WHO Launches Worldwide Hepatitis Network

August 2013

www.medicaltribune.com WHO launches worldwide hepatitis network

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NEWS AFTER HOURS

Heart patients avoid Ipoh and its former health lifestyles glory 2 August 2013 WHO launches worldwide hepatitis network

Elvira Manzano

new global movement against hepatitis which aims to bring about inter- Anational collaboration and stem the spread of this viral infection worldwide, was launched at the recent Asian Pacific Associa- tion for the Study of the Liver (APASL) congress held in Singapore. The network, a collaboration of the World Health Organization (WHO), the World Hepatitis Alliance and the Coalition for the Seventy-four percent of the world’s hepatitis B and C population reside in the Asia Pacific. Eradication of Viral Hepatitis in Asia Pacific (CEVHAP), aims to build global initiatives ments in treatment, the funding situation has and strengthen capacities to raise awareness, led to an era of neglect and spiral in deaths,” promote partnerships, mobilize resources, said Mr. Charles Gore, president of the World and provide screening, care and treatment for Hepatitis Alliance, at the network launch. 500 million people worldwide afflicted with The Asia Pacific bears the brunt of the bur- hepatitis. den, with 74 percent of the total hepatitis B “Every day, clinicians witness the signifi- population living in the region. cant challenges that national health services In Singapore, 160,000 people or 2.7 per cent face in combating viral hepatitis,” said Pro- of the population has hepatitis B or C. While fessor Lim Seng Gee, APASL 2013 chair and the country has had great success with child- a CEVHAP founding member. “We hope the hood immunization of hepatitis B, Singapore Global Hepatitis Network will inject new “cannot rest on its laurels,” said Singapore vigor into the global and regional response. Health Minister Gan Kim Yong. A systematic and coordinated response across “We need to continue to innovate and find Asia Pacific is essential to combat these dis- new ways to address our healthcare challeng- eases.” es. We need to continually invest in research According to the latest Global Burden of to help us better understand the diseases and Disease Study, 1.4 million people die from vi- develop improved, more cost-effective diag- ral hepatitis each year, similar to deaths from noses and treatments.” HIV/AIDS and higher than from tuberculosis Professor Stephen Locarnini, CEVHAP and malaria. However, until recently hepatitis joint secretary and director of the WHO Re- has not been getting the same level of atten- gional Reference Laboratory for Hepatitis B tion and resources as tuberculosis and ma- at the Victorian Infectious Diseases Reference laria. Laboratory (VIDRL), said the real challenge “The major global health funds still exclude is to make medicines accessible and afford- hepatitis and despite significant advance- able to all. “My lab is committed to devel- 3 August 2013 oping cheaper diagnostic tests and quanti- stitutions, professional organizations such tative assays to accurately diagnose chronic as APASL, patient groups, laboratories and hepatitis and monitor treatment response. If other developmental agencies that fund inter- we can only treat patients effectively, we can national health initiatives. reduce liver cancer by 50 percent, and that is “WHO will use its unique convening role the most important take-home message.” to unite a large group of people interested in After the official launch, the network will doing viral hepatitis prevention and control invite as members WHO collaborating cen- activities,” said WHO Professor Hande Har- ters and relevant UN agencies, research in- manci.

New drug corrects abnormal sleep cycles due to blindness

Laura Dobberstein the urine were measured to determine the circadian period. Study participants reported asimelteon, a novel circadian regula- night-time sleep, day-time naps and overall tor with selective agonist activity for feelings of well-being. Tmelatonin receptors, has been shown “None of the traditional medications used to improve the synchronization of circadian to treat sleep disorders or sleepiness have this rhythms in completely blind patients with ability and therefore tasimelteon has the poten- non-24 hour sleep-wake disorder. tial to be the first circadian regulator approved “Tasimelteon addresses the root cause of by the US Food and Drug Administration for this disorder by resetting the circadian clock the treatment of non-24 hour sleep-wake dis- in the brain,” explained the study’s lead au- order in the blind,” said Lockley. thor, Dr. Steven W. Lockley, neuroscientist at “This study describes a promising new Brigham and Women’s Hospital and associate therapy for sleep disturbances,” commented professor at Harvard Medical School in Bos- Dr. Joel Wommack, neuroscientist and re- ton, Massachusetts, US. “The medication is searcher at the University of Texas BioBehav- able to replace the time cue usually provided ioral Lab in Austin, Texas, US, during an in- by light and synchronize the circadian clock terview with Medical Tribune. “More detailed in totally blind people.” studies should be performed to establish a In the multicenter study, 84 patients who dose-response curve and evaluate the long- exhibited abnormal sleep cycles due to blind- term effects of this drug.” ness were randomized to double-blind treat- The study was presented at ENDO 2013, ment with either tasimelteon 20 mg or place- the Endocrine Society’s 95th Annual Meet- bo daily, given 1 hour prior to a fixed chosen ing held in San Francisco, California, US from bedtime for 6 months. The researchers collect- June 15 to 18, and was supported by Vanda ed urine samples starting 2 weeks after treat- Pharmaceuticals, which is developing ta- ment began. Melatonin and cortisol levels in simelteon. 4 August 2013 Forum Heavy burden of viral hepatitis in the Asia Pacific region

Excerpted from a presentation by Dr. Chen Ding-Shinn of the Department of Internal Medicine and Hepatitis Research Center at National Taiwan University College of Medicine and Hospital, Taipei, Taiwan, delivered at the annual conference of the Asian Pacific Association for the Study of the Liver (APASL) recently.

he Asia Pacific region has long been known to have a high prevalence of Tviral hepatitis. Identification of biomarkers of hepatitis A, B, C, D and E has enabled us to estimate the burden of these hepatitides, and to implement subsequent control measures. Despite tremendous suc- cesses, however, more needs to be done to control viral hepatitis in our region. Hepatitis A has one serotype and three genotypes in humans. Genotype analysis is very informative in investigating the molecular epidemiology of hepatitis A and with this process, we can trace the source of the virus. In highly endemic areas, hepatitis A infection usually occurs in childhood but the affected children usually remain asymptom- Chronic hepatitis B highly prevalent atic. In areas of intermediate endemicity, the Hepatitis B remains a serious problem in infection is acquired in late childhood or the region because of highly prevalent chronic early adulthood through person-to-person infection that is refractory to treatment. In the transmission, whereas in low endemicity ar- past 10 years, a series of studies mostly from eas, infection is seen in high-risk groups or the Asia Pacific have made it clear that these travelers. chronic carriers are reservoirs of the infection, With improvements in hygiene, this orally and are at risk of cirrhosis and hepatocellular transmitted infection has decreased markedly carcinoma, especially in those who carry high in the last few decades. However, this success viral loads. Hepatitis B virus (HBV) genotypes has resulted in an unintended consequence of also play a vital role in the natural history and rendering a large proportion of the younger response to specific therapies. HBV genotype population susceptible to the virus. Fortu- C infection is generally worse than that seen nately, effective vaccines against hepatitis A with genotype B. In the younger generation, virus are now available. the infection has been brought under control 5 August 2013 Forum after mass immunization against hepatitis B the Asia Pacific, and travel to these areas ap- virus in early childhood. pears to be a main risk factor for contracting Hepatitis C is another important cause of the infection, although consuming the con- morbidity and mortality in the region. The in- taminated foods is another important route fection easily becomes persistent and the chro- of the infection in some countries. While well nicity also contributes to the development of documented in several countries, the epide- cirrhosis and hepatocellular carcinoma. miology of hepatitis E remains far from clear. Although no effective immunization is Effective vaccines have been developed but available for hepatitis C, the infection ac- are not yet widely available. Two recombinant quired by parenteral route can be controlled vaccines were developed and one licensed in by preventive measures. In addition, treat- China in December 2011. ment with pegylated interferon plus ribavirin for chronic hepatitis C is effective because of Conclusion the favorable genetic makeup in Asians. There remains a heavy disease burden of viral hepatitis across the Asia Pacific region. Drop in hepatitis D cases While control measures are now available, The prevalence of hepatitis D has de- much remains to be done. Sustained efforts creased markedly in the last two decades and are needed from everyone including patients, new cases are rarely encountered now, except hepatologists, healthcare professionals, non- in Mongolia. governmental organizations and policy Hepatitis E is endemic in limited areas of makers.

READ JPOG ANYTIME, ANYWHERE. Download the digital edition today at www.jpog.com 6 August 2013 Philippine Focus DOH recognizes smoke-free communities

Dr. Maria Katrina Florcruz courages the youth from using alcohol and cigarettes. In addition, raising taxes on tobac- uring the 2013 World No Tobacco Day, co have direct effects in reducing deaths and the Department of Health (DOH) el- illnesses from tobacco-related non-commu- Devated various cities, municipalities, nicable diseases. Policies and programs for government offices and hospitals to the DOH tobacco-free environments also protect non- Red Orchid Awards Hall of Fame. These insti- smokers from the health hazards brought tutions were recognized for their achievement about by exposure to secondhand smoke. in implementing 100-percent tobacco-free en- The government offices elevated to the hall vironments for three consecutive years. of fame are the Provincial Health Office of This year’s hall of fame winners for the lo- Nueva Vizcaya and the DOH regional offices cal government units (LGU) received a trophy in Bicol and Western Visayas. and Php 500,000 grant to sustain tobacco con- The following government hospitals trol grants. The 12 LGUs are: Balanga City; are hall of fame awardees: Corazon Locsin Roxas City; Alamada, North Cotabato; Am- Montelibano, Memorial Regional Hospital, lan, Negros Oriental; Buenavista, Guimaras; Cotabato Regional and Medical Center, Luis Calatrava, Romblon; Dupax del Norte, Dupax Hora Memorial Regional Hospital, Mariano del Sur and Solano of Nueva Vizcaya; Naval, Marcos Memorial Hospital and Medical Biliran; Tantangan, South Cotabato; and Ver- Center, Nueva Vizcaya Provincial Hospi- uela, Agusan del Sur. tal, Ospital ng Palawan, Quirino Memorial The World Health Organization-Western Medical Center, Tagaytay Treatment and Pacific Regional Office (WHO-WPRO) award- Rehabilitation Center, and Western Visayas ed a medal of honor to President Benigno S. Sanitarium. Aquino III, Senator Franklin Drilon, Represen- This year, the Red Orchid Award was given tative Isidro Ungab and the members of the to the provinces of Nueva Vizcaya and Misa- Sin Tax team. The individuals recently won mis Oriental. This indicates that 100-percent the World No Tobacco Day 2013 award. tobacco-free environment is being imple- Health Secretary Dr. Enrique Ona said that mented in their respective government, hos- reforming the excise tax system took more pital and health offices. than 15 years and it was under the present Two government offices were also Aquino administration that this legislative recognized with a special award for breaking measure was prioritized and approved. new ground in tobacco control. The Philip- “The Sin Tax is the only tax reform that pine Gaming and Amusement Corporation President Aquino has truly advocated that will in Iloilo City was recognized for its efforts in not cause burden to Filipinos,” said Ona. He implementing a no-smoking casino. The Na- added that the sin tax on alcohol and tobacco tional Parks Development Committee was products will protect the health and welfare of given the Special Award for making the fa- the poor because revenues from the tax will mous Rizal Park in Manila smoke-free. help improve universal health coverage and For the complete list of finalists and win- provide access to quality health facilities. ners, visit the Beat Tobacco website at www. The Sin Tax, Ona emphasized, also dis- beat-tobacco.ph. 7 August 2013 Philippine Focus Culture-based beliefs persist in maternal and infant health care

Dr. Maria Katrina Florcruz restrictive beliefs are to be avoided. Taboos, on the other hand, are thought to bring harm recent study done by Magdalena to the infant if not followed. The investigator Ocbian from Sorsogon State College added another type of belief called predictive Aexplored the existing culture-based which gives a foresight of the events based on beliefs used by Sorsoguenos on pregnancy observed signs. and childbirth. The descriptive study was Results of the study showed that the sub- done using survey questionnaire, unstruc- jects were most aware of the IKS that a preg- tured interviews, focus group discussions and nant mother should be happy because stress observation. Culture-based beliefs and prac- may affect the baby’s health. The second belief tices, also known as indigenous knowledge is that food cravings of the pregnant mother system (IKS), are norms and standards com- should be provided; otherwise, it may lead to monly held to set expectations for behavior. abortion or cause the child to profusely sali- In the Philippines, there are numerous beliefs vate and vomit. in various regions and provinces which affect The study also showed that most of the the different aspects of family life, including locals believed that a pregnant mother should maternal and infant healt care. not wear anything around the neck to prevent The researcher conducted preliminary in- cord coil. Cold food is also not advised as this terviews of elderly mothers and health work- may make the fetus overweight. ers from communities in Sorsogon to obtain The gender of the baby is also predicted information on existing IKS on pregnancy by most locals based on the mother’s ap- and childbirth. A Likert’s Scale was devel- pearance and the shape of abdomen. A oped to measure the level of awareness and mother who is radiant and beautiful with a frequency of practice of the identified beliefs. rounded abdomen is believed to be carry- A total of 225 subjects composed of moth- ing a baby girl. On the other hand, if she ers, fathers and health workers answered the is gloomy and the abdomen is pointed, she questionnaire. will have a baby boy. Majority of the respondents were females, The subjects believed that visitors should married and belonged to the 36- to 45-year- not stand near the door when visiting a preg- old age group. Almost half of the subjects nant woman because this may cause difficult reached college level and many have income delivery. Women should hold to hard objects levels below the poverty threshold. during delivery to prevent extreme labor The gathered data on cultural beliefs were pain. classified as prescriptive, restrictive and ta- The investigator concluded that although boos. Prescriptive beliefs demand to be per- majority of the subjects reached college level, formed by any of the family members while traditional and culture-based beliefs on preg- 8 August 2013 Philippine Focus nancy and childbirth are still being practiced. The researcher recommended that cultural The beliefs often serve as guide for mother background and beliefs of patients should and other members of the family in caring for also be considered by healthcare practitioners the pregnant and nursing mothers and their in establishing maternal and infantcare pro- newborn. grams, especially in local hospitals.

