction and heart failure (Antman et al., 2008). Medications such as aspi- Coronary heart disease (CHD) is a condition in rin and clopidogrel prevent clot formation, beta which the arteries that supply the cardiac muscle, blockers reduce myocardial workload, and statin the coronary arteries, develop reduced luminal medications reduce cholesterol and stabilize cor- size due to the presence of atherosclerosis onary plaques. Angiotensin-converting enzyme (Antman, Selwyn, Braunwald, & Loscalzo, (ACE) inhibitors reduce blood pressure and resis- 2008). Atherosclerosis is a progressive condition tance in the small arteries and have been shown to that starts as fatty streaks and may result in plaque prevent cardiac events particularly in patients development and ultimately in flow-limiting who have developed left ventricular dysfunction. narrowing or occlusion of coronary arteries. The Nonpharmacologic treatment of CHD clinical manifestations of CHD include conditions includes percutaneous coronary intervention such as angina, myocardial infarction, and heart (PCI), a procedure that involves dilatation of the failure. Angina, or chest discomfort, develops due coronary artery lumen with a balloon and usually to an imbalance between myocardial oxygen followed by implant of a coronary stent (Antman demand and the available blood supply. In myo- et al., 2008). PCI has been shown to reduce car- cardial infarction, plaque rupture and clot forma- diac events in patients who present with myocar- tion at the site of rupture result in occlusion of the dial infarction or angina at rest. In some patients artery and loss of blood flow to the heart muscle. with severe CHD involving all three main coro- CHD is the major cause of one-third of all nary vessels, particularly in the setting of diabetes deaths in individuals older than 35, and one-half or reduced ventricular function, coronary artery of all middle-aged men and one-third of middle- bypass graft surgery is a better treatment option. aged women in the United States will develop In terms of behavioral interventions for preven- CHD (Lloyd-Jones, Larson, Beiser, & Levy, tion of CHD, regular aerobic exercise has been 1999). The Framingham Heart Study, a prospec- associated with improvement in multiple coronary tive cohort study of 5,209 individuals that began artery disease risk factors, including blood pres- in 1948 and has continued to collect information sure, serum cholesterol, glucose intolerance, and and add participants, has defined many of the risk body mass index (Thompson et al., 2007). In addi- factors for atherosclerotic disease through epide- tion, healthy dietary patterns have been associated miologic techniques. Risk factors for coronary with improved cardiac mortality, as well as lower heart disease include other medical conditions blood pressure and serum cholesterol (Appel et al. such as hypertension, diabetes mellitus, and 1997, 2005;Knoopsetal.,2004). The 2006 dietary dyslipidemia, as well as behavioral factors such guidelines of the American Heart Association as cigarette smoking (Lloyd-Jones et al., 2010). have emphasized maintaining a healthy dietary Atherosclerotic plaques associated with myo- pattern over a focus on specific nutrients (Lichten- cardial infarction are known to have certain fea- stein et al., 2006). Generally, the recommenda- tures that increase the propensity to develop tions encourage consumption of a variety of rupture and clot (Antman et al., 2008). Postmor- fruits, vegetables, and grain products; fat-free tem studies from cases of sudden death associated dairy products; legumes; poultry; lean meats; and with CHD have revealed plaques with thin fish, preferably oily fish, at least twice a week. fibrous caps, relatively large lipid cores, and A meta-analysis of 38 randomized controlled trials a high content of a particular type of inflamma- conducted by the Cochrane Collaboration found tory cell, macrophages. It is thought that rupture that dietary advice reduced low-density lipopro- or erosion of the thin fibrous cap results in tein cholesterol and blood pressure (Brunner, Coronary Vasoconstriction 505 C

Rees, Ward, Burke, & Thorogood, 2007). How- (2006). Low-fat dietary pattern and risk of cardiovas- ever, the largest randomized trial to date of cular disease: The women’s health initiative random- ized controlled dietary modification trial. Journal of a dietary intervention to reduce cardiovascular the American Medical Association, 295(6), 655–666. risk, the Women’s Health Initiative Dietary Mod- Knoops, K. T., de Groot, L. C., Kromhout, D., Perrin, ification Trial, found no effect on cardiovascular A. E., Moreiras-Varela, O., Menotti, A., et al. (2004). events of group and individual sessions to reduce Mediterranean diet, lifestyle factors, and 10-year mor- tality in elderly European men and women: The HALE C total fat intake and increase intake of vegetables, project. Journal of the American Medical fruits, and grains, among 48,835 postmenopausal Association, 292(12), 1433–1439. women (Howard et al., 2006). Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, A substantial literature has developed M., Daniels, S., Franch, H. A., et al. (2006). Diet and lifestyle recommendations revision 2006: A scientific documenting the link between psychosocial fac- statement from the American Heart Association tors and coronary heart disease, including depres- Nutrition Committee. Circulation, 114(1), 82–96. sion, anger, and anxiety (Albus, 2010). A meta- Lloyd-Jones, D., Adams, R. J., Brown, T. M., Carnethon, analysis of 11 prospective cohort studies of M., Dai, S., De Simone, G., et al. (2010). Executive summary: Heart disease and stroke statistics–2010 healthy individuals estimated a relative risk of update: A report from the American Heart Association. 1.64 for adverse cardiac events, including myo- Circulation, 121(7), 948–954. cardial infarction (MI) and cardiac death, associ- Lloyd-Jones, D. M., Larson, M. G., Beiser, A., & Levy, D. ated with depression (Rugulies, 2002). (1999). Lifetime risk of developing coronary heart disease. The Lancet, 353(9147), 89–92. Rugulies, R. (2002). Depression as a predictor for coronary heart disease. A review and meta-analysis. Cross-References American Journal of Preventive Medicine, 23(1), 51–61. Thompson, P. D., Franklin, B. A., Balady, G. J., Blair, S. N., ▶ Corrado, D., Estes, N. A., 3rd, et al. (2007). Exercise Ischemic Heart Disease and acute cardiovascular events placing the risks into perspective: A scientific statement from the American Heart Association Council on Nutrition, Physical Activ- ity, and Metabolism and the Council on Clinical Cardi- References and Readings ology. Circulation, 115(17), 2358–2368.

Albus, C. (2010). Psychological and social factors in cor- onary heart disease. Annals of Medicine, 42(7), 487–494. Antman, E. M., Selwyn, A. P., Braunwald, E., & Loscalzo, Coronary Heart Disease (CHD) J. (2008). Chapter 237. Ischemic heart disease. In A. S. Fauci, E. Braunwald, D. L. Kasper, S. L. Hauser, D. L. ▶ Heart Disease and Smoking Longo, J. L. Jameson, & J. Loscalzo (Eds.), Harrison’s ▶ Heart Disease and Type A Behavior principles of internal medicine (17th ed.). New York: McGraw-Hill. Appel, L. J., Moore, T. J., Obarzanek, E., Vollmer, W. M., Svetkey, L. P., Sacks, F. M., et al. (1997). A clinical trial of the effects of dietary patterns on blood pressure. Coronary Vasoconstriction The New England Journal of Medicine, 336(16), 1117–1124. Appel, L. J., Sacks, F. M., Carey, V. J., Obarzanek, E., Leah Rosenberg Swain, J. F., Miller, E. R., 3rd, et al. (2005). Effects of Department of Medicine, School of Medicine, protein, monounsaturated fat, and carbohydrate intake Duke University, Durham, NC, USA on blood pressure and serum lipids: results of the OmniHeart randomized trial. Journal of the American Medical Association, 294(19), 2455–2464. Brunner, E. J., Rees, K., Ward, K., Burke, M., & Definition Thorogood, M. (2007). Dietary advice for reducing cardiovascular risk. Cochrane Database System Reviews (4), CD002128. Coronary vasoconstriction is the process by Howard, B. V., Van Horn, L., Hsia, J., Manson, J. E., which vessels of the heart reduce their overall Stefanick, M. L., Wassertheil-Smoller, S., et al. diameter. This functional capacity is mediated C 506 Cortical Activity by a variety of intrinsic and extrinsic stimuli, and inhaled may cause of type of transient vascular may be pathologic and life-threatening. obstruction that can lead to myocardial infarction and result in death of the myocardium.

Description Cross-References

There are a variety of means by which the arterial ▶ Arteries and venous flow of the heart are affected by the ▶ Cardiovascular Disease overall circulating volume in the body. One cru- ▶ Vasoconstriction cial effector is the sympathetic nervous system, upregulated or suppressed in different situations. References and Readings The sympathetic nervous system involves the secretion of the hormones epinephrine and nor- Gelfland, E. V., Gelfland, E., & Cannon, C. (2009). epinephrine from the adrenal medulla. Other Management of acute coronary syndromes. London: Wiley. important endogenous mediators include Rose, B., & Post, T. (2010). Regulation of the effective endothelin-1, serotonin, thromboxane, and pros- circulating volume. UpToDate Online 18.3. taglandins (Rose & Post, 2010).

