Medical Tribune October 2012 SG

October 2012
ESC rolls out new practice guidelines
FORUM Health policies need to foster right environment
DEPRESSION Short-term fluoxetine, venlafaxine efficacious for depression
NuvaRing Once-Monthly Convenient Contraceptive Ring for Today's Women
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Clinical E cacy: NuvaRing vs a COC1 (30 mcg of EE and 3 mg of Drospirenone)
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NuvaRing (n=499) Adapted from Ahrendt et al.1
COC (n=484)
COC: Combined oral contraceptive EE: Ethinyl Estradiol
Study Design: An open-label, randomized, multicenter trial in 10 European countries comparing efficacy, acceptability, tolerability, and compliance of NuvaRing with a COC containing 30 mcg of EE and 3 mg of drospirenone for 13 cycles (N=983).1
Weight neutrality2
Body Weight (mean SD) per Assessment for NuvaRing and COC Groups2
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NuvaRing (n=499) COCs (n=484)
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Adapted from Milsom et al.2
Study Design: A randomized, open-label, multicenter trial (N=983) conducted in 10 European countries. Women were randomized to NuvaRing or a COC with 30 mcg of EE and 3 mg of drospirenone. Body weight measurements performed at screening and each study visit were used to estimate the mean weight change from baseline within each treatment group and the difference in weight change in the NuvaRing group vs the COC group.
Reference: 1. Ahrendt H-J, Nisand I, Bastianelli C, et al. Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 mcg of ethinyl estradiol and 3 mg of drospirenone. Contraception. 2006;74(6):451-457. 2. Milsom I, Lete I, Bjertnaes A, et al. Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 mcg of ethinyl estradiol and 3 mg of drospirenone. Hum Reprod. 2006;21(9):2304-2311. Selected Safety Information Contraindications: Presence or history of venous thrombosis or thromboembolic events, with or without pulmonary embolism Presence or history of arterial thrombosis (e.g. cerebrovascular accident, myocardial infarction) or prodromi of a thrombosis (e.g. angina pectoris or transient ischemic attack). Known predisposition for venous or arterial thrombosis, with or without hereditary involvement such as Activated Protein C (APC) resistance, antithrombinIII deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant) History of migraine with focal neurological symptoms Diabetes mellitus with vascular involvement The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see under Special warnings and precautions for use) Pancreatitis or a history thereof if associated with severe hypertriglyceridemia Presence or history of severe hepatic disease as long as liver function values have not returned to normal Presence or history of liver tumors (benign or malignant) Known or suspected malignant conditions of the genital organs or the breasts, if sex steroidinfluenced Undiagnosed vaginal bleeding Known or suspected pregnancy Hypersensitivity to the active substances or to any of the excipients of NuvaRing Warnings/Precautions: 1. Circulatory Disorders Epidemiological studies have suggested an association between the use and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism These events occur rarely 2. Tumors The most important risk factor for cervical cancer is persistent human papilloma virus (HPV) infection Epidemiological studies have indicated that longterm use of COCs contributes to this increased risk, but there continues to be uncertainty about the extent to which this finding is attributable to confounding effects, like increased cervical screening and difference in sexual behavior including use of barrier contraceptives, or a causal association It is unknown how this effect relates to NuvaRing A metaanalysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using COCs The excess risk gradually disappears during the course of the 10 years after cessation of COC use Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer 3. Other conditions: Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal Recurrence of cholestatic jaundice which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of COCs Diabetic women should be carefully monitored while using NuvaRing especially in the first months of use Deterioration of Crohns disease and colitis ulcerosa has been reported in association with the use of hormonal contraceptives Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst using NuvaRing Women who may not be able to insert NuvaRing correctly or may lose the ring if she has prolapse of the uterine cervix, cystocele, and/or rectocele, severe or chronic constipation Women may occasionally experience vaginitis. Adverse Events: Common ( 1/100) includes vaginal infection, depression, libido decreased, headache, migraine, abdominal pain, nausea, acne, breast tenderness, genital pruritus female, dysmenorrhoea, pelvic pain, vaginal discharge, weight increased, medical device discomfort, vaginal contraceptive device expelled.
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COC: Combined oral contraceptive EE: Ethinyl Estradiol
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MSD Pharma (Singapore) Pte Ltd
Please read the full prescribing information before prescribing NuvaRing.
150 Beach Road #31-00 Gateway West Singapore 189720 Tel: (65) 6508 8400 Fax: (65) 6296 0005 http://www.msd-singapore.com
WOMN-1037663-0022 08/12
October 2012
ESC rolls out new practice guidelines

Elvira Manzano
ive new practice guidelines from the European Society of Cardiology (ESC) recommend new agents, devices and therapeutic options for managing valvular disease, ST segment elevation myocardial infarction (STEMI), heart failure (HF), atrial fibrillation (AF) and cardiovascular disease (CVD) prevention. A consensus statement was also issued on the latest universal definition of myocardial infarction (MI). For valvular disease, the importance of a collaborative approach between cardiologists and cardiac surgeons working as a heart team has been emphasized. For the first time, transaortic valve implantation (TAVI) is recommended in patients with severe symptomatic aortic stenosis (AS) who are unsuitable for surgery, but only in hospitals with cardiac surgery on site. TAVI should not be performed in patients at intermediate risk for surgery. Mitral valve repair is the preferred technique in mitral regurgitation, when the repair is considered durable. Mitraclip device may be considered in high-risk or inoperable patients resistant to optimal medical therapy. In HF, the key changes from the 2008 ESC guidelines include a new indication for mineralocorticoid antagonist (MRA) eplenerone in patients with systolic HF and mild symptoms, broadening the indication to essentially all HFREF patients remaining symptomatic despite treatment with a beta-blocker and ACE inhibitor or ARB. Ivabradine is now recommended to be added to an ACE inhibitor, beta-blocker and MRA for HF-REF patients in sinus rhythm with a persistently high heart rate (>70 bpm).
The new guidelines include a range of new options for managing heart conditions.
The use of cardiac resynchronization therapy (CRT) has been expanded to patients with mild symptoms. Those with a left ventricular ejection fraction (LVEF) of 35 percent or lower, sinus rhythm, and left bundle-branch block QRS morphology, however, benefit the most from the device. The guidelines also recognize the increasing importance of cardiac MRI and include mid-regional proBNP as a rule-out blood test in patients with acute HF. Reperfusion therapy is recommended for all STEMI patients within 12 hours of first symptoms, and beyond the 12-hour window period if there is persistent pain and ECG changes. Clopidogrel and aspirin are recommended for fibrinolysis. Dual antiplatelet therapy is indicated for up to 12 months in those having primary PCI, a minimum of 1 month for those receiving a bare metal stent and 6 months for a drug-eluting stent. For stroke prevention, the use of CHA2DS2VASc score instead of the CHADS2 score is now recommended for identifying at-risk patients, and new oral anticoagulants such as
October 2012 Catheter ablation is advised for patients with symptomatic paroxysmal AF who have failed antiarrhythmic medications (Class IA). The guidelines on CVD prevention focus on CVD risk, why prevention is needed, and who should benefit from it. CV risks are classified as very high, high, moderate and low. Strong recommendations are given on diet, smoking, hypolipidemic medications, exercise and other behavioral risk factors. The ESC also released the latest definition for five types of MI and their clinical implications. The consensus document now recognizes that small amounts of myocardial injury or necrosis can be detected by biochemical markers and imaging.
dabigatran, rivaroxaban or apixaban are now considered preferable to vitamin K antagonists (Class IIA). Dual antiplatelet therapy with aspirin and clopidogrel, or aspirin only, may be considered in patients who refuse anticoagulation. Percutaneous closure of the left atrial appendage (LAA) may be considered in those with thromboembolic risk who cannot be managed with oral anticoagulants in the long term. Vernakalant has been introduced as a new antiarrhythmic agent for rapid cardioversion of recent onset AF, with few exceptions. The guidelines also highlight the revised use of dronedarone for paroxysmal or persistent AF. However, it is contraindicated in permanent AF and heart failure.
Tai chi can benefit patients with COPD

Elvira Manzano
modified tai chi program may improve the exercise capacity and quality of life of patients with chronic obstructive pulmonary disease (COPD), new research has shown. In a randomized controlled trial, patients assigned to tai chi were, on average, able to walk 55 meters (95% CI 31 to 80) farther and 384 seconds (95% CI 186 to 510) longer at 12 weeks compared with a control group. [Eur Respir J 2012; DOI:10.1183/09031936.00036912] An important finding from our study was the significant improvement in balance and muscle strength following Sunstyle tai chi training, which has the potential to reduce the risk of falls in people with COPD, said one of the study authors Dr.
Tai chi improved muscle strength and balance in study patients.
October 2012 tion. Significant improvements in balance, strength and performance were also observed in the tai chi group. The effects of tai chi were comparable to what can be achieved during conventional pulmonary rehabilitation. This is good news for people with COPD because it gives them more fitness choices, said lead study author Ms. Regina Wai Man Leung of Concord Repatriation General Hospital and the University of Sydney, Australia. With increasing numbers of people being diagnosed with COPD, it is important to provide different options for exercise that can be tailored to suit each individual, added Leung, a cardiorespiratory physiotherapist. The authors said the study provides compelling evidence that tai chi may be an effective alternative training modality for people with COPD who have limited or no access to pulmonary rehabilitation. The high degree of adherence with both formal and at-home training and practice suggests that the program is feasible for COPD patients, even for those with comorbidities, they concluded.
Jennifer Alison, from the University of Sydney, Australia. Lower limb muscle weakness and impaired gait and balance are common in people with COPD and are major risk factors for falls. In the study, patients were randomized to a 12-week tai chi program, consisting of a 2-hour session each week, or standard COPD treatment without exercise. The majority of the patients were males. Average age was 73, with co-morbidities that included osteoarthritis, hypertension, dyslipidemia and coronary heart disease. On days when patients were not on sessions, they practiced tai chi at home for 30 minutes. Compared with the control group, patients on tai chi exercise performed 75 percent better in the walking test and had a significantly higher score in the Chronic Respiratory Disease Questionnaire, which indicates better quality of life. Additionally, tai chi was associated with moderate intensity exercise as demonstrated by a 53-percent reserve in oxygen consump-
October 2012
Forum
Health policies need to foster right environment

Excerpted from a presentation by Professor Salim Yusuf, lead researcher of the PURE study and director of the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, during the 2012 European Society of Cardiology Congress held recently in Munich, Germany.
ealth is intrinsically related to wealth. The Prospective Urban Rural Epidemiological (PURE) study, a survey of 153,996 adults from 628 urban and rural communities in 17 countries, has highlighted the discrepancies in lifestyle and diet between high-income and low-income nations. The average fruit and vegetable consumption per day should be 500 grams or 5 servings, but surprisingly, our analysis of PURE showed that one-third of the countries of the world are not consuming adequate amount. The consumption of fruits and vegetables increased among nations with a higher gross domestic product (GDP) and wealth index, but this was offset by an increase in the amount of energy obtained from total and saturated fats, as well as from protein. Energy from total fat, saturated fats and protein increased almost linearly with increasing incomes. Carbohydrate intake, on the other hand, made up approximately 65 percent of energy from diets in poor nations this is because carbohydrates are a cheap source of energy with the percentage declining in wealthier nations. Regarding smoking, the decision to smoke in women depends not only on GDP or wealth but also on cultural factors, including religion. In men, there is a clear inverse
Recreational exercise alone wont solve the obesity epidemic problem.
relationship between GDP and wealth and smoking status. Approximately 45 percent of men in the poorest countries smoke compared with 20 percent of men in the richest countries. Men started smoking at approximately the same age and frequency in all countries, but the rate of quitting is markedly higher in higher-income countries. This is important because the focus of smoking should be on quitting. Its the people who are alive today and who are smoking today who will die in the next 40 years from tobacco. If you can get people to quit, then the children will not start. This is what we call epidemiological transition, and this is what determines risk factors. In terms of physical activity, the amount of recreational physical activity increased with increasing GDP and wealth, but
October 2012
Forum
demic really requires a change in environment. We can yell at people and say, exercise 30 minutes a day. But it is not going to be enough. Its about one-fourth of the difference of lost physical activity which means that in the future, we will all be on treadmills. While there are creative solutions, the key point is to understand that recreational exercise wont solve the problem and the entire environment needs to be redesigned. Thats where policy comes in. We really need to create the right environment.
this increase was offset by a reduction in the amount of obligatory physical activity that is transport-related, job related and household-related activity required for physical labor. Overall, the net result was a reduction of approximately 2,000 [metabolic equivalent task] METS/minute/week, or 2.7 hours of brisk walking every day, among countries with higher incomes. There is no way unless you are a marathon runner that we are going to overcome the decrease in activity due to the changing environment. The obesity epi-
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The 100 very Academic first joint scientific sessions Nearly Speakers, with the American Thoracic Society 15 Sessions and 6 Special Topics
American Thoracic Society (ATS)

