ALLENTOWN CME CONFERENCE
Sam Study Group - Early Childhood Illness...... Menopause and Post Gynecological Reproductive Care ...... Pulmonary Function Tests – Basic Interpretation for Primary Care ...... Dyslipidemia – New Guidelines ...... Transitioning Patients with Autism from Pediatric to Adult Practices ...... Herbs, Supplements and Athletes ...... Tools to Treat Adult Patients with Obesity: An Update on Bariatric Surgery and Pharmacologic Agents Case Studies of Common Behavioral Health Scenarios...... Opioid Prescribing: Safe Practice, Changing Lives ...... Act 31 Child Abuse Recognition ...... Integrating Genetic Testing into Family Medicine - Part I, an Overview ...... Drugs of Abuse ...... VTE: Beat the Clot! ...... Pre-Operative Assessment in the Office ...... ENT Review ...... CSI (Clinical Skin Investigation) Introduction to Dermoscopy ...... Integrating Genetics into Family Practice – Part II ...... Achieving Glycemic Control: When Optimized Basal Insulin Isn’t Adequate...... Physician Burnout ...... Tackling the Top Three Most Common Ailments…Low Back Pain, Depressed Mood and “I Think I Have Bronchitis” ...... Return to Top
Sam Study Group – Early Childhood Illness
Sam Study Group - Early Childhood Illness Americo Fraboni, MD, East Carolina University & David Weismiller, MD, ScM, FAAFP, East Carolina University
Disclosures:
Speakers have no disclosures and there are no conflicts of interest.
The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products.
The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices.
Because of the content of this presentations, handouts are not allowed to be posted online. Register at PAFP.com for the next SAM session at Pittsburgh CME Conference scheduled for March 10-13, 2016.
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Menopause and Post Gynecological Reproductive Care
Menopause and Post Gynecological Reproductive Care Nguyet-Cam Vu Lam, MD, St. Luke’s FMR Disclosures:
Speaker has no disclosures and there are no conflicts of interest.
The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products.
The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Menopause and Post Gynecological Reproductive Care
Nguyet-Cam Vu Lam, MD, FAAFP Associate Program Director St. Luke’s Family Medicine Residency
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Disclosure
Dr. Nguyet-Cam Vu Lam has no conflict of interest, financial agreement, or working affiliation with any group or organization.
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Objectives
Understand the physiologic changes that happen to women as they move through the menopausal transition. Understand routine preventive care for post- reproductive women. Recognize common gynecologic issues in post- reproductive women with some understanding of diagnosis and treatment options Know the indications, contraindications, risks and benefits of hormone replacement therapy.
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1 Definition
Menopause is defined as the permanent cessation of menses. 12 months of amenorrhea. Median age at menopause is 51 years old (range 40-58). With life expectancy approaching 80 years, the average women is postmenopausal for 1/3 of her life. Family physician can address both management of menopausal symptoms as well as preventive health care measure. 4
Perimenopause
Most women start to have physiologic changes associated with menopause in years prior to the final menstrual period. Menopausal transition has fluctuated hormone levels as ovarian function starts to decrease. Serum estradiol and progesterone decrease and follicle-stimulating hormone levels increase. These changes result in menopausal symptoms such as vasomotor (hot flushes) and vaginal symptoms.
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Case: 54 years old woman come for routine visit Tearful, afraid that her marriage of 20 years is falling apart. She and her husband argue frequently; patient alternates between tearful and angry for no apparent reason. Last menstrual period 2 years ago 6-7 hot flashes daily—disrupt her sleep several nights/week. Intercourse is painful, decreased interest Exam: thin pale vaginal epithelium, all other exam within normal limit 6
2 What do you want to do as her family physician?
Many women with menopausal symptoms that significantly impair their quality of life never report them to their physician. Approaching the subject with perimenopausal women, rather than waiting for them to initiate the discussion is an important first step. Common menopausal symptoms including hot flushes, atrophic vaginitis, insomnia, diminished libido, and hair loss, can be treated successfully with a variety of hormonal and non-hormonal agents. Many women find it challenging to deal with both the physical and emotional ramifications of this new phase in life. 7
Hot flushes: How often? How severe?
Sudden sensation of extreme heat in upper body, face, neck, chest lasting 1-5 minutes. In up to 75% of menopausal women. Most severe in the first 2 years of menopause. (lasting a median 4-10.2 years) Broad spectrum of frequency and severity. Risk factors for greater severity and frequency: Surgically or chemically induced menopause Elevated body mass index History of tobacco use
African American ethnicity 8
What is the most effective treatment for perimenopausal vasomotor symptoms? A. Compounded bioidentical hormones B. SSRI’s C. Estrogen or Estrogen/progesterone combination D. Gabapentin
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3 Options for treating hot flashes
Hormone therapy (HT): Estrogen alone or estrogen-progesterone combination Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) or selective serotonin- norepinephrine reuptake inhibitors (SNRIs) Antiepileptic: gabapentin (900mg/day) Antihypertensive: Clonidine, Methyldopa Herbal supplements: Black cohost, Mg, Omega-3- fatty acid, Red clover, St. John’s wort. Lifestyle/alternative: Acupuncture, avoidance of triggers, physical activity, yoga 10
Systemic HT-Level A evidence
Systemic HT, with estrogen alone or in combination with progestin, is the most effective therapy for vasomotor symptoms related to menopause. Low-dose and ultra low systemic doses of estrogen are associated with a better adverse effect profile than standard doses and may reduce vasomotor symptoms in some women.
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Systemic HT-Level A evidence
Given the variable response to HT and the associated risks, it is recommended that health care providers individualize care and treat women with the lowest effective dose for the shortest duration that is needed to relieve vasomotor symptoms. The risks of combined systemic HT include thromboembolic disease and breast cancer.
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4 A critical look at HT
Estrogen/progesterone combination for women with intact uterus, and estrogen alone for those who’ve had a hysterectomy is highly effective, alleviating hot flushes and other menopausal symptoms 80-90% of the time. Women health initiative in 2002 reported increased risk of breast cancer, coronary heart disease, stroke, and venous thromboembolism in women aged 50-77 years after 5 years of combined HT.
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HT-reanalysis of the WHI
Women <60 years old and within 10 years of the onset of menopause, HT appeared to be a safe short-term treatment. Women >60years old and at risk for cardiovascular disease or breast cancer or both, should not take HT. Cochrane review of HT in 2012 stated that HT should not be used for primary or secondary disease prevention because the risks of use outweigh the benefits.
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Ways to minimize risk with HT
Limit duration of HT to the shortest treatment required Use a transdermal delivery system (lower risk of thromboembolism) Prescribe low-dose HT regimen.
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5 Discontinuation
Discontinuation of HT may associated with recurrent vasomotor symptoms in 50% women. ACOG recommends against routine discontinuation of systemic estrogen at age 65 years. The decision to continue HT should be individualized and based on a woman’s symptoms and the risk-benefit ratio, regardless of age. (Level C)
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Contraindications to menopausal hormone therapy Active liver disease Active or recent arterial thromboembolic disease Current, past or suspected breast cancer Known hypersensitivity to the active substance of the therapy Known or suspected estrogen-sensitive malignant conditions Porphyria cutanea tarda (absolute contraindication) Undiagnosed genital bleeding Untreated endometrial hyperplasia Untreated hypertension 17
Other hormones
Progestin: used as an add-on agent to estrogen therapy to prevent endometrial hyperplasia and endometrial cancer in women with a uterus. There is some evidence that progestin may improve vasomotor symptoms, but limited data on the safety of progestin alone compared to estrogen-progesterone preparations. Testosterone: no benefit for treatment of vasomotor symptoms.
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6 Compounded bioidentical hormones
Some women prefer compound hormones, individualized based on results of blood and saliva testing. Bioidentical hormones are plant-derived hormones that are chemically similar or structurally identical to those produced by the body. Market as safer and more effective. There is limited evidence of their efficacy. Lack of standardization resulting in variations in formulations and dosages. 19
What’s the evidence?
Data do not support the use of progestin-only medications, testosterone, or compounded bioidentical hormones for the treatment of vasomotor symptoms. (Level B)
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Non-hormonal medications and vasomotor symptoms SSRIs, SNRIs, clonidine, and gabapentin are effective alternatives to HT for the treatment of vasomotor symptoms related to menopause. (Level A) Paroxetine is the only non-hormonal therapy that is approved by the FDA for the treatment of vasomotor symptoms. (Level A)
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7 Antidepressants and hot flushes
Both SSRIs and SNRIs help to reduce the severity and frequency of hot flushes because they target neurotransmitters involved in the hypothalamic thermoregulation center. Women who have hot flushes have 2X increase in risk for depression Venlafaxine, desvenlafaxine, and paroxetine have been shown to provide best vasomotor symptom relief (67% vs 15% in placebo).
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Other agents and hot flushes
Clonidine (central acting antihypertensive) and antiepileptic (gabapentin) may alleviate hot flushes, but none is an optimal treatment. Clonidine (0.1 mg/day) has been shown to be effective in both oral and transdermal form, but less benefit compared to HT. Gabapentin (900mg/day) reduces the frequency of hot flushes, but cause nausea, headache, dizziness, and confusion. Both clonidine and gabapentin are not FDA approved for treatment of vasomotor
symptoms in menopause. 23
Behavior and lifestyle changes and hot flushes Exercise has not been found to improve or worsen hot flushes, but does improve mood swings associated with menopause. Lifestyle changes such as limiting alcohol, decrease spicy food intake, avoiding hot drinks, eliminating caffeine may decrease frequency and severity of hot flushes. Layering of clothing, maintaining lower ambient temperature, and consuming cool drinks are reasonable measures for the management of
vasomotor symptoms. (Level B) 24
8 Alternative therapies?
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Acupuncture/Herbal remedies and hot flushes In 2010, Cochrane meta-analysis of 30 placebo- controlled trials of high levels of phytoestrogen for treatment of vasomotor symptoms showed no evidence of benefit. Currently, there are insufficient data to support the use of herbal remedies for menopausal vasomotor symptoms. The herbal treatments that have been studied are: black cohosh, ginseng, St. John’s wort, and ginkgo biloba, dong quai. Acupuncture: no benefit over placebo for vasomotor symptoms. Reflexology: not significantly reduce vasomotor symptoms compared to non-specific foot massage.
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Menopausal symptom: vaginal atrophy
Vaginal atrophy is a direct consequence of the hypoestrogenic state associated with menopause. About 10-40% of menopausal women will have 1 or more symptoms of vaginal atrophy. Symptoms: vaginal or vulvar dryness, discharge, itching, dyspareunia Thinning of vaginal epithelium, and loss of ruggae can be seen 2-3 years after the onset of menopause.
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9 Vaginal atrophy
Measures of sexual dysfunction are noted to be present at higher rates in women with vaginal atrophy than in unaffected menopausal women. These symptoms may have a negative effect on the woman’s quality of life, self-esteem, and sexual intimacy.
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Menopausal symptom: vaginal atrophy (continue) Common symptoms include: vaginal dryness (75%) Dyspareunia (38%) Itching, unusual discharge, pain (15%) Urinary tract infection secondary to atrophic vaginitis are common. Only 25% of women report them to their physicians.
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Which of the following is true regarding postmenopausal atrophic vaginitis?
A. Vaginal cream is the preferred vehicle for delivering vaginal estrogen. B. Urinary symptoms may include dysuria, hematuria, increased frequency of urination and incontinence. C. Regular sexually activity is harmful to overall vaginal health. D. Vaginal moisturizers help to reverse atrophic vaginal changes.
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10 Treating atrophic vaginitis
HT Lubricants and moisturizers Topical estrogen: creams, pesary, tablets, vaginal ring Sexual activity: mechanical stretching; increased vaginal blood flow
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Topical estrogen and atrophic vaginitis
Estrogen therapy effectively alleviates atrophic vaginal symptoms related to menopause. Local therapy is advised for the treatment of women with only vaginal symptoms. Level A HT should not be considered for atrophic vaginitis alone in view of safety concern. However when using it for vasomotor symptoms, patient may find that their vaginal dryness improves. Adverse effects include itching, pain, vaginal discharge, and vaginal bleeding. Endometrial proliferation has not been found to occur within 24 months of continuous use 32
Topical estrogen and atrophic vaginitis (cont) Up to 90% patients using local estrogen show improvement in atrophic symptoms within 3 weeks. Systemic absorption of estrogen is minimal and will declines with use as the thinness of the vaginal epithelial layer resolves. Lowest effective dose should always be chosen for a patient. The 3-months estradiol-releasing vaginal ring is preferred to cream because of greater comfort, ease of use, and satisfaction. 33
11 Estrogen Agonists and Estrogen Antagonists Raloxifene and tamoxifene are not effective for the treatment of menopausal vaginal symptoms Ospemifene (60 mg/day) improves vaginal atrophy without stimulating the endometrium The FDA approved ospemifene for treating moderate to severe dyspareunia in post menopausal women. (Level A)
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Water-soluble lubricants and moisturizers Non-estrogen water-based or silicone-based vaginal lubricants and moisturizers may alleviate vaginal symptoms related to menopause. (Level B) Short term relief. A variety of OTC lubricants are effective at alleviating dyspareunia. Limited long term benefit Some lubricants may also damage condoms.
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Painful intercourse—Lost of interest in sex Many menopausal women notice a decline in libido, often related to frequent hot flushes or dyspareunia due to atrophic vaginitis. Treatment of the underlying conditions should be first line therapy. Sustained release bupropion (300mg/d) has been shown to increase both sexual arousal and satisfaction in women who are not depressed. Testosterone therapy can be added to HRT to improve libido
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12 Insomnia
Insomnia is a common complaint of menopausal women. This could be unrelated to, or as a consequences of hot flashes. Eszopiclone (3mg qhs) has been shown to alleviate insomnia related hot flashes. With sufficient sedation, night sweats and hot flashes go unnoticed and both sleep and mood improve Magnolia bark supplements: may be preferred sleeping aid for women who doesn’t want sedating hypnotic. This herbal remedy has been found to decrease anxiety, irritability, and insomnia related to menopause. There is limited research on long-term
benefits and adverse effects. 37
Hair thinning
Up to 26% of women develop thinning hair at the onset of menopause due to the relative increase in circulating androgens that occurs as estrogen production decreases. Spironolactone has been shown to be a safe and effetive intervention Topical minoxidil (2%) may be helpful in women with hair loss. Cyproterone acetate is also effective. This is administered as an oral contraceptive agent. Up to 88% women have no progression or hair loss
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Back to our case…
After discussion of treatment options, patient decided to take venlafaxine for her hot flushes and mood swings. She also use estrogen ring to decrease atrophic vaginitis. At 6 months follow up, patient reported that frequency of hot flashes is down to 1-2 /week, and rarely disrupt her sleep. Patient’s mood also improved, and her pain during intercourse had resolved. She was arguing with her husband much less often and currently has a happy marriage!!!
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13 Health Maintenance for Postmenopausal Women Preventive Care Recommendations: Lifestyle modifications, screening, early identification, and appropriate intervention may prevent many chronic conditions that cause morbidity and mortality during menopausal years
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U.S. Preventive Services Task Force (USPSTF) recommendation statement The USPSTF recommends against the use of combined estrogen and progestin for the prevention of chronic conditions in postmenopausal women. Grade D recommendation The USPSTF recommends against the use of estrogen for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy. Grade D recommendation
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The USPSTF recommendation
This only applies to postmenopausal women who are considering hormone therapy for the primary prevention of chronic conditions, not for those who want to use hormonal therapy to treat menopausal symptoms such as hot flashes or vaginal dryness. Benefit: reduction of total fractures and hip fracture Harms: increase in breast cancer, PE, stroke, DVT, gallbladder disease, dementia, urinary
incontinence 42
14 Osteoporosis:
Half of all postmenopausal women will have an osteoporotic fracture during their lifetime
AAFP/USPSTF: Screen women older than 65 years or starting at 60 years in women at high risk of osteoporotic fractures. Grade B
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Calcium and Vitamin D
Average dietary calcium intake for postmenopausal women in the US is about 600mg/day. NIH recommends that all women 65 years and older take 1500 mg of calcium/day, so most women will need to take supplement. The AAFP/USPSTF recommends vitamin D supplementation to prevent falls in community dwelling adults aged 65 or older who are at increased risk for fall. Grade B
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Obesity
The AAFP/USPSTF recommends screening all adults for obesity. Clinicians should offer or refer patients with a body mass index (BMI) of 30 kg/m2 or higher to intensive, multicomponent behavioral interventions. Grade B
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15 Physical activity
Regular weight-bearing exercise can reduce the risk of developing osteoporotic fracture in postmenopausal women. The AAFP/USPSTF recommends exercise or physical therapy and vitamin D supplementation in community-dwelling adults aged 65 years or older who are at increased risk for falls. Grade B
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Tobacco use
Cigarette smoking has been associated with earlier onset of natural menopause.
Both AAFP and USPSTF: level A Screen all adults for tobacco use and provide interventions for smoking cessation
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Aspirin
The AAFP/USPSTF recommends the use of aspirin for women age 55 to 79 years when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in gastrointestinal hemorrhage. Grade A
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16 Blood pressure
AAFP/USPSTF: Grade A Blood pressure screening is recommended in adults 18 years and older.
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CHD in women
Coronary heart disease is the most common cause of death in women About 1 in 2 women develops CHD and 1 in 3 dies from it
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Cholesterol
The AAFP/USPSTF recommends screening women aged 45 and older for lipid disorders if they are at increased risk for coronary heart disease. Grade A
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17 Diabetes
The AAFP/USPSTF recommends screening for type 2 diabetes in asymptomatic adults with sustained blood pressure (either treated or untreated) greater than 135/80 mm Hg. Grade B
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Breast cancer
Breast cancer is the most common non-skin malignancy diagnosed in women and the second leading cause of caner-related death. AAFP/USPSTF: recommended biennial screening mammography for women aged 50 to 74 years. Grade B. AAFP/USPSTF: women aged 40-49 to be screened with mammography; This should be an individualized decision. Grade C.
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Cervical cancer
AAFP/USPSTF: Screening for cervical cancer in women age 21 to 65 years with cytology every 3 years or, for women 30 to 65 years who want to lengthen the screening interval, screening with a combination of cytology and HPV testing every 5 years. Grade A
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18 Colorectal cancer
The AAFP/USPSTF recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy, in adults, beginning at age 50 years and continuing until age 75 years. Grade A
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What is the USPSTF recommendation for lung cancer screening?
A. Annual screening for lung cancer with low-dose CT in adults ages 55-80 who have a 30 pack-year smoking history and currently smoke or have quit in within past 15 years. B. Annual screening for lung cancer with chest x-ray in adults ages 55-80 who have a 30 pack-year smoking history and currently smoke or have quit in within past 15 years. C. There is no recommendation for screening since the harm of radiation and unnecessary intervention outweighs the benefit of lung cancer detection. D. Biennial screening for lung cancer with low-dose CT in adults ages 55-80 who have a 30 pack-year smoking history and currently smoke or have quit in within past 15 years.
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Lung cancer
The USPSTF recommended annual screening with low-dose computed tomography in adults aged 55-80 who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Grade B. Screening should be discontinue once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the willingness to
have curative lung surgery. 57
19 Lung Cancer
AAFP: evidence is insufficient to recommend for or against screening for lung cancer with low-dose computed tomography (LDCT) in persons at high risk for lung cancer based on age and smoking history. ACS: clinicians should initiate a discussion about lung cancer screening with patients aged 55-74 years who have at least a 30–pack-year smoking history, currently smoke, or have quit within the past 15 years, and who are in relatively good
health. 58
References:
Management of menopausal symptoms. Practice Bulletin No. 141. American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;123:202-16 Dickson, GM. Menopause management: How you can do better. J of Fam Practice. 2012;61(3): 138-145. Hill DA, Hill SR. Counseling patients about hormonal therapy and alternatives for menopausal symptoms. Am Fam Physician. 2010;82(7): 801-807. Randel, A. AACE Releases guidelines for menopausal hormone therapy. Am Fam Physician. 2012;86(9):865-867. Rao, SS et al. Health Maintenance for Postmenopausal women. Am Fam Physician. 2008;78(5):583-591. http://www.uspreventiveservicestaskforce.org http://www.aafp.org/patient-care/clinical-recommendations.html 59
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Pulmonary Function Tests – Basic Interpretation for Primary Care
Pulmonary Function Tests – Basic Interpretation for Primary Care Andrew Goodbred, MD, St. Luke’s Family Medicine Residency Program Disclosures:
Speaker has no disclosures and there are no conflicts of interest.
The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products.
The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Pulmonary Function Testing Basic Interpretation for Primary Care Andrew J. Goodbred, MD Clinical Faculty –St. Luke’s Family Medicine Residency Bethlehem, PA 1
Disclosure
• Dr. Andrew J. Goodbred has no conflict of interest, financial agreement, or working affiliation with any group or organization.
2
Objectives
• To understand the basics of the PFT procedure • To establish a step‐by‐step approach for interpreting PFTs • To discuss a brief differential diagnosis for different classes of abnormalities • To understand the grading system used to grade lung disease severity based on PFTs
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1 A Case for PFTs
• Mr. Adam Vair is a 55 yo male who reports that for “quite some time” he’s had progressive intermittent cough that seems to often worsen when he’s sick. • He smoked 1 pack per day for 20 years, quitting 5 years ago. • Mr. Vair works as an engineer in a chemical plant • He has a history of seasonal 4 allergies
What is Mr. Vair’s problem?
• Asthma?
• COPD?
• Fibrotic disease caused by possible work exposures?
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Indications for PFTs • Evaluate unexplained symptoms (chest pain, cough, etc) • Evaluate undiagnosed signs (chest deformity, crackles, etc) • Further evaluate abnormal testing (CXR, ABG) • Measure effect of disease on pulmonary function (sarcoidosis) • Screening in the exposed (smokers, occupational exposures, etc) • Pre‐operative evaluation • Monitoring treatment for known disease 6 • Research • And Many More
2 Choosing Wisely
• The 2007 Choosing Wisely guidelines recommended against treating asthma without PFT confirmation
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The Information Gained
• Volumes
• Diffusion capacity
• Response to bronchodilators
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The Machine
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Image courtesy of Cleveland Clinic
3 The Procedure
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Image courtesy of nhlbi.nih.gov
Volumes
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Image courtesy of Cleveland Clinic
Flow‐Volume Loop
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Image courtesy of Morgan Scientific
4 Which Volumes are most Important?
• FEV1 • FVC ‐ The volume of air ‐ The sum of the expelled over the first inspiratory capacity and full second of expiration the expiratory reserve volume
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Diffusion Capacity
• What it tests – • How it’s done – interaction of: ‐ Full exhalation ‐ Alveolar structural ‐ Inhalation of mixed gas integrity (usually carbon ‐ Capillary structural monoxide, helium, integrity oxygen and nitrogen) ‐ The ability to transfer ‐ Held for ten seconds, gas between the two followed by exhalation ‐ Analysis of gas mix determines rate of CO transfer 14
Response to Bronchodilator
• Short‐acting beta agonist medication is administered after the initial testing to assess for any change in patient’s performance
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5 Ensuring Quality of Exam
• Exhalation of at least 6 seconds • FEV1 and FVC within 0.2L of each other on two best efforts • Flow‐volume loops are free from artifact
Courtesy of AAFP.org
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Courtesy of AAFP.org
Interpreting Your Results
a Stepwise approach
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6 19
Courtesy of AAFP.org
Is the FEV1/FVC ratio low?
• Low is defined as: 1. <70% of the value predicted (GOLD Criteria) 2. Most institutions use ATS criteria due to greater sensitivity in most populations, with the exception of older patients with COPD 20 GOLD criteria are recommended in the dx of patients over 65 with risk factors for development of COPD** IF SO… 21 7 Obstruction! • If the FEV1/FVC is LOW, then an obstructive defect is likely present. Courtesy of nsgmed.com 22 23 24 Courtesy of AAFP.org 8 Is the FVC low too? Defined as: • If FVC is NORMAL, 1. 25 26 Low FEV1/FVC, Normal FVC • In this setting, where a pure obstructive defect seems to be present, a trial of short acting beta‐ agonist bronchodilator is performed to assess for responsiveness 27 9 So, Define “Responsive” • In adults, there must be an improvement in FEV1 or FVC of 12% AND 200mL • In children, an improvement in FEV1 or FVC of 12% is the only required criterion If these criteria are met, then the patient has… 28 ASTHMA! 29 Image courtesy of Morgan Scientific If the Obstruction is Irreversible… α1‐antitrypsin deficiency Bronchiectasis Bronchiolitis obliterans Chronic obstructive pulmonary disease Cystic fibrosis Silicosis (early) 30 10 31 Courtesy of AAFP.org FEV1/FVC low and FVC low • Restrictive pattern • If a bronchodilator trial • Mixed pattern ELEVATES the FVC over • Pure obstruction with the LLN or >80% of gas trapping (COPD) predicted (child) then obstruction with gas trapping (COPD) is confirmed • If NOT, then full PFTs are performed to assess for restrictive defect 32 But what if the FEV1/FVC ratio is normal or increased? 33 11 34 Courtesy of AAFP.org Is the FVC decreased? • Defined as 35 36 12 Restrictive Disease • The differential diagnosis is extensive, but is broken down into etiologies based in 1. The chest wall 2. Drug reactions 3. Interstitial lung disease 4. Neuromuscular disease 37 38 Courtesy of AAFP.org Where does the Diffusion Capacity Come in? • Both restrictive and obstructive processes have extensive differential diagnoses, which may be teased apart by taking the diffusion capacity into account 39 13 Important Common Patterns to know • Obstruction with HIGH DLCO –asthma • Obstruction with NORMAL DLCO –asthma, chronic bronchitis, bronchiectasis • Obstruction with LOW DLCO – emphysema, CF • Restriction with NORMAL DLCO –chest wall and neuromuscular disorders • Restriction with LOW DLCO –exposures, pulmonary fibrosis, TB, sarcoidosis 40 A Note on Severities • For both obstructive and restrictive processes, severity is graded based upon the FEV1 Severity FEV1 (% of predicted) Mild >70 Moderate 60‐69 Moderately Severe 50‐59 Severe 35‐49 Very Severe <35 41 So How About Our Patient? 42 14 What was his FEV1/FVC? • FEV1/FVC: 66% • LLN: 75% 43 44 Courtesy of AAFP.org What was his FVC? • FVC: 5.18L • LLN: 4.34L 45 15 46 Courtesy of AAFP.org Bronchodilator Trial • After a trial of bronchodilator, his FEV1 increased by 225mL, for a percentage change of 13% 47 Courtesy of AAFP.org So What Does Mr. Vair Have? • ASTHMA!! 48 16 References • Johnson, JD. A Stepwise Approach to the Interpretation of Pulmonary Function Tests. American Family Physician 2014 Mar 1;89(5):359‐366. • Pulmonary Function Testing. UpToDate.com Accessed 12/10/14. Updated July 2014. • Gildea, Thomas R. “Pulmonary Function Testing.” Cleveland Clinic Medical Education. Clevelandclinicmeded.com. Accessed 12/10/14. 49 17 Return to Top Dyslipidemia – New Guidelines Dyslipidemia – New Guidelines Kristen L. Jones, DO, St. Luke’s Family Medicine Residency Program Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Dyslipidemia: The New Guidelines Kristen Jones, D.O. November 6, 2015 1 Disclosure Dr. Kristen Jones has no conflict of interest, financial agreement, or working affiliation with any group or organization. 2 Learning Objectives Review updated recommendations for the treatment of cholesterol levels to reduce atherosclerotic cardiovascular risk; Identify the groups most likely to benefit from cholesterol- lowering statin therapy; Identify characteristics that predispose individuals to statin adverse reactions. 3 1 Background… 2013 – approved by American College of Cardiology and American Heart Association Recommendations were derived from randomized trials, meta-analyses, and observational studies reviewed as early as 2008 and sponsored by National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations. Expert panel was to interpret the evidence and “craft” recommendations No evidence was considered beyond 2011. Updates to these guidelines began in 2014 4 Background… Expert Panel comprised of: 16 people, including primary care physicians, cardiologists, endocrinologists, and experts in clinical lipidology, clinical trials, cardiovascular epidemiology and guideline development Peer Reviewed by 23 expert reviewers and representatives of federal agencies, under the observation of NHLBI. Then, reviewed by 4 expert reviewers nominated by ACC and AHA. 5 Initially Endorsed by: American Association of Cardiovascular and Pulmonary Rehabilitation American Pharmacists Association American Society for Preventive Cardiology Association of Black Cardiologists Preventive Cardiovascular Nurses Association Women Heart: The National Coalition for Women with Heart Disease 6 2 Scope of Guidelines Provide/update recommendations for treatment of cholesterol levels to reduce atherosclerotic cardiovascular disease (ASCVD) risk ASCVD includes coronary heart disease, stroke, peripheral artery disease Recommendations are intended as the foundation of treatment of cholesterol for primary and secondary prevention of ASCVD in women and men 21 years of age and older 7 *Please Note* The data they reviewed identifies those most likely to benefit from cholesterol –lowering statin therapy 8 What’s New? Focus on ASCVD Risk Reduction: 4 statin benefit groups A new perspective on LDL –C and or non-HDL –C treatment goals Global Risk Assessment for Primary Prevention Safety Recommendations Role of Biomarkers and Noninvasive Tests Future Updates to the Blood Cholesterol Guideline 9 3 Focus on ASCVD Risk Reduction: 4 statin benefit groups Potential for an ASCVD risk reduction benefit clearly exceeds the potential for adverse effects in adults with Individuals with clinical ASCVD Individuals with LDL ≥ 190 Individuals 40 to 75 years old with diabetes with LDL 70-189 Individuals without clinical ASCVD or diabetes who are 40-75 with LDL 70-189 AND estimated 10 year ASCVD risk of 7.5% or higher 10 11 12 4 A New Perspective on LDL and Non- HDL Goals RCT evidence shows that ASCVD events are reduced by using the maximum tolerated statin intensity. Use of LDL targets may result in under –treatment with evidence based statin therapy or overtreatment with non statin drugs that not been shown to reduce ASCVD events 13 Global Risk Assessment for Primary Prevention Use of new Pooled Cohort Equations is recommended to estimate 10 year ASCVD risk in both white and black men and women who do not have clinical ASCVD Input includes the following Gender Age Race Total Cholesterol HDL Systolic BP Treatment for BP? DM? 14 Smoking Status Safety RCTS were used to identify important safety considerations in individuals receiving treatment and to determine statin adverse effects Expert guidance is provided on management of statin – associated adverse effects, including muscle symptoms 15 5 Safety: Recommendations Appropriate selection of brand and dose of statin should be based on Patient characteristics Level of ASCVD risk Potential for adverse effects 16 Characteristics predisposing individuals to statin ADR’s Multiple or serious comorbidities, including impaired renal or hepatic function History of previous statin intolerance or muscle disorders Unexplained ALT elevations >3 times upper limit of normal Patient characteristics or concomitant use of drugs affecting statin metabolism >75 years of age 17 When to order CK levels CK should NOT be routinely ordered Baseline CK is reasonable for patients believed to be at increased risk for adverse muscle events based on Personal or family history of statin intolerance Muscle disease Clinical presentation Concomitant drug therapy that might increase risk of myopathy During statin therapy, it is reasonable to measure CK in individuals with Muscle symptoms (pain, tenderness, stiffness, cramping, weakness) Generalized fatigue 18 6 More safety considerations… Evaluate and treat muscle symptoms following these steps 1. to avoid unnecessary discontinuation of statins – obtain thorough history prior to to initiating statin 2. if unexplained muscle symptoms or fatigue: stop statin. Evaluate with CK, creatinine, and urinalysis for myoglobinuria 19 More safety considerations… If mild to moderate muscle symptoms: 1. Stop statin 2. Evaluate for other causes 3. If muscle symptoms resolve and there is no contraindication – give the patient the original or a lower dose of the same statin to establish a causal relationship 4. If causal relationship exists – discontinue that statin and begin a low dose of a different statin once symptoms resolve Once a low dose of statin is tolerated, gradually increase the dose as tolerated 5. If no causal relationship, and symptoms are coming from an unrelated condition – resume statin therapy at original dose 20 More safety considerations… Baseline ALT levels should be performed before initiating statin It is reasonable to measure hepatic function during treatment if symptoms suggesting hepatotoxicity arise Decreasing the statin may be considered if LDL levels are <40 on two consecutive occasions 21 7 & yes, even MORE safety considerations… It may be harmful to initiate simvastatin at 80 mg daily or increase to this dose Individuals on statins should be evaluated for new onset DM according to current diabetes screening guidelines Use caution in individuals >75 years of age 22 What if statins aren’t an option? For Statin intolerant individuals or those who have less than anticipated therapeutic response, one may consider “Nonstatins” Key points Prepare for more monitoring Don’t use gemfibrozil with patients on statins b/c of increased risk of rhabdomyolysis Consider fenofibrate with a low or moderate intensity statin if the benefits from ASCVD risk reduction or triglyceride lowering (when >500) are judged to outweight the risk for ADR’s 23 Role of Biomarkers and Noninvasive Tests There is a concern about other factors that may indicate elevated ASCVD risk, but were not included in the pooled cohort equations In selected individuals who are not in 1 of the 4 statin groups, additional factors may be considered to inform treatment decision making LDL >160 or other evidence of genetic hyperlipidemia Family h/o premature ASCVD w onset < 55 years in first degree male or < 65 in first degree female CRP ≥ 2 CAC score (coronary artery calcium score) ≥300 Agston Units ABI <0.9 Elevated lifetime risk of ASCVD 24 8 *Additional Note* No recommendations made for Greater than 75 years of age, unless ASCVD is present Individuals with a need for hemodialysis – OR- New York Heart Association Class II, III, or IV heart failure 25 Future Updates This is not a comprehensive approach to lipid management, only focuses on treatments proven to reduce ASCVD events. Just some of the future questions to be addressed are: The treatment of hypertriglyceridemia Use of Non HDL in decision making Optimal age for initiating statin therapy to reduce lifetime risk of ASCVD Subgroups of individuals with heart failure or undergoing hemodialysis that might benefit from statins Long term effects of statin associated new onset diabetes and management 26 Another Area of Concern The calculator! Article in Lancet by Ridker and Cook highlights this Calculator has not been prospectively tested for accuracy in predicting CV risk May overestimate risk in those without atherosclerotic disease 27 9 AAFP weighs in… ENDORSED WITH QUALIFICATIONS, JUNE 2014 Summary of Recommendations Individuals with LDL-C ≥ 190 mg/dL or triglycerides ≥ 500 mg/dL should be evaluated for secondary causes of hyperlipidemia. Adults ≥ 21 years of age with a primary LDL-C ≥ 190 mg/dL should be treated with high intensity statin therapy unless contraindicated. Adults 40-75 years of age with an LDL-C 70-189 mg/dL without clinical ASCVD or diabetes and an estimated ten-year ASCVD risk ≥ 7.5% should be treated with moderate to high intensity statin therapy. Adults 40-75 years of age with diabetes mellitus and an LDL-C 70-189 mg/dL should be treated with moderate intensity statin therapy. Individuals ≤ 75 years of age who have clinical ASCVD should be treated with high intensity statin therapy unless contraindicated. There is not enough evidence to recommend for or against treating blood cholesterol to target levels. There is not enough evidence to recommend the use of non-statin medication combined with statin therapy to further reduce ASCVD events. 28 AAFP weighs in… Qualifications The guideline uses a CVD risk assessment tool that has not been validated and may overestimate risk. The risk cut-off of 7.5%, rather than 10%, will significantly increase the number of individuals on statins. Many of the recommendations were based on expert opinion, although the key points are evidence based. Seven of the 15 (16) members of the guideline panel had conflicts of interest. 29 AAFP weighs in… “The most important trend is toward shared decision- making.” 30 10 31 References http://www.aafp.org/patient-care/clinical- recommendations/all/cholesterol.html Keaney JF Jr, Curfman GD, Jarcho JA. A pragmatic view of the new cholesterol treatment guidelines. N Engl J Med 2014;370:275-278 Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PWF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;00:000–000. 32 11 Return to Top Transitioning Patients with Autism from Pediatric to Adult Practices Transitioning Patients with Autism from Pediatric to Adult Practices Edward (Ted) Brodkin, MD, Center for Autism Research at the Children’s Hospital of Philadelphia James Connell, Ph.D, A. J. Drexel Autism Institute Disclosures: Speakers have no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Autism Spectrum Disorders and Transition to Adult Care James Connell, PhD Associate Professor A.J. Drexel Autism Institute Drexel University Edward S. Brodkin, MD Associate Professor of Psychiatry Director, Adult Autism Spectrum Program Perelman School of Medicine at the University of Pennsylvania 1 Disclosure • James Connell, PhD has no conflict of interest, financial agreement, or working affiliation with any group or organization. • Edward S. Brodkin, MD has no conflict of interest, financial agreement, or working affiliation with any group or organization. • This session may contain discussion of unapproved or investigational uses of products or devices as indicated. 