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Smart Rx. Every Time. 9 August 2013 Philippine Focus

TREATMENT FOCUS: CARDIOLOGY

ST2 biomarkers and risk stratification in heart failure

Dr. Maria Katrina Florcruz

here has been an increase in the local prevalence of heart failure Tover the past years. This statistic is rising quickly and the need for prognostication and predicting possible outcomes in these patients is becoming very important. According to Dr. Antoni Bayes-Genis, chairman of Cardiology of the Hospital Uni- versitari Germans Trias i Pujol (HUGTiP) in class II or class III may be more stable but are Barcelona, approximately 7 percent of the at risk of experiencing sudden cardiac death. general population has heart failure. Based “Fibrosis is one of the many pathophysi- on age groups, the prevalence of heart failure ological processes that may also affect the increases from 1 percent (45 to 54 years old) myocardium. Cardiac fibrosis leads to left to almost 19 percent for those who are more ventricular stiffness and this produces dys- than 74 years old. synchrony and systolic dysfunction and final- “We are talking about a big epidemic in the ly heart failure,” Bayes-Genis said. He added world,” said Bayes-Genis. In 2004, the peak that cardiac fibrosis also produces tissue het- prevalence of heart failure among Europeans, erogeneity, anisotropy and re-entry arrhyth- regardless of gender, occurs at age 40. By the mias, which place the patient at risk of sud- year 2050, he said that the age group with the den cardiac death. most heart failure will be those between 60 to 65 years old. In routine practice, we cannot ‘‘ afford measurement of two or Natural evolution of heart failure Bayes-Genis said patients who suffer an more biomarkers initial myocardial damage, such as myocardial infarction, have a 30-percent risk of being Hence, there is a need to protect these pa- readmitted in six months. At the same time, tients and to identify which of them will have these patients will have poor quality of life. a worse prognosis and will be at risk of suf- On the other hand, patients who belong to fering sudden cardiac death, added Bayes- 10 August 2013 Philippine Focus

Genis. Currently, biomarkers such as ST2 are risk of patients. Through this, clinicians will being used by clinicians as an aid in predict- be able to identify the low- and high-risk pa- ing the prognosis of cardiac patients. tients. In acute decompensated heart failure, ST2 ST2 biomarker and the role of IL-33 has an additive value to another biomarker The biomarker ST2, first reported in 1989, is called N-terminal pro-brain natriuretic pep- a member of the interleukin-1 receptor fam- tide (NT-proBNP). When both biomarkers are ily. In 2002, it was found that ST2 is being ex- low, the long term prognosis of the patient is pressed in cardiac tissues and it is actively in- good. If only NT-proBNP is elevated, the pa- volved in fibrotic response to injury. tient has moderate risk. If both ST2 and NT- Through alternative splicing and process- proBNP are elevated, hazard ratio goes up. ing, two main isoforms are formed: ST2 Li- Hence, ST2 helps in re-classifying a patient gand (ST2L) and soluble ST2. The ST2L is a from moderate to high risk, explained Bayes- membrane-bound isoform while the soluble Genis. ST2 is the circulating isoform which can be Several multicenter studies have also measured through blood samples. shown that ST2 and NT-proBNP may be used The ligand of ST2 is IL-33 and it acts as the to identify patients at risk of sudden cardiac key player in fibrosis. Bayes-Genis explained death. When the levels of both biomarkers are that high ST2 levels block the cytokine IL-33 low, there is a 4-percent risk of sudden cardiac due to decoy binding. In normal situations, death. The risk increases to 72 percent when fibroblast produces IL-33 that binds to ST2L. biomarker levels increase to high levels. This in turn activates MyD88 and a number of intracellular signaling pathways in the myo- ST2 in mortality prediction models cytes to act as cardioprotective agents, there- A mortality prediction model called Bar- by preventing fibrosis and remodeling. celona bio-heart failure calculator was devel- When the level of circulating ST2 is too oped to assess the usefulness of a multi-mark- high, IL-33 will instead bind to soluble ST2 er strategy for risk stratification in a cohort of and this will eventually cause fibrosis and ambulatory patients with heart failure. In the remodeling. ST2, therefore, in cardiac medi- study, according to Bayes-Genis, three bio- cine is not a marker for stretch and inflam- markers were utilized: NT-proBNP, ST2 and mation. Rather it is a marker for fibrosis high sensitive troponin T (hs-TnT). These bio- and remodeling. “Clinical use is not affected markers reflect monocyte injury (for hs-TnT), by obesity and renal impairment,” Bayes- myocardial stretch (for NT-proBNP) and ven- Genis added. tricular fibrosis and remodeling (for ST2). Multivariable Cox regression analysis was ST2 and heart failure prognostication done on 11 clinical variables along with the Bayes-Genis discussed studies which show biomarkers. All three biomarkers showed that as the New York Heart Association Heart higher significance in the model compared to Failure Classification symptom severity in- other clinical variables such as renal function creases, ST2 level increases. This implicates and ejection fraction. that ST2 level correlates with 1-year mortality Five mortality prediction models were 11 August 2013 Philippine Focus then developed. Model one contained only For outpatient monitoring, if the first and 11 clinical variables while models two to five second measurement are both below the nor- included the biomarkers. Results of the study mal cut-off value of 35 ng/mL, the progno- showed that all models with biomarkers were sis is good. If the ST2 level started high and better compared to model one. then goes down in the second measurement, “Re-classification … makes a biomarker re- the patient has 2-percent higher risk of death. ally relevant to clinical practice,” Bayes-Genis Single values of ST2 can also readily provide said. The addition of NT-proBNP and hs-TnT an identification of risk. to the model reclassified 4 percent of the pa- Bayes-Genis added that ST2 levels may also tients. Upon addition of ST2, 9.6 percent of help predict a patient’s response to mineralo- the patients were reclassified. When hs-TnT corticoid receptor antagonists (MRAs) be- and ST2 were combined, almost 14 percent of cause studies have shown that MRA attenuat- the patients were re-classified, indicating its ed remodeling more in patients with a higher stronger predictive value. baseline ST2.

ST2 for monitoring and therapy guidelines ST2 in clinical practice Bayes-Genis further mentioned that ST2 has Bayes-Genis said the single cut-off point of also been found to have value in monitoring 35 ng/mL has been routinely used in his in- and therapy guidelines. If the value of ST2 institution, to identify low risk patients.Repeat- creases three or four days after admission, the ed measurements of ST2, on the other hand, patient has a high risk of mortality in 90 days. is being used to monitor drug-up titration, stratify risk, and evaluate high-risk patients Re-classification … makes a for sudden cardiac death. “In routine practice, we cannot afford mea- ‘‘ biomarker really relevant to surement of two or more biomarkers. So we clinical practice use NT-proBNP for diagnosis and st2 for prognosis-monitoring,” Bayes-Genis added.

READ JPOG ANYTIME, ANYWHERE. Download the digital edition today at www.jpog.com 12 August 2013 Philippine Focus

CONFERENCE COVERAGE

44th Annual Convention and Scientific Meeting of the Philippine Heart Association, 29-31 May 2013, EDSA Shangri-La Hotel, Mandaluyong City

Cardiac involvement common in SLE patients

lead to the development of various cardiac Dr. Carol Tan diseases such as pericarditis, myocarditis and Libman-Sacks endocarditis. Anti-phospho- ardiac diseases are frequently found lipid antibodies, which are commonly pres- in patients with systemic lupus ery- ent in patients with SLE, are associated with Cthematosus (SLE), according to Dr. thrombotic events in the coronary arteries, Milagros Yamamoto, cardiologist from the heart valve dysfunction and intramyocardial University of Santo Tomas Hospital in Manila. vasculopathy. “Over 50 percent of patients with lupus The most commonly recognized cardiac will have cardiac manifestations. Pericarditis, problem in SLE is pericarditis, stated Yama- myocarditis, endocarditis, valvular deformi- moto. ties, coronary artery disease, and myocardial Clinical pericarditis is estimated to occur in infarction are all common in patients with 25 percent of patients with SLE, while asymp- SLE,” said Yamamoto. tomatic pericarditis manifesting as pericardi- The speaker said that numerous studies al effusion is detected by echocardiography in have shown the impact of cardiac disease 40 percent of patients with SLE. in the morbidity and mortality of patients Typical signs and symptoms involve po- with SLE. A retrospective cohort study con- sitional precordial or substernal chest pain, ducted by Trager and Ward in 2001 showed dyspnea, fever, tachycardia and decreased that the three most common causes of death heart sounds. The diagnosis can be confirmed in SLE are disease activity, infection and car- by electrocardiogram (ECG) findings of el- diovascular disease. A Philippine study done evated ST segments and peaked T waves. by Navarro from 2007 to 2012 reported that A common cardiac problem in SLE, myo- 19 percent of SLE deaths were due to cardiac carditis is largely subclinical and is usually involvement. only detected post-mortem. Clinical detection Yamamoto explained that cardiac involve- of myocarditis ranges from 3 to 15 percent, ment in SLE is brought about by autoantibod- and typical signs and symptoms include dys- ies which cause immune complex formation pnea, tachycardia, and arrhythmias. and deposition. The immune complexes serve Myocarditis can also progress to ventricu- as initial triggers for inflammation, which lar dysfunction, dilated cardiomyopathy and 13 August 2013 Philippine Focus heart failure. There are no typical findings on Libman-Sacks endocarditis, a verrucous ECG. Echocardiographic studies cannot defi- endocarditis of valve leaflets, papillary mus- nitely diagnose myocarditis, but global hypo- cles and the mural endocardium are also com- kinesia is strongly suggestive. monly found in SLE. Patients with valvular The speaker added that valvular involve- lesions are at increased risk for stroke. ment in SLE is reported in 32 to 38 percent “Cardiac disease in SLE is common, but of cases. In patients with Anti-phospholip- frequently asymptomatic, and recognized id antibodies syndrome, the most frequent only when the manifestations are full-blown. cardiac manifestations are vegetations and For all patients with lupus, it is necessary thickening of the heart valves. This com- that cardiac evaluation, especially echocar- monly affects the mitral valve, manifesting diography and electrocardiogram, be done,” as regurgitation. said Yamamoto.

RV condition offers cardiac protection in TOF patients

Dr. Maria Katrina Florcruz gone prior corrective TOF surgery. Baseline demographic data, including type of surgery, frequency of phlebotomy, history of previous research conducted at the Philippine Blalock-Taussig shunt and timing of surgery Heart Center-Department of Pediatric were collected. The subjects underwent 2D ACardiology showed that right ventric- echocardiogram and were classified into two ular (RV) restrictive physiology could offer a groups based on the presence of either restric- protective effect against RV systolic dysfunc- tive or nonrestrictive physiology. The pres- tion among patients who underwent correc- ence of RV systolic dysfunction in each group tive surgery for Tetralogy of Fallot (TOF). was then determined. The Long Lead II ECG RV restrictive physiology is an important tracing of all the subjects were used to mea- long-term phenomenon after TOF repair. It sure the QRS duration and to search for ven- has been shown to prevent the development tricular arrhythmia. of pulmonary regurgitation and its early pres- Majority of the subjects had nonrestrictive ence predicts the occurrence of RV restriction physiology and were between 13 to 19 years later in life. The investigators of this cross- old. Based on the type of surgical repair, 50 sectional study aimed to determine the preva- percent of all the subjects underwent non- lence of RV restrictive physiology and its as- transannular patch (TAP) repair and 70 per- sociation with RV systolic dysfunction among cent of this subset developed nonrestrictive post-operative TOF patients. physiology. Most of the subjects who had TAP All 69 subjects included in the study were repair developed restrictive physiology. Both between 1 to 18 years old and have under- RV restrictive and nonrestrictive physiology 14 August 2013 Philippine Focus occurred as early as 1 to 2 years post-opera- The investigators concluded that post- tively. operative TOF patients may develop RV RV systolic dysfunction was present in 60 restrictive physiology in as early as one to percent of all the subjects and among those two years after operation. TAP repair favors with history of phlebotomy and prior Blalock- the development of RV restrictive physi- Taussig shunt. ology. RV systolic dysfunction was more Among patients with restrictive physiolo- common in patients with non-restrictive gy, 42 percent had RV systolic function while physiology. This lead the investigators to 58 percent had none. Seventy-three percent of conclude that RV restrictive physiology may subjects with nonrestrictive physiology de- offer a protective effect against RV systolic veloped RV systolic dysfunction. dysfunction.

Exercise programs are underutilized in CAD patients

Ian Carlos Achero and 31 percent reduction in CHD mortality. Even with the numerous benefits of exercise, common barriers to enrolment such nly 11 to 20 percent of patients with as lack of physician referral, transportation stable coronary artery disease (CAD) problems and limited access hinder patients. Oparticipate in supervised rehabilita- “The major reason for dropout in the Philip- tion programs, according to Dr. Helen Ong- pines in most cardiac rehabilitation programs Garcia, chair of the Philippine Heart Associa- is geographic,” said Ong-Garcia. tion Council on Cardiac Rehabilitation. Citing Food and Nutrition Research Insti- The dropout rates reach up to 50 percent tute data, Ong-Garcia added that for prima- after three to six months. Ong-Garcia added ry prevention of cardiovascular disease, the that because of the vast underutilization of prevalence of physical inactivity among Fili- cardiac rehabilitation, a large number of heart pino adults is 70 to 90 percent depending on disease patients do not enjoy the benefits of the activity measured. exercise. “It speaks a lot about our attitudes cultural- Some of the benefits Ong-Garcia listed ly, and the education to our patients,” she said. were improved endothelial function, re- Reassuring patients of the safety of recom- duced platelet “stickiness,” reduced risk mended exercise is also important because of CAD and increased high density lipo- some patients believe exercise can bring harm protein levels. The speaker also cited a Co- if they have heart disease. “A lot of our pa- chrane meta-analysis which found that tients are very much scared of undergoing CHD patients who underwent exercise had exercise for fear of what they hear with mar- 27 percent reduction in all-cause mortality athon runners,” Ong-Garcia said. She also 15 August 2013 Philippine Focus emphasized the responsibility of doctors to can be explored with the patient and an alter- perform an assessment of patients’ ability to native approach may be suggested. conduct exercise safely. Similar to the ESC, the American Heart According to Ong-Garcia, the European Association and American Association of Society of Cardiology (ESC) recommended Cardiovascular and Pulmonary Rehabilita- that doctors should assess the exercise capac- tion recommended proper formulation of an ity and ischemic threshold using a stress test exercise program tailored for an individual. before advising patients to participate in an Both aerobic exercises (eg, walking, treadmill, exercise program. Based on the risk assess- cycling) and resistance exercises (eg, dumb- ment, patients can be advised whether to go bells, weight machines, elastic bands) were on their own exercise program or to a medi- suggested for optimal cardiac rehabilitation. cally supervised one. Warm-up, cool-down and flexibility exer- Informing patients of the lifelong continu- cises were recommended to be included in ation of physical conditioning and the risk of each session. The exercise prescription should relapse is also important because barriers to be updated routinely and when patient con- adherence (eg, physical, social, psychological) dition warrants, concluded Ong-Garcia.

Shockwave therapy improves ischemic heart symptoms

Dr. Carol Tan treating patients with IHD was evaluated. All 65 subjects included in the study were diagnosed to have coronary artery disease, refrac- recent study conducted by Dr. Les- tory or stable angina, ischemic cardiomyop- ter Uy and colleagues from St. Luke’s athy, and heart failure (NYHA Class I or II) AMedical Center showed that Extracor- and underwent ESMR therapy at St. Luke’s poreal Shockwave Myocardial Revasculariza- Medical Center. tion (ESMR) significantly improved symp- Patients with to NYHA Class III or IV, had toms and quality of life among patients with intravascular thrombus, with severe lung and ischemic heart disease (IHD). valvular disease, or experienced acute coro- The researchers discussed that ESMR is a nary events and stroke were excluded from promising alternative to the treatment of IHD the study. in patients with refractory angina or patients Results showed that majority of the patients with co-morbidities to whom the standard experienced improvement in symptoms after treatment of coronary artery bypass grafting ESMR therapy, as validated by the Seattle An- (CABG) and percutaneous coronary interven- gina Questionnaire. The patients reported de- tion cannot be done. crease in severity and frequency of chest pain, In this study, the effectiveness of ESMR in increased exercise tolerance, and over-all im- 16 August 2013 Philippine Focus provement in quality of life after ESMR ther- of low intensity shock waves in ESMR therapy. There was also significant improvement apy stimulates the release of angiogenesis- in the left ventricular end diastolic volume. mediating growth and proliferation factors However, there was no significant difference to induce local growth of new blood vessels. in the ejection fraction and stress LVEDV of The new vessels act as collaterals to improve patients after ESMR. blood flow to the ischemic myocardium that Patients who underwent ESMR had signifi- is unapproachable by surgery and catheter- cant increase in ejection fraction based on 2D based interventions. Echocardiography. Myocardial perfusion of The study concluded that ESMR showed ischemic areas also improved based on myo- promise as an alternative treatment for cardial perfusion segment analysis. patients with refractory angina and those not ESMR therapy was generally well toler- amenable to revascularization. However, the ated, with no reported adverse events such investigators recommended further stud- as arrhythmias, acute coronary events and ies involving larger population groups to bleeding episodes. provide stronger evidence regarding the The researchers explained that the delivery effectiveness of ESMR therapy.