Keynote Speakers: English Sessions Highlights

Prof. Chunxue Bai President of the 8th ISRD & ATS in China Forum 2012 Professor of Medicine and Chairman of Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University Prof. Monica Kraft President of American Thoracic Society Professor of Medicine, Vice Chair of Research for Department of Medicine and Director of the Duke Asthma, Allergy and Airway Center at Duke University Medical Centre Dr. Asrar Malik Distinguished Professor and Head of the Department of Pharmacology, University of Illinois College of Medicine Schweppe Familly Distinguished Professor of Pharmacology
Mechanical Ventilation Sleep Apnea Update Biomarkers and Therapeutic Strategies in Airway Diseases State-of-the-art Ventilation Strategy Highlight on COPD Management ALI Forum - Mechanism and New Drug Target Plenary Session - Message from ATS Infection and Immunity Translational Respiratory Medicine
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UBM Medica Shanghai E-mail: secretariat@isrd.org
October 2012
Singapore Focus
Genes linked to glaucoma
esearchers in Singapore have discovered three genes associated with a type of glaucoma that is a leading cause of blindness among Chinese people. A genome-wide association study compared 1,854 cases of Primary Angle Closure Glaucoma (PACG) with 9,608 controls across five sample collections in Asia and verified the findings with a further 1,917 PACG cases and 8,943 controls from another six sample collections. Three new genetic loci were reported to have strong associations with PACG. The disease occurs when the intraocular pressure builds because the iris bends forward and prevents fluid from draining out of the eye. It affects about 15 million people worldwide, a majority of whom are Asians. Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG, the researchers said. The research was a collaboration between the Singapore Eye Research Institute, Singapore National Eye Centre, Genome Institute of Singapore, National University of Singapore, National University Hospitals Department of Ophthalmology and Tan Tock Seng Hospital.
HSA launches clinical trials registry
he Health Sciences Authority (HSA) in Singapore recently launched a complete registry of all clinical trials conducted in Singapore. The registry will be an easy portal for patients to find appropriate clinical trials to join and receive potentially expensive treatments for little to no cost or to seek new treatment options when their current ones are not working. The registry may help boost the number of local participants in clinical trials, who have often been culled from overseas. It is also an important tool for demonstrating to pharmaceutical companies that Singapore is an efficient and regulated place to get clinical trials approved and set up quickly. The registrys current list includes about 370 trials and the database is sortable by product, sponsor, trial location and therapeutic area.
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October 2012
Singapore Focus
Singaporeans have poor diabetes self-management

ingaporeans with type 2 diabetes report poor habits and a low level of interest in managing their diabetes, according to a survey of 157 local patients. Its complacency and not wanting to know more, said Dr. Kevin Tan Eng Kiat, consultant endocrinologist and vice president of the Diabetic Society of Singapore. There is the patients own inertia and doctors not being able to tell them what [metrics] are very important to know. The survey was carried out at diabetes walk-in centers in 2011. The majority of respondents had been diagnosed for between 2 and 10 years. Less than 20 percent of respondents were aware of the key metrics of blood glucose, including HbA1c, fasting plasma glucose, and postprandial glucose, and what they indicated. Seventy-six percent of respondents were not sure or not interested to know more about these measurements. We have to educate doctors that these are important things patients should know, Tan said. The survey was a joint effort between the Diabetic Society of Singapore, AstraZeneca and Bristol-Myers Squibb.
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references: 1. Decramer M. Tiotropium as essential maintenance therapy in COPD. Eur Respir Rev. 2006;15:5157. 2. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2010. www.goldcopd.org. Accessed June 24, 2011. 3. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128-1138. 4. ODonnell DE, Flge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23(6):832-840. 5. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19(2):217-224. 6. IMS Health Data, Q2 2011. 7. Vogelmeier C, Hederer B, Glaab T, et al; for the POET-COPD Investigators. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011;364(12):1093-1103. 8. Troosters T, Celli B, Lystig T, et al; for the UPLIFT Investigators. Tiotropium as a first maintenance drug in COPD: secondary analysis of the UPLIFT trial. Eur Respir J. 2010;36(1):65-73. 9. Tashkin DP, Celli B, Senn S, et al; for the UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;9(15):1543-1554. 10. Data on file. Boehringer Ingelheim International GmbH; 2009. 11. Data on file. Boehringer Ingelheim International GmbH; 2011. 12. Tonnel AB, Perez T, Grosbois JM, Verkindre C, Bravo M-L, Brun M; for the TIPHON study group. Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD. Int J Chron Obstruct Pulmon Dis. 2008;3(2):301-310.
SPIRIVA was developed by Boehringer Ingelheim and is being copromoted by Pfizer Inc
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For medical professional only.
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October 2012
Singapore Focus
Osteoarthritis training workshops target GPs

Rajesh Kumar
newly established expert panel on osteoarthritis (OA) is intended as an educational resource for Singapore GPs. The panel, comprising a sports medicine physician, an orthopaedic surgeon, a rheumatologist and a GP specializing in OA, is organizing a series of training workshops to help GPs refresh their knowledge base and expertise on the subject. Two upcoming training sessions are planned for 20 October at Singapore General Hospital (SGH) and 23 November at Changi General Hospital (CGH).
We all experience aches and pains but it could be something more serious
patients sometimes dont realize that
The panel members will also act as expert media commentators on OA to raise public awareness on the importance of early detection and various treatment options. OA affects an estimated 40 percent of Singaporeans at some stage of their lives and, according to SingHealth, only about 10 percent seek treatment. We all experience aches and pains but patients sometimes dont realize that it could be something more serious. So they dont discuss it with their primary healthcare physician, said Dr. Darryl Chew, GP at the E Medical Clinic and a member of the expert panel. The lack of awareness among patients could be one very real reason why OA can go
undiagnosed, and unfortunately untreated, until the disease further progresses to a much worse severity. OA is common among the elderly over 70 years of age due to gradual deterioration of joint cartilage. Young people who are active in high-impact sports are also at higher risk due to meniscus damage sustained from sports injuries. But young patients think knee OA cant affect them. In case of aches and pains, they apply ice packs and muscle creams, and take NSAIDs thinking it will go away in time. This delays their diagnosis and worsens the symptoms, said Chew. Early detection can not only help slow disease progression, but may also delay the need for the most aggressive interventions such as joint replacement surgery. NSAIDs, surgery and physical therapy are the most commonly prescribed treatments, but the expert panel plans to also raise awareness about viscosupplementation which helps delay disease progression and manage chronic pain. Obesity, a sedentary lifestyle, genetics and improper exercise techniques are among the main culprits, which need to be adequately addressed for a long term resolution of patients pain and suffering. Other members of the panel include Dr. Benedict Tan, sports medicine physician at CGH, Dr. Darren Tay, orthopaedic surgeon at SGH, Dr. Carol Tan, geriatrician at Raffles Hospital, and Dr. Yoon Kam Hon, rheumatologist at the Arthritis and Rheumatism Specialist Medical Centre.
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October 2012
Singapore Focus
and couples should be seeking and receiving when planning to start a family, especially for those facing difficulty in conceiving, said Wong. These results also highlight the need for more public education and awareness on the impact of age and medical problems on fertility, as well as the infertility treatment options available, he added. Many women believed that fate plays a part in fertility problems. In Singapore, 59 percent of women believed that infertility is Gods will and 42 percent attributed it to bad luck. The single greatest barrier to seeking help in Singapore, Korea, Hong Kong and Taiwan is the perceived high cost associated with fertility treatment, although the Singapore government subsidizes up to three IVF cycles. Asian countries have among the lowest fertility rates in the world and the declining birth rates are a cause for concern. Merck Serono commissioned the study to better understand Asian womens decision-making considerations around having a baby. Insights from this study will (hopefully) assist healthcare professionals and policy makers in addressing this acute challenge, said Mr. Tim Kneen, Merck Serono regional vicepresident for Asia Pacific.
Knowledge gaps in Asian women on fertility

Rajesh Kumar
recent study of 1,000 women across 10 Asian countries, including Singapore, has highlighted critical knowledge gaps on fertility, main causes of infertility and treatment options. Only 36 percent of the women surveyed, all under 35 who were trying to conceive for at least 6 months, understood that women generally have a lower chance of getting pregnant in their 40s, compared with their 30s. Also, only 43 percent knew that a couple is classified as infertile if they fail to conceive after 1 year of trying, while 32 percent knew that a healthy lifestyle does not necessarily guarantee fertility. Researchers also noticed a widespread lack of knowledge about male fertility issues around 40 percent of women did not know that a man may be infertile even if he can achieve an erection and produce sperm. The Starting Families Asia study was commissioned by Merck Serono in collaboration with Professor PC. Wong, senior consultant and head of the division of reproductive endocrinology and infertility at the National University Hospital Womens Centre. The results could be indicative of the potential barriers to the help that women
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October 2012
Singapore Focus
well are more likely to make healthy lifestyle changes recommended by their doctors, said HPB chief executive Mr. Ang Hak Seng. The toolkit was developed as a convenient and user-friendly tool in Singapores four languages to help healthcare professionals proactively give tailored evidence-based health advice to patients who are at risk of developing or mismanaging chronic conditions. It takes into consideration the fact that busy healthcare professionals have limited capacity and time, and is therefore designed to enable them to assess patients quickly and give brief but effective advice, said Ang. HPB is organizing a national conference to share best practices with all health professionals and will conduct capacity building courses for them. By October-end, it also plans to sign Memorandums of Understanding with the Singapore Physiotherapy Association, Pharmaceutical Society of Singapore, and Singapore Association of Occupational Therapists for the development of a health promoting curriculum, engagement of allied health professionals in providing effective health advice and intervention and their mobilization during HPBs outreach efforts to raise health literacy.
HPB launches health choices toolkit for GPs

Rajesh Kumar
he Health Choices Toolkit launched by the Health Promotion Board (HPB) aims to equip GPs and other healthcare professionals with the necessary tools to improve their patients health literacy and help modify their lifestyle risk factors for chronic diseases. Focusing on smoking, obesity, stress and unsafe sexual practices, the kit consists of a practice manual, a tabletop flip chart for use during patient consultation, a poster and information brochures to prompt patients to start or continue conversations about their lifestyle habits and a dedicated webpage for viewing case videos and downloading resources. A Physical Activity Advice Tool (PAAT) is also included to help physicians assess their patients quickly, give brief advice and provide tailored counseling. PAAT takes the 3As brief approach (Ask, Advise and Action) as well as the 5As intensive approach (Ask, Advise, Assess, Assist and Arrange) to counseling and provides clear steps for conducting guided dialogue with patients about making lifestyle changes. Studies show that people who are un-
Dengue drug trial seeks patients

Rajesh Kumar
Ps in Singapore and the neighboring regions of Johor Bahru, Batam and Bintan are being urged to quickly identify and refer patients with dengue fever to SingHealth
for testing the efficacy of a drug against the disease. The double-blind, randomized, placebocontrolled proof-of-concept CELADEN* trial is testing whether celegosivir lowers the amount of viremia and diminishes fever and
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October 2012
Singapore Focus
pain to a greater extent, compared with patients who receive standard care involving fluids and paracetamol. Patients must have confirmed dengue fever of less than 48 hours, be in generally good health, and not be taking blood thinners or have a history of gastrointestinal disorders, said project manager associate professor Cynthia Sung of the program in emerging infectious diseases at Duke-NUS Graduate Medical School, Singapore. Dengue can be confirmed with a simple blood test that takes 10-15 minutes to get the result. Free diagnostic test kits are being made available to GPs who choose to be a part of the trial. GPs are the first line of health care professionals who patients contact when they get dengue, said Sung. The only way to know if celgosivir is an active drug is to study its effects on people who have dengue fever. It would be a world first if we can show activity. At least 50 patients with confirmed dengue will be required to stay at the investigational medicine unit at Singapore General Hospital for 5 days and will need to return for 3 short outpatient visits the following week. The researchers will monitor their blood counts, hematocrit, drug concentrations, and immunological status. All medical care and treatment is free, and patients will receive a generous cash payment. Our challenge is to let the GP communities know the importance of getting patients tested early in the course of disease to determine if they suspect dengue, Sung added. The symptoms of dengue are sudden onset of fever, headache, retro-orbital pain and muscle and joint pain. Symptoms such as watery eyes, nasal congestion or cough typically associated with common influenza or cough and cold are absent in dengue, which could make it easier to distinguish.
Selected patients will receive medical care and treatment for free.
Two other drugs have been tested against dengue chloroquine in Brazil and balapiravir in Vietnam. But neither has shown efficacy against the endemic tropical disease. The Sanofi-Pasteur tetravalent vaccine that was trialed recently showed only 30 percent efficacy, dashing hopes for a viable vaccine in the immediate future. But vaccines are used as a preventative measure and are not useful after a patient has contracted an acute disease like dengue. That leaves celegosivir as the only potential antiviral solution for dengue for the time being, said Sung. CELADEN is funded by the STOP Dengue consortium, from a National Medical Research Council grant. GPs can check out www.celaden.sg or call dengue hotline: +658155 6283 / 6293 for more details.
*CELADEN: Celegosivir as a treatment against dengue
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October 2012
Singapore Focus
Genotyping can help avoid SJS/TEN in epileptic patients

Rajesh Kumar
sian patients with a particular genetic trait have a higher risk of developing StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) when treated with the antiepileptic drugs carbamazepine and phenytoin. But genotyping for human leukocyte agent variant (HLA)-B*1502 allele and providing more expensive alternate anti-epileptic drugs to those who test positive is cost-effective for Singaporean Chinese and Malays, but not for Singaporean Indians, a local research has revealed. The researchers used patient data to develop a statistical model that took into account costs of epilepsy treatments and genotyping, reductions in quality of life and increased costs resulting from SJS/TEN complications, the prevalence of the risk allele, the positive predictive value (PPV) of genotyping, life expectancy, and other factors. [Neurology 2012; 79:1259-1267] The options were treatment with carbamazepine or phenytoin without genotyping or providing more expensive drugs that do not induce SJS/TEN to all patients without genotyping. Compared with no genotyping and providing carbamazepine to all, genotyping at the cost of $205 per patient results in an incremental cost-effectiveness ratio of $38,620/qualityadjusted life year (QALY) for Chinese patients, $8,420/QALY for Malays, and $122,530/QALY for Indians in Singapore, said researcher Ms. Dong Di of the Duke-NUS Graduate Medical School, Singapore. Lower amount denotes higher cost-effectiveness. With an odds ratio of 1,357, PPV of 5.6 per-
Genotyping is cost-effective for Singaporean Chinese and Malays
cent and negative predictive value of 99.9 percent, the HLA-B*1502 testing can have applications for the Han Chinese, Malaysians and south Indians in other countries. The allele is absent among US Caucasians, Hispanics, native Americans and Africans, but has 5 percent to 27 percent prevalence in the Han Chinese, Malays, Thais, Filipinos and Vietnamese. However, the absence of this allele in other groups does not mean they cannot develop SJS/TEN, cautioned Associate Professor Eric A. Finkelstein, deputy director of the Health Services & Systems Research Program at Duke-NUS. Also, lack of cost-effectiveness is no reason to not offer targeted therapy to low-risk Singaporean Indians who could potentially pay for higher treatment costs to avoid SJS/TEN altogether, said Finkelstein. Carbamazepine and phenytoin are also used for trigeminal neuralgia, bipolar disorders and other neurological conditions and the same evidence on cost effectiveness can guide treatment decisions in those Asian patients.
16
October 2012
Singapore Focus
Extended-release metformin makes dosing easier