2 Learning Objectives • Describe the two defining features of autism spectrum disorder • Name three major challenges of transition to adulthood in autism spectrum disorder • Identify two indications for medication uses in autism spectrum disorder – Will be able to list the major limitation of medication treatment – Will be able to name the indication for behavioral treatment in autism spectrum disorder 3 1 Autism Spectrum Disorders • The defining features of autism spectrum disorders are impairment in the following: – 1. Social interaction and Social Communication Deficits – 2. Restricted, repetitive, or stereotyped patterns of interest or behavior 4 Symptom domain #1: Social Interaction • Social interaction symptoms (early appearing, often starting as early as age 1‐2 years) – Lack of attention to faces – Reduced eye contact – Lack of social or emotional reciprocity – Difficulties in perceiving, responding appropriately to, and expressing emotions – Difficulty in perceiving and using nonverbal social cues – Failure to develop peer relationships appropriate to developmental level 5 Symptom Domain #1: Social communication • Absence of language OR delayed language development • Stereotyped and repetitive use of language or idiosyncratic language – Echolalia – Using only single words to communicate • Lack of varied, spontaneous imaginative social play appropriate to developmental level in children • Impairment in the ability to initiate or sustain a conversation with others • Deficits in prosody (tone of voice), “pragmatics” of language (tailoring language to social demands) 6 2 Symptom Domain #2: Restricted and Repetitive Behavior • Stereotyped or repetitive motor mannerisms – Rocking, spinning, hand or finger flapping or twisting • Restricted interests – Encompassing preoccupation with restricted interests that is abnormal in intensity or focus (e.g. train schedules) • Inflexible (rigid) adherence to specific, nonfunctional routines or rituals (“insistence on sameness”) • Preoccupation with parts of objects 7 Associated Behavioral Phenotypes • Intellectual disability – Seen in ~40% of individuals with autism spectrum disorders • Other more subtle cognitive features – Complex information processing (Minshew et al) • Difficulties with complex sensory, motor, memory, language and concept formation • Seizures – In up to 30% of patients with autism spectrum disorders – Bimodal peaks of onset of seizures in both early childhood and adolescence • Anxiety symptoms, OCD‐like sx’s, depression 8 Associated Behavioral Phenotypes (continued) • Tantrums/aggressive behaviors and self‐injurious behaviors • Hyperactivity, ADHD‐like symptoms • Savant skills (10% of individuals with autism spectrum disorders)—outstanding ability in one narrow area, e.g. calender calculation, musical or artistic ability • Sensory sensitivities—to sound, sight, smell, taste or touch • Sleep difficulties 9 3 Prevalence of Autism Spectrum Disorders: Centers for Disease Control and Prevention • Autism Spectrum Disorders (broad definition) • – Prevalence: 1 in 68 children – Male:Female ratio 5:1 – 1 in 42 boys – 1 in 189 girls 10 CDC Autism and Developmental Disabilities Monitoring (ADDM) 11 Findings: • ≈ 20,000 people with autism in Pennsylvania in 2005 • Given the trend, that number has reached 25,000‐30,000 12 4 2005: just over 1,400 adults with autism 2010: 179% increase to 3,825 2015: 621% increase to 10,140 2020: 1,292% increase to 19,587 13 Challenges of Transition to Adulthood • Typical Challenges: – Completing secondary or post‐secondary education – Transitioning from educational setting to work setting – Developing social and communication skills necessary for adult life – Engaging with peers and the community – Developing independence / ability to function once one’s parents become elderly or pass away 14 REPORTS PUBLISHED: Statewide Summary Service Needs Barriers & Limitations to Accessing Services Unwanted Outcomes: Police Contact & Emergency Hospital Care Getting a Diagnosis & Follow‐up Care Employment Challenges Family Impact Report Recommendations 15 5 Without effective supports, we see: Homelessness Crisis intervention Hospitalizations Chemical restraints Justice Intersections High family stress Individuals with autism living at home with aging parents or siblings 16 Treatments for Autism Spectrum Disorders • Initial evaluation • Behavioral – Applied Behavior Analysis (ABA) – Floortime – Social skills groups • Pharmacological – Atypical antipsychotics – SSRIs • Other (not well studied—be skeptical!) – Eliminating particular foods/ingredients from diet – Megavitamin therapies – Sensory integration 17 PACT ‐ • Provider Agency Consultation Therapy – The need • BAS needs assessment • Census data – The model • Medical model with extensive EBP in ABA • Nursing • Navigation • Social Work • Clinical Psyc – Goals • Comprehensive case conceptualization for complex cases • Evidence‐based therapeutic approaches • Build internal capacity 18 6 Interdisciplinary treatment team • Physicians and nurses • Behavior Analysts (Board Certified Behavior Analysts) • Teachers • Psychologists • Social workers • Speech‐Language Pathologists • Occupational Therapists 19 Case conceptualization • Complex case referral form • Standardized ASD evaluation forms – If mis or under diagnosis is a concern • Case conceptualization – Team approach • Reason for referral – Including physical health, mental health, daily activities, work, behavioral health, med management, behavioral health – Holistic approach – Considers available supports for tx follow through, intervention portability, staff development • Treatment recommendations • Follow‐up consultation 20 Etiology of autism spectrum disorders • Very rare causes of autism‐like phenotype: particular environmental insults – Prenatal infections – Teratogens: Valproate • Minority of cases of autism (<10% of cases)—known etiology, relatively “simple” genetics – Single gene syndromes – Chromosomal translocations, duplications, triplications • Majority of cases of autism—unknown etiology, highly heritable, complex genetics, multiple genes are involved – Combination of common gene variants and copy number variants (CNVs) – Neural cell adhesion molecules (neuroligins, neurexins, cadherins) 21 7 Very rare causes of autism‐like phenotype: known environmental insults • Prenatal teratogens – Thalidomide – Valproic acid – Misoprostol • Prenatal infections – Prenatal rubella infection? (now very rare due to widespread immunization) • Children followed with “autism” following prenatal rubella have had dramatic improvements in their autism‐like symptoms over time, suggesting possible misdiagnosis – Haemophilus influenzae – Cytomegalovirus – Other infections 22 Large Brain in ASD Brain enlarged ~ 5% “White matter” connections enlarged ~ 8% Images from Robert T. Schultz, Ph.D.23 Converging DTI, sMRI, fMRI and behavioral evidence • Underactive temporal lobe social nodes Fusiform Face Area: (1) abnormal size/morphology Salience Detector (2) abnormal connections (Amygdala) (3) low activity levels 24 8 Other Environmental Factors • Increased risk with increased paternal age – increased point mutations in DNA – Increased copy number variants in DNA • Air pollution exposure • Others?? 25 Minority of cases of autism spectrum disorders (<10% of cases): relatively “simple” genetics • Fragile X syndrome (1‐3% of cases of autism) • Rett syndrome • SHANK3 • Neurexins: CNTNAP2 • Neuroligins • Turner syndrome • Tuberous sclerosis (1% of cases of autism) • 15q11‐13 duplications • Other rare chromosomal abnormalities – Cytogenetic abnormalities in individuals with autism have been found on virtually every chromosome 26 Fragile X Syndrome • Accounts for 1‐3% of cases of autism • Approximately 30% of Fragile X patients are on the autism spectrum • Fragile X is a common inherited form of mental retardation • Caused by a trinucleotide (CGG) expansion in the FMR1 gene on chromosome X. This expansion prevents expression of the fragile X mental retardation protein (FMRP). 27 9 Fragile X Syndrome Incidence: 1 in 3,000 males, 1 in 6,000 females Symptoms • Moderate to severe mental retardation • Autistic-like features: Shyness, poor eye contact, social anxiety, hyperactivity, hand flapping/biting • Sleep Disorders •Seizures • Long narrow faces with large ears (connective tissue abnormalities) • Dendritic spine abnormalities in the brain Hyperextensible joints Macroorchidism 28 Maternally‐inherited chromosome 15q11‐q13 duplications • Phenotype – Maternally inherited 15q11‐q13 duplication: Autistic phenotype (range of severity among patients, including no phenotype, i.e. not full penetrance) when the duplication is inherited from the mother, as well as ataxia, language delay, epilepsy, mental retardation, facial dysmorphology – Paternally inherited 15q11‐q13 duplication: No phenotype (or very low penetrance phenotype) 29 Chromosome 15q11-q13 deletions – Paternally inherited deletions: Prader-Willi syndrome • Mild to moderate intellectual disability • hyperphagia and obesity • temper tantrums, OCD sx’s • short stature, small hands and feet • hypogonadism – Maternally inherited deletions: Angelman syndrome • Severe intellectual disability with lack of speech • aggressive behaviors • excessive inappropriate laughter • hyperactivity •seizures •ataxia 30 10 Other Disorders with Symptoms that may Overlap with ASD in Adults • Schizophrenia, negative symptoms • Schizophrenia “spectrum”: e.g. schizotypal • Other personality disorders: schizoid, avoidant • Social anxiety disorder, obsessive‐compulsive disorder 31 ASD vs. Schizophrenia • Onset of symptoms by 3 years of • Onset of symptoms in age adolescence or adulthood • Social withdrawal and • Overt hallucinations or delusions restricted/repetitive behaviors not driven by hallucinations or delusions • • Typically no smoking or drug use Smoking and drug use is common • • Less likely to have a criminal Sometimes a criminal history history • A substantial percentage have • A smaller percentage has marked intellectual disability intellectual disability 32 Medications in ASD • Verify diagnosis – High dose antipsychotics unlikely to reduce the restricted/repetitive behaviors of ASD, and may make things worse • Meds should be used, if necessary, as part of a comprehensive treatment plan, not as a sole treatment • Patients with ASD may respond to lower doses and be more sensitive to side effects • Depression and anxiety are common co‐morbid symptoms in ASD that can respond to meds 33 11 Limits of Pharm Rx Currently • No good agents to treat at least 2 out of 3 of the core defining symptoms domains of ASD – Social behavior symptoms – Language / communication impairments 34 Targets of Drug Rx in ASD • Interfering repetitive behaviors – Repetitive motor mannerisms, inflexible adherence to nonfunctional routines or rituals – Serotonin Reuptake inhibitors • Irritability / aggression – Impulsive aggression, severe temper tantrums, self‐injurious behaviors – Antipsychotics, especially risperidone • Hyperactivity / inattention – Stimulants – Non‐stimulants • Depression – SSRIs and others • Anxiety – SSRIs and others 35 Meds used in ASD • Risperidone, aripiprazole, and other antipsychotics – Can be helpful in minimizing aggressive and self‐injurious behaviors • SSRIs – For depression or anxiety – Repetitive behaviors?? • Methylphenidate or atomoxetine (Strattera) – For ADHD like symptoms • Antiepileptic Drugs, e.g. valproate • To treat seizures • To reduce maladaptive behaviors (irritability) 36 12 Serotonin Reuptake Inhibitors • Fluoxetine (significant symptom reduction in double blind, placebo controlled studies), escitalopram, fluvoxamine (in adults) • Target symptoms: interfering repetitive behaviors • Repetitive motor mannerisms, inflexible adherence to nonfunctional routines or rituals • Repetitive ordering, hoarding, telling or asking, touching, tapping, rubbing, self damaging or mutilating behaviors • Possibly more effective in adults than in children 37 Antipsychotics • Risperidone (FDA approved), aripiprazole (FDA approved), olanzapine, haloperidol • Target symptoms: irritability, tantrums, aggression • May also reduce stereotypy and hyperactivity • Adverse effects of atypical antipsychotics: weight gain, sedation, metabolic changes, EPS 38 ADHD drugs • Methylphenidate, atomoxetine (NE reputake inhibitor), clonidine (alpha‐2 adrenergic agonist), guanfacine (alpha‐2 adrenergic agonist) • Target symptoms: hyperactivity, inattention • Children with ASD are less responsive to these meds (effective in only about 50% of patients) and are more likely to have adverse effects (e.g. irritability with methylphenidate) compared with children with ADHD (no ASD) 39 13 ADHD drugs • Methylphenidate—more likely to cause adverse effects, e.g. irritability • Atomoxetine—significant benefit, with minimal adverse effects • Clonidine and guanfacine—use may be limited by drowsiness, but can be helpful in children with sleep disturbance 40 Treating Social and Communication Disabilities: Non‐pharmacologic approaches • Currently, the only adequate way to address the social and communication disabilities (the core features of ASD) are through non‐ pharmacologic treatments • Pharmacologic treatment alone is not adequate in most cases—should be done in conjunction with non‐pharmacologic treatment 41 Purposes of non‐pharmacologic treatment • To build skills – Social skills – Language and communication skills • To reduce interfering behaviors – e.g. if patients can communicate their needs, then there may be less tantrums 42 14 Treatment goals: skill acquisition and behavior reduction Treatment targets focused on skill Treatment targets focused on acquisition behavior reduction • Academic – school activities • Communication – e.g., requesting, • General symptoms – “Of ASD” labeling, receptive, expressive • Problem behaviors – SIB, agg, • Higher Cog. Functioning – complex destruction, tantrums, hazardous problem-solving or inappropriate bx • Interpersonal – social interaction • Restricted, repetitive, non- • Learning readiness – following instruction, attending functional patterns of bx, • Motor skills – fine and gross motor interests or activity – speech, • Personal Responsibility motor, thought •Play • Sensory or emotional regulation • Self-regulation – modify level of arousal • Placement – where intervention occurs 43 Questions?? • To hear more about PACT, or request a case consult, email Dr Connell [email protected] 44 15 Return to Top Herbs, Supplements and Athletes Herbs, Supplements and Athletes Neilson M. Matthews, IV, MD, Lehigh Valley Health Network Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. 1 Athletes and Dietary Supplements NEIL MATHEWS, M.D., FAAFP, CAQSM LEHIGH VALLEY FAMILY MEDICINE RESIDENCY/SPORTS MEDICINE FELLOWSHIP NOVEMBER 6, 2015 2 Disclosures Dr. Neil Mathews has no conflict of interest, financial agreement, or working affiliation with any group or organization. I have nothing to disclose, but my wife does leave whole-food supplements out for me to take in morning, which I do. 3 Objectives To be able to list reasons athletes use dietary supplements (DS) To understand the issues related to consumption of DS, including efficacy, purity, quality, and athlete testing To be able to list the DS that have shown to aid athletic performance and explain how they work 1 4 Epidemiology $60 Billion industry/$20 B in US alone Since 1994, products from 4,000 to 55,000; 1,000 companies > 100,000,000 people take supplements 85% of elite track and field athletes take at least one DS (J of Sports Science, Apr 2009) Bailey, J of Nutrition 2011 70% don’t tell physicians 44% think physician doesn’t know much 67% don’t tell of use before surgery 30% drug/supplement interaction Why Take a 5 Supplement? Correct nutritional deficiency- sound evidence-Iron or B12 deficiency Treat medical disease or condition-good evidence-B2 and Magnesium for migraine prophylaxis Improve health or optimize performance-sparse or poor evidence Last reason is why most athletes take supplements 6 Reasons Athletes Take Supplements “I can’t get everything I need from my diet” In few cases is this true; may need review c Nutritionist “I don’t have time to prepare and cook meals” Does take time; need to plan; help from Nutritionist “Everyone is using them and they will have an advantage over me” Companies pray on fears; not true, but often slim margin from 1st to 4th place “Supplement recommended by my doctor” Limited training for most physicians “Natural and organic way to enhance health” More to come on this; not proven and often not natural Note: 50% of Olympic-caliber athletes would take a banned substance if they would win all competitions for 5 years, but die from adverse effects 2 Dietary Supplement 7 Regulation Dietary Supplement Health and Education Act of 1994 (DSHEA) FDA regulates DS Manufacturer responsible for product safety before marketing and that label is truthful and not misleading Post-market, FDA responsible for monitoring safety and inspecting product info Federal Trade Commission (FTC) responsible for truth in advertising- needs to be symptom-specific, not disease-oriented 8 FDA Oversight 51% of Class 1 FDA recalls since 2004 are for supplements Food additives regulated more stringently than DS 2003- Ban on Kava (Nutraingredients) 2009- Warning placed on Hydroxycut products after number serious side effects and 1 death 2010- Voluntary recall of “Off Cycle II Hard Core”-contained aromatase inhibitor Emergen-C warned about untruthful advertising A Note on Quality 9 Consumer Grade DS: Drug store/Health food store Cheapest ingredients to max profits and shelf life Artificial ingredients, colors, fillers, preservatives, binders Minimum amount active ingredient Professional Grade DS: Full label disclosure Standardization of herbal extracts Therapeutic dosages 3rd party testing 3 10 Testing Depending on athlete, will have one or more governing body that oversees their participation 3 PED categories: All time: Anabolics, hormones In competition: Stim, steroids, THC In selected sports: B-blocker, alcohol Therapeutic Use Exemption (TUE)- Approval for banned substance Applied for before compete Documented need Not use to enhance performance over tx medical issue 11 “But I swear I 12 didn’t cheat!” Jessica Hardy-set 2 world records in 2008, never made it to Beijing Positive for Clenbuterol; tested and found in her DS, one of her sponsors! Accepted one year ban, not usual 2 LaShawn Merritt-World champion 400 m Positive for DHEA from Extenze Did not read label; 2 year ban Scott Moninger-multiple victories in road cycling Positive for norandrosterone from OTC DS he bought in convenience store One year ban 4 13 World Anti-Doping Agency (WADA) WADA does NOT distinguish between deliberate cheating and inadvertent doping Athlete is responsible for everything that enters their body 14 What’s in There? 50% of 33 brands creatine in Europe exceed limits for one contaminant Non-medicine contaminants include pesticides, bugs, animal feces, lead, broken glass Chemical contaminants include stimulants, anabolic steroids, aromatase inhibitors, GH releasing peptide, IGF1 in growth promoter Risk with allergies-fillers rice, wheat, and soy Watson P etal, Med Sci Sports Exer, 2009-just 2.5 mcg norandro in creatine DS (0.00005%) resulted positive urine/doping violation DNA Barcoding 15 Study Newmaster SG et al, BMC Medicine 2013 DNA barcodes for 44 herbal products; detect contamination and substitution Results: 33% contaminated or filler that was not listed 69% substituted 48% authenticated 2/12 companies authentic product and no sub, contaminants, or fillers 5 16 NSF Certified for Sport Recognized by NFL, MLB, PGA, NHL Participating manufacturers Label content, facility inspections, ongoing monitor of manufacturing and product analysis BUT, still do not guarantee any product is safe or pure therefore it is still buyer beware Does not assess efficacy App available for smartphones-lists companies and specific products 17 Types of Athletes and Exercise Endurance athlete-long bouts of exercise (run, swim, cycle, team- soccer) Sprint athlete-short bouts (track sprints, team-football, volleyball) Strength athlete-power exercises (weight lifting, football linemen) Many DS tested in non-athletes and results extrapolated to athletics What may actually help one athlete, may be ergolytic to another 18 A Good Diet Need to have first If well balanced diet, no vitamin or mineral supplement are required “Eat the Rainbow” Better to get nutrients in natural state instead of pill form Vegetarians, and especially vegans, at risk-diets low in energy, protein, fat, Iron, Calcium, Vit D, Riboflavin, Zinc, B12 6 19 Creatine Most well studied DS ever Naturally occurs in body (mostly in muscles) and in many foods (meat and fish) Complex amino acid Can only hold so much; reach saturation in few days USA consumes 4 M Kg creatine/year Allowed by IOC, NCAA, pro sports ACSM recommends NOT use if < 18 yo 2001 report-62/1103 adolescents on creatine, ?lead to steroid use 20 Creatine Effects: increase strength, increase free fat mass, increase performance in short repetitive bouts of high intensity exercise (30-90 seconds), faster regeneration of ATP between bouts, increased muscle mass NOT proven benefit aerobic training or performance Can be taken as loading dose 20-30 gm/d for 5-7 days, then maintenance 2-4 gm/day; extra cannot be stored or used Responders and non-responders; vegetarians at risk Side effects-most common: weight gain (fluid), GI upset, diarrhea, muscle cramping Caution in patients with kidney disease, liver disease, diabetes Excellent safety profile, especially if taken as recommended Now, 20+ new novel creating preparations-pitch better absorbed-no research to prove 21 Vitamin D- “The Sunshine Vitamin” Steroid hormone affecting calcium metabolism, bone health, muscle strength, immune function, and balance 71% general population with low levels 50-70% kids Rates doubled 1994-2004; poor diet, limited exposure to sun At risk-Northern latitudes, indoor athletes (80% v 48%), vegetarians, image sports (gymnasts, skaters) 25 (OH) D is best indicator of status 7 22 Vitamin D Emerging evidence to support direct impact on athletic performance via enhancement muscle function (Close GL, J Sports Sci 2013) NFL players released for injury or poor performance had significantly lower levels Vit D compared to other players (Maroon JC, Am J Sports Med 2015) Indirectly affects performance via immunity-higher number URI in deficient group General accepted levels Adequate: 30-100 ng/ml Borderline: 20-30 ng/ml Deficient: <20 ng/ml Many believe current RDA is not adequate Peak neuromuscular performance at levels near 50 ng/ml Toxicity rare with supplementation Screen: Stress fx, recurrent infection, MSK pains, everyone??? 23 Whey Protein Includes all amino acids, good source BCAA Easier to absorb than soy or casein ADA-average protein needs: Non-athlete: 0.8 g/kg/d Endurance: 1.2-1.4 Strength: 1.6-1.7 Caution with athletes with renal disorders, lactose intolerance, dairy allergies No side effects up to 2 gm/kg/day 24 Whey Protein/BCAA Prevent negative Nitrogen balance, aid protein synthesis especially during high intensity exercise; synthesize, repair, and maintain skeletal muscle proteins; prevent fatigue and overtraining Important source of energy in prolonged endurance exercise (soccer, tennis, running, swimming, cycling) Good in post-exercise smoothie-take within 20-30 minutes of bout, mix with CHO 3:1 protein 8 25 Caffeine Stimulant, methylxanthine similar to theophylline Claims-decreased level of exertion, increase mobilization of FFA and rate lipid metabolism; conserve glycogen Peaks 1-2 hours after ingest Average American-2 cups coffee per day 84% athletes believe improves concentration 73% believe is ergogenic Allowed by IOC, WADA-watch list NCAA-limit 15 ug/ml urine; have to drink 6 cups coffee hour before activity 26 Caffeine ACSM-may be effective, ?ethics if ergogenic Side effects-jitteriness, palpitations, anxiety, insomnia, arrhythmias Caution with energy drinks and caffeine powder Next to MVI, most popular DS c teens and young adults 24 oz drink contains 500 mg caffeine (4-5 c/coffee); Guarana 2007-2011: ER visits doubled for caffeine intox, most > 40 yo FDA advisory-pure caffeine powder c 2 deaths young men Powder 1 tsp=25 cups/coffee Available on internet Drinks often combined with alcohol use 27 Others with some good evidence… Alkalinizing agents (Sodium Bicarbonate)-improves anaerobic endurance performance through increased pre-exercise pH and increased buffering ability L-arginine-improves aerobic endurance exercise performance through increased plasma nitrite levels and reduced O2 consumption during submaximal exercise Beta-alanine-Improves aerobic and anaerobic endurance performance through increased carnosine content and improves intracellular buffer capacity Nitrate-improves aerobic endurance exercise performance-increases plasma nitrate levels, reduces O2 consumption, reduces ATP cost of muscle force production, and inhibits fall in muscle PhosphorylCreatine content during contractions “Dietary Supplements for Athletes: Emerging Trends and Recurring Themes”; Maughan RJ et al, J of Sp Sciences, 2011. 9 28 As for the rest of them… No convincing evidence for most other DS If has, is limited, poorly studied, flawed studies Fat burners, immune boosters, steroid enhancers, testosterone boosters Some do work! Study found AAS contamination in many DS manufactured in Holland (25.8%), Austria (22.7), UK (22.7), USA(18.8)- Geyer et al, 2004. 29 Helpful Resources American College of Sports Medicine (acsm.org) National Center for CAM (www.nccam.nih.gov) Food and Drug Administration (fda.gov) Office of Dietary Supplements (ods.od.nih.gov) US Anti-Doping Agency (www.usada.org) GlobalDRO.org-website for Olympics/International National Center for Drug Free Sport (www.drugfreesport.com) “Position of American Dietetics Assoc., Dieticians of Canada, and ACSM: Nutrition and Athletic Performance” J. of ADA 2009 Academy of Nutrition and Dietetics (eatright.org) Local Sports Nutritionist/Registered Dietician (RD) 30 Summary for Family Physicians Athletes, and many others, are using DS and many are not aware of the risks and limited benefits Ask about use in non-judgmental way when covering meds and vitamins Few have proven beneficial effects Be aware of special circumstances regarding elite, competitive athletes (restrictions and testing) Start with improving diet first before recommending DS; consider referral to Sports Nutritionist Use abundant, reputable resources to educate athlete and yourself 10 31 Thank You! Contact Info: [email protected] 11 Return to Top Tools to Treat Adult Patients with Obesity: An Update on Bariatric Surgery and Pharmacologic Agents Tools to Treat Adult Patients with Obesity: An Update on Bariatric Surgery and Pharmacologic Agents Robin Schroeder, MD, FAAFP, Lehigh Valley Weight Management Center Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. This activity was funded in part by an educational grant from Takeda Pharmaceuticals U.S.A., Inc. at the Allentown CME Conference, which had no control over the content. Tools to Treat Adult Patients with Obesity: An Update on Bariatric Surgery and Pharmacologic Agents Robin Schroeder, MD, FAAFP [email protected] Diplomate, American Board of Obesity Medicine Medical Director, Lehigh Valley Weight Management Center PAFP, November 6, 2015 1 Disclosure • Dr. Robin Schroeder has no conflict of interest, financial agreement, or working affiliation with any group or organization. 2 Which surgical procedure for weight loss is performed most often in the US today? A. Gastric banding B. Sleeve gastrectomy C. Roux‐en‐Y gastric bypass D. Revision 3 1 Patients who have had a weight loss surgery procedure should not take NSAIDS. A. True B. False 4 Which of the following weight loss medications is not approved for long term use? A. phentermine ER/topirimate ER (Qsymia) B. lorcaserin (Belviq) C. liraglutide (Saxenda) D. phentermine (Adipex) 5 Objectives • Describe the bariatric pre‐surgical, surgical and post‐surgical processes • Perform long‐term primary care management of post‐bariatric surgery patients • Describe the use of the currently available weight loss medications 6 2 Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2014 ¶ Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to prevalence estimates before 2011. *Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%. Within Subsets of Patients with Overweight and/or Obesity Deranged endocrine and Abnormal and pathologic immune responses physical forces Sick Fat Disease (SFD) (Adiposopathy) Fat Mass Disease (FMD) • Endocrine/metabolic: • Biomechanical/structural: ‒ Elevated blood glucose ‒ Stress on weight‐bearing joints ‒ Elevated blood pressure ‒ Immobility ‒ Dyslipidemia ‒ Tissue compression (i.e., sleep ‒ Other metabolic diseases apnea, gastrointestinal reflux, high blood pressure, etc.) ‒ Tissue friction (i.e., intertrigo, etc.) Reference/s: [1] [2] [3] [4] [5] [6] [7] 8 Fat Mass Disease Cardiovascular • Congestive heart failure and cor pulmonale • Varicose veins • Thromboembolic events (i.e., pulmonary embolus, stroke, etc.) • Hypertension (i.e., compression of kidney) Pulmonary • Dyspnea • Obstructive sleep apnea • Hypoventilation syndrome • Pickwickian syndrome • Asthma Neurologic • Intracranial hypertension (pseudotumor cerebri) due to increased intra- abdominal pressure, sleep apnea, etc. • Stroke (see “cardiovascular”) • Nerve entrapment (i.e., meralgia paresthetica, carpal tunnel syndrome,Reference/s: [17] [18] etc.) 9 3 Fat Mass Disease Musculoskeletal • Immobility • Myalgias • Osteoarthritis (e.g. knees, hips) • Altered center of gravity • Low back pain • Impaired balance Gastrointestinal • Gastrointestinal reflux • Hernias Integument • Stria distensae (skin stretch • Skin tags marks) • Intertrigo (i.e. bacterial, fungal • Stasis pigmentation skin fold infections) • Venous stasis ulcers • Carbuncles • Cellulitis Reference/s: [17] [18] 10 Adiposopathy (Sick Fat Disease) Pathophysiology • Impaired adipogenesis • Adipocyte organelle dysfunction (endoplasmic reticulum, mitochondria, etc.) • Increased circulating free fatty acids • Pathogenic adipose tissue endocrine responses • Pathogenic adipose tissue immune responses • Pathogenic consequences to other body organs such as fatty liver, vasculopathies (endothelial dysfunction, atherosclerosis, hypercoagulation), etc. Reference/s: [4] [6] [19] [20] 11 Adiposopathy (Sick Fat Disease) Anatomic Abnormalities • Adipocyte hypertrophy • Increased visceral, pericardial, perivascular, and other peri- organ adiposity • Growth of adipose tissue beyond vascular supply • Increased adipose tissue immune cells • “Ectopic” fat deposition in other body organs (liver, muscle, possibly pancreas, etc.) Reference/s: [4] [6] [19] [20] 12 4 Adiposopathy (Sick Fat Disease) Other Body Organs Adiposopathy most often results in metabolic disease when accompanied by: • Dysfunction other body organ • Limitations in the metabolic “flexibility” of other body organs Metabolic health is dependent upon the interactions or crosstalk with adipose tissue and other body organs: • Liver • Muscle • Pancreas • Immune system • Heart and vasculature • Brain • Endocrine glands • Intestine Reference/s: [4] [6] [19] [20] • Other body organs 13 Adiposopathy (Sick Fat Disease) Clinical Manifestations • High blood glucose (prediabetes • Insulin resistance mellitus, type 2 diabetes mellitus) • Hepatosteatosis (fatty liver) • High blood pressure • Hyperuricemia and gout • Metabolic syndrome • Cholelithiasis • Adiposopathic dyslipidemia • Acanthosis Nigricans ‒ Increased triglyceride levels • Nephrolithiasis ‒ Decreased high-density • Glomerulopathy lipoprotein cholesterol levels • Pro-thrombotic predisposition ‒ Increased atherogenic particle • Neuropsychiatric diseases (such as number (increased worsening depression due to apolipoprotein B) adiposopathic immune and ‒ Increased proportion of small, endocrine responses) dense, low-density lipoprotein • Asthma (due to adiposopathic particles immune and endocrine responses) ‒ Increased triglyceride-rich • Worsening of other inflammatory lipoproteins diseases (osteoarthritis, ‒ Increased lipoprotein-remnant atherosclerosis, etc.) lipoproteins Reference/s: [3] [4] [6] [7] [21] 14 Eat Fewer Calories than you Burn = Lose Weight Simple? Obesity pages S1‐S26, 7 JUL 2015 DOI: 10.1002/oby.21140 15 http://onlinelibrary.wiley.com/doi/10.1002/oby.21140/full#oby21140‐fig‐0004 5 Please Respond…Obesity often occurs when eating is used as a form of compensation for lack of love or attention. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 16 Elements of Intensive Lifestyle Management 1) Food Plan (Multiple methods are effective) • Restrict/reduce intake of certain food types (low carbohydrate for metabolic syndrome, low fat) • Set a caloric goal (1,200‐1,500 kcal/day for women, 1,500‐1,800 kcal/day for men, adjusted for body weight) • Specify a caloric deficit (500 or 750 kcal/ day) • Consider patient preferences and health status when iden fying a diet―a variety of approaches can produce weight loss 17 Elements of Intensive Lifestyle Management 2) Increased Physical Activity • Start with where they are and increase, either duration or intensity Ideal Plan – Aerobic activity > 150 min/week for weight loss – Resistance training to preserve lean mass – Stretching/Flexibility – Balance/Core 18 6 Elements of Intensive Lifestyle Management 3) Behavioral Interventions ‐ critically important Ideal • Face‐to‐face sessions (≥14 with a trained interventionist over the first 6 months) • Maintain efforts over 1 year • Incorporate strategies such as goal‐ setting and self‐monitoring • May need to refer to a counselor 19 CMS Coverage for Intensive Behavioral Therapy • For Medicare beneficiaries with obesity, who are competent and alert at the time that counseling is provided and whose counseling is furnished by a qualified primary care physician or other primary care practitioner and in a primary care setting, CMS covers: • One face‐to‐face visit every week for the first month; • One face‐to‐face visit every other week for months 2‐6; • One face‐to‐face visit every month for months 7‐12, if the beneficiary meets the 3kg weight loss requirement during the first six months as discussed below. https://www.cms.gov/Outreach‐and‐Education/Medicare‐Learning‐Network‐ MLN/MLNMattersArticles/downloads/MM8874.pdf 20 Adjunct Therapies or Tools Obesity pages S1‐S26, 7 JUL 2015 DOI: 10.1002/oby.21140 21 http://onlinelibrary.wiley.com/doi/10.1002/oby.21140/full#oby21140‐fig‐0002 7 Misperception‐Surgery is a Cop‐out Truth: • Individuals affected by obesity are resistant to long‐term weight loss by diet and exercise for a variety of physiological reasons • Surgery is a tool that impacts the gut‐brain‐ adipose tissue hormonal cycle Adapted from ASMBS website 22 Misperception: Most people who have metabolic surgery regain their weight Truth: • “Successful” weight loss is a loss of at least 50% of excess body weight and the impact on quality of life • Longitudinally, most surgical patients maintain their weight loss • Up to 50% may regain some weight (5%) two or more years after surgery Adapted from ASMBS website 23 Misconception: Metabolic surgery is very dangerous Truth: • Risk of death within 30 days is 0.13 %; less than cholecystectomy and hip replacement • Multiple studies have now shown that the benefits of bariatric surgery far outweigh the risks as compared to those who did not have surgery Adapted from ASMBS website 24 8 Misconception: Bariatric surgery causes serious vitamin and mineral deficiencies Truth: • Malabsorption can cause deficiencies and are totally avoidable with current recommendations • The current guidelines are increasingly evidence‐based and simpler than in the past Adapted from ASMBS website 25 Please Respond…In many cases, obesity is the result of a biological disorder. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 26 Bariatric Surgery in U.S. ‐ 2015 Total Procedures: 179,000 Sleeve gastrectomy 51% RYGB 27% Revisions 11.5% Gastric banding 9.5% Other 1% 27 9 Definition of Success • 50% Excess Body Weight (EBW) lost • Fewer chronic illnesses • Decreased number of medications taken • No more CPAP • Quality of Life improvements • Can walk one mile • My entire life will be better • REALISTIC EXPECTATIONS 28 Most Common Surgical Procedures Sleeve gastrectomy Roux‐en‐Y gastric bypass (sleeve) (RYGB or bypass) 29 Pre‐operative Recommendations • Complete H & P – assess co‐morbidities, weight loss history, commitment, exclusions for surgery • Lab – CMP, lipid profile, CBC, HgbA1C – iron studies, B12, folic acid, 25‐hydroxyvitamin D – additional evaluation as indicated • Identify and optimize the most common obesity‐related and post‐operative conditions 30 10 Pre‐operative Recommendations • Nutrition evaluation by and RD – Ability to incorporate nutritional and behavioral changes • Psychosocial‐behavioral evaluation – Active psych illness, substance abuse • Pregnancy counseling – Avoid pre‐op and 12‐18 months post‐op • Tobacco cessation counseling – smoking leads to poor wound healing 31 Pre‐operative Recommendations Consider • Cardiopulmonary evaluation – polysomnography, ECG, additional evaluation if cardiac disease or pulmonary hypertension suspected • GI evaluation – H.pylori screening in high prevalence areas – gallbladder evaluation – upper endoscopy if clinically indicated • Abdominal pain from non‐surgical causes can be challenging to diagnose 32 Pre‐operative Recommendations • Age‐ and risk‐appropriate cancer screening – Surgeons count on the PCP • Weight loss via medical nutrition therapy – Benefit not clear except in pt with diabetes – Often done 2 weeks pre‐op – Can reduce liver volume – Can improve access for laparoscopic procedure 33 11 Requirements‐Insurance Specific • Plan exclusions • 3 or 6 month program – Can be individual components, or – Via Interdisciplinary team/Center • Frequent changes to requirements 34 Please Respond…Obesity is usually caused by overeating. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 35 Post‐surgery • Avg. 1‐2 nights in hospital • Avg. 2 weeks out of work • Diet advanced from clears, liquids, to purees – Most recommend about one month to regular food – Adequate hydration (usually > 1.5 L/day) • Adjust postoperative medications, as needed – Diabetes meds should be decreased at discharge • Metformin should be continued – Blood sugar monitoring critical in first weeks – Hypertension meds require close attention 36 12 Post‐operative Care Usually done by the surgeon: 1, 3 months – CBC, CMP 6 months – CBC, CMP, lipids, – B12 (if supplemented), 25‐ vitamin D‐OH, folic acid, iron studies, iPTH – 24 hour urine calcium 37 Post‐surgery and Ongoing Recommendations • Two multivitamins/day • Calcium citrate 1200‐1500 mg/day • B12 1000 mcg/day (PO or intranasal) • Elemental iron 45‐60 mg/day • Vitamin D3, at least 3000 IU/day (titrate to >30ng/mL Surgery for Obesity and Related Diseases 9 (2013) 159‐191 38 Ongoing Care • Avoid NSAIDs • Avoid pregnancy for 12‐18 months Support dietary, behavioral, and physical activity changes and recommendations – Support groups (program provided) – Behavioral counseling (refer if indicated) – Physical activity (it is important!) 39 13 Ongoing Care Most surgeons/programs try to follow patients for at least five years, but patients sometimes stop going. Annually • lipid profile, CMP, CBC, 25‐ vitamin D‐OH, B12, folic acid, iron studies, iPTH • 24‐hour urinary calcium • Bone density (DXA) at 2 years 40 Check if Symptomatic Symptoms Check level Unexplained anemia, fatigue, persistent diarrhea, cardiomyopathy, metabolic selenium bone disease Hair loss (after first year), pica, dysgeusia, erectile dysfunction zinc Anemia, neutropenia, myeloneuropathy, impaired wound healing copper Excessively rapid weight loss, protracted vomiting, excessive alcohol use, thiamine neuropathy or encephalopathy or heart failure 41 Please Respond…Most obese people cause their problem by not getting enough exercise. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 42 14 Lap Band • Band needs to be filled to create restriction/lead to weight loss • Reflux is common, but should be evaluated with upper GI • Many more complications than anticipated for the “least invasive” procedure 43 44 Laparoscopic Adjustable Gastric Banding A surgical procedure where an adjustable band is placed around the upper stomach creating a small pouch. The band diameter is adjustable through introduction of saline via a subcutaneous port that can be accessed from the upper abdomen. General Potential Acute Complications Potential Chronic Complications • Outpatient procedure • Band too tight with • Weight regain or no weight • Recovery usually one gastrointestinal obstructive loss week symptoms (i.e., dysphagia) • Band slippage, erosion, • Contra‐indications: • Leakage of gastric contents ulceration, port infection, ‒ Poor surgical candidate into abdomen disconnection, and ‒ Severe physical • Hemorrhage displacement disorder • Gastrointestinal bleeding • Esophageal dilation ‒ Intolerance to general • Infection • Rare nutrient deficiencies if anesthesia • Cardiac dysrhythmias persistent vomiting or marked ‒ Pregnancy • Atelectasis and pneumonia and sustained decrease in ‒ Drug or alcohol • Deep vein thrombosis nutritional intake addiction • Death • Depression ‒ Untreated esophagitis • Potential need to re‐operate Reference/s: [5] [177] [178] 45 15 Sleeve Gastrectomy A surgical procedure wherein the stomach is reduced to about 25 percent of its original size by the surgical removal of a large portion of the stomach along the greater curvature, resulting in a narrower sleeve or tube-like structure. General Potential Acute Complications • Hospital stay = 1‐2 days • Gastrointestinal obstruction • Recovery = 1‐2 weeks • Hemorrhage • Contra‐indications: • Gastrointestinal bleeding ‒ Poor surgical candidate • Anastomotic staple line leaks ‒ Severe psychiatric disorder • Infection ‒ Intolerance to general anesthesia • Cardiac dysrhythmias ‒ Pregnancy • Atelectasis and pneumonia ‒ Drug or alcohol addiction • Deep vein thrombosis ‒ Untreated or severe esophagitis • Pulmonary emboli ‒ Barrett’s esophagus • Rhabdomyolysis ‒ Severe gastroparesis • Dehydration ‒ Achalasia • Death ‒ Previous gastrectomy ‒ Previous gastric bypass ‒ Sometimes used as a staged approach to Reference/s: [5] [178] [179] ggastric bypassyp 46 Sleeve Gastrectomy Potential Chronic Complications • Weight regain or lack of long‐term weight • Other nutritional and mineral deficiencies loss (i.e., deficiencies of vitamins A, C, D, E, B, • Marginal ulcers and K, folate, zinc, magnesium, thiamine, • Esophageal dilation etc.) • Dumping syndrome with reactive • Anemia (often related to mineral and hypoglycemia nutrition deficiencies) • Small bowel obstruction caused by internal • Metabolic acidosis hernias or adhesions • Bacterial overgrowth • Luminal stenoses (stomal narrowing) • Kidney stones (oxalosis) • Anastomotic staple‐line leak • Neuropathies (resulting from nutritional • Fistula formation deficiencies) • Gallstones • Osteoporosis (often caused by calcium • Calcium deficiency deficiency and chronically elevated • Secondary hyperparathyroidism parathyroid hormone levels) • Iron deficiency • Depression • Protein malnutrition • Potential need to re‐operate Reference/s: [5] [178] [179] 47 Gastric Bypass A surgical procedure wherein the stomach is divided into a large residual section and a smaller section (pouch) that is attached to a limb of the small intestine at variable distances from the first part of the small intestine, largely bypassing the stomach and part of the duodenum. General Potential Acute Complications • Gastrointestinal obstruction • Hospital stay = 2‐4 days • Hemorrhage • Recovery = 1‐2 weeks • Gastrointestinal bleeding • Contra‐indications: • Anastomotic leaks ‒Poor surgical candidate • Infection ‒Severe psychiatric disorder • Cardiac dysrhythmias ‒Intolerance to general anesthesia • Atelectasis and pneumonia ‒Pregnancy • Deep vein thrombosis ‒Drug or alcohol addiction • Pulmonary emboli ‒Untreated esophagitis • Rhabdomyolysis ‒Unwillingness or an inability for • Dehydration appropriate long‐term follow up • Death Reference/s: [5] [177] [178] [179] 48 16 Gastric Bypass Potential Chronic Complications • Weight regain • Marginal ulcers • Protein malnutrition • Esophageal dilation • Other nutritional and mineral deficiencies • Dumping syndrome with reactive (i.e., deficiencies of vitamins A, C, D, E, B, and hypoglycemia K, folate, zinc, magnesium, thiamine, etc.) • Small bowel obstruction caused by internal • Anemia (often related to mineral and hernias or adhesions nutrition deficiencies) • Anastomotic stenoses (stomal narrowing) • Neuropathies (resulting from nutritional • Gallstones deficiencies) • Calcium deficiency • Osteoporosis (often caused by calcium • Secondary hyperparathyroidism deficiency and chronically elevated • Bacterial overgrowth parathyroid hormone levels) • Kidney stones (oxalosis) • Depression • Metabolic acidosis • Potential need to re‐operate • Iron deficiency Reference/s: [5] [177] [178] [179] 49 Comparison of Outcomes for Bariatric Surgical Procedures Outcome Overall Sleeve RYGB gastrectomy Excess body weight lost (%) median* 1 to 2 years 60 to 70 33 to 85 48 to 85 3 to 6 years 50 to 60 46 to 66 53 to 77 7 to 10 years 50 NA 25 to 68 Remission of diabetes mellitus < 1 year 80 56 to 68 56 to 84 1 to 3 years 72 80 46 to 81 15 years 30 NA NA Mortality 30 days (%) 0.08 0.296 0.20 to 0.50 > 30 days (%) 0.31 0.11-0.34 0.14-0.21 7-15 years 30 to 40% lower than those not having surgery NA = not available *Excess body weight is the total preoperative weight minus ideal weight. 