Coronary Vasoconstriction in Acute Coronary Cortical Activity Syndromes and Variant (Prinzmetal’s) Angina Acute coronary syndromes, a term encompassing ▶ Brain Wave unstable angina and myocardial infarction, are brought about by a variety of pathophysiological changes that include coronary vasoconstriction. Cortical Dementia Myocardial infarctions are clinical sequelae of plaque disruption and clot formation over ▶ Alzheimer’s Disease the plaque. Other elements involve platelet ▶ Dementia activation, dysregulation of the coagulation system, imbalance of myocardial oxygen demand, and finally plaque rupture resulting in vessel Corticosteroids occlusion and cell death (Gelfland, Gelfland, & Cannon, 2009). Coronary vasoconstriction, ▶ Glucocorticoids induced by local and circulating levels of vasocon- strictors, also contributes to ischemia or infarction. Prinzmetal’s angina is another clinical Corticotropin-Releasing Hormone syndrome that involves coronary vasoconstric- (CRH) tion without plaque disruption. Also referred to as variant angina, Prinzmetal’s angina is Jennifer Heaney primarily caused by vasospasm without plaque School of Sport and Exercise Sciences, disruption and thrombus formation. While The University of Birmingham, Edgbaston, many Prinzmetal’s patients also have atheroscle- Birmingham, UK rotic lesions, the clinical presentation and electrocardiogram changes are caused by func- tional narrowing from coronary vasoconstriction. Definition Coronary vasoconstriction is the central mechanism of myocardial infarction caused Corticotropin-releasing hormone (CRH) or corti- by cocaine. As an analogue of sympathetic cotropin-releasing factor is a hormone that is outflow, cocaine that is smoked, injected, or secreted by the hypothalamus. It is one of the Cortisol 507 C hypophysiotropic hormones, a group of hor- processes and is particularly well known for its mones produced by the hypothalamus that affect role in the body’s response to physical and psy- the anterior pituitary gland; CRH stimulates the chological stress. These characteristics combined secretion of adrenocorticotropic hormone with its high potency and multitude of physiolog- (ACTH) from the anterior pituitary. CRH plays ical effects make cortisol a hormone of prime a key role in the endocrine response to stress as it interest for research in the area of behavioral is involved in one of the initial stages of activa- medicine. C tion of the hypothalamic-pituitary-adrenal axis (HPA axis) (Martin, Reichlin, & Brown, 1977). CRH is not only produced in response to stress Description but exhibits a circadian rhythm of secretion across a 24-h period as a result of input from the Biosynthesis and Basic Characteristics central nervous system (Martin et al., 1977). Con- Cortisol is mainly synthesized and secreted from sequently, hormones that are produced in the zona fasciculata of the adrenal cortex. In addi- response to CRH, ACTH and cortisol, also dem- tion, it is also produced in smaller amounts in other onstrate a circadian pattern of secretion tissues, including hair follicle cells, the placenta, (Greenspan & Forsham, 1983). and the brain (Ito et al., 2005). The main precursor for the production of cortisol is cholesterol from which it is derived via two alternative paths Cross-References involving several intermediate metabolic steps. As most other hormones, cortisol is secreted in ▶ ACTH a pulsatile fashion with marked circadian rhyth- micity and a mean production ranging from 8 to 25 mg/24 h (mean production: 13 mg/24 h). Due References and Readings to its relatively small size (molecular weight: 362.5 Da) and its lipophilic nature, cortisol is Greenspan, F. S., & Forsham, P. H. (1983). Basic and able to freely diffuse in and out of target cells. clinical endocrinology. Los Altos, CA: Lange Medical Publications. Martin, J. B., Reichlin, S., & Brown, G. M. (1997). Clin- Cortisol in Blood ical neuroendocrinology. Philadelphia: F.A. Davis. Following its synthesis in the adrenal cortex, cortisol is secreted into the blood stream where most of it binds to transport proteins. Approxi- mately 70% of cortisol molecules are bound to Cortisol cortisol-binding globulin (CBG or transcortin) via high-affinity receptors. A further 15–20% of Tobias Stalder and Clemens Kirschbaum cortisol is bound to lower-affinity receptors of Chair of Biopsychology, Technische Universit€at albumin while an additional 5% is also bound to Dresden, Dresden, Saxony, Germany erythrocytes. Hence, only about 5–10% of corti- sol circulates as an unbound or “free” hormone in the blood. Following the free hormone hypothesis Definition (Mendel, 1989), only this unbound fraction of cortisol can enter target cells and is thus biolog- Cortisol (or “hydrocortisone”) is a steroid hor- ically active while the larger part of bound corti- mone which is essential for life. It is produced in sol serves as an inactive reservoir. It is assumed the adrenal cortex and is predominantly regulated that mechanisms influencing the level of circulat- by the neuroendocrine hypothalamus-pituitary- ing transport proteins play an important role in adrenal (HPA) axis. Cortisol fulfills vital func- regulating the functional potency of the cortisol tions in the regulation of various homeostatic signal. Estimates of the biological half-life (T1/2) C 508 Cortisol of unbound cortisol in blood range from 60 to and proteins in the cell membrane and cytoplasm 115 min. The bioavailability of cortisol is thus as well as membrane MR and GR. relatively long compared to other hormones, such Tissue effects of cortisol are markedly as epinephrine or ß-endorphin, which show a T1/2 influenced by enzymatic action within target in the range of seconds to a few minutes. cells. Here, two variants of the enzyme 11b-hydroxysteroid dehydrogenase (11b-HSD) Physiological Actions are of particular importance. 11b-HSD type 1, Mechanisms of Signal Transduction which predominates in adipose and hepatic tis- Cortisol binds to two main types of receptors, the sues, converts inactive cortisone to active cortisol mineralocorticoid (MR) and glucocorticoid and thus has an amplifying effect on local cortisol receptors (GR). The two receptor types differ action. On the other hand, 11b-HSD type 2 is with regard to their affinity for cortisol with primarily found in the kidneys and placenta MRs showing a 6–10 times higher affinity than where it converts cortisol to its inactive metabo- GRs. As a result, about 90% of MRs are occupied lite cortisone. throughout the day, while higher GR occupancy is only reached at times of peak cortisol secretion Effects of Cortisol or during stress responses. Besides their affinity Cortisol has a wide range of effects on target for cortisol, MRs and GRs also differ in terms of tissues throughout the body. Indeed, cortisol is their distribution pattern with cortisol-responsive so essential that humans cannot survive removal MRs being predominantly located in the kidneys of the adrenal glands unless glucocorticoid and limbic structures of the brain, while GRs replacement is provided. The effects of cortisol are expressed widely throughout the brain as are often permissive rather than direct, which well as in peripheral tissues (De Kloet, Joe¨ls, & means that it frequently does not initiate an action Holsboer, 2005). but provides an environment for the action to take The “classical” mechanism of cortisol action place. Importantly, while being adaptive at nor- comprises its genomic effects. Unbound cortisol mal concentrations of cortisol, many of its actions is able to freely diffuse into the cells of the can have deleterious effects at aberrant concen- body where it binds to high-affinity receptors trations. Both excessive levels and underproduc- in the cytoplasm. While unoccupied receptors tion of cortisol have been implicated in the are guarded by heat-shock-proteins (HSP), etiology of various diseases (Chrousos, 2009). cortisol binding releases the HSP which enables the cortisol-receptor complex to enter the cell Effects on Carbohydrate and Lipid nucleus. Here it binds to specific sites of the Metabolism deoxyribonucleic acid (DNA) and acts as Cortisol is the primary glucocorticoid in humans, a transcription factor to alter the cell’s protein which hints to the fact that one of its pivotal biosynthesis. Subsequently, the cortisol-receptor functions lies in facilitating the mobilization of complex is transported back into the cytoplasm. energy resources. It enhances gluconeogenesis in Here it disintegrates and the cortisol molecule, the liver and reduces glucose uptake into muscle which may have been structurally altered, exits and adipose tissue, which increases the amount the cell into the extracellular space. of glucose available for the body. Cortisol also While the time course of genomic effects of crucially augments the conversion of protein to cortisol is relatively slow ranging from several glycogen and thus helps to maintain hepatic minutes to hours, cortisol also affects cell func- glycogen stores on which other hormones, like tion via faster non-genomic mechanisms. These glucagon, can subsequently act to increase glu- mechanisms influence a wide range of intracellu- cose levels. Cortisol also increases the break- lar processes and are of importance across many down of proteins stored in muscle, bone, and peripheral as well as central structures. Targets of connective tissue and inhibits protein synthesis non-genomic cortisol action might include lipids in non-hepatic tissues which increases the Cortisol 509 C amount of protein available for gluconeogenesis. Effects on Brain and Cognition Importantly, while this catabolic action is physi- Cortisol is able to enter the brain where it affects ologically beneficial at adequate concentrations a wide range of neuronal processes and cognitive of cortisol, at excessive levels, it results in the functions. Cortisol exerts these actions both via depletion of protein stores which can manifest in the slower genomic pathways as well as via fast symptoms such as thinning of the skin, reduced non-genomic effects which directly affect the muscle mass, or osteoporosis. responsivity of neuronal networks. Via these C Besides aiding proteolysis, cortisol is also pathways, cortisol interacts with the neurotrans- assumed to facilitate the mobilization of free mitter systems (including noradrenergic, seroto- fatty acids from fat depots which further supports nergic, dopaminergic and cholinergic, and gluconeogenesis. However, cortisol may also GABAergic neurotransmission) as well as with have stimulatory effects on appetite and calorie neuropeptidergic systems, e.g., oxytocin and intake and leads to enhanced fat deposition arginine vasopressin. in abdominal and facial areas. Under conditions One of the best described effects of cortisol on of chronically elevated cortisol secretion, e.g., in cognitive functions is an enhancing influence on Cushing’s syndrome, this leads to a characteristic the encoding and consolidation of emotionally pattern of central adiposity, as well as fat deposi- relevant information under arousing conditions tions in the face (“moon face”) and at the neck (de Quervain et al., 2009). However, while corti- (“buffalo hump”). sol may enhance memory consolidation, acutely elevated cortisol levels are also associated with Effects on Electrolyte Metabolism impaired memory retrieval, particularly of The effects of cortisol on sodium and water reten- declarative memory, as well as with tion are considerably weaker than those of aldo- compromised working memory function. Despite sterone, the primary mineralocorticoid hormone the involvement of other brain regions (e.g., hip- in humans. However, this lack in potency is pocampus and medial prefrontal cortex), close outweighed by the approximately 200-fold reciprocal interactions between cortisol and nor- higher concentrations of cortisol compared to adrenergic neurotransmission in the basolateral aldosterone which indicates that cortisol also nucleus of the amygdala are assumed to be of plays an important role electrolyte metabolism. particular importance for the modulation of these effects on memory. Besides effects on Immunological Effects memory, a stimulatory influence of cortisol on Cortisol is the most potent endogenous immuno- psychological arousal has also been reported. suppressive substance with strong anti- Similarly, cortisol can lead to increased ampli- inflammatory effects. Virtually all steps involved tude and decreased latency of EEG event-related in the local inflammatory response to injury, e.g., potentials and heightened EEG frequency. dilation of capillaries or tissue swelling, are In addition to these actions under normal func- inhibited by cortisol. It also decreases leukocyte tioning, pharmacological administration of high recruitment and effectiveness at the site of inflam- doses of glucocorticoids has been associated with mation. These effects of cortisol have long been profound psychoactive effects (Lupien, Maheu, recognized and used in anti-inflammatory drug Tu, Fiocco, & Schramek, 2007). These include treatments. Cortisol also profoundly suppresses the experience of psychiatric symptoms, such as the immune response to antigens, e.g., by reducing depression, mania, and psychotic episodes, often the number and activity of thymus-derived lym- collectively referred to as “steroid psychosis.” phocytes (T-cells). In addition, cortisol inhibits Interestingly, during the initial phase of treat- other components of the immune response such ment, elevations of mood and euphoria are often as cytokine synthesis, proliferation and differenti- seen while dysphoric mood states and depression ation of monocytes as well as activity of macro- predominate with prolonged treatment. This is phages and natural killer cell. in line with the fact that Cushing’s syndrome, C 510 Cortisol i.e., chronic endogenous hypercortisolemia, is a strong increase during the second half of also frequently associated with depression and/or sleep. Upon morning awakening, an additional other psychiatric symptoms which usually subside rise in cortisol levels for approximately with successful treatment. Importantly, chronic 30–40 min post-awakening is seen (the “cortisol exposure to excessive amounts of cortisol has awakening response,” CAR; Fries, Dettenborn, & also been associated with hippocampal atrophy Kirschbaum, 2009) which results in circadian and cell death as well as with deficits in hippocam- peak levels being reached. Subsequently, cortisol pus-dependent cognitive functioning. This effect levels show a gradual decline over the remainder might play a particular role with regard to the of the day until they again reach nadir levels cognitive decline often seen with older age. during the first half of sleep.

Regulation Response to Physiological and Psychological Overview Stress The synthesis and secretion of cortisol from the A prominent feature of cortisol secretion is its adrenal cortex is predominantly controlled by the marked increase in response to both physiologi- neuroendocrine HPA axis, a signaling cascade cal as well as psychological stress. With regard to involving the release of corticotropin-releasing the former, cortisol responses have been shown hormone (CRH) and adrenocorticotropin hor- following intense exercise or hard physical work. mone (ACTH) as well as numerous other sub- For a significant cortisol response to occur under stances, specifically neuropeptides. Both the these conditions, exercise has to be highly intense activity of the HPA axis as well as the secretion or sustained with a maximum oxygen uptake of cortisol occur in a pulsatile fashion with (VO2max) over 70%. The cortisol response to approximately 12–18 ultradian pulses per 24-h exercise shows no habituation after repeated span. The concentration of circulating cortisol is exposure. In addition to exercise and intense determined by the frequency and amplitude of physical work, a range of other physical condi- individual pulses. The release of cortisol via the tions have been shown to result in cortisol HPA axis is under tight negative feedback con- responses, e.g., pain and physical trauma, hypo- trol, with cortisol inhibiting its own secretion by glycemia, hypoxemia, increased insulin levels, or downregulating levels of CRH and ACTH. consumption of a protein-rich meal. Besides regulation via the HPA axis, there is It is now well established that cortisol secre- also considerable evidence that levels of ACTH tion also responds strongly to psychologically and cortisol can dissociate under various condi- challenging conditions. The magnitude of this tions, suggesting additional extra-pituitary regula- response is dependent on both, external factors tory mechanisms. Here, sympathetic innervations and characteristics of the individual. Situations of the adrenal gland via the splanchnic nerve are containing both uncontrollable and social- likely to be of special importance. This pathway is evaluative elements tend to result in the largest assumed to particularly modulate cortisol secre- cortisol responses (Dickerson & Kemeny, 2004). tion by altering adrenal sensitivity to ACTH and is A wide range of psychological factors (e.g., likely to involve both intra-adrenal paracrine inter- appraisal of the situation, personality traits, cop- actions as well as direct splanchnic innervation of ing and attributional style, perceived social the adrenal cortex (Bornstein, Engeland, Ehrhart- support, or adverse early life experiences) as Bornstein, & Herman, 2008). well as physiological predispositions (sex, age, or genetic factors) have been shown to influence Basal Secretion the magnitude of the cortisol stress response The secretion of cortisol is subject to consider- (Foley & Kirschbaum, 2010). In contrast to the able circadian variation: Following a circadian response to physiological challenge, the cortisol nadir during the early night, cortisol levels show response to psychological stress shows Cortisol 511 C considerable habituation following repeated active cortisol in human research (Kirschbaum & exposure to the same stress-eliciting situation. Hellhammer, 1994). A potential limitation relating to both blood Measurement and salivary assessments of cortisol is that single Modern laboratory methods allow for rapid and spot samples only reflect cortisol secretion during economic cortisol determination in different the acute sampling situation. Since many situa- matrices. Most frequently, cortisol levels are tional variables are known to influence cortisol C measured in blood, saliva, or urine samples secretion (see above), drawing conclusions which usually provide information on cortisol regarding overall functional cortisol status from production and levels over relatively short time such “spot data” can be misleading. intervals (minutes to days). A recent addition to this methodology is the measurement of cortisol Urine concentrations in hair which is assumed to pro- A considerable amount of circulating cortisol is vide an index of integrated cortisol secretion over metabolized and excreted into urine. The assess- prolonged periods of up to several months. ment of urinary cortisol metabolites thus provides a measure of cumulative cortisol secretion over Blood Plasma or Serum the time period during which urine samples were The assessment of cortisol in blood (both plasma collected. By using an extended collection period and serum) reflects acutely circulating concentra- of, e.g., 24 h, the respective results are less tions and thus provides a valuable approach for influenced by momentary fluctuations in cortisol assessing momentary cortisol levels or dynamic levels but integrate overall secretory patterns changes in cortisol secretion. Importantly, the over the sampling period. assessment of total cortisol in blood comprises both bound and unbound cortisol and their separa- Hair tion can be time consuming and thus expensive. The examination of endogenous cortisol concen- Consequently, blood assessments are not best trations in human hair has recently been intro- suited for assessing the bioavailable fraction of duced as a new measure of steroid hormone cortisol. In addition, blood sampling bears determination. As it is assumed that cortisol is a minor risk of infection and through its invasive incorporated into the hair shaft during hair nature may itself trigger an acute cortisol stress growth, the examination of cortisol levels in response. a specific hair segment is believed to provide a retrospective index of cumulative cortisol secre- Saliva tion over the period during which the respective As with cortisol assessments in blood, salivary hair segment has grown. Given a hair growth rate measurements also reflect acutely circulating cor- of approximately 1 cm/month, the examination of tisol levels. However, as only unbound cortisol a 3 cm hair segment should allow the assessment can passively diffuse into saliva, salivary cortisol of cumulative cortisol levels over a 3 months levels only represent the free, biologically active period. This largely extended window of exami- fraction. Importantly, the level of salivary corti- nation combined with the possibility of sol is unrelated to salivary flow rate and shows a retrospective assessment highlights the poten- only a minimal time lag of 1–2 min to plasma tial of hair cortisol analysis as an important future cortisol levels. In addition, saliva sampling is an research tool (Stalder & Kirschbaum, in press). unintrusive and generally well-accepted method which may easily be carried out under ambula- Cross-References tory conditions. Salivary cortisol assessments are thus increasingly used as the method of ▶ Corticosteroids choice to determine acute levels of biologically ▶ Corticotropin-Releasing Hormone (CRH) C 512 Cortisone