Radha Chitale
n extended-release version of metformin reduces the number of medication doses type 2 diabetes patients need to take each day. The formulation, a combination therapy with the DPP-4 inhibitor saxagliptin is now available in Singapore and should be on the market within a few months. This is the first and only fixed dose combination that can be dosed once a day, said Dr. Nancy Bohannon, director of Clinical Research at the Cardiovascular Risk Reduction Program at St. Lukes Hospital in San Francisco, California, US. That really improves the compliance to the medication. The proportion of Singaporeans with diabetes increased from 8.2 percent in 2004 to 11.3 percent in 2010, according the 2011 National Registry of Diseases. Almost half of Singaporeans with diabetes are unaware they have the disease. Current international guidelines recommend metformin monotherapy plus diet control and increased exercise as initial therapy.
However, if the blood sugar indicator HbA1c level is above 7.6 percent, combination therapy (metformin plus a DPP-4 inhibitor) is recommended as first line therapy in addition to lifestyle changes. [Diabetes Care 2009;32:193203; Endocr Pract 2009;15:540-559] A 2009 trial comparing metformin plus saxagliptin with metformin plus placebo in treatment-naive diabetic patients demonstrated an HbA1c reduction of 2 percent with metformin alone and 2.5 percent with metformin/saxagliptin combination therapy. [Diabetes Obes Metab 2009;11:611-622] The results showed that 60 percent of patients reached target HbA1c levels (<7 percent) on combination therapy compared with 41 percent of those on metformin alone. The trial used the immediate release form of metformin but this was determined to be bioequivalent to extended-release metformin, Bohannon said. Adverse effects of extended-release metformin, in particular gastrointestinal effects, were determined to be less severe than those of immediate-release metformin.
Kidney cancer rate on the rise in Singapore

Elvira Manzano
octors have sounded the alarm over the increasing number of kidney cancer cases being seen in Singapore. Cases have gone up by 80 percent since 2003, and advanced kidney cancer accounts
for 30 percent of all kidney cancers in the country. Prior to 2005, kidney cancer did not factor in the top 10 cancers in Singapore. Now, it is the ninth most common cancer in men in Singapore, mirroring what is happening in the West, said Dr. Tan Min Han, an oncologist
17
October 2012
Singapore Focus
from the National Cancer Centre Singapore (NCCS). Even more worrying is that approximately 20 percent of patients present in an advanced stage. Tan said the increase is partly due to increased detection of tumors on computed tomography (CT) scans. More cases are being picked up at early stages. Tumors as small as 3-5 cm that might have gone unnoticed, or cannot be palpated by physicians just like in breast cancer, can be detected by the scan. As a result, doctors are now seeing more cases of kidney cancer about 160 to 200 cases a year compared with 60 to 70 cases in 1997. Rising obesity rates and smoking are the two other most common reversible factors that contribute to the increase, Tan said. A healthy weight and smoking prevention can therefore cut the risk. Other risk factors are age, gender, family history, hypertension, long-term dialysis and genetic syndromes. Incidence rates peak between 60 to 70 years of age. Men have 1.5 times higher risk than women. Once metastatic disease develops, 5-year survival is from 0 to 20 percent, and half of patients undergoing curative surgery are likely to experience relapse at distant sites. Kidney cancer is unpredictable, however there are new therapeutic options available for patients, said Dr. Tay Miah Hang, consultant medical oncologist at OncoCare Cancer Centre, Singapore. Renal cell carcinoma, although highly resistant to radiotherapy and chemotherapy, can be treated. Life expectancy can be prolonged and complications arising
from disease progression can be reduced. Pazopanib, the sixth targeted therapy approved for the treatment of advanced kidney cancer, blocks the growth of new blood vessels needed for tumor development. In a study involving 435 patients with advanced kidney cancer, treatment with pazopanib achieved median progression-free survival (PFS) of 9.2 months vs. 4.2 months for placebo (HR 0.46, P<0.001). The effect was observed both in treatment-nave patients (HR 0.40) and in those pre-treated with cytokine therapy (HR 0.54). [J Clin Oncol 2010;28:1061-1068] As with all medications, pazopanib has its own side effects including diarrhea, hypertension and hair color changes, Tay said. Patients with advanced kidney cancer should consult their doctors as to what medication may work best for them. As for Singapores aging population who are at risk, he said early diagnosis is recommended.
18
October 2012
Singapore Focus
18/10/12
Singapore Events
16/10/12
GP-CME Management of Diabetic Nephropathy

Info : National Healthcare Group (NHG) Polyclinics Tel : +65 6896 2071 Website : http://www.nhg.com.sg/events. asp?eventgroup=4 16/10/12
GP-CME Constipation in the Elderly

GP-CME Updates in COPD Management

GP-CME Management & Referrals of Common Skin Conditions

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GP Workshop Knee Osteoarthritis/ Viscosupplementation Injector

Location : St Andrews Community Hospital, Seminar Room, Level 2 Time : 1:00 PM to 4:30 PM RSVP : jamie_chen@cgh.com.sg by 9/11/12
GP-CME Updates in COPD Management

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19
October 2012
Conference Coverage
European Society of Cardiology Congress, 25-29 August, Munich, Germany
Aspirin can be dropped in PCI patients on oral anticoagulants

Christina Lau
atients on oral anticoagulants (OAC) undergoing percutaneous coronary intervention (PCI) should be treated with clopidogrel, but not aspirin, according to the first randomized trial to assess optimal antithrombotic therapy in this high-risk group of patients. The trial showed that dual therapy with OAC and clopidogrel causes less bleeding than triple therapy with OAC, aspirin and clopidogrel, and is safe with respect to preventing thrombotic and thromboembolic complications. Long-term OAC therapy is obligatory in most patients with atrial fibrillation (AF) and in those with mechanical heart valves. Over 30 percent of these patients have concomitant ischemic heart disease and, if they need to undergo PCI, aspirin and clopidogrel are indicated, said lead investigator Professor Willem Dewilde of the TweeSteden Hospital in Tilburg, the Netherlands. Until now, no prospective randomized data were available on the optimal antithrombotic therapy for these patients, he continued. Although triple therapy seems logical for the prevention of stroke and stent thrombosis, it often causes serious bleeding complications and the need to discontinue aspirin and clopidogrel. The WOEST* study included 573 patients from the Netherlands and Belgium, who were already on OAC for AF or mechanical valves and were undergoing PCI. The primary endpoint was occurrence of all bleeding events after 1 year, classified according to the TIMI (Thrombosis in Myocardial Infarction) bleeding criteria. Second-
ary endpoints were the combination of stroke, death, MI, stent thrombosis and target vessel revascularization, and all individual components of the primary and secondary endpoints. At 1 year after PCI, patients in the dual therapy group had significantly lower incidence of bleeding (19.5 vss 44.9 percent; HR=0.36; P<0.001] and overall mortality [2.6 vs. 6.4 percent; HR=0.39; P=0.027) than those in the triple therapy group, reported Dewilde. They had no increase in thrombotic or thromboembolic events compared with those on triple therapy. Although the trial was open-label and had a limited number of patients, Dewilde suggested that the findings have important implications for future treatment and guidelines. We propose that a strategy of OAC plus clopidogrel, without aspirin, could be applied in this group of highrisk patients on OAC when undergoing PCI, he said. Commenting on the findings, discussant Dr. Marco Valgimigli from Ferrara, Italy pointed out that one bleeding event could be avoided by omitting aspirin in only four patients. While the reductions were mostly in minimal [6.5 vs. 16.7 percent] and minor bleeding [11.2 vs. 27.2 percent], the difference in major bleeding between the dual and triple therapy groups might have become significant with larger numbers, he said. With the important findings from WOEST, the taboo of discontinuing or omitting aspirin in the contemporary environment has been broken.
*WOEST: What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing
20
October 2012
Conference Coverage
difference vs. valsartan was no longer significant. Patients treated with LCZ696 also had reduced left atrial size and improved symptoms (as measured by New York Heart Association [NYHA] Functional Classification), both of which became significant vs. valsartan by week 36. LCZ696 was generally well tolerated, with fewer serious and overall adverse events than valsartan, said Solomon. Results from PARAMOUNT are encouraging, and LCZ696 is currently being tested in a trial of 8,000 HF patients with reduced ejection fraction. In another study, spironolactone was shown to improve cardiac function and structure, and reduce neuroendocrine activation in 422 patients with symptomatic diastolic HF. In the international phase IIb AldoDHF trial, 12-month treatment with the aldosterone receptor antagonist improved diastolic function, induced structural reverse remodeling, and reduced NT-proBNP levels and blood pressure compared with placebo, reported Professor Burkert Pieske of the Medical University of Graz in Austria. However, the treatment did not improve exercise capacity, NYHA class or quality of life. Spironolactone was shown to be safe, without severe adverse events. The drug can be considered in patients with diastolic HF, for improving cardiac function and blood pressure control, suggested Pieske.
*PARAMOUNT = Prospective compArison of ARNI with ARB on Management Of heart failUre with preserved ejectioN fraction **Aldo-DHF = Aldosterone Receptor Blockade in Diastolic Heart Failure
Investigational drug shows promise in HF

Christina Lau
novel angiotensin receptor neprilysin inhibitor LCZ696 has demonstrated beneficial effects in heart failure (HF) patients with preserved ejection fraction in a phase II trial. LCZ696 is a first-in-class agent comprising the molecular moieties of a neprilysin inhibitor and the angiotensin receptor inhibitor (ARB) valsartan as a single compound. Its dual mechanism of action is believed to restore the altered neurohormonal balance in HF with preserved ejection fraction. In the PARAMOUNT* study, the efficacy and safety of LCZ696 was compared with that of valsartan in 308 patients from 13 countries. [Lancet 2012; DOI:10.1016/S01406736(12)61227-6] HF with preserved ejection fraction accounts for up to half of HF cases, and is associated with substantial morbidity and mortality. However, no therapies have been shown to improve clinical outcomes in this condition, said lead investigator Professor Scott Solomon of the Harvard Medical School and the Brigham and Womens Hospital in Boston, Massachusetts, US. Results showed that after 12 weeks of therapy, LCZ696 significantly reduced levels of NT-probBNP by 23 percent compared with valsartan (P=0.005). NTproBNP is a marker of cardiac wall stress, and levels are increased in HF patients, explained Solomon. The greater reduction in NT-proBNP achieved with LCZ696 was sustained to 36 weeks, although the
21
October 2012
Conference Coverage
Niacin/laropiprant well tolerated in HPS2-THRIVE trial

Alexandra Kirsten
ore than three-quarters of patients taking long-term extended release niacin/laropiprant (ERN/LRPT) in the HPS2-THRIVE* trial have tolerated treatment, according to preliminary results. HPS2-THRIVE is the largest study so far to assess whether adding ERN/LRPT to statin therapy can further lower cardiovascular risk. In the trial, a total of 25,673 patients with occlusive arterial vascular disease from the UK, Scandinavia and China were randomized to receive long-term treatment with either ERN/LRPT 2 mg or placebo, in addition to simvastatin therapy. The primary endpoint included major vascular events after a median follow-up of 4 years. The preliminary results suggest that about 76 percent of the patients can tolerate long-term ERN/LRPT treatment. A safety analysis suggested that myopathy occurred in 0.5 percent of patients treated with simvastatin 40 mg and ERN/LRPT, however, the vast majority of these cases were found in patients with Chinese descent.
Niacin has been shown to be an effective HDL-raising agent.
The preliminary results
suggest that about 76 percent LRPT treatment
of the patients can tolerate long-term ERN/
These observations have resulted in a label change for simvastatin and ERN/LRPT, explained lead study author Professor Jane Armitage, consultant in Public Health
Medicine at the University of Oxford, England, addingthatpatientsofChinesedescentshouldnot receive simvastatin 80 mg with cholesterolmodifying doses of niacin-containing products. Niacin did not show any clear adverse effects on the liver in the trial, but known cutaneous and gastrointestinal side effects were confirmed. Niacin has been shown to be an effective HDL-raising agent, but randomized trial evidence for beneficial cardiovascular effects is limited. Most previous studies have been performed using fibrates, which raise HDL cholesterol only modestly, and those studies produced mixed results. Moreover, the tolerability of niacin has been limited by flushing and cutaneous side-effects, which appear to be mediated largely by prostaglandin D. These side effects can be substantially reduced by laropiprant, a selective prostaglandin D receptor antagonist. Further results from the HPS2-THRIVE are expected to be released in 2013.
*HPS2-THRIVE: Heart Protection Study 2 -Treatment of HDL to Reduce the Incidence of Vascular Events
22
October 2012
Conference Coverage
European Society of Cardiology Congress, 25-29 August, Munich, Germany
Aliskiren use not advised in type 2 diabetics with renal impairment