50 Multiple references, available. New Procedures FDA Approval 8/15 (for patients with BMI of 30‐40) – ORBERA™ and – ReShape™ Intragastric Balloons Short term, no ghrelin suppression ASMBS views these balloon devices as a bridge between medications and bariatric surgery 51 17 Revisional Procedures Surgical • Band to sleeve or RYGB • Sleeve to RYGB (for refractory reflux) • Sleeve plus duodenal switch • Revision of RYGB (older pouches were larger) • Band over bypass (uncommon) Non‐surgical: ROSE, StomaphyX endoscope procedure –Not very effective Experimental: lap band plus gastric plication 52 Please Respond…Most obese people eat more than non‐obese people. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 53 Adjunct Therapies/ TOOLS Obesity pages S1‐S26, 7 JUL 2015 DOI: 10.1002/oby.21140 54 http://onlinelibrary.wiley.com/doi/10.1002/oby.21140/full#oby21140‐fig‐0002 18 Medication and Obesity First, Do No Harm 55 Identify and Manage Concomitant Pharmacotherapy That Might Alter Body Weight Cardiovascular Medications Diabetes Mellitus Medications May increase body weight May increase body weight • Some beta‐blockers • Most insulins ‒ Propranolol • Sulfonylureas ‒ Atenolol • Thiazolidinediones ‒ Metoprolol • Meglitinides • Dihydropyridine (“dipine”) calcium channel blockers May decrease body weight ‒ Nifedipine • Metformin ‒ Amlodipine • Glucagon‐like peptide‐1 ‒ Felodipine agonists • Sodium glucose co‐ transporter 2 inhibitors • Alpha glucosidase inhibitors Reference/s: [7] [18] [57] [69] 56 Identify and Manage Concomitant Pharmacotherapy That Might Alter Body Weight Hormones Anti‐seizure Medications May increase body weight May increase body weight • Glucocorticoids • Carbamazepine • Estrogens • Gabapentin • Valproate May decrease body weight • Progestins May decrease body weight • Testosterone • Lamotrigine • Topiramate • Zonisamide Reference/s: [18] [57] [73] [74] [75] [76] 57 19 Identify and Manage Concomitant Pharmacotherapy That Might Alter Body Weight Mood Stabilizers Migraine Medications May increase body weight May increase body weight • Gabapentin • Amitriptyline • Lithium • Gabapentin • Valproate • Paroxetine • Vigabatrin • Valproic acid • Some beta‐blockers Variable/neutral effects on body weight • Carbamazepine (sometimes May decrease body weight reported to increase body • Topiramate weight) • Lamotrigine (sometimes reported to decrease body weight) • Oxcarbazepine Reference/s: [18] [57] [73] [74] [75] [76] 58 Identify and Manage Concomitant Pharmacotherapy That Might Alter Body Weight Antipsychotics Hypnotics May substantially increase body weight May increase body weight • Clozapine • Diphenhydramine • Olanzapine • Zotepine May have limited effects on body weight • Benzodiazepines May somewhat increase body weight • Melatonergic hypnotics • Asenapine • Trazodone • Chlorpromazine • Iloperidone • Paliperidone • Quetiapine • Risperidone • Sertindole • Lithium Variable/neutral effects on body weight • Amisulpride • Aripiprazole • Haloperidol Reference/s: [18] [57] [73] [74] [75] • Lurasidone 59 • Ziprasidone Identify and Manage Concomitant Pharmacotherapy That Might Alter Body Weight Human Immunodeficiency Chemotherapies Virus (HIV) Medications May increase body weight May increase body weight • Tamoxifen • Some highly active antiretroviral • Cyclophosphamide therapies (HAART) protease • Methotrexate inhibitors without HIV • 5‐fluorouracil lipodystrophy • Aromatase inhibitors • Corticosteroids May decrease body weight • Some highly active antiretroviral therapies (HAART) protease inhibitors with HIV lipodystrophy Reference/s: [18] [57] [73] [74] [75] 60 20 Please Respond…The majority of obese people have poor eating habits that lead to their obesity. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 61 Anti-obesity Medications Adjunct to nutritional, physical activity, and behavioral therapies Objectives: • Treat disease ‒ Adiposopathy or sick fat disease (SFD) ‒ Fat mass disease (FMD) • Facilitate management of eating behavior • Slow progression of weight gain/regain • Improve the health, quality of life, and body weight of the patient with overweight or obesity Reference/s: [55] [159] 62 Pathologic Metabolic and/or Fat Mass Consequences of Increased Body Fat • 5-10 percent weight loss may improve adipocyte and adipose tissue metabolic and immune function – 5-10 percent weight loss may improve metabolic disease • 5-10 percent weight loss may improve abnormal and pathologic physical and mechanical forces – 5-10 percent weight loss may improve fat mass diseases Reference/s: [8] [160] [161] 63 21 When to Prescribe Medication for the Treatment of Obesity • History of difficulty achieving and maintaining weight loss with life style intervention alone (diet, physical activity, behavior change still need to happen) • Sufficient health risk to justify Tx with a med • BMI 30 or more or 27 with comorbidity • For weight maintenance • No contraindication 64 How to Choose? • Consider medical history and current medications • Shared decision making • Medical conditions (diabetes, depression, migraines, CVD, HTN, glaucoma) • Potential for pregnancy • Certain amount of trial and error • Insurance coverage/financial 65 Pharmacotherapy Examples of anti‐obesity Examples of anti‐obesity medications approved 1999 or medications approved 2012 and before beyond • Phentermine • Lorcaserin • Diethylpropion • Phentermine HCL/topiramate • Phendimetrazine extended release • Benzphetamine • Naltrexone HCL/bupropion HCL • Orlistat extended release • Liraglutide Reference/s: [500] [502] 66 22 Sympathomimetics Approved for Short Term Drug‐generic Dosage Mech of Common Side Contraindications Action Effects Phentermine AdipexP 37.5 mg Norepi‐ Headache, Anxiety disorders, (DEA class IV) Ionamin 30 mg releasing elev BP/HR, history of heart ‐longest ½ life 15‐37.5 mg/d agent insomnia, dry disease, uncontrolled mouth, HTN, seizure MAO constipation, inh, preg, palpitations, hyperthyroidism, changes in glaucoma, history of libido drug abuse Diethylpropion Tenuate 75mg SR Norepi‐ Similar to Similar to above (DEA class IV) 1x/day releasing above, ‐shorter ½ life 25mg 3x/day agent different pt response Phendiametra‐ Bontril 105mg SR Norepi‐ Similar Similar to above zine 36 mg. 2‐3x/day releasing, (DEA class III) dopaminergic 67 Please Respond…Obesity is rarely caused by a lack of willpower. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 68 Medications Approved for Chronic Weight Management Mechanism of Response Drug Dosing Action Evaluation Orlistat (Xenical) Pancreatic lipase inhibitor 120 mg orally with each Not addressed in label meal containing fat Lorcaserin (Belviq) 5‐HT2C serotonin agonist Little 10 mg orally twice daily Stop if <5% loss at 12 weeks affinity for other serotonergic receptors Phentermine/ Sympathomimetic Orally in the morning: At 12 weeks, op on to ↑ to TopiramateER Anticonvulsant (GABA 3.75 mg/23 mg ×14 days 11.25 mg/69 mg ×14 days, receptor modulation, 7.5/46 mg ×14 days then 15 mg/96 mg; (Qsymia) carbonic anhydrase inhibition, Stop if <5% loss at 12 weeks glutamate antagonism) on top dose NaltrexoneSR/ Opioid receptor antagonist Orally1 tab (8 mg/90 mg) Stop if <5% loss at 12 weeks BupropionSR Dopamine/noradrenaline 1 in am ×1 week; reuptake inhibitor 1 in am 1 in pm ×1 week; (Contrave) 2 in am 1 in pm ×1 week; 2 in am 2 in pm Liraglutide 3.0 mg GLP‐1 receptor agonist Inject subcutaneously (any Stop if <4% weight loss at (Saxenda) time of day); Initiate at 0.6 16 weeks mg per day ×1 week. In weekly intervals, increase the dose by 0.6 mg/week until a dose of 3.0 mg is 69 reached 23 Medications Approved for Chronic Weight Management: Drug/cost Caution Contraindications Side Effects Orlistat ↑cyclosporine Chronic malabsorption; All the symptoms of exposure; rare liver cholestasis, pregnancy and steatorrhea (oily failure; concomitant breastfeeding spotting, flatulence with multivitamin advised, discharge, increased gall bladder disease, defecation, etc.) warfarin, antiepileptic meds, Lorcaserin SSRI, SNRI/MAOI, St. Pregnancy and Headache, nausea, dry John’s wort, triptans, breastfeeding mouth, dizziness, buproprion, fatigue, constipation dextromethorphan, priapism, hypoglycemia if on other antidiabetic meds Phentermine/ Fetal toxicity; acute Glaucoma; active suicidal Insomnia, Topiramate myopia; cognitive ideation, hyperthyroidism; paraesthesias, dysfunction; metabolic MAOIs; pregnancy and dysgeusia, dizziness, dry ER acidosis; hypoglycemia breastfeeding mouth 70 Medications Approved for Chronic Weight Management Drug Cost Caution Contraindications Side Effects Naltrexone SR/ Suicidality, BP, HR,↑ Seizure disorder, Nausea, Bupropion SR seizure risk, glaucoma, uncontrolled HTN, vomiting, hepatotoxicity chronic opioid use, headache, MAOIs, Pregnancy and dizziness, breastfeeding insomnia Liraglutide 3.0mg Thyroid c‐cell tumors Patients with a personal Nausea, in rodents, acute or family history of vomiting, pancreatitis, acute medullary thyroid diarrhea, gallbladder disease, carcinoma or Multiple constipation, serious hypoglycemia Endocrine Neoplasia, dyspepsia, if used with insulin Pregnancy and abdominal pain secretagogue, heart breastfeeding rate increase; use caution in renal impairment; hypersensitivity reactions can occur; monitor for depression or suicidal thoughts. 71 Please Respond…People can be addicted to food, just as others are addicted to drugs, and these people usually become obese. A. Strongly Disagree B. Disagree C. Somewhat Disagree D. Neutral E. Somewhat Agree F. Agree G. Strongly Agree 72 24 Weight Bias • We all have bias • First, we must recognize it 73 Which surgical procedure for weight loss is performed most often in the US today? A. Gastric banding B. Sleeve gastrectomy C. Roux‐en‐Y gastric bypass D. Revision 74 Patients who have had a weight loss surgery procedure should not take NSAIDS. A. True B. False 75 25 Which of the following weight loss medications is not approved for long term use? A. phentermine ER/topirimate ER (Qsymia) B. lorcaserin (Belviq) C. liraglutide (Saxenda) D. phentermine (Adipex) 76 Questions? 77 26 Return to Top Case Studies of Common Behavioral Health Scenarios Case Studies of Common Behavioral Health Scenarios Matthew Wintersteen, Ph.D, Thomas Jefferson University/Jefferson Medical College Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Rethinking Adolescent Behavioral Health in Primary Care: Case Studies of Common Behavioral Health Scenarios Matthew B. Wintersteen, Ph.D. Thomas Jefferson University Department of Psychiatry & Human Behavior Philadelphia, PA 1 Disclosures • Dr. Matthew B. Wintersteen has no conflict of interest, financial agreement, or working affiliation with any group or organization. 2 Learning Objectives • Participants will learn about the common presentation of several behavioral health problems in primary care; • Participants will develop strategies to talk with patients experiencing behavioral health difficulties; • Participants will develop skills on effective referral of patients to behavioral health services and providers. 3 1 Case 1: Jimmy 4 Key Points from Video Vignette 1 • Fairly typical presentation for youth (particularly boys) • Some symptoms present: – Headaches – Sleep problems – Poor appetite 5 Key Points from Video Vignette 2 • Psychosocial assessment rolled into routine elements of exam • Brief assessment • Symptoms: – Increased stress at school – Increased social isolation – Decreased engagement in activities – Sleep impairment – Hopelessness – Irritability and mood lability – Increased cannabis use • Acknowledges morbid ideation • Denies suicidal ideation 6 2 Key Points from Video Vignette 3 • PCP persisted in asking about suicide risk despite patient’s initial denial • PCP re‐established trust by educating patient about depression and suicide – Listed symptoms – “Named” the problem • PCP remained calm throughout 7 Case 2: Katie 8 Katie: 17‐year‐old white female • Primary complaints: – Somatic complaints –headaches, stomach – Nausea and vomiting • Parent reports less eating – Sleep problems – difficulty falling asleep • Additional concerns: – Poor concentration at school • Grades declining (As Cs) – Generally hanging out in room while at home • No concerns about cleanliness or grooming 9 3 Concerns about Katie • Medical concerns? • Behavioral health? – Depression? – ADHD? – Anxiety? – Eating disorder? – Trauma? 10 How do we improve the chances of getting valid and reliable data? 11 Key Points (Shea, 2002) 1. Any hesitancy may = suicidal thoughts, even if followed by denial of these thoughts. 2. “No, not really” may = SI, but clinician may not be interested due to lack of serious consideration 3. Pay attention to body language indicative of deception or anxiety 4. Taking notes during assessment may = clinician disinterest – The clinician can document the assessment while also reviewing the accuracy of the information during a summary 5. Avoid any evidence of personal discomfort during the assessment interview. 6. Avoid appearing hurried – Individuals with borderline personality disorder, in particular, may be thrown into a state of emotional dysregulation when feeling rushed (Linehan, 1993). 12 4 Key Points –Adolescent Specific 1. Confidentiality limitations – Ethical obligation to inform, and the adolescent’s and parents’ right to know, about the limits of confidentiality prior to conducting any interviews. – Developing a strong therapeutic relationship may help reduce an adolescent’s underreporting and improve help seeking behaviors. 2. Strengthening interpersonal connections is a developmental marker of adolescence, thus their ability to talk about interpersonal experiences and to do so in an interpersonal context may be underdeveloped. 3. It can be helpful to talk about the adolescent’s fears of disclosing how he or she really feels. 4. Emphasize a team approach to managing the crisis. 5. Clinicians should always model hopefulness. 6. Do not be afraid to say the word “suicide” 13 6 Techniques to Generate Valid Data (Shea, 2002) 1. Behavioral Incident – Technique of asking about specific behavioral events or concrete trains of thought, not opinions. 2. Shame Attenuation – Meeting clients where they are emotionally, to help reduce shame in reporting. 3. Gentle Assumption – Designed to elicit sensitive material by gently making assumptions about the presence of some behaviors or thoughts. • For example, instead of asking an adolescent, “do you drink alcohol?” the clinician might begin with, “tell me about your alcohol use.” This suggests to the adolescent that the clinician is aware that alcohol use is a possible behavior and it is acceptable to discuss it. 14 6 Techniques to Generate Valid Data (Shea, 2002) 4. Symptom Amplification – Based on the assumption that patients often downplay the frequency or amount of their disturbing behavior. 5. Denial of the Specific – Denial of generic may not = denial of specific. – Do not combine more than one example into each question, or the clinician may find it necessary to then determine which example was being affirmed. 6. Normalization – Normalizing experiences, particularly for youth, may help generate an atmosphere where the individual’s experience is not unique or that he or she is not the “only one” affected by something, and that this experience can be discussed. 15 5 Now what? How do I improve my referral system? 16 Building a Referral Network • If you have a Medical Home, behavioral health should be included: – Behavioral health consultants – Social workers – Therapists • What if you don’t have a Medical Home? – Identify local BH providers • Insurance panels, MH/MR office, internet – Reach out and make the case – Host a meet‐and‐greet 17 Correspondence Regarding This Presentation May be Directed to: Matthew B. Wintersteen, Ph.D. Assistant Professor, Director of Research Thomas Jefferson University/Jefferson Medical College Department of Psychiatry & Human Behavior Division of Child & Adolescent Psychiatry 833 Chestnut Street, Suite 210 Philadelphia, PA 19107 (215) 503‐2824 – phone (215) 503‐2852 –fax [email protected] 18 6 Return to Top Opioid Prescribing: Safe Practice, Changing Lives Opioid Prescribing: Safe Practice, Changing Lives Edwin Salsitz, MD, Mount Sinai Beth Israel Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Presented by CO*RE Collaboration for REMS EducationPresented by CO*RE www.core-rems.orgCollaboration for REMS Education www.corerems.org Collaborative for REMS Education Collaborative for REMS Education Faculty Information Edwin Salsitz, MD, FASAM Assistant Professor of Medicine Icahn School of Medicine at Mount Sinai Medical Director Office-based Opioid Therapy, Mount Sinai Beth Israel New York City. New York DISCLOSURE: Dr. Salsitz and all staff involved with this content declare that neither they nor members of their immediate families have had financial relationships with the manufacturers of goods or services discussed, or corporate supporters of this event. 2 | © CO*RE 2015 Collaborative for REMS Education Collaborative for REMS Education On July 9, 2012, the Founded in June, 2010, the Food and Drug Collaborative on REMS Education Administration (FDA) (CO*RE), a multi disciplinary team of approved a Risk 10 partners and 3 cooperating Evaluation and organizations, has designed a core Mitigation Strategy curriculum based on needs assessment, (REMS) for extended- practice gaps, clinical competencies, release (ER) and long- and learner self-assessment to meet acting (LA) opioid the requirements of the FDA medications. REMS Blueprint. www.core-rems.org 3 | © CO*RE 2015 Collaborative for REMS Education 1 Organizations Founding Partners Strategic Partners American Pain Society (APS) Physicians Institute for Excellence in Medicine American Academy of Hospice and Palliative which coordinates 15 Medicine (AAHPM) state medical societies American Association of Nurse Practitioners Medscape (AANP) American Academy of American Academy of Physician Assistants (AAPA) Family Physicians American Osteopathic Association (AOA) American College of American Society of Addiction Medicine (ASAM) Emergency Physicians California Academy of Family Physicians (CAFP) (New in 2015) Healthcare Performance Consulting (HPC) Interstate Postgraduate Medical Association (IPMA) Nurse Practitioner Healthcare Foundation (NPHF) 4 | © CO*RE 2015 Collaborative for REMS Education Content Development/Planner/Reviewer Disclosures The following individuals disclose no relevant financial relationships: David Bazzo, MD Professor of Family Medicine, University of California San Diego School of Medicine Professor, Department of Family and Community Medicine, University of Kentucky College of Medicine Roberto Cardarelli, DO, COI NOTE: While Dr. Cardarelli is PI on a Pfizer grant, his employing institution (U of KY) receives those funds MPH to compensate for Dr. Cardarelli’s time. Ronald Crossno, MD Senior National Medical Director, Gentiva Health Services, Rockdale, TX Katherine Galluzzi, DO Professor and Chair, Department of Geriatrics, Philadelphia College if Osteopathic Medicine, Philadelphia, PA Carol Havens, MD Family physician and addiction medicine specialist, The Permanente Medical Group, Sacramento, CA Randall Hudspeth PhD, Practice and Regulation Consultant in Advanced Practice Pain Management and Palliative Care APRN‐CNP, FRE, FAANP Edwin A. Salsitz, MD, Beth Israel Medical Center, Division of Chemical Dependency; Assistant Professor, Albert Einstein College of FASM Medicine Barbara St. Marie, PhD, Supervisor, Pain and Palliative Care; Adult and Gerontology Nurse Practitioner, Pain Management, Associate ANP‐BC Faculty, University of Iowa College of Nursing, Iowa City, IA Cynthia Kear, CHCP, MDiv Senior Vice President, California Academy of Family Physicians, San Francisco, CA Jerri Davis, CHCP Director, Continuing Professional Development, California Academy of Family Physicians Robin and Neil Heyden Staff, CO*RE Operations Team, Heyden TY, Alameda, CA Julie Bruno, MSW LCSW Director, Education and Training, American Academy of Hospice and Palliative Medicine, Chicago, IL Anne Norman, DNP, Associate Vice President of Education, American Association of Nurse Practitioners APRN, FNP‐BC Marie Michelle‐Leger, MPH, PA‐C Director, Clinical Education, American Academy of Physician Assistants, Alexandria, VA Eric D. Peterson, EdM, Senior Director, Performance Improvement CME, American AcademyCollaborative of Physician Assistants for REMS Education FACEHP CO*RE Staff Disclosures The following individuals disclose no relevant financial relationships: Public Health Project Manager, Department of Research and Development, American Osteopathic Stephanie Townsell, MPH Association, Chicago, IL Sharon McGill, MPH Director, Department of Quality and Research, American Osteopathic Association, Chicago, IL Jennifer Reinard Education Manager, American Pain Society Catherine Underwood, MBA, CAE Chief Executive Officer, American Pain Society, Chicago, IL Arlene Deverman, CAE, CFRE Vice President, Professional Development, American Society of Addiction Medicine Penny Mills, MBA Executive Vice President and CEO, American Society of Addiction Medicine Chevy Chase, MD Thomas McKeithen Jr, BS, MBA Partners, Healthcare Performance Consulting Inc., Fleming Island, FL Chris Larrison Kate Nisbet, BBA, MBA Director of Health Systems Education, Interstate Postgraduate Medical Association Mary Ales, BA Executive Director, Interstate Postgraduate Medical Association, Madison, WI Pam Jenkins‐Wallace, MS, NP Program Director, NPHF Continuing Education Program Phyllis Zimmer, MN, FNP, FAAN President, Nurse Practitioner Healthcare Foundation, Bellevue, WA Sara Bennett Project Manager, Physicians’ Institute for Excellence in Medicine Adele Cohen, MS, PCMH CCE Senior Vice President, Physicians’ Institute for Excellence in Medicine, Atlanta, GA Piyali Chatterjee Director, Medical Education, Medscape, LLC New York ,NY Cyndi Grimes, CCMEP CME/CE Director, Medscape, LLC, New York, NY Sarah Williams, PhD Scientific Director, Medscape, LLC, New York, NY Cynthia Singh Director, Grants and Foundation Development, American College of Emergency Physicians Lori Foley Director, Strategic Partnerships, American College of Emergency Physicians, Irving, TX 6 | © CO*RE 2015 Collaborative for REMS Education 2 Acknowledgement Presented by the California Academy of Family Physicians, a member of the Collaborative on REMS Education (CO*RE), 13 interdisciplinary organizations working together to improve pain management and prevent adverse outcomes. This educational activity is supported by an independent educational grant from the ER/LA Opioid Analgesic REMS Program Companies. Please see http://ce.er-la- opioidrems.com/IwgCEUI/rems/pdf/List_of_RPC_Co mpanies.pdf for a listing of the member companies. This activity is intended to be fully compliant with the ER/LA Opioid Analgesic REMS education requirements issued by the US Food & Drug Administration. 7 | © CO*RE 20132015 Collaborative for REMS Education Products Covered by this REMS Brand Name Products Generic Products • Avinza® morphine sulfate ER capsules • Fentanyl ER transdermal • Butrans® buprenorphine transdermal system systems • Dolophine® methadone hydrochloride tablets • Methadone hydrochloride • Duragesic® fentanyl transdermal system tablets • Embeda® morphine sulfate/naltrexone ER capsules • Methadone hydrochloride oral concentrate • Exalgo® hydromorphone hydrochloride ER tablets • Hysingla® ER (hydrocodone bitartrate) ER tablets • Methadone hydrochloride oral solution • Kadian® morphine sulfate ER capsules • MethadoseTM methadone hydrochloride tablets • Morphine sulfate ER tablets • MS Contin® morphine sulfate CR tablets • Morphine sulfate • Nucynta® ER tapentadol ER tablets ER capsules • Opana® ER oxymorphone hydrochloride ER tablets • Oxycodone hydrochloride ® • OxyContin oxycodone hydrochloride CR tablets ER tablets • Targiniq™ oxycodone hydrochloride/naloxone hydrochloride ER tablets • Zohydro® hydrocodone bitartrate ER capsules 8 | © CO*RE 2015 Collaborative for REMS Education © CO*RE 2014 WHY PRESCRIBER EDUCATION IS IMPORTANT Introduction 9 | © CO*RE 2015 Collaborative for REMS Education 3 Prescribers of ER/LA Opioids Should Balance: The benefits The risks of prescribing of serious ER/LA opioids adverse to treat pain outcomes ER/LA opioid analgesics should be prescribed only by health care professionals who are knowledgeable in the use of potent opioids for the management of pain 10 | © CO*RE 2015 Collaborative for REMS Education Opioid Misuse/Abuse is a Major Public Health Problem Improper use of any opioid can result in serious AEs including overdose & death This risk can be greater w/ ER/LA opioids ER opioid dosage units contain more Methadone is a potent opioid with opioid than IR formulations a long, highly variable half-life In 2012 In 2011 37 million Americans age ≥12 488,004 ED visits involved had used an opioid for nonmedical use of opioids nonmedical use some • Methadone involved in 30% of time in their life prescription opioid deaths SAMHSA. (2013). Results from the 2012 National Survey on Drug Use and Health: Detailed Tables. NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD. SAMHSA. (2013). Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD. CDC. CDC Vital Signs. Prescription Painkiller Overdoses. Use and abuse of methadone as a painkiller. 2012. FDA. Questions and Answers: FDA approves a Risk Evaluation and Mitigation Strategy for Extended-Release and Long-Acting Opioid Analgesics. www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm309742.htm. 2012. 11 | © CO*RE 2015 Collaborative for REMS Education In 2011 41,340 Americans DIED FROM DRUG POISONINGS Nearly 17,000 deaths involved prescription opioids In 2008 NCHS Data Brief, No. 166, September 2014. http://www.cdc.gov/nchs/data/databriefs/db166.htm (accessed on 1/6/15). CDC. Policy Impact: Prescription Painkiller Overdoses. http://www.cdc.gov/homeandrecreationalsafety/rxbrief/ (Historical content - 2008 data) (accessed on 1/6/15). 12 | © CO*RE 2014 Collaborative for REMS Education 4 First-Time Use of Specific Drugs Among Persons Age ≥ 12 (2012) 3 2.5 2.4 2 1.9 1.5 1.4 1 0.9 0.7 0.6 0.6 Number in millions 0.5 0.4 0.2 0.2 0.1 0 SAMHSA. (2013). Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD. 13 | © CO*RE 2015 Collaborative for REMS Education Learning Objectives Describe appropriate patient assessment for treatment with ER/LA opioid analgesics, evaluating risks and potential benefits of ER/LA therapy, as well as possible misuse. Apply proper methods to initiate therapy, modify dose, and discontinue use of ER/LA opioid analgesics, applying best practices including accurate dosing and conversion techniques, as well as appropriate discontinuation strategies. Demonstrate accurate knowledge about how to manage ongoing therapy with ER/LA opioid analgesics and properly use evidence-based tools while assessing for adverse effects. Employ methods to counsel patients and caregivers about the safe use of ER/LA opioid analgesics, including proper storage and disposal. Review/assess general and product-specific drug information concerning ER/LA opioid analgesics and identifying potential adverse effects of ER/LA opioids. 14 | © CO*RE 2015 Collaborative for REMS Education Misuse, abuse, divergence and overdose of ER/LA opioids is a major public health crisis. YOU and YOUR TEAM can have an immediate and positive impact on this crisis while also caring for your patients appropriately. 15 | © CO*RE 2015 Collaborative for REMS Education 5 © CO*RE 2014 ASSESSING PATIENTS FOR TREATMENT WITH ER/LA OPIOID ANALGESIC THERAPY Unit 1 16 | © CO*RE 2015 Collaborative for REMS Education Balance Risks Against Potential Benefits Conduct thorough H&P Comprehensive benefit- and appropriate testing to-harm evaluation Benefits Include Risks Include • • Analgesia Overdose (adequate pain control) • Life-threatening respiratory depression • Improved Function • Abuse by patient or household contacts • Misuse & addiction • Physical dependence & tolerance • Interactions w/ other medications & substances • Risk of neonatal withdrawal syndrome w/ prolonged use during pregnancy • Inadvertent exposure/ingestion by household contacts, especially children Chou R, et al. J Pain. 2009;10:113-30. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. 2010. FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. Modified 08/2014. www.fda.gov/downloads/ Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf 17 | © CO*RE 2015 Collaborative for REMS Education Adequately DOCUMENT all patient interactions, assessments, test results, & treatment plans 18 | © CO*RE 2015 Collaborative for REMS Education 6 Clinical Interview: Patient Medical History Illness relevant to (1) effects or (2) metabolism of opioids 1. Pulmonary disease, constipation, nausea, cognitive impairment 2. Hepatic, renal disease Illness possibly linked to substance abuse, e.g.: Hepatitis HIV Tuberculosis Cellulitis Trauma, Cardiac Pulmonary STIs burns disease disease Chou R, et al. J Pain. 2009;10:113-30. Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc., 2010. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. 2010. 19 | © CO*RE 2015 Collaborative for REMS Education Clinical Interview: Pain & Treatment History Description of pain Onset/ Variations / Location Intensity Quality Duration Patterns / Rhythms What relieves the pain? What relieves the pain? What causes or increases pain? Effects of pain on physical, emotional, and psychosocial function Patient’s pain & functional goals Heapy A, Kerns RD. Psychological and Behavioral Assessment. In: Raj's Practical Management of Pain. 4th ed. 2008;279-95. Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc., 2010. 20 | © CO*RE 2015 Collaborative for REMS Education Clinical Interview: Pain & Treatment History, cont’d Pain Medications Past use Current use • Query state PDMP where available to confirm patient report • Contact past providers & obtain prior medical records • Conduct UDT Dosage • For opioids currently prescribed: opioid, dose, regimen, & duration ‒ Important to determine if patient is opioid tolerant General effectiveness Nonpharmacologic strategies & effectiveness 21 | © CO*RE 2015 Collaborative for REMS Education 7 Perform Thorough Evaluation & Assessment of Pain Components of Order diagnostic Seek objective patient evaluation tests (appropriate confirmatory data for pain to complaint) General: vital signs, Musculoskeletal Exam appearance, posture, • Inspection gait, & pain behaviors • Palpation Cutaneous or • Percussion trophic findings • Auscultation Neurologic exam • Provocative maneuvers Lalani I, Argoff CE. History and Physical Examination of the Pain Patient. In: Raj's Practical Management of Pain. 4th ed. 2008;177-88. Chou R, et al. J Pain. 2009;10:113-30. 22 | © CO*RE 2015 Collaborative for REMS Education Assess Risk of Abuse, Including Substance Use & Psychiatric Hx Obtain a complete Hx of current & past substance use • Prescription drugs • Illegal substances Social history also relevant • Alcohol & tobacco ‒ Substance abuse Hx does not prohibit treatment w/ ER/LA opioids but may Employment, cultural require additional monitoring & expert background, social consultation/referral network, marital history, • Family Hx of substance abuse & legal history, & other psychiatric disorders behavioral patterns • Hx of sexual abuse 23 | © CO*RE 2015 Collaborative for REMS Education Risk Assessment, cont’d Understand & Be knowledgeable use addiction about risk factors Conduct a UDT or abuse for opioid abuse screening tools • Personal or family • Assess potential • Understand Hx of alcohol or risks associated limitations drug abuse w/ chronic opioid therapy • Younger age • Manage patients • Presence of using ER/LA psychiatric opioids based on conditions risk assessment 24 | © CO*RE 2015 Collaborative for REMS Education 8 Risk Assessment Tools: Examples Administered Tool # of items By Patients considered for long-term opioid therapy: ORT Opioid Risk Tool 5patient SOAPP® Screener & Opioid Assessment for Patients w/ Pain 24, 14, & 5 patient DIRE Diagnosis, Intractability, Risk, & Efficacy Score 7 clinician Characterize misuse once opioid treatments begins: PMQ Pain Medication Questionnaire 26 patient COMM Current Opioid Misuse Measure 17 patient PDUQ Prescription Drug Use Questionnaire 40 clinician Not specific to pain populations: CAGE-AID Cut Down, Annoyed, Guilty, Eye-Opener Tool, 4 clinician Adjusted to Include Drugs RAFFT Relax, Alone, Friends, Family, Trouble 5patient DAST Drug Abuse Screening Test 28 patient SBIRT Screening, Brief Intervention, & Referral to Treatment Varies clinician 25 | © CO*RE 2015 Collaborative for REMS Education Opioid Risk Tool (ORT) Mark each box that applies Female Male 1. Family Hx of substance abuse Administer Alcohol 1 3 Illegal drugs 2 3 On initial visit Prescription drugs 4 4 2. Personal Hx of substance abuse Prior to opioid Alcohol 3 3 therapy Illegal drugs 4 4 Prescription drugs 5 5 Scoring (risk) 3. Age between 16 & 45 yrs 1 1 0-3: low 4. Hx of preadolescent sexual abuse 3 0 5. Psychologic disease 4-7: moderate ADD, OCD, bipolar, schizophrenia 2 2 Depression 1 1 ≥8: high Scoring Totals: Webster LR, Webster RM. Pain Med. 2005;6:432-42. 26 | © CO*RE 2015 Collaborative for REMS Education Screener & Opioid Assessment for Patients with Pain (SOAPP)® Identifies patients as at high, moderate, or low risk for misuse of opioids prescribed for chronic pain How is SOAPP® administered? Usually self- Prescribers should May be completed administered in have a completed as part of an waiting room, & scored SOAPP® interview w/ a exam room, or while making nurse, physician, prior to an opioid treatment or psychologist office visit decisions SOAPP® Monitoring Recommendations. https://painedu.org/soapp/SOAPP_Monitoring_Recommendations.pdf The SOAPP® Version 1.0 Tutorial. https://painedu.org/soapp-tutorial_01.asp 27 | © CO*RE 2015 Collaborative for REMS Education 9 Before Initiating Chronic Opioid Therapy Recognize that high risk patients, including those w/ significant psychiatric co-morbidities, may require specialty care Chronic opioid therapy may not be possible in the absence of needed specialty care Patients at risk for obstructive sleep apnea (OSA) are at increased risk for harm w/ use of chronic opioid therapy • Consider use of a screening tool for OSA • Refer patients for proper evaluation & treatment when indicated • Seek to ensure patients with OSA are compliant w/ treatment Pennsylvania Department of Drug and Alcohol Programs and Health. Pennsylvania Medical Society. Pennsylvania Guidelines on the Use Opioids to Treat Chronic Noncancer Pain. 2014. www.portal.state.pa.us/portal/server.pt/document/1432037/pamed_chronic_guidelines_pdf&sa=U&ei=djLuVKDoAYq_ggSNt4LwDg&ved= 0CAUQFjAA&client=internal-uds-cse&usg=AFQjCNEHB4iFzijNv8DoJztH4KSfb5gMwA 28 | © CO*RE 2013 Collaborative for REMS Education When to Consider a Trial of an Opioid Potential benefits are likely to outweigh risks Failed to adequately respond to nonopioid & nondrug interventions Continuous, around-the-clock opioid analgesic is needed for an extended period of time Pain is chronic and severe No alternative therapy is likely to pose as favorable a balance of benefits to harms Chou R, et al. J Pain. 2009;10:113-30. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. 2010. 29 | © CO*RE 2015 Collaborative for REMS Education When to Consider a Trial of an Opioid, cont’d 60-yr-old w/ chronic disabling OA pain • Nonopioid therapies not effective, IR opioids provided some relief but experienced end-of-dose failure • No psychiatric/medical comorbidity or personal/family drug abuse Hx ‒ High potential benefits relative to potential risks ‒ Could prescribe opioids to this patient in most settings w/ routine monitoring 30-yr-old w/ fibromyalgia & recent IV drug abuse • High potential risks relative to benefits (opioid therapy not 1st line for fibromyalgia) • Requires intensive structure, monitoring, & management by clinician w/ expertise in both addiction & pain ‒ Not a good candidate for opioid therapy Chou R, et al. J Pain. 2009;10:113-30. 30 | © CO*RE 2015 Collaborative for REMS Education 10 When to Consider a Trial of an Opioid, cont’d Selection of patients between these 2 extremes requires: Careful Structuring of care assessment & to match risk characterization In patients w/ Hx of substance abuse of patient risk or a psychiatric comorbidity, this may require assistance from experts in managing pain, addiction, or other mental health concerns In some cases opioids may not be appropriate or should be deferred until the comorbidity has been adequately addressed ‒ Consider referral Chou R, et al. J Pain. 2009;10:113-30. 31 | © CO*RE 2015 Collaborative for REMS Education Referring High-Risk Patients Prescribers should Understand when to appropriately refer Also check your state high-risk patients to regulations for pain management or requirements addiction specialists Chou R, et al. J Pain. 2009;10:113-30. 32 | © CO*RE 2015 Collaborative for REMS Education Special Considerations: Elderly Patients Does patient have medical problems that increase risk of opioid-related AEs? Respiratory depression more likely in elderly, cachectic, or debilitated patients • Altered PK due to poor fat stores, muscle wasting, or altered clearance • Monitor closely, particularly when − Initiating & titrating ER/LA opioids − Given concomitantly w/ other drugs that depress respiration • Reduce starting dose to 1/3 to 1/2 the usual dosage in debilitated, non- opioid-tolerant patients • Titrate dose cautiously Older adults more likely to develop constipation • Routinely initiate a bowel regimen before it develops Is patient/caregiver likely to manage opioid therapy responsibly? American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. J Am Geriatr Soc. 2009;57:1331- 46. Chou R, et al. J Pain. 2009;10:113-30. 33 | © CO*RE 2015 Collaborative for REMS Education 11 Special Considerations: Pregnant Women Managing chronic pain in pregnant women is challenging, & affects both mother and fetus Potential risks of opioid therapy to the newborn include: • Low birth weight • Neonatal death • Premature birth • Prolonged QT syndrome • Hypoxic-ischemic brain injury • Neonatal opioid withdrawal syndrome Given these potential risks, clinicians should: • Counsel women of childbearing potential about risks & benefits of opioid therapy during pregnancy & after delivery • Encourage minimal/no opioid use during pregnancy, unless potential benefits outweigh risks If chronic opioid therapy is used during pregnancy, anticipate & manage risks to the patient and newborns Chou R, et al. J Pain. 2009;10:113-30. 34 | © CO*RE 2015 Collaborative for REMS Education Special Considerations: Children (<18 years) Safety & effectiveness of most ER/LA opioids unestablished Pediatric analgesic trials pose challenges Transdermal fentanyl approved in children aged ≥2 yrs Oxycodone ER dosing changes for children ≥ 11 yrs (see Unit 6) Most opioid studies focus on inpatient safety Opioids are common sources of drug error Opioid indications are primarily life-limiting conditions Few children with chronic pain due to non-life-limiting conditions should receive opioids When prescribing opioids to children: Consult pediatric palliative care team or pediatric pain specialist or refer to a specialized multidisciplinary pain clinic Berde CB, et al. Pediatrics. 2012;129:354-64. Gregoire MC, et al. Pain Res Manag 2013;18:47-50. Mc Donnell C. Pain Res Manag. 2011;16:93-8. Slater ME, et al. Pain Med. 2010;11:207-14. 