▶ Glucocorticoids ▶ Hypothalamic-Pituitary-Adrenal Axis Cost Analysis

References and Readings ▶ Cost-Minimization Analysis

Bornstein, S. R., Engeland, W. C., Ehrhart-Bornstein, M., & Herman, J. P. (2008). Dissociation of ACTH and gluco- corticoids. Trends in Endocrinology and Metabolism, 19, 175–180. Cost Identification Chrousos, G. P. (2009). Stress and disorders of the stress system. Nature Review of Endocrinology, 5(7), ▶ Cost-Minimization Analysis 374–381. De Kloet, E. R., Joe¨ls, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Reviews Neuroscience, 6, 463–475. De Quervain, D. J., Aerni, A., Schelling, G., & Cost-Benefit Analysis (CBA) Roozendaal, B. (2009). Glucocorticoids and the regu- lation of memory in health and disease. Frontiers in ▶ Neuroendocrinology, 30, 358–370. Benefit Evaluation in Health Economic Studies Dickerson, S. S., & Kemeny, M. E. (2004). Acute stressors and cortisol responses: A theoretical integration and synthesis of laboratory research. Psychological Bulle- tin, 130, 355–391. Foley, P., & Kirschbaum, C. (2010). Human hypothala- Cost-Comparison Analysis mus-pituitary-adrenal axis responses to acute psycho- social stress in laboratory settings. Neuroscience & ▶ Cost-Minimization Analysis Biobehavioral Reviews, 35, 91–96. Fries, E., Dettenborn, L., & Kirschbaum, C. (2009). The cortisol awakening response (CAR): Facts and future directions. International Journal of Psychophysiology, 72, 67–73. Cost-Effectiveness Ito, N., Ito, T., Kromminga, A., Bettermann, A., Takigawa, M., Kees, F., et al. (2005). Human hair 1 2 follicles display a functional equivalent of the hypo- Stephen Birch and Amiram Gafni 1 thalamic-pituitary-adrenal axis and synthesize corti- Clinical Epidemiology and Biostatistics sol. The FASEB Journal, 19, 1332–1334. (CHEPA), McMaster University, Hamilton, Kirschbaum, C., & Hellhammer, D. H. (1994). Salivary ON, Canada cortisol in psychoneuroendocrine research – Recent 2 developments and applications. Psychoneuroendo- Department of Clinical Epidemiology and crinology, 19, 313–333. Biostatistics, Centre for Health Economics and Lupien, S. J., Maheu, F., Tu, M., Fiocco, A., & Schramek, Policy Analysis, McMaster University, T. E. (2007). The effects of stress and stress hormones Hamilton, ON, Canada on human cognition: Implications for the field of brain and cognition. Brain and Cognition, 65, 209–237. Mendel, C. M. (1989). The free hormone hypothesis: A physiologically based mathematical model. Endo- Definition crine Reviews, 10, 232–274. Stalder, T., Kirschbaum, C. (in press). Analysis of cortisol in hair – State of the art and future directions. Cost-effectiveness is concerned with improving Brain, Behavior and Immunity. doi:10.1016/j. the performance of a health care system by ensur- bbi.2012.02.002. ing the resources available to a health care system are used in their most productive way. This can only be achieved through careful consideration of the full consequences and opportunity costs of Cortisone introducing a new health care program in the context or setting in which it is to be introduced. ▶ Glucocorticoids Appropriate evaluation methods must be Cost-Effectiveness 513 C employed to accommodate this information and more than the existing intervention. To provide avoid simplifying assumptions that threaten the the greater effects of the new treatment, the num- evaluation’s validity. ber of other unrelated treatments must be reduced to release resources to support the additional costs of the new treatment. Here the decision-maker Description looks to the economist for “inputs” to the deci- sion-making process – in particular decision rules C Economic evaluation has been defined as “ensur- for CEA. ing that the value of what is gained from an activity outweighs the value of what has to be sacrificed” (Wiliams 1983). Hence, economic The Decision Rules of CEA evaluation reflects the fundamental principles of economics that (1) resources are scarce, The traditional analytical tool of CEA is the (2) choices are made between alternative uses of incremental cost-effectiveness ratio (ICER), resources, and (3) a particular deployment of the incremental cost of the new program divided resources involves forgoing the benefits gener- by the incremental effects of the new program. ated from alternative deployments of the same Maximum health gain from available resources is resources. Hence, it requires consideration of produced under the following decision rules: both outcome measurement and opportunity The league table rule: Select programs in cost. Cost-Effectiveness Analysis (CEA) is the ascending order of ICER (i.e., project with lowest most common methodology of economic evalu- ICER first) until available resources are ation in health care, aimed at informing decision- exhausted. makers faced with constrained resources. For The threshold ICER rule: Select programs a particular level of health care resources, which with ICER less than or equal to l, the shadow need not be the current level, the challenge is to price of the budget. choose from among all possible health care pro- Because ICERs have not been estimated for all grams the combination of programs that maxi- programs currently delivered in health care sys- mizes total health benefits produce. tems, comprehensive league tables are not avail- The theoretical basis for CEA derives from able and the league table rule cannot be followed. a decision-maker with a fixed budget choosing The threshold rule has provided the basis for between many possible programs based on economic evaluation guidelines in many jurisdic- a comparison of the difference in effects tions. In each case the use of CEA is linked to between a program under consideration and the addressing the problem of maximizing health current way of serving the same patient popula- improvements from available resources. tion (incremental effects), and the difference in This solution is based on assumptions of per- costs between the two programs (incremental fect divisibility and constant returns to scale in costs). Where incremental costs and incremental all programs. Yet, such conditions do not hold effects have different signs, the solution is triv- generally in health care decision-making. One ial, for example, the new program costs more cannot divide up an investment to fit whatever (i.e., reduces resources available for other budgetary amount is available. A manager must unrelated programs) and produces less effects purchase an entire Magnetic Resonance Imaging than the current program. Similarly with nega- (MRI) machine, it is not divisible, it is all or tive incremental costs and positive incremental nothing. Apart from such physical constraints effects, a “win-win,” no substantial reflection on divisibility, some programs may not be divis- is required. In most cases, however, a new ible because of political or ethical constraints. intervention involves incremental effects and It is ethically problematic to offer vaccination incremental costs with the same sign, for exam- to only 50% of children. Increasing investment ple, the intervention is more effective but costs in a particular program may not produce C 514 Cost-Effectiveness proportionally equal increases in outcomes as available resources. This is determined by program coverage expands from highest need/ constructing the ICER league table, but requires most severe patients to lesser need/severity information on the incremental costs and effects groups. So the additional outcomes produced of all possible programs. Hence, the threshold from investing resources in a program may dimin- value required to make decisions that produce ish with the scale of the program. Even if the the maximization of health gains from available program under evaluation does exhibit constant resources cannot be determined even if the theo- returns to scale the opportunity, cost of the pro- retical assumptions hold. gram is likely to have non-constant returns in the sense that increased resource requirements for the new program mean the decision-maker has to Extending Economic Evaluation to “dig deeper” into his existing budget to fund it. Identify Efficiency Improvements After resources from the least productive current program have been exhausted he must look to For an intervention to represent an efficient use of other more productive programs meaning that resources the additional effects it generates must the marginal opportunity cost of the program exceed the effects forgone from the most produc- increases with size. tive alternative use of the same resources. Hence, Because decision-makers are faced with efficiency cannot be established only by refer- choices between programs of different sizes, and ence to the resources required and outcomes the opportunity costs of programs depend crucially produced by a particular intervention. Informa- on program size, the different programs are not tion on alternative uses of those resources is also directly comparable. The ICER is the average cost needed and so efficiency is context-specific. Even per Quality Adjusted Life Year (QALY) or the where incremental costs and effects of an inter- inverse of the average rate of return on additional vention are identical in different settings, it does investments required by a program. Comparisons not mean the efficiency of that intervention is the of ICERs across programs ignore problems intro- same in all settings. duced by the different sizes of programs. They do If economics is to inform decision-makers not compare like with like. Moreover, decision- about the efficiency of investments, traditional makers cannot purchase individual units of approaches to CEA and the use of ICERs are QALYs. Each program produces a “package” insufficient. Mathematical approaches to of QALYs, and the average price per QALY may constrained maximization, such as integer pro- differ by program size. Consequently the ICER gramming (IP), solve the decision-maker’s prob- threshold decision-rule is not sufficient to maxi- lem and are the only universal approach to ranking mize health effects from available resources. programs according to efficiency under a resource There is no theoretical justification for asserting constraint. The key requirement of the IP approach that the strategy with the lowest cost-effectiveness is that the specification of the problem (i.e., objec- ratio is the most desirable one. tive function and constraints) must accurately To adopt the threshold ICER approach in the reflect the decision-maker’s problem setting. absence of the theoretical assumptions requires The substantial data requirements of the IP an unspecified supply of resources with constant approach, specifically the incremental costs and marginal opportunity cost. Anything further from effects of all programs together with the the reality of decision-making is hard to imagine. resources available for investment, may be diffi- Even if the assumptions are accepted for cult to satisfy. However, these requirements the purposes of the theoretical model, the prob- reflect the complex nature of the decision- lem of determining a threshold remains. Under maker’s problem. the model, the threshold is given by the opportu- An alternative practical approach is available nity cost of the marginal program funded from (Birch & Gafni 1992; Gafni & Birch 1993) which Cost-Effectiveness Analysis (CEA) 515 C satisfies a modified objective of an unambiguous Cross-References increase in health improvements from available resources (i.e., an objective of improving, as ▶ Benefit Evaluation in Health Economic Studies opposed to maximizing, efficiency). This requires that the health improvements of the pro- posed program be compared with the health improvements produced by that combination of References and Readings C programs that have to be given up to generate sufficient funds for the proposed program. Only Birch, S., & Gafni, A. (1992). Cost-effectiveness/utility analyses: Do current decision rules lead us to where we where the health improvements of the proposed want to be? Journal of Health Economics, 11, program exceed the health improvements of the 279–296. combination of programs to be given up does Birch, S., & Gafni, A. (2003). Economics and the evalu- the new technology represent an improvement ation of health care programmes: Generalisability of methods and implications for generalisability of in the efficiency of resource utilization. The results. Health Policy, 64, 207–219. approach does not rely on an arbitrarily deter- Birch, S., & Gafni, A. (2006a). Decision rules in economic mined threshold value to ascertain the efficiency evaluation. In A. Jones (Ed.), The Elgar companion to of the program, nor is it dependent on unrealistic health economics (pp. 492–502). Cheltenham: Edward Elgar. assumptions about perfect divisibility and con- Birch, S., & Gafni, A. (2006b). The biggest bang for the stant returns to scale. Instead, the source of buck or bigger bucks for the bang: The fallacy of additional resource requirements is identified the cost-effectiveness threshold. Journal of Health and the implications of canceling programs to Services Research and Policy, 11, 46–51. Drummond, M. (1980). Principles of economic appraisal generate these resources form part of the analysis. in health care. Oxford: Oxford University Press. Iterative application of this efficiency-improving Drummond, M., Sculpher, M., Torrance, G., O’Brien, B., approach would eventually lead to efficiency & Stoddart, G. (2005). Methods for the economic eval- maximization as opportunities to further improve uation of health care programmes. New York: Oxford University Press. efficiency are exhausted. Gafni, A., & Birch, S. (1993). Guidelines for the adoption Concern with maximizing health improvements of new technology: A potential prescription for from available resources may be just one of several uncontrolled growth in expenditures and how to objectives that decision-makers face. For example, avoid it. Canadian Medical Association Journal, 148, 913–917. political considerations associated with providing Gafni, A., & Birch, S. (2006). Incremental cost- equal access to services and providing greater effectiveness ratios (ICERs): The silence of the priority to health improvements of specific popula- lambda. Social Science and Medicine, 62, tion groups may be important goals. However, the 2091–2100. Weinstein, M., & Zeckhauser, R. (1973). Foundations presence of multiple objectives and constraints of cost effectiveness analysis for health and does not reduce the importance of adopting medical practices. Journal of Public Economics, 2, a constrained maximization model as the basis for 147–157. analysis. It remains important that whatever goals Wiliams, A. (1983). The economic role of health indica- tors. In G. Teeling-Smith (Ed.), Measuring the social are identified, these must be pursued efficiently in benefits of medicine (pp. 63–67). London: Office of order to avoid wasting resources. The explicit iden- Health Economics. tification of each objective and constraint enables the full range of policy concerns to be incorporated systematically into the analysis. Hence, the com- plex objectives faced by decision-makers, far from limiting the role of economic analysis, represent Cost-Effectiveness Analysis (CEA) precisely the challenges that the economic model of constrained maximization is intended to ▶ Benefit Evaluation in Health Economic Studies accommodate. ▶ Cost-Effectiveness C 516 Cost-Minimization Analysis