Alexandra Kirsten
liskiren, a direct renin inhibitor, should not be used to lower blood pressure in type 2 diabetics at high risk of cardiovascular and renal events, according the findings of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). The treatment may even be harmful in these patients, said lead study author Professor Hans-Henrik Parving from the University of Copenhagen, Denmark In the ALTITUDE study, a total of 8,561 patients with type 2 diabetes and renal impairment were randomized to double-blind treatment with either aliskerin 300 mg or placebo once daily, in addition to an angiotensin coverting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). The primary analysis was the time to the first event for the composite endpoint of cardiovascular death, resuscitated death, non-fatal myocardial infarction and stroke, unplanned hospitalization for heart failure, onset of end-stage renal disease or doubling of baseline creatinine. After the monitoring committee found an increased rate of side effects associated with active treatment, the trial was stopped prematurely. At a median follow-up of 32 months, the primary endpoint had occurred in 767 patients taking aliskiren (17.9 percent) and in 721 assigned to placebo (16.8 percent) [95%
Aliskiren may do more harm than good in type 2 diabetics with renal problems.
CI 0.98-1.20, P=0.14]. Corresponding rates of stroke in each group were 3.4 percent and 2.7 percent, respectively (95% CI 0.98-1.60, P=0.070). Laboratory results showed albuminuria levels to be 14 percent lower in aliskirentreated patients, while increases in serum creatinine appeared similar in the two groups. Patients in the aliskiren group experienced significantly increased serum potassium levels of 6 mmol/L (8.8 percent vs. 5.6 percent for placebo), and higher rates of hypotension (12.1 percent vs. 8.0 percent, respectively). These results do not support the administration of aliskiren on top of standard therapy in type 2 diabetic patients at high risk for cardiovascular and renal events, concluded Parving. Aliskiren is the first in the class of drugs called direct renin inhibitors. It was approved in 2007 in the EU and US under the brandnames Rasilez and Tekturna, respectively, for the treatment of essential (primary) hypertension either as monotherapy or in combination with other medications.
ACE inhibitors
- The treatment of choice to reduce overall cardiovascular risk in hypertension management

The renin-angiotensin-aldosterone system (RAAS) plays a key role in regulating blood pressure and its inhibition is one of the important anti-hypertensive strategies. At a recent symposium in Singapore, renowned cardiologist Professor Frank Ruschitzka, presented clinical evidence from large scale randomised clinical trials establishing angiotensin-converting-enzyme (ACE) inhibitors to be the number one choice for hypertension and cardio-protection.
ACE inhibitors versus ARBs: Myths and Facts
Professor Frank Ruschitzka
Heart Failure/Transplantation Clinic University Clinic Zurich Switzerland
or left ventricular dysfunction, which reported a significant reduction of 14% in all cause mortality, 19% in cardiovascular mortality, 18% in myocardial infarction, and a 23% reduction in stroke.2 In addition, there was a 42% reduction in cardiac arrest, an 8% reduction in myocardial revascularization and a 24% reduction in hospitalization for heart failure with ACE inhibitor based treatment.2
reduction in recurrent stroke in the PROGRESS trial over four years [Figure 2].5 The combination has also been associated with significant reduction in all cause mortality in type 2 diabetes patients in the ADVANCE randomised controlled trial.
The Class Effect Myth: Are ACE inhibitors and sartans created equal?
In contrast, in the TRANSCEND trial, ARB telmisartan based therapy failed to prevent cardiovascular death, myocardial infarction, stroke, or heart failure hospitalisation in ACE inhibitor intolerant subjects with cardiovascular disease when compared to placebo.7 Further in the PRoFESS study, telmisartan compared to placebo did not significantly lower the rate of recurrent stroke. Similarly, in the NAVIGATOR trial, valsartan therapy over 5 years did not reduce the rate of cardiovascular events for patients with impaired glucose tolerance and established cardiovascular disease or risk factors.9 Of particular concern is the increased risk of myocardial infarction and a trend towards increased risk of stroke reported with valsartan as compared to amlodipine based therapy in the VALUE study on hypertensive patients with high cardiovascular risk.10 More recently in the ACTIVE I trials, the study investigators concluded that irbesartan did not reduce cardiovascular events in patients with atrial fibrillation.11 Cough is one of the troublesome side-effects of ACE inhibitor therapy; however this often resolves over time, and the rate of treatment discontinuation due to cough remains low. In contrast side-effects such as hypotension and renal causes, which are more frequently associated with ARB therapy than ACE inhibitors, results in permanent treatment discontinuation in greater proportion of patients, as reported in the VALIANT study.12
The pathophysiology of hypertension involves several factors and its management necessitates an individualised approach; with treatments tailored to an individuals patient profile. International consensus guidelines recommend the stratification of cardiovascular risk of individual patients to quantify prognosis as well as to determine an optimal treatment approach based on individual risk profile. For example a patient with Grade 1 hypertension (SBP: 140-159; DBP: 90-99) with no other additional risk factors would be advised to make lifestyle changes for several months before a drug treatment was initiated. However, a patient having similar Grade 1 hypertension with concurrent presence of three or more risk factors or diabetes would require immediate drug treatment and intensive lifestyle changes.
Preferred combination approach to hypertension management

Since several mechanisms are involved in the pathogenesis of hypertension; most patients require combination therapy to ensure optimal blood pressure control. Due to their complementary modes of action, ACE-inhibitors and calcium antagonists are the combination therapy of first choice.3 This was demonstrated in the ASCOT-BPLA, a multicentre randomized controlled trial in 19,257 patients with hypertension and at least three other cardiovascular risk factors who were randomised to amlodipine plus perindopril or atenolol and bendroflumethiazide based therapy. Following 5.5 years follow up, patients on the perindopril and amlodipine combination reported significantly fewer fatal and non-fatal stroke (P=0.0003), total cardiovascular events and procedures (P<0.0001), and all-cause mortality (P=0.025) as compared to those patients on atenolol and thiazide diuretic based regimen. Patients on perindopril plus amlodipine were also less likely to develop new onset diabetes, renal impairment and cardiovascular events and procedures [Figure 1].4 The combination of perindopril and thiazide like diuretic indapamide has also demonstrated meaningful
Figure 1: Benefits of Perindopril/Amlodipine over Atenolol/Diuretic (ASCOT) in hypertensive patients at risk (N = 19,257)4 Total
Nonfatal MI + CHD death Cardiovascular mortality Total mortality Total coronary events Fatal and nonfatal stroke cardiovascular events and procedures New-onset diabetes mellitus Renal impairment
The evidence underscores that hypertension cannot be treated in isolation as just blood pressure. It is part of the whole cardiovascular continuum and the ultimate treatment goal should be to reduce overall morbidity and mortality
Role of RAAS targeted therapy in the management of hypertension
Angiotensin II plays a central role in organ damage; treatment of hypertension should thus focus on reducing angiotensin levels. ACE inhibitors and angiotensin receptor blockers (ARB) are the two main drug classes that act on the RAAS. However, while ACE inhibitors reduce angiotensin II levels and increase bradykinin; ARBs have an antagonist action only on AT1 receptors, one of the four types of angiotensin receptors present.
0 -5
Percentage
-10 -15 -20 -25 -30 -35
-10%
-11%
-13% -23%
Conclusion
-16% -15%
-24%
The ASCOT patient: Hypertention with 3 or more CV risk factors
-30%
P. Sever, Lancet 2005
Figure 2: Perindopril/Indapamide Prevents Stroke (PROGRESS) in post stroke patients (N=6105)

Proportion with stroke (%)
20 15 10 5 0 0 1 2 3 4
Moreover, receptor blockade by an ARB conversely triggers substantial increase in angiotensin II levels
The benefits of ACE inhibitor therapy in reducing cardiovascular risks was demonstrated in the EUROPA, wherein 12,218 patients with stable coronary artery disease and no apparent heart failure were randomized to receive an ACE inhibitor perindopril or a matching placebo. After a mean follow-up period of 4.2 years, treatment with perindopril was found to confer a 20% relative risk reduction in cardiovascular death, myocardial infarction, or cardiac arrest.1 This has been further corroborated in a meta-analysis of ACE inhibitor trials in coronary artery disease patients without heart failure
f/u 3.9y RRR - 28% ARR -3.7% NNT 27
An overview of the current evidence base confirms that ACE inhibitors, especially perindopril, are the treatment of choice for hypertension. When a combination of agents is required for optimal cardiovascular risk reduction, concurrent therapy of perindopril with calcium channel antagonist (such as amlodipine) and a statin may be considered ideal.
References
1. Fox KM, et al. Lancet. 2003 Sep 6;362(9386):782-8. 2. Danchin N et al. Arch Int Med. 2006;166:787-796. 3. 2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press. 2007;16(3):135-232. 4. Dahlf B, et al. Lancet. 2005 Sep 10-16;366(9489):895-906. 5. PROGRESS Collaborative Group. Lancet. 2001 Sep 29;358(9287):1033-41. 6. Patel A; et al. Lancet. 2007 Sep 8;370(9590):829-40. 7. Yusuf S, et al. Lancet. 2008 Sep 27;372(9644):1174-83. 8. Yusuf S, et al. N Engl J Med. 2008 Sep 18;359(12):1225-37. 9. McMurray JJ et al. N Engl J Med. 2010 Apr 22;362(16):1477-90. 10. Julius S, et al. Lancet. 2004 Jun 19;363(9426):202231. 11. Connolly SJ. N Engl J Med. 2011 Mar 10;364(10):928-38. 12. Pfeffer MA, et al. N Engl J Med. 2003 Nov 13;349(20):1893-906.
Placebo P<0.0001 Perindopril Indapamide
Follow-up (years)
Figure 3: Perindopril/Indapamide reduces All-cause Mortality in type 2 Diabetes (ADVANCE); (N=11,140)6

Cumulative incidence (%)
20
HR 0.86 (95% CI 0.75-0.98), P=0.025 Placebo

10
Perindopril-indapamide
0 0 6 12 18 24 30 36 42 48 54 60
Sponsored as a service to the medical profession by Servier. Editorial development by UBM Medica. The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage howsoever arising is hereby disclaimed. 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced by any process in any language without the written permission of the publisher. UBM Medica Asia Pte Ltd 3 Lim Teck Kim Road, #10-01 Genting Centre, Singapore 088934 Tel: (65) 6223 3788 Fax: (65) 6221 4788 E-mail: enquiry.sg@ubmmedica.com Website: www.ubmmedica.com
Number at risk
Placebo 5571 Pre-ind 5568 5535 5533 5493 5500 5433 5455
Follow-up (months)
5397 5416 5340 5377 5282 5334 5211 5277 4955 5014 2126 2165
EUROPA = European Trial on Reduction of cardiac events with Perindopril in stable coronary artery disease. ASCOT-BPLA = Anglo Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm. PROGRESS = Perindopril pROtection aGainst REcurrent Stroke. ADVANCE = Action in Diabetes and Vascular Disease: PreterAx and DiamicroN MR Controlled Evaluation. TRANSCEND = Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease. PRoFESS = Prevention Regimen for Effectively Avoiding Second Strokes. NAVIGATOR = Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research. VALUE = Valsartan Antihypertensive Long-term Use Evaluation. ACTIVE I = Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events. VALIANT = VALsartan In Acute myocardial iNfarcTion.
24
October 2012
Conference Coverage
European Respiratory Society Annual Congress, 1-5 September, Vienna, Austria
Long-distance running raises pulmonary edema risk

Dr. Yves St. James Aquino
recent study found that marathon running can trigger pulmonary edema, which may be associated with physical signs of breathlessness, severe cough and heart attack or respiratory failure in severe cases. Marathon running is worldwide. Halfa-million people ran the marathon in the United States this past year and in 2010. And therefore, this is a big topic, said lead author Dr. Gerald Zavorsky. Researchers from the US and Italy aimed to determine if pulmonary edema develops from long-distance running, characterizing its incidence and severity. In addition, researchers wanted to determine if the resulting edema is related to finishing time. The study involved 26 runners who participated in the 2011 Steamtown Marathon held in Scranton, Pennsylvannia, US. The marathon started at an elevation of 452 meters above sea level, with a net drop to 291 meters at the finish line. The study noted that all runners finished with times between 142 and 289 minutes. To quantify the presence of edema, posteroanterior and lateral chest radiographs of the runners were taken the day before the race, then 19, 56 and 98 minutes after finishing the race. Three radiologists were tasked to do the radiograph interpretation. The readers worked independently and were not in contact with each other. They were also not told
Half of runners tested within 20 minutes of completing a marathon had some level of pulmonary edema.
which radiographs were taken before or after the race. Four radiographic characteristics were assessed, including peri-bronchial cuffing, loss of definition of vascular markings, pulmonary opacification and blurring of hilar silhouette. The quantification of edema ranged from 0 or no edema to 8 or severe edema. The scores from each reader were then averaged. Results showed that 50 percent of runners had some level of pulmonary edema 20 minutes after the race, and 20 percent of those runners develop moderate to severe pulmonary edema. In four runners (15 percent), mild to moderate pulmonary edema was even retained 1 hour after finishing the
25
October 2012
Conference Coverage
According to Zavorsky, potential causes may include stress failure of pulmonary capillaries, fluid-electrolyte imbalances, and increased permeability pulmonary edema. However, the most likely cause is increased pulmonary wedge pressure, whereby pressure within pulmonary artery force out fluid into the interstitium. While pulmonary edema can be a negative consequence of marathon running, regular exercise can also keep you fit and healthy. We do not yet know the impact of this finding on long-term health of runners, concluded Zavorsky.
marathon. Upon further evaluation, the study found that women were at 13 times higher risk compared with men in the development of pulmonary edema (odds ratio 12.8, r2 0.31, P=0.038). No correlation was established between marathon time and the development of pulmonary edema, which suggests the risk of edema may be prevalent across all abilities. However, none of these athletes with radiologic finding of pulmonary edema exhibited signs such as difficulty of breathing or coughing of blood.
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26
October 2012
Conference Coverage
Flight hypoxia assessment inappropriate for pediatrics