Hypertension increasing among Filipinos

Dr. James Salisi control rates had been low. Fifty-eight percent of those with hypertension had target organ damage. Stroke, the most common cause of report of the Council on Hyperten- mortality among hospital-based population, sion (COH) of the Philippines re- had high correlation with uncontrolled hy- Avealed that the prevalence of hypertension, microvasculopathy, risk factors pertension in the country steadily increased and poor compliance. Majority had uncon- from 11 percent in 1992 to 25 percent in 2008; trolled hypertension and poor compliance. and by 2012 the prevalence has risen to 28 In this study, the subject population has percent. This finding adds to the evidence of a wider age range from adolescent age and the burgeoning hypertension epidemic in the older; more parameters such as arm circum- country. ference, waist and hip, BMI, target organ Because of the rise in hypertension preva- damage for stroke, ischemic heart disease, lence and its complications, the COH saw nephropathy, peripheral vascular disease and the need for an updated and a more in-depth retinopathy were included. study of the hypertension problem in the As an update of previous studies on hy- country. pertension, Presyon3 sought to determine Previous studies have documented that the prevalence of hypertension by age group, awareness, treatment, compliance and BP assess patient awareness, obtain treatment 17 August 2013 Philippine Focus profile and control rate and to determine the The COH further mentioned that treatment prevalence of target organ damage. rate was relatively high at 75 percent but the The council did a prospective, multi-staged, 57-percent compliance rate needs improve- stratified, nationwide survey on hyperten- ment. Blood pressure (BP) control rate was sion. Subjects aged 12 years old and above, of 27 percent among treated subjects and the either sex, regardless of socio-economic sta- most common drug used was beta-blocker. tus and health condition were included in the Seventy-five percent of hypertensive patients study. consulted a physician and majority of the sur- COH used questionnaires, documentation veyed population were aware of the need for by PRESYON- affiliated physicians, physical lifetime drug maintenance. examination findings, and laboratory tests to “So, we see the alarming progressive in- assess and define target organ damage in the crease of prevalence of the problem in our heart, brain, kidney, eyes and peripheral vas- country. We are now the second in terms of cular system. The study surveyed a total of the epidemic of hypertension so we expect 626 pediatric (12 to 18 years old), 3,334 adult more problems coming,” said the director of (>18 years old), and 333 elderly populations. Philippine Heart Association Dr. Jorge Sison. The prevalence of hypertension increases “Because of the progressively increasing by age with 1 percent in pediatric population, prevalence and the complications of hyper- 28 percent in adults and 54 percent in the elderly. tension, we need to study hypertension to Among the hypertensive adults in the survey, know how to address and attack the problem 32 percent were not aware of their condition. in the Philippines,” Sison said. 18 August 2013 Philippine Focus

BEYOND THE CLINIC

A doctor’s curious hobby: Dragonflies

Dr. James Salisi

hile he may be known in Davao City for confiscating photos of a Wburning hospital, he is also known among dragonfly experts for discovering and documenting the little-known species of dragonflies in the Philippines. Dr. Reagan Joseph Villanueva is controver- sial among the press who has accused him of harassing them when a fire hit the Davao Dr. Reagan Joseph Villanueva at Aliwagwag falls in Davao Oriental Mental Hospital where he works as a resident- in-training of the Department of Psychiatry of He took Bachelor of Science in Biology at the Southern Philippines Medical Center. the Ateneo de Davao University and gradu- “So far I have described three genera and ated in 2002. He then entered medical school over a dozen species. I am also working at at Davao Medical Foundation. Upon receiv- various stages the description of over 30 new ing his medical degree in 2006, his plan was species. I was able to join and assess few doz- to start a good practice, work in the farm, en species of Philippine odonata for the In- conduct researches and “torment students to ternational Union of Conservation of Nature make good research not just as a requirement (IUCN) red list,” Villanueva said. Odonata is to finish a course.” an order of carnivorous insects that include After obtaining his license to practice med- dragonflies and damselflies. icine, he divided his time between Loreto Dis- Medicine runs in the family. Villanueva’s trict Hospital in Dinagat Islands and Kabacan mother is a psychiatrist who runs a rehabili- Specialist Hospital in Kabacan, North Cota- tation center in Davao City. He considers his bato. On the side, he explored the vast moun- mother as an influence in his decision to be- tains of Dinagat Islands, documented over 60 come a physician. species of odonate and discovered two new “Wala ako other profession maisip to take species of damselflies and one new species of up except medicine. My mother is a doctor dragonfly. and the people around me always told me to His interest in odonate follows a childhood become a doctor when I was a child. I think penchant for collecting, discovering and label- these are the driving factors of my choice to ing things around him. As a teenager growing become a doctor,” he said. up in Northern Mindanao, he started collect- 19 August 2013 Philippine Focus ing Philippine coins and then changed his in- From 2008 to 2012 he received several terest to collecting insects. grants from the International Dragonfly Fund “Initially it was a general insect collec- and World Dragonfly Association that took tion and when I started to search for names him to Siargao, Bucas Grande, Diomabok for each species I collected, I stumbled into Lake in Davao, Sarangani, Tawi-tawi, Isabela one of the country’s limitation: the lack of and Palawan. specialist for each insect group,” Villanueva He has been a co-investigator in the Philip- related. pine Aquatic Invertebrate Survey from 2009 to This gap in Philippine entomology prompt- date, the Chicago Board of Trade Endangered ed Villanueva to seek out experts here and Species from 2009 to 2010, and the Plecoptera abroad and started his path into the field of Survey in Compostela Valley province under cataloguing Philippine odonata. Rufford Small Grant from 2013 until next year. “I emailed several experts both Filipino and foreigners, unfortunately only the odo- I do not consider my nata people answered my email. Since then, I biological research ‘work’ but focused my interest on odonata and discard- rather a form of play ed the rest of my collection,” he said. Through this correspondence, he was in- In 2009, he received the Martin Fellowship troduced to Mr. Matti Hamalainen, a food from the Netherlands Center for Biodiversity sanitation expert in Finland and now a dedi- (NCB), a globally competitive fellowship de- cated odonata expert who has named more signed for young and promising researchers than 80 of these species. Hamalainen intro- in the fields of geology and zoology. duced Villanueva to other experts in the field While successful in entomology, Villan- of odonata research. ueva has never leaving the field of medicine Villanueva considers Hamalainen as his completely. He was offered a job in Leiden, mentor. He urged Villanueva to publish re- South Holland under the director of NCB Mr. search on the subject, to expand his work from merely collecting specimen to system- The world is very huge atically describing them for other experts and and there are so many things that the rest of the world to know. As a result, Vil- lanueva is presently a well-published author await each curious mind of odonate researches with over 30 scientific publications and several articles contributed Jan Van Tol but he refused. to books on the same subject. “My biological study is only a hobby of What started out as a high school hobby mine. It is my venue to divert myself from the has eventually taken him all over the country troubles of hospital life. I do not consider my to survey forests and far-flung areas in search biological research ‘work’ but rather a form of of dragonflies and damselflies. Villanueva has play,” Villanueva related. received numerous grants and projects both In 2010, he decided to pursue psychiatry as here and abroad to conduct odonate research a specialty and started residency training in in the Philippines. Davao Mental Hospital. Closer to home and 20 August 2013 Philippine Focus close to the practice of his mother who is also illnesses in the country, genomics and related a psychiatrist, he has less time for fieldwork. drugs. But this has not stopped him from sending re- When asked what he would advise young search assistants out in the field to collect spec- researchers and medical students, Villanueva imens for his on-going researches and writing emphasized the importance of having goals about them. In fact he has at least two new and looking for a hobby that will benefit other species whose names will be out next year. people as well. “I am happy where I am now. I do not think “The world is very huge and there are so it is worthwhile to shift to another career. As many things that await each curious mind. This a medical doctor, I have to proceed into medi- is what I want and dream for many young stu- cal research also; a sandwich of biological dents— to pursue biological science as a career and medical research. Biologically, I think I or as a past time. Mark your goals. There are so am on the way already, but for medical, I am many things that will distract you. Look for a just a sprouting seed,” he said. He wants to hobby that will not benefit you alone, but has fu- do research on the prevalence of psychiatric ture use for the majority in general,” he said.

A hobby transforms into scientific discoveries This year, Dr. Reagan Villanueva studied a small odonata collection from Talaingod in Davao del Norte. He explored four major sites in Barangay Santo Niño from December 26-30, 2012. The survey found 35 species under 11 families and one new species comprising the first odonatological record in the province of Davao del Norte. The survey also found Coeliccia exoleta population, which is considered a vulnerable species in the IUCN Red List of Threat- ened Species. [Journal of IDF. Rep 59(2013):1-26] In 2012, one of Villanueva and colleague’s surveys involved the study of odonata population in the Sulu region, one of the least explored faunal regions in the country. The survey showed 58 species under eight families, with one new species of damselfly and several possibly new species of dragonflies. The researchers noted that the socio-political situation, which involves kidnapping and piracy of rebel groups, in the area makes regular exploration difficult. [Journal of IDF. Rep 55(2012):1-32] Villanueva’s earlier surveys have brought him to Babuyan and Batanes group of islands, Polillo Island, Siargao Island, Bucas Grande Island and Catanduanes Island, among others. 21 August 2013 Philippine Focus

MARKET WATCH

Aspen Philippines celebrates South African Freedom Day

alda pastilles were served at the South African Freedom Day celebration held last April 26 at VMakati Shangri-La Hotel. The night event attend- ed by Aspen executives and local and foreign diplomats. With its cool, refreshing sensation, Valda pastilles comple- mented the multicultural South African “rainbow” cuisine served during the event. Chef Johan van Tonder, complex sous chef Anne Tarryn Posthumus and pastry chef Roberta Crisp from Emperor’s Palace were present to showcase the delicious cuisine. South African Ambassador to the Philip- pines Agnes Nyamande-Pitso personally chose the menu. “South Africans like to do things in style. You will find Valda pastilles [on your tables]. ...Your breath is so refreshing after you have those Valda pastilles,” said Nyamande-Pitso.

Omron encourages regular home BP monitoring

mron, a trusted healthcare brand, recently part nered with Filipino television host and Oweatherman Kuya Kim Atienza to advocate the importance of blood pressure monitoring as part of healthy lifestyle. Dr. Raffy Castillo of the Philippine Society of Hyperten- sion (PSH) said blood pressure should be measured accurately for proper diagnosis and monitoring. “Digital blood pressure monitoring devices are required to be recognized by medical authorities before it is considered to be accurate and reliable enough for home use,” he added. Omron is a global healthcare brand and it is the only one verified and accredited by the PSH. Omron’s wide range of home-use blood pressure monitors allow individuals to take a more hands-on role in managing and monitoring their health at home. 22 August 2013 Philippine Focus

MARKET WATCH

PsorCARE aims for optimal psoriasis treatment

EO Pharma, an independent research-based pharmaceu- tical company, collaborated with the Psoriasis organiza- Ltions in the Asia and the Pacific (PsorAsia) in developing the “Psoriasis Coach All-Round Education” (PsorCARE) Pro- gram. Launched last June 25, the program aims to enhance the counselling skills of health care practitioners for optimal patient- provider relationship. “We want patients with psoriasis to know that trained support is available and that it is possible for them to live life as normally as possible,” said Mr Ricky Teo, Area Director (South Asia), LEO Pharma Asia Pte Ltd. PsorAsia President Josef De Guzman said there is a need to bridge the gap between giving medical treatments and providing patient support. “Programs such as PsorCARE is an essential platform that allows us to share sustainable approaches with healthcare providers to help them address the high prevalence in treatment non-adherence and respond to the patient’s unmet needs,” he added.

Public awareness on prevention of HPV-related diseases increases

uman papillomavirus (HPV) is one of the most common sexually transmitted infections. Although it is known to cause cervical can- Hcer, there has been an increasing public awareness on other dangers that come with HPV. HPV is believed to cause genital warts and some cancers, such as those of the vulva, vagina, anus and genital area. Most recently, HPV has been associated with oropharyngeal cancers. Moreover, the virus is highly transmissible and can be obtained through skin-to-skin contact and sexual intercourse. HPV vaccination, regular screening, and healthy lifestyle are the most important ways to prevent HPV-related cervical and other genital cancers and genital warts. The public is encouraged to talk to their doctors to learn more about different ways of preventing HPV-related diseases. 23 August 2013 Philippine Focus

MARKET WATCH

Asian Hospital recognized for commitment to maternal health

he Asian Hospital and Medical Center (AHMC) recently received the Certificate of Commitment as a TMother-Baby Friendly Hospital from the Department of Health Center for Health Development of the National Capital Region (DOH CHD-NCR). The Mother-Baby Friendly Hospital Initiative (MBFHI) is a global program of the WHO and the United Nations Children’s Fund which encourages hospitals to promote breastfeeding, especially during the first six months of life. AHMC’s Department of Obstetrics and Gynecology staff MBFHI is being implemented in AHMC through its Department of Obstetrics and Gynecology and the Department of Pediatrics. Both clinical and non-clinical members of these departments underwent training to better understand the importance of breastfeeding. The award is AHMC’s first step towards its mission of becoming a fully-accredited Mother-Baby Friendly Hospital by the DOH. AHMC continues to offer family-oriented labor and delivery as well as quality maternity services to provide special care to mothers and their babies.