(Briggs & O’Brien, 2001) and, furthermore, Cost-Minimization Analysis that other economic evaluation methods such as cost-utility, cost-benefit, and cost-effectiveness Alejandra Duenas analyses are more comprehensive, given that School of Management, IESEG, Paris, France they allow for the comparison of interventions with different effectiveness outcomes and the incorporation of uncertainty. Synonyms Cross-References Cost analysis; Cost identification; Cost- comparison analysis ▶ Cost-Effectiveness Analysis (CEA)

References and Readings Definition Briggs, A. H., & O’Brien, B. J. (2001). The death of cost- This term refers to an economic evaluation tool. minimization analysis? Health Economics, 10(2), 179–184. Cost-minimization analysis is mostly applied Kobelt, G. (2002). Health economics: An introduction to in the health sector and is a method used to mea- economic evaluation (2nd ed.). London: Office of sure and compare the costs of different medical Health Economics. interventions. The principal limitations of this cost evaluation method are that it can only be used to compare treatments that provide the same benefits Cost-Utility Analysis (CUA) or effectiveness (identical outcomes, e.g., thera- peutic effects); moreover, costs need to be deter- ▶ Benefit Evaluation in Health Economic Studies mined accurately. In this way, a decision maker can choose the treatment with the lowest total cost. The assessment of costs is performed by identify- Couple Therapy ing the study’s perspective, all the resources used, and quantifying them into physical units. The most ▶ Couple-Focused Therapy common perspectives are societal perspective ▶ Therapy, Family and Marital (includes all costs incurred by health care services, social services, patients, and society in general) and third-party payer perspective (includes the Couple-Focused Therapy costs incurred by an insurance company, a gov- ernment, etc.). In order to quantify the resources Beate Ditzen1 and Tanja Zimmermann2 used, a physical unit is defined, such as the number 1Division of Clinical Psychology and of hospital days, the time that a nurse spends with Psychotherapy, Department of Psychology, a patient, number of doctors’ visits, etc. Once the University of Zurich, Binzmuhlestrasse, Zurich, units are defined and quantified, they are translated Switzerland to costs by multiplying the unit costs by the num- 2Department of Clinical Psychology, ber of units used. Psychotherapy and Diagnostics, University of The use of this tool is rather limited as it is Braunschweig, Braunschweig, Germany difficult to demonstrate that the efficacy of two or more interventions is equivalent. A common application of cost-minimization analysis is the Synonyms comparison of generic drugs in order to achieve market approval. Some experts consider that Couple therapy; Marital therapy; Marriage cost-minimization analysis is no longer useful counseling Couple-Focused Therapy 517 C

Definition questioning and modulating presumptions about the positive (or more often negative) motives of Couple-focused therapy (CFT) is a psychological each partner and thereby try to prevent negative therapy with the focus of attention on the rela- behavior. tionship between two individuals rather than on one individual. The aim of CFT is to enable Psychoanalytical Therapy a better level of functioning in couples – married Psychoanalytical CFT attempts to discover C or unmarried – who are experiencing distress in early developmental conflicts in relation to the their relationship. Couples may seek CFT for present interpersonal interactions within the a variety of reasons, such as distress in terms of couple. In this approach, couples are thought to finances, sexuality, communication, infidelity, or be able to improve their relationship through individual psychopathology as well as physical a better understandingofhowearlyparent- health problems with an impact for the couple. child interactions might influence later behavior Consequently, CFT will differ according to the in adulthood. respective relationship problems. Moreover, cou- ple interventions may also vary based on the Emotion-Focused Therapy phase of the relationship during which they As indicated by the name, the main emphasis in occur: Whereas primary prevention programs or emotion-focused CFT is on the identification couple education (e.g., the Prevention and Rela- and expression of emotional needs in the couple tionship Enhancement Program, PREP, from relationship. In particular, the expressions of Howard Markman) might be offered for preven- underlying feelings are supposed to change the tion of future distress relatively early in the rela- perception of the partner and motivate behavior tionship, CFT is usually called for when severe change. problems are present. In general, the first step of CFT is to identify Integrative Therapy the areas of dissatisfaction in the relationship, and In a number of more recent approaches, to implement a treatment plan to which both researchers have combined a variety of treatment partners are willing to agree. Based on this treat- strategies within a consistent theoretical ment plan, therapy sessions will differ according framework, resulting in integrated treatment to the chosen model or the philosophy behind the models (among others the Enhanced therapy. In the following, some of the best-known Cognitive-Behavioral Couple Therapy by Epstein approaches will be briefly characterized. and Baucom (2003), or the Integrative Behavioral Couple Therapy by Jacobson and Christensen Behavior-Focused Therapy (1998); also see Snyder (1999), Snyder, Castellani, Traditionally, behavior-focused therapy is based and Whisman (2006)). on the idea that both partners (possibly involun- CFT programs are broadly evaluated treat- tarily) tend to reward and punish specific behav- ment options with effect sizes in the range of iors during the development of their relationship. d ¼ 0.72 for communication and relationship Consequently, this behavior exchange is an satisfaction, whereas in comparison typically no important treatment focus (e.g., by providing changes in marital quality in untreated couples encouragement of positive behavior) in behav- are observed (Baucom, Hahlweg, & Kuschel, ioral couple therapy. 2003). However, it should be noted that CFT is no guarantee that the relationship will improve, Cognitive-Behavioral Therapy and there are couples who might benefit more With its roots in behavioral therapy, cognitive- from ending their relationship than from continu- behavioral CFT has enriched the focus on behav- ing it. This makes the overall evaluation of CFT ior with the perspective on couples’ beliefs a challenging topic in behavioral medicine (cf., regarding the relationship. Therapists aim at Christensen, Baucom, Vu, & Stanton, 2005). C 518 Covariance Components Model

Cross-References Definition

▶ Cognitive Behavioral Therapy (CBT) A co-worker is a person who a worker works with, ▶ Marital Satisfaction in their role as worker. Co-workers can share their knowledge and expertise when others are faced with problems or novel situations; this can be References and Readings especially useful when alternative solutions are not readily accessible. The co-worker relationship Baucom, D. H., Hahlweg, K., & Kuschel, A. (2003). Are can also have effects on workplace dynamics, waiting-list control groups needed in future marital individual stress level, and relationships. Positive therapy outcome research? Behavior Therapy, 34, 179–188. relationships between co-workers can be seen Christensen, A., Baucom, D. H., Vu, C. T., & Stanton, S. as supportive and beneficial in dealing with day- (2005). Methodologically sound, cost-effective to-day problems and strains arising from research on the outcome of couple therapy. Journal employment (Deery, Iverson, & Walsh, 2010), of Family Psychology, 19(1), 6–17. Epstein, N. B., & Baucom, D. H. (2003). Enhanced cog- and positive relationships can increase job satisfac- nitive-behavioral therapy for couples. Washington, tion, job involvement, and organizational commit- DC: American Psychological Association. ment (Dur & Sol, 2008). This supportive Jacobson, N. S., & Christensen, A. (1998). Acceptance relationship may be more likely to occur in and change in couple therapy: A therapist’s guide to transforming relationships. New York: Norton. interactionally intense and high stress settings and Snyder, D. K. (1999). Affective reconstruction in the can help one cope with high job demands. The pace context of a pluralistic approach to couples therapy. and intensity for the work can be regulated through Clinical Psychology: Science and Practice, 6(4), collaboration between co-workers, and workplace 348–365. Snyder, D. K., Castellani, A. M., & Whisman, M. A. norms are often established through co-worker (2006). Current status and future directions in couple interaction and collaboration (Deery et al., 2010). therapy. Annual Review of Psychology, 57, 317–344. Co-worker relationships can be influenced by a variety of personality traits. Matching co-workers into groups based on these personal- ity traits can lead to strong group cohesion and can create an effective team (Tett & Murphy, Covariance Components Model 2002). Additionally, supportive and positive co- workers can promote an environment where new ▶ Hierarchical Linear Modeling (HLM) ideas are easily and comfortably discussed, which also has positive impacts on the group (Joiner, 2007). Conversely, a mismatch of per- sonality traits can have negative impacts on Co-workers group dynamics (Tett & Murphy, 2002).

Karen Jacobs1, Miranda Hellman2, Cross-References Jacqueline Markowitz2 and Ellen Wuest2 1Occupational Therapy, College of Health and ▶ Communication, Nonverbal Rehabilitation Science, Sargent College, Boston University, Boston, MA, USA 2Boston University, Boston, MA, USA References and Readings

Deery, S. J., Iverson, R. D., & Walsh, J. T. (2010). Coping Synonyms strategies in call centres: Work intensity and the role of co-workers and supervisors. British Journal of Indus- trial Relations, 48, 181–200. doi:10.1111/j.1467- Associate; Collaborator; Colleague 8543.2009.00755.x. C-Reactive Protein (CRP) 519 C

Dur, R., & Sol, J. (2008). Social interaction, co-worker influence of the macrophages and monocytes at altruism, and incentives. Amsterdam: Tinbergen the site of the inflammation. Interleukin (IL)-6 Institute. Joiner, T. (2007). Total quality management and perfor- has been shown to be most important for CRP mance: The role of organization support and production, but other cytokines, such as IL-1, co-worker support. International Journal of Quality tumor necrosis factor-alpha, interferon gamma, and Reliability Management, 24, 617–627. as well as glucocorticoids, can also play a role. doi:10.1108/02656710710757808. C Tett, R. P., & Murphy, P. J. (2002). Personality and Interestingly, specific combinations of these fac- situations in co-worker preference: Similarity tors can both enhance as well as inhibit CRP and complementarity in worker compatibility. Journal production (Gabay & Kushner, 1999; Pepys & of Business Psychology, 17, 223–243. Hirschfield, 2003). The function of CRP is to restore normal structure and function of the tissue that has been affected. CRP recognizes and mediates the elim- ination of pathogens through activation of the C-Reactive Protein (CRP) complement system (Gabay & Kushner, 1999; Pepys & Hirschfield, 2003). Even though the Jet Veldhuijzen van Zanten aim of the initial increase in CRP is to combat School of Sport and Exercise Sciences, infection and acute inflammation, chronically The University of Birmingham, Edgbaston, raised levels have been associated with negative Birmingham, UK effects for health. Particular attention has been paid to the association between high levels of CRP and increased risk for atherosclerosis and Synonyms cardiac events; high levels of CRP have been implicated in the pathogenesis, progression, and Acute phase proteins; Inflammatory markers complications of atherosclerotic plaques (Ridker, 2004). CRP can be readily assessed in serum using Definition commercially available (high-sensitivity) assays. As the clearance rate of CRP remains stable, the C-reactive protein (CRP) is an important increases in serologically determined CRP are protein of the acute-phase response, which is a indicative of CRP production. Following the nonspecific physiological and biochemical stimulus, it takes on approximately 6 h until an response to infection, inflammation, and tissue increase is detectable in the serum. The half-life damage. Increases in CRP are found during infec- of CRP is less than 24 h. tion, chronic inflammatory diseases, and follow- ing a myocardial infarction. Strenuous exercise and psychological stress can also induce Cross-References increases in CRP, albeit to a lesser extent com- pared to the physiologically more traumatic ▶ Biomarkers events described above. Therefore, levels of ▶ Cardiovascular Risk Factors CRP can be reflective of both acute and chronic ▶ Inflammation inflammation (Gabay & Kushner, 1999). The CRP molecule consists of five calcium- binding nonglycosylated protomers in a pentameric symmetry. CRP is mainly produced References and Readings by hepatocytes, even though other sources have Gabay, C., & Kushner, I. (1999). Acute-phase proteins and also been reported. The production is stimulated other systemic responses to inflammation. The New by cytokines, which are released under the England Journal of Medicine, 340, 448–454. C 520 Crohn’s Disease (CD)