Dr. Yves St. James Aquino
ritish Thoracic Society (BTS) recommendations on hypoxic flight assessment are not appropriate for pediatric patients, according to a study by UK researchers. The study involved 107 children age 0.1 to 19.2 years who were referred for a variety of conditions including muscular dystrophy, cystic fibrosis, severe asthma, long-term ventilation, long-term oxygen therapy and sleep breathing disorders. The BTS recommendations aim to enhance safety for passengers with lung problems who are travelling by air, reduc ing the number of in-flight emergencies due to respiratory disease. The BTS established upper and lower thresholds for no inflight oxygen required at percutaneous oxygen saturation (SpO2) >95 percent or in-flight oxygen needed at SpO2 <92 percent. The study was a retrospective audit of patients referred to a pediatric respiratory function laboratory. The hypoxic chal lenge test as described by Gong et al suggests the maximum cabin altitude of 2,438 meters (8,000 feet) can be simulated at sea level with a gas mixture containing 15 percent oxygen in nitrogen [Am Rev Respir Dis 1984;130:9806]. According to the researchers, the test protocol used 100 percent nitrogen to dilute the contents of a body plethysmograph to a fraction of inspired oxygen (FiO2) of 15 percent, before assessing the SpO2 profile
for 20 minutes. Based on the BTS criteria, failure in the hypoxic challenge constituted a mean SpO2 of less than 90 percent when breathing FiO2 15 percent. Hypoxic chal lenge testing is the pre-flight test of choice for patients with hypercapnia, according to BTS [ Thorax 2002;57:289304]. Results showed that out of the 107 children, of which 58 percent were female, 83 percent ( N=89) had a baseline SpO2 of greater than 95 percent in FiO2 21 percent. In addition, 29 percent of the patients were noted to be hypoxic in FiO2 15 percent. The study noted that if BTS criteria were to be applied in this pediatric sample, 17 percent ( N =18) would be referred and only 10 percent ( N=11) would be detected with hypoxia at mean SpO2 of <90 percent in FiO2 15 percent. However, if all referrals regardless of the BTS criteria will be assessed, 35 percent would be detected to have hypoxia. For mean SpO2 desaturation to <85 percent, use of BTS criteria would result in detection of 6.5 percent of cases versus all referral detection of 15 percent. Based on the results, the BTS recom mendations for referral for hypoxic flight assessment are not appropriate for pediatrics, according to the study. It added that using sea level SpO2 <95 percent as a cutoff for referring patients will result in detection of fewer patients who desaturate in hypoxic conditions. Researchers concluded that children with respiratory disease should be considered for a hypox ic challenge test irrespective of sea-level SpO2 percent.
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October 2012
Conference Coverage
Personal Perspectives
One of the major activities of the European Respiratory Society is this annual congress and its been steadily growing, growing not only in numbers, its been growing in importance, its growing in global perspective For lung diseases, there is a huge disparity in health care models, huge disparity in how to care for certain patients. Infectious diseases, HIV/AIDS, lung cancer, COPD are diseases that you know occur everywhere. Dr. Klaus Rabe, President, European Respiratory Society, Professor, University of Kiel, Germany
Its been an adventure. Its good because we could just go anywhere we want to go. For the lectures it is subdivided into four topics. If you do not want the next topic, you go to the next hall. We try to find topics that are relevant to our subspecialty. We just attended a pulmonary rehab session, because of the updates and we plan to set up our own program. Dr. Ma. Bernardita Chua, Consultant, Perpetual Succour Hospital of Cebu, Philippines
Its already my fourth ERS, and Im a PhD fellow. The topics of my PhD which I can also follow here are physical activities and comorbidities in COPD patients. There are a lot of sessions I have checked in my personal agenda. They were very good; the symposia especially are very nice. Hans van Remoortel, PhD Fellow, University Hospital Gasthuisberg, The Netherlands
The topics I attended were not too bad. It depends on the subject. Yesterday, I attended four sessions which were very interesting. The topics Im interested in are COPD, pulmonary hypertension, interstitial lung disease and infections. Dr. Masoongo Masoongo, Consultant, Arras Hospital, France
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October 2012
Conference Coverage
First global standards on assessing lung function

Rajesh Kumar
he first global standards on assessing lung function in different age groups and ethnicities, established through international collaboration, promise to revolutionize the way physicians diagnose and manage lung disease. Spirometry is the standard test for measuring lung function. In the absence of a global benchmark for interpreting its results, someone described as abnormal in one clinic can be labeled as normal in another. Also, an adolescent can see his/her level of lung function decrease dramatically when the care is transferred from pediatric to adult clinic. Similar errors can occur if the individual patients ethnicity and associated difference in body composition or stature are not taken into account. Multinational researchers part of the Global Lung function Initiative (GLI) 2012, set up by the European Respiratory Society to establish a consensus on the topic, assessed data from 74,187 healthy nonsmokers aged 3 to 95 years to derive reference spirometric prediction equations for Caucasians (N=57,395), African Americans (N=3,545), and North (N=4,992) and Southeast Asians (N=8,255), including appropriate age-dependent lower limits of normal. [ERJ 2012: DOI: 10.1183/09031936.00080312] Forced expiratory volume in 1 second
(FEV1) and forced vital capacity (FVC) between ethnic groups differed proportionally from that in Caucasians. For individuals not represented by the above four groups, or of mixed ethnicity, a composite equation taken as the average of the above equations was established. The first standard lung growth chart developed as a result of these equations will help better identification of children most likely to benefit from treatment, thereby avoiding unnecessary medication for those who dont need it, said Dr. Janet Stokes of the Great Ormond St Hospital in London, UK, while describing the clinical implications. The chart will also improve diagnosis and management of chronic obstructive pulmonary disease, thus enhancing independence and quality of life in the elderly, said Stokes. The GLI-2012 lung growth chart will also allow patients to understand the health of their lungs and more effectively manage their condition, or take steps to prevent development or progression of lung disease, added Ms. Monica Fletcher, chair of the European Lung Foundation in Sheffield, UK. Subsequent additional data from the Indian subcontinent, Arab, Polynesian, Latin American countries, and Africa will further improve the equations in the future. However, their widespread use will depend on timely implementation by manufacturers of spirometry devices, said the researchers.
29
October 2012
Conference Coverage
Home factors impact on kids asthma medication compliance

Elvira Manzano
amily lifestyle and issues at home may negatively affect childrens adherence to asthma medication. In a study of 93 children with asthma conducted in the Netherlands, 72 percent used >80 percent of prescribed doses for asthma. However, almost 30 percent had poor adherence rates. Barriers to adherence include parental and financial problems, as well as having busy parents. Another common and striking finding was that children (8 to 12 years) were given full responsibility to take their medication without parental support or supervision, resulting in poor adherence. [ERJ 2012. E-pub ahead of print] The findings emphasized how crucial it is for health care professionals treating children with asthma to carefully assess these potential barriers so that appropriate interventions can be put in place to correct the problems, said lead study author Dr. Paul Brand, from the University Medical Centre, Groningen, Netherlands. Good adherence is achievable. In fact, median adherence rate in the study was 93 percent at first month and 90 percent at third month. But when we conducted in-depth interviews on 20 parents, 12 with low adherence and 8 with high adherence, as to what might be preventing their children from following their treatment plan, they presented several lifestyle factors, Brand said.
Some parents do not succeed in getting their kids with asthma to take their meds.
Some parents, the delegators and strugglers, did not succeed in getting their children to take their medication properly. They said a range of things going on in their lives prevented their children from adhering to the treatment plan. Their responses included: when he was 8, we felt that he got to take [the medication] himself. One parent even said: Forcing never works it becomes a struggle, and we never do that. Their answers were compared using an electronic monitoring system. Although parents in the low adherent group expressed intentions to strictly follow the treatment plan at the outset, they failed to do so during the course of the study, Brand said. Struggling families therefore require tailored support.
30
October 2012
Conference Coverage
It can be chaotic having four children and when we have given our son, Alex, responsibility over his medication to control his asthma, we have found his adherence slip away. We are conscious of this now and would encourage other parents to keep a close eye on their childs level of adherence, and to spot potential barriers before they become a problem.
He said comprehensive asthma care may prevent intentional non-adherence, and addressing parental illness and medication beliefs is important. Excessive responsibility for medicines to school-aged children drives non-adherence, he concluded. The results were supported by Mr. David Supple, a parent of an asthmatic child. Speaking about his own experience, he said:
Inhaled glutathione may help cystic fibrosis patients

Radha Chitale
preliminary trial on inhaled glutathione (GSH) showed that it can improve lung capacity in cystic fibrosis (CF) patients with moderate to severe airways obstruction. CF is a chronic genetic disease that causes mucus to build up in the lungs, digestive tract, and other areas of the body, and affects about 70,000 people worldwide, many of them children. Glutathione is an antioxidant therapy used as a first-line defense for the lungs against oxidative stress. Lead researcher Dr. Cecilia Calabrese of Second University of Naples in Italy reported that three previous studies on inhaled GSH in CF patients have shown promising outcomes in terms of forced expiratory volume in 1 second (FEV1) and peak expiratory flow, but these were performed on a limited number of patients and only one study was placebo-controlled. In the current trial, 94 CF patients from Italy over age 6 were divided into a pedi-
atric group (6-18 years) and an adult group (>18 years) and randomized to inhaled GSH (10 mg/kg) or placebo. Patients were excluded from the trial if they demonstrated a decrease in FEV1 greater than 15 percent during a GSH inhalation test, where FEV1 is evaluated before inhalation and 10 and 60 minutes after inhalation. FEV1 was evaluated with spirometry at months 1, 3, 6, 9 and 12. Patients were questioned about their lifestyle, frequency of exacerbations, hospital admissions and antibiotic use at months 1, 6 and 12. Preliminary results showed that inhaled GSH is well tolerated by both pediatric and adult CF patients. Pediatric patients on GSH therapy did not demonstrate significant increases in FEV1 at 3 and 6 months after beginning therapy compared with the placebo group. Mean FEV1 levels at months 0, 1, 3 and 6 were 95.6 22.6 percent, 96.3 23.1 percent, 96.4 19.5 percent and 97.1 20.8 percent in the GSH group, respectively, and 101.1 17.8 percent, 98.3 15.3 percent, 100.4 18.7 percent and
31
October 2012
Conference Coverage
respectively. However, pooled data on all patients with FEV1 80 percent showed that significant improvement persisted 6 months after beginning therapy. Mean FEV1 increased to 62.6 15/1 percent at 6 months from 58.3 13.2 percent at baseline (P=0.04). Preliminary results seem to show that inhaled GSH therapy is able to induce a significant increase of FEV1 in CF patients affected by moderate to severe airway obstruction, Calabrese said.
98.6 19.3 percent in the placebo group, respectively. Adults did show moderate increases in FEV1 with GSH therapy compared with placebo but this trend did not reach significance after 6 months. Mean FEV1 levels at months 0, 1, 3, and 6 were 63.3 15.3 percent, 68.1 17.4 percent, 67.3 16 percent and 67.0 16.5 percent in the GSH group, respectively, and 66.7 21.3 percent, 66.5 18 percent, 64.5 18.9 percent and 64.0 20.2 percent in the placebo group,
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Lactation: Administration should only be considered if the expected benefi t to the mother is greater than any possible risk to the foetus or child. Adverse Reactions: Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. Salmeterol:- tremor, subjective palpitations, oropharyngeal irritation, muscle cramps, headache. Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles) may occur. Fluticasone propionate:Hoarseness & candidiasis (thrush) of the mouth & throat. Possible systemic effects include Cushings syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. Salmeterol/fluticasone propionate clinical trials:- Common: Hoarseness/dysphonia, throat irritation, headache, candidiasis of mouth & throat & palpitations. Overdose: Signs & symptoms of salmeterol overdose include tremor, headache, tachycardia, increases in systolic blood pressure & hypokalaemia. If higher than approved doses of Seretide are continued over prolonged periods, significant adrenocortical suppression is possible. Please read the full prescribing information prior to administration, available from GlaxoSmithKline Pte Ltd, 150 Beach Rd, Gateway West #22-00, Singapore 189720. Tel: +65 6232 8338. Fax: +65 6291 9737. Full prescribing information available on request. Seretide and Accuhaler are trademarks of the GlaxoSmithKline Group of companies. Abbreviated prescribing information based on IPI12SI. oedema & angioedema, bronchospasm & anaphylactic shock. Reports of oropharyngeal irritation & muscle cramps. Fluticasone propionate:- Hoarseness & candidiasis (thrush) of the mouth & throat. Uncommon: cutaneous hypersensitivity reactions. Rare: hypersensitivity reactions e.g. angioedema (mainly facial & oropharyngeal oedema), respiratory symptoms (dyspnoea and/or bronchospasm) & very rarely anaphylactic reactions. Very rare: hyperglycaemia, anxiety, sleep disorders & behavioural changes, including hyperactivity and irritability (predominantly in children). Possible systemic effects include Cushings syndrome, Cushingoid features, adrenal suppression, growth retardation in children & adolescents, decrease in bone mineral density, cataract & glaucoma. Salmeterol/fluticasone propionate clinical trials:- Common: Hoarseness/dysphonia, throat irritation, headache, candidiasis of mouth & throat and palpitations. Overdose: Signs & symptoms of salmeterol overdosage: tremor, headache, tachycardia, increases in systolic blood pressure & hypokalaemia. If higher than approved doses of Seretide are continued over prolonged periods, significant adrenocortical suppression is possible. There have been very rare reports of acute adrenal crisis, mainly occurring in children exposed to higher than approved doses over prolonged periods (several months or years); observed features have included hypoglycaemia associated with decreased consciousness and/or convulsions. Please read the full prescribing information prior to administration, available from GlaxoSmithKline Pte Ltd, 150 Beach Rd, Gateway West #22-00, Singapore 189720. Tel: +65 6232 8338. Fax: +65 6291 9737. Full prescribing information available on request. Seretide Evohaler is a trademark of the GlaxoSmithKline Group of companies. Version abbrev (IPI10SI).
Singapore Abbreviated Prescribing Information