35 | © CO*RE 2013 Collaborative for REMS Education 355 | © CO*RE 2015 Unit 1 Pearls for Practice Document EVERYTHING Conduct a Comprehensive H&P General and pain-specific Assess Risk of Abuse Compare Risks with Expected Benefits Determine Whether a Therapeutic Trial is Appropriate 36 | © CO*RE 2015 Collaborative for REMS Education 12 © CO*RE 2014 INITIATING THERAPY, MODIFYING DOSING, & DISCONTINUING USE OF ER/LA OPIOID ANALGESICS Unit II 37 | © CO*RE 2015 Collaborative for REMS Education Federal & State Regulations Comply w/ federal & state laws & regulations that govern the use of opioid therapy for pain Federal State • Code of Federal Regulations, Title • Database of state statutes, 21 Section 1306: rules governing regulations, & policies for the issuance & filling of pain management prescriptions pursuant to section – www.medscape.com/resource/pain/opioid-policies 309 of the Act (21 USC 829) – www.painpolicy.wisc.edu/database-statutes- – www.deadiversion.usdoj.gov/21cfr/cfr/2106cfrt.htm regulations-other-policies-pain-management • United States Code (USC) - Controlled Substances Act, Title 21, Section 829: prescriptions – www.deadiversion.usdoj.gov/21cfr/21usc/829.htm 38 | © CO*RE 2015 Collaborative for REMS Education Chronic Opioid Therapy Chronic pain is best treated using an interdisciplinary, multi-modal approach Opioids should rarely be used as a sole treatment modality Consider opioids as an option within the context of multimodality therapy Treatment team often includes: • Patient & family • Behavioral health provider • Primary provider • ≥1 specialist • Physical therapist Patient outcomes are optimized when several treatments are used in a coordinated manner, eg: • Activating physical therapy • Proper use of medications & • Cognitive-behavioral therapy interventions when indicated Reliance on only one medication or treatment modality can lead to inadequate pain control & increased risk of harm Pennsylvania Department of Drug and Alcohol Programs and Health. Pennsylvania Medical Society. Pennsylvania Guidelines on the Use Opioids to Treat Chronic Noncancer Pain. 2014. www.portal.state.pa.us/portal/server.pt/document/1432037/pamed_chronic_guidelines_pdf&sa=U&ei=djLuVKDoAYq_ggSNt4LwDg&ved= 0CAUQFjAA&client=internal-uds-cse&usg=AFQjCNEHB4iFzijNv8DoJztH4KSfb5gMwA 39 | © CO*RE 2013 Collaborative for REMS Education 13 Opioid Prescribing: Additional Considerations Use caution in patients also taking benzodiazepines, due to increased risk of serious AEs When increasing a dose of chronic opioid therapy, counsel patient on the risk of cognitive impairment • Patient’s ability to drive or safely do other activities is affected • Risk is increased when opioids are taken w/ other centrally acting sedatives, including alcohol & benzodiazepine Total daily doses of >100 mg/day of oral MED is not associated w/ improved pain control, but w/ significant increase in risk of harm • Carefully consider if opioid doses >100 mg/day of oral MED are indicated • Consultation for specialty care may be appropriate for such patients MED = morphine equivalent dose Pennsylvania Department of Drug and Alcohol Programs and Health. Pennsylvania Medical Society. Pennsylvania Guidelines on the Use Opioids to Treat Chronic Noncancer Pain. 2014. www.portal.state.pa.us/portal/server.pt/document/1432037/pamed_chronic_guidelines_pdf&sa=U&ei=djLuVKDoAYq_ggSNt4LwDg&ved= 0CAUQFjAA&client=internal-uds-cse&usg=AFQjCNEHB4iFzijNv8DoJztH4KSfb5gMwA 40 | © CO*RE 2013 Collaborative for REMS Education Initiating Treatment Prescribers should regard initial treatment as a therapeutic trial May last from several weeks to several months Decision to proceed w/ long-term treatment should be intentional & based on careful consideration of outcomes during the trial Progress toward meeting Presence of opioid- therapeutic goals related AEs Changes in underlying Changes in psychiatric or pain condition medical comorbidities Identification of aberrant drug-related behavior, addiction, or diversion Chou R, et al. J Pain. 2009;10:113-30 41 | © CO*RE 2015 Collaborative for REMS Education ER/LA Opioid-Induced Respiratory Depression Chief hazard of Manifested by Instruct opioid agonists, reduced urge to patients/family including breathe & members to ER/LA opioids decreased call 911* • If not immediately respiration rate • Managed w/ close recognized & treated, • Shallow breathing observation, may lead to supportive measures, respiratory arrest • CO2 retention can & opioid antagonists, & death exacerbate opioid depending on sedating effects • Greatest risk: initiation patient’s clinical of therapy or after status dose increase Chou R, et al. J Pain. 2009;10:113-30. FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafety InformationforPatientsandProviders/UCM311290.pdf 42 | © CO*RE 2015 Collaborative for REMS Education 14 ER/LA Opioid-Induced Respiratory Depression More likely to occur Reduce risk • In elderly, cachectic, or debilitated • Proper dosing & titration are patients essential – Contraindicated in patients w/ • Do not overestimate dose when respiratory depression or conditions converting dosage from another that increase risk opioid product • If given concomitantly w/ other – Can result in fatal overdose w/ drugs that depress respiration first dose • Instruct patients to swallow tablets/capsules whole – Dose from cut, crushed, dissolved, or chewed tablets/capsules may be fatal, particularly in opioid-naïve individuals FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf 43 | © CO*RE 2015 Collaborative for REMS Education Initiating & Titrating: Opioid-Naïve Patients Monitor patients Individualize dosage by Drug & dose selection closely titration based on is critical for respiratory efficacy, tolerability, depression & presence of AEs Some ER/LA opioids or Especially within 24-72 h Check ER/LA opioid dosage forms are only of initiating therapy & product PI for minimum recommended for increasing dosage titration intervals opioid-tolerant patients Supplement w/ IR • ANY strength of transdermal fentanyl or hydromorphone ER analgesics (opioids • Certain strengths/doses of & nonopioid) if pain other ER/LA products (check is not controlled drug PI) during titration The ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life-threatening respiratory depression. www.er-la-opioidrems.com/IwgUI/rems/pdf/important_safety_information.pdf. 2012. Chou R, et al. J Pain. 2009;10:113-30. FDA. Blueprint for Prescriber Education for ER/LA Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafety InformationforPatientsandProviders/UCM311290.pdf 44 | © CO*RE 2015 Collaborative for REMS Education Initiating: Opioid-Tolerant Patients If opioid tolerant – no restrictions on which products can be used Patients considered opioid tolerant are taking at least – 60 mg oral morphine/day – 25 mcg transdermal fentanyl/hr – 30 mg oral oxycodone/day – 8 mg oral hydromorphone/day For 1 Wk – 25 mg oral oxymorphone/day Or Longer – An equianalgesic dose of another opioid Still requires caution when rotating a patient on an IR opioid to a different ER/LA opioid The ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life-threatening respiratory depression. www.er-la-opioidrems.com/IwgUI/rems/pdf/important_safety_information.pdf. 2012. 45 | © CO*RE 2015 Collaborative for REMS Education 15 Opioid Rotation Definition: Change from an existing opioid regimen to another opioid w/ the goal of improving therapeutic outcomes or to avoid AEs attributed to the existing drug, e.g., myoclonus Rationale: Differences in pharmacologic or other effects make it likely that a switch will improve outcomes • Effectiveness & AEs of different mu opioids vary among patients • Patients show incomplete cross-tolerance to new opioid – Patient tolerant to 1st opioid can have improved analgesia from 2nd opioid at a dose lower than calculated from an EDT Fine PG, et al. J Pain Symptom Manage. 2009;38:418-25. Knotkova H, et al. J Pain Symptom Manage. 2009;38:426-39. Pasternak GW. Neuropharmacol. 2004;47(suppl 1):312-23. 46 | © CO*RE 2015 Collaborative for REMS Education Equianalgesic Doses Opioid rotation requires calculation of an approximate equianalgesic dose Equianalgesic dose is a construct derived from relative Relative potency estimates opioid potency estimates • Potency refers to dose required • Ratio of doses necessary to produce a given effect to obtain roughly equivalent effects • Calculate across drugs or routes of administration • Relative analgesic potency is converted into an equianalgesic dose by applying the dose ratio to a standard 47 | © CO*RE 2015 Collaborative for REMS Education Equianalgesic Dose Tables (EDT) Many different versions: Published Online Online Interactive Smart-phone apps Vary in terms of: Whether ranges Equianalgesic values are used Which opioids May or may not include transdermal opioids, rapid-onset are included: fentanyl, ER/LA opioids, or opioid agonist-antagonists 48 | © CO*RE 2015 Collaborative for REMS Education 16 Example of an EDT for Adults Equianalgesic Dose Usual Starting Doses Drug SC/IV PO Parenteral PO 5-15 mg q3-4hr 2.5-5 mg SC/IV q3-4hr Morphine 10 mg 30 mg (IR or oral solution) ( 1.25 – 2.5mg) ( 2.5-7.5 mg) 5-10 mg q3-4 Oxycodone NA 20 mg NA ( 2.5 mg) 5 mg q3-4h ( 2.5 mg) Hydrocodone NA 30 mg NA 1-2 mg q3-4hr 0.2-0.6 mg SC/IV q2-3hr Hydromorphone 1.5 mg 7.5 mg ( 0.5-1 mg) ( 0.2mg) 49 | © CO*RE 2015 Collaborative for REMS Education Limitations of EDTs Single-dose potency studies using a specific route, conducted in patients w/ limited opioid exposure Did Not Consider Chronic dosing High opioid doses Other routes Gender, ethnicity, Comorbidities or advanced age, or Different pain types organ dysfunction concomitant medications Inter-patient Direction of switch Incomplete cross- variability in from 1 opioid to tolerance among pharmacologic another mu opioids response to opioids 50 | © CO*RE 2015 Collaborative for REMS Education Utilizing Equianalgesic Doses Incomplete cross-tolerance & inter-patient variability require use of conservative dosing when converting from one opioid to another Equianalgesic dose a starting point for opioid rotation Intended as General Guide Calculated dose of new drug Closely follow patients based on EDT must be during periods of dose reduced, then titrate the adjustments new opioid as needed Follow conversion instructions in individual ER/LA opioid PI, when provided 51 | © CO*RE 2015 Collaborative for REMS Education 17 Guidelines for Opioid Rotation Reduce calculated equianalgesic dose by 25%-50%* Select % reduction based on clinical judgment Calculate Closer to 50% reduction if Closer to 25% reduction equianalgesic patient is if patient dose of new opioid from • Receiving a relatively • Does not have these EDT high dose of current characteristics opioid regimen • Is switching to • Elderly or a different medically frail administration route of same drug *75%-90% reduction for methadone 52 | © CO*RE 2015 Collaborative for REMS Education Guidelines for Opioid Rotation, cont’d If switching to methadone: • Standard EDTs are less helpful in opioid rotation to methadone • In opioid tolerant patients, methadone doses should not exceed 30-40 mg/day upon rotation. • Consider inpatient monitoring, including serial EKG monitoring • In opioid-naïve patients, methadone should not be given as an initial drug If switching to transdermal: • Fentanyl, calculate dose conversion based on equianalgesic dose ratios included in the PI • Buprenorphine, follow instructions in the PI 53 | © CO*RE 2014 Collaborative for REMS Education Guidelines for Opioid Rotation, cont’d Have a strategy to frequently assess analgesia, AEs and withdrawal symptoms Titrate new opioid dose to optimize outcomes & safety Dose for breakthrough pain (BTP) using a short-acting, immediate release preparation is 5%-15% of total daily opioid dose, administered at an appropriate interval If oral transmucosal fentanyl product is used for BTP, begin dosing lowest dose irrespective of baseline opioid dose NEVER use ER/LA opioids for BTP 54 | © CO*RE 2015 Collaborative for REMS Education 18 Breakthrough Pain in Chronic Pain Patients Patients on stable ATC opioids may Therapies Consider adding experience BTP Disease progression • Directed at cause • PRN IR opioid trial based or a new or of BTP or on analysis of benefit unrelated pain precipitating factors versus risk ‒ Risk for aberrant drug-related • Nonspecific behaviors symptomatic therapies ‒ High-risk: only in conjunction w/ to lessen impact frequent monitoring & follow-up of BTP ‒ Low-risk: w/ routine follow-up & monitoring • Nonopioid drug therapies • Nonpharmacologic treatments 55 | © CO*RE 2015 Collaborative for REMS Education Reasons for Discontinuing ER/LA Opioids No progress toward Intolerable & Pain level decreases in therapeutic goals Unmanageable AEs stable patients Nonadherence or Aberrant behaviors suggestive unsafe behavior of addiction &/or diversion • 1 or 2 episodes of increasing dose • Use of illicit drugs or without prescriber knowledge unprescribed opioids • Sharing medications • Repeatedly obtaining opioids • Unapproved opioid use to treat from multiple outside sources another symptom (e.g., insomnia) • Prescription forgery • Multiple episodes of prescription loss 56 | © CO*RE 2015 Collaborative for REMS Education Challenge: The Broken Stereotype Ms. Yeun seems like a “good” patient. She Red Flag: has never abused opioids previously. She has been in the practice a long time, has never been a problem, and in fact, is rather Making enjoyable. She always brings Christmas assumptions cookies for the staff around the holidays. about a patient’s risk Action: Require all patients receiving opioids factors without to follow a treatment plan and adhere to objective defined expectations. Evaluate risk in all evidence patients. Use patient-provider agreements, contracts, or other tools. 57 | © CO*RE 2015 Collaborative for REMS Education 19 Unit 2 Pearls for Practice Treat Initiation of Opioids as a Therapeutic Trial Anticipate ER/LA Opioid-Induced Respiratory Depression It can be immediately life-threatening Be Conservative and Thoughtful In Dosing When initiating, titrating, and rotating opioids First calculate equinalgesic dose, then reduce dose appropriately Discontinue ER/LA opioids slowly and safely 58 | © CO*RE 2015 Collaborative for REMS Education © CO*RE 2014 MANAGING THERAPY WITH ER/LA OPIOID ANALGESICS Unit III 59 | © CO*RE 2015 Collaborative for REMS Education Informed Consent Before initiating a trial of opioid analgesic therapy, confirm patient understanding of informed consent to establish: Analgesic & functional goals of treatment The potential for & how to manage: • Common opioid-related AEs Expectations (e.g., constipation, nausea, sedation) • Other serious risks (e.g., abuse, addiction, respiratory depression, overdose) Potential risks • AEs after long-term or high-dose opioid therapy (e.g., hyperalgesia, endocrinologic or Alternatives to opioids sexual dysfunction) 60 | © CO*RE 2015 Collaborative for REMS Education 20 Patient-Prescriber Agreement (PPA) Document signed by both patient & prescriber at time an opioid is prescribed Clarify treatment plan & goals of treatment w/ patient, patient’s family, & other clinicians involved in patient’s care Assist in patient education Inform patients about the risks & benefits Document patient & prescriber responsibilities 61 | © CO*RE 2015 Collaborative for REMS Education Consider a PPA Reinforce expectations for appropriate & safe opioid use • Obtain opioids from a • Commitments to return for single prescriber follow-up visits • Fill opioid prescriptions at a • Comply w/ appropriate designated pharmacy monitoring • Safeguard opioids – E.g., random UDT & pill counts – Do not store in medicine • Frequency of prescriptions cabinet • Enumerate behaviors that – Keep locked (e.g., use a may lead to opioid medication safe) discontinuation – Do not share or sell medication • An exit strategy • Instructions for disposal when no longer needed 62 | © CO*RE 2015 Collaborative for REMS Education Periodic Review Reassess patients on chronic opioid therapy periodically & as warranted by changing circumstances Monitoring should include documentation of: Response to therapy: • Pain intensity • Physical & mental functioning, including activities of daily living • Assessment of progress toward achieving therapeutic goals Presence of AEs Adherence to prescribed therapies Presence of aberrant drug-related behaviors (ADRBs) Increase frequency of ongoing monitoring for patients identified to be at increased risk of ADRBs Pennsylvania Department of Drug and Alcohol Programs and Health. Pennsylvania Medical Society. Pennsylvania Guidelines on the Use Opioids to Treat Chronic Noncancer Pain. 2014. www.portal.state.pa.us/portal/server.pt/document/1432037/pamed_chronic_guidelines_pdf&sa=U&ei=djLuVKDoAYq_ggSNt4LwDg&ved= 0CAUQFjAA&client=internal-uds-cse&usg=AFQjCNEHB4iFzijNv8DoJztH4KSfb5gMwA 63 | © CO*RE 2013 Collaborative for REMS Education 21 Monitor Patients During Opioid Therapy Therapeutic risks & Periodically assess benefits do not Identify patients continued need for remain static opioid analgesic Affected by change in • Who are benefiting from Re-evaluate underlying underlying pain opioid therapy medical condition condition, coexisting • Who might benefit more if clinical presentation disease, or w/ restructuring of changes psychologic/ social treatment or receiving circumstances additional services (e.g., addiction treatment) • Whose benefits from treatment are outweighed by risks 64 | © CO*RE 2015 Collaborative for REMS Education Monitor Patients During Opioid Therapy, cont’d Patients requiring more Periodically evaluate: frequent monitoring include: • Pain control • High-risk patients – Document pain intensity, pattern, • Patients taking high opioid doses & effects • Functional outcomes – Document level of functioning – Assess progress toward achieving therapeutic goals • Health-related QOL • AE frequency & intensity • Adherence to prescribed therapies 65 | © CO*RE 2015 Collaborative for REMS Education Anticipate & Treat Common AEs most common AE; does not Nausea & tend to diminish over Constipation resolve with time vomiting days or weeks . Initiate a bowel regimen before constipation develops . Increase fluid & fiber intake, stool Oral & rectal antiemetic therapies as needed softeners, & laxatives . Opioid antagonists may help prevent/treat opioid-induced bowel dysfunction Drowsiness & Pruritus & tend to diminish over tend to wane over time sedation myoclonus days or weeks Counsel patients about driving, work & home Treatment strategies for either condition safety as well as risks of concomitant exposure largely anecdotal to other drugs & substances w/ sedating effects Chou R, et al. J Pain. 2009;10:113-30 66 | © CO*RE 2015 Collaborative for REMS Education 22 Monitor Adherence and Aberrant Behavior Routinely monitor patient adherence to treatment plan • Recognize & document aberrant drug-related behavior – In addition to patient self-report also use: • State PDMPs, where available • UDT – Positive for nonprescribed drugs – Positive for illicit substance – Negative for prescribed opioid • Family member or caregiver interviews • Monitoring tools such as the COMM, PADT, PMQ, or PDUQ • Medication reconciliation (e.g., pill counts) PADT=Pain Assessment & Documentation Tool 67 | © CO*RE 2015 Collaborative for REMS Education Address Aberrant Drug-Related Behavior Behavior outside the boundaries of agreed-on treatment plan: Behaviors that are less Behaviors that are more indicative of aberrancy indicative of aberrancy Unsanctioned dose escalations or Multiple dose escalations or other other noncompliance w/ therapy noncompliance w/ therapy despite on 1 or 2 occasions warnings Unapproved use of the drug to Prescription forgery treat another symptom Openly acquiring similar drugs Obtaining prescription drugs from from other medical sources nonmedical sources 68 | © CO*RE 2015 Collaborative for REMS Education Prescription Drug Monitoring Programs (PDMPs) 48 states have an operational PDMP 1 state & DC have enacted PDMP legislation, not yet operational 1 state has no legislation Individual state laws determine • Who has access to PDMP information • Which drug schedules are monitored • Which agency administers the PDMP • Whether prescribers are required to register w/ the PDMP • Whether prescribers are required to access PDMP information in certain circumstances • Whether unsolicited PDMP reports are sent to prescribers 69 | © CO*RE 2015 Collaborative for REMS Education 23 PDMP Benefits Record of a patient’s Provide warnings of controlled substance potential misuse/abuse prescriptions • Some are available • Existing prescriptions not online 24/7 reported by patient • Opportunity to discuss • Multiple w/ patient prescribers/pharmacies • Drugs that increase overdose risk when taken together • Patient pays for drugs of abuse w/ cash Prescribers can check their own prescribing Hx 70 | © CO*RE 2015 Collaborative for REMS Education Pennsylvania Prescription Monitoring Program No access for prescribers or dispensers in current system New system planned to go into effect June 30, 2015: ABC-MAP (Achieving Better Care by Monitoring All Prescriptions Program) Planned improvements: • Expands access to prescribers & dispenser & others • Dispensing of controlled substances reported within 72 hours • Prescribers required to query the system: ‒ for each patient the first time a controlled substance is prescribed ‒ if prescriber believes that patient may be abusing or diverting drugs • Allows use of delegates (employees) to access the database Pennsylvania Medical Society. Prescription Drug Database Soon a Reality for PA Physicians. October 2014. www.pamedsoc.org/database National Alliance For Model State Drug Laws. Compilation of State Prescription Monitoring Maps. June 2014. www.namsdl.org/library/593BC7A6-1372-636C-DD7A83E6A8F6F0BC 71 | © CO*RE 2013 Collaborative for REMS Education Aberrant Drug-Related Behavior (ADRB) For patients at high risk for ADRB consider: • Increasing frequency of ongoing monitoring • Referral for specialty care, including psychological, psychiatric, & addiction experts In patients who have engaged in ADRBs: Carefully determine if risks associated w/ chronic opioid therapy outweigh documented benefit Consider: • Restructuring therapy (frequency or intensity of monitoring) • Referral for assistance in management • Discontinuing chronic opioid therapy for patients who engage in ADRBs repeatedly Provide appropriate referral for addiction evaluation & treatment Pennsylvania Department of Drug and Alcohol Programs and Health. Pennsylvania Medical Society. Pennsylvania Guidelines on the Use Opioids to Treat Chronic Noncancer Pain. 2014. www.portal.state.pa.us/portal/server.pt/document/1432037/pamed_chronic_guidelines_pdf&sa=U&ei=djLuVKDoAYq_ggSNt4LwDg&ved= 0CAUQFjAA&client=internal-uds-cse&usg=AFQjCNEHB4iFzijNv8DoJztH4KSfb5gMwA 72 | © CO*RE 2013 Collaborative for REMS Education 24 PDMP Unsolicited Patient Threshold Reports Reports automatically generated on patients who cross certain thresholds when filling prescriptions. Available in some states. E-mailed to prescribers to Prescribers review records to confirm it is whom prescriptions were your patient & you wrote the prescription(s) attributed attributed to you If you wrote the prescription(s), patient If inaccurate, contact safety may dictate need to discuss the PDMP patient w/ other prescribers listed on report • Decide who will continue to prescribe for the patient & who might address drug abuse concerns. 73 | © CO*RE 2015 Collaborative for REMS Education Rationale for Urine Drug Testing (UDT) Help to identify drug misuse/addiction • Prior to starting opioid treatment Assist in assessing adherence during opioid therapy • As requirement of therapy w/ an opioid • Support decision to refer UDT frequency is based on clinical judgment Depending on patient’s display of aberrant behavior Check state regulations for and whether it is sufficient to requirements document adherence to treatment plan 74 | © CO*RE 2015 Collaborative for REMS Education Main Types of UDT Methods Initial testing w/ IA drug panels: • Classify substance as present or absent according to cutoff • Many do not identify individual drugs within a class • Subject to cross-reactivity • Either lab based or at POC Identify specific drugs &/or metabolites w/ sophisticated lab-based testing; e.g., GC/MS or LC/MS* • Specifically confirm the presence of a given drug – e.g., morphine is the opiate causing a positive IA* • Identify drugs not included in IA tests * GC/MS=gas chromatography/ mass spectrometry • When results are contested IA=immunoassay LC/MS=liquid chromatography/ mass spectrometry 75 | © CO*RE 2015 Collaborative for REMS Education 25 Detecting Opioids by UDT Most common opiate IA GC/MS or LC/MS will drug panels identify specific opioids • Detect “opiates” morphine & • Confirm presence of codeine, but doesn’t distinguish a drug causing a positive IA • Do not reliably detect • Identify opioids not included in semisynthetic opioids IA drug panels, including – Specific IA panels can be ordered semisynthetic & synthetic for some opioids • Do not detect synthetic opioids • Identify opioids not included in (e.g., methadone, fentanyl) IA drug panels, including semisynthetic & synthetic – Only a specifically directed IA panel will detect synthetics opioids 76 | © CO*RE 2015 Collaborative for REMS Education Interpretation of UDT Results Demonstrates recent use Positive • Most drugs in urine have detection times of 1-3 d Result • Chronic use of lipid-soluble drugs: test positive for ≥1 wk Does not diagnose • Drug addiction, physical dependence, or impairment Does not provide enough information to determine • Exposure time, dose, or frequency of use Does not diagnose diversion Negative • More complex than presence or absence of a drug in urine Result May be due to maladaptive drug-taking behavior • Bingeing, running out early • Other factors: eg, cessation of insurance, financial difficulties 77 | © CO*RE 2015 Collaborative for REMS Education Interpretation of UDT Results, cont’d Be aware Differences exist between IA test menu panels vary Testing technologies & • Cross-reactivity patterns methodologies evolve – Maintain list of all patient’s prescribed & OTC drugs – Assist to identify false-positive result • Cutoff levels Time taken to Opioid metabolism may eliminate drugs explain presence • Document time of last use & of apparently quantity of drug(s) taken unprescribed drugs 78 | © CO*RE 2015 Collaborative for REMS Education 26 Examples of Metabolism of Opioids Codeine Morphine 6-MAM* Heroin t½=25-30 min t½=3-5 min Hydrocodone Hydromorphone Oxycodone Oxymorphone *6-MAM=6-monoacetylmorphine 79 | © CO*RE 2015 Collaborative for REMS Education Interpretation of UDT Results Use UDT results in conjunction w/ other clinical information Investigate unexpected results Schedule appointment Discuss w/ the lab w/ patient to discuss unexpected/abnormal results Chart results, interpretation, & action Do not ignore the unexpected positive result May necessitate closer monitoring &/or referral to a specialist Gourlay DL, et al. Urine Drug Testing in Clinical Practice. The Art & Science of Patient Care. Ed 4. 2010. 80 | © CO*RE 2015 Collaborative for REMS Education ER/LA Opioid Use in Pregnant Women No adequate & well-controlled studies Only use if potential benefit justifies the risk to the fetus Be aware of the pregnancy status of your patients If prolonged use is required during pregnancy: • Advise patient of risk of neonatal withdrawal syndrome • Ensure appropriate treatment will be available 81 | © CO*RE 2015 Collaborative for REMS Education 27 Be Ready to Refer Be familiar w/ referral sources for abuse or addiction that may arise from use of ER/LA opioids SAMHSA substance SAMHSA mental abuse treatment health treatment facility locator facility locator http://findtreatment.samhsa.gov/Treatme http://findtreatment.samhsa.gov/MHTreat ntLocator/faces/quickSearch.jspx mentLocator/faces/quickSearch.jspx 82 | © CO*RE 2015 Collaborative for REMS Education Unit 3 Pearls for Practice Anticipate and Treat Common Adverse Effects Use Informed Consent and Patient Provider Agreements Use UDT and PDMP as Valuable Sources of Data About your Patient However, know their limitations Monitor Patient Adherence, Side Effects, Aberrant Behaviors, and Clinical Outcomes Refer Appropriately if Necessary 83 | © CO*RE 2015 Collaborative for REMS Education © CO*RE 2014 COUNSELING PATIENTS & CAREGIVERS ABOUT THE SAFE USE OF ER/LA OPIOID ANALGESICS Unit IV 84 | © CO*RE 2015 Collaborative for REMS Education 28 Use Patient Counseling Document to help counsel patients Download: www.er-la- opioidrems.com/IwgUI/rems/pdf/patient_co unseling_document.pdf Order hard copies: www.minneapolis.cenveo.com/pcd/SubmitOr ders.aspx FDA. EXTENDED-RELEASE (ER) AND LONG-ACTING (LA) OPIOID ANALGESICS RISK EVALUATION AND MITIGATION STRATEGY (REMS). Modified 08/2014. www.fda.gov/downloads/ Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf 85 | © CO*RE 2015 Collaborative for REMS Education Counsel Patients About Proper Use Instruct patients/ Explain caregivers to • Product-specific information about • Read the ER/LA opioid the prescribed ER/LA opioid Medication Guide • How to take the ER/LA opioid as received from pharmacy prescribed every time an ER/LA opioid is dispensed • Importance of adherence to dosing regimen, handling • At every medical missed doses, & contacting appointment explain all their prescriber if pain cannot medications they take be controlled 86 | © CO*RE 2015 Collaborative for REMS Education Counsel Patients About Proper Use, cont’d Counsel patients/caregivers: • On the most common AEs of ER/LA opioids • About the risk of falls, working w/ heavy machinery, & driving • Call the prescriber for advice about managing AEs • Inform the prescriber about AEs Prescribers should report serious AEs to the FDA: www.fda.gov/downloads/AboutFDA/ReportsManualsForms /Forms/UCM163919.pdf or 1-800-FDA-1088 87 | © CO*RE 2015 Collaborative for REMS Education 29 Warn Patients Never break, chew, crush or snort an oral ER/LA tablet/capsule, or cut or tear patches prior to use • May lead to rapid release of ER/LA opioid causing overdose & death • When a patient cannot swallow a capsule whole, prescribers should refer to PI to determine if appropriate to sprinkle contents on applesauce or administer via feeding tube Use of CNS depressants or alcohol w/ ER/LA opioids can cause overdose & death • Use with alcohol may result in rapid release & absorption of a potentially fatal opioid dose • Other depressants include sedative-hypnotics & anxiolytics, illegal drugs 88 | © CO*RE 2015 Collaborative for REMS Education Warn Patients, cont’d Misuse of ER/LA opioids can lead to death • Take exactly as directed* • Counsel patients/caregivers on risk factors, signs, & symptoms of overdose & TAKE 1 TABLET BY MOUTH opioid-induced respiratory depression, GI EVERY 12 HOURS obstruction, & allergic reactions OXYCONTIN 10 MG • Call 911 or poison control Qty: 60 TABLETS 1-800-222-1222 *Serious side effects, including death, can occur even when used as recommended Do not abruptly stop or reduce the ER/LA opioid use • Discuss how to safely taper the dose when discontinuing 89 | © CO*RE 2015 Collaborative for REMS Education Co-Prescribing Naloxone Naloxone: • An opioid antagonist Available as: • Reverses acute opioid-induced respiratory depression • Naloxone kit but will also cause withdrawal and reverse analgesia (w/ syringes, needles) • Administered intramuscularly and subcutaneously • EVZIO™ (naloxone • Intranasal formulation currently under consideration HCl) auto-injector with the FDA What to do: • Encourage patients to create an ‘overdose plan’ • Involve and train family, friends, partners and/or caregivers • Check expiration dates and keep a viable dose on hand • In the event of known or suspected overdose, administer Naloxone and call 90 | © CO*RE911. 2015 Collaborative for REMS Education 90 | © CO*RE 2015 30 When to Consider Co-Prescribing Naloxone: Those at a higher risk for opioid overdose including… • Taking opioid high-doses for pain (50 mg/day equiv) • Receiving rotating opioid medication regimes (at risk for incomplete cross tolerance) • On opioid preparations with increased overdose risk • With respiratory disease (COPD, emphysema, asthma) • With renal or hepatic impairment • Concurrent benzodiazepine use 91 | © CO*RE 2015 Collaborative for REMS Education Pennsylvania Naloxone Law Act 139 Senate Bill 1164 was signed into law by Governor Tom Corbett in late Sept. as Act 139 of 2014. This legislation allows first responders including law enforcement, fire fighters, EMS or other organizations the ability to administer a medication known as naloxone, a life-saving opioid reversal medication, to individuals experiencing an opioid overdoes. The law also allows individuals such as friends or family members that may be in a position to assist a person at risk of experiencing an opioid related overdose to obtain a prescription for naloxone. Additionally, Act 139 provides immunity from prosecution for those responding to and reporting overdoses. 92 | © CO*RE 2013 Collaborative for REMS Education Protecting the Community Caution Patients • Sharing ER/LA opioids w/ others may cause them to have serious AEs – Including death • Selling or giving away ER/LA opioids is against the law • Store medication safely and securely • Protect ER/LA opioids from theft • Dispose of any ER/LA opioids when no longer needed – Read product-specific disposal information included w/ ER/LA opioid 93 | © CO*RE 2015 Collaborative for REMS Education 31 Source of Most Recent Rx Opioids Among Past-Year Users (2011-2012) 0.2% 1.8% 4.3% 5.1% Free: friend/relative 1 doctor 14.9% Bought/took: friend/relative Other 54.0% Drug dealer/stranger 19.7% >1 doctor Bought on Internet SAMHSA. (2013). Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD. Collaborative for REMS Education 94 | © CO*RE 2015 Educate Parents: Not in My House Step 1: Monitor . Note how many pills in each prescription bottle or pill packet . Keep track of refills for all household members . If your teen has been prescribed a drug, coordinate & monitor dosages & refills . Make sure friends & relatives—especially grandparents— are aware of the risks . If your teen visits other households, talk to the families about safeguarding their medications 95 | © CO*RE 2015 Collaborative for REMS Education Rx Opioid Disposal New “Disposal Act” expands ways for patients to dispose of unwanted/expired opioids Decreases amount of opioids introduced into the environment, particularly into water Collection receptacles Voluntarily maintained by: Call DEA Registration Call Center at • Law enforcement 1-800-882-9539 to find a local collection • Authorized collectors, including: receptacle . Manufacturer . Distributer . Reverse distributer Mail-back packages . Retail or hospital/clinic pharmacy • Including long-term care Obtained from authorized collectors facilities Local take-back events Last DEA National • Conducted by Federal, State, tribal, or Prescription Drug local law enforcement Take-Back Day on • Partnering w/ community groups September 26, 2015 DEA. Federal Register. 2014; 79(174):53520-70. Final Rule. Disposal of Controlled Substances. [Docket No. DEA-316] www.deadiversion.usdoj.gov/fed_regs/rules/2014/2014-20926.pdf DEA. Disposal Act: General Public Fact Sheet. www.deadiversion.usdoj.gov/drug_disposal/fact_sheets/disposal_public.pdf Collaborative for REMS Education 96 | © CO*RE 2015 32 Prescription Drug Disposal Pennsylvania has >330 permanent drop- off locations Located in Police Departments & Sheriff’s Offices To locate a drop-box, visit: http://webserver.health.state.pa.us/health/cust om/DrugTakebackLocations.asp?COUNTY=All 97 | © CO*RE 2013 Collaborative for REMS Education Other Methods of Opioid Disposal If collection receptacle, mail-back program, or take-back event unavailable, throw out in household trash • Take drugs out of original containers • Mix w/ undesirable substance, e.g., used coffee grounds or kitty litter – Less appealing to children/pets, & unrecognizable to people who intentionally go through your trash • Place in sealable bag, can, or other container – Prevent leaking or breaking out of garbage bag • Before throwing out a medicine container – Scratch out identifying info on label 98 | © CO*RE 2015 Collaborative for REMS Education Prescription Drug Disposal FDA lists especially harmful medicines – in some cases fatal w/ just 1 dose – if taken by someone other than the patient • Instruct patients to check medication guide Flush down sink/toilet if no collection receptacle, mail-back program, or take-back event available • As soon as they are no longer needed – So cannot be accidentally taken by children, pets, or others • Includes transdermal adhesive skin patches – Used patch worn for 3d still contains enough opioid to harm/kill a child – Dispose of used patches immediately after removing from skin • Fold patch in half so sticky sides meet, then flush down toilet • Do NOT place used or unneeded patches in household trash – Exception is Butrans: can seal in Patch-Disposal Unit provided & dispose of in the trash 99 | © CO*RE 2015 Collaborative for REMS Education 33 Challenge: The Daughter’s Party Red Flag: Your patient’s daughter, Jody, stole her father’s opioids from his bedside Patients do not drawer to take to a “fishbowl party”. safeguard their Her best friend consumed a mix of opioid opioids and alcohol and died of an medications correctly overdose. Action: Always counsel patients about safe drug storage; warn patients about the serious consequences of theft, misuse, and overdose. Tell your patients that taking another person’s medication, even once, is against the law. 100 | © CO*RE 2015 Collaborative for REMS Education Unit 4 Pearls for Practice Establish Informed Consent Counsel Patients about Proper Use Appropriate use of medication Consequences of inappropriate use Educate the Whole Team Patients, families, caregivers Tools and Documents Can Help with Counseling Use them! 101 | © CO*RE 2015 Collaborative for REMS Education © CO*RE 2014 GENERAL DRUG INFORMATION FOR ER/LA OPIOID ANALGESIC PRODUCTS Unit V 102 | © CO*RE 2015 Collaborative for REMS Education 34 General ER/LA Opioid Drug Information Prescribers should be knowledgeable about general characteristics, toxicities, & drug interactions for ER/LA opioid products: ER/LA opioid Respiratory Constipation analgesic products depression is the most are scheduled is the most common under the Controlled serious long-term Substances Act & opioid AE AE can be misused & abused Can be immediately Should be life-threatening anticipated 103 | © CO*RE 2015 Collaborative for REMS Education For Safer Use: Know Drug Interactions, PK, & PD Some ER/LA products rapidly CNS depressants can potentiate release opioid (dose dump) when sedation & respiratory depression exposed to alcohol Some drug levels may increase without dose dumping Use w/ MAOIs may increase respiratory depression Can reduce efficacy of diuretics Certain opioids w/ MAOIs can cause Inducing release of antidiuretic hormone serotonin syndrome Drugs that inhibit or induce CYP Methadone & buprenorphine can enzymes can increase prolong QTc interval or lower blood levels of some opioids 104 | © CO*RE 2015 Collaborative for REMS Education Opioid Tolerant Tolerance to sedating & respiratory-depressant effects is critical to safe use of certain ER/LA opioid products, dosage unit strengths, or doses Patients must be opioid tolerant before using • Any strength of transdermal fentanyl or hydromorphone ER • Certain strengths or daily doses of other ER products Opioid-tolerant patients are those taking at least • 60 mg oral morphine/day • 25 mcg transdermal fentanyl/hr • 30 mg oral oxycodone/day FOR 1 WK • 8 mg oral hydromorphone/day OR LONGER • 25 mg oral oxymorphone/day • An equianalgesic dose of another opioid 105 | © CO*RE 2015 Collaborative for REMS Education 35 Key Instructions: ER/LA Opioids Individually titrate to Times required a dose that provides to reach adequate analgesia steady-state plasma & minimizes concentrations adverse reactions are product-specific Continually Refer to product re-evaluate to assess information for maintenance of titration interval pain control & emergence of AEs 106 | © CO*RE 2015 Collaborative for REMS Education Key Instructions: ER/LA Opioids, cont’d When an ER/LA During chronic opioid is no therapy, longer required, especially for If pain increases, gradually titrate non-cancer- attempt to dose downward related pain, identify to prevent signs periodically source, while & symptoms of reassess the adjusting dose withdrawal in continued need physically for opioids dependent patients Do not abruptly discontinue 107 | © CO*RE 2015 Collaborative for REMS Education Common Drug Information for This Class Dosage reduction Limitations Relative potency for hepatic or of usage to oral morphine renal impairment • Reserve for when See individual drug PI • Intended as general guide alternative options (eg, • Follow conversion non-opioids or IR opioids) instructions in individual PI are ineffective, not tolerated, or otherwise • Incomplete cross- inadequate tolerance & inter-patient variability require • Not for use as an conservative dosing when as-needed analgesic converting from 1 • Not for mild pain or pain opioid to another not expected to persist for – Halve calculated an extended duration comparable dose & titrate • Not for acute pain new opioid as needed 108 | © CO*RE 2015 Collaborative for REMS Education 36 Transdermal Dosage Forms Do not cut, damage, chew, or swallow Exertion or exposure Prepare skin: clip - Rotate location of to external heat can not shave - hair & application lead to fatal overdose wash area w/ water Monitor patients w/ fever for Metal foil backings are not signs or symptoms of safe for use in MRIs increased opioid exposure 109 | © CO*RE 2015 Collaborative for REMS Education Drug Interactions Common to this Class Concurrent use w/ other CNS Avoid concurrent use of depressants can increase risk partial agonists* or mixed of respiratory depression, agonist/antagonists† with hypotension, profound full opioid agonist sedation, or coma May reduce analgesic effect &/or Reduce initial dose of one precipitate withdrawal or both agents Concurrent use w/ May enhance neuromuscular anticholinergic medication blocking action of skeletal increases risk of muscle relaxants & increase urinary retention & respiratory depression severe constipation May lead to paralytic ileus *Buprenorphine; †Pentazocine, nalbuphine, butorphanol 110 | © CO*RE 2015 Collaborative for REMS Education Drug Information Common to This Class Use in opioid- Contraindications tolerant patients • See individual PI for products • Significant respiratory depression which: • Acute or severe asthma in an – Have strengths or total daily doses unmonitored setting or in only for use in opioid-tolerant absence of resuscitative patients equipment – Are only for use in opioid-tolerant • Known or suspected patients at all strengths paralytic ileus • Hypersensitivity (e.g., anaphylaxis) • See individual PI for additional contraindications 111 | © CO*RE 2015 Collaborative for REMS Education 37 Unit 5 Pearls for Practice Patients MUST be opioid-tolerant in order to safely take most ER/LA opioid products Be familiar with drug-drug interactions, pharmacokinetics and pharmacodynamics of ER/LA opioids Central nervous system depressants (alcohol, sedatives, hypnotics, tranquilizers, tricyclic antidepressants) can have a potentiating effect on the sedation and respiratory depression caused by opioids. 