Pepys, M. B., & Hirschfield, G. M. (2003). C-reactive discussed for pathogenesis. Data on expression protein: a critical update. Journal of Clinical Investi- suggest that macrophages and epithelial cells gation, 111, 1805–1812. Ridker, P. M. (2004). High-sensitivity C-reactive protein, could be the locus of the primary pathophysiolog- inflammation, and cardiovascular risk: From concept ical defect and that T-cell activation might to clinical practice to clinical benefit. American Heart be a secondary effect inducing chronification of Journal, 148, S19–S26. the inflammation, presumably as a backup mech- anism to insufficient innate immunity. Genetic predisposition, ethnicity, smoking behavior, nutri- tion habits, and enhanced drug intake are discussed Crohn’s Disease (CD) as further risk or modulating factors. No causal therapy is currently available for Crohn’s disease. Kyung-Eun Choi and Jost Langhorst Though not curable, glucocorticoids, Kliniken Essen Mitte, Klinik fur€ Naturheilkunde aminosalicylates, antibiotics, immunomodula- und Integrative Medizin, Universit€at tory substances, enteral (specific diets) or paren- Duisburg-Essen, Am Deimelsberg 34a, teral feeding (under avoidance of the digestive Essen, Germany tract), and surgical procedures can alleviate symptoms’ severity (Akobeng & Thomas, 2007; Butterworth, Thomas, & Akobeng, 2008). Ninety Synonyms percent of the patients concerned have to undergo surgery at least once in their lifetime, and 20% of English: Regional enteritis operated patients will undergo further surgery Latin: Enteritis regionalis Crohn; Enterocolitis within the next 5 years. regionalis; Ileitis terminalis; Morbus Crohn (MC) Due to a lack of well-designed randomized controlled trials in the field of behavioral medi- cine, only insufficient evidence is available so far Definition to make firm conclusions about the efficacy of different psychotherapeutic treatment options Crohn’s disease is a chronic inflammatory disor- for induction of remission in Crohn’s disease. der which can affect the entire gastrointestinal Neither any specific personality traits nor any fam- (GI) tract. It is most commonly located in the ily structures in correlation with the occurrence of terminal ileum and the proximal colon but may Crohn’s disease have hitherto been clearly identi- involve any part of the GI tract. Its incidence in fied. Although a causal relationship with critical middle Europe is around 1.5–8.5% and its prev- life events and/or stress has not been established so alence around 0,036%. The inflammations gener- far, Crohn’s disease creates an immense burden on ally appear in outlined sections, affect all laminae patients and is a critical strain on patients and of the intestinal wall, and cause abscesses and relatives. Consequently, psychological changes fistulae. Key symptoms are persistent diarrhea, (including higher values of depression, anxiety, abdominal pain, fever, weight loss, and rectal and/or emotional instability) are very often bleeding. The course of the disease can be described observed. From the point of view of behavioral with recurrent relapses and symptom-free intervals, medicine, a behavioral therapy is thus as reason- bothofwhichvaryinlengthandstrength. able as for any other severe chronic disease for which no cure exists. Besides psychotherapy (behavioral, conflict-oriented, psychodynamic, or Description supportive), relaxation techniques (progressive muscle relaxation, autogenic training) as well as In genetically susceptible individuals impaired stress management training can be useful in con- and inappropriate immune responses to microbial junction with standard medical interventions. Such antigens of commensal microorganisms are interventions do often not directly affect the course Crossover Design 521 C of the disease, but patients’ mental condition and illness-related quality of life improve. Crossover Design Generally, a positive course of the disease mainly depends on the patients’ compliance. J. Rick Turner Active coping strategies and a problem solution Cardiovascular Safety, Quintiles, Durham, orientation were identified as best predictors for NC, USA a shorter duration of inflammations and longer C relapse-free episodes. The following coping strat- egies were mostly beneficial in the management of Synonyms the disease: “accurately adhere to medical advice,” “be trustful in medical practitioners,” “seek for Repeated measures design further information,” “actively cope with prob- lems,” and “encourage yourself.” The probability of actually receiving an adequate medicinal ther- Definition apy is enhanced with greater compliance. If the relationship between the physician and patient is Subjects in a crossover design study are assigned disturbed or if the patient has no adequate coping to receive two or more treatments in a particular strategies, the additional use of psychological sequence. Imagine a study in which some sub- interventions should be recommended with higher jects receive Treatment A on a given day (the first priority. Especially with phobic reactions after period) and a week later receive Treatment B (the diarrhea, comorbidity with depression and/or anx- second period). Others subjects (usually close to iety, or other acute psychological conflicts, an equal number) would receive Treatment B first a supportive psychological therapy should be ini- and then, 1 week later, receive Treatment A. Such tiated. Besides solving acute conflicts, general a study would be described as having a two- aims of such interventions should lie in an period, two-treatment, two-sequence crossover enhancement of the relaxation ability and design. Crossover designs can involve various strengthening of individual coping strategies. numbers of treatments, sequences, and periods. In these designs, individual subjects are random- Cross-References ized to treatment sequences (as opposed to treat- ment groups as occurs in parallel groups study ▶ Anxiety designs). ▶ Compliance The primary advantage of the crossover ▶ Coping Strategies design is that each subject serves as his or her own control, providing data in each treatment arm of the study. The design also has some dis- References and Readings advantages, one of which can be difficulty in interpreting the results. Since all subjects receive Akobeng, A. K., & Thomas, A. G. (2007). Enteral nutri- tion for maintenance of remission in Crohn’s disease. more than one treatment there can be a carryover Cochrane Database of Systematic Reviews(3). effect from one or more early periods to subse- doi:10.1002/14651858.CD005984.pub2. Art. No.: quent periods, leading to a biased estimate of CD005984. the treatment effect(s) of interest. Butterworth, A. D., Thomas, A. G., & Akobeng, A. K. (2008). Probiotics for induction of remission in Crohn’s disease. Cochrane Database of Systematic Reviews(3). doi:10.1002/14651858.CD006634.pub2. Cross-References Art. No.: CD006634. Longo, D. L., Fauci, A. S., Kasper, D. L., Hauser, S. L., ▶ Jameson, J. L., & Loscalzo, J. (2011). Harrison’s Bias principles of internal medicine (2v.) (18th ed.). ▶ Parallel Group Design New York: McGraw Hill Professional. ▶ Randomization C 522 Cross-Sectional Study

intervention, i.e., they are not good for answer- Cross-Sectional Study ing research questions. Nonetheless, they may be useful for generating hypotheses (asking J. Rick Turner questions) that can subsequently be further Cardiovascular Safety, Quintiles, Durham, investigated in randomized controlled trials. NC, USA