Seretide Accuhaler Active Ingredient: Salmeterol xinafoate & fluticasone propionate. Indications: Indicated in the regular treatment of asthma where use of a combination (bronchodilator and inhaled corticosteroid) has been found to be appropriate. Indicated for the symptomatic treatment of patients with severe COPD (FEV1 <50% predicted normal) & a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy. Dosage and Administration: For oral inhalation only. Asthma: Adults & adolescents 12 years old: One inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) twice daily or One inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) twice daily or One inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) twice daily. Children 4 years old: One inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) twice daily. Chronic Obstructive Pulmonary Disease (COPD) For adult patients the recommended dose is one inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) twice daily. For full dosing recommendations please refer to prescribing information. Contraindications: History of hypersensitivity to any of the ingredients. Warnings & Precautions: Seretide Accuhaler is not for relief of acute symptoms. Treatment with Seretide should not be stopped abruptly in patients with asthma due to risk of exacerbation. Therapy should be titrated-down under physician supervision. For patients with COPD therapy cessation may be associated with symptomatic decompensation & should be supervised by a physician. There was an Seretide Evohaler Active Ingredient: Salmeterol/fluticasone propionate Indications: Indicated in the regular treatment of asthma where use of a combination product (long-acting beta2-agonist & inhaled corticosteroid) is appropriate: patients not adequately controlled with inhaled corticosteroids and as needed inhaled short acting beta2-agonist or patients already adequately controlled on both inhaled corticosteroids and long-acting-beta2-agonist. Note: Seretide 25/50 mcg strength is not appropriate in adults with severe asthma. Dosage and Administration: For oral inhalation only. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. Patients should be given the strength of Seretide containing the appropriate fluticasone propionate dosage for the severity of their disease. Asthma - Adults & adolescents 12 years old: Two inhalations of 25 mcg salmeterol & 50 mcg fluticasone propionate twice daily or two inhalations of 25 mcg salmeterol & 125 mcg fluticasone propionate twice daily or two inhalations of 25 mcg salmeterol & 250 mcg fluticasone propionate twice daily. Children 4 years old: Two inhalations of 25 mcg salmeterol & 50 mcg fluticasone propionate twice daily. No data is available for use of Seretide in children <4 years old. Special patient groups: There is no need to adjust the dose in elderly patients or in those with renal or hepatic impairment. Contraindications: Patients with a history of hypersensitivity to any of the ingredients. Warnings & Precautions: Not for relief of acute symptoms. Patients should not be initiated on Seretide during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Treatment with Seretide should not be stopped abruptly due to risk of exacerbation. Therapy should be titrated-down under physician supervision. Administer with caution in patients with active or quiescent pulmonary
increased reporting of pneumonia in studies of patients with COPD receiving Seretide. Use with caution in patients: with active or quiescent pulmonary tuberculosis, thyrotoxicosis, pre-existing cardiovascular disease & who are predisposed to low levels of serum potassium. Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods e.g. Cushings syndrome, Cushingoid features, adrenal suppression, growth retardation in children & adolescents, decrease in bone mineral density, cataract & glaucoma. The possibility of impaired adrenal response should always be borne in mind in emergency and elective situations likely to produce stress and appropriate corticosteroid treatment considered. Regular monitoring of height of children receiving prolonged treatment & adrenocortical function are recommended. Withdrawal of systemic therapy should be gradual & patients encouraged to carry a steroid warning card. Caution when prescribing to patients with a history of diabetes mellitus & when strong CYP3A4 inhibitors are co-administered with Serevent (component of Seretide). Interactions: Avoid both non-selective & selective beta-blockers. Concomitant use of fluticasone propionate & ritonavir should be avoided, unless the potential benefi t to the patient outweighs the risk. Studies have shown that other inhibitors of cytochrome P450 3A4 produce negligible and minor increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Nevertheless, care is advised when co-administering potent cytochrome P450 3A4 inhibitors as there is potential for increased systemic exposure to fluticasone propionate. Pregnancy and tuberculosis, thyrotoxicosis, pre-existing cardiovascular disease and who are predisposed to low levels of serum potassium. Possible systemic effects may occur with any inhaled corticosteroid e.g. Cushings syndrome, Cushingoid features, adrenal suppression, growth retardation in children & adolescents, decrease in bone mineral density, cataract & glaucoma. Regular monitoring of height of children receiving prolonged treatment with inhaled corticosteroid & adrenocortical function are recommended. Withdrawal of systemic therapy should be gradual & patients encouraged to carry a steroid warning card. Caution when prescribing to patients with a history of diabetes mellitus. Concomitant use of fluticasone propionate & ritonavir should be avoided, unless the potential benefi t to the patient outweighs the risk of systemic corticosteroid side-effects. Interactions: Both non-selective & selective beta-blockers should be avoided. Concomitant use of fluticasone propionate & ritonavir should be avoided, unless the potential benefi t to the patient outweighs the risk of systemic corticosteroid side-effects. Caution should be exercised when other potent cytochrome P450 3A4 inhibitors are coadministered with fluticasone propionate. In a drug interaction study, coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in increased plasma fluticasone propionate exposure and reduced plasma cortisol AUC, but had no effect on urinary excretion of cortisol. Pregnancy and Lactation: Administration during pregnancy &lactation should only be considered if the expected benefi t to the mother is greater than any possible risk to the foetus or child. Adverse Reactions: Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. Salmeterol:- tremor, subjective palpitations and headache. Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles) may occur. Uncommon: rash. Very rare: arthralgia, hyperglycaemia, hypersensitivity reactions, including anaphylactic reactions e.g.
References: 1. Kavuru M et al. J allergy Clin Immunol. 2000;105:1108-1116. 2 . Lundback B et al. Respir Med. 2009;103:348-355. 3. Bateman ED et al. Am J Respir Crit Care Med. 2004;170(8):836-844. 4 . Woodcock AA et al. Prim Care Respir J. 2007; 16(3):155-161. 5. Seretide Accuhaler & Evohaler Abbreviated Prescribing Information (IPI10SI, IPI12SI). 6. GINA, Global Strategy for Asthma Management and Prevention. Updated 2009 http://ginasthma.com/GuidelineItem. asp?|I=2&12=IIntld=1561. 7. Bateman ED et al. Am J respire Crit Care Med 2004;170(8):836-844.
GlaxoSmithKline Pte Ltd 150 Beach Rd Gateway West #22-00, Singapore 189720. Tel: +65 6232 8338 Fax: +65 6291 9737
Post-h Po Post-h t-ho t-hoc oc analysis naly naly ysis of GOAL. GOAL. OAL Med Me e ian an resc esc cue-f e free ree e days y (% (%) %) ove % over r weeks weeks w ek k 1-52 -52,, st -52 stratu stratu atu tu tum um 2 2: Se Ser Sere e tid tiid 88% tide 8 vs vs FP P 72% (p<0. <0 001) 001 7. ** Po ** ostst stt hoc ca anal nalysis ysis s of o GOAL G AL. Me GO Median ian sym mptom-fre ptom om-fr free d f da ays (%) %) over ver e week wee we e s 1-52, 1-52 52, 5 2, s stra r tum um 2:: Seretide Sere tid 74. tide 74 2% vs FP 74 FP 51. 51.0% % (p<0. p 001) 01)7.
SG/SER/10082011/B
For Medical and Healthcare Professionals Information Only
33
October 2012
Depression
Depression, other mental disorders increase risk of early death

Radha Chitale
ental disorders such as depression, bipolar disorder and schizophrenia, which may not require hospitalization due to severity, can still increase risk of premature death, according to a long-term study of Swedish. Mental disorders have been associated with increased mortality, but the evidence is primarily based on hospital admissions for psychoses, said the researchers, who compiled data from psychiatric interviews with Swedish men of mean age 18.3 years who were conscripted for military service over a mean 22.6 years of follow up through national registries. When diagnosed at conscription, depression was associated with double the risk of premature death (age-adjusted hazard ratio of 1.81) and the presence of bipolar disorder increased the risk of death by more than 5 times (age-adjusted hazard ratio of 5.55). [Arch Gen Psychiatry 2012;69:823-831] In total, 1.09 million men were conscripted between 1969 and 1994 of which 5.6 percent were diagnosed at conscription with a mental disorder. Compared with men without mental illnesses, men who were diagnosed later upon admission to a hospital had mortality hazard ratios of 5.46 for neurotic and adjustment disorders and 11.2 for substance abuse disorders not including alcohol. Men admitted to hospital for psychiatric reasons following conscription numbered 60,333,
10,665 of whom were already diagnosed during conscription. The mortality risk associated with other diagnoses after adjusting for age, socioeconomic status, blood pressure, body mass index, intelligence, and education included hazard ratios of 1.53 for depression, 5.19 for bipolar disorder, 2.52 for schizophrenia, 1.88 for personality disorders, 1.62 for other non affective psychoses, 1.48 for neurotic and adjustment disorders, 2.38 for alcohol-related disease and 2.68 for other substance abuse. The associations were partially attenuated by adjusting for smoking, alcohol intake, intelligence, education and late-life socioeconomic status but were not affected by early-life socioeconomic status, body mass index or blood pressure. During the follow up period, 15,110 men died. Age stratification of the 4,879 men who were diagnosed during hospitalization who died subsequently showed that mortality risk was five to 11 times higher for men born between 1951 and 1958 and seven to 29 times higher for men born between 1968 and 1976. The mortality risk remained significantly elevated even after excluding about 20-32 percent of deaths considered suicide. This might be due to more severe disease, particularly in the group diagnosed early, the researchers noted. The results of the all-male study population were further limited by potentially unmeasured factors such as comorbid illness, lifestyle, medications and varying access to healthcare, the researchers said.
34
October 2012
Depression
Heart attack increases spouse depression, anxiety

Elvira Manzano
he death of a spouse from heart attack increases the risk of depression and anxiety in the surviving partner, requiring an increased use of psychotropic medications, a large Danish study has found. Losing a spouse or having a spouse experiencing a non-fatal MI is a major public health issue for which there is very little awareness among physicians and policy makers, said study author Dr. Emil Fosbl, a cardiologist and researcher at Denmarks Gentofte University Hospital, Hellerup, Denmark. People involved with patient care should be aware of spouses mental reactions after a life-threatening event such as an MI. I would like to see a more formal way of screening spouses for depression in relation to the event, but also subsequently. Using data from Danish national registries, Fosbl and colleagues compared the incidence of hospital system contact (hospital admission or ambulatory visit), use of antidepressants and benzodiazepines, and suicide among spouses of patients who had fatal and non-fatal MI (16,506 and 44,566, respectively) for the first time with those whose spouses died or were hospitalized for other causes (49,518 and 131,564, respectively). The study found the incidence of depression was significantly higher among spouses of patients who had myocardial infarction (MI), fatal or nonfatal, compared with those whose spouses had non-MI events (pre-post, P<0.0001). Overall, the use of antidepres-
sants was higher in the year after MI deaths (incident rate ratio [IRR] 3.30, 95% CI 2.97 3.68) compared with the year before, peaking at 2 months post event (IRR 5.72, 95% CI 4.85-6.74). The use of benzodiazepines also increased a month after MI deaths (IRR 46.4, 95% CI 42.250.0). The results also applied to spouses of patients who had non-fatal MI (P<0.001). Moreover, spouses of patients who died from MI were more likely to commit suicide than those who lost them to other causes (0.24 vs. 0.17 percent, P=0.07). [Eur Heart J 2012. Epub ahead of print] A standardized mental screening program could potentially prevent many spouses from being depressed or taking their own lives, Fosbl told Medical Tribune. It would also be interesting to see in a formalized study [to determine] whether screening could reduce depression in spouses after a fatal or non-fatal MI. Although previous studies have shown that the death of a spouse can affect an individuals health and life expectancy, death from MI which can often occur suddenly and unexpectedly appears to have a larger psychological impact on the spouse than death from other causes.One does not have time to prepare psychologically for the death compared with, for example, cancer, Fosbl said. The study implies that clinical attention needs to be paid to both the patient, who is suffering from the physical and mental trauma, and the spouse, who has to live through the event alongside the patient, the authors concluded.
35
October 2012
Depression
Short-term fluoxetine, venlafaxine efficacious for depression