112 | © CO*RE 2015 Collaborative for REMS Education © CO*RE 2014 SPECIFIC DRUG INFORMATION FOR ER/LA OPIOID ANALGESIC PRODUCTS Unit VI 113 | © CO*RE 2015 Collaborative for REMS Education Specific Characteristics Know for opioid products you prescribe: Drug Dosing Formulation Strength substance interval Use in opioid- Product- Relative Key tolerant specific safety potency to instructions patients concerns morphine Specific information about Specific drug interactions product conversions, if available For detailed information, refer to online PI: DailyMed at www.dailymed.nlm.nih.gov Drugs@FDA at www.fda.gov/drugsatfda 114 | © CO*RE 2015 Collaborative for REMS Education 38 Morphine Sulfate ER Capsules (Avinza) Dosing interval • Once a day • Initial dose in opioid non-tolerant patients is 30 mg • Titrate in increments of not greater than 30 mg using a minimum of 3-4 d intervals Key • instructions Swallow capsule whole (do not chew, crush, or dissolve) • May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing; use immediately • MDD:* 1600 mg (renal toxicity of excipient, fumaric acid) • Alcoholic beverages or medications w/ alcohol may result in rapid Drug release & absorption of potentially fatal dose interactions • P-gp* inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold Opioid-tolerant • 90 mg & 120 mg capsules for use in opioid-tolerant patients only Product- specific safety • None concerns * MDD=maximum daily dose; P-gp= P-glycoprotein 115 | © CO*RE 2015 Collaborative for REMS Education Buprenorphine Transdermal System (Butrans) Dosing • One transdermal system every 7 d interval • Initial dose in opioid non-tolerant patients on <30 mg morphine equivalents & in mild-moderate hepatic impairment: 5 mcg/h • When converting from 30 mg-80 mg morphine equivalents, first taper to 30 mg morphine equivalent, then initiate w/ 10 mcg/h • Titrate in 5 or 10 mcg/h increments by using no more than 2 patches of the 5 or 10 mcg/h system(s) w/ minimum of 72 h prior between dose adjustments. Total dose from all patches should be ≤20 mcg/h Key • Maximum dose: 20 mcg/h due to risk of QTc prolongation instructions • Application • Apply only to sites indicated in PI • Apply to intact/non-irritated skin • Prep skin by clipping hair; wash site w/ water only • Rotate application site (min 3 wks before reapply to same site) • Do not cut • Avoid exposure to heat • Dispose of patches: fold adhesive side together & flush down toilet 116 | © CO*RE 2015 Collaborative for REMS Education Buprenorphine Transdermal System (Butrans) cont’d • CYP3A4 inhibitors may increase buprenorphine levels • CYP3A4 inducers may decrease buprenorphine levels Drug interactions • Benzodiazepines may increase respiratory depression • Class IA & III antiarrythmics, other potentially arrhythmogenic agents, may increase risk of QTc prolongation & torsade de pointe Opioid- • 7.5 mcg/h, 10 mcg/h, 15 mcg/h, & 20 mcg/h for use in opioid- tolerant tolerant patients only Drug-specific • QTc prolongation & torsade de pointe safety • Hepatotoxicity concerns • Application site skin reactions Relative potency: oral • Equipotency to oral morphine not established morphine 117 | © CO*RE 2015 Collaborative for REMS Education 39 Methadone Hydrochloride Tablets NOTE: While the dosing information below reflects the 8/20/14 FDA Blue Print, the CO*RE Expert Clinical Faculty believe it to be (Dolophine) too aggressive and perhaps a risky approach. CO*RE Expert Clinical Faculty discourages methadone for opioid naïve patients Dosing as an initial drug and recommends 4-5 d intervals for dosing • Every 8 to 12 h interval adjustments. • Initial dose in opioid non-tolerant patients: 2.5 – 10 mg • Conversion of opioid-tolerant patients using equianalgesic tables can result in overdose & death. Use low doses according to table in full PI Key • Dosage adjustments using a minimum of 1-2 d intervals instructions • High inter-patient variability in absorption, metabolism, & relative analgesic potency • Opioid detoxification or maintenance treatment only provided in a federally certified opioid (addiction) treatment program (CFR, Title 42, Sec 8) • Pharmacokinetic drug-drug interactions w/ methadone are complex − CYP 450 inducers may decrease methadone levels − CYP 450 inhibitors may increase methadone levels Drug − Anti-retroviral agents have mixed effects on methadone levels interactions • Potentially arrhythmogenic agents may increase risk for QTc prolongation & torsade de pointe • Benzodiazepines may increase respiratory depression FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf 118 | © CO*RE 2013 Collaborative for REMS Education Methadone Hydrochloride Tablets (Dolophine) cont’d Opioid- • Refer to full PI tolerant • QTc prolongation & torsade de pointe Drug- • Peak respiratory depression occurs later & persists longer than specific analgesic effect safety • concerns Clearance may increase during pregnancy • False-positive UDT possible Relative potency: • Varies depending on patient’s prior opioid experience oral morphine 119 | © CO*RE 2015 Collaborative for REMS Education Methadone: Additional Considerations Use caution w/ administration of methadone Administration of methadone to treat chronic pain is associated w/ increased risk of harm Be aware of the special pharmacokinetics of methadone Need for careful dosing & monitoring Pennsylvania Department of Drug and Alcohol Programs and Health. Pennsylvania Medical Society. Pennsylvania Guidelines on the Use Opioids to Treat Chronic Noncancer Pain. 2014. www.portal.state.pa.us/portal/server.pt/document/1432037/pamed_chronic_guidelines_pdf&sa=U&ei=djLuVKDoAYq_ggSNt4LwDg&ved= 0CAUQFjAA&client=internal-uds-cse&usg=AFQjCNEHB4iFzijNv8DoJztH4KSfb5gMwA 120 | © CO*RE 2013 Collaborative for REMS Education 40 Fentanyl Transdermal System 12, 25, 37.5*, 50, 62.5*, 75, 87.5*, and 100 mcg/hr (Duragesic) (*These strengths are available only in generic form) Dosing • Every 72 h (3 d) interval • Use product-specific information for dose conversion from prior opioid • Hepatic or renal impairment: use 50% of dose if mild/moderate, avoid use if severe • Application − Apply to intact/non-irritated/non-irradiated skin on a flat surface Key − Prep skin by clipping hair, washing site w/ water only instructions − Rotate site of application − Titrate using a minimum of 72 h intervals between dose adjustments − Do not cut • Avoid exposure to heat • Avoid accidental contact when holding or caring for children • Dispose of used/unused patches: fold adhesive side together & flush down toilet 121 | © CO*RE 2015 Collaborative for REMS Education Fentanyl Transdermal System (Duragesic), cont’d Specific contraindications: • Patients who are not opioid-tolerant Key instructions • Management of − Acute or intermittent pain, or patients who require opioid analgesia for a short time − Post-operative pain, out-patient, or day surgery − Mild pain • CYP3A4 inhibitors may increase fentanyl exposure • CYP3A4 inducers may decrease fentanyl exposure Drug interactions • Discontinuation of concomitant CYP P450 3A4 inducer may increase fentanyl plasma concentration Opioid-tolerant • All doses indicated for opioid-tolerant patients only • Accidental exposure due to secondary exposure to unwashed/unclothed application site Drug-specific safety • Increased drug exposure w/ increased core body temp or fever concerns • Bradycardia • Application site skin reactions Relative potency: • See individual PI for conversion recommendations from prior opioid oral morphine 122 | © CO*RE 2015 Collaborative for REMS Education Morphine Sulfate ER-Naltrexone Tablets (Embeda) Dosing interval • Once a day or every 12 h • Initial dose as first opioid: 20 mg/0.8 mg • Titrate using a minimum of 1-2 d intervals • Swallow capsules whole (do not chew, crush, or dissolve) Key instructions • Crushing or chewing will release morphine, possibly resulting in fatal overdose, & naltrexone, possibly resulting in withdrawal symptoms • May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediately • Alcoholic beverages or medications w/ alcohol may result in rapid release Drug & absorption of potentially fatal dose interactions • P-gp inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold Opioid-tolerant • 100 mg/4 mg capsule for use in opioid-tolerant patients only Product-specific • None safety concerns 123 | © CO*RE 2015 Collaborative for REMS Education 41 Hydromorphone Hydrochloride ER Tablets (Exalgo) Dosing interval • Once a day • Use conversion ratios in individual PI • Start patients w/ moderate hepatic impairment on 25% dose prescribed for patient w/ normal function • Renal impairment: start patients w/ moderate on 50% & patients w/ Key instructions severe on 25% dose prescribed for patient w/ normal function • Titrate in increments of 4-8 mg using a minimum of 3-4 d intervals • Swallow tablets whole (do not chew, crush, or dissolve) • Do not use in patients w/ sulfite allergy (contains sodium metabisulfite) Drug interactions • None Opioid-tolerant • All doses are indicated for opioid-tolerant patients only Product-specific • Allergic manifestations to sulfite component adverse reactions Relative potency: • ~5:1 oral morphine to hydromorphone oral dose ratio, use conversion oral morphine recommendations in individual product information 124 | © CO*RE 2015 Collaborative for REMS Education Hydrocodone Bitartrate (Hysingla ER) Extended–Release Tablets, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, and 120mg Dosing • Once a day interval • Opioid-naïve patients: initiate treatment with 20 mg orally once daily. • During titration, adjust the dose in increments of 10 mg to 20 mg every 3 to 5 days until adequate analgesia is achieved. • Swallow tablets whole (do not chew, crush, or dissolve). • Consider use of an alternative analgesic in patients who have difficulty Key swallowing or have underlying gastrointestinal disorders that may predispose instructions them to obstruction. • Take one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth. • Use 1/2 of the initial dose and monitor closely for adverse events, such as respiratory depression and sedation, when administering Hysingla ER to patients with severe hepatic impairment or patients with moderate to severe renal impairment. 125 | © CO*RE 2015 Collaborative for REMS Education Hydrocodone Bitartrate (Hysingla ER), cont’d • CYP3A4 inhibitors may increase hydrocodone exposure. • CYP3A4 inducers may decrease hydrocodone exposure. • Concomitant use of Hysingla ER with strong laxatives (e.g., Lactulose) that Drug interactions rapidly increase GI motility may decrease hydrocodone absorption and result in decreased hydrocodone plasma levels. • The use of MAO inhibitors or tricyclic antidepressants with Hysingla ER may increase the effect of either the antidepressant or Hysingla ER. Opioid-tolerant • 80 mg is only for use in opioid tolerant patients. • Use with caution in patients with difficulty swallowing the tablet or underlying gastrointestinal disorders that may predispose patients to obstruction. • Esophageal obstruction, dysphagia, and choking have been reported with Hysingla ER. • In nursing mothers, discontinue nursing or discontinue drug. QTc Drug-specific safety prolongation has been observed with Hysingla ER following daily doses of concerns 160 mg. • Avoid use in patients with congenital long QTc syndrome. This observation should be considered in making clinical decisions regarding patient monitoring when prescribing Hysingla ER in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QTc interval. • In patients who develop QTc prolongation, consider reducing the dose. Relative potency: • See individual PI for conversion recommendations from prior opioid oral morphine Collaborative for REMS Education 126 | © CO*RE 2015 42 Morphine Sulfate ER Capsules (Kadian) Dosing interval • Once a day or every 12 h • PI recommends not using as first opioid • Titrate using minimum of 2-d intervals Key instructions • Swallow capsules whole (do not chew, crush, or dissolve) • May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediately • Alcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dose of morphine Drug interactions • P-gp inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold Opioid-tolerant • 100 mg & 200 mg capsules for use in opioid-tolerant patients only Product-specific • None safety concerns 127 | © CO*RE 2015 Collaborative for REMS Education Morphine Sulfate CR Tablets (MS Contin) Dosing interval • Every 8 h or every 12 h • Product information recommends not using as first opioid. Key instructions • Titrate using a minimum of 1-2 d intervals • Swallow tablets whole (do not chew, crush, or dissolve) • P-gp inhibitors (e.g., quinidine) may increase Drug interactions absorption/exposure of morphine by ~2-fold • 100 mg & 200 mg tablet strengths for use in opioid-tolerant Opioid-tolerant patients only Product-specific • None safety concerns 128 | © CO*RE 2015 Collaborative for REMS Education Tapentadol ER Tablets (Nucynta ER) Dosing interval • Every 12 h • 50 mg every 12 h is initial dose in opioid non-tolerant patients • Titrate by 50 mg increments using minimum of 3-d intervals • MDD: 500 mg • Swallow tablets whole (do not chew, crush, or dissolve) Key instructions • Take 1 tablet at a time w/ enough water to ensure complete swallowing immediately after placing in mouth • Dose once/d in moderate hepatic impairment (100 mg/d max) • Avoid use in severe hepatic & renal impairment • Alcoholic beverages or medications w/ alcohol may result in rapid Drug interactions release & absorption of a potentially fatal dose of tapentadol • Contraindicated in patients taking MAOIs Opioid-tolerant • No product-specific considerations Product-specific • Risk of serotonin syndrome safety concerns • Angio-edema Relative potency: • Equipotency to oral morphine has not been established oral morphine 129 | © CO*RE 2015 Collaborative for REMS Education 43 Oxymorphone Hydrochloride ER Tablets (Opana ER) • Every 12 h dosing, some may benefit from asymmetric (different Dosing interval dose given in AM than in PM) dosing • Use 5 mg every 12 h as initial dose in opioid non-tolerant patients & patients w/ mild hepatic impairment & renal impairment (creatinine clearance <50 mL/min) & patients >65 yrs • Swallow tablets whole (do not chew, crush, or dissolve) Key instructions • Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouth • Titrate in increments of 5-10 mg using a minimum of 3-7 d intervals • Contraindicated in moderate & severe hepatic impairment • Alcoholic beverages or medications w/ alcohol may result in Drug interactions absorption of a potentially fatal dose of oxymorphone Opioid-tolerant • No product-specific considerations • Use with caution in patients who have difficulty swallowing or Product-specific underlying GI disorders that may predispose to obstruction (e.g. small safety concerns gastrointestinal lumen) Relative potency: • Approximately 3:1 oral morphine to oxymorphone oral dose ratio oral morphine 130 | © CO*RE 2015 Collaborative for REMS Education Oxycodone Hydrochloride CR Tablets NEW (OxyContin) Extended Release Tablets DOSING INFO 10mg, 15mg, 20,mg, 30mg, 40mg, 60mg and 80 mg Dosing interval • Every 12 h • Initial dose in opioid non-tolerant patients: / 10 mg every 12 h • Titrate using a minimum of 1-2 d intervals • Hepatic impairment: start w/ ⅓-½ usual dosage • Renal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosage Key instructions • Consider other analgesics in patients w/ difficulty swallowing or underlying GI disorders that predispose to obstruction. Swallow tablets whole (do not chew, crush, or dissolve) • Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouth • CYP3A4 inhibitors may increase oxycodone exposure Drug interactions • CYP3A4 inducers may decrease oxycodone exposure • Single dose >40 mg or total daily dose >80 mg for use in opioid-tolerant patients Opioid-tolerant only Product-specific • Choking, gagging, regurgitation, tablets stuck in throat, difficulty swallowing tablet safety concerns • Contraindicated in patients w/ GI obstruction Relative potency: • Approximately 2:1 oral morphine to oxycodone oral dose ratio oral morphine Collaborative for REMS Education 131 | © CO*RE 2015 Oxycodone Hydrochloride CR Tablets (OxyContin) Extended Release Tablets, con’t 10mg, 15mg, 20,mg, 30mg, 40mg, 60mg and 80 mg For Adults: • Single dose greater than 40 mg or total daily dose greater than 80 mg are for use in adult patients in whom tolerance to an opioid of comparable tolerance has been established. • When a dose increase is clinically indicated, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose. For Pediatric Patients (11 years and older) Key instructions • For use only in opioid tolerant pediatric patients already receiving and tolerating opioids for at least five (5) consecutive days with a minimum of 20 mg per day of oxycodone or its equivalent for at least 2 days immediately preceding dosing with Oxycodon ER. Renal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosage • If needed, pediatric dose may be adjusted in 1 to 2 day intervals. • When a dose increase is clinically indicated, the total daily oxycodone dose usually can be increased by 25% of the current daily dose. • Opioids are rarely indicated or used to treat pediatric patients with chronic pain. • The recent FDA approval for this oxycodone formulation was NOT IMPORTANT: intended to increase prescribing or use of this drug in pediatric pain 132 | © CO*RE 2015 treatment. Review the product informationCollaborative and adhere for toREMS best Education practices in the literature. 44 Oxycodone Hydrochloride/Naloxone Hydrochloride ER Tablets (Targiniq ER) Dosing interval • Every 12 h • Opioid-naïve patients: initiate treatment w/ 10mg/5mg every 12 h • Titrate using min of 1-2 d intervals • Do not exceed 80 mg/40 mg total daily dose (40 mg/20 mg q12h) • May be taken w/ or without food Key instructions • Swallow whole. Do not chew, crush, split, or dissolve: this will release oxycodone (possible fatal overdose) & naloxone (possible withdrawal) • Hepatic impairment: contraindicated in moderate-severe impairment. In patients w/ mild impairment, start w/ ⅓-½ usual dosage • Renal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosage Drug • CYP3A4 inhibitors may increase oxycodone exposure interactions • CYP3A4 inducers may decrease oxycodone exposure • Single dose >40 mg/20 mg or total daily dose of 80 mg/40 mg for opioid- Opioid-tolerant tolerant patients only Product-specific • Contraindicated in patients w/ moderate-severe hepatic impairment safety concerns Relative potency: • See individual PI for conversion recommendations from prior opioids oral morphine 133 | © CO*RE 2015 Collaborative for REMS Education Hydrocodone Bitartrate ER Capsules (Zohydro ER) Dosing interval • Every 12 h • Initial dose in opioid non-tolerant patient is 10 mg Key instructions • Titrate in increments of 10 mg using a min of 3-7 d intervals • Swallow capsules whole (do not chew, crush, or dissolve) • Alcoholic beverages or medications containing alcohol may result in rapid release & absorption of a potentially fatal dose of Drug interactions hydrocodone • CYP3A4 inhibitors may increase hydrocodone exposure • CYP3A4 inducers may decrease hydrocodone exposure • Single dose >40 mg or total daily dose >80 mg for use in Opioid-tolerant opioid-tolerant patients only Product-specific • None safety concerns Relative potency: • Approximately 1.5:1 oral morphine to hydrocodone oral dose ratio oral morphine 134 | © CO*RE 2015 Collaborative for REMS Education Naloxone (Narcan) • IM or SQ: onset 2-5 minutes, duration >45 min Dosing interval • IV: onset 1-2 min, duration 45 minutes • Monitor respiratory rate • Monitor level of consciousness for 3-4 hours after expected peak of blood Key instructions concentrations • Note that reversal of analgesia will occur Drug • Larger doses required to reverse effects of buprenorphine, butorphanol, interactions nalbuphine, or pentazocine • Assess signs and symptoms of opioid withdrawal, may occur within 2 min – 2 hrs Opioid-tolerant • Vomiting, restlessness, abdominal cramps, increased BP, temperature • Severity depends on naloxone dose, opioid involved & degree of dependence • Ventricular arrhythmias, hypertension, hypotension, nausea & vomiting Product-specific • safety concerns As naloxone plasma levels decrease, sedation from opioid overdose may increase 135 | © CO*RE 2015 Collaborative for REMS Education 45 Summary Prescription opioid abuse & overdose is a national epidemic. Clinicians must play a role in prevention Be familiar w/ how to Understand how to initiate therapy, Know how to manage assess patients for modify dose, & ongoing therapy w/ treatment discontinue use of ER/LA opioids w/ ER/LA opioids ER/LA opioids Know how to counsel Be familiar w/ general patients & caregivers & product-specific about the safe drug information use of ER/LA opioids, concerning including proper ER/LA opioids storage & disposal 136 | © CO*RE 2015 Collaborative for REMS Education IMPORTANT! Thank you for completing the post-activity assessment for this CO*RE session. Your participation in this assessment allows CO*RE to report de-identified numbers to the FDA. A strong show of engagement will demonstrate that clinicians have voluntarily taken this important education and are committed to patient safety and improved outcomes. THANK YOU! 137 | © CO*RE 2015 Collaborative for REMS Education ER/LA Opioids REMS Knowledge Test 1. Among the risk factors contained in screening tools for predicting aberrant drug-related behavior in patients receiving opioids for chronic pain are family and personal history of substance abuse, legal problems, history of preadolescent sexual abuse, psychological problems and A. Age (12-15 years) B. Age (16-45 years) C. Age (46-75 years) D. Age ( ≥ 76 years) E. Risk is even across age 2. Which of the following is most important to consider when determining a starting dosage of an extended-release/long-acting opioid? A. Calculation of equianalgesic dosage B. Presence of cross-tolerance C. Potential for adverse events D. Assessment of individual needs E. Starting dosage listed in the package insert 3. A 55-year-old man who is being treated for chronic low back pain after undergoing laminectomy comes for follow-up evaluation. A trial of oxycodone ER therapy is planned. Completion of which of the following is the most appropriate step before initiation of therapy? A. Oswestry Disability Index B. Roland Morris Disability Questionnaire C. Patient-Prescriber Agreement D. MRI of the lumbar spine E. Routine blood tests 138 | © CO*RE 2013 Collaborative for REMS Education 46 ER/LA Opioids REMS Knowledge Test 4. A 63-year-old woman with a history of spinal stenosis and peripheral neuropathy secondary to breast cancer treatment comes for evaluation because of increasingly severe back pain. She reports that the pain started two weeks ago after doing yard work. She underwent chemotherapy 12 years ago. Medications include an opioid. Which of the following is the most appropriate next step? A. Assure the patient that the heightened sensitivity to pain is to be expected B. Reevaluate the underlying medical condition C. Refer the patient to physical therapy and administer a short-acting opioid as necessary D. Increase extended-release/long-acting opioid therapy dosage for up to one month E. Consider adding an adjuvant analgesic for neuropathic pain 5. Use of ER/LA opioids in pediatric patients <18 years of age deserves special consideration because A. Safety & effectiveness of most ER/LA opioids has not been established in this population B. Many children experience chronic pain conditions with indications for ER/LA opioids C. Starting doses of opioids are reduced by one-third to one-half that in adults D. Opioid risk screening tools have not been validated in this population E. Many state laws require consultation with a pediatric pain specialist or pain clinic 6. A 20-year-old woman is brought to the emergency department because of the sudden onset of anxiety and confusion after taking her mother’s tapentadol for a severe toothache earlier that evening. The patient has a history of atypical depression treated with selegiline, a MAO inhibitor. She appears agitated and flushed. Temperature is 37.9°C (100.3°F), pulse rate is 103/min, respiratory rate is 24/min, and blood pressure is 117/76 mm Hg. Vision examination shows ocular clonus. Physical examination shows mild hyperreflexia throughout but more noticeable on the lower extremities, and bilateral ankle clonus. Which of the following is the most likely diagnosis? A. Anticholinergic delirium B. Neuroleptic malignant syndrome C. Serotonin syndrome D. Sympathomimetic toxicity E. Torsades de pointes 139 | © CO*RE 2013 Collaborative for REMS Education ER/LA Opioids REMS Knowledge Test 7. An inappropriate method to dispose of unused opioid medication is: A. Return the medication to a pharmacy B. DEA drug take-back event C. Mix into cat litter before putting in the regular trash D. Dispose of medication in the regular trash E. Flush down the toilet 8. The most important reason a patient should be counseled to never break, cut, chew, or crush a ER/LA opioid tablet or cut or tear patches is because: A. The medicine will expire B. It is against the law C. The dose will be less than prescribed D. The patient may die 9. To avoid inadvertent overdose and death a patient should be counseled to avoid co- administration of an extended-release/long-acting opioid with which of the following? A. Alcohol B. Diphenhydramine C. St John’s wort D. Aspirin E. Methamphetamine 140 | © CO*RE 2013 Collaborative for REMS Education ER/LA Opioids REMS Knowledge Test 10. Which of the following extended-release/long-acting opioids is most likely to induce a peak respiratory depression that occurs later and persists longer than the analgesic effect? A. Fentanyl transdermal patch B. Hydromorphone ER C. Methadone D. Oxycodone CR E. Tapentadol ER 11. When using an equianalgesic table to rotate opioids (other than methadone), an important step to account for incomplete cross-tolerance among mu opioids includes: A. Initiatie the new opioid at the calculated equianalgesic dose B. Increase the calculated equianalgesic dose by 10%-30% C. Reduce calculated equianalgesic dose by 25-50% D. Convert and total all opioids to oral morphine equivalents E. Refer to the package insert for appropriate supplemental rescue dose 141 | © CO*RE 2013 Collaborative for REMS Education 47 ER/LA Opioids REMS Knowledge Test 12. Which of the following most accurately reflects the potency of certain oral opioid analgesics relative to oral morphine? A. Hydromorphone ER > oxymorphone ER> oxycodone > morphine B. Hydromorphone ER > oxymorphone ER > morphine > oxycodone C. Oxymorphone ER > hydromorphone ER > morphine > oxycodone D. Oxymorphone ER > hydromorphone ER > oxycodone > morphine 13. A 35-year-old man with chronic pain is beginning a trial therapy with morphine extended release- naltrexone. Which of the following is the minimum interval for dose titration? A. Two days B. Three days C. Five days D. Seven days E. Nine days 14. A positive result of hydromorphone of a urine drug toxicology test for a patient on prescribed morphine can be interpreted as A. Use of heroin in past month B. Proof of supplemental hydromorphone C. Presence of the oxycodone metabolite D. Presence of the morphine metabolite E. Presence of semisynthetic opioids 142 | © CO*RE 2013 Collaborative for REMS Education Thank you! www.core-rems.org 143 | © CO*RE 2014 Collaborative for REMS Education 48 Return to Top Act 31 Child Abuse Recognition Training Act 31 Child Abuse Recognition Training Q. Thomas Novinger, MD, MBA, Blue Cross of NEPA & Valerie Rode, MSW, Lehigh County County Office of Children and Youth Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Because of the content of this presentations, handouts are not allowed to be posted online. Return to Top Integrating Genetic Testing into Family Medicine - Part I, an Overview Integrating Genetic Testing into Family Medicine - Part I, an Overview Brian Stello, MD, Lehigh Valley Health Network Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Integrating Genomics in Family Medicine 1 Disclosures • Disclosure of Relevant Financial Relationships: The presenter has no financial relationships to disclose. • Disclosure of Off-Label and /or Investigative Uses: The presenter(s) will not discuss off label use and /or investigational use in this presentation. 2 Have You Ever … • Referred a patient for genomic testing? • Had a patient ask about the benefits of genomic testing? • Had a patient discuss their genomic test results with you? 3 1 Objectives • Understand the background of genomics related to Primary Care. • Discuss the implications of genomics and pharmacogenomics for Primary Care. • Characterize the clinical activity and attitudes related to genomics in a population of Primary Care clinicians. 4 What Is Genomics? • Study of all genes in an organism including. o Nuclear and extranuclear genes (DNA, mRNA, protein) o Mapping and sequencing of genes o Gene expression under various conditions (e.g. environment, pharma) 5 Genome To Proteome • The genome refers to the complete set of DNA in an organism. • Any single gene is expressed in a protein. • The proteome refers to all the proteins in a cell or an organism. • The interaction of proteins within the proteome and with the environment define the expression of the genome. 6 2 History of the Human Genome Project • HGP formally started in 1993 and ended in 2003. • The project goals was to discover the estimated 20,000-25,000 human genes and their component base sequencing (over 3 billion DNA base subunits). 7 Principles of Genetics In the Context of Disease • Genetic variation necessary for survival of our species. • Maladaptive genetic variation comes to our attention as disease. • Complex disease is a result of the interaction between the genome and the environment. 8 Integrating Genomics 9 3 Personalized Medicine • Personalized Medicine proposes the customization of an individual’s healthcare based primarily on his/her genome. • Personalized Medicine suggests that knowing a patient’s genome will allow the patient and his/her doctor to tailor tests and treatments. 10 The Promise of Personalized Medicine • Predictive Medicine o Genomic markers of disease risk that may allow patients to make choices about lifestyle, environment, and treatment. • Pharmacogenomics o Choosing medications based on genomics to • Enhance benefit by matching the medicine to the patient. • Reduce adverse events. 11 The 4 P’s of Personalized Medicine 12 4 ACCE Framework • Analytical validity – genomic test results need to be accurate and reliable. • Clinical validity – reliable results are of consistent clinical significance. • Clinical utility – there is a clear benefit for intervention based on genomic test results. • Ethical, legal, and social implications are openly discussed. 13 Tiered Approach to Integrating Genomics • Tier 1 – recommended for clinical use by evidence-based panels and supported by systematic review of 1 evidence. 2 • Tier 2 – validity and promising evidence of clinical utility, but lack 3 evidence-based recommendations. • Tier 3 – inadequate validity or utility. 14 Single‐Gene Disease • Single-gene disorders tend to present as severe disease that is seen early in life (e.g. cystic fibrosis). • Inheritance of single-gene disorders is Mendelian. • Many single-gene disorders are so severe that progeny dies in utero. • Genetic therapy is typically aimed at treating single-gene disorders. 15 5 Examples of Single‐Gene Testing • Prenatal Testing o Fetal Cells in Maternal Blood (FCMB) o Transcervical retrieval of trophoblasts o Chorionic Villus sampling o Percutaneous Umbilical Blood Sampling (PUBS) o Amniocentesis • Newborn Screening 16 Complex Disease • Complex disease is much more frequent than single-gene disease. • Complex disease (cancer, heart disease, diabetes, etc.) are the major contributors to morbidity and mortality in developed and developing countries. • Complex disease is typically the result of multiple gene products interacting with each other and with the environment. • Genomics for complex disease are probabilistic and not deterministic. 17 Single‐Gene vs. Complex Disease • A single-gene disorder is usually expressed early in development and, therefore, may have limited prevention and treatment options. • Complex genetic disease is slow developing, and therefore often amenable to treatment. 18 6 Complex Disease Pedigrees Disease‐specific pedigrees will soon be utilized to optimize risk stratification and assist with appropriate allocation of resources for disease prevention and early discovery. It is necessary that both patients and health care providers have access to these pedigrees because they are dynamic and clinical interpretation changes with time. Image adapted from The American Journal of Medicine. Integration of Genomics in Primary Care. Eric A. Larson MD, Russell A. Wilke MD, PhD. © 2015 19 Treating Complex Disease • Because of its slow development, complex diseases can be treated by o Changing the environment (e.g. lifestyle) o Early intervention (e.g. early screening, removing a precancerous lesion) o Interacting with the body’s proteins (e.g. pharmaceuticals) 20 Pharmacogenomics • Pharmacogenomics (PGx) is the study of how individual genetic differences affect drug response. o Predict benefit o Anticipate adverse reactions • The ultimate aim of PGx is to use a patient’s genome to use only those drugs that would be beneficial and avoid those that are ineffective or even harmful. 21 7 Current Pharmacotherapy Disease Cohort Standard Drug and Dose Benefit Benefit No Benefit No Benefit No Side Effects Side Effects No Side Effects Side Effects 22 Pharmacogenomics Disease Cohort Pharmacogenomic Therapy Benefit Benefit Benefit 23 Applications of PGx • Human Epidermal Growth Factor Receptor 2 (HER2/neu) testing of patients with metastatic breast cancer to determine responsiveness to trastuzumab (Herceptin). • Guided warfarin dosing by testing for Cytochrome P450 2C9 (CYP2C9) and Vitamin K Epoxide Reductase Complex subunit 1 (VKORC1). 24 8 Chronic Disease Applications of PGx • Genomically-guided treatment would allow choice of the most effective medications for patients. • Likewise, we would avoid using medication when the individual’s genomics suggests the risk of adverse effects. • Theoretically, this would improve outcomes and reduce healthcare costs. 25 Primary Care Physician Perspective • Primary Care Physicians Experience and Confidence with Genetic Testing and Perceived Barriers to Genomic Medicine. Journal of Family Medicine. 2015;2(2). o Chambers CV, Axell-House DB, Mills G, Bittner-Fagnan H, Rosenthal MP, Johnson M, Stello B. 26 In the last 6 months have you ordered genetic testing? 0% 19% No ans Yes No 81% 27 9 Genetic Testing Ordered Testing (n) Cancer Risk 28 Prenatal 11 Other 11 Pharmacogenomics 9 Micro array 6 28 Physician Confidence 100% 90% 80% 70% 60% 50% Very high confidence 40% High 30% confidence Somewhat 20% confident 10% Low confidence 0% Take a thorough Build a family Assess risk of Order genetic Discuss the Counsel Counsel family genetic medical history hereditary testing for risks, benefits patients about patients about history pedigree chart disorders hereditary and limitations whether or not risk reduction cancers of genetic to have genetic strategies testing for counseling (lifestyle hereditary changes, cancers screening, medical therapy) based on the results of genetic testing 29 Role of Genomics 30 10 Working With Patients 31 Integrating Genomics in HIT o Identify genomic data with high validity and clinical utility (i.e. Tier 1 data). o Develop structured data storage for EHRs. o Integrate genomic data into condition-specific, rules-based decision support. o Provide the decision support to patients and clinician at the point of care. 32 Virtues and Vices of Personalized Genomic Medicine Juengst E, et al. After the revolution? Ethical and social challenges in ‘personalized genomic medicine.’ Personalized Medicine. 2012 June 1;9(4):429-39. 33 11 Amara’s Law o“We tend to overestimate the effect of a technology in the short run and underestimate the effect in the long run.” • Roy Amara, Institute for the Future 34 12 Return to Top Drugs of Abuse Drugs of Abuse Elena Khromenko, MD, Sacred Heart Family Medicine Residency Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Handouts for this presentation are currently unavailable. Return to Top VTE: Beat the Clot! VTE: Beat the Clot! William Sonnenberg, MD, Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Pennsylvania Academy of Family Physicians November 7, 2015 Allentown, PA Venous Thromboembolism 1 BEAT THE CLOT 2 Faculty and curriculum development team Our faculty and planners have completed disclosure of interest statements. Drs. Olson and Dressner, and Mss. Shelly Rodrigues, Jerri Davis and Mary Ales declare that in the past 12 months neither they nor any members of their families have had a financial interest in organizations supporting this activity. Dr. Flores declares that in the David Garcia, Christopher Flores, Mark Dressner, Cheri Olson, MD past 12 months he has received Advisory Board MD MD MD Family Medicine honoraria from Aerocrine and Hematology and Family Medicine Family Medicine Faculty, La Crosse ResMed. Dr. Garcia declares Long Beach, CA Mayor Family that in the past 12 months he Internal Medicine Faculty, Loma Linda has served as a consultant for Professor of University School of Medicine Boehringer Ingelheim, Bristol Medicine, Division Medicine Residency Program Myers Squibb, Daiiichi Sankyo and Pfizer and received of Hematology research support from Daiichi University of Sankyo and Janssen. Washington School CAFP’s Committee on of Medicine Continuing Professional Development reviews and resolves all COI disclosures. Today’s f aculty 3 William R. Sonnenberg, MD Past President, PAFP Titusville, PA Dr. Sonnenberg declares that in the past 12 months neither he nor his spouse/partner have had any financial relationships commercial entities who might support this project. 1 Sponsors and support 4 This activity is sponsored by the California Academy of Family Physicians. It has been developed as part of the work of the TEAM-A Partnership, a 10-organization collaboration seeking to improve the care of patients with AFib and VTE conditions. This initiative is supported by an unrestricted educational grant from Bristol-Meyers- Squibb/Pfizer. VTE: Beat the Clot 5 • Online VTE community for you facilitated by us • Private! Secure! • Interact, share, learn REQUEST an invitation to join via email: [email protected] type “yammer” in subject line Questions for today 6 1.How do I complete the initial assessment and management ? 2.How long do I treat? 3.What about peri-operative and peri- procedural care? 2 DVT and PE 7 • Kills 4-5 times as many as breast cancer • 300,000 deaths per year • Number one preventable cause of hospital related deaths • 10% of hospital deaths • #1 killer of pregnant women Initial Assessment and Management 8 Claire 9 49-year-old woman. Unilateral leg pain and swelling 4 days after completing a 10.5 hour air flight.. HR 104, BP normal, pO2 91% on room air No history of DVT/PE in primary relatives. Left leg swollen, no circulatory insufficiency. Compression ultrasonography shows acute femoral vein thrombosis (left leg). 3 Classic Signs of DVT 10 • All have low predictive value • Homans’ sign • Edema • Tenderness • Warmth • Redness Differential Diagnosis of DVT 11 • 75% of suspected DVT will have other cause • Ruptured Baker’s cyst • Cellulitis • Muscle tear or cramp • Muscle hematoma • Superficial phlebitis Wells Criteria for DVT 12 Clinical Feature Points Pts Risk Active Cancer 1 Leg paralysis, immobile 1 ≥3 High 75% Bedridden > 3 days 1 Local vein tenderness 1 1 -2 Mod 17% Entire leg swollen 1 0Low 3% Unilateral swelling > 3 cm 1 Unilateral pitting edema 1 Superficial veins 1 Likely alternative -2 4 D-Dimer Tests 13 • Vary widely in sensitivity and specificity • Positive test does not raise likelihood of DVT • Good sensitivity • Wells < 2 and negative D-dimer less than 0.4% likelihood • Negative predictive value 94% Doppler Ultrasonography 14 • Most widely used • Normal study in high risk patient not good enough • Repeat in 7 days • Old clot, new clot - same on U/S • Inaccurate in pelvis or small calf vessels • Obesity or edema hurts accuracy • False positive in superficial phlebitis, popliteal cysts, or abscess Superficial Femoral Vein 15 • DEEP VEIN! • 24% of respondents would have anticoagulant (FP, IM, Chairpersons, lab directors) • 93% of vascular labs use term 5 Assuming Claire’s diagnosis is correct: 16 The most important next step in the management of this patient is: A. Measure d-dimer concentration B. Perform CT angiogram (helical/spiral CT) of the chest C. Administer anticoagulation (in therapeutic doses) D. Administer systemic thrombolysis (IV tissue plasminogen activator) E. Perform pharmaco-mechanical thrombolysis (local therapy) You can download medical apps, like the Wells scale, to assist you in your assessment. http://www.mdcalc.com/wells-criteria-for- dvt/ As you continue to treat Claire: 17 Which of the following would NOT be an indication for treatment over and above anticoagulation? A. Pulmonary embolism with systemic hypotension and tachycardia, but normal arterial oxygen saturation B. Iliac vein thrombosis with phlegmasia cerulea dolens (possibly compromised circulation) C. Common femoral vein thrombosis greater than 6 cm in length D. Pulmonary embolism with biochemical and echocardiographic evidence of right ventricular strain Claire 18 Does this information change your treatment of Claire? . She has a diagnosis of VTE . Is Claire at risk for complications of pulmonary embolism? . Would you assign her high or low risk? 6 Low-risk PE may be treated out of hospital 19 Pooled analysis of > 1,200 patients with acute low-risk PE (all treated as outpatients; 11 studies) 90-day Event Rate Outcome (95% CI) Recurrent VTE 1.47% (0.47 to 3.0%) Fatal PE 0.47% (0.16 to 1.0%) Major Bleeding 0.81% (0.37 to 1.42%) Fatal ICH 0.29% (0.06 to 0.68%) Overall Mortality 1.58% (0.71 to 2.80%) Piran et al. Thromb Res. 2013 Nov;132(5):515-9. 20 Multiple screening tools exist to assist you in assigning risk. The Pulmonary Embolism Severity Index (PESI) Score What does this mean for Claire? Predictors B‐Coefficients Points Assigned (95% C1) Demographic characteristics Class 1 – Low risk Age, per year 0.03 (0.02‐0.03) Age, in years Class 5 – Jump on this right now! Male sex 0.17 ((0.02‐0.032) + 10 Co‐morbid conditions In a study reported by Jimenez et al Cancer 0.87 (0.71‐1.03) + 30 Chest 2007 vol. 132(1):P 7-8, of 10,354 Heart failure 0.31 (0.14‐0.49) + 10 patients with 30-day PE risk Chronic lung disease 0.30 (0.12‐0.47) + 10 stratification, 953 died: Clinical findings Pulse > 110/min 0.60 (0.44‐0.76) + 20 Class Death Systolic blood pressure < 100mm Hg 0.86 (0.67‐1.04) + 30 PESI I 1.1 (0.7–1.7) Respiratory rate > 30/min 0.41 (0.23‐0.58) + 20 PESI II 3.1 (2.5–4.0) Temperature <36 C0.42 (0.25‐0.59) + 20 PESI III 6.5 (5.5–7.6) Altered mental status 1.50 (1.30‐1.69) + 60 PESI IV 10.4 (9.0–11.9) Arterial oxygen saturation <90% 0.58 (0.37‐0.79) + 20 PESI V 24.5 (22.7–26.9) Point total and risk classes: < 65=Class I, 66‐85=Class II, 86‐105=Class III, 106‐125+Class IV, >125=Class V Aujesky, D. et al J Respir Crit Care Med. 2005;172,1041-1046. Is anticoagulation sufficient? Yes/No, why? Can I treat Claire outside the hospital? If Yes. Why, and how? If No. What are the situations that merit in- hospital treatment? Discussion questions 21 7 Of the following treatments for acute DVT/PE, which does not require an antecedent course of heparin (i.e. can be given as monotherapy from the outset)? A. Dabigatran 150 PO BID B. Rivaroxaban 15 mg PO BID C. Edoxaban 5 mg PO QD D. Warfarin 5 mg PO QD What medication should I prescribe for Claire? 22 Of the following treatments for acute DVT/PE, which does not require an antecedent course of heparin (i.e. can be given as monotherapy from the outset)? A. Dabigatran 150 PO BID B. Rivaroxaban 15 mg PO BID C. Edoxaban 5 mg PO QD D. Warfarin 5 mg PO QD What medication should I prescribe for Claire? 