Cross-References Definition ▶ Absolute Risk A cross-sectional study describes a group of ▶ Hierarchy of Evidence subjects at one particular point in time (Campbell, ▶ Randomized Controlled Trial Machin, & Walters, 2007). ▶ Relative Risk All study designs and methodologies have advantages and disadvantages. The randomized controlled trial, which is placed at the top of the References and Readings Hierarchy of Evidence by some researchers and therefore is considered a very strong source of Campbell, M. J., Machin, D., & Walters, S. J. (2007). evidence, has some disadvantages: They are Medical statistics: A textbook for the health sciences (4th ed.). Chichester, UK: Wiley. lengthy, expensive, and may be limited in how well results from them can be generalized to the treatment’s effect in the general population in real-world clinical circumstances. The cross-sectional study is usually compara- CT Scan tively quick and easy to conduct. Examples of its implementation include the use of an interview ▶ CAT Scan survey and conducting a mass screening program. ▶ Computerized Axial Tomography (CAT) Scan Additional advantages are that many risk factors can be studies at the same time, and that they are suitable for studying rare diseases. Disadvantages include the following: Cultural and Ethnic Differences • Only one disease outcome can be studied at once. Sana Loue • Temporal relationships can be difficult to Department of Epidemiology & Biostatistics, identify. Since the survey provides Case Western Reserve University, School of a snapshot of information at one time, it is Medicine, Cleveland, OH, USA not possible to address the issue of which item of interest that is currently present may have caused (influenced) another item that is Definition also currently present. • The selection of control subjects can be The recognition of culture and its components as problematic. a complex and fluid process, rather than a static • From a statistical perspective, only relative construct, is critical to attempts to understand the risk can be obtained. cultural influences on health and health behavior; • Focusing on the subjects, lack of recall and culture cannot be reduced to a single variable or recall bias can be of concern. construct. • Data derived from these studies cannot mean- Twelve features are essential to an under- ingfully be used to test the effectiveness of an standing of a culture: history, social status, points Cultural and Ethnic Differences 523 C of interaction within and between social groups, by race, and the meaning or significance associ- value orientations, verbal and nonverbal lan- ated with a particular designation have varied guage and communication processes, family life over time, place, and purpose of designation, processes, healing beliefs and practices, religion both in the United States and elsewhere (Loue, and religious practices, art and other forms of 2006). Additionally, shifting perceptions of self- expression, dietary preferences and practices, identity and self-worth may also influence how an recreational forms, and manner and style of individual self-designates at any particular time C dress (Hogan-Garcia, 2003). The subjective com- and place. Unfortunately, epidemiological litera- ponents of culture, such as beliefs, values, and ture has frequently confused ethnicity and culture explanatory cognitive frameworks, are commu- and race by equating ethnicity with country of nicated both verbally and nonverbally; the objec- origin and/or skin color and culture with ethnicity tive component of culture consists of rules or race, based upon the assumption that any relating to individual and group behavior observed differences seen between groups are (Hogan-Garcia, 2003). Culture is constructed by the result of true and fixed genetic or cultural and exists and operates at the levels of the indi- differences between the groups (Karlsen, 2004). vidual and the group and changes over time Additionally, reference to a particular culture, (Nagel, 1994). Individuals who ascribe to ethnicity, or race assumes and implies homoge- a particular culture share an identity and neity within the classification being used. How- a framework for understanding the world. ever, within every group, differences exist with Too often, culture is erroneously assumed to respect to socioeconomic status, religion, age, be synonymous with ethnicity. However, ethnic- understandings of health and illness, educational ity and culture represent quite different concepts. and employment opportunities, social status and Ethnicity is a function of both one’s self- power, and access to services. It is important identification and the identification by others of to recognize that although classifications based membership in a specific group based on specific on culture and ethnicity may be useful as a short- characteristics, such as biological characteristics, hand, they are not unitary constructs. A full nationality, language, and/or religion (Yinger, understanding of the mechanisms that may 1994); it is a function of both cultural history underlie health disparities requires a more in- and psychological identity (Melville, 1988). depth understanding that is possible only through Like culture, one’s ethnic identity may change the examination of the relevant constitutive due to changes in one’s self-perception and the elements. social context in which one lives. Additionally, The politics of HIV/AIDS illustrates the con- individuals may claim membership in various fusion that often surrounds culture, ethnicity, and cultures and/or ethnicities simultaneously, and race. The human immunodeficiency virus (HIV), may prioritize these memberships differently the causative agent of AIDS, is transmitted depending on any variety of circumstances. As through the exchange of various bodily fluids, an example, an individual may simultaneously such as semen, vaginal fluid, breast milk, and consider herself Polish, Russian, Christian, blood. Approximately 1 year after the identifica- nondenominational, female, and American. tion of the first observed cases of the disease, the The concept of ethnicity has also been used Centers for Disease Control and Prevention confused in the literature with the concept of race. (CDC) labeled Haitians a “risk group,” meaning Like ethnicity, the concept of race has been used that anyone who was Haitian was believed to be to explain perceived differences in appearance at increased risk of contracting and transmitting and behavior across individuals and groups, the virus by virtue of their group membership, based on the erroneous assumption that each rather than as a function of their individual race is associated with distinct, fixed physical behaviors (Schiller, Crystal, & Lewellen, 1994). and behavioral characteristics. However, the Here, individuals’ ethnicity and race were pre- definition of race, the classification of individuals sumed to be congruent with culture and “culture” C 524 Cultural and Ethnic Differences was presumed to be a factor in disease transmis- Clinicians who are unfamiliar with the client’s sion. Ironically, this categorization of all Haitians culture may erroneously interpret the client’s as a risk group reflects US biomedical culture behavior as symptomatic of bipolar disorder with respect to its understanding at the time of when it is not, or may erroneously ascribe behav- disease process and the meanings of culture, eth- ior to cultural influences when the behavior nicity, and race. actually indicates the presence of bipolar disor- der. Similar diagnostic errors have been noted in the context of schizophrenia. The overdiagnosis Description of schizophrenia among African Americans has been attributed in part to providers’ lack of cul- Culture influences almost every aspect of illness, tural understanding and their consequent misin- including how an illness is identified, defined, and terpretation of cultural mistrust as paranoia and made meaningful; the timing and onset of the ill- miscommunications between the provider and ness; the symptomatology; the course and outcome the patient. Too, clinicians unfamiliar with the of the illness; how individuals, families, providers, client’s culture may be more likely to prescribe and others respond to an experience of the illness; or to refrain from prescribing particular pharma- and how individuals seek, utilize, and respond cologic treatments based on misunderstandings to treatment (Kleinman, 1988). It is beyond the of the client’s behavior. scope of this entry to review the role of culture in Culture also plays a role in the prevalence, each of these aspects across all diseases. Instead, experience, and course of epilepsy. Epilepsy is the role of culture as it relates to disease diagnosis, a brain disorder that is characterized by symptomatology, and treatment is examined in the a predisposition to generate seizures, with neuro- context of several chronic diseases. biological, cognitive, psychological, and social As an example, the prevalence of bipolar dis- consequences. Research findings indicate that order appears to vary across cultures. Bipolar the prevalence of the disorder is higher in devel- disorder is a serious, chronic mental illness char- oping countries compared to more developed acterized by manic and depressive episodes countries (Mac et al., 2007). In some cultures (Type I) or hypomanic episodes and major and religious groups, such as some Asian Indian depressive recurrences (Type II). The disorder and Muslim communities, consanguineous mar- is associated with impairments in the quality riages, that is, between blood relatives such as of life, increased rates of suicide, and high finan- first cousins, is customary. Parental consanguin- cial costs. However, the prevalence of bipolar ity had been found to be associated with an disorder varies across countries. The consump- increased risk of certain forms of epilepsy. It is tion of omega-3 fatty acids found in seafood important to recognize, however, that not all appears to serve a protective effect for individ- Asian Indian and Muslims enter into consanguin- uals who consume large quantities of seafood eous marriages and some individuals who are over their lives, suggesting that nutritional habits neither Asian Indian nor Muslim may do so. play a role in the development of the disease Individuals may search for an explanation for (Noaghiul & Hibbeln, 2003). their seizures, which are often unpredictable and Cultural aspects are also implicated in the may be uncontrollable. Explanatory models of symptomatology and management of bipolar dis- epilepsy differ across cultures. Individuals from order. The manic phase of bipolar disorder is Western developed nations are more likely to characterized by an “excessive involvement in ascribe to a biomedical model of the disease, activities,” that often assumes the form of sexual whereas individuals of other cultural back- indiscretions and buying sprees. However, how grounds may attribute the cause of epilepsy to this excessive involvement manifests may have witchcraft, divine punishment, bad luck, or to be reformulated so as to be consistent with the supernatural forces (Allotey & Reidpath, 2007; cultural context in which the individual lives. Mac et al., 2007). The existence of such vast Cultural and Ethnic Differences 525 C differences in beliefs regarding the causation of Obesity and physical inactivity have been the illness between a patient and a provider may implicated as factors in the development of type seriously impede communication and adversely 2 diabetes (Hussain et al., 2007). Accordingly, affect their ability to work together to control the cultural factors that encourage or promote over- seizures (Reynolds, 2000). The beliefs that indi- eating and a sedentary lifestyle and/or constrain viduals hold regarding their illness also have efforts to eat healthily and exercise more may implications for their willingness to adhere to play a role in the development of the disease C prescribed treatment, the extent to which they and its progression. Diet and exercise must both utilize alternative treatments, and their daily be managed by individuals within the context of functioning. Individuals who believe that their their everyday lives and their interactions with illness lasts only as long as their seizure lasts others. Standards of modesty in dress may dimin- may refuse to take medication on an ongoing ish individuals’ opportunities to engage in vigor- basis, resulting in an inability to control the sei- ous exercise, attempts to participate in religious zures. Alternative treatments, such as smoke fasting rituals may predispose individuals to inhalation, herbal preparations, and dietary treat- hypoglycemia, and the consumption of tradi- ments, may be sought; some of these may be tional foods, such as those prepared with butter toxic, leading to additional illness. Daily func- or that are fried, may thwart attempts at weight tioning may be limited, not because of the effects reduction. Additionally, the standard for what of the epilepsy itself, but because individuals and constitutes an ideal body or weight varies across even their health care providers may believe that cultures. In some contexts, obesity may signify individuals with epilepsy must restrict their activ- privilege and affluence, an announcement to the ities, including the avoidance of sun exposure, larger world that the individual is able to afford strenuous exercise, and the obligations demanded the more costly “status” foods such as meat, by regular employment (Allotey & Reidpath, butter, and sweets. The ability to refrain from 2007; Mac et al., 2007). The belief that epilepsy physical exertion, such as that associated with is a contagious disease, common in many coun- exercise, may also signal higher social and finan- tries, may cause people to avoid touching an cial status. Individuals’ self-identities may be individual who is experiencing a seizure, even intimately linked to their adherence to specified though some forms of help might reduce the behavioral norms; their participation in social, likelihood of injury to the individual experienc- religious, and/or other activities; and their rela- ing the seizure (Mac et al., 2007). tionships with others. Consequently, clinicians’ Type 2 diabetes mellitus, which is increasing efforts to persuade their patients to modify behav- in prevalence worldwide, results from an interac- iors may be perceived by the patient not as tion between genetic, environmental, and behav- a necessary change in lifestyle to prevent disease ioral factors. Numerous studies have reported and improve health, but rather as a potential loss differences in the prevalence of type 2 diabetes of one’s identity, status, and membership in across various ethnic groups. For example, South a particular group. Asian migrants have been found to have a higher In some instances, individuals’ interpretations prevalence of type 2 diabetes compared to West- of their symptoms may impede their receipt of erners; African Americans have been reported to potentially helpful treatments. As an example, have a higher prevalence compared to Whites the term “ataque de nervios,” literally an attack (Hussain, Claussen, Ramachandran, & Williams, of nerves, is utilized by many Puerto Ricans to 2007). These distinctions, which presume refer to their response to a specific traumatic a nonexistent homogeneity within the named event, such as a death in the family or betrayal groups and heterogeneity across groups, can by one’s spouse. (Ataque de nervios is often only serve as a foundation for additional study. referred to in the psychiatric literature as One must search further for the underlying expla- a culture-bound syndrome.) That response may nations for these observed differences. include fainting, dizziness, shortness of breath, C 526 Cultural and Ethnic Differences weakness, and/or chest pain. The individual may both the batterer and the battered. Our perception experience feelings of sadness and depression, of disease necessarily impacts our prevalence nervousness and insecurity, or irritability and estimates, how the affected individual interprets anger. The experience of an ataque communi- his or her experience, the course of the individ- cates to others in a culturally and socially accept- ual’s illness, and how we as individuals, clini- able manner one’s feeling that the world has gone cians, and a society respond to the individual in out of control. the context of that experience. An ataque may occur in the absence of any pathology, but in some circumstances may be Implications indicative of an underlying anxiety, affective, or Much emphasis has been placed on clinicians’ panic disorder. Individuals suffering from ataques need to develop cultural competence in order to may dismiss out of hand the possibility that such better communicate with and counsel their patients. experiences suggest an underlying disorder for However, all too often, efforts to inculcate cultural which they might seek treatment. However, the competence reduce culture to a laundry list of converse is also true: Clinicians who are unfamil- characteristics attributed to a particular group, iar with the cultural meaning of ataques may mis- characteristics that are presumed to be true of all interpret the patient’s experiences as indicative of members of that named group and to exist across pathology when they represent instead a time-lim- time and place. Such efforts fail to recognize the ited, culturally sanctioned response to trauma. fluid nature of culture at the individual and group As an example of how cultural change can levels, the complexity of culture, the heterogeneity impact the diagnosis, prevalence, and treatment that exists within larger groups, and the similarities of a disease or disorder, consider how under- that exist across groups. standings of homosexuality have varied over the A focus on the development of cultural humil- last 40 years. Once considered a mental illness, ity, rather than cultural competence, is more individuals who were diagnosed as homosexual likely to lead to improved communication were subjected to therapeutic interventions to between providers and their patients, between transform their sexual orientations. Cultural researchers and their research participants, and change both within the medical profession and across diverse communities. In contrast to cul- within the larger society in the United States tural competence, which focuses on substantive provided the impetus to declassify homosexuality issues and may lead to both stereotyping and per se as a mental illness requiring treatment. The a false sense of security derived from “knowing,” prevalence of the “illness,” the “course of ill- cultural humility focuses on process as a key ness,” and the “prognosis” were thus dependent element, requiring that the individual remain on whether the underlying orientation was to be open to continual learning, engage in continual considered an illness at all. Similarly, cultural self-reflection and self-critique, and attempt to change at a societal level has transformed our equalize the power imbalances that are inherent understanding of alcohol abuse from that of in the provider-patient or researcher-participant a moral defect, to an individual medical problem, relationship (Tervalon & Murray-Garcia, 1998). to a public health issue; our perception of partner Improved communication and understanding violence as a legitimate response to a partner’s across cultural differences may ultimately lead failure to fulfill role obligations, to a medical to improved health for individuals and commu- diagnosis of the battered partner as a masochist, nities and a reduction in health disparities. to a public health and criminal justice issue. Once treated through prayer, alcohol abuse is now seen as amenable to counseling, pharmacologic treat- Cross-References ments, and, under some circumstances, legal intervention. Similarly, remedies for partner vio- ▶ Acculturation lence have broadened to include counseling for ▶ Chronic Disease Management Cultural Competence 527 C

▶ Chronic Disease or Illness Tervalon, M., & Murray-Garcia, J. (1998). Cultural humil- ▶ Cultural Competence ity vs. cultural competence: A critical distinction in ▶ defining physician training outcomes in multicultural Cultural Factors education. Journal of Health Care for the Poor and ▶ Ethnic Identities and Health Care Underserved, 9(2), 117–125. ▶ Health Behavior Change Yinger, J. M. (1994). Ethnicity: Source of strength? ▶ Health Behaviors Source of conflict? Albany, NY: State University of New York Press. ▶ Health Beliefs C ▶ Health Communication ▶ Illness Behavior ▶ Norms ▶ Self-identity Cultural Awareness ▶ Sociocultural Differences ▶ Cultural Competence

References and Readings Cultural Competence Allotey, P., & Reidpath, D. (2007). Epilepsy, culture, identity, and well-being: A study of the social, cultural, and environmental context of epilepsy in Cameroon. Elva Arredondo Journal of Health Psychology, 12(3), 431–443. Division of Health Promotion and Behavioral Fadiman, A. (1997). The spirit catches you and you fall Sciences, San Diego State University, San Diego, down. New York: Farrar, Strauss Giroux. CA, USA Hogan-Garcia, M. (2003). The four skills of cultural diver- sity competence: A process for understanding and practice. Pacific Grove, CA: Brooks/Cole. Hussain, A., Claussen, B., Ramachandran, A., & Synonyms Williams, R. (2007). Prevention of type 2 diabetes: A review. Diabetes Research and Clinical Practice, 76, 317–326. Cultural awareness; Cultural sensitivity Karlsen, S. (2004). ‘Black like Beckham’? Moving beyond definitions of ethnicity based on skin colour and ancestry. Ethnicity & Health, 9(2), 107–137. Definition Kleinman, A. (1988). Rethinking psychiatry. New York: The Free Press. Loue, S. (2006). Assessing race, ethnicity, and gender in Cultural competence is defined as a set of con- health. New York: Springer. gruent behaviors, attitudes, and policies that Mac, T. L., Tran, D.-S., Quet, F., Odermatt, P., Preux, P.-M., come together in a system, agency, or among & Tan, C. T. (2007). Epidemiology, aetiology, and clinical management of epilepsy in Asia: A systematic professionals to facilitate effective work in review. Lancet Neurology, 6, 533–543. cross-cultural situations (Cross et al., 1989). Melville, M. B. (1988). Hispanics: Race, class, or ethnic- Linguistic competence is an important compo- ity? Journal of Ethnic Studies, 16(1), 67–83. nent of cultural competency because language is Nagel, J. (1994). Constructing ethnicity: Creating and recreating ethnic identity and culture. Social Prob- a key aspect of culture. lems, 41, 152–176. “Culture” is defined as an integrated pattern of Noaghiul, S., & Hibbeln, J. R. (2003). Cross-national learned human behaviors (e.g., styles of commu- comparisons of seafood consumption and rates of nication, customs) and beliefs (e.g., views on bipolar disorder. American Journal of Psychiatry, 160, 2222–2227. roles and relationships) shared among groups Reynolds, E. H. (2000). The ILAE/IBE/WHO global cam- (Robins, Fantone, Hermann, Alexander, & paign against epilepsy: Bringing epilepsy “out of the Zweifler, 1998; Donini-Lenhoff & Hendrick, shadows”. Epilepsy & Behavior, 1, S3–S8. 2000). The word “competence” implies having Schiller, N. G., Crystal, S., & Lewellen, D. (1994). Risky business: The cultural construction of AIDS risk the capacity to function effectively with a cultural groups. Social Science & Medicine, 38, 1337–1346. group (Cross, Bazron, Dennis, & Isaacs, 1989). C 528 Cultural Competence