Rajesh Kumar
he antidepressants fluoxetine and venlafaxine are efficacious as short-term therapy for major depressive disorders in all age groups, according to a large meta-analysis. The researchers pooled data from more than 9,100 patients of all ages with major depressive disorder who had been included in a total of 41 randomized clinical trials of fluoxetine (N=20 trials) and venlafaxine (N=21 trials). They carried out a reanalysis of all person-level longitudinal data for the first 6 weeks of active treatment. [Arch Gen Psychiatry 2012;69:572-579] They found that patients in all age groups had significantly greater improvement compared with those receiving placebo, although the differential rate of improvement was largest for adults receiving fluoxetine (34.6 percent greater than those receiving placebo). Youth had the largest difference in response rates (24.1 percent in treated vs. control) and remission rates (30.1 percent), with adult differences generally in the 15.6 percent (remission) to 21.4 percent (response) range. Geriatric patients had the smallest drugplacebo differences, an 18.5 percent greater rate of improvement, 9.9 percent for response and 6.5 percent for remission. Also, immediate-release venlafaxine produced larger effects than extended-release venlafaxine, and baseline severity did not affect symptoms.
This is the first research synthesis in this area to use complete longitudinal personlevel data from a large set of published and unpublished studies. Most studies included in the meta-analysis were designed for achieving regulatory approval and do not demonstrate the maximum effect a drug can produce. Some studies were as short as 6 weeks whereas the maximum effect during an acute treatment episode is likely 12 weeks or longer, the researchers argued. The [current] study highlights many of the limitations of meta-analysis that combine evidence from multiple RCTs, concluded the researchers. It further highlights advantages of more complete personal-level analysis when such data are available and increases the need for caution regarding interpretation of meta-analytic results when person-level data are not available.
36
October 2012
News
PPIs safe for long-term use

Saras Ramiya
elected proton pump inhibitors (PPIs) are safe for long-term use in patients with chronic gastrointestinal (GI) conditions, a study shows. The new landmark international study looked at the long-term effects of pantoprazole in patients with chronic GI conditions such as peptic ulcers and reflux esophagitis. [Aliment Pharmacol Ther 2012;36(1):37-47] Following healing of peptic ulcers or reflux esophagitis during 4 to 12 weeks treatment with pantoprazole (40 to 80 mg/day), patients received open-label maintenance treatment with pantoprazole (40 to 160 mg/day) for up to 15 years in a single center combined study. Safety assessments were conducted using endoscopy, clinical examination and laboratory investigations. The safety set, which comprised 142 adults who received continued pantoprazole treatment for over 15 years, showed healing rates of 95.8 percent after 12 weeks without increased risks of specific serious conditions like stomach cancer. This study shows that pantoprazole effectively controls the production of acid and heals upper gastrointestinal ulcers and wounds in the long term without identifiable side effects, said principal investigator Professor G. Brunner, of the Division of Gastroenterology and Hepatology, University Medical School, Hannover, Germany, in a press release based on a regional GI media summit organized by Takeda Pharmaceutical Company Limited in Kuala Lumpur. In light of this longest safety data on pantoprazole, doctors and patients have even
Expanding waistlines across Asia have contributed to increased incidence of severe and chronic gastrointestinal conditions.
more assurance that PPI therapy is safe for long term treatment of severe GERD and gastrointestinal conditions, he added. GI problems on the rise GI disorders in Asia have been increasing in prevalence, as shown in studies. As a result of dietary changes, rising obesity and stress in many parts of Asia, doctors are now seeing a rising number of cases of severe and chronic GI conditions, such as GERD, peptic ulcers and heartburn, said Dr. Denis C. Ngo, of the University of Santo Tomas (UST) Hospital, Manila. [J Gastroenterol Hepatol 2008:23:8-22] In the Philippines, the prevalence of erosive esophagitis rose from 2.9 percent to 6.3 percent over 6 years; in Malaysia, the incidence rose from 2.0 percent to 8.4 percent over a 10year period; time trend studies showed that esophagitis rates in Taiwan more than doubled from 5.0 percent to 12.6 percent over a 7-year period. [J Gastroenterol Hepatol 2007;22:1650-5, Aliment Pharmacol Ther 2009;29:774-80, J Clin Gastroenterol 2009;43:926-32] The prevalence of symptom-based GERD in Eastern Asia (China, Japan, Korea and Taiwan) rose from 5.2 percent in 2005 to 8.5 per-
37
October 2012
News
erable lower quality of life greater than that observed in other chronic conditions such as diabetes, arthritis or congestive heart failure. [Dig Dis 2004;22(2):108-14] There is a high prevalence of GERD in individual Asian countries, ranging from 12.4 percent in Taiwan and up to 17 percent in China, and 29.8 percent in Hong Kong. [J Neurogastroenterol Motil 2011;17(1):14-27, World J Gastroenterol 2004;10:1647-51, Aliment Pharmacol Ther 2003;18:595-604] These conditions are so severe that patients do not require just quick relief for GI conditions, but more sustained control with proton pump inhibitors (PPIs) over the long term, said Ngo.
cent in 2010. [BMC Gastroenterol 2010;10:94] In Malaysia, the incidence of reflux esophagitis increased from 2.7 percent to 9.0 percent during the time period from 1991-1992 to 2000-2001, while Indonesias Cipto Mangunkusumo Hospital reported the prevalence of GERD increasing from 5.7 percent in 1997 to 25.1 percent in 2002. [Gastroenterology 2004;126:A443, Canc Res Treat 2003;5:83] Currently, 2.5 percent to 4.8 percent of Asians experience weekly symptoms of heartburn and/or acid regurgitation. [Gut 2005;54:710-7] Besides heartburn, patients with GERD and gastrointestinal disorders suffer difficulty swallowing (dysphagia), reduced vitality, disturbed sleep and consid-
New algorithm for managing diabetes across cultures

Radha Chitale
new algorithm for type 2 diabetes management focuses on nutritional therapy and has been adapted to accommodate global cultural differences in disease expression and management. Dr. Jeffrey Mechanic, clinical professor of Medicine, Endocrinology, Diabetes and Bone Disease Mount Sinai School of Medicine, New York, New York, US, who led the Task Force for Development of Transcultural Algorithms in Nutrition and Diabetes, noted that algorithms are simpler and clearer to use than cumbersome clinical practice guidelines, which are often based on evidence from very specific populations, typically from the US or Europe, and are difficult to implement in different cultural contexts.
There really may be a fallacy in generalizing information conducted on a sub-population of the human race and then dictating those guidelines to another population, he said. After reviewing existing clinical guidelines and other research, the resulting Transcultural Diabetes Nutrition Therapy Algorithm (tDNA) focuses on the lifestyle changes or lifestyle modifications portion referenced by clinical guidelines to make it a detailed step-by-step guide to disease management, focusing on nutrition. [Curr Diab Rep 2012;12:180-194] For example, research showed that patients from Hong Kong are reluctant to see a nutritionist compared with an MD, the Philippine palate may not take to a milky liquid
38
October 2012
News
[Curr Diab Rep 2012;12:213-219] Among Asian Indians, there is a wide range of socio-economic factors that affect diabetes prevention and treatment, including sedentary lifestyle, high poverty rate, malnourishment, the effect of festivals and holidays on appointments and routines, and a higher body fat to muscle mass ratio, which speeds the rate of disease onset. [Curr Diab Rep 2012;12:204-212] Some of the changes to nutritional recommendations are general recommendations for weight loss in overweight individuals in the Taiwanese and Chinese populations while Indians are recommended to lose weight slowly by 7-10 percent over 1 year, compared with a standard 500-1000 kcal/day target to reduce weight by 5-10 percent outlined in guidelines from the American Diabetes Association. Nutritional recommendations for carbohydrate, protein, fat cholesterol, fiber and sodium intakes, as well as how to manage them using nutritional supplements, also differ between countries. Currently, Mechanic said the task force is in the process of validating the tDNA with prospective cohort trials to determine if the algorithm is more effective at controlling diabetes than standardized therapy.
drink, nor would the Malaysian palate, unless it were chocolate flavored. Mechanic said that Chinese doctors are still debating the upper limit of healthy body mass index, another example of the need for an adaptable diabetes management rubric. The process outlined by the tDNA is to gather data on an individuals disease status as well as their ethno-cultural background and lifestyle, stratify their risk status, determine a plan of action (nutrition and exercise plan), assess with a follow up evaluation and modify the therapeutic plan where necessary. Plans can be specific to those with obesity, hypertension, blood sugar levels, etc. And unlike clinical guidelines, the tDNA can be used for prevention using nutritional therapy instead of focusing on using drugs for disease management. From this basic algorithm, diabetes and nutrition experts from around Southeast Asia, Hong Kong and Taiwan were invited to tweak specific recommendations based on cultural needs and habits. The Asian application of the tDNA takes into account the earlier diabetes onset, and lower cut-off values for healthy body mass indices and waist circumference of this population compared with a western population.
Higher vitamin C intake may help reduce heart disease, stroke

Rajesh Kumar
he recommended dietary allowance (RDA) of vitamin C should be raised to at least 200 milligrams per day for
adults to prevent heart disease and stroke, experts have suggested. The current RDA for this vitamin in most countries is less than half of what it should be, because medical experts insist on evalu-
39
October 2012
News
inflammation, poor immune response and atherosclerosis. Even marginal deficiency of vitamin C can lead to malaise, fatigue, and lethargy, the researchers noted, while healthier levels can enhance immune function, reduce inflammatory conditions such as atherosclerosis, and significantly lower blood pressure. Critics have suggested that some of these differences are simply due to better overall diet, not vitamin C levels, but the researchers noted that some health benefits correlate even more strongly to vitamin C plasma levels than fruit and vegetable consumption alone. Dr. Amber Bastian, dietician at the Centre of Excellence (Nutrition), Health Promotion Board Singapore, said her organization updated its RDA for vitamin C earlier this year. It is 105mg for men and 85mg for women, which is quite progressive as it is higher than Australia (45mg), US (75mg females, 90mg males), WHO (45mg) and Malaysia (70mg), said Bastian. [This RDA] was developed based on current evidence of the amount needed to provide antioxidant protection, rather than to prevent scurvy which is what was traditionally used, she said, adding that the board regularly reviews its dietary recommendations to provide up-to-date recommendations based on the most recent evidence. Typically, each serving of fruit has around 35mg of vitamin C, while a serving of vegetable has around 40mg. People would achieve an intake of about 150mg per day if they follow HPBs current recommendation of two servings each of fruits and vegetables per day, added Bastian.
ating this natural but critical nutrient the same way they do pharmaceutical drugs and reach faulty conclusions, said lead author Dr. Balz Frei, professor and director of the Linus Pauling Institute at Oregon State University in Corvallis, Oregon, US. [Crit Rev Food Sci Nutr 2012; 52:815-829] Rather than just prevent the vitamin C deficiency disease of scurvy, Frei said it is appropriate to seek optimum levels that will saturate cells and tissues, pose no risk, and may have significant effects on public health at almost no expense. Significant numbers of people around the world are deficient in vitamin C, and theres growing evidence that more of this vitamin could help prevent chronic disease, he said. Studying micronutrients the same way as testing pharmaceutical drugs, through phase III randomized placebo-controlled trials, almost ensures that scientists will find no beneficial effect, said the researchers. Such trials are ill suited to demonstrate the disease prevention capabilities of substances that are already present in the human body and are required for normal metabolism, they added. Some benefits of micronutrients in lowering chronic disease risk also show up only after many years or even decades of their optimal consumption a factor often not captured in shorter-term clinical studies, they pointed out. The US and European researchers reviewed metabolic, pharmacokinetic, laboratory and demographic studies and concluded higher levels of vitamin C could help reduce chronic diseases such as heart disease, stroke, cancer, and the underlying issues that lead to them, such as high blood pressure, chronic
The Changing Panorama Of Womens Health:
Navigating New Frontiers

22-24 August 2013 Visit www.Sicog2013.com for more details soon!
41
October 2012
News
Surgery superior in patients with carpal tunnel syndrome

Rajesh Kumar
reatment with surgery was significantly more effective than local steroid injection in alleviating symptoms of carpal tunnel syndrome (CTS) over a 2-year follow up period, a Spanish study has found. In the prospective, randomized clinical trial, researchers studied the effects of surgical decompression versus local steroid injection by randomly assigning 80 wrists to surgical decompression and 83 to local steroid injection following a clinical diagnosis and neurophysiological confirmation of CTS in 101 patients. [Rheumatology 2012;51:1447-1454] The primary end point at 2-year follow-up was the percentage of wrists that reached a >20 percent improvement in the visual analogue scale score for nocturnal paresthesia. Both treatment groups had comparable severity of CTS at baseline. Fifty-five wrists in the surgery group and 48 wrists in the injection group completed the follow-up. In the intent-to-treat analysis, 60 percent of the wrists in the injection group and 69 percent in the surgery group achieved a 20 percent response for nocturnal paresthesia (P<0.001). Although the clinical relevance of those differences remains to be defined, the findings are not entirely unexpected as each of the two procedures has its own benefits and disadvantages, said Dr. Chew Li-Ching, consultant in the department of rheumatology and immunology at Singapore General Hospital (SGH). The injection can be easily delivered at the point of care. However, usually, it provides temporary relief only compared with surgery. At
Wrist surgery is more effective at treating carpal tunnel syndrome than local steroid injections.
SGH, we are well supported by hand surgeons, [therefore] access to surgery has not proven to be an issue, said Chew. Injection is still an acceptable standard of care for CTS, especially if the patients symptoms and findings on neurophysiological testing are mild to moderate. The more severe cases such as those associated with weakness and muscle wasting would usually warrant surgery. Although randomization based on wrists rather than patients could be considered the studys limitation, CTS is often a bilateral condition and the approach is consistent with the standard of care in clinical practice which consists of treating both wrists in cases of bilateral CTS, said the researchers. We also felt that by randomizing only the most symptomatic wrist in the bilateral cases, we could have a biased selection [and] the results of the study would not represent the real severity of CTS in the general populationit would transform CTS into a more severe disease than it really is.
42
October 2012
News
Stress healthy lifestyle changes to men with prostate cancer