Personalized molecular medicine opens at The Medical City

he Medical City (TMC) recently established the Institute of Per- sonalized Molecular Medicine (IPPM), with the aim of expand- Ting the Regenerative Medicine program of the institution. Per- sonalized Molecular Medicine believes that every patient has a unique synergy of genetic make-up, history and lifestyle such that when treating patients, no two individuals or diseases are the same. Led by Dr. Samuel Bernal, the institute brings together scientists and clinicians from various specialized medical fields in developing and de- livering interventions that respond to wellness and illness at the molecular level. Dr. Alfredo Bengzon, DOH secretary Dr. Enrique IPPM offers Stem Cell Transplant, Molecular Profiling, Individualized Ona, Dr. Samuel Bernal Chemotherapy, Umbilical Cord Services, Targeted Biotherapy, and Adaptive Immunotherapy. “IPPM helps elevate The Medical City’s personalized customized care even more. The IPPM places TMC as one of the world’s most advanced healthcare institutions,” said Dr. Alfred Bengzon, president and CEO of TMC. 24 August 2013 Philippine Focus

Conference Calendar

AUGUST UPCOMING

4th Annual Postgraduate Course of the Asian Midyear Convention of the Philippine Society of Hospital and Medical Center Department of Nephrology Anesthesiology October 4-6, 2013 August 10, 2013 Venue: L’ Fisher Hotel, Bacolod City Venue: Palms Country Club Ballroom, Filinvest City, Info: Philippine Society of Nephrology Muntinlupa City Telephone: (+632) 687 1198 Info: Asian Hospital and Medical Center Department of Email: [email protected] Anesthesiology Website: http://www.mypsn.org Telephone: (+632) 876 5724 Email: [email protected] 7th International Congress of the Asian Society Website: http://www.asianhospital.com Against Dementia and 11th Alzheimer’s Disease and Related Disorder Conference SEPTEMBER October 10-12, 2013 Venue: Radisson Blue Hotel, Cebu City Info: Dementia Society of the Philippines 19th Annual Convention of the Philippine Telephone: (+63 932) 731 3001 loc 2214 Association for the Email: [email protected] Study of Overweight and Obesity Website: http://www.dementia.org.ph September 6, 2013 Venue: Crowne Plaza Galleria Manila, Ortigas Center, 15th Annual Scientific Meeting of the Osteoporosis Pasig City Society Info: Philippine Association for the Study of of the Philippines Foundation Overweight and Obesity October 18, 2013 Telephone: (+632) 632 1533 or 359 9268 Venue: Century Park Hotel, Malate, Manila Email: [email protected] Info: Osteoporosis Society of the Philippines Foundation Website: http://www.obesity.org.ph Telephone: (+632) 723 0101 loc 2002 Email: [email protected] 25th All-in-one (All Subspecialties) Postgraduate Course of the 3rd Asia Pacific Association for the Study of the Liver- Philippine Children’s Medical Center Single Topic Conference on Hepatocellular Carcinoma September 17-18, 2013 November 21-23, 2013 Venue: Crowne Plaza Galleria Manila, Ortigas Center, Venue: Radisson Blue Hotel, Cebu City Pasig City Info: Asia Pacific Association for the Study of the Liver- Info: Philippine Children’s Medical Center Hepatology Society of the Philippines Telephone: (+632) 924 6601 loc 338 or 240 Telephone: (+632) 961 3014 Email: [email protected] Email: [email protected] Website: http://www.liverphil.org

64th Annual Convention of Philippine Orthopedic Association November 13-16, 2013 Venue: EDSA Shangri-La Hotel, Mandaluyong City Info: Philippine Orthopedic Association Telephone: (+632) 667 3926 or (+632) 667 3946 Email: [email protected] or [email protected] Website: http://www.philortho.org Golden Gate Bridge

Journal of Paediatrics, Obstetrics & Gynaecology

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26 August 2013 Conference Coverage

23rd Conference of the Asian Pacific Association for the Study of the Liver 2013, June 6-10, Singapore REVEALED: Hepatitis B viral load critical to infection clearance

Radha Chitale clearance were HBV-DNA levels at baseline, where a higher viral load correlated with lower seroclearance (p<0.001). Conversely, se- ut of about 400 million people with roclearance was significantly associated with chronic hepatitis B virus (HBV), 75 a drop in serum HBV-DNA, with an adjusted percent of those infected live in the O odds ratio of 4.17. Asia Pacific region. Since HBV is strongly “The spontaneous seroclearance of HBeAg, linked to the development of cirrhosis and HBV-DNA and HBsAg occurs consecutively liver cancer, the infection rate constitutes a in the natural history of chronic hepatitis B,” significant public health challenge. Chen said. Risk predictors, such as the one detailed In the study, the researchers noted that this in the REVEAL-HBV* study, which trace the finding had significant clinical implications natural history of chronic HBV infection, have for the treatment of chronic HBV. shown that viral load is a major predictor for Other risk predictors for hepatocellular clearing viral proteins. carcinoma (HCC) and cirrhosis are old age, “This risk calculator has very good calcula- male gender, alcohol consumption and a his- tions and [is] also accurate,” said study lead tory of HCC, in addition to biological gradi- Dr. Chien-Jen Chen, of the Academia Sinica ents of serum liver enzymes, HBV-DNA and and National Taiwan University in Taipei, antigen levels. Taiwan. Chen said collaborative studies on external The REVEAL-HBV study was a communi- cohorts have corroborated the accuracy of the ty-based trial that included 3,087 adults with risk calculators for liver disease progression chronic HBV. Serum samples were collected at found in the REVEAL-HBV study. baseline between 1991 and 1992, and during “The estimated cumulative lifetime risk of follow-up exams. Serum samples were tested cirrhosis and HCC in chronic HBV patients for HBV antigens (HBsAg and HBeAg), serum is 42 percent and 22 percent, [respectively],” HBV-DNA, and anti-hepatitis C virus serosta- Chen said. “HBV viral load is a major pre- tus. [Gastroenterology 2010;139:474-482] dictor for the spontaneous seroclearance of Over 24,892 person-years of follow-up, HBeAg.” HBsAg seroclearance occurred in 562 participants – a 2.26 percent annual seroclearance *REVEAL-HBV: Risk Evaluation of Viral Load Elevation rate. The most significant predictor of sero- and Associated Liver Disease/Cancer-HBV. 27 August 2013 Conference Coverage

23rd Conference of the Asian Pacific Association for the Study of the Liver 2013, June 6-10, Singapore

Oncolytic immunotherapy promising in sorafenib-refractory HCC

Christina Lau 1 and 3, and sorafenib from week 4,” said Heo. “Most patients were heavily pretreated and had extensive tumor burden at baseline.” sian patients with advanced hepa- Response rate (RR) was 47 percent for JX- tocellular carcinoma (HCC) refrac- 594 (IV followed by IT), increasing to 75 per- Atory to sorafenib may benefit from cent when this was followed by sorafenib. an investigational oncolytic immunotherapy Disease control rate (DCR) was 62 and 59 per- known as JX-594, as it showed antitumor ac- cent, respectively, for the two regimens. tivity in a recent phase II trial. “For patients failing sorafenib, RR was 43 “JX-594 consists of a vaccinia virus back- percent for IV/IT JX-594 and 80 percent for IV/ bone engineered to target solid tumors both IT JX-594 followed by sorafenib. DCR was 65 systemically and locally. It is armed with the and 59 percent, respectively,” Heo reported. granulocyte-macrophage colony-stimulating Median survival was 9.1 months for all factor [GM-CSF] gene for induction of im- evaluable patients and 17.3 months for mune attack on cancer, and the Lac-Z gene for sorafenib-naïve patients. monitoring,” said Dr. Jeong Heo of the Pusan “JX-594 was well tolerated, with flu-like National University School of Medicine, Pu- symptoms being the most common adverse san, Korea. effects,” said Heo. “Toxicities of sorafenib JX-594 has a novel multi-pronged mecha- were consistent with previous reports.” nism of action. It works by direct infection and More recently, Heo and colleagues con- destruction of cancer cells, immune-mediated ducted a phase II trial to determine the op- killing, and tumor vascular shutdown that oc- timal dose of JX-594, given by IT injection in curs within 5 days of treatment. [Nat Rev Can- up to 5 nodules, in 30 patients with heavily- cer 2009;9:64-71; Sci Transl Med 2013;5:185ra63; pretreated advanced HCC (sorafenib naïve, Cancer Res 2013;73:1265-1275] 80 percent). [Nat Med 2013;19:329-336] In a phase II trial of 25 Korean patients “DCR at week 8 was the same for high-dose with advanced HCC (sorafenib failure, n=20; and low-dose JX-594 [47 and 46 percent],” he sorafenib naïve, n=5), JX-594 demonstrated noted. “RR and DCR were equivalent at injected anti-tumor activity with similar response rates and distant non-injected tumors at both doses.” in both sorafenib-refractory and sorafenib- However, survival was significantly relat- naïve patients. [International Liver Cancer ed to dose (median, 14.1 months for high dose Association Annual Meeting 2012; abstract vs 6.7 months for low dose; hazard ratio, 0.39; 2012-1304] p=0.020). “Patients in the trial were first treated with “A phase IIb trial is ongoing to investigate an intravenous [IV] dose of JX-594, followed the effect of JX-594 in HCC patients failing by intra-tumoral [IT] doses of JX-594 at weeks sorafenib,” he said. 28 August 2013 Conference Coverage

Personal Perspectives

I’m particularly interested in getting new information ‘‘ about liver immunology, as well as immunobiology and immunopathology, and immune responses in the pathogenesis of chronic liver diseases. What I learned from this meeting will beuseful when I go back to my country.

Dr. Eman G. El Ahwany Professor of Immunology, Immunology Department, Theodor Bilharz Research Institute, Egypt

The sessions are educational as most studies are from the Asia-Pacific region. We ‘‘ used to follow guidelines from the West, which may not be suitable for Asians. So it’s interesting to learn novel therapies tailored for Asian patients. Currently, there is no specific therapy for acute hepatitis B yet the new data reported here, as well as the new agents in development, look promising.

Dr. Donald Miranda Medical Section, Endoscopy Unit, Metropolitan Medical Center and Research Center, Davao City, Philippines

What’s really interesting with APASL is that we get the Asia-Pacific vision of ‘‘ things that we don’t usually get from the EASL. Asians have different genetics and HBV genotypes, and identification of these genotypes will be useful to understand the source of infection and to predict an individual’s clinical outcome.

Dr. Florence Herschke Senior Scientist, HBV Virology, Janssen Infectious Diseases (J&J), Beerse, Belgium

There are a couple of logistical problems. The venues had some issues. But the talks ‘‘ have been very nice. It was really good to hear the Asian perspective on hepatitis B and C. I hope I can also network with other researchers to see how they work and to get new ideas.

Anna Gronert Alvarez PhD Candidate, Gastroenterology, Hannover Medical School, Hannover, Germany 29 August 2013 Conference Coverage

European League Against Rheumatism (EULAR) 2013 Annual European Congress of Rheumatology, June 12-15, Madrid, Spain

EULAR updates RA recommendations

Leonard Yap does not advocate the use of biologics as an initial DMARD strategy since the treat-to-tar- he European League against Rheuma- get approach will lead to similar overall out- tism (EULAR) presented a revised ver- comes. Tsion of its rheumatoid arthritis (RA) “These recommendations were based on management recommendations. three extensive literature reviews of the effi- The revised recommendations focus more cacy and safety of biological and conventional on the patient and encourage shared decision- DMARDs, and address a number of common making between the patient and the special- misinterpretations of the 2010 guidelines,” ist about the best care, said Dr. Josef Smolen, said Smolen. director of the EULAR Research Center Data- “As already stated in 2010, by advocating base and professor at the Division of Rheuma- the use of synthetic DMARDs, rather than tology, Medical University of Vienna, Austria. biologics, as the first-line treatment this approach avoids the over-treatment of 20 to 50 The revised recommendations percent of patients with early RA, who will achieve the treatment target with such initial ‘‘ focus more on the patient therapy,” he said. Low-dose glucocorticoids should also be They outline patient treatment targets, hier- considered in combination with DMARDs for archy of therapeutic approach (stratifications up to 6 months, but should be tapered as soon of risk) and the issue of disease-modifying an- as clinically feasible. However, in patients ti-rheumatic drugs (DMARDs) covering the failing to respond to this treatment within 6 spectrum of conventional systemic DMARDs months and when poor prognostic factors are (csDMARDs), biologic DMARDs (bD- present, biologic DMARDs (tumor necrosis MARDs), targeted synthetic (tsDMARD) and factor [TNF]-inhibitors, abatacept or tocili- biosimilars (bsDMARD). zumab – or under certain circumstances ritux- As with the previous 2010 edition, the 2013 imab) should be administered in combination recommendations advocate the efficacy of cs- with MTX. DMARDS, and combination therapy as first- Patients who have failed to respond to an line treatment. They also regard all biologic initial bDMARD should receive a different agents as similarly effective and safe as first- bDMARD. In the same manner, patients who line therapy, Smolen said. have failed to respond to an initial TNF-inhib- The update reiterates the preference for the itor may receive a different one, or a biologic use of biologics in combination with metho- with an alternative mode of action. If biologic trexate (MTX) rather than monotherapy. It treatment has failed, tofacitinib may be con- 30 August 2013 Conference Coverage sidered where approved. structure. However, until more safety data “Although the European Medicines Agen- are available and efficacy judged in clinical cy has not approved tofacitinib hitherto, it practice, tofacitinib is only recommended af- has been approved by the US FDA as well as ter at least one biological has failed – in fact, in Japan and Russia. Having weighed up the many task force members felt it should be evidence, the task force is convinced of its used after two biological treatment failures,” efficacy on clinical outcomes, function and he added.

BMI a good indicator of remission in RA

Leonard Yap patients’ chance of successful remission,” she added. The study found that patients who were verweight and obese patients are less obese or overweight had higher disease activ- likely to achieve successful remission ity and a higher disability index than their nor- Oin early rheumatoid arthritis (ERA) mal counterparts. The disease remission rates compared with those of normal weight, a for obese and overweight patients were also study has shown. significantly lower than their normal counter- Such patients required 2.4 times more anti- parts, 40 versus 60 percent, respectively. tumor necrosis factor (TNF) therapy through- The study examined 346 ERA patients with out the study than normal weight partici- symptom duration <12 months that were cat- pants without achieving similar remission egorized into one of three body mass index outcomes. [Abstract OP0178] (BMI) classes (normal weight, overweight “Obesity and rheumatoid arthritis are both and obese) and treated according to a treat-to- on the rise, with devastating effects on indi- target strategy aimed at remission. The strat- viduals and society as a whole. These data re- egy included strict follow-up visits, treatment inforce the link between obesity and inflam- with methotrexate up to 25 mg/week with ste- mation, and establish that BMI is one of the roids, and combination with a TNF blocker if few modifiable variables influencing the ma- at least a good response according to EULAR jor outcomes in RA,” said Dr. Elisa Gremese criteria* was not obtained. from the Division of Rheumatology, Catholic Body weight is one of the few modifi- University of the Sacred Heart, Rome, Italy. able factors influencing the outcomes in “Obesity and overweight should be taken early RA patients. In early RA, obesity and into account as a biomarker of severity of RA overweight are factors which are both as- and as a target for therapeutic intervention at sociated with worse outcomes, ie, higher multiple levels (weight loss, choice of right disease activity, lower remission rates and RA therapy) to achieve better outcomes for greater use of anti-TNF therapy, said the our patients. researchers. “There is an urgent need to address the issues of overweight and obesity to improve † BMI - measure of body fat defined as body mass- di 31 August 2013 Conference Coverage

vided by the square of an individual’s height. * EULAR response criteria: individual patients are classified Normal weight BMI <25 kg/m2, overweight as non-, moderate, or good responders, dependent on the ex- 25-30 kg/m2, obese >30 kg/m2. tent of change and the level of disease activity reached.

Personal Perspectives

II think [EULAR 2013] is very good. The key thing is that we need a forum that ‘‘ brings people together, and exchanging ideas and views. I think the great thing with EULAR is that it brings together patients and healthcare professionals. The best way of dealing with these conditions is the multi-professional, multidisci- plinary way, with the problem in the center, the patient and the healthcare professionals around trying to find solutions.

Professor Anthony Woolf Bone and Joint Decade Foundation, Truro, England

I like this congress very much. I have been to practically all EULAR congresses so ‘‘ far. I like the atmosphere and the posters are very well presented. I like the WIN [What is New] sessions, they are a wonderful overview of what is new over the past year and also the HOT [How to Treat] sessions. I think these are very successful and very good tracks. In my field of epidemiology and outcomes, I think that we have very good papers [presented].