Description • Cultural competence consists of ensuring that the needs of the cultural group are met A key reason for cultural competence in health by the practitioners and health service organi- services administration and public health is to zations. It involves being aware of and recog- deliver the highest quality of care to all patients, nizing group differences and having insight regardless of race or ethnicity, cultural or religious into one’s cultural values. In this level, orga- background, or English proficiency (Betancourt, nizations and public health practitioners are Green, & Carrillo, 2002). Another important rea- able to operate effectively in different cultural son for delivering culturally competent care is to contexts. reduce and eliminate health disparities in health • Cultural proficiency is a more advanced status of diverse people and to enhance the quality standard than cultural competence and incorpo- of services and health outcomes. Racial and ethnic rates all of the concepts of cultural competence, minorities are more likely to die from many life- but a higher level of awareness, knowledge, and threatening diseases compared to members of the skills. Culturally proficient practitioners and majority group. One likely contributor to the dis- organizations strive to be innovative and crea- parities in health outcomes and mortality is biased tive in developing and implementing interven- care stemming from conscious or unconscious tions and evaluation tools. racial stereotypes (LaVeist, 2002). The Cultural Competence Framework Cross et al. (1989) proposed a Cultural Com- involves five essential elements that help health petence Continuum Framework that ranges from care organizations and public health practitioners “cultural destructiveness” where health services change from not understanding the importance of can create harm to “cultural proficiency” where cultural competence to practicing it. These com- health care services are responsive to the health ponents include: (1) developing a regard for beliefs, practices, and cultural and linguistic diversity or demonstrating an awareness and needs of diverse cultural groups. Descriptions of commitment to learning about cultural differ- each of the levels in the continuum follow: ences; (2) conducting cultural self-assessment or • Cultural destructiveness refers to attitudes, prac- encouraging organizations to take this process tices, and policies within an organization or into account; (3) understanding the dynamics system that are harmful to a cultural group. inherent when cultures interact; (4) accessing cul- This level represents a lack of understanding tural knowledge or demonstrating a commitment and unwillingness to learn about other cultures. to integrating lessons learned into the health care • Cultural incapacity involves the lack of capac- delivery skills; and (5) adapting to diversity or ity to respond to the needs of a cultural group. developing strategies that translate cultural com- These practices may consist of disproportion- petency into system change and clinical practice. ately allocating resources that may ultimately Culturally competent care would involve benefit one group at the expense of another. changing from a “one size fits all” model of care • Cultural blindness consists of considering all to a model in which care is responsive to different people or groups the same, without acknowl- cultural communities. Organizations can aim to edging cultural nuances. This can lead to achieve cultural competence by assuring diver- forced assimilation to institutional attitudes sity among board members, staff, and providers, that may blame members of cultural groups enhancing data collection, providing effective for their circumstances. and translation services, and incorporating cul- • Cultural pre-competence involves a commit- tural competence skill development and educa- ment to social and civil justice. In this level, it tion. An organization can identify their level of is recognized that continuous expansion of cultural competence through the use of measures cultural knowledge and resources to address that assess cultural attitudes, practices, structures, the needs of cultural groups are needed. and policies of programs. Acquiring these data Cultural Factors 529 C can help determine areas of weakness to inform Definition the training needed to strengthen cultural and linguistic competency. Culture: Culture is a complex system that includes beliefs and values that are socially transmitted within groups who have similar backgrounds and Cross-References experiences. Culture is often used to refer to indi- viduals from the same racial and ethnic group, but C ▶ Cultural and Ethnic Differences culture is distinct from one’s race or ethnicity. ▶ Cultural Factors Cultural beliefs and values create motivational ▶ Diversity force, or provide the underlying rationale or impe- tustobehave,think,andfeelinacertainway.Most References and Reading empirical research has focused on understanding the association between health behaviors and cul- Betancourt, J. R., Green, A. R., & Carrillo, E. J. (2002). tural beliefs and values related to religion and Cultural competence in health care: Emerging frame- spirituality, temporal orientation, and collectivism works and practical approaches. New York: The and individualism (Kagawa-Singer, Dadia, Yu, & Commonwealth Fund. Surbone, 2010). Cross, T., Bazron, B., Dennis, K., & Isaacs, M. (1989). Towards a culturally competent system of care Religion and spirituality: Spirituality and reli- (Vol. 1). Washington, DC: Georgetown University gion are related but distinct factors that have been Child Development Center, CASSP Technical Assis- shown to influence conceptualizations about tance Center. diseases. Spirituality is defined as having Donini-Lenhoff, F. G., & Hendrick, H. L. (2000). Increas- ing awareness and implementation of cultural compe- a personal relationship with a higher power and tence principles in health professions education. faith, and may be a process used to find meaning Journal of Allied Health, 29(4), 241–245. in one’s life, while religion is defined as a set of LaVeist, T. (2002). Race, ethnicity and health: A public practices and beliefs (e.g., dogma, doctrines) that health reader. San Francisco: John Wiley & Sons. Robins, L. S., Fantone, J., Hermann, J., Alexander, G., & are shared by a community or group. Religion can Zweifler, A. (1998). Improving cultural awareness and be thought of as behavioral manifestations of sensitivity training in medical school. Academic Med- one’s spirituality (Taylor, 2001). icine, 73(Suppl. 10), S31–S34. Temporal orientation: Temporal orientation is defined as one’s cognitive focus of their behaviors, thoughts, and affect in terms of past, Cultural Consonance present, or future domains. Individuals may think, feel, or act based on perceived conse- ▶ Cultural and Ethnic Differences quences that are immediate (present orientation), will happen in the future (future orientation), or has happened in the past (past orientation) (Nuttin, 1985). Cultural Factors Individualism and collectivism: Individualism and collectivism are beliefs and values related to Chanita H. Halbert social processes and interactions. Individualism School of Medicine, University of Pennsylvania, is characterized by placing greater value on per- Philadelphia, PA, USA sonal autonomy, responsibility, and freedom of choice whereas collectivism is characterized by values that include group responsibility and deci- Synonyms sion making and maintaining harmonious rela- tionships with others (Triandis, McCusker, & Folk health beliefs; Myths Hui, 1990). C 530 Cultural Factors

Description screening as recommended included beliefs that less emphasis is placed on screening to prevent Association Between Cultural Factors, Health future health outcomes because the future cannot Behaviors, and Racial and Ethnic Background be changed or guaranteed. In a community-based By the year 2050, it is estimated that the racial sample of African American women, present and ethnic composition of the USA will change time orientation was associated with never hav- dramatically and groups that are currently minor- ing a mammogram, but women who had greater ities will make up the majority of the US popula- levels of future temporal orientation were most tion. In anticipation of this, and the poorer health likely to participate in genetic counseling for outcomes that these groups continue to experi- BRCA1 and BRCA2 mutations and receive test ence, efforts are focusing on developing more results. Greater levels of future temporal orienta- effective strategies for health promotion and dis- tion were also associated with uptake of genetic ease prevention by addressing cultural beliefs and counseling for BRCA1 and BRCA2 mutations in values related to health behaviors. Cultural fac- samples that consisted mostly of white women tors are now being addressed as part of health (Brown & Segal, 1996; Boyer, Williams, behavior interventions based on studies which Callister, & Marshall, 2000). have shown that these factors are associated Religion and Spirituality. Religion and spiri- with health behaviors. Racial and ethnic group tuality have been examined extensively as pre- differences in cultural beliefs and values also dictors of health behaviors and beliefs. For provide support for addressing these factors as instance, explanatory models for cancer among part of health promotion and disease prevention African American and Hispanic women include efforts. These findings are summarized in the the belief that cancer is due to God’s will. Other sections below (Smedley, Stith, Nelson, & Insti- work has shown that religious and spiritual tute of Medicine (U.S.), 2003). beliefs influence decisions about seeking treat- Temporal Orientation. As described above, ment for breast cancer symptoms and other health temporal orientation is defined as one’s cognitive behaviors. Lannin and colleagues found that reli- focus of their behaviors, thoughts, and affect in gious and spiritual beliefs, such as prayer about terms of past, present, or future domains. Studies cancer can lead to healing, were associated with have shown that future temporal orientation pro- a greater delay in seeking treatment for breast motes greater psychological well-being, avoid- cancer symptoms. African American women ance of risky health behaviors, and adherence to were significantly more likely than white preventive health behaviors and beliefs, whereas women to endorse these beliefs. Similar findings present temporal orientation is associated with have been reported for Hispanics; faith in God reduced adherence. There are also racial differ- was influential in determining the length of time ences in temporal orientation. For example, between symptom recognition and seeking care Brown and Segal found that African Americans in Hispanic men and women. Studies have also reported greater levels of present temporal orien- shown that religion and spirituality are important tation related to hypertension management com- coping resources following breast cancer diagno- pared to whites. Individuals with higher levels of sis in African American, Hispanic, and white present temporal orientation reported lower per- women; however, the importance of these needs ceptions of susceptibility to adverse effects of may differ depending on one’s racial or ethnic uncontrolled disease, perceived fewer benefits background. For example, while 25% of white of hypertension medication, and reported greater cancer patients reported five or more spiritual perceptions of burden from the negative aspects needs following their cancer diagnosis, signifi- of medication. Similar results were reported in cantly more African American (41%) and His- a qualitative study of perceptions of cervical panic (61%) women reported five or more cancer screening in Hispanic women. Women in spiritual needs. African American women were this study reported that reasons for not obtaining significantly more likely than white women to use Cultural Factors 531 C

God as a source of support following diagnosis. individualism were associated with an increased African American prostate cancer survivors also likelihood of eating the recommended number of reported significantly greater levels of religiosity servings of fruits (Boykin, Jagers, Ellison, & compared to white prostate cancer survivors. Albury, 1997; Sabogal, Marin, & Perez-Stable, African American men have also been shown to 1987). be significantly more likely than white men to report that faith contributes to good health and Measurement of Cultural Factors C faith in God played a role in health-seeking Although cultural beliefs and values are socially behaviors among Hispanic men. Other work has transmitted and shared among individuals with shown that while religion is very important to the similar racial backgrounds and experiences, these majority of adults diagnosed with disease and one factors are most often measured as an individual third of healthy adults pray for health conditions, difference characteristic using self-report mea- African American men and women were signifi- sures. Research is now being conducted to cantly more likely than white men and women to develop instruments that measure cultural beliefs be willing to allocate time with health care pro- and values within specific situational contexts. viders to discuss spiritual issues rather than health care concerns (Lannin et al., 1998; Moadel et al., Integration of Cultural Factors into Health 1999; Kub et al., 2003). Promotion and Disease Prevention Collectivism and Individualism. Individualism Cultural tailoring is an approach that has been used and collectivism may also contribute to health to promote adherence to a wide range of health behaviors and beliefs, but less empirical data are behaviors that include cancer screening, HIV risk available on these associations. But studies have reduction, and informed decision making about examined the relationship between constructs genetic testing for inherited disease risk. The pre- that are similar to individualism and collectivism. mise of cultural tailoring is that information and Communalism, for example, is defined as having messages that are customized to one’s culturally greater recognition of the interdependence of basedbeliefsandvalueswillbemoreeffective people, particularly family members and fami- than generic approaches because they address lism is defined as having a stronger identification issues and ways of thinking and coping that are with and attachment to family members. most salient to an individual. Culturally tailored Prior studies have shown that communalism is interventions have had mixed results. For instance, associated with collectivism and African Ameri- Halbert and colleagues developed and evaluated cans and Hispanics have been shown to have a culturally tailored genetic counseling (CTGC) greater endorsement of collectivism (e.g., protocol for African American women as part of interdependence, group responsibility) and fami- a randomized trial. The CTGC protocol included lism compared to whites. Other work has shown standardized probes to elicit discussion about cul- that greater levels of social integration and the tural factors that have been shown to influence size of one’s social network were associated with decisions about genetic counseling among African adherence to breast and cervical cancer screening American women (e.g., spiritual and religious among Mexican, Cuban, and Central American beliefs, communalism). For example, women women. Thompson and colleagues found that were asked what aspects of their spiritual and reli- African American women who declined to par- gious beliefs influence their decision to have ticipate in genetic counseling and testing for genetic testing to facilitate discussion about the inherited breast cancer risk reported significantly role of these factors in decision making about greater concerns about the impact of testing genetic testing for BRCA1/2 mutations. Women on family members compared to women who who received CTGC reported greater levels of sat- participated in counseling and testing. Further, isfaction compared to those who received standard in a national sample of African American, genetic counseling (SGC), but there were no differ- white, and Hispanic adults, greater levels of ences in uptake of BRCA1/2 test results between C 532 Cultural Factors women who were randomized to CTGC and SGC. Cross-References Further, women randomized to CTGC and SGC did not differ in terms of psychological outcomes such ▶ Cultural and Ethnic Differences as changes in risk perception and cancer worry ▶ Ethnicity compared to decliners. In other research, Kreuter ▶ Religion/Spirituality and colleagues found that African American women liked culturally relevant health education materials that addressed fruit and vegetable intake References and Readings and mammography using four cultural constructs (religiosity, racial pride, collectivism, and time ori- Boyer, L. E., Williams, M., Callister, L. C., & Marshall, E. S. entation) better than materials that were tailored to (2000). Hispanic women‘s perceptions regarding cervi- behavioral constructs. However, women who cal cancer screening. Journal of Obstetric, Gynecologic, received both types of education materials (behav- and Neonatal Nursing, 30, 240–245. Boykin, A. W., Jagers, R. J., Ellison, C. M., & Albury, A. ioral and culturally relevant materials) were most (1997). Communalism: Conceptualization and mea- likely to obtain a mammogram and had greater surement of an Afrocultural social orientation. Journal increases in fruit and vegetable consumption com- of Black Studies, 27, 409–418. pared to women who received culturally relevant Brown, C. M., & Segal, R. (1996). Ethnic differences in temporal orientation and its implications for hyperten- materials, those tailored to behavioral constructs sion management. Journal of Health and Social only, and women in the control condition (Kreuter Behavior, 37, 350–361. et al., 2005; Kalichman, Kelly, Hunter, Murphy, & Halbert, C. H., Kessler, L., Troxel, A. B., Stopfer, J. E., & Tyler, 1993; Halbert, Kessler, Troxel, Stopfer, & Domchek, S. (2010). Effect of genetic counseling and testing for BRCA1 and BRCA2 mutations in African Domchek, 2010). American women: A randomized trial. Public Health These findings raise questions about how to Genomics, 13(7–8), 440–448. develop interventions that are effective in terms Kagawa-Singer, M., Dadia, A. V., Yu, M. C., & Surbone, A. of addressing cultural beliefs and values and pro- (2010). Cancer, culture, and health disparities: Time to chart a new course? CA: A Cancer Journal for Clini- moting health behavior change. One issue may be cians, 60, 12–39. that previous culturally tailored interventions have Kalichman, S. C., Kelly, J. A., Hunter, T. L., Murphy, been based on conceptualizations of cultural fac- D. A., & Tyler, R. (1993). Culturally tailored tors that are not specific to different health promo- HIV-AIDS risk-reduction messages targeted to Afri- can-American urban women: Impact on risk sensitiza- tion and prevention behaviors. Studies have shown tion and risk reduction. Journal of Consulting and that different cultural values are elicited depending Clinical Psychology, 61, 291–295. on situational characteristics and context; but Kreuter, M. W., Sugg-Skinner, C., Holt, C. L., Clark, E. M., existing instruments that measure cultural factors Haire-Joshu, D., Fu, Q., et al. (2005). Cultural tailoring for mammography and fruit and vegetable intake among do not relate specifically to different health behav- low-income African-American women in urban public iors (e.g., medication adherence, avoidance of risk health centers. Preventive Medicine, 41,53–62. factors, early detection) that define the spectrum of Kub, J. E., Nolan, M. T., Hughes, M. T., Terry, P. B., health promotion and disease prevention and, Sulmasy, D. P., Astrow, A., et al. (2003). Religious importance and practices of patients with a life threat- therefore, may be less sensitive for interventions ening illness: Implications for screening protocols. studies that aim to address these factors. Applied Nursing Research, 16, 196–200. Lannin, D. R., Mathews, H. F., Mitchell, J., Swanson, M. S., Swanson, F. H., & Edwards, M. S. (1998). Influence of socioeconomic and cultural factors on Conclusions racial differences in late-stage presentation of breast cancer. Journal of the American Medical Association, Cultural beliefs and values are important to 279, 1801–1807. a wide range of health promotion and disease Moadel, A., Morgan, C., Fatone, A., Grennan, J., Carter, J., Laruffa, G., et al. (1999). Seeking meaning and hope: prevention efforts. Empirical evidence is emerg- Self-reported spiritual and existential needs among an ing on how to address these factors as part of ethnically-diverse cancer patient population. Psycho- health behavior interventions. oncology, 8, 378–385. Cystic Fibrosis 533 C