23 Traditional Preferred Treatment Plan for Most Patients * 24 . Prescribe 5-7 days of injectable anticoagulant (e.g. LMWH 1 mg/kg BID) . Prescribe 7 days of warfarin (e.g. 5 mg daily) . Arrange appropriate follow-up appointments, care and activities *Long-term LMWH preferred for cancer-associated VTE 8 Unfractionated Heparin 25 • APPT 1.5 to 2.3 control • Bleeding, thrombocytopenia • Higher in >65, recent surgery, PUD, liver disease, occult cancer, bleeding problems • Major complications 2% • Can stop when INR exceeds 2.0, 4-5 days Heparin-Induced Thrombocytopenia 26 • Develops 5-10 days after start of heparin, surgery resets the clock • May happen within 100 days of previous Rx • 19 days after stopping heparin • Mean platelet count 60,000 • Hypercoagulability, thrombosis occurs 1/3 of the time Risk of HIT 27 • 1/5000 • 1-2% in cardiac surgery • 10x higher in unfractionated heparin • Higher with major surgery • Medical therapy • Rare in obstetrical patients 9 Heparin-Induced Thrombocytopenia 28 Management HIT 29 • Platelet factor 4-heparin antibody test if clinical features suggest HIT • High negative predictive value • Low positive predictive value • Stop heparin immediately • Use alternative anticoagulants • Argatroban, danaparoid, fondaparinux, or bivalirudin • Cannot use LMWH or Coumadin Low-Molecular-Weight Heparin 30 • Longer ½ life • Fixed, weight based dosing • Thrombocytopenia less likely • Equal to heparin in DVT • Out patient therapy safe and cost effective • Stable hemodynamically • No renal failure • Stable home environment 10 Nonpharmacologic Measures 31 • Limb elevation • Local heat • Minimal activity • Bathroom, kitchen • Graded compression stockings • 50% reduction in postphlebitic syndrome Challenges with Warfarin 32 Are there similar challenges with the DOACS? Aspirin? Clopidogrel? . Delayed onset/offset . Unpredictable dose response . Narrow therapeutic range . Drug-drug, drug-food interactions . Problematic monitoring . INR should be determined at least weekly during initiation and at least Ansell J, et al. Chest. 2001;119(1 monthly when INR is in range and stable Suppl):22S-38S. Hirsh J, et al. Chest. 2001;119(1 Suppl):64S-94S. . Slow reversibility January CT, et al. J Am Coll Cardiol. 2014;64(21):e1-76. doi: 10.1016/j.jacc.2014.03.022. Epub 2014 Mar 28. Warfarin Necrosis 33 • Typically in first several days • Mainly in Protein C deficiency • Inhibition of Protein C stronger than K-dependent coagulation factors • Protein C is anticoagulant 11 Warfarin Herbal Interactions 34 • Ginkgo – increase bleeding • St. John Wort – interfere with warfarin • Ginseng – increase bleeding • Garlic – not dietary, only supplement; increase bleeding • Ginger – increase bleeding Inferior Vena Cava Filter 35 • Indicated when PE reoccurs on anticoagulation • Lower 12 day rate but no difference at two years • Not first line therapy AC alone vs. AC + Filter for PE 36 When do you treat more aggressively? A study done by Mismetti et al. JAMA. Clinical Outcomes for Patients with at Least 1 Event in the PREPIC2 Trial 2015;313(16):1627-1635, showed:Group, No. with Events (%) 399 Patients randomized Clinical Outcomes Filter Group n=200 Control Group n=199 At 3 Months 200 Randomized to the Recurrent pulmonary embolism (primary efficacy outcome) c 6 (3.0) 3 (1.5) retrievable inferior vena Fatal 6 (3.0) 2 (1.0) Nonfatal 0 (0.0) 1 (0.5) cava plus the Recurrent deep vein thrombosis 1 (0.5) 1 (0.5) anticoagulation group Recurrent venous thromboembolism 7 (3.5) 4 (2.0) Major bleeding 8 (4.0) 10 (5.0) (filter group) Death 15 (7.5) 12 (6.0) At 6 Months Recurrent pulmonary embolism c 7 (3.5) 4 (2.0) 199 Randomized to the Fatal 6 (3.0) 3 (1.5) anticoagulation group Nonfatal 1 (0.5) 1 (0.5) Recurrent deep vein thrombosis 1 (0.5) 2 (1.0) alone (control group) Recurrent venous thromboembolism 8 (4.0) 6 (3.0) Major bleeding 13 (6.5) 15 (7.5) Death 21 (10.6) 15 (7.5) 12 ACCEPTED indications for? 37 IVC placement? tPA in PE? tPA in DVT? Recent DVT/PE with . Hypotension, not . Compromise of tissue absolute contraindication corrected with volume perfusion (dusky, painful, to anticoagulants resuscitation swollen extremity) . Deterioration (falling BP, . ?Ilio-femoral thrombosis? increased HR or O2 requirement) despite AC . long term follow-up therapy data suggest reduction of post-thrombotic . ? Evidence of RV “strain”; syndrome) ? Elevated troponin . More data to come from the ‘ATTRACT’ trial Meyer et al. N Engl J Med 2014;370:1402-11. Konstantinides S. N Engl J Med Enden et al. Lancet. 2012 Jan 7;379(9810):31-8. 2008;359:2804-13. Vedantham et al. Am Heart J. 2013 Apr;165(4):523-530. Catheter-Directed Thrombolysis 38 • No mortality improvement (1.2% vs 0.9%) • More bleeding and transfusions (11.1% vs 6.5%) • Pulmonary embolus (17.9% vs 11.4%) • Vena cava filter (34.8% vs 15.6%) • Longer LOS and cost JAMA Intern Med. 2014;174(9):1494-1501 39 DOACs for Venous Thrombosis Rivaroxaban Dabigatran Apixaban Edoxaban XARELTO® PRADAXA® ELIQUIS® SAVAYSA® . 15 mg b.i.d. for 3 . 150 mg b.i.d. . 10 mg b.i.d. for 7 . Daily (60 mg; or 30 weeks days mg for renal . 5 days of impairment or low . then 20 mg once parenteral . then 5 mg b.i.d. weight) daily treatment needed before dabigatran . Can be used . 5 days parenteral . Can be used WITHOUT (LMWH) treatment WITHOUT parenteral heparin needed before parenteral heparin treatment first edoxaban treatment first FDA Approval Status (for VTE) Approved Nov 2012 Approved Apr 2014 Approved Aug 2014 Approved Jan 2015 13 Novel Anticoagulants 40 Reasons NOT to treat acute PE/DVT with DOACs 41 . Severe renal insufficiency (Cr Cl < 30 mL/min) . Weight > 120 kg or < 50 kg . tPA use contemplated . PATIENT CANNOT AFFORD MEDICATION . No reversal agent in the case of severe/life- threatening bleed . Known “pro-thrombotic state” . HIT, cancer, antiphospholipid syndrome Clinicians’ own discomfort using DOACs can also be a barrier to prescribing these agents to patients. 42 Warfarin and DOACs Quick Comparison Warfarin Dabigatran1 Rivaroxaban2 Apixaban3 Edoxaban4 Coumadin Pradaxa Xarelto Eliquis Savaysa VKORC1 Target Factors II, VII, Thrombin IX, X Factor Xa T (max) 72-96 hours 2 hours 2.5-4 hours 3 hours 2-3 hours 5-9 hours healthy, Half-life 40 hours 14-17 hours 8-15 hours 8-10 hours 9-13 hours elderly Every 4 weeks Monitoring or PRN Not needed 1. Connolly SJ, et al. N Engl J Med. 2009;361(12):1139- Administration Once daily Twice daily Once daily Twice daily Once daily 1151. 2. Patel MR, et al. N Engl J Med. 2011;365(10):883-891. Cytochrome 80% renal, 3. Granger CB, et al. N Engl Metabolism 35% renal 25% renal 35% renal P450 20% fecal J Med. 2011;365(11):981- 992. 4. Giugliano RP, et al. N Ecarin clotting time, Engl J Med. Assay PT/INR 2013;369(22):2093-2104. thrombin time Anti-Xa activity 14 Limitations and Concerns 43 Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban Continuous monitoring X Heparin overlap often necessary X Limited experience with reversal XXXX Accumulation in renal dysfunction X X +/- X Wartak SA, Bartholemew JR. Cleve Clin J Lack of experience treating Med. 2011;78(10):657-664. bleeding XXXXGulseth MP, et al. Pharmacotherapy. 2011;31(12):1232-1249. Patel JP, et al. Br J Haematol. Limited experience in 2011;155(2):137-149. elderly, obese XXXXConnolly SJ, et al. N Engl J Med. 2011;364(9):806-817. Granger CB, et al. N Engl J Med. High acquisition cost 2011;365(11):981-992. XXXXGiugliano RP, et al. N Engl J Med. 2013;369(22):2093-2104. DOACs: Comparing risk of bleeding among different anticoagulant medications This is44 for Afib, but the bottom line is important! 30‐day event rates (%) Trial RE‐LY ROCKET‐AF ARISTOTLE dabigatran warfarin rivaroxaban warfarin apixaban warfarin Stroke or systemic 0.5 0.5 0.3 0.4 0.4 0.6 embolism Major bleed 5.1 4.6 0.99 0.79 1.6 1.9 Healey et al. Circulation. 2012. Sherwood et al. Circulation. 2014. Garcia et al. Blood. 2014. Meta-Analysis: NOACS VS Warfarin 45 30 25 20 10 0 Hemorrhagic Intracranial All-Cause Major GI -10 Stroke Hemorrhage Mortality-10 Hemorrhage Hemorrhage -20 -14 -30 -40 -50 -51 -52 RELATIVE RISK TO WARFARIN (%) WARFARIN TO RISK RELATIVE -60 Adapted from Ruff CT, et al. Lancet 2013 Online; S0140-6736(13)623 15 General Comments 46 • Reduce hemorrhagic strokes by 50% • Tissue factor in CSF?? • No dietary interaction • All are non-inferior to warfarin Reversal Agents? 47 • Aripazone – D-arginine compound • Apixaban, edoxaban, rivaroxaban, dabigatran, heparin, LMWH • Single injection • Andexanet – modified factor Xa molecule • Apixaban, edoxaban, Rivaroxaban • Sops up anti-Xa anticoagulant • Idarucizumab – antibody fragment against dabigatran • dabigatran Idarucizumab for Dabigatran Reversal 48 • Monoclonal antibody fragment binds dabigatran 350x more than thrombin • Complete reversal in 88% – 98% of patients within minutes • 1/90 patients had thrombotic event within 72 hours • Approved Oct 2016 • $3500 per dose 16 Treatment Duration 49 Claire 50 Clot provoked by travel Prescribed rivaroxaban Under your care for 3 months She’s asked how long she has to remain on the medication Clots: Provoked or Unprovoked? 51 . Provoked blood clot . Unprovoked clot . Management and workups different 17 Provoked Clots 52 Claire’s clot – caused by extended air travel – is a provoked clot. . Better in near term mortality and in long term limb health . Little work up or additional testing is needed . Stop anticoagulation after the appropriate duration Unprovoked Clots According to Bagin,53 Lancet, 2000, unprovoked clots are nearly 2x more likely to recur as provoked clots. . Fare poorly / limb threatening . Commonly associated with an underlying condition . Need work up According to Kearon et al. Annals of Internal Medicine, males are at higher risk for recurrence than females. 100 Patients with First Unprovoked DVT 54 ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ 18 One Year off Anticoagulation Medications 55 ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺ ☺☺☺☺☺☺☺☺☺☺ ☺ ☺ ☺☺☺☺☺ ☺☺☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺ ☺ ☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺ ☺= recurrent VTE Kearon, et al. NEJM 1999, vol 340. Agnelli, et al. Ann Int Med 2003, vol 139. Ridker, et al. NEJM April, 2003 Two Years off Anticoagulation Medications 56 ☺☺☺ ☺☺☺☺☺☺☺☺☺☺ ☺☺☺☺ ☺ ☺☺☺☺☺☺☺☺☺☺☺☺☺☺☺ ☺ ☺☺☺☺☺☺☺☺☺☺ ☺ ☺ ☺☺☺☺ ☺ ☺☺☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺ ☺ ☺ ☺☺☺☺☺☺ ☺☺☺ ☺☺☺☺☺ ☺ ☺☺☺ ☺☺☺☺☺☺☺☺☺☺☺☺ ☺= recurrent VTE Kearon, et al. NEJM 1999, vol 340. Agnelli, et al. Ann Int Med 2003, vol 139. Ridker, et al. NEJM April, 2003. D-dimer for Warfarin Duration? 57 • D-dimer abnormal in 223/608 pts one month after stopping warfarin for PE or DVT • Resumption of warfarin or placebo in + D- dimer group • 15% events in stopped group • 2.9% events in treated group • Hazard ratio of 4.26 N Engl J Med. 2006 Dec 28;355(26):2797 19 DVT/PE Risk Factors 58 Genetic Acquired Circumstantial Genetic Clotting Problems 59 • Anticlotting deficiencies far more common than clotting deficiencies • Failure to neutralize or control generation of thrombin • 50% of DVT or PE’s have anticlotting deficiencies Bauer KA et al. Ann Intern Med 2001;135: 367-73 Age of Onset of Thrombophilia's 60 • Mean age 35-40 • As young as second decade with multiple hereditary risk factors Martinelli I et al. Blood 92:2352 1998 20 Genetic Risk Factors - Common 61 • Factor V Leiden (1993) • Prothrombin mutation G20210A (1996) • Methylenetetrahydrofolate reductase gene mutation • 5-15% of white and East Asian Genetic Risk Factors - Rare 62 • Antithrombin III deficiency • Hyperhomocystinemia • Dysfibrinogenemia Factor V Leiden 63 • Identified 1993 • Autosomal dominant • Variant of Factor V that cannot be inactivated by activated Protein C • 5% of North American Caucasians 21 Leiden V 64 Suspect with Increased Risk of • Thrombosis under • Miscarriage age 45 • Clots in pregnancy • Family history • Clots on BCP’s • 30% of DVT have mutation (35x risk) • Doubles lifetime • Clots with smokers risk of DVT (30x risk) Leiden V and other Risk Factors 65 Risk Factor Relative Risk Obesity 8 OCP 11-41 3rd Gen OCP 50 HRT 7-16 Air travel 14-16 Minor injury 50 Cancer 12 Homocysteine 22 Genetics in Medicine (2011) 13, 1–16; doi:10.1097/GIM.0b013e3181faa0f2 Why so Common? 66 • Less blood loss during • Menses • Childbirth • Cardiac surgery • No increased risk • Arterial thrombosis • MI in older pts • CVA 22 Gene Mutation 20210A 67 • 2.3% in healthy persons • More common in Southern Europeans • Rare in Asians and Africans • Relative thrombosis risk 2.8% • 18% of patients with thrombosis Antithrombin Deficiency 68 • Breaks up fibrin and factor X • Relatively resistant to heparin • Autosomal dominant, 1/2000 • Tw o t y p e s • Type 1 – quantitative • Type 2 – qualitative • Acquired in renal failure – lost in urine Timing of Tests 69 • Thrombosis ↓ antithrombin III, protein C, protein S • Heparin ↓ antithrombin III 30% • Warfarin ↓↓ protein C and S • Perform tests 2 weeks after completing warfarin • Can check factor V Leiden, hyperhomocysteinemia, and antiphospholipid antibody anytime Ramzi DW and Leeper KV. AFP, June 15, 2004 23 Acquired Risk Factors 70 • Antiphospholipid antibodies • Renal disease (renal loss of thrombin) • Paroxysmal nocturnal hemoglobinuria Antiphospholipid Antibody 71 • Primary in 53% • Secondary to SLE, RA, TA • Consider in thrombosis and recurrent miscarriages • May promote placental thrombosis Circumstantial Risk Factors 72 • Immobilization after trauma or surgery • Medications • Oral contraceptives • Estrogen • Evista • Tamoxifen • Pregnancy • Cancer (Trousseau’s Syndrome) 24 Hospital Risk Factors 73 • Age over 40 • Immobility • CHF • Stroke • COPD • Anesthesia • Obesity Strong Risk Factors (OR > 10) 74 • Fracture (hip or leg) • Hip or knee replacement • Major general surgery • Major trauma • Spinal cord injury Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 suppl 1):19–116 Intermediate Risk Factors (OR 2-9) 75 • Arthroscopic knee surgery • Oral contraceptive • Central venous lines therapy • • Chemotherapy Paralytic stroke • Pregnancy/postpartum • Chronic heart or respiratory failure • Previous venous thromboembolism • Hormone therapy • Thrombophilia • Malignancy Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 suppl 1):19–116 25 Weak Risk Factors (OR <2) 76 • Bed rest longer than three days • Immobility due to sitting (e.g., car or air travel longer than eight hours) • Increasing age • Laparoscopic surgery 2 • Obesity (BMI > 40 kg per m ) • Pregnancy/antepartum • Varicose veins Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 suppl 1):19–116 Oral Contraceptives 77 • 4x increase in thromboembolism • 3rd generation progesterones carry twofold greater risk than earlier generations Thrombophilia Summary 78 . Antiphospholipid antibody testing is probably appropriate for many patients with spontaneous VTE . More comprehensive testing may be indicated with strong family history . Testing may be indicated for selected patients with a high risk of recurrence . For example, in some patients with prior VTE who are planning pregnancy 26 Trousseau’s Syndrome 79 • 8% of idiopathic DVT will found to have cancer within 2 years • 60% of occult cancers dx after unprovoked thromboembolism • Low grade DIC from a pro- coagulant tissue factor • Armand Trousseau diagnosed own fatal pancreatic carcinoma Cancer Screening after Unprovoked Thromboembolism? 80 • 854 pts with unprovoked DVT • Labs, CXR, breast, cervical, prostate screen • Above and abdominal/pelvic CT • 33 occult cancers found (3.9%) • 14 occult cancers in limited screen (3.2%) • 19 occult cancers in limited screen + CT (4.5%) • No mortality benefit Carrier M et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1506623 Pregnancy 81 • Relative risk of 4.3 • C-section relative risk 13.3 v. vaginal delivery • PE more common postpartum • D-dimer increases in pregnancy, normal not established Dresang Lee T. et al. AFP, June 15, 2008, p 1709 27 Risk Factors in Pregnancy 82 • Hyperemesis – dehydration and immobility • High BMI • Immobility • Thrombophilia • C-section Greer, IA; N Engl J Med 2015; 373:540-547 Differences in Pregnancy 83 Pregnancy Nonpregnant Clinical Suspicion 4% 30% Confirmed Left leg 78-90% 55% Illofemoral vein 72% 9% Treatment in Pregnancy 84 • LMWH heparin preferred • Coumadin contraindicated in pregnancy, ok in breast feeding • No direct thrombin inhibitors – cross placenta 28 85 Increased Major Bleeding Risk? Risk Factors . Concomitant Antiplatelet and other meds . Advanced Age . Prior Major Bleeding . Anemia . Uncontrolled Hypertension . INR variability and target range . Alcohol Predominantly derived from data in patients with Atrial Fibrillation. Lip et al. Thrombosis and Hemostasis, 2011. 106: 997-1011. Assessing Bleeding Risk: HAS-BLEDScore 3 is highly86 predictive of bleeding events HAS-BLED is recommended by major international guidelines HAS-BLED Score Bleeds/100 Patients* . Hypertension 01.13. Abnormal liver/renal function 11.02 . Stroke history 21.88 . Bleeding predisposition 33.74 48.70. Labile INRs 5 12.50 . Elderly (>65) Any score 1.56 . Drugs/alcohol use *p=.007 for trend of increasing bleeding risk with increasing score. Lip GY, et al. J Am Coll Cardiol. 2011;57(2):173-180, Omran H, et al. Thromb Haemost. 2012;108(1):65-73. Camm AJ, et al. Europace. 2010;12(10):1360-1420., Caims JA, et al. Can j Cardiol. 2011;27:74-90. Treat Proximal DVT or PE 87 (unprovoked) at least 3 months A Suggested Approach . Ensure the patient is up-to-date on age-appropriate cancer screening and perform careful physical exam and review of systems. . Discuss risks/benefits of extended therapy with all patients . Encourage extended therapy for patients who: . Male . Previous VTE . PE (rather than DVT) as their index event . Poor cardiopulmonary reserve . Low risk of AC-related bleeding . Test young patients for antiphospholipid syndrome before permanently discontinuing. . Consider d-dimer testing if other factors equivocal. 29 Warfarin Duration 88 Minimum Strength of Event Duration Recommendation First with reversible risk 3 months A factor First embolic episode 6 months A Recurrence 12 months B Continuing Risk Factor 12 months B Isolated calf vein 6-12 weeks A thrombosis Long Term Aspirin After Discontinuation of Anticoagulation 89 • Meta-analysis of 2 trails, 1225 patients • 100 mg aspirin after warfarin • Recurrent DVT 1/3 lower in aspirin group • 5.1% vs. 7.5% recurrent DVT • No difference in bleeding • Less MI, CVA or CV death in aspirin group Simes J, Becattini C, Agnelli G, et al. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation. 2014;130(13):1062-1071. Peri-Operative and Peri-Procedural Care 90 30 Claire 91 At 2.5 months under your care … She is still taking the AC medication as prescribed She recently had a gall bladder attack She is now scheduled to have the gallbladder removed What is Claire’s bleed risk? Is Claire92 at HIGH risk for a bleed during the procedure? Higher Risk Lower Risk Urological Minor dental Pacemaker Derm Large colonic polyps Cataract Bowel Extensive tissue injury Pericardial/intracerbral/ epidural Risk for VTE 93 . High . Recent VTE . Severe thrombophilia . Moderate . VTE 3-12 mos . Nonsevere thrombophilia . Recurrent VTE . Active cancer . Low . VTE > 12 mos and no other risk factors 31 For patients on Warfarin 94 . Most can simply interrupt without bridging . Bridging increases the risk of bleeding and likely has no benefit for any patient except those at the highest risk of thrombosis Clark NP. JAMA Intern Med. 2015 Jul;175(7):1163-8 Douketis J. NEJM. 2015 (this is a study of AF pts but shows that bridging clearly increases the risk of post-procedure bleeding) Is bridging necessary? These95 questions are important as family physicians complete pre-op physicals. • Should I consider alternative anticoagulants during the postoperative period when risk of bleeding is high or if postoperative bleeding occurs? • How long do I hold patients on anticoagulation Warfarin Dabigatran1 Rivaroxaban2 Apixaban3 Edoxaban4 medications?Coumadin Pradaxa Xarelto Eliquis Savaysa 5-9 hours healthy, Half-life 40 hours 14-17 hours 8-15 hours 8-10 hours 9-13 hours elderly Many procedures can be performed safely without NOAC interruption Need more data to select patients and procedures Short-term interruption of DOAC (in AF) is associated with low 30-day risk of stroke Bridging likely not needed (except for patients who cannot take oral medication) For patients whose procedure requires interruption 24 – 48 hours likely sufficient if renal function normal Longer interruptions if renal impairment and/or high-risk procedure More data anticipated from P.A.U.S.E.* Prospective cohort study with standardized interruption schedule Procedures and interruptions summary 96 * NCT 02228798 32 She had an uncomplicated provoked DTV. She was treated with a DOAC for three months. During her treatment she had her gallbladder removed with no issues. Claire is no longer taking AC medications and is flying to Barcelona to meet her family for her 50th birthday celebration! Claire has ongoing questions about DVTs and is excited to use the EMMI Solutions app recommended by her family physician to learn more about prevention. How is Claire? 97 Flying and Aspirin for DVT Prevention 98 • Risk is between 0-40/100,000 • 29% risk reduction with aspirin • NNT 8,600 for high risk • NNT 34,000 for low risk Ferrari et al. Chest 1999 115:400-444 Tools and resources are available 99 February 2012; 141(2_suppl) Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines www.teamanticoag.com http://bit.ly/1jr35aS 33 VTE: Beat the Clot 100 • Online VTE community for you facilitated by us • Private! Secure! • Interact, share, learn REQUEST an invitation to join via email: CME‐[email protected] type “yammer” in subject line Thank you 101 34 Return to Top Pre-Operative Assessment in the Office Pre-Operative Assessment in the Office Richard Terrence Martin, MD, Sacred Heart Hospital Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Preoperative Assessment of the Geriatric Patient in the Office R. Terry Martin M.D. Program Director Sacred Heart Hospital Geriatric Fellowship Disclaimer Dr. R. Terry Martin has no conflict of interest, financial agreement, or working affiliation with any group or organization. Objectives 1. To be able to assess the risk factors of postoperative delirium based upon cognitive assessment, depression screening and functional assessment of the patient preoperatively. 2. To preform an appropriate preoperative assessment through history, physical, labs and diagnostic tests based on the cardiopulmonary risk preoperatively and during hospitalization. 3. To optimize the patient’s status preoperatively to reduce hospital complications, length of stay and nursing home admissions for rehabilitation 4. To optimize patient medications by review utilizing the Beer’s list (AGS 2015) to reduce delirium and complication postoperatively 1 The highest rate of postoperative complications in the older patient undergoing surgery is: A. Cardiac complications B. Delirium C. Pulmonary complications D. Falls E. Infections Stopping tobacco abuse preoperatively reduces the risk of postoperative complications by which of the following percentages: A. 0% B. 5% C. 10% D. 13% E. 15% Which one of the following list is given a level of evidence rating of “A”: A. CBC is indicted for all preoperative assessments in all surgeries. B. BMP should be completed to assess for electrolyte and renal function preoperatively in all surgeries. C. Patient with S & S of cardiovascular disease should undergo an EKG. D. Patients in their usual state of health undergoing cataract surgery do not require preoperative testing. E. Random glucose or A1C measurement should be done if abnormal result would change perioperative management. 2 Importance of Preoperative Assessment of Elderly 2007 - > 65 Elderly 2006 Fastest =37% of numbers will “Baby growing hospital 35.3 % of nearly Boomers” segment of discharges inpatient and double from started 2011 elderly is > but 43% of 32.1% of 2010 to 2050 85 hospital days outpatient to 20% of care procedures Approach to Elderly ≠ Adult Risks are different pre and post-op(Multi-organ involvement) More co-morbid diseases compounded with physiologic deteriorating organ function (less able to handle stress) Less cognitive reserve capacity(more delirium) Polypharmacy and adverse drug reactions(more delirium) Potential for post-op complications are greater Require more preoperative preparation for surgery Less functional capacity and more require placement for rehab Approach to Elderly Cognitive ability and Capacity for surgery Can patient under stand the consent for surgery and risks of surgical complications? Must document baseline mental status Must have family member to confirm mental status and history Assessment: Mini-Cog test = 3 object recall and clock draw 3 Mini-Cog Test 3 Item Recall and Clock Draw 1. GET THE PATIENT’S ATTENTION, THEN SAY: “I am going to say three words that I want you to remember now and later. The words are: Banana Sunrise Chair “Please say them for me now.” Give the patient 3 tries to repeat the words. If unable after 3 tries, go to next item. Mini- Cog Test 2. SAY ALL THE FOLLOWING PHRASES IN THE ORDER INDICATED: “Please draw a clock in the space below. Start by drawing a large circle. Put all the numbers in the circle and set the hands to show 11:10 (10 past 11).” If not completed after 3 minutes terminated the test. 3. SAY: “What were the three words I asked you to remember? Mini –Cog Scoring 3 item RECALL (0‐3 points) •1 point for each correct word CLOCK DRAW (CDT): •Clock draw (0 or 2 points): 0 points for abnormal clock 2 points for normal clock • Number 1‐12 in correct order and placement inside circle •2 hands ‐ one point to 11 and other to 2 4 Mini-Cog Interpretation Positive for Cognitive Impairment Negative for Cognitive Impairment 1‐2 recall + 0 recall normal CDT 1-2 recall 3 recall (CDT + Abnormal not required) CDT Mini-Cog vs MMSE Sensitivity Specificity Time to completion Mini-Cog 76% 89% 2-4 min. MMSE 71% 94% 5-12 min. “24” cut point Depression Screening PHQ-2 Risk Factors: Female Disability Sleep Disturbance Prior depression Cognitive Impairment Living alone New medical illness Multiple co-morbidities 5 SCREENING FOR DEPRESSION Patient Health Questionnaire-2 (PHQ-2) 1. In the past 12 months, have you ever had a time when you felt sad, blue, depressed, or down for most of the time for at least two weeks? MOOD 2. In the past 12 months, have you ever had a time, lasting at least two weeks, when you didn’t care about the things that you usually care about or when you didn’t enjoy the things that you usually enjoy? ANHEDONIA One positive response requires full depression evaluation Assessment of Depression with Positive PHQ 2 • GDS - Geriatric Depression Scale for non demented patients 15 minutes to administered for 30 item form 8 minutes for 15 item form 3 minutes for 5 item for that has Sensitivity 94% Specificity 81% • Cornell Scale for Depression in Dementia 20 minutes to administered for 19 items Sensitivity 93% and Specificity 97% Same questions are asked to patient and informant(2 separate) Based on Assessor direct rating rather than informant and patient GDS 5 item II. Criteria: Questions (abnormal or positive answers in parentheses) Are you basically satisfied with your life? (No) Do you often get bored? (Yes) Do you often feel helpless? (Yes) Do you prefer to stay at home rather than going out and doing new things? (Yes) Do you feel pretty worthless the way you are now? (Yes) Two positive answers suggests depression 6 Consequences of depression Increase Discharge to TCF/SNF for rehab Decreased Prolonged LOS Motivation for rehab Post-op delirium + Increase pain complications perception Increase analgesic use CARDIAC RISK STRATIFICATION FOR NONCARDIAC SURGICAL PROCEDURES (BASED ON REVISED CARDIAC RISK INDEX) Risk Examples Low (< 1%) Endoscopic procedures, superficial surgery, cataract surgery, breast surgery, ambulatory surgery Intermediate Intraperitoneal and intrathoracic surgery, cardiac (1-5%) endarterectomy, head and neck surgery, orthopedic surgery, prostate surgery Vascular Aortic/other major vascular surgery, peripheral vascular surgery (>5%) Reprinted from Journal of the American College of Cardiology, Vol 54(22), Fleischmann KE, Beckman JA, Buller CE, et al., 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade, p2102-2128, 2009, with permission from Elsevier. ACC/AHA Guidelines 7 ESTIMATING ENERGY REQUIREMENTS FOR VARIOUS ACTIVITIES52 Metabolic Equivalents (METs) Can you … 1 MET Take care of yourself? Eat, dress, and use the toilet? Walk indoors around the house? Walk a block or two on level ground at 2 to 3 mph (3.2 to 4.8 kph)? 4 METs Do light work around the house like dusting or washing dishes? Climb a flight of stairs or walk up a hill? Walk on level ground at 4 mph (8.4 kph)? Run a short distance? Move heavy furniture? Participate in moderate recreational activity like golf, bowling, dancing, doubles tennis, or throwing a baseball or football? >10 METs Participate in strenuous sports like swimming, singles tennis, football, basketball, or skiing? Reprinted from Journal of the American College of Cardiology, Vol 54(22), Fleischmann KE, Beckman JA, Buller CE, et al., 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade, p2102-2128, 2009, with permission from Elsevier. EKGs Not Recommended for low risk procedure if asymptomatic Recommended Intermediate or vascular surgery Known ischemic heart disease, PVD, CVA, HF, arrhythmias, CKD, COPD Noninvasive Stress Test Not recommended Intermediate risk surgery if no CVD clinical risk factors All low-risk surgeries Recommended for Intermediate and Vascular Surgeries 3 or more CVD clinical risk factors Functional capacity < 4 METs 1-2 clinical risk factors + < 4 METs 8 Pulmonary Complications Pulmonary Complications appear Day 4 vs Day 1 Cardiac Similar prevalence to cardiac adverse events. In elective abdominal procedures, pulmonary complications occurred > cardiac adverse events and longer LOS. Highest total hospital costs compared with post-op infectious, thromboembolic, and cardiac adverse events, and required the longest median LOS Pulmonary vs. Cardiac Complications ORIF hip with either general or spinal anesthesia Cardiac complications 8% Pulmonary complications 4% OVERALL CARDIAC PULMONARY MORTALITY COMPLICATIONS COMPLICATIONS 30 days 22% 17% 1 Year 36% 44% Pulmonary Risk factors Age > 60 Functional dependence ADL’s > IADL’s HF OSA Pulmonary HTN Delirium ( hip fracture 26 % pre-op and 40% overall in hospital) Creatinine > 1.5 mg/dl Weight Loss > 10 lbs. in 6 months Serum albumin < 3.5 mg/dl 9 Pre-Op Recommendations for Preventing Pulmonary Complications Optimization of pulmonary function in COPD and Asthma (delay surgery if necessary) Smoking cessation (conflicting studies) May increase pulmonary complications < 8 weeks of cessation Meta-analysis smoking cessation = no increase in pulmonary complications Pre-op Inspiratory Muscle training for thoracic surgery Select Chest x-rays and PFT’s Pulmonary Complications Atelectasis – Rx: out of bed Day 1 and incentive spirometry Bronchitis/Pneumonia Exacerbation of preexisting pulmonary disease Bronchospasm PE ARDS Prolonged Mechanical Ventilation PFT’s and Chest X-Ray Chest X-ray 14,650 pts. - 23% abnormal - changed management 3% of time Abnormal chest x-ray was predicted from H&P Chest x-ray should be obtain with known cardiopulmonary disease If >50 yrs. undergoing upper abdominal, thoracic or AAA surgery PFT’s H&P superior for non-thoracic surgeries at predicting complications 10 Medication Review/Elimination 50% of > 60 yrs. have 5 or more meds/supplements predicting 80- 100% chance of drug-drug interactions Beer’s List Medication (potential inappropriate)- AGS 2015 Many drugs renal cleared but eGFR on lab slips do not reflect renal function in Elderly due to loss of muscle mass and organ deterioration( liver and renal) Calculate eGFR with Cockcroft-Gault Formula > Modification of Diet in Renal Disease Study Equation (MDRD) eGFR= (140-Age) x Body wt. (kgs.) / 72x Cr = Male (X .85 female) Cockcroft – Gault Calculation 82 years female for elective cholecystectomy with weight of 130 lbs. and serum creatinine 1.3. LAB slip states eGFR (nomogram) = 49 ml/min(CKD 3) By Cockcroft –Gault calculation 31.06 ml/min ( ≈ CKD 4) Reduce dosages: Antibiotics Novel Oral Anticoagulants (NOAC shouldn’t be used) Fluids Digoxin, etc. Pre-op Testing Geriatric Patients Test Recommend- Indication ations Hemoglobin All Except Cataracts Particularly >80 BUN/Cr All Major surgery DM, CAD, ACE/ARB, NSAIDS Myeloproliferative disorders WBC NO Splenomegaly, Lymphadenopathy, Infections Spontaneous bleeding, easy bruising, Platelet Count NO myeloproliferative disorders 11 Pre-op Testing Geriatric Patients Test Recommend- Indication ations PT/INR Vascular Procedures, Cardiac, Cancer PTT NO surgery, Neurosurgery, Spinal procedures Electrolytes NO CKD, HF, Diuretics, digoxin, ACE/ARBs Glucose NO DM, Obesity Medication to Hold Pre-0p DM Sulfonylureas - Midnight (fasting) Metformin - 2 days before and after Thiazolindinedones - 3 days before GLP 1 Agonists - Midnight DPP 4 Inhibitors –Midnight Long acting Insulin regular dose substitute - 0.2– 0. 4 U/Kg/Day + Geriatric sliding scale Medication to Hold Pre-Op CVS ASA High risk CVD – continue Low risk CVD – Hold 7 days before Clopidigril – 5 days NSAIDS – 2 days Coumadin – 5 days NOAC (Dabigatran, Rivaroxaban, Apixaban) 2 days all are renal cleared Don’t use GFR < 30 ml/min. (CKD 4 & 5) Cockcroft-Gault formula Loop Diuretics – Midnight (NPO) 12 Meds to Continue β – Blockers – TX Goal is resting HR 60-70 as optimal DO NOT START new β – blocker Pre-op ACE and ARB continued All inhalers continued Smoker advise continue to smoke until after surgery as Risk ≤ Stopping “Clearance” Should be a communication to Surgeon and Anesthesiologist 72 years old obese male with COPD, OSA, DM, CAD and PVD which are well controlled. He has been evaluated with EKG, Stress test, chest x-ray CBC, CMP which are within normal limits (Attached). His functional capacity is ≥ 4 METs. Cognitively he is intact on Mini-Cog with 5/5. He was instructed to hold his ASA for 7 days, metformin for 2 days before surgery. He is to take 30 U of Lantus SQ in AM on the day of surgery (approx. ½ of usual dosage). Patient will bring and use his CPAP setting of 12 for 7 hours nightly. I would recommend Incentive Spirometry, out of bed and ambulate Day 1, O₂ saturation of 92-94 % and VTE prophylaxis and utilization of a low dose Geriatric Sliding Scale for his DM. “Clearance” • Do not hesitate to cancel elective surgery if the patient has not been optimized with his chronic diseases • Don’t write “cleared for surgery” due to medical/legal issues 13 eGFR per calculation is the best representation of a geriatric patient renal function if the following is given: A. Age, weight and Height B. BMI and serum creatinine C. Serum creatinine, BUN and age D. Height, weight and serum Creatinine E. Age, weight and serum creatinine Which of the following medication should not be held in a high risk surgery A. Clopidigril B. Aspirin C. Glyburide D. Metformin E. Furosemide When utilizing the Mini‐Cog test for cognition, which of the following indicates normal cognitive function: A. 3/3 recall and 2/2 clock draw B. 2/3 recall and 0/2 clock draw C. 0/3 recall and 2/2 clock draw D. 1/3 recall and 0/2 clock draw 14 Major References 1. Fleischer LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. J AM Coll Cardiol. 2014; 64(22): 77-137 2. Chow WB, Rosenthal RA, Merkow RP, Ko CY, Esnaola NF. Optimal Preoperative Assessment of the Geriatric Surgical Patient: Best practice Guidelines: ACS NSQIP/AGS JACS. 2012: 215(4): 453 – 466 3. Preoperative Cardiac Risk Assessment. BMJ Best Practices: BMJ update June 16, 2015 15 Return to Top ENT Review ENT Review Robert Langan, MD, St. Luke's Family Medicine Residency Program Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Otolaryngology Potpourri Robert C. Langan, MD, FAAFP Program Director St. Luke’s Family Medicine Residency Bethlehem, PA 1 Neither I nor my family have any financial interest or relationship with any proprietary entity producing health care goods or services 2 Goals & Objectives 1. Review pertinent ENT anatomy 2. Describe presentations, signs, and symptoms of common ENT disorders as well as laboratory and diagnostic studies 3. Discuss non‐pharmacologic and pharmacologic therapy of common ENT disorders 4. Identify indications for ENT referral 3 1 According to the IDSA, which antibiotic is first line for the treatment of acute bacterial sinusitis? A. High‐dose amoxicillin B. Amoxicillin‐clavulanic acid C. Trimethoprim‐sulfamethoxazole D. Levofloxacin E. Clarithromycin 4 According to the AAP, diagnosis of acute otitis media requires which of the following? A. Moderate to severe middle ear effusion (MEE) B. New onset otorrhea without otitis externa C. Mild MEE AND <48 hours of ear pain/erythema of the tympanic membrane D. A or B or C E. A and B and C 5 The preferred first line treatment for allergic rhinitis is: A. Sedating antihistamines B. Non‐sedating antihistamines C. Intranasal corticosteroids D. Intranasal cromolyn E. Leukotriene receptor agonists 6 2 Outer Ear 7 Otitis Externa • 98% caused by bacteria (Pseudomonas, Staph aureus) • RF: swimming, eczema, seborrhea, trauma • Diagnosis: – Acute onset AND ear pain AND ear canal edema/erythema – Fever, otorrhea, lymphadenitis, TM erythema unnecessary • Treatment: – Effective (NNT = 2) – No evidence that 1 topical antibiotic is superior to another – Topical steroids improve resolution of symptoms – No RCT evaluating preventive measures (ear plugs, acetic acid, avoiding self cleaning) 8 Necrotizing Otitis Externa • Formerly called “malignant” OE • Usually caused by Pseudomonas • More common in diabetics, elderly • Spread of infection from canal to temporal bone • Presents with severe ipsilateral ear pain • Urgent ENT evaluation: – Debridement – IV and topical anti‐Pseudomonal antibiotics 9 3 Middle Ear 10 11 Acute Otitis Media Guideline • AAP (2013), endorsed by AAFP • Applies to healthy children aged 6 months to 2 years • Diagnosis requires: – Moderate to severe middle ear effusion (MEE) OR – New onset otorrhea without otitis externa OR – Mild MEE AND <48 hours of ear pain/erythema of TM • Parental suspicion of OM and ear tugging have the highest positive likelihood ratio (3) • Treat pain (how to treat not specified) 12 4 When to Treat AOM AGE SEVERE* NONSEVERE 6 months‐ Antibiotics Antibiotics for bilateral OM 23 months Antibiotics or observation** for unilateral OM >24 months Antibiotics Antibiotics or observation** for bilateral OR unilateral OM *SEVERE: Moderate/severe otalgia, otalgia for >48 hours, temperature >102.2° F (39° C) **OBSERVATION requires follow up with initiation of antibiotics if symptoms do not improve in 48-72 hours. 13 AOM Initial Treatment • High‐dose amoxicillin (90 mg/kg/day) is the preferred 1st line antibiotic for patients who are not allergic AND have not received amoxicillin in the last 30 days • If amoxicillin has been used in the last 30 days OR conjunctivitis is present, high dose amoxicillin‐clavulanic acid is recommended 14 AOM Treatment • PCN Allergic (non‐severe) – Cefdinir 14 mg/kg/day in 1 or 2 daily doses – Cefuroxime 30 mg/kg/day in 2 daily doses – Cefpodoxime 10 mg/kg/day in 2 daily doses – Ceftriaxone 50 mg/kg/day IM • Clindamycin 30‐40 mg/kg/day in 3 daily doses • Macrolides, TMP/SMX not recommended • DURATION: 10 days (<2 years old) 7 days (>2 years old) 15 5 Other AOM Pearls • Prophylactic antibiotics not recommended • Consider PE tubes for 3 episodes of AOM/6 months OR 4 episodes/12 months • Encourage exclusive breastfeeding for the first 6 months • Avoid passive tobacco exposure • Appropriate vaccinations 16 OTITIS MEDIA WITH PERFORATION 1. Otorhea + AOM: Treat like AOM. 2. Traumatic Perforation: Small perforations (<30%) usually heal spontaneously in 4-6 weeks. Large perforations or perforations in specific professions (i.e. pilots) need ENT. 3. Keep ear dry. 4. Avoid ototoxic eardrops (gentamicin, neomycin, tobramycin). 5. Pain from AOM DECREASES with perforation; if pain INCREASES consider mastoiditis. 17 SEROUS OTITIS MEDIA 1. May be post-AOM (4-6 weeks). 2. Other causes include AR, exposure to tobacco, other URI. 3. More common in children; usually asymptomatic. 4. Treat underlying conditions (i.e. allergic rhinitis, avoidance of tobacco). 5. Hearing test for speech delay, persistent (>4-6 months) SOM. 6. Role of PE tubes. 