Professor Angela Zink German Rheumatism Research Center, Berlin, Germany

Madrid is a nice city and some very exciting studies have been presented. It is a ‘‘ very good chance to interact with colleagues. It has been fantastic and great fun. Professor Ernest Choy Cardiff University, Wales 32 August 2013 Conference Coverage

73rd Scientific Sessions of the American Diabetes Association, June 21-25, Chicago, Illinois, US

Lifestyle intervention not shown to reduce CV events in obese diabetics

Elvira Manzano

lifestyle intervention program that focuses on weight loss and exercise A helps control blood sugar and cho- lesterol in obese diabetics, according to the updated results of the Look AHEAD* trial, but is not effective at reducing cardiovascular events such as myocardial infarction (MI) and stroke. At a median follow-up of almost 10 years, there were no significant differences in the composite primary endpoints of cardiovascular mortality and morbidity between patients receiving lifestyle intervention and the control group (1.83 vs 1.92 events per 100 person-years; p=0.51). [N Engl J Med 2013; doi:10.1056/NEJMoa1212914]

Lead study author Dr. Rena Wing of the However, changes in activity and diet can safely reduce weight. Alpert Medical School, Brown University, in Rhode Island, US, said several factors could account. “The study shows that activity and have led to the neutral effect on cardiovascu- diet can safely reduce weight – and keep that lar outcomes, one of which was greater use weight off – in patients with type 2 diabetes.” of statins in the control group. The weight The intervention was also associated with loss achieved in the intervention group may lower risks of kidney disease and retinopa- also have been insufficient to reduce the risk thy, as reported separately by other investi- of cardiovascular disease or that the educa- gators at the ADA meeting. Other benefits tion sessions provided to the control group reported during the early years of the trial diminished any between-group difference in included improvement in glycemic control the event rates. and cardiovascular risk factors, reductions Although there was no clear evidence of in urinary incontinence, sleep apnea and de- cardiovascular benefit in the trial, Wing said pression, and enhanced mobility. some positive effects should be taken into The study involved 5,145 overweight or 33 August 2013 Conference Coverage obese patients with type 2 diabetes random- reduce weight as well as the need for and ized to lifestyle intervention (target weight the cost of medications, and can help pa- loss 7 percent of body weight) or support and tients achieve remission from diabetes in education using conventional approaches. some cases. [N Engl J Med 2013; doi:10.1056/ Weight loss was greater (6 vs 3.5 percent) NEJMe1306987] at the study’s conclusion, while blood pres- The investigators have reaffirmed the im- sure and HbA1c were lower in the interven- portance of lifestyle approaches as one of tion group compared with controls. The trial the foundations of modern diabetes care, was terminated early based on futility at a Gerstein said. As for the cardiovascular out- median follow-up of 9.6 years. comes, he added that inspection of the con- In an accompanying editorial, Dr. Hertz- fidence intervals should allow clinicians to el C. Gerstein, an endocrinologist and pro- reassure parents that intensive lifestyle inter- fessor at McMaster University and Hamil- vention is unlikely to cause harm and may ton Health Sciences in Hamilton, Ontario, provide a modest benefit. Canada, said clinicians can now clearly as- sert that changes in activity and diet safely *Look AHEAD: Action for Health in Diabetes 34 August 2013 Conference Coverage

73rd Scientific Sessions of the American Diabetes Association, June 21-25, Chicago, Illinois, US Exercise turns ‘bad’ fat ‘good’

Radha Chitale muscle tissue, which senior investigator Dr. Laurie Goodyear of the Joslin Diabetes Center xercise training helps develop fat that and Harvard Medical School in Boston, Mas- is more metabolically active than fat sachusetts, said was a huge surprise. Ethat results from sedentary behavior, “You don’t need a lot of exercise to cause according to two studies in mice and humans. dramatic adaptations to subcutaneous adi- The resulting “good fat” can lead to metabolic pose tissue,” she said. changes that improve glucose tolerance and The mouse study carried on with trans- control the effects of a fatty diet. planting the trained brown fat into sedentary “Exercise really can train your fat,” said mice which were given a high-fat diet. These lead author Dr. Kristin Stanford, a postdoc- mice had improved glucose tolerance and toral fellow at the Joslin Diabetes Center in insulin sensitivity for 12 weeks of follow-up Boston, Massachusetts, US. “Exercise train- compared with sham-treated mice. ing has beneficial effects on subcutaneous The transplanted adipose tissue in these adipose tissue that contributes to improved sedentary mice also appeared to neutralize systemic glucose homeostasis.” the effects of a high-fat diet as there was no In the mouse study, mice were caged with difference in body weight, and glucose levels or without an exercise wheel for 11 days. An remained lower than those in sham-treated analysis of their subcutaneous adipose tissue mice fed normal or high-fat diets. showed that the mice which exercised had Stanford hypothesized that the white smaller adipose cells with less lipid in each adipose tissue produced secreted proteins cell and the cells had more mitochondria, responsible for improvements in glucose making them “browner” – more metaboli- uptake, specifically in brown adipose and cally active. skeletal muscle tissues. A group of 10 relatively fit men who exer- Despite the apparent success of trained fat cised at high intensity 5 days per week for 12 transplants in mice, Goodyear would not rec- weeks showed similar changes to their subcu- ommend similar procedures in humans, say- taneous white adipose tissue (SWAT) in that ing exercise was still the best way to achieve it became “browner.” The men achieved at optimal fat levels. least a 10 percent increase in maximal aerobic “I would argue that, in fact, the lack of capacity. exercise is just as important or maybe even A genetic analysis of the mice and men more important than the increase in high-fat showed that a significant number of genes feeding and increased caloric consumption and metabolic pathways had changed, and [leading to the] huge increase in rates of type more genes changed in the fat tissue than 2 diabetes worldwide,” she said. 35 August 2013 Conference Coverage

73rd Scientific Sessions of the American Diabetes Association, June 21-25, Chicago, Illinois, US Artificial pancreas reduces nocturnal hypoglycemia in T1DM

Rajesh Kumar the two groups. The mean AUC for nocturnal hypoglycemic events was 37.5 percent lower n artificial pancreas system reduced in the threshold-suspend group than in the the duration and incidence of noc- control group. The events occurred 31.8 per- Aturnal hypoglycemia in patients with cent less frequently in the threshold-suspend type 1 diabetes mellitus (T1DM) in ASPIRE*, group than in the control group (1.5 vs 2.2 per the first randomized trial of its kind. patient-week; p<0.001). The system, which included an insulin After 1,438 instances at night in which the pump, software and sensors that continu- pump was stopped for 2 hours, the mean ously track blood glucose levels, reduced the sensor glucose value was 92.6 mg/dL (5.1 incidence of nocturnal hypoglycemia events mmol/L). Four patients (all in the control by 32 percent and the duration and severity group) had a severe hypoglycemic event; no of those incidents by 38 percent by shutting patients had diabetic ketoacidosis. off insulin delivery for 2 hours once glucose “This technology promises to be valuable to levels had fallen below a predefined thresh- patients today and is a key step in the develop- old value of 70 mg/dL. [N Engl J Med 2013; Jun ment of a fully automated artificial pancreas 22: Epub ahead of print] for people with diabetes,” said principal inves- The threshold-suspend feature is part of tigator Dr. Rich Bergenstal, executive director the MiniMed 530 G system (Medtronic) which of the International Diabetes Center at Park is currently pending approval by the US Food Nicollet in St. Louis Park, Minnesota, US. and Drug Administration, while the sensor “The next step is to continue to refine the augmented insulin pump is already available shut off and restart of insulin to prevent hy- internationally. poglycemia, then to program the pump to be Researchers randomly assigned 247 pa- able to safely add more insulin when the glu- tients with T1DM and documented nocturnal cose is too high.” hypoglycemia to receive sensor-augmented The pump can be manually overridden insulin-pump therapy with or without the if patients wake up and want to drink some threshold-suspend feature (n=126 and 121, re- juice to raise their blood glucose levels, rather spectively) for 3 months. The primary safety than waiting for 2 hours for levels to return to normal. If they do not wake up, insulin de- outcome was the change in the HbA1c level, and efficacy outcome was the area under the livery automatically resumes after the 2-hour curve (AUC) for nocturnal hypoglycemic period. events. Two-hour threshold-suspend events were analyzed with subsequent sensor glucose val- *ASPIRE: Automation to Simulate Pancreatic Insulin ues. Changes in HbA1c values were similar in Response (ASPIRE) In-home study. 36 August 2013 Conference Coverage

73rd Scientific Sessions of the American Diabetes Association, June 21-25, Chicago, Illinois, US Insulin glargine not linked to raised cancer risk

Elvira Manzano on the primary endpoints of heart attack or stroke, suggesting that daily insulin to control aily use of basal insulin glargine in blood sugar levels does not accelerate cardio- patients with diabetes or pre-diabetes vascular events. [N Eng J Med 2012;367:319-28] Ddid not increase the risk of cancer nor In the current analysis, only 7.6 percent of did it lead to worse outcomes in a sub-analy- the patients developed cancer. This translates sis of the ORIGIN* trial. to 1.32 cancer events per 100 person-years for Researchers found no difference in the both treatment groups. Patients who experi- risk of cancer among patients receiving in- enced a cancer event tended to be older, be sulin glargine and those given standard of current or ex-smokers, have a higher frequen- care (hazard ratio [HR], 0.94; p=0.52). Rates cy of alcohol intake, and have had a prior car- of death from cancer were also no different diovascular event. at 0.51 and 0.54 per 100 person-years, respec- Session co-chair Assistant Professor Bessie tively. [Abstract 385-OR] Young of the University of Washington in Se- “Daily exposure to glargine had a neutral attle, said the new data are “very reassuring” effect on cancer events, including any cancer, given that there was no increase in the inci- new or recurrent cancers, cancer mortality, dence of cancer among patients receiving in- and subtypes of cancer,” said lead study au- sulin glargine after over 5 years of follow-up. thor Dr. Louise Bordeleau of McMaster Uni- As insulin is a potential growth factor, there versity in Hamilton, Ontario, Canada. “This were early concerns it may cause cancer. was not modulated by metformin or sulfonyl- As the only randomized trial to specifi- urea [treatment], HbA1c levels, or weight.” cally address risk of cancer in patients receiv- ORIGIN included 12,537 patients (mean ing insulin glargine vs standard care, “this is age, 63.5 years) from 40 countries with early the best evidence we have so far [that insu- type 2 diabetes or pre-diabetes but without lin glargine does not increase cancer risk],” active cancers and who were at high risk for Bordeleau said. cardiovascular disease. They were random- Dr. Craig Currie, an epidemiologist from ized to one daily injection of insulin glargine Cardiff University, Wales, however, said the or standard care, defined as clinician judg- trial does not adequately answer the question ment with no insulin until patients were un- of whether insulin promotes cancer in pa- controlled on at least two oral diabetes drugs tients with type 2 diabetes. “They were saying and annual screening for pre-diabetics, for an they used a very low dose of insulin glargine, average of 6 years. The study was a 2×2 facto- but they could have split it into high and low rial design, with the other group randomized dose to find an association,” he said. to omega-3 fatty acids or placebo. Results from the main trial, reported in * ORIGIN: Outcome Reduction with an Initial Glargine 2012, showed that glargine had no effect Intervention 37 August 2013 Conference Coverage

73rd Scientific Sessions of the American Diabetes Association, June 21-25, Chicago, Illinois, US Intensive glucose controls reduces risk of T1DM complications

Radha Chitale US National Institutes of Health. The DCCT demonstrated that lowering HbA1c to 7 per- ntense blood glucose control significantly cent, compared with the then-standard 9 per- reduces risks of eye, kidney and cardio- cent, in people with T1DM reduced an array Ivascular diseases among patients with of complications by 35-75 percent and estab- type 1 diabetes mellitus (T1DM), according to lished a new standard of care. [N Engl J Med the latest results of a large, long-term study 1993;329:977-86] spanning three decades. Intermittent follow-up results from the sub- Patients who reached an HbA1c target of 7 sequent Epidemiology of Diabetes Interven- percent had a 46 percent reduced risk of reti- tions and Complications (EDIC) trial, which nopathy (as well as lower risk of focal laser is ongoing, have demonstrated continued therapy and any ocular surgery), a 39 percent benefits of intensive therapy such as reduced reduced risk of microalbuminuria, and a 61 risk of cardiovascular disease and stroke, de- percent reduced risk of macroalbuminuria layed onset of hypertension, and preserved (p<0.0001 for all). estimated glomerular filtration rate (eGFR). “The reduction in impaired kidney function “Those treatment effects were almost all represents a major finding since kidney failure explained by differences in the levels of HbA1c increases the risk of subsequent heart disease during the former intensive and convention- and death more than any other complica- ally treated groups during the DCCT,” said tions,” said Dr. Ian deBoer, a trial investigator principal investigator Dr. John Lachin of from the University of Washington in Seattle, George Washington University in Rockville, Washington, US. Maryland, US. The researchers also quantified the under- Thirty years after the DCCT trial was recognized musculoskeletal complication launched, researchers continue to follow-up cheiroarthropathy, which includes carpal tun- on 95 percent of the surviving cohort. nel syndrome and difficulty flexing the fingers “This demonstrates the importance of con- and shoulders, and found it affects 50-60 per- tinued follow-up and long-term results from cent of type 1 diabetics. About one-third had interventions in diabetes,” said Dr. Judith at least one such complication while 20 per- Fradkin, director of the Division of Diabetes, cent had at least two, 10 percent had at least Endocrinology and Metabolic Diseases at the three, and 3 percent had four or more. Only 34 National Institute of Diabetes and Digestive percent did not have any such complications. and Kidney Diseases, part of the US National These findings are based on new results Institutes of Health in Bethesda, Maryland, US. from a 20-year follow-up of the 10-year “What matters to people is what is going to Diabetes Control and Complications Trial happen to them over the course of their life… (DCCT), launched in 1983 and funded by the We’ve found out incredibly important things 38 August 2013 Conference Coverage both about the effect of the therapy and about contemporary therapy and the results are the course of T1DM in today’s world with very hopeful.”