Nuttin, J. (1985). Future time perspective and motivation: theory and research method. Hillsdale, NJ: Erlbaum. Cynicism Sabogal, F., Marin, B. V., & Perez-Stable, J. (1987). Hispanic familism and acculturation: what changes and what doesn‘t? Hispanic Journal of Behavioral ▶ Hostility, Cynical Sciences, 9, 397–412. ▶ Hostility, Measurement of Smedley, B. D., Stith, A. Y., Nelson, A. R., & Institute of ▶ Hostility, Psychophysiological Responses Medicine (U.S.). (2003). Committee on understanding C and eliminating racial and ethnic disparities in health care. In Unequal treatment: Confronting racial and ethnic disparities in health care. Washington, DC: National Academy Press. Taylor, E. J. (2001). Spirituality, culture, and cancer care. Seminars in Oncology Nursing, 17, 197–205. Cystic Fibrosis Triandis, H. C., McCusker, C., & Hui, C. H. (1990). Multimethod probes of individualism and collectiv- Kristen K. Marciel1 and Judy A. Marciel2 ism. Journal of Personality and Social Psychology, 1Department of Psychology, University of 59, 1006–1020. Miami, Coral Gables, FL, USA 2Perioperative Services, East Tennessee Children’s Hospital, Knoxville, TN, USA Cultural Sensitivity

▶ Cultural Competence Synonyms

CF Custodian Definition ▶ Family, Caregiver Cystic fibrosis (CF), a genetic recessive illness, occurs in 1 of 3,500 live births each year in the CVD Prevention United States and currently affects approximately 30,000 people, predominantly Caucasians ▶ Cardiovascular Disease Prevention (Cystic Fibrosis Foundation [CFF], 2008). In 1962, average life expectancy was 10 years of age; however, the current life expectancy of Cynical Distrust a person with CF is approximately 37 (CFF, 2009). More than 46% of people registered with the CF Foundation are adults. Adults with ▶ Hostility CF now participate in many developmentally- ▶ Hostility, Cynical appropriate aspects of life which were previously ▶ Hostility, Measurement of rare for this population, including completing ▶ Hostility, Psychophysiological Responses high school (92%), working part- or full-time (48%), and marrying or living with a partner (38%; CFF, 2008). As people with CF are living Cynical Hostility longer, there is a need for effective transition from pediatric to adult health care. ▶ Hostility CF is caused by a single genetic defect. There ▶ Hostility, Cynical are over 1,500 known mutation variations with ▶ Hostility, Measurement of the most common defect being the Delta F508 ▶ Hostility, Psychophysiological Responses mutation (Farrell et al., 2008). In 1989, this defect C 534 Cystic Fibrosis was identified on chromosome 7 (Riordan et al., The Cystic Fibrosis Foundation (CFF) was 1989). When working properly, the cystic fibrosis established in 1955 (CFF, 2008); this organiza- transmembrane conductance regulator gene tion accredits the more than 115 care centers, produces a protein which transports chloride manages a patient registry, develops evidence- and sodium across cells, particularly in submuco- based practice guidelines, and provides funding sal glands. In CF, this abnormal electrolyte for research. The CFF Therapeutics Pipeline transport results in the production of thick, sticky includes 33 interventions at various stages of mucus, affecting the pulmonary, gastrointestinal, development, including medications to treat pancreatic, and reproductive systems (Welsh & symptoms, potentiators and correctors to address Smith, 1995). Cycles of infection and inflamma- the basic defect, and gene therapy to prevent tion result in significant lung damage. Approxi- disease. mately 90% of patients with CF experience pancreatic insufficiency, resulting in difficulty absorbing fats and proteins which leads to Cross-References undernutrition. Some patients develop CF-related diabetes, liver damage, and bone disease. ▶ Pulmonary Function About 98% of men are infertile due to the absence, malformation, or blockage of the vas deferens. Women have better reproductive References and Readings capabilities, though conception is often difficult due to excessive cervical mucus. Cystic Fibrosis Foundation. (2008). Patient registry 2006 Diagnostic criteria for CF include both annual report. Bethesda, MA: Author. Cystic Fibrosis Foundation. (2009). 2009 annual report. clinical features and laboratory results (Farrell Bethesda, MA: Author. et al., 2008). Laboratory tests include newborn Eiser, C., Zoritch, B., Hiller, J., Havermans, T., & Billig, S. screening (occurring in all 50 states since 2010), (1995). Routine stresses in caring for a child with cystic quantification of sweat chloride, and genetic test- fibrosis. Journal of Psychosomatic Research, 39(5), 641–646. ing. Median age of diagnosis is 6 months of age Farrell, P. M., Rosenstein, B. J., White, T. B., Accurso, F. J., (CFF, 2008), with approximately 70% of children Castellani, C., Cutting, G. R., Durie, P. R., Legrys, V. A., diagnosed before 1 year of age (Walters & Mehta, Massie, J., Parad, R. B., Rock, M. J., Campbell, P. W. 2007). A very vigorous treatment regimen is (2008). Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis instituted at the time of diagnosis. Some 90% of Foundation consensus report. Journal of Pediatrics, morbidity and mortality is due to progressive 153(2), S4–S14. lung disease. Lung function, as measured by per- Orenstein, D. M. (1997). Cystic fibrosis: A guide for cent predicted of forced expiratory volume in one patient and family (2nd ed.). Philadelphia: Lippincott-Raven. second, slowly declines over time, at a rate of Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., approximately 1–2% each year (Rosenthal, Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., 2007). Given the multiple systems affected by Plavsic, N., Chou, J. L., Drumm, M. L., CF, treatments typically include antibiotics Iannuzzi, M. C., Collins, F. S., & Tsui, L. C. (1989). Identification of the cystic fibrosis gene: Cloning and (oral, nebulized, and intravenous), enzyme characterization of complementary DNA. Science, replacement therapy, airway clearance, nebulized 245(4922), 1066–1073. bronchodilators, nebulized mucolytic agents, and Rosenthal, M. (2007). Physiological monitoring of older aggressive nutritional therapies, ranging from children and adults. In M. Hodson, D. Geddes, & A. Bush (Eds.), Cystic fibrosis (3rd ed., pp. 345–352). increasing caloric intake to enteral nutritional London: Hodder Arnold. feedings (Eiser, Zoritch, Hiller, Havermans, & Walters, S., & Mehta, A. (2007). Epidemiology of cystic Billig, 1995; Orenstein, 1997). The medical reg- fibrosis. In M. Hodson, D. Geddes, & A. Bush (Eds.), imen is extremely complex and time consuming, Cystic fibrosis (3rd ed., pp. 345–352). London: Hodder Arnold. which results in significant challenges for Welsh, M. J., & Smith, A. E. (1995). Cystic fibrosis. adherence. Scientific American, 273, 52–59. Cytokines 535 C

being discovered, these terms are now considered Cytokine-Induced Depression to be obsolete. Although the IL designation is still used, it is anticipated that a nomenclature based ▶ Sickness Behavior on cytokine structures will eventually become established. Cytokines and their receptors are categorized according to two major structural families: C • The hematopoietin family: Cytokines – Includes growth hormones – Includes many IL implicated in both innate Briain O. Hartaigh and adaptive immunity School of Sport and Exercise Sciences, • The TNF family: The University of Birmingham, Edgbaston, – Also functional in both innate and adaptive Birmingham, UK immunity – Includes many members that are membrane bound Synonyms Both major structural families of cytokines are thought to play an active role in local and sys- Chemokines; Interleukins; Lymphokines; temic effects that contribute toward innate and Monokines adaptive immunity. The effect of a particular cytokine on a given cell depends on the cytokine, its extracellular Definition abundance, the presence and quantity of the com- plementary receptor on the cell surface, and 1. Low molecular weight proteins that stimulate downstream signals activated by receptor binding or inhibit the differentiation, proliferation, or (the last two factors may vary by cell type). When function of immune cells. a cytokine binds to a receptor, a signal is trans- 2. Small cell-signaling protein molecules that are mitted into the cell which activates particular secreted by numerous cells of the body in genes and, in turn, alters the activity of the cell. order to affect the behavior of other cells that Once activated, these cells are capable of produc- bear receptors for them. ing other cytokines. Each individual cytokine can 3. Extensively involved in intercellular have several different functions depending on communication. which cell(s) it binds to. Cytokines are strongly involved in regulating immune function. For example, in lymphocyte Description activation, both T and B cells critically depend on receiving signals delivered by specific cyto- Cytokines are small cell-signaling protein mole- kines that bind to receptors on their cell mem- cules weighing approximately 25 kDa. Based on branes. Likewise, cytokines are influential in their presumed function, cell of secretion, and promoting or inhibiting local and systemic target of action, cytokines were previously inflammation. referred to as lymphokines, interleukins (IL), Considering cytokines are multifunctional, it and chemokines. These terms were generally remains complex to simplify these molecules in used in an attempt to develop a standardized order to give a precise account. This is due to: nomenclature for molecules that were secreted 1. The redundant (sharing the same properties) by and which acted on cells of the body. How- effect of cytokines ever, due to an ever-increasing number of cyto- 2. Multifunctional properties of cytokines kines with diverse origins, structures, and effects (pleiotropy) C 536 Cytotoxic T Cell Differentiation Factor

3. Several cells may be capable of producing the References and Readings same cytokine 4. The ability of cytokines to act synergistically Janeway, C. A., Travers, P., Walport, M., & Shlomchik, or antagonistically with each other M. J. (2005). Immunobiology: The immune system in health and disease (6th ed.). London: Garland Science. Therefore, it is easier to imagine that these Roitt, I. M., & Delves, P. J. (2001). Essential immunology important protein molecules work in a network (10th ed.). Oxford: Blackwell Science. to promote or inhibit the interaction of the Staines, N., Brostoff, J., & James, K. (1993). Introducing immune system with other physiological sys- immunology (2nd ed.). London: Mosby. tems, by which they remain mutually dependent on each other.

Cytotoxic T Cell Differentiation Cross-References Factor

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