18 6 TYPE A: NORMAL TYPE B: MIDDLE EAR FLUID TYMPANOGRAMS TYPE C: SINUS/ALLERGY CONGESTION 19 Hearing Loss 20 Screening for Hearing Loss: Infants • All newborns should be screened for hearing loss prior to 1 month of age (USPSTF B) • OtoacousticAuditory brainstem response • Children who fail both should see ENT/audiology within 3 months • RF: NICU ≥ 2 days Family History of hereditary hearing loss Craniofacial abnormalities Congenital syndromes 21 7 Screening for Hearing Loss: Geriatrics • Inadequate evidence to recommend for or against screening for hearing loss in adults (USPSTF I) • Increasing age is the leading RF for hearing loss • Hearing aids improve self‐reported hearing, communication, and social functioning • Prevention: Avoid loud noises Hearing protection Tobacco cessation Check medications 22 Hearing Loss • CONDUCTIVE: hearing loss due to the conductive pathway of the ear – Cerumen impaction, swelling of external auditory canal, TM perforation, effusion • SENSORINEURAL: hearing loss due to problems with the inner ear/8th cranial nerve; most common type of hearing loss – Persistent noise exposure, presbycusis, familial/genetic factors, postinflammatory, tumor 23 Testing for Hearing Loss WEBER TEST RINNE TEST • Tuning fork on forehead • Tuning fork at mastoid, then ear • Sound radiates to side with • Should still hear sound conductive hearing loss • Abnormal in conductive loss • Sound radiates away from • Unhelpful for sensorineural loss sensorineural loss Audiology evaluation is superior to both Weber and Rinne for evaluation of hearing loss. 24 8 Hearing Loss Pearls • Sudden sensorineural hearing loss: ENT evaluation • Unilateral hearing loss in adults: consider acoustic neuroma; test of choice is MRI • Unilateral hearing loss + tinnitus + dizziness: consider Ménière’s Disease • Avoid loud noises for 14 hours prior to hearing tests 25 Dizziness 26 Dizziness • May encompass dysequilibrium, syncope, lightheadedness, or vertigo • VERTIGO: the sensation of spinning or whirling that occurs as a result of a disturbance in balance • Causes: vestibular neuritis (labyrinthitis), benign paroxysmal positional vertigo, Ménière’s Disease 27 9 Vestibular Neuritis • One of the most common etiologies of vertigo • Caused by inflammation of the vestibular portion of the 8th cranial nerve • Usually viral; may occur after URI • Intense symptoms that improve over several days; hearing unaffected • Nausea and/or vomiting common • Treat with vestibular suppressant medication (meclizine) short term, fluids 28 BPPV • Caused by otoconia (calcium carbonate crystals) that have become free floating and enter one of the semicircular canals • Sudden turning of the head/arising from bed in the morning creates intense vertigo that lasts for less than 30 seconds • Meclizine ineffective • Treat with Dix‐Hallpike maneuver, vestibular therapy 29 30 10 Ménière’s Disease • Precise etiology unknown; thought to be due to distention of endolymphatic space • Intense, episodic vertigo (lasting minutes to hours) associated with hearing loss, tinnitus • Treatment is difficult • ENT evaluation, salt restriction, thiazide diuretics 31 Facial Nerve Disorders 32 Facial Nerve Paralysis 33 11 Bell’s Palsy •Sudden onset, unilateral •Idiopathic, but felt to be due to HSV 1 •Do not routinely screen for Lyme Disease, DM •Imaging if symptoms do not improve with treatment •Prednisone 60-80 mg daily x 7 days; start as soon as possible •No evidence for effectiveness of antivirals + prednisone 34 Ramsay Hunt Syndrome • Varicella zoster infection of geniculate ganglion of facial nerve • Facial nerve paralysis accompanied by severe pain and vesicular eruption in external auditory canal; pain precedes rash by hours to days • Rash may not be present • May represent up to 20% of cases of Bell’s Palsy •No good evidence that antivirals, corticosteroids help but usually treated similarly to Bell’s Palsy •Less likely to have complete resolution compared to Bell’s Palsy 35 Allergic Rhinitis 36 12 AR Definitions (AAOHNS, 2014) • Inflammatory, IgE‐mediated disease • Characterized by nasal congestion, rhinorrhea, sneezing, nasal itching • May be classified according to: – Temporal Pattern (seasonal, perennial, episodic) – Frequency of symptoms (intermittent, persistent) – Severity (mild, severe) • Classification scheme clinically not useful • PE: clear rhinorrhea, nasal congestion, pale nasal mucosa, red/watery eyes 37 AR Pearls • Recommend allergy testing only for patients who do not respond to empiric therapy, when the diagnosis is uncertain, or when knowledge of specific allergens is needed to target therapy • Do not routinely recommend imaging for patients • Environmental modification may be recommended • Evaluate patients for asthma, atopic dermatitis 38 AR Treatment • Nasal steroids are first line medical treatment • Non‐sedating antihistamines (NSAH) for patients with primarily sneezing/itching • Leukotriene receptor antagonists (LTRA) should not be primary therapy UNLESS asthma is also present • Combination therapy is reasonable if monotherapy does not control symptoms • Recommend immunotherapy for patients who fail combination therapy • No recommendations about herbal therapy based on lack of strong evidence 39 13 Sinusitis 40 Signs and Symptoms of Sinusitis Sign/Symptom PPV NPV Preceded by URI 81% 88% Facial pain/pressure/fullness 77% 75% Purulent rhinorrhea 61% 55% Maxillary toothache 56% 59% Nasal obstruction 43% 35% DIAGNOSIS OF ACUTE SINUSITIS: Up to 4 weeks of purulent rhinorrhea accompanied by nasal obstruction OR facial pain/pressure/fullness (AAOHNS, ACP, AAFP, IDSA) 41 Acute Bacterial Rhinosinusitis • IDSA (2013) recommends treatment for: – Persistent and not improving (≥ 10 days) – Severe symptoms (≥ 3‐4 days) OR – “Double sickening” • Assess risk of antibiotic resistance – Age <2 years or >65 years – Antibiotics within the past month – Hospitalized in the past 5 days – Co‐morbidities (incl. immunocompromised) 42 14 Acute Bacterial Rhinosinusitis • Low Risk of Resistance: – 1st Line antibiotic x 5‐7 days • High Risk of Resistance: – 2nd Line antibiotic for 7‐10 days • Worsening: – Broaden coverage, consider imaging/ENT evaluation 1st LINE: Amoxicillin/Clavulanate 2nd LINE: Amoxicillin/Clavulanate (high dose; 2 grams/day) PCN ALLERGIC: Doxycyline or Respiratory Fluoroquinolone or Clindamycin AND Cefiximine 43 Acute Bacterial Rhinosinusitis • Adjuvant Therapy: – Intranasal Steroids (h/o AR) – Saline irrigation • NOT Recommended: – Topical decongestants – Oral decongestants – Antihistamines 44 Chronic Sinusitis DEFINTION (AAOHNS) At least 2 of the following for >12 weeks: A. Facial pressure/pain B. Nasal obstruction* C. Nasal discharge* D. Reduction in smell At least 1 of the following signs of inflammation: A. Nasal polyps (rhinoscopy/endoscopy) B. Edema/purulence of middle meatus C. Inflammation on CT of paranasal sinuses 45 15 Chronic Sinusitis Recommendations (JAMA 2015) • Topical steroids for all patients ( Grade A) • High volume (>100 mL) saline irrigation for all patients ( Grade A) • AR: Consider NSAH, LTRA • Sinus surgery for persistent symptoms (Grade C) POLYPS NO POLYPS Oral steroids (14‐21 d) Clarithromycin (90 d) Doxycycline (21 d) Oral steroids (14‐21 d) Culture (per ENT) Culture (per ENT) AR: Allergic Rhinitis; NSAH: Non-Sedating Antihistamine; LTRA: Leukotriene- Receptor Antagonist 46 Salivary Gland Disorders 47 Salivary Gland Disorders • Acute suppurative sialadenitis: – Bacterial infection (usually S. aureus) after duct obstruction – More common in hospitalized, debilitated patients, use of anticholinergic medications – Affects 1 gland, usually parotid – Warm compresses, oral hygiene, antibiotics, ? drainage • Recurrent/chronic sialadenitis: – Repeated episodes of sialadenitis causes fibrosis of duct – Imaging, ENT to try to identify cause of obstruction – Surgical therapy 48 16 Salivary Gland Disorders • Bilateral salivary gland enlargement: viral infection, HIV, autoimmune disorder (Sjögren’s disease) • Mumps is the most common cause of non‐ suppurative acute sialadenitis – Vaccination has decreased the incidence by 99% • Salivary gland tumors are uncommon – Red Flags: pain, facial paresis, fixation of the mass, associated lymphadenopathy – Parotid tumors usually benign, submandibular/ submaxillary more likely to be malignant 49 Head and Neck Cancer 50 Head & Neck Cancer Pearls • SCC most common type of primary cancer • Biopsy lymph nodes present for greater than 6 weeks OR if constitutional symptoms are present • Be suspicious of hard and nonmobile lymph nodes • Traditional risk factors: abuse of tobacco, alcohol • HPV‐associated oropharyngeal cancer – Younger age, associated with oral sex, better survival, better response to treatment – Presents with neck mass, sore throat, dysphagia – HPV vaccines seem to be effective at ↓ incidence • Contrast‐enhanced CT is the imaging test of choice 51 17 Questions? 52 References 1. Wax, MK. Primary Care Otolaryngology, 2nd Edition. American Academy of Otolaryngology—Head and Neck Surgery Foundation. 2004. 2. www.entnet.org 3. Wilson KF, et al. Salivary gland disorders. Am Fam Physician 2014;89(11):882‐8. 4. Albers JR, Tamang S. Common questions about Bell’s palsy. Am Fam Physician 2014;89(3):209‐12. 5. Uscategui T, Doree C, Chamberlain IJ, Burton MJ. Antiviral therapy for Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD006851. 6. Uscategui T, Doree C, Chamberlain IJ, Burton MJ. Corticosteroids as adjuvant to antiviral treatment in Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006852. 53 References 7. Rudmik L, Soler ZM. Medical therapies for adult chronic sinusitis: a systematic review. JAMA 2015;314(9):926‐39. 8. Moore KA, Mehta V. The growing epidemic of HPV‐positive oropharyngeal carcinoma: a clinical review for primary care providers. J Am Board Fam Med 2015;28:498‐503. 9. Haynes J, et al. Evaluation of neck masses in adults. Am Fam Physician 2015;91(10):698‐706. 10. Harmes KM, et al. Otitis media: diagnosis and treatment. Am Fam Physician 2013;88(7):435‐40. 54 18 Return to Top CSI (Clinical Skin Investigation) Introduction to Dermoscopy CSI (Clinical Skin Investigation) Introduction to Dermoscopy Deborah A. Bren, DO, LVPG Family Medicine - Orefield Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Introduction to Dermoscopy 1 Disclosure Dr. Deborah Bren has no conflict of interest, financial agreement, or working affiliation with any group or organization. 2 Introduction Deborah A. Bren, DO Family Physician Lehigh Valley Physician Group USF Assistant Professor FM FM Resident Preceptor, LVPG Philadelphia College of Osteopathic Medicine 1984 3 1 It’s a very ancient saying, But a true and honest thought, That if you become a teacher, By your pupils you’ll be taught The King and I, “Getting to Know You” By Rodgers & Hammerstein 4 Bar Harbor, Maine 5 American Dermoscopy Meeting Faculty Ashfaq A. Marghoob, MD Ralph Braun, MD Natalia Jaimes, MD Michael Marchetti, MD George Martin, MD Steven O’Day, MD Margaret Oliviero, ARNP, MSN Harold Rabinovitz, MD Richard Usatine, MD Each summer in a National Park Course Content: Fundamentals Pearls Interactive 6 http://www.americandermoscopy.com/ 2 7 8 9 3 10 Why Should I Learn About Dermoscopy? If you like to do procedures! If you think about how much and how often we see skin! Long wait times for pt’s to get into dermatology, shorter if you have a biopsy result Patients may have complained about dermatologists once or twice? 11 Memorial Sloan- Kettering Cancer Center Dermoscopy workshop Yearly, each fall in NYC http://www.mskcc.org/events/ 12 4 American Academy of Family Physicians Yearly fall scientific assembly Dermoscopy workshops http://www.aafp.org/events/assembly.html 13 AAFP Sponsors a course Skin Problems and Diseases Includes a Dermoscopy workshop http://www.aafp.org/cme/ 14 American Academy of Dermatology Many lectures and workshops at it’s national meetings www.aad.org 15 5 Dermoscopy On-Line http://www.dermoscopy.org/ Website from Italy Includes free dermoscopy tutorial 16 International Dermoscopy Society http://www.dermoscopy-ids.org/ 17 18 6 Dermoscopy Apps Dermoscopy Two Step Algorithm Usatine Media Richard Usatine, MD Co-sponsored by Dermlite Free on iTunes and Android store 19 Let’s get started 20 Photo Credit: Kevin Wynosky What is a Dermoscope? 21 7 Handheld instrument w/ magnifying lens and a light source that removes surface glare + allows us to see structures that are not visible to the naked eye. Often has a polarized and nonpolarized option. 22 23 Why Use a Dermoscope? Stethoscope for the skin Like a using a Fundoscope for examining the eye Dermatologists say that performing a skin inspection w/o a dermoscope is like listening to someone’s lungs w/o a stethoscope. 24 8 Old “ABCD” Method Assymmetry Borders (irregular) Color (variation) Diameter ( > 6mm) 25 Using Technology Total Body Photography Comparative + Differential recognition ABCDE Dermoscopy Analytical recognition Differential recognition Comparative recognition Gives microscopic morphology Confocal Microscope Analytical recognition Akin to an ultrasound of skin Gives fuzzy-cellular morphology Histopathology 26 Gives cellular morphology Confocal microscope 27 9 More of the Why Aids in early detection of skin cancers Melanoma BCC SCC Early Detection Decreases Mortality Morbidity Healthcare Costs Non-invasive technique based on pattern recognition Increases our sensitivity & specificity 28 More of the Why Helps to determine where to biopsy Helps to discern if Malignant Melanoma is present Minimizes the frequency of removing benign lesions Maximizes our diagnostic accuracy Manages patient’s angst 29 Benign to Malignant Ratio Improved diagnostic accuracy after a 1-2 year “learning period” In one study: Baseline: 13.75 Dermoscopy Year 1: 22.5 Dermoscopy Year 2: 7.86 Source: Terushkin V, et al. (2011) Arch Dermatol 146(3):343-344 30 10 Specificity & Sensitivity If you only examine lesions that clinically concern you, then dermoscopy only improves your specificity. If you examine lesions that do not clinically concern you, dermoscopy will improve your sensitivity 31 32 Dermoscopy in General Dermatology Classic: tumors and nevi Hair Disorders (Trichoscopy) Infections and Infestations (Entomodermoscopy) Inflammatory (Inflammoscopy) Nail fold capillaries (Capillaroscopy) Treatment 33 11 Infections & Infestations Tinea Nigra Molluscum contagiosum Warts (general and genital) Scabies (burrows and mites) Lice Use a glass slide, baggie, or disposable covers now available to protect device and pts 34 Scabies 35 Inflammoscopy Psoriasis Dermatitis Pityriasis rosea Discoid Lupus Erythematous 36 12 Hair Disorders Non-Scarring Alopecias Scarring Alopecias 37 Types of Dermoscopy Non – polarized (Conventional) Polarized non contact Polarized contact 38 Non-Polarized Dermoscopy Contact + Liquid interface Superficial layers Comedo like openings will be more conspicuous Milia - like cysts visible only with NPD Superficial blue-White Veils (due to orthokeratosis) 39 13 Polarized Dermoscopy Source:Polarized and Nonpolarized Dermoscopy The Explanation for Observed Differences Yan Pan, BMedSc; et al 40 Arch Dermatol. 2008; 144(6):828-829 Polarized Dermoscopy Contact or non-contact Deep layers of epidermis and papillary dermis White color more conspicuous Pink and red colors more conspicuous Blue-gray ovoid nests/globules Granularity Crystalline structures 41 Non-Polarized Polarized Non- Contact contact Superficial Deeper layers + structures vasculature (Like milia-like cysts More vascular in SK’s) blush Blue-White Veil is White shiny areas more conspicuous (crystalline lines in Steel-blue color in melanoma + blue nevus will be rosettes in SCC) more homogenous 42 14 The Blink Sign Toggling between Polarized and Non Polarized light source Highlights specific structures due to differences in depths imaged Unveils crystalline structures Article by Ralph Braun, MD, et al in Arch Dermatol 2011;14:520 43 Contact Dermoscopy Alcohol Gel Preferred for nail evaluation Water Mineral oil Hand sanitizer Take care not to press too hard! 44 Segovia, Spain 45 15 Take Pictures of Your Images! Connection kits for iPhones, iPads, etc. Before biopsy or excision Confirm diagnosis after path report received Accelerates learning Up-load them 46 Take Pictures of Your Images! 47 Usatine’s Tips for Storage and Retrieval •Label photo with name of diagnosis •Picasa = free program from Google •Don’t use patient names or MRN’s on files •Find photo by date 48 16 49 Pattern Recognition 50 51 17 52 53 Two Step Algorithm: Differentiating melanocytic from nonmelanocytic lesions 54 18 Analytical Analysis Presence or absence of specific colors and structures Structure morphology Typical/regular vs atypical/irregular Color and structure distribution 55 Step sectioning < 2% of the lesion is evaluated Source: imgarcade.com 56 Dermoscopy Colors Melanin Main chromophore in pigmented skin lesions Depends on anatomic location and concentration in the skin Will range from black to blue, even gray Can be Light brown to dark brown Hemoglobin Red blood cells Pink to red colors Collagen Fibers Found in dermis White in color 57 19 Dermoscopy Structures Pigment network Reticulation Grid-like or honeycomb pattern consisting of intersecting pigmented lines and hypopigmented holes Typical With few exceptions = Nevi Atypical Melanoma and dysplastic nevi 58 59 60 20 61 62 Pigment network 63 21 Pigment network 64 Dermoscopy Structures Pseudonetwork Can be found in melanocytic and non-melanocytic pigmented lesions of the face 65 Pseudonetwork 66 22 Dermoscopy Structures Structureless Areas Usually hypopigmented compared with surrounding lesion but not in comparison to surrounding normal skin In nevi found within the nevus In melanoma, Usually found at periphery of lesion 67 68 Soure: uda.dermoscopy-ids.org Dermoscopy Structures Blotches Dark brown to black Usually homogenous Obscures visualization of underlying structures Nevi Homogenous and central Melanoma Heterogenous, multiple hues Located off center 69 23 70 uda.dermoscopy-ids.org Dermoscopy Structures Dots < 0.1mm in diameter Black, brown, gray, bluish Nevi Located toward center of lesion Can overlie the network lines Melanoma not associated with network Located in periphery of lesion 71 Dermoscopy Structures Peppering/Granularity Blue-White Veil over flat areas Tiny blue-gray granules Can be a sign of regression Can be seen in melanocytic and non- melanocytic lesions Nevi Area usually < 10% of whole surface area Melanoma Area tends to encompass > 50% of the surface area 72 24 Dots and Peppering 73 Source: Dermoscopymadesimple.blogspot.com.au Dermoscopy Structures Globules > 0.1mm; round to oval structures Brown, black, blue-gray or red Nevi Similar size, shape and color Symmetric distribution Melanoma Different shape, size, color Random distribution 74 Globules 75 25 Dermoscopic Structures Streaks Radially arranged, linear projections of dark pigment at periphery of lesion Emanate from tumor and radiate towards normal skin Brown to black Spitz Nevi Arranged circumferentially around the entire perimeter of the lesion Melanoma Located focally at the perimeter 76 Pigmented lesion with radial streaming and regression 77 Spitz Nevus 78 26 Dermoscopic Structures Negative pigment network Serpiginous interconnecting hypopigmented lines that surround irregularly shaped brown structures Resemble elongated and curvilinear globular structures sausages May be seen in congenital nevi Most likely associated with Spitz nevi and Melanoma 79 negative pigment network 80 Atypical Pigment Network © DS Medica S.r.l. 81 27 Dermoscopic Structures Chrysalis/crystalline White shiny linear streaks Seen only with polarized dermoscopy Oriented parallel and sometimes perpendicular to each other Scars Dermatofibromas BCC Lichen-planus like keratosis Melanomas Spitz nevi 82 83 Chrysalis/crystalline 84 28 Crysalis structures 85 Dermatofibroma Source: Dermnetnz.org 86 Dermoscopic Structures Regression structures Blue-White Veil over flat/macular areas White scar-like depigmentation Often combined with or adjacent to blue-gray areas or peppering Lighter than surrounding skin Appears shiny white w/ polarized dermoscopy Melanoma Less commonly, nevi and lichen- planus like keratosis 87 29 Blue Gray Veil Melanoma 88 Source: dermoscopy.wordpress.com Blue Gray Veil 89 Dermoscopic Structures Regression Structures Blue-White Veil over palpable/raised areas Irregular, confluent blue pigmentation Overlying white “ground glass” haze Nevi Homogenous White hue Located in center of lesion Melanoma Heterogeneous Prominent Asymmetrical 90 30 Blue Gray Veil, Irregular Globules, Pseudolacunae 91 Source: www.dermoscopy.org 92 Blue Nevus 93 31 94 Dermoscopic Structures Vascular Structures Pink hue (milky red areas) Isolated blood vessels with varying morphologies 95 The vascular pattern may be quite distinctive and allow diagnosis of a pink skin lesion, in the absence of pigmentation or dermoscopic structures. If using a contact dermoscope, take care not to press down on pink lesions, which will exsanguinate the vessels and make diagnosis more difficult. 96 32 Arborizing Vessels 97 Source: www.melanomaclinic.com.au 98 Vessel Morphology Amelanocytic Melanoma Dotted or atypical or corkscrew or pink blush or polymorphic vessels Benign Melanocytic Nevus Comma-shaped vessels SK Hairpin vessels, with white halo BCC Irreg. arborizing vessels SCC in situ Focal grouped glomerular vessels Hemangiomas Uniform red, blue or purple vessels Telangiectasias Dilated linear & branced vessels Hemorrhage Red-blue lacunes w/n tumor Psoriasis Uniform globular vessels 99 Adapted from dermnetnz.org 33 Deb’s notes to self: Polymorphic vessels = BAD Vessels as dots = SCC Glomerular vessels and scale = SCC If you see PINK, stop and think 100 Focal Glomerular Vessels SCC in situ 101 Pink Blush Amelanocytic Melanoma Source: DermnetNZ.org 102 34 Telangiectasias Source: DermnetNZ.org 103 Dermoscopic Structures Milia – Like Cysts Round whitish or yellowish structures Shine brightly under nonpolarized dermoscopy 104 Seborrheic Keratosis Source: www.dermoscopy.org 105 35 Dermoscopic Structures Comedo-like openings Blackhead-like plugs on surface of lesion Usually associated with SK’s 106 107 Dermoscopic Structures Ridges and fissures Cerebriform surface Gyri (ridges) Sulci (fissures) Associated with SK’s 108 36 SK fissure-like Source: dermnetnz.org 109 110 Dermoscopic Structures Fingerprint – like structures Thin light brown lines that do not interconnect to form a meshwork pattern Feature of lentigo or early SK 111 37 SK fingerprints Source: dermnetnz.org 112 SK fat fingers 113 114 38 Dermoscopic Structure Moth – eaten border Concave invaginations of lesion border Associated with solar lentigo 115 Solar Lentigo 116 Solar Lentigo 117 Source: dermnetnz.org 39 118 Congenital Nevus 119 120 40 121 122 123 41 124 Dermoscopic Structures Leaf – like areas Brown to gray-blue discrete bulbous structures Create shapes that resemble leaves Highly specific for BCC 125 126 42 Dermoscopic Structures Spoke – wheel – like structures Well circumscribed brown to gray-blue- brown radial projections meeting at a darker brown central hub Highly specific for BCC 127 128 BCC look alike 129 43 Dermoscopic Structures Large blue-gray ovoid nests Large, well circumscribed areas Larger than globules In the absence of a network, these structures are highly specific for BCC 130 Large Blue Gray Ovoid Nests 131 Source: dermnetnz.org Large Blue Gray Ovoid Nests 132 Source: dermnetnz.org 44 Dermoscopic Structures Multiple blue-gray non- aggregated globules Round Well-circumscribed structures Resemble small ovoid nests In absence of a pigment network, suggests BCC 133 Multiple Blue Gray Non Aggregated Globules Source: DermNet NZ 134 Dermoscopic Structures Lacunae Red, maroon, or black lagoons Seen in angiomas and angiokeratomas 135 45 Hemangioma 136 Dermoscopy Structures Rosettes White 4 leafed clover- shaped structures Only w/ polarized light dermoscopy Suspect SCC 137 SCC w/ rosettes 138 46 SCC in situ Rosettes 139 140 141 47 142 143 Acral lesions: Soles and Palms 144 48 Lattice Pattern 145 Source: Dermnetnz.org Lattice pattern 146 Source: Dermnetnz.org Parallel Furrow Pattern 147 Source: Dermnetnz.org 49 Fibrillar Pattern Source: Dermnetnz.org 148 149 150 50 Fibrillar pattern Source: Dermnetnz.org 151 Fibrillar pattern dysplastic nevus sole 152 Source: Dermnetnz.org Mixed pattern 153 51 Parallel ridge pattern melanoma 154 Source: Dermnetnz.org 155 156 52 Return to Top Integrating Genetics into Family Practice – Part II Integrating Genetics into Family Practice – Part II Brian Stello, MD, Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Case Studies in Personalized Medicine Brian Stello, MD Lehigh Valley Hospital 1 Disclosures • Disclosure of Relevant Financial Relationships: The presenter has no financial relationships to disclose. • Disclosure of Off‐Label and /or Investigative Uses: The presenter will not discuss off label use and /or investigational use in this presentation. 2 Objectives • Analyze case studies involving genomic medicine. • Appraise the validity of the genomic information in each case. • Discuss the relevant bioethical issues in each case. • Draft an educational format for genomics in primary care 3 1 ACCE Framework Analytical validity –genomic test results need to be accurate and reliable. Clinical validity – reliable results are of consistent clinical significance. Clinical utility –there is a clear benefit for intervention based on genomic test results. Ethical, legal, and social implications are openly discussed. 4 Tiered Approach to Integrating Genomics into Practice • Tier 1 – recommended for clinical use by evidence‐based panels and supported by systematic review of evidence • Tier 2 – validity and promising evidence of clinical utility, but lack evidence‐based recommendations • Tier 3 – inadequate validity or utility 5 Caveat •Genomic makeup in complex disease is probabilistic, not deterministic. 6 2 Case No. 1 Andrea is a 34‐year‐old bank executive. Her mother was diagnosed with breast cancer six years ago and is now disease free. Her father has Type II Diabetes. Her maternal grandfather is in a nursing home dementia unit. She jogs for exercise 5 days a week. She has about 5 drinks a week, usually wine. She occasionally smokes when drinking. Her BMI is 23 and she has no know medical problems. Adapted from Nuffield Council on Bioethics 7 Case No. 1 • Recently, she received an email offering her personal genetic testing to screen for genes that may put her at risk for future disease. The price was affordable and the process seemed simple. Curious to know her risk, she requests a kit and sends in a saliva sample. • She makes an appointment to discuss her results with you. 8 Andrea’s Results Condition Est. Lifetime Risk Avg. Population Risk Alzheimer’s Disease 19% 11% Breast Cancer 13% 13% Type II Diabetes 16.5% 19% Heart Attack 38% 28% Hypertension 40% 40% Lung Cancer 4% 7.5% Osteoarthritis 34% 33% 9 3 Questions To Consider • Does this testing benefit Andrea? • She is concerned she is at increased risk for Alzheimer’s Disease and Heart Attack. How would you discuss her increased risks? • Are there modifiable environmental risks that might interact with genetic risks? • Her husband’s family has a history of premature MI (i.e. men younger than 55), and he takes cholesterol medication. She wants to know if she should have genetic testing for her 6‐ year‐old son. What is your advice? 10 Case No. 2 • James is a 42‐year‐old man coming in for his insurance‐ approved wellness exam. • He has a history of hypertension. He smokes a pack of cigarettes a day, does not exercise and has 1‐2 drinks a day. He describes himself as a “meat and potatoes” man and only occasionally eats fruits and vegetables. • He has had no previous cancer screenings. • His BMI is 28. • Adapted from the National Coalition for Health Professional Education in Genetics 11 Case No. 2 • In his family history, James’ older brother was diagnosed with colorectal cancer two years ago, at the age of 45. His mother was diagnosed with endometrial cancer at age 49. A paternal aunt was diagnosed with breast cancer at age 63. His maternal grandmother was diagnosed with pancreatic cancer at age 67. 12 4 Questions to Consider • Is James at average, increased (moderate) or high risk for colorectal cancer (CRC)? • How should James be screened for CRC? • Would you recommended for genetic counseling/testing for James? • What would you recommend for James’ 46‐year‐old sister? 13 Creating a Pedigree Female Identified Patient Male Unknown gender 14 Deceased 15 5 Pancreatic Cancer Age 67 Endometrial Breast Cancer Cancer Age 63 Age 49 Colorectal Cancer Age 45 16 Pancreatic Cancer Age 67 Endometrial Breast Cancer Cancer Age 63 Age 49 Colorectal Cancer Age 45 17 Pancreatic Cancer Age 67 Endometrial Breast Cancer Cancer Age 63 Age 49 Colorectal Cancer Age 45 18 6 Case No. 3 • Jasmine is a 22‐year‐old woman went to Planned Parenthood to start oral contraceptives. • On her intake sheet at Planned Parenthood, she checked the box for a family history of blood clotting. • She was told she had to have her doctor’s permission before starting because of that history. 19 Case No. 3 • Jasmine is a smoker, about 10 cigarettes a day. • Her older sister has a six‐month‐old boy. The pregnancy was complicated by preecclampysia • On her mother’s side of the family, her uncle had a blood clot in his 30s and another in his 40s, and is now on blood thinners • Her grandmother had a stroke at age 59. 20 Questions to Consider • If Jasmine stops smoking, has she eliminated her risk for developing venous thromboembolism on OCPs? • Should anyone in Jasmine’s family be tested for inherited thrombophilias? • Should Jasmine be on anticoagulants? • What forms of birth control would you recommend for Jasmine? 21 7 Developing Genomic Education and Integration for Primary Care • What key elements need to go into primary care education to manage genomics? • Consider attitudes, knowledge, and skills. 22 Attitudes • All health professionals should: • appreciate the sensitivity of genetic information and the need for privacy and confidentiality. • seek coordination and collaboration with an interdisciplinary team of health professionals. • Core Competencies for All Health Care Professionals. National Coalition for Health Professional Education in Genetics. 2007. www.nchpeg.org 23 Knowledge • How identification of disease‐associated genetic variations facilitates development of prevention, diagnosis, and treatment options. • The interaction of genetic, environmental, and behavioral factors in predisposition to disease, onset of disease, response to treatment, and maintenance of health. • The difference between clinical diagnosis of disease and identification of genetic predisposition to disease (genetic variation is not strictly correlated with disease manifestation). • Core Competencies for All Health Care Professionals. 24 8 Knowledge • The potential physical and/or psychosocial benefits, limitations, and risks of genetic information for individuals, family members, and communities. • The ethical, legal and social issues related to genetic testing and recording of genetic information (e.g., privacy, the potential for genetic discrimination in health insurance and employment). • Core Competencies for All Health Care Professionals. 25 Skills • Explain effectively the reasons for and benefits of genetic services. • Assure that the informed‐consent process for genetic testing includes appropriate information about the potential risks, benefits, and limitations of the test in question. • Core Competencies for All Health Care Professionals. 26 9 Lynch syndrome Lynch syndrome/hereditary non- polyposis colon cancer fact sheet Clinical features Lynch syndrome (LS) is caused by a mutation in a mismatch repair (MMR) gene. Individuals with LS are at increased risk for colon and other cancers, including gastric, urinary tract, brain, small bowel, pancreatic, hepatobiliary and sebaceous carcinoma. Women with LS are at increased risk for endometrial and ovarian cancer. Diagnosis of LS An individual should meet Amsterdam II criteria or have a mutation that is identified by molecular genetic testing of the MMR genes. Clinical diagnosis of LS: The Amsterdam II criteria define the minimum requirements for a clinical diagnosis of Lynch syndrome. There should be at least three relatives with a Lynch/HNPCC-associated cancer (cancer of the colorectum, endometrium, small bowel, ureter or renal pelvis) and … • One should be a first-degree relative to the other two • At least two successive generations should be affected • At least one should be diagnosed before age 50 • Familial adenomatous polyposis should be excluded • Tumors should be verified by pathological examination Inheritance Autosomal dominant Gene(s) Mismatch repair genes MLH1 & MSH2 (mutation present in about 90 percent of LS families) MSH6 (mutation present in about 7–10 percent of LS families) PMS2 (mutation present in <5 percent of LS families) Non-mismatch repair genes EPCAM (mutation present in 1–3 percent of LS families) Genetic testing Direct gene testing is available commercially. To identify colorectal cancer patients who may have LS, the current recommendations are to begin by ordering microsatellite instability (MSI) or immunohistochemistry (IHC) testing on the tumor sample. This can be performed by a pathologist on archived tumor blocks from a surgical specimen. These tests detect either an increased number of Colorectal Cancer Fact Sheets: Lynch syndrome | 1 Lynch syndrome microsatellite repeats (MSI, a hallmark of impaired mismatch repair gene activity), or the absence of the protein products of the mismatch repair genes (IHC). MSI/IHC have known utility for colorectal and endometrial cancers but are not routinely recommended for other cancers. If either test is positive, meaning that the mismatch repair genes appear to be impaired, then continue on to genetic testing that can determine which mismatch repair gene is mutated. Whenever possible, begin this genetic testing on an affected family member. The identification of a mutation confirms the diagnosis of LS. If a mutation is not identified, a diagnosis of LS can neither be confirmed nor ruled out; this result must be interpreted in the context of the patient’s MSI/IHC results, family and personal history and test limitations. See “Overview of testing for Lynch syndrome tool” for more information. Colon cancer risk General population Lynch syndrome Mean age at cancer onset (LS) Male 5.6% 28–75%* 44–61 years Female 5.3% 24–52%* 44–61 years *lower risks w/MSH6, PMS2 gene mutations Associated cancer risks* Type of cancer General population Lynch syndrome Mean age at cancer onset (LS) Endometrium 2.7% 27–71% 46–62 years Ovary 1.6% 3–13% 43 years Other (stomach, <1% Stomach: 2–19% Variable hepatobilliary, Urinary tract: 1–12% urinary tract, etc.) Others: 1–7% *Increased risks for additional primary colon cancers Non-cancer findings:keratoacanthomas, sebaceous adenomas Screening recommendations (See “Screening guidelines tool”): 1. Colonoscopy: every one to two years starting at age 20–25 or two to five years prior to the earliest colon cancer in the family if diagnosed under age 25. 2. If colon cancer is found, consider removal of entire colon and continue annual screening for rectal cancer. 3. Consider prophylactic removal of the colon in cases where regular screening with colonoscopy cannot be performed. 4. Females: consider annual endometrial sampling and transvaginal ultrasound. 5. Consider prophylactic hysterectomy with bilateral salpingo-oophorectomy after childbearing is complete. 6. Consider annual urinalysis. 7. Consider EGD with extended duodenoscopy and polypectomy at two to three year intervals beginning at age 30. Screening references: NCCN Colorectal Cancer Screening Guidelines, V.2.2011. nccn.org/professionals/physician_gls/f_guidelines.asp ACG Guidelines for Colorectal Cancer Screening 2009. http://s3.gi.org/physicians/guidelines/CCSJournalPublicationFebruary2009.pdf Vasen, H., Watson, P., Mecklin, J.-P., & Lynch, H. (1999). New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology, 116(6), 1453–1456. 11-0456:2/12:jt:Updated Feb 2012 Colorectal Cancer Fact Sheets: Lynch syndrome | 2 Inherited Thrombophilia Fact Sheet Inherited thrombophilia is a genetic tendency toward venous thromboembolism (VTE) the usually presents in patients under age 50 and is often recurrent. The most frequent causes are mutations of Factor V Leiden or prothrombin genes, which account for 50 to 60 percent of cases. Other defects in protein S, protein C, and antithrombin (i.e. antithrombin III) account for most of the rest. About 50% of the VTE events in patients with inherited thrombophilia have an acquired risk factor, such as smoking, oral contraceptive use, recent surgery, or pregnancy. Genetic causes of thrombophilia Mechanism/factor Population Prevalence Inheritance Pattern Risk of VTE by Age 60 Deficiency of anticoagulants Antithrombin III < 1% Autosomal dominant 60% Protein C < 1% Autosomal dominant 50% Protein S 1% Autosomal dominant 33% Mechanism/factor Population Prevalence Inheritance Pattern Lifetime Risk of VTE Increased procoagulants Factor V Leiden 3-7% Autosomal dominant 5-20% Prothrombin G20210A 1-4% Autosomal dominant 10-20% Elevated homocysteine 10-15% Multifactorial Not yet determined Adapted from Up To Date Genetic Diagnostic Testing and Presymptomatic Testing Genetic diagnostic testing is done when a patient is offered a genetic test based on symptoms and signs already present. The purpose is to rule out a genetic cause of current symptoms. Presymptomatic testing is when an at-risk individual, who is asymptomatic at the time, carries a mutant gene that may increase the risk of developing disease at some point in the future. Typically, an effected family member has had a positive genetic diagnostic test. “Red Flags” Suggesting Inherited Thrombophilia Recurrent VTE, or spontaneous VTE VTE at a young age Recurrent miscarriage Thrombosis in unusual sites (e.g. sagittal sinus) or multiple thrombi Coronary or cerebral thrombosis at an early age (Men < 50, Women < 60) Adapted from Genetics in the Physician Assistance’s Practice Return to Top Achieving Glycemic Control: When Optimized Basal Insulin Isn’t Adequate Achieving Glycemic Control: When Optimized Basal Insulin Isn’t Adequate Louis Kuritzky, MD, University of Florida Disclosures: Speaker discloses that he is on the advisory board of Amgen, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Lilly, Novo Nordisk, Sanofi, and Takeda Pharmaceuticals. He is on the speakers’ bureau for Amgen, Lilly, and Novo Nordisk. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. This activity was funded in part by an educational grant from Novo Nordisk Inc. at the Allentown CME Conference, which had no control over the content. Achieving Glycemic Control: When Optimized Basal Insulin Isn’t Adequate AAFP State Chapter Meeting Louis Kuritzky MD Clinical Assistant Professor Emeritus Department of Community Health and Family Medicine College of Medicine University of Florida, Gainesville 1 Statements of Sponsorship and Support This CME symposium is sponsored by: This CME symposium is supported by an educational grant from Sanofi US Diabetes. 2 Register at: www.pcmg-us.org 3 Learning Objectives After completing this program, the primary care provider should be able to: • Identify patients who have reached the likely maximum benefits of their optimized basal insulin • Compare medications available for use in combination with basal insulin to lower postprandial glucose • Compare the outcomes of patients treated with the addition of prandial insulin vs a GLP-1RA to basal insulin 4 CME Information This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) and the American Academy of Family Physicians (AAFP). AAFP designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians, should claim only the credit commensurate with the extent of their participation in the activity. 5 Faculty Disclosure Louis Kuritzky, MD discloses that he is on the advisory board for Amgen, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Lilly, Novo Nordisk, Sanofi, and Takeda Pharmaceuticals. He is on the speakers’ bureau for Amgen, Lilly, and Novo Nordisk. 6 Despite a fasting plasma glucose from 80-130 mg/dL, basal insulin may not be enough to reduce the HbA1C to <7.0% if: A. The total basal insulin dose exceeds 0.4 units/kg-day B. The patient experiences severe, nocturnal, or frequent symptomatic hypoglycemia C. The bedtime blood glucose is >38 mg/dL higher than the pre- breakfast blood glucose D. Weight increases or remains stable 7 Optimized basal insulin is best characterized as: A. A fasting plasma glucose of 80-130 mg/dL B. Minimizing the incidence of mild, symptomatic hypoglycemia C. The dosing regimen that achieves a balance between the efficacy and safety/tolerability of basal insulin and patient factors D. The dose of basal insulin below which severe hypoglycemia does not occur 8 The class of glucose-lowering agents with the greatest efficacy for lowering postprandial glucose is: A. Biguanide B. Sulfonylurea C. Sodium glucose linked transporter-2 inhibitor D. Glucagon-like peptide-1 receptor agonist 9 A head-to-head comparison of lispro vs exenatide twice daily over 30 weeks, both in combination with optimized glargine plus metformin showed: A. HbA1C reduction: exenatide ≈ lispro B. Nocturnal hypoglycemia: exenatide > lispro C. Glargine dose: exenatide < lispro D. Treatment satisfaction: exenatide < lispro 10 Case Study- Alison • 48 yo female diagnosed with T2DM 8½y ago • 10 months ago •HbA1c 8.6%, FPG 138-164 mg/dL despite metformin + SU • Basal insulin added, SU discontinued • Basal insulin titrated; now 58 units (0.56 units/kg) at dinner •HbA1c 7.6% • Glucose: fasting 92-133 mg/dL; bedtime 162-190 mg/dL • 2 episodes of symptomatic hypoglycemia during past 3 mos; last episode causing a fall At diagnosis Insulin initiated Now Body weight (kg) 97.3 99.1 102.5 2 BMI (kg/m ) 33.5 34 35.4 11 Patients with Diabetes Have Basal and Prandial Hyperglycemia Mealtime/Prandial Basal hyperglycemia 250 hyperglycemia 200 150 Type 2 Diabetes 100 50 Healthy Plasma Glucose (mg/dL) Glucose Plasma 0 6 AM 12PM 6 PM 12 AM 6 AM Time of Day 12 Adapted from: Riddle M. Pract Cardiol. 1986;12:65‐79. Desirable Clinical Effects of Basal Insulin • Basal analog insulin1 • Long-acting (24 hours) • Peakless (doses <0.5 units/kg) • Reduces hepatic glucose production (gluconeogenesis, glycogenolysis) and lipogenesis • Primarily targets fasting plasma glucose • Approximately 60% of patients with T2DM can achieve HbA1c ≤7.0% with basal insulin (+ oral agents) if taken CONSISTENTLY2 13 1. Unger, J. Diabetes Therapy. 2011;2 (1):40‐50. 2. Holman RR, et al. N Engl J Med. 2009;361:1736‐1747. What is Meant by Optimized Basal Insulin? Safety/Tolerability Efficacy • Minimize hypoglycemia • HbA at goal 1c • Severe • ≤7% for this patient • Nocturnal • FPG 80‐130 mg/dL • Minimize weight gain Patient Factors • Needs, interests, capabilities • Schedule/Lifestyle • Occupation • SMBG American Diabetes Association. Diabetes Care. 2015;38(Suppl 1):S1‐S93. 14 Philis‐Tsimikas A. Am J Med 2013;126:S21‐S27. When Basal Insulin May Not Be Enough to Achieve Glycemic Control HbA1c >7.0%, despite FPG 80-130 mg/dL And… Total basal insulin dose exceeds 0.5-1 unit/kg/day1 Severe, nocturnal, or frequent symptomatic hypoglycemia Difference between bedtime and AM (BeAM) blood glucose >55 mg/dL2 Less likely to achieve HbA1c ≤7.0% Increased risk of nocturnal hypoglycemia Weight gain 1. Inzucchi S, et al. Diabetes Care. 2012;35:1364-1379. 15 2. Zisman A, et al. ADA Scientific Sessions 2011; Abstract 1121-P. Is More Basal Insulin Better? Increasing doses of basal insulin may lead to diminishing returns Moreover, • Reduction in Mean Glargine Dose 50 250 the HbA1C End of 4‐ plateaus week run‐in 47 units • Incidence of (U) Mean 40 period (0.48 units/kg) hypoglycemia 198 Insulin 200 (blood Dose 30 mg/dL FPG glucose ≤56 mg/dL) rises 25 units (mg/dL) Insulin 20 over time 149 150 Daily mg/dL 10 FP 10 units 117 Total mg/dL 0 100 02 4 6 8 2 Week of Treatment 4 N=367 In combination with 1 or 2 oral agents 16 Riddle MC, et al. Diabetes Care. 2003;26(11):3080-3086. Avoiding Overbasalization • If the basal insulin dose is correct, the bedtime BG should be about the same as the next morning’s FPG (assuming no prandial insulin at nighttime) • If the BG decreases significantly overnight (ie, BeAM>55 mg/dL), the basal dose is too high • If the BG increases significantly overnight, the basal dose is too low • Caution to avoid Dawn Phenomenon BeAM, bedtime to pre‐breakfast 17 Glycemic Effects of Glucose-Lowering Medications Glycemic Effects Fasting Plasma Glucose Lowering Neutral Mild Moderate Moderate/ Marked Neutral •Basal Insulin •Metformin Lowering •Bromocriptine •Colesevelam Mild •SGLT‐2i •TZD Glucose •DPP‐4i •AGi •SU Moderate •Meglitinide •Pramlintide Moderate/ •Rapid‐/ Short‐ Postprandial acting Insulin Marked •GLP‐1R Agonista aFPG lowering: mild‐ albiglutide, exenatide BID; moderate‐ dulaglutide, exenatide QW, liraglutide Handelsman Y, et al. Endocr Pract. 2015;21(Suppl 1):1-87. 18 Inzucchi SE, et al. Diabetes Care 2015;38(1):140-149. Garber AJ et al. Endocr Pract. 2013;19(Suppl 2):1-48. As a patient’s HbA1c approaches 7%, controlling the postprandial glucose ___ the fasting plasma glucose. A. Becomes more important than B. Becomes less important than C. Remains as important as 19 Fasting vs Postprandial Glucose Contribution to HbA1c 100% 30% 80% 50% 55% 60% 60% 70% 40% 70% Contribution 50% 20% 45% 40% 30% 0% <7.3 7.3‐8.4 8.5‐9.2 9.3‐10.2 >10.2 HbA1c Range (%) Postprandial Plasma Glucose Fasting Plasma Glucose 20 Importance of Postprandial Glucose Increasing 2‐hour PPG is associated with an increasing risk of all‐cause mortality, particularly for PPG ≥200 mg/dL 2 Upper Limit of Normal for PPG Mortality 1.5 Cause ‐ 1 All of Risk 0.5 Relative Two‐Hour Plasma Glucose (mg/dL) <100 100‐109 110‐119 120‐129 130‐139 140‐149 150‐159 160‐169 170‐179 180‐189 190‐199 200+ 21 Sorkin JD, et al. Diabetes Care 2005;28:2626‐2632. Importance of Postprandial Glucose (cont) Hyperglycemic spikes following every meal induce oxidative stress, endothelial dysfunction, and inflammatory reactions. 22 Node K, et al. Cardiovasc Diabetol. 2009;8:23. Case Study- Alison • 48 yo female diagnosed with T2DM 8½y ago • Current Treatment • Metformin + basal insulin 58 units at dinner • Glucose levels •HbA1c 7.6% • Fasting 92-133 mg/dL • Bedtime 162-190 mg/dL • 2 episodes of symptomatic hypoglycemia during past 3 mos; last episode causing a fall How should her treatment be modified? 