Triple therapy offers superior efficacy in newly diagnosed T2DM

Rajesh Kumar In subjects receiving triple therapy, HbA1c decreased from 8.6 to 6.1 percent at 6 months nitial triple therapy with metformin, pio- and remained stable at 6.1 percent at 24

glitazone and exenatide results in greater months. With conventional therapy, HbA1c Iand more durable HbA1c reduction com- declined to 6.1 percent at 6 months and then pared with conventional sequential add-on increased to 6.6 percent at 24 months (p<0.01). therapy, and caused weight loss, rather than More subjects in the conventional arm weight gain, in patients with newly diagnosed failed to achieve the HbA1c treatment goal type 2 diabetes mellitus (T2DM) according to of <6.5 percent (46 vs 22 percent; p<0.0001). a study. Despite significantly lower HbA1c, triple Guidelines recommend lowering HbA1c therapy subjects had a much lower rate of hy- as close to normal as possible in patients with poglycemia compared with subjects receiv- diabetes while avoiding hypoglycemia, but ing conventional therapy (46 percent vs 15 no study has so far examined the optimal percent; or 2.1 vs 0.27 events per subject-year; therapy to achieve this goal, said the study p<0.0001). researchers. They sought to compare the ef- Of note, triple therapy was associated with ficacy and safety of initiating triple therapy in significantly greater mean body weight loss new-onset T2DM or first starting with metfor- compared with conventional therapy (-1.2 kg min, followed by sequential addition of sulfo- vs +3.6 kg; p=0.02). nylurea and basal insulin. [Abstract: 384OR] “Triple therapy targets the core metabolic They randomized 147 newly diagnosed defects eg, insulin resistance and beta-cell T2DM patients (mean age, 45 years; body dysfunction that are responsible for hyper- mass index (BMI), 36 kg/m2; HbA1c, 8.6 per- glycemia,” said co-researcher Dr. Muham- cent; diabetes duration, 5.6 months) to receive mad Abdul-Ghani of the University of Texas initial combination therapy with metfor- Health Science Center in San Antonio. min (1000→2000 mg/day) plus pioglitazone “[It] is more effective and safer than therapy (15→45 mg/day) plus exenatide (5→10 μg/ simply aimed at lowering plasma glucose lev- day BID) (triple therapy, n=71), or escalat- els without correcting the underlying patho- ing dose of metformin (1000→2000 mg/day) physiologic disturbances present in T2DM.” followed by sequential addition of glipizide Abdul-Ghani’s take-home message for (5→20 mg/day) and then basal insulin to physicians: “Treat the disease [diabetes] and maintain HbA1c <6.5 percent (conventional not the symptom [hyperglycemia], and treat therapy, n = 76). the patient, not his or her blood sugar.” 39 August 2013

Industry UPDATE

Industry Update brings you updates on disease management and advances in phar- macotherapy based on reports from symposia, conferences and interviews, as well as latest clinical data. This month’s updates are made possible through unrestricted educational grant from Wyeth Consumer Health

Building on a young child’s assets for success in school and life...... P40

www.MIMS.com

Smart Rx. Every Time. 40 Industry Update

Building on a young child’s assets for success in school and life

In 1905, French psychologist Dr Alfred Binet invented the first usable intelligence test known as the intelligence quotient orIQ. For years, this test has been used to correlate a child’s mental and chronological age to assess intelligence. Decades later,developmental psychologist and educator, Professor Howard Gardner, proposed that people do not Thomas Armstrong, have just one type ofintelligence, but rather multiple forms - a unique PHD combination of potentials, strengths and intelligences to enable them to succeed in life. Professor Thomas Armstrong, Executive Director of the American Institute for Learning and Human Development and renownedauthor and educator, was invited to talk about the theory of multiple intelligences (MI). He lectured on each type and elaborated through examples how to recognize, identify and cultivate these in young children.

or years, a child’s IQ has been used to Professor Armstrong, an advocate of MI, assess and determine his level of intel- discussed each of these intelligences and- Fligence, but IQ testing proposes that shared the various ways to develop them in there is only one kind of intelligence in a infants and young children. person – a measurable intelligence that one is born with and cannot change, however, The first form of intelligence he discussed when one looks at the myriad of people who was linguistic intelligence or the intelligence have succeeded in various aspects of human of the written and spoken word. It is the type endeavor, it appears that there is not just one displayed by writers, editors and orators. form of intelligence. Word intelligence can manifest as early as the infant starts to babble and can be en- In the 1980s, Professor Howard Gardner hanced by exposing him to situations where proposed the theory of MI which suggests family members are conversing. In a toddler, that each individual possesses a unique mix this can be developed by giving him books of intelligences that could help him reach his or a pen and paper, but without any pressure potential, solve problems and create prod- on him to read or write. ucts of value within one or more cultural set- Logical intelligence, like linguistic in- tings. In essence, one’s success cannot rely telligence, also develops early in life. This on and be measured by IQ alone. is exemplified by a child who experiments 41 Industry Update

in order to figure out causes and effects, must be able to get along, share and de- and patterns and regularities. Ways to en- velop reciprocal relationships with others. hance logical intelligence include having Playing with other children is therefore en- him listen to counting songs and number couraged. rhymes and engaging him in manipulative play. Closely related to interpersonal intelligence is intrapersonal intelligence – the With regard to spatial intelligence or the ability to reflect on oneself, on life and make ability to perceive and visualize objects decisions. Giving children space and op- outside the self and inside the mind, Pro- portunities to mirror emotions and express fessor Armstrong suggests picture books, them can help them develop into self-smart building blocks and providing art-related children. activities. About a decade ago, Professor Howard Gard- Bodily kinesthetic intelligence is the in- ner added an eighth type of intelligence – telligence of the whole body and the hands. one displayed by children who love animals Playing with clay and blocks provides good and who are fascinated by their surround- tactile stimulation and allows infants and ings. They prefer being outside exploring toddlers to learn with their hands. Providing nature to being indoors playing with toys. a safe environment for toddlers to run and Naturalistic inclinations should be acknowl- play in promotes learning through move- edged and encouraged too, said Professor ment and exploration. Armstrong, by allowing them to play outside and to be around plants and animals. Musical intelligence is often classified as a talent rather than a form of intelligence, said MI in children is generally determined and Professor Armstrong, but the theory of MI influenced by different factors including ge- states otherwise. He explained that music is netics, prenatal care, the social-emotional an important aspect of life, a source of inspi- bonding between the mother and child, ration and a vehicle of expression. To devel- cognitive stimulation and proper nutrition. op this, Professor Armstrong recommends The theory of MI also states that all theintel- exposing infants and young children to lul- ligences usually work together, that all chil- labies, providing music to sing to and sound dren have and can develop all forms, and effects to appreciate, and toy musical instru- that there are many ways to be smart within ments to play with. each form of intelligence. Compared to the others, the next two forms In conclusion, Professor Armstrong of intelligences develop much later and stressed that IQ may not be enough and may require children to go through some ex- even be limiting, if used as the sole basis of periences first. Interpersonal intelligence children’s intelligence. There are multiple confers skills in negotiation, mediation and forms of intelligence and when recognized, manipulation. Children who display this are developed and encouraged in children, will good at reading faces, according to Profes- help them to succeed in school and in life in sor Armstrong. To develop this, children many ways. 42 Industry Update

REFERENCES: 1. Armstrong, Thomas. Neurodiversity in the Classroom: Strength-Based Strategies to Help Students with Special Needs Achieve Success in School and Life. Alexandria, VA: ASCD, 2012. 2. Armstrong, Thomas. The Power of Neu- rodiversity: Unleashing the Advantages of Your Differently Wired Brain. Cambridge, MA: DaCapo/Perseus, 2010. 3. Armstrong, Thomas. Multiple Intelligences in the Classroom, 3rd Ed. Alexandria, VA: ASCD, 2009. 4. Armstrong, Thomas. 7 Kinds of Smart: Identifying and Developing Your Many Intel- ligences: Revised and Updated with Information on 2 New Kinds of Smart. New York: Plume, 1999. 5. Armstrong, Thomas. In Their Own Way: Discovering and Encouraging Your Child’s Multiple Intelligences. New York: Tarcher/Putnam-Penguin, 2000. 6. Armstrong, Thomas. You’re Smarter Than You Think: A Kids’ Guide to Multiple Intelligences. Minneapolis, MN: Free Spirit, 2003. 7. Armstrong, Thomas. The Myth of the A.D.D. Child: 50 Ways to Improve Your Child’s Behavior and Attention Span without Drugs, Labels, or Coercion. New York: Plume, 1997. 8. Gardner, Howard. Frames of Mind: The Theory of Multiple Intelligences. New York: Basic Books, 1983. 9. Gardner, Howard et al (eds). Building on Children’s Strengths: The Experience of Project Spectrum. New York: Teachers College Press, 1998. 10. Gardner, Howard. Multiple Intelligences: New Horizons in Theory and Practice. New York: Basic Books, 2006. Sponsored Symposium Highlights odern understanding in the anagement of acute pain

For the past two decades, acute pain and chronic pain have been recognised as significant public health issues. However, despite such increased attention, effective pain control remains suboptimal. At a recent symposium, organised by Menarini Asia Pacific, a renowned expert in the field of Pain Medicine shared insights into pain management and the role of an innovative non-steroidal anti-inflammatory drug.

trometamol has the shortest average time to reach maximum plasma concentrations (tmax), which equates to most rapid absorption rate. It also has a smaller variability range than dexketoprofen and racemic ketoprofen.

Dr Magdi Hanna Figure 1. Comparison of bioavailability between dexketoprofen trometamol, Analgesics & Pain Research Unit (APRU) dexketoprofen acid form, and ketoprofen6 London, UK

Pain is a complex and dynamic process that involves three major “players” that include inflamma- 3,5 tion, ion channels, and nerve injury. 3 In the spectrum of acute pain, the mechanisms of tissue damage, sensitisation of the neural system, nociception, inflammatory pain, and neuropathic pain are implicated. The interplay of these 2,5 mechanisms explains the differences in the pattern, intensity, character, and duration of pain, espe- 2 cially between various surgical procedures. Ketoprofen 50 mg 1,5 1 The scope of postoperative pain Dexketoprofen 25 mg Approximately 80% of patients have reported postoperative pain,1 and the characteristics of such 0,5 pain dramatically vary across countries. In most patients, pain becomes worse after discharge (g/ml) concentrations Plasma 0 from the hospital, which may result in hospital readmission, and a consequential increase in 0 2 4 6 8 10 Time (h) healthcare costs. Several barriers to the effective control of postoperative pain have been identified. These include fragment pain care received from surgeons, anesthetists, nurses, and patients; delayed involvement Fast onset of action and enhanced efficacy.Dexketoprofen trometamol has shown a of the acute pain team; provision of treatment in response to pain or absence of preemptive pain faster onset of analgesic efficacy compared with its free acid form. Such superior efficacy of pain management; heavy reliance on opioids; utilisation of sedatives or anesthetics instead of analge- relief in 15 minutes was also seen in the treatment of acute musculoskeletal injuries.7 In a dental sics; and administration of monotherapy for pain. setting, dexketoprofen is morePre-op effective education, than dipyrone preparation, in reducing planning post-surgical dental pain.8 In this regard, there is an urgent need for improvement of postoperative pain treatment, including its organisational, pathophysiological, and pharmacological aspects.2 Early identification of Dexketoprofen and postoperative pain patients at risk of chronic postoperative pain is recommended. In a double-blind, randomised Pre- and intra trial, - opthe analgesia patients andreceiving “physiological intra-muscular stabilisation” (IM) dexketoprofen had lower pain intensity scores than those receiving IM ketoprofen. Those receiving IM dexketoprofen Multi-modal analgesia for postoperative pain also had the lowest total consumption of morphine, which was statistically significant compared with placebo (p < .0003).9 This confirms the optimal analgesic efficacy and morphine-sparing effect Novel techniques for postoperative pain management have been developed to improve patient Postoperative analgesia “Acute rehabilitation” outcomes. There appears to be a shift towards multi-modal analgesia, which is thought to reduce of the drug. 3,5 doses of analgesic consumption, improve anti-nociception due to synergistic or additive effects, • Multimodal drugs • Surgical care and reduce severity of side effects from combined drugs. Future trends of• 3Early multimodal deletion of opioidsanalgesics• Early in pain use of management the oral route In identifying the appropriate drug combinations, physicians should understand the mecha- Recent studies are2,5• directedNon-drug towards modalities the potential • Physical benefits and of mentalmultimodal “reactivation” analgesia paradigms in nism of each drug as confounding results may be obtained. In a randomised trial, adding non-ste- the pre-emptive and postoperative management of pain. The use of pre-emptive analgesics was 2 roidal anti-inflammatory drugs (NSAIDs) to the opioid treatment reduced morphine requirements found to decrease the hospital length of stay followingKetoprofen total joint 50 arthroplasty.mg 10 It effectively facilitat- 3 and opioid-related side effects in the early postoperative period. ed pain relief, mobility,1,5 and recovery in patients who had mini cholecystectomy in a day care set-up.11 A drug combination may be considered clinically rewarding if the following conditions are satis- Furthermore, the1 extended administration of multimodal analgesics is recommended, which is Dexketoprofen 25 mg fied: amplification of efficacy (pain relief); improved response rate; reduced side effects; and smaller to be initiated from pre-operative phase to at least one week beyond the postoperative phase. Ap- doses of drugs used. 0,5

propriate drug (g/ml) concentrations Plasma combinations should be considered, including opioids, NSAIDs, or calcium channel alpha-2-delta ligands.0 Strategies which target prevention of chronic pain and implementation of 0 2 4 6 8 10 Time (h) Traditional NSAIDs and cyclo-oxygenase (COX)-2 selective inhibitors an algorithm for the management and rehabilitation of acute pain (Figure 2)12 are also suggested. The adverse effects of traditional NSAID administration have become increasingly prevalent. Prob- lems in the gastrointestinal tract, cardiovascular system, central nervous system, and kidneys are Figure 2. Algorithm for acute pain management and rehabilitation constantly encountered. In the United States and European regions, gastric bleeding is the third most common cause of death, in which the widespread use of NSAIDs may be involved. In order to improve the outcome for NSAIDs, COX-2 selective inhibitors were developed. COX-2 Pre-op education, preparation, planning selectivity reduced the risk of gastrointestinal problems. While a better gastrointestinal profile was achieved, these newer drugs have been associated with unfavorable cardiovascular and neurologi- cal adverse effects. The addition of nitric oxide is purported to enhance the efficacy and safety of this Pre- and intra - op analgesia and “physiological stabilisation” drug class, although poor bioavailability and absorption remains to be a major setback. Evidence shows that the efficacy of COX-2 selective inhibitors is similar to that of the traditional NSAIDs, thus failing to justify the additional cost of the former. A significant increase in congestive heart failure, Postoperative analgesia hypertension, and stroke cases has also been documented. In addition, the substantial reduction in “Acute rehabilitation” opioid requirements do not equate to a reduction in side effects, particularly in episodes of nausea and vomiting. • Multimodal drugs • Surgical care • Early deletion of opioids • Early use of the oral route • Non-drug modalities • Physical and mental “reactivation” Superior analgesic and anti-inflammatory effects of dexketoprofen Unlike COX-2 selective inhibitors, dexketoprofen (Ketesse) acts by inhibiting the two cyclooxyge- nase enzymes, which are principally devoted to catalyse the synthesis of different types of prosta- Conclusion glandins and thromboxanes. It is the S (+) enantiomer of the racemic ketoprofen, which is a racemic Understanding the dynamic mechanism of pain is essential for the continuous development of mixture of “S” and “R” enantiomers; alternatively, levoketoprofen is the R (-) enantiomer. modern pain control techniques. Recent studies have shown the superiority of dexketoprofen to other NSAIDS as part of the multimodal analgesic approach; thus, the incorporation of this new Stereoselectivity. In experimental models, dexketoprofen proved to be a highly effective inhibi- drug into the standard of care for pain may be useful. Furthermore, teamwork among nurses, anaes- tor of COX-1 and COX-2, at least twice as powerful as racemic ketoprofen and 40 times as powerful thetists, surgeons, and patients continues to be vital for the efficient control and rehabilitation of as levoketoprofen. acute pain.

Peripheral and central sensitisation. Peripherally, dexketoprofen acts by inhibiting the sensitisation of pain receptors induced by locally released prostaglandins. Centrally, a growing References: 1. Apfelbaum J, et al. Anesth Analg 2003;97:534-540. 2. Benhamou D, et al. Pain 2008;136:134-141. 3. Cepeda M, et al. Anesthesiology 2005;103:1225-132. 4. Mazario J, body of evidence confirms the decreased “central sensitisation phenomenon” with dexketoprofen, et al. Brain Res 1999;816:512-517. 5. Cabré F, et al. J Clin Pharmacol 1998;38:27S-32S. 6. Barbanoj M, et al. J Clin Pharmacol 1998;38:33S-40S. 7. Leman P, et al. Emerg 4 which leads to the inhibition of painful stimuli transmission to the upper nervous system. Med J 2003;20:511-513. 8. Bagán J, et al. J Clin Pharmacol 1998;38:55S-64S. 9. Hanna M, et al. Br J Clin Pharmacol 2003;55:126-133. 10. Duellman T, et al. Orthopedics.

2009;32:167. 11. Amjad N, et al. J Pak Med Assoc 2002;52:291-296. 12. Macintyre P, et al. 2010. Acute Pain Management: Scientific Evidence, ANZCA & FPM, Melbourne. KETESSE/062013/011 Improved tolerability profile.In a rat model trial, dexketoprofen conferred no significant ulcerogenic effect; however, ulcerogenesis was noted in rats receiving racemic ketoprofen.5 Dexke- Sponsored as a service to the medical profession by A.Menarini Asia Pacific Holdings Pte Ltd toprofen is also associated with improved quality of sleep as well as low incidence of nausea and vomiting. Editorial development by MIMS. The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage however so arising is hereby disclaimed. © 2013 MIMS. All rights reserved. No part of this publication may be reproduced by any process in any language without the written permission of the publisher. Better bioavailability. Possibly owing to its trometamine salt component, dexketoprofen tro- MIMS Pte Ltd, 6 Shenton Way, #15-08, Tower Two, Singapore 068809. Tel: +65-6290 7400 Fax: +65-6290 7401 metamol has been shown to have a more favorable pharmacokinetic profile than racemic ketopro- Email: [email protected] Website: www.mims.com fen and the acid form of dexketoprofen (Figure 1).6 Among these drug formulations, dexketoprofen

MT-Menarini ASEAPS2013 Sym Ht_FINAL_2.indd 1 7/24/13 11:20 AM 44 August 2013

® 1 References: 1. Ketesse® product monograph (oral). 2. Bagán JV, Arranz JSL, Valencia E, Santamaria J, Eguidazu I, Horas M, Forns M, Zapata A, Artigas R, Mauleon D. Clinical comparison of dexketoprofen trometamol and Ketesse is an innovative, next-generation NSAID. As a pure dipyrone in postoperative dental pain. J Clin Pharmacol 1998;38(12 Suppl):55S–64S. 3. Marenco JL, Perez M, 1-4 Navarro FJ, Martinez FG, Beltran J, Salvatierra D, Alonso A, Ballarin M, Eguidazu I, Zapata A, Horas M, Torres F, enantiomer, it offers high analgesic efficacy at low doses, Artigas R, Mauleon D. A multicenter, randomised, double-blind study to compare the efficacy and tolerability of dexketoprofen trometamol versus diclofenac in the symptomatic treatment of knee osteoarthritis. Clin Drug Invest while its tromethamine salt formulation means it is absorbed 2000;19(4):247–56. 5. Zippel H and Wagenitz A. A multicentre, randomised, double-blind study comparing the efficacy and tolerability of intramuscular dexketoprofen versus diclofenac in the symptomatic treatment of acute low back 5 6 pain. Clin Drug Invest 2007;27(8):533–43. 6. Barbanoj MJ, Gich I, Artigas R, Tost D, Moros C, Antonijoan RM, Garcia fast, resulting in rapid pain relief in as little as 15 minutes. ML, Mauleon D. Pharmacokinetics of dexketoprofen trometamol in healthy volunteers after single and repeated oral doses. J Clin Pharmacol 1998;38(12 Suppl):33S–40S. 7. Leman P, Kapadia Y, Herington J. Randomised controlled trial With an excellent tolerability profile compared to other of the onset of analgesic efficacy of dexketoprofen and diclofenac in lower limb injury. Emerg Med J 2003;20(6):511–3. 7,8 ® 8. Carne X, Rios J, Torres F. Postmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol KETESSE/022013/005 for mild to moderate acute pain treatment in primary care. Methods Find Exp Clin Pharmacol 2009;31(8):533–40. 9. NSAIDs, Ketesse is an evolution in NSAID choice. Moore RA and Barden J. Systematic review of dexketoprofen in acute and chronic pain. BMC Clin Pharmacol 2008;8:11.

A.Menarini Asia Pacific Holdings Pte Ltd. 30 Pasir Panjang Road #08-32 Mapletree Business City Singapore 117440 www.menariniapac.com Ketesse® is a Registered Trademark of A. Menarini. 45 August 2013 News Heart patients avoid healthy lifestyles

Laura Dobberstein

any coronary heart disease and stroke patients have not taken im- Mportant steps towards a healthier lifestyle, according to a recent Canadian study. “Observational data indicate that following an acute coronary syndrome, those who ad- here to a healthier lifestyle have a lower risk of recurrent events,” said lead study author Dr. Many heart patients appear to avoid healthy lifestyle options, despite Koon Teo, of McMaster University, Hamilton, overwhelming evidence that such lifestyle options can reduce recurrent Ontario, Canada, and colleagues. events. In their study, of 7,159 people who had ex- and legislative measures than countries with perienced stroke or coronary heart disease, lower incomes. 81.5 percent quit smoking or never smoked, “Although the findings of this study are 35.1 percent undertook high levels of physi- unsurprising, this is an important study to cal activity and 39 percent had healthy diets. remind ourselves – medical professionals, Overall, 14.3 percent did not exhibit any of the patients and even health care policy makers three recommended behaviors, 42.7 percent – that we are really still not doing a good job displayed only one of these behaviors, 30.6 in the area of preventive medicine,” said Dr. percent demonstrated two behaviors and only Tan Kok Soon, a Singapore-based cardiologist 4.3 percent had all three behaviors. Healthy with Mt. Alvernia Medical Centre and Park- behaviors were more frequent in high income way East Medical Centre. countries and less frequent in the lower income Tan stressed the importance of healthy life- countries. The result was most pronounced style choices as a major component of cardiovas- with regards to smoking cessation. cular disease management and suggested pa- Teo and colleagues gathered the data from tients and doctors approach changes in diet and an existing prospective cohort study compris- exercise gradually as incremental change is more ing 153,996 adults across 17 countries between likely to be sustainable than sudden change. January 2003 and December 2009. “An unhealthy lifestyle usually has been These results could help medical profession- formed over a lifetime and is unfortunately als enhance prevention of cardiovascular dis- often pleasurable to the patient. Trying to ease by providing understanding of how cer- change this entrenched enjoyable behavior tain demographics adopt healthy behaviors. and habit is therefore in itself very difficult,” The authors hypothesized that high-in- said Tan who encourages his patients to dis- come countries have more strategies to pro- cuss their condition and lifestyle. mote healthy lifestyle changes, particularly “Once you have established cardiovascular when it comes to smoking cessation. For ex- disease, your risk of another event [heart at- ample, higher income countries devote more tack, stroke] is high. Continuing with an un- resources to smoking cessation programs, healthy lifestyle would only increase the risk education on tobacco and active taxation substantially,” said Tan. Sponsored Symposium Highlights Nitric Oxide and the Future of Cardiovascular Management During the 44th Annual Convention of the Philippine Heart Association held at the EDSA Shangri-La Hotel in Manila, Nobel prize awardee Professor Louis Ignarro discussed the protective role of nitric oxide (NO) in the cardiovascular system, highlighting its contribution to the well-recognised benefits of the novel antihypertensive nebivolol. Dr Romeo Divinagracia further explained how unique features of nebivolol account for its improved efficacy and tolerability versus first- and second-generation beta-blockers.

In animal studies, nebivolol has also been found to inhibit aortic The role of nitric oxide and nebivolol in cardiovascular treatment smooth muscle cell proliferation by inhibiting ornithine decarboxylase Professor Louis Ignarro (ODC) and polyamine production.6 Furthermore, it exhibits a Department of Molecular and Medical Pharmacology complementary antioxidant activity, through which the pathological University of California, Los Angeles reactive oxygen species (ROS)-induced depression of intracellular NO USA levels can be prevented.5 Since the discovery of nitric oxide (NO) and cyclic guanosine a cascade of reactions that ultimately lead to vascular smooth muscle Nebivolol is a racemic combination of d-nebivolol and l-nebivolol monophosphate (cGMP) as vascular smooth muscle relaxants relaxation, improvement in blood flow and inhibition of blood clotting that differs chemically from other beta-blockers, with an absolutely many years ago, a great deal of basic and clinical research has been by interfering with platelet aggregation. symmetrical configuration developing from a central nitrogen conducted on the physiological and pathophysiological roles of NO in atom.7 Neither nebivolol nor its enantiomers show any intrinsic cardiovascular function.1 To date, NO is known to elicit a protective and Non-pharmacological factors that normally increase endogenous sympathomimetic activity or undesirable beta-blocker effects, such as beneficial action in many disease states such as essential hypertension, synthesis of NO include aerobic exercise and a healthy diet, whereas a decrease in cardiac output. stroke, coronary artery disease, vascular complications of diabetes, eating fatty or salty meals and having a sedentary lifestyle produce 1,2 the opposite effect. Aside from nitroglycerin, there are very few drugs impotence and other disorders involving the vascular system (Figure 1). Clinically, the efficacy and safety of nebivolol were demonstrated in available that utilise the NO system to manage hypertension, prevent endothelial dysfunction and atherosclerosis, reduce oxidative stress the SENIORS study, a large trial involving patients with a history of Figure 1. Multiple systems affected by nitric oxide hospital admission for heart failure within the previous year or known 1,2 or inhibit vascular smooth muscle proliferation. Other potential uses physiology 8 may also include the treatment of memory disorders, irritable bowel ejection fraction of 35% or below. In this study, 2,128 patients aged 70 syndrome, bladder incontinence and glaucoma. years or above were randomly assigned to receive nebivolol (titrated from 1.25 mg once daily to 10 mg once daily) or placebo. Genito- Cardio Vascular CNS Nebivolol is a unique and highly cardioselective beta-1-adrenergic Urinary receptor blocker that possesses additional vasodilator properties After a mean follow-up of 21 months, the primary outcome, which was attributable to NO (Figure 2). It relaxes vascular smooth muscle a composite of all-cause mortality or cardiovascular hospital admission primarily by endothelium-dependent mechanisms involving beta- (time to first event), occurred in 31.1% of patients on nebivolol adrenergic receptors.4 Specifically, nebivolol appears to interact compared with 35.3% of those on placebo (hazard ratio [HR] 0.86, 95% with the endothelial NO pathway in two complementary ways. It confidence interval [CI] 0.74-0.99; P=0.039). There was no significant Anti- stimulates NO synthase (NOS) activity and reduces the NO-scavenging Pulmonary NO Inflammatory influence of age, gender or ejection fraction on the effect of nebivolol radical superoxide anion, by redirecting deranged NOS activity from on the primary outcome. Death from all causes occurred in 15.8% and 5 superoxide to NO production. 18.1% on nebivolol and placebo, respectively (HR 0.88; 95% CI 0.71– Figure 2. Mechanism of action of nebivolol 1.08; P=0.21). With its distinctive dual action of endothelium-induced NO-mediated NOS Gastro- Host Defense Many vasodilation leading to decreased total peripheral resistance with a Intestinal Others Arginine NO concomitant lowering of blood pressure, coupled with its peculiar highly selective antagonism of beta-1 receptors, nebivolol is currently CNS, central nervous system; NO, nitric oxide. arginase NEBIVOLOL recommended for the treatment of essential hypertension and mild and moderate chronic heart failure, in addition to standard therapies. Nitric oxide is a unique, gaseous, lipid-soluble molecule synthesised Ornithine Good hypertension control has been shown to produce up to a 25% in mammalian cells that readily diffuses through cell membranes and acts as a neurotransmitter in specialised vascular beds.1 Previously reduction in the risk of myocardial infarction, a 35% decrease in the risk ODC NO 9-11 recognised as the endothelium-derived relaxing factor (EDRF), NO is of stroke and a 45% reduction in risk of heart failure. biosynthesised endogenously from L-arginine, oxygen and reduced Putrescine References nicotinamide adenine dinucleotide phosphate (NADPH) by various 1. Ignarro LJ. J Physiol Pharmacol 2002;53(4 Pt 1):503-514. NO synthase (NOS) enzymes. 2. Rajfer J, et al. N Engl J Med 1992;326:90-94. Spermidine Spermine 3. Ignarro LJ. Proc Natl Acad Sci U S A 2002;99:7816-7817. 4. de Groot AA, et al. J Cardiovasc Pharmacol 2003;42:232-236. The NO pathway was found to be responsible for the vasodilating and 5. Ignarro LJ. Blood Press Suppl 2004;1:2-16. antianginal effects of nitroglycerin more than a century after the drug 6. Ignarro LJ, et al. Nitric Oxide 2002;7:83-90. 7. Ignarro LJ. Cardiovasc Ther 2008;26:115-134. 3 Polyamines for Cell Growth was initially discovered. Being a free radical with a short half-life, NO 8. Flather MD, et al. Eur Heart J 2005;26:215-225. 9. Chobanian AV, et al. JAMA 2003 21;289:2560-2572. reacts not only with oxygen, but also with iron and sulphur species and 10. Neal B, et al. Lancet 2000;356:1955-1964. owes much of its biological activity to its unpaired electron, initiating NO, nitric oxide; NOS, nitric oxide synthase; ODC, ornithine decarboxylase. 11. Pohl MA, et al. J Am Soc Nephrol 2005;16:3027-3037.