23 Healthy eating, weight control, increased physical activity & diabetes education Mono- therapy Metformin Efficacy* high Hypo risk low risk Weight neutral/loss Side effects GI / lactic acidosis Metformin Costs low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific+ factors): Metformin Metformin Metformin Metformin Metformin Metformin + + + + This is + Insulin +(basal) Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal) therapy† dione inhibitor inhibitorAlison’s agonist Efficacy* high high intermediate intermediate high …highesthighest Hypo risk moderate risk low risk low risk low risk low risk high risk Weight gain gain neutral losscurrent loss …high riskgain Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia Costs low low high treatmenthigh high …gain variable If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (orderMetformin…hypoglycemia not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin Metformin Metformin Metformin Metformin…variable Metformin + + + + + + + Triple Sulfonylurea Thiazolidine- DPP-4 SGLT-2 GLP-1 receptor Insulin (basal) dione Inhibitor Inhibitor agonist therapy + + + These + are the + Insulin +(basal) TZD SU SU options SU for SU TZD or DPP-4-i or DPP-4-i or TZD or TZD or +TZD or DPP-4-i intensifying § or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or InsulinTZD or SGLT2-i or GLP-1-RA or GLP-1-RA or Insulin§ basal or Insulininsulin§ or GLP-1-RA § § or Insulin or Insulin or DPP‐4i If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move toor injectables, SGLT2 (2) on‐ GLP-1I RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + or GLP‐1 RA Combination American Diabetes Association Diabetes Care, American Diabetes Association, 2015. Copyright and all rights reserved. Material from this injectable Basal Insulin + Mealtime Insulin or GLP-1-RA therapy‡ publication has been used with the permission of the American Diabetes Association. Inzucchi SE, et al. Diabetes Care 2015;38(1):140‐149. Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-024 Glycemic Effects of Glucose-Lowering Medications Glycemic Effects Fasting Plasma Glucose Lowering Neutral Mild Moderate Moderate/ Marked Neutral •Basal Insulin •Metformin Lowering •Bromocriptine •Colesevelam Mild •SGLT‐2i •TZD Glucose •DPP‐4i •AGi •SU Moderate •Meglitinide •Pramlintide Moderate/ •Rapid‐/ Short‐ Postprandial acting Insulin Marked •GLP‐1R Agonista aFPG lowering: mild‐ albiglutide, exenatide BID; moderate‐ dulaglutide, exenatide QW, liraglutide Handelsman Y, et al. Endocr Pract. 2015;21(Suppl 1):1-87. 25 Inzucchi SE, et al. Diabetes Care 2015;38(1):140-149. Garber AJ et al. Endocr Pract. 2013;19(Suppl 2):1-48. Other Considerations in Selecting Therapy to Lower Postprandial Glucose • Medication Factors • Patient Factors • Magnitude/Durability • Body weight of response • Regularity/Quality of • Mechanism of action meals • Requirement for • Variations in physical functioning -cell activity/work schedule • Adverse events • Hypoglycemia • Warnings/Contraindi- awareness/tolerance cations • Adherence • Cost/Insurance 26 Pathophysiologic Mechanisms in Hyperglycemia of T2DM CNS: Delayed satiety Kidney: Glucose reabsorption Gut: Diminished incretin effect Muscle and Altered intestinal glucose absorption adipose tissue: BLOOD Glucose uptake GLUCOSE Liver: Hepatic glucose secretion Pancreas: Insulin secretion Glucagon secretion 27 Healthy eating, weight control, increased physical activity & diabetes education Mono- therapy Metformin American Diabetes Association Diabetes Care, Efficacy* high American Diabetes Association, 2015. Copyright and Hypo risk low risk all rights reserved. Material from this publication has Weight neutral/loss been used with the permission of the American Side effects GI / lactic acidosis Diabetes Association. Costs low Inzucchi SE, et al. Diabetes Care 2015;38(1):140‐149. If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin Metformin Metformin Metformin Metformin Metformin + + + + + + Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal) therapy† dione inhibitor inhibitor agonist Efficacy* high high intermediate intermediate high highest Hypo risk moderate risk low risk low risk low risk low risk high risk Weight gain gain neutral loss loss gain Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia Costs low low high high high variable If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin Metformin Metformin Metformin Metformin Metformin + + + + + + Triple Sulfonylurea Thiazolidine- DPP-4 SGLT-2 GLP-1 receptor Insulin (basal) dione Inhibitor Inhibitor agonist therapy + + + + + + TZD SU SU SU SU TZD or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin§ or SGLT2-i or GLP-1-RA or GLP-1-RA or Insulin§ or Insulin§ or GLP-1-RA § § or Insulin or Insulin If HbA1c target not achieved after ~3 months of triple therapyMetformin and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin ++ Combination injectable Basal Insulin + Mealtime Insulin or GLP-1-RA therapy‡ Basal Insulin + Mealtime Insulin or GLP‐1 RA 28 Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0 Case Study- Alison • HbA1c 7.6% • FPG 92‐133 mg/dL Metformin + • Bedtime 162‐190 mg/dL Basal Insulin • Symptomatic hypoglycemia • Weight gain Which should be added? Rapid‐/Short‐ GLP‐1 Receptor SGLT‐2 DPP‐4 Inhibitor acting Insulin Agonist Inhibitor 29 Case Study- Alison (cont) Alison… Rapid‐/Short‐ GLP‐1 Receptor DPP‐4 Inhibitor SGLT‐2 Inhibitor acting Insulin Agonist is • Further • Additional injection • Immune‐mediated • Genital yeast concerned hypoglycemia • Transient N/V dermatologic infections about: • Further weight • ?Acute pancreatitis effects • Polyuria gain • C‐cell • ?Acute • Volume • Potential for hyperplasia/medul‐ pancreatitis depletion/hypo‐ multiple daily lary thyroid tumors • ?Heart failure tension/dizziness injections in animals hospitalizations • LDL‐C • Creatinine (transient) likes: • Potential for weight • Potential for no • Potential for loss further weight gain weight loss • Low risk of • Low risk of • Low risk of hypoglycemia hypoglycemia hypoglycemia • Potential for • Oral • Oral reducing basal insulin dose 30 Inzucchi S, et al. Diabetes Care. 2015;38:140‐149. Bolus Insulin vs GLP-1RA in Combination with Optimized Basal Insulin + Metformin • Adults with T2DM •HbA1c 7.0-10.0% • Receiving insulin glargine plus metformin R Exenatide 10‐20 mcg BID Glargine A (Basal Insulin ≥10%) 315 optimiza- Those N tion over who D 12 wks to didn’t 30 weeks O 1:1 achieve achieve M FPG HbA1c ≤100 ≤7.0%... I 312 mg/dL Z Lispro TID (Basal Insulin 33‐50%) E 31 Diamant M, et al. Diabetes Care. 2014;37;2763‐2773. Bolus Insulin vs GLP-1RA in Combination with Optimized Basal Insulin + Metformin (cont.) 0 Exenatide BID Lispro TID ‐0.5 (%) 1c HbA ‐1 ∆ ‐1.5 0 6 12 18 24 30 Weeks Following Randomization American Diabetes Association Diabetes Care, American Diabetes Association, 2014. Copyright and all rights reserved. Material from this 32 publication has been used with the permission of the American Diabetes Association. Diamant M, et al. Diabetes Care. 2014;37;2763‐2773. Bolus Insulin vs GLP-1RA in Combination with Optimized Basal Insulin + Metformin (cont.) ∆Fasting Glucose* (mg/dL) Blood Glucose (mg/dL) # 15 200 Exenatide BID Lispro TID 10 *P=0.002 for all time points except 0 175 5 0 150 ‐5 # 125 ‐10 Dotted line: At randomization #P<.001 Solid line: Study end ‐15 100 0 6 12 18 24 30 Weeks Following Randomization American Diabetes Association Diabetes Care, American Diabetes Association, 2014. Copyright and all rights reserved. Material from this 33 publication has been used with the permission of the American Diabetes Association. Diamant M, et al. Diabetes Care. 2014;37;2763‐2773. Bolus Insulin vs GLP-1RA in Combination with Optimized Basal Insulin + Metformin (cont.) Change in Key Endpoints* Safety 3 50 Exenatide BID Lispro TID 2 *P<.001 for all key endpoints 40 1 30 Patients 0 of 20 ‐1 Percent ‐2 10 ‐3 0 34 Diamant M, et al. Diabetes Care. 2014;37;2763‐2773. Bolus Insulin vs GLP-1RA in Combination with Optimized Basal Insulin + Metformin (cont.) Study Results: Summary HbA1c reduction Exenatide = Lispro FPG reduction Exenatide > Lispro PPG reduction Exenatide Lispro Minor hypoglycemia Exenatide < Lispro Nocturnal hypoglycemia Exenatide < Lispro Weight change Exenatide Lispro Glargine dose Exenatide > Lispro Treatment satisfaction Exenatide > Lispro 35 Diamant M, et al. Diabetes Care. 2014;37;2763‐2773. Basal insulin in combination with a GLP-1R agonist does not lead to a: A. Higher incidence of major hypoglycemia (<54 mg/dL) compared with basal insulin alone B. 1-2 kg average weight loss compared with basal insulin alone C. 0.5-0.7% average HbA1c reduction compared with either alone 36 Exenatide BID vs. Placebo Add-on Therapy to Insulin Glargine + Oral Agents T2DM R Exenatide 10 mcg BID A N 137 •HbA 7.1-10.5% 1c D • Receiving insulin 30 weeks O 1:1 glargine alone or in M combination with I metformin or 122 pioglitazone or both Z E Placebo 37 Buse JB, et al. Ann Intern Med. 2011;154:103‐112. Exenatide BID vs. Placebo as Add-on Therapy to Insulin Glargine + Oral Agents (cont.) % Achieving HbA1c ∆Body Weight (kg) ∆Insulin Dose <7.0% (U/kg) 0.25 100 1 0.2 75 0.5 * 0 0.15 50 ‐0.5 0.1 25 ‐1 0 0.05 ‐1.5 Exenatide BID Placebo ‐2 * *P<.001 0 38 Buse JB, et al. Ann Intern Med. 2011;154:103‐112. Exenatide BID vs. Placebo as Add-on Therapy to Insulin Glargine + Oral Agents (cont.) 220 200 180 (mg/dL) 160 Level 140 * * * * Glucose 120 * ** 100 Fasting Morning 2h Pre‐Lunch Lunch 2h PP Pre‐Dinner Dinner 2h 0300 Hours PP PP Glargine + Exenatide; baseline Glargine + Placebo; baseline *P<.001 for between‐group difference; Glargine + Exenatide; 30 wks Glargine + Placebo; 30 wks **P<.01 for between‐group difference Buse JB, et al. Ann Intern Med. 2011;154:103‐112. 39 With permission Copyright 2011, The American College of Physicians Exenatide BID vs. Placebo as Add-on Therapy to Insulin Glargine + Oral Agents (cont.) Hypoglycemic Events (events/patient‐year) 1.5 There were no episodes of major hypoglycemia (blood glucose < 54 mg/dL 1 resulting in loss of consciousness or seizure responding to 0.5 glucose/glucagon, or requiring assistance) 0 Exenatide BID Placebo 40 Buse JB, et al. Ann Intern Med. 2011;154:103‐112. Insulin Detemir as Add-on Therapy to Metformin + Liraglutide: Study Design • Patients with T2DM treated with metformin (HbA1C 7-10%) or metformin + SU (HbA1C 7- 8.5%) • 12-wk run-in: SU DC’d; liraglutide initiated, titrated to 1.8 mg/d • After run-in: • If HbA1C ≥7.0%: • Continued metformin + liraglutide OR • Added insulin detemir 10 units evening/bedtime and titrated to FPG 74-108 mg/dL • If HbA1C <7.0%: • Continued metformin + liraglutide (observational group) 41 DeVries JH, et al. Diabetes Care. 2012;35(7):1446‐1454. Insulin Detemir as Add-on Therapy to 1 Metformin + Liraglutide (cont.) Change in HbA1c (%) SMBG (mg/dL) 01224 200 0 Randomization 175 ‐0.5 150 # * ‐1 ** 125 *P=.0003 **P=.0244 #P=.0141 ‐1.5 100 Time (weeks) Liraglutide + Detemir 1 Weeks 0‐26 Liraglutide Liraglutide (obs) American Diabetes Association Diabetes Care, American Diabetes Association, 2012. Copyright and all rights reserved. Material from this 42 publication has been used with the permission of the American Diabetes Association. DeVries JH, et al. Diabetes Care. 2012;35(7):1446‐1454. Insulin Detemir as Add-on Therapy to 1 Metformin + Liraglutide (cont.) Change in Body Weight Rate of Minor Hypoglycemia (kg) (events/participant-year) 0 0.3 No major * hypoglycemia 0.2 occurred during ‐0.5 weeks 0‐26 0.1 ** ‐1 0 Liraglutide + Detemir Liraglutide 1Weeks 0‐26; *P=.03; **P=.004 43 DeVries JH, et al. Diabetes Care. 2012;35(7):1446‐1454. Efficacy Results from Observational Studies of Basal Insulin in Combination with a GLP-1RA HbA1c (%) Body Weight (kg) Insulin Dose (units/d) Conclusion: Combination therapy improved glycemic control without weight gain or an increased risk of hypoglycemia. From: Balena R, et al. Diabetes Obes Metab. 2013;15:485‐202. 44 Copyright 2013 John Wiley & Sons, Inc. All rights reserved GS5 GLP-1 Receptor Agonists in Combination with Insulin Approved for Use in Combination with Basal Insulin Prandial Insulin Albiglutide QW Dulaglutide QW Exenatide BID Exenatide QW Liraglutide QD 45 1. Tanzeum [package insert]. Research Triangle Park, NC: GlaxoSmithKline LLC; June 2014. 2. Trulicity [package insert]. Indianapolis, IN: Eli Lilly and Company; January 2015. 3. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc.; August 2014. 4. Bydureon [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc.; February 2015. 5. Victoza [package insert]. Princeton, NJ: Novo Nordisk; April 2013. Summary • Residual postprandial hyperglycemia may prevent achieving HbA1c target • Postprandial hyperglycemia is associated with cardiovascular risk • Basal insulin may not be enough to achieve glycemic control • Rapid-/Short-acting insulin has been the standard to lower postprandial glucose; however,… compared with thrice-daily rapid-acting insulin, a GLP-1RA provides • Similar or better glycemic control • Less nocturnal hypoglycemia • Weight loss (vs gain) • Greater treatment satisfaction 46 Despite a fasting plasma glucose from 80-130 mg/dL, basal insulin may not be enough to reduce the HbA1C to <7.0% if: A. The total basal insulin dose exceeds 0.4 units/kg-day B. The patient experiences severe, nocturnal, or frequent symptomatic hypoglycemia C. The bedtime blood glucose is >38 mg/dL higher than the pre- breakfast blood glucose D. Weight increases or remains stable 47 Optimized basal insulin is best characterized as: A. A fasting plasma glucose of 80-130 mg/dL B. Minimizing the incidence of mild, symptomatic hypoglycemia C. The dosing regimen that achieves a balance between the efficacy and safety/tolerability of basal insulin and patient factors D. The dose of basal insulin below which severe hypoglycemia does not occur 48 The class of glucose-lowering agents with the greatest efficacy for lowering postprandial glucose is: A. Biguanide B. Sulfonylurea C. Sodium glucose linked transporter-2 inhibitor D. Glucagon-like peptide-1 receptor agonist 49 A head-to-head comparison of lispro vs exenatide twice daily over 30 weeks, both in combination with optimized glargine plus metformin showed: A. HbA1C reduction: exenatide ≈ lispro B. Nocturnal hypoglycemia: exenatide > lispro C. Glargine dose: exenatide < lispro D. Treatment satisfaction: exenatide < lispro 50 Achieving Glycemic Control: When Optimized Basal Insulin Isn’t Adequate AAFP State Chapter Meeting Louis Kuritzky MD Clinical Assistant Professor Emeritus Department of Community Health and Family Medicine College of Medicine University of Florida, Gainesville 51 Return to Top Physician Burnout Physician Burnout Joanne Cohen-Katz, MD, Lehigh Valley Health Network, Julie Dostal, PhD, Lehigh Valley Health Network, & Drew Keister, MD, Lehigh Valley Health Network Disclosures: Speakers have no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Physician Burnout Building the Road to Resilience Joanne Cohen-Katz, PhD Julie Dostal, MD Drew Keister, MD © 2015 Lehigh Valley Health Network 1 Objectives After attending this session, participants will be able to: ▪ Describe the prevalence of physician burnout, the factors that contribute to burnout and the negative consequences of burnout in the lives of physicians and patients, ▪ Discuss the features of practices and physician lifestyle that can be protective against burnout, ▪ Identify the key sources of joy and inspiration in their personal and professional lives, and ▪ Create a plan for one change in their personal or professional lives that might help them to avoid burnout. 2 Conflicts of Interest ▪ None from any of the presenters have a conflict of interest, financial agreement, or working affiliation with any group or organization. 3 1 What is “Burnout”? A syndrome characterized by: ▪ A loss of enthusiasm for work (emotional exhaustion, loss of empathy) ▪ Feelings of cynicism (depersonalization) ▪ Low sense of personal accomplishment 4 OK, but who cares? ▪ 1/3 – ½ of practicing physicians affected ▪ Women 1.6 times more likely than men ▪ Burnout- predictor of mental health probs ▪ Suicide major cause of early physician death • 1.4x higher in male physicians • 2.3x higher in female physicians 5 Patient care affected ▪ Study of 891 diabetics ▪ Physicians with high empathy (56%) more likely than those with low empathy (40%) to have patients with a1c controlled (p<0.001) ▪ Similar outcomes for LCL control ▪ Controlled for gender, age, health insurance Hojat M, Louis D, Markham F, Wender R, Rabinowitz C, Gonnella J. Physicians’ Empathy and Clinical Outcomes for Diabetic Patients. Acad Med. 2011;86:359–364. 6 2 Medical Errors ▪ 7905 surgeons surveyed ▪ 8.9% reported making major medical error in last 3 mos ▪ Large, significant adverse relationship btwn error and: • Mental QOL • All 3 domains of burnout • Symptoms of depression ▪ Each 1 pnt increase in depersonalization (scale range, 0-33) assoc’d with an 11% increase risk of error ▪ Each 1 pnt increase in emotional exhaustion (scale range, 0-54) assoc’d with a 5% increase risk of error 7 Contributing Factors ▪ Often starts during med school / residency ▪ Common drivers in Canada: • Paperwork • Feeling undervalued • Frustrations with referral networks • Difficult patients • Medicolegal issues • Challenges in finding work-life balance Lee FJ, Stewart M, Brown JB. Stress, burnout, and strategies for reducing them: what's the situation among Canadian family physicians? Can Fam Physician. 2008;54:234‐235. 8 Contributing Factors- Difference in Career Stage ▪ Survey of > 7000 physicians ▪ Early Career (>10 yrs in practice): • Highest rate of depersonalization • Lowest satisfaction with choice of medicine as a career • Work-life conflict was #1 concern Dyrbye LN, Varkey P, Boone SL, Satele DV, Sloan JA, Shanafelt TD. Physician satisfaction and burnout at different career stages. Mayo Clin Proc. 2013; 88(12):1358‐1367. 9 3 Contributing Factors- Difference in Career Stage ▪ Middle Career (10-20 yrs in practice): • Worked longer hours, more frequent call • Highest burnout and emotional exhaustion rates • Lowest satisfaction with specialty choice • Biggest concerns: Frustration with administrative burden, Reimbursement issues ▪ Late career (> 20 years) • Lowest burnout rates • No particular stressors mentioned 10 AAFP position ▪ Burnout is a problem ▪ Fixing it is a task of the system ▪ We’ll leave it to them to work on that… For the rest of the hour, we will work on helping you to identify resources and planning to help yourself http://www.aafp.org/about/policies/all/physician-burnout.html 11 LINKING CULTURAL NORMS IN MEDICINE WITH BURNOUT FACTORS http://www.aafp.org/fpm/2013/0100/p25.html 12 4 Resiliency/Protective Factors http://www.aafp.org/fpm/2013/0100/p25.html. 13 Protective Factors Resiliency: Three key factors VALUES SELF-CARE INSIGHT http://www.aafp.org/fpm/2013/0100/p25.html. 14 Protective Factors Resiliency: Three key factors SELF-CARE: Taking care of the spiritual, physical and emotional parts of our lives. INSIGHT: Correcting negative thought patterns that drain and defeat us. VALUES: Knowing our work has meaning http://www.aafp.org/fpm/2013/0100/p25.html. 15 5 Protective Factors ▪ SELF-CARE • Engaging in activities that nurture and rejuvenate us – Eating well, exercise, seeing our own doctor • Investing time in the connections and community that nurture us • Maintaining boundaries between work and home 16 Protective Factors ▪ SELF-CARE • Self-care doesn’t just “happen” – Developing a self care plan – Calendaring self care time – Engaging in health coaching, counseling or garnering other supports – Balint, Mindfulness 17 Protective Factors ▪ INSIGHT: • How do we talk to ourselves about our work? – Expecting perfection of ourselves – Feeling guilty when we say no or set boundaries – Telling ourselves that self-care is simply impossible in today’s world of medicine – Ruminating over the less rewarding parts of medicine, vs. the parts that give us meaning and hope 18 6 Protective Factors ▪ INSIGHT • Countering negative thought traps can also require support: – Brief, focused psychotherapy – Mindfulness techniques – Balint groups 19 Protective Factors ▪ Values • People less likely to burn out when they feel a calling, a sense that their work is aligned with their highest values and beliefs • Remembering this in the midst of the hassles of daily life takes discipline and practice – Narrative work – Daily appreciation/gratitude practice 20 Contact Information: Joanne Cohen‐Katz, PhD Joanne.Cohen‐[email protected] Julie Dostal, MD [email protected] Drew Keister, MD [email protected] 21 7 Self Care Resources Activities: Yoga and/or Tai Chi Classes Gym membership; Exercise such as walking, jogging, swimming, and biking Regular Religious practices Journaling Meditation Mindfulness-based Stress Reduction Classes: www.lvhn.org/mindfulness Retreats, trainings/programs: www.healtherwithin.com; www.ishiprograms.org Balint groups: www.americanbalintsociety.org Apps: Meditation: Insight Timer Mindfulness App, Part 1 and 2 Headspace Fitness (Nutrition/Exercise): Runkeeper My Fitness Pal Sleep: Sleep Pillow CBT-I Coach Articles: Bein B. Mindful Communication Can help Physicians Deal With Burnout, say Study.American Academy of Family Physicians, 11/9/2009. Hojat M, Louis D, Markham F, Wender R, Rabinowitz C, Gonnella J. Physicians’ Empathy and Clinical Outcomes for Diabetic Patients. Acad Med. 2011;86:359–364. McBride JL.Making Family Practice Doable in Everyday Life. Family Practice Management. April 2003: 21-24. Nedrow A, Steckler N, Hardman J. Physician Resilience and Burnout: Can You Make the Switch? Family Practice Management. 2013 Jan/Feb: 25-30. http://www.aafp.org/fpm/2013/0100/p25.html. Zwack J, Schweitzer J, PhD. If Every Fifth Physician Is Affected by Burnout, What About the Other Four? Resilience Strategies of Experienced Physicians. Acad Med. 2013;88:382–389. Books Books of Poetry/Stories: Rachel Remen, Kitchen Table Wisdom and My Grandfather’s Blessing Mary Oliver, Why I Wake Early, New and Selected Poems Vol 1 & 2 Jalal-aldin Rumi & Coleman Barks, The Essential Rumi. David Whyte, Crossing the Unknown Sea: Work as a Pilgrimage of Identity; and The House of Belonging Books on Finding Balance and Happiness at Work: Lipsenthal Lee. Finding Balance in a Medical Life. Salzburg, Sharon. Happiness at Work. Rinpoche, Shlim, et al. Medicine and Compassion: A Tibetan Lama and an American Doctor on How to Provide Care with Compassion and Wisdom Return to Top Tackling the Top Three Most Common Ailments… Low Back Pain, Depressed Mood & “I Think I Have Bronchitis” Tackling the Top Three Most Common Ailments…Low Back Pain, Depressed Mood and “I Think I Have Bronchitis” William Sonnenberg, MD, Titusville, PA Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. Low Back Pain Low Mood Bronchitis William R. Sonnenberg, MD 1 Disclosure • Dr. William Sonnenberg has no conflict of interest, financial agreement, or working affiliation with any group or organization. 2 Learning Objectives • Recognize the red flags of low back pain that require more aggressive testing and treatment; • Learn signs of depression and bipolar depression that may not appear in textbooks; • Discuss that proper treatment of bronchitis without using antibiotics. 3 1 Low Back Pain 4 Epidemiology of LBP • 2nd most common neurologic illness in USA • 15%‐20% of adults each year • Onset ages 30‐50 • Reoccurrence 60%‐80% within 2 years • 80% have at least one episode of disabling LBP during lifetime 5 LBP ‐ Cost • 149 million lost workdays • $8.8 billion in workman’s comp cost • 28 billion in productivity cost • Rapidly increasing utilization and cost of interventions 1Pai S, Sundaram LJ. Orthop Clin North Am 2004;35:1-5; 2UMHS. Acute low back pain; 6 2005. http://cme.med.umich.edu/pdf/guideline/backpain03.pdf; 3Weinstein JN, Lurie JD, et al. Spine 2006;31:2707-2714; 4Friedly J, Chan L, et al. Spine 2007;32:1754-1760. 2 LBP ‐ Office • 2nd most symptomatic reason for office visit • 40% will go to primary care provider. • 31% will not recover within 6 months 7 Carey TS, et al. N Engl J Med. 1995;333(14):913–917. Goals of Treatment • Relieve pain • Improve function • Reduce work time lost • Education 8 85% CANNOT BE GIVEN A PRECISE DIAGNOSIS 9 3 Causes LBP 3% 0.40% 0.70% 4% 4% 0.04% 0.01% 85% Herniated Disc Compression Fx Ankylosing Spondylitis Spinal Stenosis Cancer Cauda Equina Syndrome Infection Nonspecific LBP 10 Chou R, Qaseem A, Snow V, et al. Ann Intern Med 2007;147:478‐491 Nonorganic Physical Signs Waddell Signs • Nonanatomic superficial tenderness • Simulation tests with axial loading and en bloc rotation producing pain • Distraction test or flip test in which pt has no pain with full extension of knee while seated, but the supine SLR is markedly positive • Nonanatomic weakness or sensory loss • Overreaction verbally or exaggerated body language 11 Herniated Disc • L5, S1, L4 most common • 10% still have pain at 6 weeks • Sequential MRI show partial or complete resolution at 6 months 12 4 Herniated Disc Compromise • L5 pain lower back, buttocks, side of body to foot • L4 side of flank, front of thigh, knee • S1 gluteal pain down back, calf, bottom of foot 13 Spinal Stenosis • Pseudo claudication • Pain, numbness, tingling one or both legs • Relieved by spinal flexion – improved with sitting or pushing shopping cart • CT or MRI 14 Spinal Stenosis 15 5 Red Flags • Cancer • Cauda equine syndrome • Fracture • Infection 16 Cancer or Infection Red Flags • Older than 50 or younger than 20 • History of cancer • Fever, chills or weight loss • IV drug abuse • Immunosuppression • Nighttime pain • Spinal deformity 17 Cauda Equina Syndrome Red Flag • Saddle anesthesia or paresthesia • Bladder dysfunction • Fecal incontinence • Severe or progressive neuro deficit in legs 18 6 Spinal Fracture Red Flags • Sudden onset of pain relieved by rest • Major trauma • Minor trauma • Structural deformity 19 Spondyloarthropathy Red Flags • Early morning stiffness lasting > 45 minutes • Night pain • 'Gelling' • Easier with movement/ worse after rest 20 Permanent Nerve Damage Red Flags • Muscle weakness or wasting • Loss of tendon reflexes • Positive Babinski reflex 21 7 Yellow Flags • Worker’s compensation • Litigation • Comorbid mental health issues • Socioeconomic factors 22 Ramond A, et al. Fam Pract. 2011;28(1):12–21. Physical Examination • Inspection • Palpation • Bony • Soft tissue • Range of motion • Neurologic Exam • Special tests 23 Plain Films? • Fever • Unexplained weight loss • Neurologic deficits • Alcohol or IV drugs • Older than 50 • Trauma • Otherwise don’t image in first 6 weeks (Choosing wisely) 24 Bigos S, Bowyer O, Braen G, et al. Acute low back problems in adults. Clinical practice guideline no. 14. Rockville, Md.: Agency for Health Care Policy and Research, December 1994 8 MRI v. X‐Ray? • 380 patients, mean age 35 • Randomized to rapid MRI or plain films • High disc issues MRI: 60% budge, 33% herniation • Not difference in pain or disability • Twice the surgery in MRI group 25 Jarvik et al. JAMA 2003; 289:2810 Early MRI and Disability 26 2013 Oct 15;38(22):1939‐46 Therapy Low Back Pain 27 9 Early Opioids for Low Back Pain • Highest earlier opioid users • Disabled 69 days longer • Surgery 3 times more likely • Late opioids 6 times higher • May be counterproductive to recovery • 22% risk for dependence • May be need for disc herniation 28 Webster BS et al. Spine (Phila Pa 1976). 2007;32(19):2127–2132 Sedatives and Opioids for LBP • 323 ED pts with < 2 weeks non‐traumatic, non‐ radicular LBP given Naproxen 500 mg bid #20 tablets and: • Placebo • 5mg cyclobenzaprine • 5 mg of oxycodone/325 mg of acetaminophen 29 Friedman BW, Dym AA, Davitt M I, et al. Naproxen with Cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain. JAMA. 2015 October Sedatives and Opioids for LBP RMDQ Score Change Beginning One Week Placebo 20 9.8 5mg cyclobenzaprine 19 10.1 5 mg oxycodone/325 mg 20 11.1 of acetaminophen 30 Friedman BW, Dym AA, Davitt M I, et al. Naproxen with Cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain. JAMA. 2015 October 10 Bed Rest • 2 days or less • Most don’t need bed rest • Bed rest >7 days may lead to debilitation 31 Cochrane 2010 NSAIDs • 65 trials • Slightly more effective short term for back pain without sciatica • No difference in sciatica • No NSAID was superior • No help with adding acetaminophen 32 Cochrane Review 2011 Muscle Relaxants • Cyclobenzaprine, tizanidine, metaxalone beneficial 7‐14 days, maybe 4 weeks for pain • No help with disability • Keep diazepam and Carisoprodol brief • May be additive with NSAIDs for pain 33 van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM. Muscle relaxants for non‐specific low back pain. Cochrane Database Syst Rev. 2003;(2): 11 Oral Steroids • Anecdotal case reports may help in acute radicular pain • Evidence inconclusive Chou R, Uffman LH: Nonpharmacologic therapies for acute and chronic low 34 back pain: a review of the evidence from the American College of Physicians and the American Pain Society. Annals of Internal Medicine 2007;147:492-504. Heat or Cold • Good evidence for superficial heat for muscle relaxation and analgesia for moderate back pain • Ice is inconclusive 35 Chou R, Qaseem A, Snow V, Casey D, et al: Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Annals of Internal Medicine 2007;147:478-91. Lumbar Support • No clear benefit 36 van Duijvenbode IC, Jellema P, van Poppel MN, van Tulder MW. Lumbar supports for prevention and treatment of low back pain. Cochrane Database Syst Rev. 2008;(2 12 Massage • Insufficient evidence • Not cost effective 37 Lin CW, Haas M, Maher CG, Machado LA, van Tulder MW. Cost‐effectiveness of guideline‐ endorsed treatments for low back pain: a systematic review. Eur Spine J. 2011;20(7):1024–1038. Manipulation? • 2011 Cochrane: 8 unbiased studies: • Small improvement at 1‐6 months • No effect at 12 months • Small improvement in function at one month only 38 Rubinstein SM, van Middelkoop M, Assendelft WJ, de Boer MR, van Tulder MW. Spinal manipulative therapy for chronic low‐back pain. Cochrane Database Syst Rev. 2011;(2):CD008112 TENS? • 2008 Cochrane Review of 4 studies • No better than placebo • No improvement at 2‐4 weeks • No improvement in function with validated scales 39 Khadilkar A, Odebiyi DO, Brosseau L, Wells GA. Transcutaneous electrical nerve stimulation (TENS) versus placebo for chronic low‐back pain. Cochrane Database Syst Rev. 2008;(4):CD003008 13 Traction • No benefit in high quality studies • Single or combined • Acute or chronic 40 Surgical Indications • Cauda equine syndrome • Profound neurologic deficit • Incapacitating pain after 4‐6 weeks of conservative treatment 41 AAFP CME Bulletin March 2008 Epidural Spinal Injection • 2008 Cochrane: ESI v. placebo –no difference in general improvement, pain relief, or disability • Spinal stenosis ESI + lidocaine v. lidocaine only, no improvement • 2008 literature review: no role for repeated ESI 42 Am Fam Physician. 2015 May 15;91(10):708‐714 14 Return to Work • Complete pain relief does not occur till normal activities return • Complete pain elimination is not necessary • Early return does not increase risk of injury • Off work 4‐12 weeks → 40% off for one year • Off 2 years → seldom return ever 43 Am Fam Physician. 2007 Nov 15;76(10):1497‐1502 Depression Depression is the inability to construct a future Rollo May 44 Epidemiology of Depression • Lifetime Incidence • 12% men • 20% in women • Twin studies suggest inheritability of 37% 45 15 Forced Swim Test • No chance of escape • Single injection of antidepressant increases struggling time • Excellent predictive validity 46 SIGECAPS • Sleep disturbances • Interest diminished • Guilt or feeling worthless • Energy loss • Concentration difficulties or indecisiveness • Appetite abnormalities or weight change • Psychomotor retardation or agitation • Suicidal acts or thoughts 47 PHQ‐2 • 97% sensitive, 67% specific in adults • 100% sensitive and 77% specific in the elderly • Two questions • Over the past two weeks, how often have you been bothered by any of the following problems? 1) Little interest or pleasure in doing things 2) Feeling down, depressed, or hopeless 48 Nease DE Jr, Maloin JM. Depression screening: a practical strategy. J Fam Pract. 2003;52(2):118–124 16 Integrative Treatment of Depression 49 St. John‘s Wort • Better than placebo in major depression • Similar to standard antidepressants in mild to moderate depression • Side effects: • GI upset, mild sedation, restlessness, photosensitivity at high doses • Decreases efficacy of; • TCA’s, contraceptives, cyclosporine, and antiepileptics • Increased risk of bleeding with clopidrogrel 50 SAMe • Natural amino acid involved with synthesis of neurotransmitters • May have rapid onset of action, 7 days in double blind, placebo controlled trial • May be beneficial as adjunct to SSRI • May induce hypomania 51 Kagan BL et al. Am J Psychiatry 147(5):591‐595 17 Folate • Involved in monoamine transmitter synthesis • May have role for adjunct of SSRI’s • Study with fluoxetine • Low folate –7.1% improved • Normal folate – 44.7% improved • Other studies suggest better in women 52 . J Clin Psychistry. 2004 Aug;65(8):1090‐5 B12 • Higher levels may give better clinical response to conventional antidepressants • Consider with drugs such as metformin 53 Hintikka J et al. BMC Psychiatry 2003;3:17 Exercise for Depression • SMILE study, 16 weeks • As good as sertraline • Better combined • Lost benefit if exercise stopped 54 Blumenthal JA et al. Psychosom Med 2007;69(7):587‐596 18 Light Therapy • SAD identified in 1984 • Cochrane review modest improvement • Better in morning • Sleep deprived • Adjunct to antidepressants • Side effect of hypomania • Effective in pregnancy 55 Cochrane Database Syst Rev. 2004;(2):CD004050 Antidepressant Selection • Prior treatment success • Treatment success in first degree relative • Drug interactions • Side effect profile 56 Antidepressant Selection Fatigue Prozac, Effexor, desipramine Anxiety Cymbalta, Paxil, Prozac, Zoloft Obese Prozac, Effexor, desipramine (avoid Remeron) Underweight Remeron (avoid Prozac,, desipramine Multiple Med Celexa, Zoloft Pain Cymbalta, amitriptyline, imipramine 57 19 Bipolar Depression 58 Robin Williams 1951‐2014 “Do I perform sometimes in a, in a manic style? Yes. Am I manic all the time? No. Do I get sad? Oh yeah. Does it hit me hard? Oh yeah.” 59 Bipolar Disorder: Lifetime Prevalence • 4% lifetime prevalence • 1.2% for bipolar I • No predilection for race, sex, or ethnicity • Mean onset age • 18 for bipolar I • 22 for bipolar II 60 20 Bipolar Genetics • Fivefold to 10‐fold in first‐ degree relatives • Concordance for identical twins 80% to 90% • Dizygotic twins approximately 15% 61 Bipolar I & II 1Mania 2Hypomania 1 3 Dysthymia 4Major Depression Happy 2 1+4 Bipolar I 2+4 Bipolar II 2+3 Cyclothymia 3 Sad 4 62 2000 National DMDA Bipolar Survey • Misdiagnosis occurred in 69% • Most frequent misdiagnosis • Depression (60%) • Anxiety Disorder (26%) • Schizophrenia (28%) • Borderline or antisocial personality disorder (17%) • Alcohol/substance abuse (14%) • 35% of patients wait 10 years or more for correct diagnosis 63 21 When to Suspect Bipolar Disorder • Earlier age of onset before 25 • “Leaden” depression • Higher attack frequency • Family history –5 different genes • “ugly pedigree” –many family members depressed, anxious, addicted, acting out • Anergia • Hypersomnia • Hyperphagia 64 When to Suspect Bipolar Disorder • Behavioral disruptions • Tempestuous interpersonal • Legal • Job problems • Attention deficit 65 When to Suspect Bipolar Disorder • Look better in office • Antidepressant failure –3 or more failures diagnostic clue • Antidepressant induced activation in first two weeks • Seasonal pattern –certain time of year • “Good too soon” 66 22 Unipolar vs. Bipolar Symptom Bipolar Unipolar Anhedonia Severe Moderate Hypersomnia 44% 18% Persistently 45% 0% depressed mood Psychomotor Severe Moderate retardation 67 Unipolar vs. Borderline Personality Symptom Bipolar Borderline Duration mood Weeks or Hours swings months Manic episodes World conquests Yell and shout Fine, as long as Relationships Rocky not manic Off meds Anything, “break Manic triggers Sleep up with interference boyfriend” 68 Five Factors Pointing to Bipolar Depression Symptoms Previous or Current Manic Episode Treatment Response Family History RX emergent mania “Loaded” Poor Rx Response Multiple Rx failures Early Age of Onset Course of Symptoms Younger than 25 Abrupt onset and Termination 69 23 Comorbidities • 60‐70% alcohol and/or other substance abuse • About 50% attempt suicide • 15% will succeed • 43% anxiety disorders • 1/3 overweight 70 Bipolar II • Not a milder Bipolar I • psychosocial morbidity, substance abuse, and suicide attempts just as common • More common in females • “breeds true”, runs in families • Tend to stay in category 71 Clinical Course • Age of first psychiatric impairment 18.7 years • First treatment 22 years • Mean age of first hospitalization age 25 • Average manic episode last 4 months • Average depressive episode 6‐9 months • First cycle averages 5 years • by 4th cycle has dropped to one year 72 24 Medical Disease • Twice as likely to die from: • Infectious disease • Cancer • Cardiovascular disease 73 Comparative Treatment Costs Annual Health Condition Care Cost Bipolar Disorder $3416 Diabetes $3083 Depression $2570 General Outpatient $1462 74 Simon GE, Unutzer J. Psychiatr Serv. 1999 SCREENING QUESTIONS • Have you ever had a period of a week or so when you felt so happy and energetic that your friends told you that you were talking too fast or that you were behaving differently and strangely? • Has there been a period when you were so hyper and irritable that you got into arguments with people? 75 25 DIGFAST • Distractibility • Indiscretion (pleasurable activities) • Grandiosity • Flight of ideas • Activity increase • Sleep deficit (decreased need) • Talkativeness (pressured speech) 76 WHIPLASHED • W Worse or Wired when taking antidepressants • H Hypomania or mood swings • I Irritable, hostile • P Psychomotor retardation or agitation • L Loaded family history • A Abrupt onset or termination of depressive bouts • S Some have energy bursts before depression • H Hyperphagia and Hypersomnia • E Early onset depression (<25 yrs) • D Delusions, hallucinations 77 Symptomatic Almost Half Their Lives 9% 6% 32% 53% Asymptomatic Depressed n=146 Manic/hypomanic 12.8 year follow-up Cycling/mixed 78 Judd et al. Arch Gen Psychiatry 2002 26 Acute Bronchitis 79 How Common? • Respiratory infection 50% of acute conditions • 5% of population each year • 90% seek medical attention 80 Benson, V et al. Vital Health Stat 10. 1998;199:1‐428 Acute Bronchitis • Cough, maybe productive • Wheezing, fever or both • Pneumonia not suspected • May last 3 weeks 81 27 Natural History • URI symptoms for first 4 days, doesn’t improve after one week • Develops cough, wheeze for 2‐3 weeks • 40% have reduced FEV1 for 5‐6 weeks • Cough may last over 4 weeks • mean of 18 days 82 Richard P. Wenzel, M.D., and Alpha A. Fowler, III, M.D. N Engl J Med 2006; 355:2125‐2130 Diagnosis • Resp rate < 24 • Temp < 100.5⁰ F • Pulse < 100 • Purulent sputum not good predictor • 70% sensitive and specific 83 Metlay, JP et al. JAMA 1997;278:1440‐1445 Abnormal Vitals • No abnormal vital signs associated with < 1% risk of pneumonia • RR > 20 • HR > 100 • Temp > 37.8⁰C 84 Metlay JP, et al, JAMA 1997; 278:1440‐1445 28 Etiologies Viral –90% Bacterial • Adenovirus • Bordetella pertussis • Coronavirus • Chlamydia pneumonia • Influenza A and B • Mycoplasma pneumonia • Metapneumovirus • Parainfluenza virus • Respiratory syncytial virus • Rhinovirus 85 Wenzel RP, Fowler AA III. Clinical practice. Acute bronchitis. N Engl J Med. 2006;355(20):2125–2130 Cold Mediators Bradykinin – Cytokines – Local Symptoms Systemic Symptoms • Sore throat • Fever and Chills • Nasal congestion • Headache • Watery eyes • Fatigue • Cough • Malaise • Anorexia • Nausea • Depression 86 Symptomatic Management • Maybe antitussives, no evidence • Expectorants ineffective • β agonists for wheezing • No oral steroids 87 Schroeder K, Fahey T. Over‐the‐counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2004;(4):CD001831 29 Antibiotics • 90% are viral, 10%‐30% multiple viruses • Viral shedding is often decreasing at presentation • 2/3 are treated with antibiotics • 55% of our patients believe they help for URI’s • 25% use left over antibiotics 88 Do Antibiotics Help? • NNT 5.6 for cough reduction at follow‐up • No change in activity limitations • Number needed to harm 16.7 89 Smucny JJ, Becker LA, Glazier RH, McIsaac W. Are antibiotics effective treatment for acute bronchitis? A meta‐analysis. J Fam Pract. 1998;47(6):453–460 When to Use Antibiotics • Pertussis treatment is considered to reduce transmission • No difference in duration of symptoms 90 30 Consider Pertussis • 12% ‐ 35% of cough over 14 days • Post‐tussive emesis • Paroxysms of coughing • Inspiratory whoop 91 CDC, Amer College of Chest Physicians Pertussis Clinical Course 92 Serologic Markers • Procalcitonin decreased antibiotic use • 83% vs. 44% • No difference in outcomes 93 Christ‐Crain M, et al. Lancet. 2004;363(9409):600–607. Christ‐Crain M, et al. Am J Respir Crit Care Med. 2006;174(1):84–93. 31 Ibuprofen or Amox/Clav ? • Adults 18‐70 • One week symptoms, cough,, discolored phlegm • One other SX; dyspnea, wheezing, chest discomfort or pain • Amox/clav or ibuprofen 600 tid or placebo • Outcome measure days of cough 94 BMJ 2013;347:f5762 Ibuprofen or Amox/Clav ? • Days of cough • Side effects • 9 days ibuprofen (95% CI 8‐ • 12% amox/clav 10 days) • 5% ibuprofen • 11 days amox/clav (95% CI • 3% placebo 10‐12 days) • 11 day placebo (95% CI 8‐14 days) 95 BMJ 2013;347:f5762 Amoxicillin for Acute LRTI in Primary Care, Pneumonia Not Suspected 96 The Lancet Infectious Diseases 2013 13, 123‐129DOI 32 Rate of ABX Use for Acute Bronchitis • 3000 visits for acute bronchitis, 1996‐2010 • Extended macrolides increased from 25% to 40% • Other broad spectrums prescribed 1/3 of the time • Education is not working 97 Michael L. Barnett, MD1; Jeffrey A. Linder, MD, MPH1 JAMA. 2014;311(19):2020‐2022 ABX for Adults With Acute Bronchitis in USA, 1996‐2010 98 JAMA. 2014;311(19):2020-2022 Why is Mucous Green? • Not Bacteria • Green protein myeloperoxidase from neutrophil and monocyte granules 99 33 Green Mucous ≠ Bacterial Infection 100 Antibiotics v. Low Dose Vitamin C • 230 pts with acute bronchitis treated with vitamin C or azithromycin • No difference at days 3 and 7 • 89% of both recovered • No difference in return to work or school 101 Evans AT, Husain S, Durairaj L, Sadowski LS, Charles‐Damte M, Wang Y. Azithromycin for acute bronchitis: a randomised, double‐blind, controlled trial. Lancet. 2002;359(9318):1648–1654 Do Antibiotics Prevent Pneumonia • 814,000 patients, 1.5 million visits • 65% Dx with bronchitis • Significant minor adverse side effects in treated group • Less hospitalizations for pneumonia in antibiotic group • NNT is 12,225 102 Meropol SB et al. Ann Fam Med March/April 2013 vol. 11 no. 2 165‐172 34 Cochrane Review • 11 studies. 3841 patients • 0.46 days reduction in cough • 0.64 days less of feeling ill • Number needed to harm 5 103 Smith SM et al. JAMA 312:2678‐9 Managing Antibiotic Expectations • Call it a “chest cold” • Set realistic expectations, about 3 weeks • Explain antibiotics don’t help; create resistance and side effects • Doesn’t prevent pneumonia • Consider “pocket” script 104 35