Figure 3. Pharmacological and therapeutic profile of Nevibolol – an overview of a novel beta-blocker nebivolol Dr Romeo Divinagracia President, Philippine Society of Hypertension Professor of Medicine (Emeritus) University of the East Ramon Magsaysay Memorial Medical Centre NEBIVOLOL Past president, Philippine Society of Critical Care Medicine Quezon City, Philippines

Endothelium-induced ß1-adrenoceptor Beta-blockers are considered one of the most important The primary indications for which nebivolol has been developed and NO-mediated effects antagonism pharmacological innovations of the twentieth century, having studied include systemic hypertension, heart failure and coronary revolutionised the management of angina pectoris. Thus, three artery disease.4 In hypertensive patients, nebivolol has been shown to generations of beta-blockers have already been developed for the increase cardiac output and decrease peripheral vascular resistance treatment of angina and hypertension since the 1960s, differing mainly with a mild bradycardic action.5 Its effects on haemodynamic Haemodynamic profile in their receptor selectivity and their ability to induce vasodilation.1 parameters at rest and at peak exercise in hypertensive patients Unlike their earlier counterparts, third-generation beta-blockers are with diastolic dysfunction are similar to those of atenolol, although Antihypertensive efficacy generally associated with a greater decrease in blood pressure, less nebivolol is associated with a lower reduction in the cardiac index, a Better tolerability than the older or no increase in plasma glucose and plasma lipids, and less or no greater increase in the stroke volume index and a decline in the mean decrease in nocturnal melatonin secretion. pulmonary artery pressure and pulmonary wedge pressure.6 Beta Blockers Among the third-generation beta-blockers, nebivolol demonstrates Apart from offering greater convenience due to its once-daily oral antioxidant properties and is the only agent that works by increasing dosing, nebivolol may provide more cardiovascular benefits than Sponsored as a service to the medical profession by A. Menarini vascular NO availability as a consequence of stimulation of NO release traditional agents, particularly in non-Caucasians and in patients with Asia Pacific Pte Ltd. Editorial development by MIMS. The opinions expressed in this (Figure 3). The NO-mediated endothelial effects have been found to isolated systolic hypertension, diabetes, peripheral vascular disease, publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage howsoever prevent atherosclerosis, vascular smooth muscle proliferation, and and obstructive respiratory comorbidities. arising is hereby disclaimed. platelet aggregation—all important contributors to the pathogenesis © 2013 MIMS. All rights reserved. No part of this publication 2 References may be reproduced by any process in any language without the of myocardial infarction and other cardiovascular complications. 1. Ram CV. Am J Cardiol 2010;106:1819-1825. written permission of the publisher. 2. Horn HR. Medscape Family Medicine. http://www.medscape.org/viewarticle/466799_2. Accessed June Combined with its powerful beta-1 adrenergic receptor antagonism, 17, 2013. MIMS Pte Ltd 6 Shenton Way Tower 2 #15-08 Singapore 068809. 3. Ignarro LJ. Cardiovasc Ther 2008;26:115-134. Tel: (65) 6290 7400 Fax: (65) 6290 7401 E-mail: enquiry.sg@mims. nebivolol exhibits excellent antihypertensive efficacy and better 4. Münzel T, Gori T. J Am Coll Cardiol 2009;54:1491-1499. 5. Kamp O, et al. Am J Cardiol 2003;92:344-348. com Website: www.mims.com tolerability than the older beta-blockers.3 6. Nodari S, et al. Eur J Heart Fail 2003;5:621-627.

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48 August 2013 In Practice Diagnosing and managing hip impingement

Dr. Martin John Director, Orchard Health Clinic, Singapore UK Registered Osteopath (GOsC) MSc, BSc(Hons)Ost, MBA S.A.C. Dip: Advanced Psychology, Sports Electro-Therapy, Sports Injuries & Nutritional Therapy

ip impingement syndrome, or fem- oro-acetabular impingement (FAI) Hsyndrome, is a pathological condition that is seen in mostly young and middle- aged adults. It is an important condition to recognize as it can result in chronic pain and reducing normal function, and be associated with labral tears and progressive osteoarthritis (OA) of the hip, which can often lead to surgical intervention. Currently, there is no conclusive research on the exact etiology of FAI. However, certain pathological changes of the femur and acetabulum do predispose individuals to develop the condition. The main criterion for those who may be susceptible to FIA is based on people who have anatomically anomalous findings such as hypermobile joint conditions or an irregularly shaped femoral head, neck or acetabulum. • Examination of passive movements inflex- ion and internal rotation of the hip Diagnosis • Imaging to diagnose any alteration in nor- Definitive diagnosis of FAI is made through mal anatomical features of the femoral imaging studies such as X-ray, MRI or CT head, neck or acetabulum scan. Early diagnosis can be made by: • Consideration of any conditions pre-dis- • Noticing if the patient exhibits chronic posing the patient to hypermobility of the groin or hip pain, especially in middle- joints. aged women who take part in exercises The main challenge of hip impingement is that are flexibility-centered such as dance that the symptoms can be easily confused with and yoga or in sports that need a greater other conditions like simple groin strains, ear- degree of hip flexion such as cycling ly onset hip OA or hip dysplasia. A full his- 49 August 2013 In Practice tory of both the time scale of the condition ment. After surgery, physical rehabilitation of and its aggravating factors can help overcome the hip is beneficial due to potential atrophy, this. Looking at passive movements, func- contracture or pain in returning to normal ac- tional movements and activity can be greatly tivity. beneficial when deciding whether to continue There is a great deal of debate around cur- with imaging diagnostic tests. rent treatment practices. Surgery may be beneficial in the short and mid-term, but long- A patient who exhibits term evidence of improvement is lacking in the scientific community. In addition, it may poor control of hip stabilizers be impossible for a patient to return to their combined with increased previous level of sporting activity after sur- use of movement muscles gery. For this reason, GPs often prefer the use of anti-inflammatory medication or steroid could alter the correct centric injection as pain relief. control of the femoral head due to a greater influence Treatment and prevention with osteopathy From an osteopathic point of view, func- of phasic muscles on the hip tion of the hip and its supporting muscles compared with tonic ones are a key area in both recognizing and preventing FAI. As the hip is a ball and socket If there are no underlying congenital chang- joint, its structure demands a full move- es, early stage FIA is only clinically diagnos- ment in a ball and socket manner within a able and is still an area of debate, as it will not centered axis of movement. If the underly- show up on imaging. Congenital, middle and ing function of the joint is not expressed late stages of FIA will show up on imaging or a dysfunction movement pattern is -fol and are considered the gold standard with lowed for too long, it will eventually lead to MRI preferable for seeing middle stages due a change in the structure. to it being able to assess labral tears. Osteopathy treatment can include pain relief through soft tissue techniques like mas- Common treatment practices sage and heat modalities, and exercises to im- FIA is normally treated conservatively prove overall hip function. with physical therapy to improve function Posture, anatomical mechanics and life- and relieve pain. Surgical intervention is of- style are also considered highly relevant in ten administered in more severe cases when FAI treatment. An osteopath looks for any a patient suffering from hip pain for ape- imbalance between muscles that aid in sta- riod longer than 6 months tests positive on bilizing the hip and controlling axial move- any orthopedic special tests and for imaging ment by being close to the center of axis such changes in anatomy. Surgery most commonly as psoas muscles, and those muscles that consists of using hip arthroscopy to perform are meant more for moving the hip but also either any or all of the following: peri-acetab- can influence the hip joint, such as rectus ular osteotomy, hip dislocation and debride- femoris. 50 August 2013 In Practice

A patient who exhibits poor control of tions, the same consideration should be given hip stabilizers combined with increased use to the hip. Activities often given as advice by of movement muscles could alter the correct GPs such as swimming, yoga or cycling may centric control of the femoral head due to a actually be poor choices of exercise for those greater influence of phasic muscles on the hip with FAI. Excessive instability can be a great- compared with tonic ones. er problem to FIA than weight bearing. Un- derstanding that weight bearing alone is not Understanding stability vs flexibility the only factor in hip involvement may help a In much the same way that instability or in- patient get correct treatment far faster and adequate control of muscles in the shoulder are prevent the possibility of more serious arthrit- now considered important in shoulder condi- ic conditions. 51 August 2013 Calendar AUGUST

9th Singapore International Congress of 49th Annual Meeting of the European Association Obstetrics & Gynaecology for the Study of Diabetes 22/8/2013 to 24/8/2013 23/9/2013 to 27/9/2013 Location: Singapore Location: Barcelona, Spain Info: Scientific secretariat, MIMS Info: EASD Secretariat Tel: (65) 6290 7400 Email: [email protected] Email: [email protected] Website: www.easd.org Website: www.sicog2013.com 13th Asian Federation of Sports Medicine Asia-Pacific League of Associations for Congress Rheumatology Symposium 25/9/2013 to 28/9/2013 29/8/2013 to 1/9/2013 Location: Kuala Lumpur, Malaysia Location: Bali, Indonesia Info: AFSM Organizers Info: Kenes Asia Email: [email protected] Tel: (65) 6292 4710 Website: www.13afsm.com Email: [email protected] Website: www2.kenes.com/aplar/Pages/home.aspx National Skin Centre Dermatology Update 2013 European Society of Cardiology Congress 26/9/2013 to 28/9/2013 Location: Singapore 31/8/2013 to 4/9/2013 Info: Mrs. Alice Chew, Conference Secretariat, National Location: Amsterdam, Netherlands Skin Centre (S) Pte Ltd Info: ESC Secretariat Tel: (65) 6350 8405 Email: www.escardio.org/Pages/contactus.aspx Email: [email protected] Website: www.escardio.org/ESC2013 Website: www.nsc.gov.sg/showcme.asp?id=149

Primary Care Forum 2013 and the 4th Singapore SEPTEMBER Health & Biomedical Congress 2013 27/9/2013 to 28/9/2013 European Respiratory Society Annual Congress Location: Singapore Tel: (65) 6496 6684 / (65) 6496 6682 7/9/2013 to 11/9/2013 Email: [email protected] Location: Barcelona, Spain Website: www.pca.sg/events Info: ERS 2013 c/o K.I.T. Group Email: [email protected] European Cancer Congress 2013 (ECCO-ESMO- Website: www.erscongress2013.org ESTRO) 27/9/2013 to 1/10/2013 Asian Pacific Digestive Week Location: Amsterdam, Netherlands 21/9/2013 to 24/9/2013 Info: ECCO Secretariat Location: Shanghai, China Tel: (32) 2 775 02 01 Info: APDWF Secretariat Fax: (32) 2 775 02 00 Tel: (65) 6346 4402 Email: [email protected] Email: [email protected] Website: eccamsterdam2013.ecco-org.eu/ Website: www.gastro2013.org/

21st World Congress of Neurology 21/9/2013 to 26/9/2013 Location: Vienna, Austria Info: Kenes International Email: [email protected] Website: www2.kenes.com/wcn/Pages/Home.aspx 52 August 2013 Calendar UPCOMING

Taiwan Digestive Disease Week 2013 4/10/2013 to 6/10/2013 Location: Taipei, Taiwan Info: Congress Secretariat Email: [email protected] Website: www.tddw.org

13th International Workshop on Cardiac Arrhythmias - Venice Arrhythmias 2013 27/10/2013 to 29/10/2013 Location: Venice, Italy Info: VeniceArrhythmias 2013 Organizing Secretariat Tel: (39) 0541 305830 Fax: (39) 0541 305842 Email: [email protected] Website: www.venicearrhythmias.org

9th International Symposium on Respiratory Diseases 8/11/2013 to 10/11/2013 Location: Shanghai, China Info: MIMS, China Email: [email protected] Website: www.isrd.org/

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Spore JAN/FEBNOV/DEC 2012 2012 Vol. Vol. 38 38 No. No. 1 6 Your partner in paediatric and O&G practice JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

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PAEDIATRICS Dietary Intervention in Eczema

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Infectious Disease in Pregnancy

Newborn Stem Cells: Types, Functions and Basics for Obstetricians

CME ARTICLE Postmenopausal Bleeding

NOV/DEC 2012 Vol. 38 No. 6 Your partner in paediatric and O&G practice

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JPOG(P-O-D)206x276_0113.indd 1 1/17/13 11:53 AM 54 August 2013 After Hours

IPOH AND ITS FORMER GLORY

Ipoh was once a boomtown, when tin mining was at its zenith. The ‘tin rush’ can be compared to that of San Francisco’s gold rush of the mid-1800s, which brought people from all over to congregate and clamor for the riches of the land. The industry collapsed in the 1980s, crippling the local economy. The glory days may be long gone, but the charms remain, Leonard Yap writes.

had recently the opportunity to visit Ipoh, the trains run like a Swiss watch – on time, albeit for half a day. In the spirit of carpe most of the time. Idiem (Latin for ‘seize the day’) I was hell Ipoh is approximately 220 km from Kuala bent on making the best out of the time I had. Lumpur and the former tin-mining capital of One of the great things about Ipoh today is the country. These days, the city is dependent that you are only a train ride away from Kuala on agriculture, particularly rubber and palm Lumpur. Being a big believer in public trans- oil. Tourism is a significant breadwinner, with port and a fan of trains, I hopped on one of the state’s plentiful natural attractions like the the spanking new electric trains that ply Ipoh limestone caves of Gua Tempurung and its and Kuala Lumpur. It takes only 3 hours and proximity to Cameron Highlands. 55 August 2013 After Hours

Disembarking from the train, you are During the colonial days, the higher echelons greeted by a magnificent train station. The ar- of society would gather at the exclusive Ipoh chitecture, reminiscent of many British colo- Royal Club, which is adjacent to the field. It nial stations, employs the Neo-Moorish/Mu- continues to be the place for cricket lovers and ghal/Indo-Saracenic/Neo-Saracenic style. The you can watch a game if you arrive at the right most eye-catching features of the station are time of day. the Moorish dome, whitewashed walls and If you still have energy for more strolling, the great pillars. The station once housed a there is Little India located not too far away. hotel aptly called the Majestic Station Hotel. It Peer through the windows of shops selling is currently closed for renovation. If you plan clothes, gold and various cooking imple- on taking a taxi from the station, be ready to ments. Many of these cooking implements are haggle over the fare as the taxis do not use imported from India, and you can get good meters. deals on pressure cookers and big, but por- If you are willing to put those legs to the table, flour mills. Yes, they sell those! test, it may well be worth it. Walking to the You can then head to the river, where it east of the railway station you will bump into might be a bit cooler. Sungai Kinta skirts the some pretty imposing architecture, more rem- city and is a decent distraction from the city. nants of British rule. There is the Ipoh High You can watch people lounging by the river or Court and City Hall, which feature the famil- even fishing. It may not be the cleanest river iar whitewashed walls and dominant pillars. you have ever seen, but it has gotten a lot bet- Not too far off are the state mosque and the ter than it used to be. Birch Memorial Clock Tower. The tower was One of the things that caught my eye dur- named after James Wheeler Woodford Birch, ing my visit was the buildings, particularly the a British Resident Minister serving as govern- old shops. Many of them have been around ment advisor to the Sultan of Perak in 1874. for many years, some pre-World War 2 or He was assassinated by a local Malay chief, even older. These buildings have a lot of char- who accused Birch of being arrogant and in- acter and if buildings could talk, what stories sensitive to local customs. they would tell! Some look like they have had Continue to roam deeper and you will head better days and many remain abandoned. towards the ‘center’ of old Ipoh. The center is Who knows, maybe someday when Ipoh marked by the Ipoh Padang, a cricket/foot- finds another boom, it will live again in ball field that used to hold important events. glory.

IPOH AND ITS FORMER GLORY 56 August 2013 Humor

“I’m sorry that you feel so depressed. It’s probably not a good time to talk to you about your funeral “Any history of death in your family?” arrangements!”

“This crash diet of yours ... I tried it yesterday and “The results are clear and irrefutable. You are due for an autopsy!?” haven’t lost any weight!”

“Let’s see if your blood pressure is “I thought going to a group high today. If it is, you can’t blame it “I’m afraid I’ve done all I can do. hug was a nice idea!” on white coat syndrome!” Now it’s time for my lunch!” MIMS CurrentVideo Series Opinion in

BY DOCTORS FOR DOCTORS GastroenterologyBy Doctors • For Doctors

Professor David Lieberman Professor Nimish Vakil Dr Markus Cornberg shares his perspective on the present and talks about management of patients with discusses the management of chronic future of colorectal cancer screening. refractory GERD. hepatitis B. “There is a lot of potential to prevent “Successful treatment of refractory GERD “The aim of therapy should be the cure many cancers if we can improve the rate requires thorough investigation of the patient or control of HBV infection without the of CRC screening.” situation.” need for life-long treatment.”

MIMS Video Series features interviews with leading experts.

In this Series, find out what these medical experts have to say about latest updates in the management of refractory GERD, the management of chronic hepatitis B and the present & future of colorectal cancer screening.

Got a spare 5 minutes? Go to www.mims.asia/video_series SCAN TO WATCH VIDEO

Brought to you by MIMS

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