Rajesh Kumar
en diagnosed with prostate cancer are less likely to die from the cancer than from largely preventable conditions such as heart disease, according to a study that examined the cause of death in more than 700,000 men with prostate cancer in the US and Sweden. Our results are relevant for several million men living with prostate cancer, said lead author Dr. Mara Epstein of the Harvard School of Public Health in Boston, Massachusetts, US. [J Natl Cancer Inst 2012; DOI: 10.1093/jnci/djs299] We hope this study will encourage physicians to use a prostate cancer diagnosis as a teachable moment to encourage a healthier lifestyle, which could improve the overall health of men with prostate cancer, increasing both the duration and quality of their life. The researchers examined causes of death among prostate cancer cases recorded in the U.S. Surveillance, Epidemiology, and End Results program (N490,000 men from 1973 to 2008) and the nationwide Swedish Cancer and Cause of Death registries (N210,000 men from 1961 to 2008). During the study period, prostate cancer accounted for 52 percent of all reported deaths in Sweden and 30 percent of reported deaths in the US among men with prostate cancer. However, only 35 percent of Swedish men and 16 percent of US men diagnosed with prostate cancer died from this disease. In both populations, the risk of prostate cancer-specific death declined, while the risk of death from heart disease and non-prostate cancer remained constant. The 5-year cumulative incidence of death
A healthy lifestyle can boost the duration and quality of life in men with prostate cancer.
from prostate cancer was 29 percent in Sweden and 11 percent in the US. While the incidence of prostate cancer has greatly increased in recent decades, the likelihood that a newly diagnosed man in developed countries will die from the disease has declined. Widespread use of the prostatespecific antigen (PSA) test is believed to be the reason, as it has helped diagnose a higher proportion of men with lower-risk forms of the disease. In the study, death rates from prostate cancer varied by age and calendar year of diagnosis, with the highest number of deaths from the disease among men diagnosed at older ages and those diagnosed in the earlier years of the surveys (especially in the years before the introduction of PSA screening). Our study shows that lifestyle changes such as losing weight, increasing physical activity, and quitting smoking, may indeed have a greater impact on patients survival than the treatment they receive for their prostate cancer, said senior co-author Dr. Hans-Olov Adami, professor of epidemiology at Harvard School of Public Health.
43
October 2012
Calendar
October
23rd Great Wall International Congress of Cardiology (GW-ICC) Asia Pacific Heart Congress (APHC) 2012
11/10/2012 to 14/10/2012 Location: Beijing, China Info: Secretariat Office of GW-ICC & APHC (Shanghai Office) Tel: (86) 21-6157 3888 Extn: 3861/62/64/65 Fax: (86) 21-6157 3899 Email: secretariat@heartcongress.org Website: www.heartcongress.org
8th International Symposium on Respiratory Diseases & ATS in China Forum 2012
9/11/2012 to 11/11/2012 Location: Shanghai, China Info: UBM Medica Shanghai Ltd. Tel: (86) 21-6157 3888 Extn: 3861/62/64/65 Fax: (86) 21-6157 3899 Email: secretariat@isrd.org Website: www.isrd.org
42nd Annual Meeting of the International Continence Society

15/10/2012 to 19/10/2012 Location: Beijing, China Tel: (41) 22 908 0488 Fax: (41) 22 906 9140 Email: ics@kenes.com Website: www.kenes.com/ics
3rd Annual Meeting of the American 6 Association for the Study of Liver Diseases
9/11/2012 to 13/11/2012 Location: Boston, Massachusetts, US Info: American Association for the Study of Liver Diseases Tel: (1) 703 299 9766 Website: www.aasld.org
Upcoming
National Diagnostic Imaging Symposium
2/12/2012 to 6/12/2012 Location: Orlando, Florida, US Info: World Class CME Tel: (980) 819 5095 Email: office@worldclaswscme.com Website: www.cvent.com/events/national-diagnosticimaging-symposium-2012/event-summaryd9ca77152935404ebf0404a0898e13e9.aspx
th Asian-Pacific Society of Atherosclerosis 8 and Vascular Diseases Meeting

20/10/2012 to 22/10/2012 Location: Phuket, Thailand Info: Asian-Pacific Society of Atherosclerosis and Vascular Diseases Tel: (66) 2940 2483 Email: apsavd@lawson-marsh.com Website: www.apsavd2012.com
November
012 Scientific Sessions of the American 2 Heart Association
3/11/2012 to 7/11/2012 Location: Los Angeles, California, US Info: American Heart Association Tel: (1) 214 570 5935 Email: sessionsadmin@heart.org Website: www.scientificsessions.org
Asian Pacific Digestive Week 2012

5/12/2012 to 8/12/2012 Location: Bangkok, Thailand Tel: (66) 2 748 7881 ext. 111 Fax: (66) 2 748 7880 E-mail: secretariat@apdw2012.org Website: www.apdw2012.org
World Allergy Organization International Scientific Conference (WISC 2012)

6/12/2012 to 9/12/2012 Location: Hyderabad, India Info: World Allergy Organization Tel: (1) 414 276 1791 Fax: (1) 414 276 3349 E-mail: WISC@worldallergy.org Website: www.worldallergy.org
44
October 2012
Calendar
54th American Society of Hematology Annual Meeting

8/12/2012 to 11/12/2012 Location: Georgia, Atlanta, US Info: American Society of Hematology Tel: (1) 202 776 0544 Fax: (1) 202 776 0545 Website: www.hematology.org
17th Congress of the Asian Pacific Society of Respirology

14/12/2012 to 16/12/2012 Location: Hong Kong Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 Fax: (852) 2559 6910 E-mail: info@apsr2012.org Website: www.apsr2012.org
16th Bangkok International Symposium on HIV Medicine

16/1/2013 to 18/1/2013 Location: Bangkok, Thailand Info: Ms. Jeerakan Janhom (Secretariat) Tel: (66) 2 652 3040 Ext. 102 Fax: (66) 2 254 7574 E-mail: jeerakan.j@hivnat.org Website: www.hivnat.org/bangkoksymposium
28th Congress of the Asia-Pacific Academy of Ophthalmology

17/1/2013 to 20/1/2013 Location: Hyderabad, India Info: APAO Secretariat Tel: (852) 3943 5827 Fax: (852) 2715 9490 Email: secretariat@apaophth.org Website: www.apaoindia2013.org
Asian Pacific Society of Cardiology 2013 Congress

21/2/2013 to 24/2/2013 Location: Pattaya, Thailand Info: Kenes Asia (Thailand Office) Tel: (66) 2 748-7881 Fax: (66) 2 748-7880 Email: apscoffice2013@apsc2013.org Website: http://www2.kenes.com/apsc2013/pages/home. aspx
45
October 2012
After Hours
Radha Chitale
hen they first went up, the enormous splayed towers encased in geometric scaffolding, what would become supertrees, standing bare behind the Marina Bay Sands hotel in Singapore recalled a factory more than a home for flora and fauna. But my recent visit to the National Parks Boards ambitious Gardens by the Bay show the area has transformed from a wasteland of construction into a unique botanical park well on its way to becoming an iconic example of sustainability in urban landscaping. The over S$1 billion project covers 101 hectares of reclaimed land and includes lakes, sky walks, cultural gardens and two biomes that house 220,000 plant varieties from around the world. The supertrees are clustered in several spots around the park and are vertical
46
October 2012
After Hours
gardens between 25 and 50 meters high. Their scaffolding holds ferns, flowering climbers and bromeliads that will eventually grow to cover the entire structure. The towers also function to cool the biomes, are air exhaust receptacles and are fitted with photovoltaic cells that harvest solar energy to light up the supertrees at night. The horticultural attractions of the Gardens are in the domed glass biomes. Walking into the Cloud Forest biome, one goes from sea level to 1,800 meters above and the sharp temperature drop is a welcome change from the heat outside. The waterfall at the entryway cascades down a mini mountain top covered in pitcher plants and other flowers and shrubs that thrive in cool, moist conditions. I may have mistakenly expected a wilderness of scented flowers from the Flower Dome, but the manicured central flower field is colourful enough and made a pretty picture for one couple dressed up for wedding photos, seated on matching forest thrones in a bed of gerber daisies, complete with a small gazebo in the background. The Flower Dome also features garden plants from a variety of regions such as baobab trees from Africa, wine palms from South America and olive groves from the Mediterranean. Both biomes end with educational exhibits detailing the carbon cycle, different energy sources, the science of polar ice caps, and threats to plants from urbanization and climate change. The Gardens manage to incorporate a lot of educational information across the park. Plaques studded among the portion of the Gardens that are free to the public describe the varieties of plants, what their uses are, how sustainable elements have been incorporated into the building and a smorgasbord of trivia. The plants in the biomes, by contrast, are not obviously labelled, probably to indicate that one should rent the self-guided audio tour. Beyond well-developed biomes, the Gardens are still a project in progress, with clear spots yet to be filled with plants, evidenced by patches of exposed black soil and empty wiring and trellises for plants to take over. Although the National Parks Boards vision of a City in a Garden germinated the Gardens by the Bay, the vista of Singapores central business district looms over the park creating a sense that this is still a garden a very large garden in a city. But that is a question of semantics. At its most basic, the Gardens by the Bay put more plants in an urban space, and that is a good thing.
47
October 2012
After Hours
Medicinal Plants
Several plants in the Gardens by the Bay have medicinal properties. These plants are located all over the park and are selected because they have strong cultural connections to the garden they are in or they are native to the climate.
Lemon Gum (Corymbia citriodora)
Australia Garden, Flower Dome

- Relieves arthritic pain, alleviates nasal congestion, antiseptic properties Tree Aloe (Aloe barberae)
South African Garden, Flower Dome

- Antimicrobial properties, soothes skin, anti-inflammatory Monkey Puzzle Tree (Araucaria araucana)
South American Garden, Flower Dome

- Produces a resin used to treat ulcers and sores Olive Tree (Olea Europaea)
Olive Grove, Mediterranean Garden, Flower Dome

- M etabolism inducer, reduced LDL cholesterol, blood pressure, and blood sugar levels Lavender (Lavandula dentate)
Mediterranean Garden, Flower Dome

- R educes insomnia, alopecia, anxiety, stress-related disorders, post-operative pain Tongkat Ali (Eurycoma longifolia)
Malay Heritage Garden

- Increases testosterone production, anti-malarial and anti-microbial properties Curry Tree (Murraya koenigii)
Indian Heritage Garden

- Anti-diabetic, anti-oxidant, anti-inflammatory, hepatoprotective Camphor (Cinnamomum camphora)
Indian Heritage Garden

- Anasthetic, anti-microbial Weeping willow (Salix babylonica)
Chinese Heritage Garden

- Antirheumatic, astringent, source of salicylic acid Mulberry (Morus alba)
Chinese Heritage Garden

- Antimicrobial, antioxidant, hypolipidemic
48
October 2012
Humor
Dont try to move or go anywhere. We will be right back!
Theres no cure, because you are perfectly healthy!
I said I was sorry!
If you the worst happens, can I Do have to go on and on keephow yourgross lawn mower? about the whole thing is?
What your husband is experiencing, its what we call rigor mortis, making it difficult for him to relax!
Sure, some of my patients became very sick after the operation, and others have died, but none of them seriously!
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October 2012

ESC rolls out new practice guidelines

FORUM Health policies need to foster right environment

DEPRESSION Short-term fluoxetine, venlafaxine efficacious for depression

NuvaRing Once-Monthly Convenient Contraceptive Ring for Today's Women

NuvaRing is 99% effective, just like a COC1

NuvaRing (n=499) Adapted from Ahrendt et al.1

NuvaRing (n=499) COCs (n=484)

Adapted from Milsom et al.2

COC: Combined oral contraceptive EE: Ethinyl Estradiol

MSD Pharma (Singapore) Pte Ltd

Please read the full prescribing information before prescribing NuvaRing.

ESC rolls out new practice guidelines

Tai chi can benefit patients with COPD

Tai chi improved muscle strength and balance in study patients.

Health policies need to foster right environment

Recreational exercise alone wont solve the obesity epidemic problem.

Please visit www.isrd.org for further details

American Thoracic Society (ATS)

Congress Secretariat Office

Genes linked to glaucoma

HSA launches clinical trials registry

Singaporeans have poor diabetes self-management

when COPD symptoms impact everyday life

SPiriVA* once-daily COPD maintenance treatment provides...

Boehringer Ingelheim Singapore Pte Ltd

For medical professional only.

Osteoarthritis training workshops target GPs

patients sometimes dont realize that

Knowledge gaps in Asian women on fertility

HPB launches health choices toolkit for GPs

Dengue drug trial seeks patients

Genotyping can help avoid SJS/TEN in epileptic patients

Genotyping is cost-effective for Singaporean Chinese and Malays

Extended-release metformin makes dosing easier

Kidney cancer rate on the rise in Singapore

GP-CME Management of Diabetic Nephropathy

GP-CME Constipation in the Elderly

GP-CME Updates in COPD Management

GP-CME Management & Referrals of Common Skin Conditions

GP-CME Early Intervention in Psychosis

GP Workshop Knee Osteoarthritis/ Viscosupplementation Injector

GP-CME Updates in COPD Management

European Society of Cardiology Congress, 25-29 August, Munich, Germany

Aspirin can be dropped in PCI patients on oral anticoagulants

Investigational drug shows promise in HF

Niacin/laropiprant well tolerated in HPS2-THRIVE trial

Niacin has been shown to be an effective HDL-raising agent.

The preliminary results

suggest that about 76 percent LRPT treatment

of the patients can tolerate long-term ERN/

European Society of Cardiology Congress, 25-29 August, Munich, Germany

Aliskiren use not advised in type 2 diabetics with renal impairment

- The treatment of choice to reduce overall cardiovascular risk in hypertension management

Preferred combination approach to hypertension management

-10 -15 -20 -25 -30 -35

The ASCOT patient: Hypertention with 3 or more CV risk factors

Figure 2: Perindopril/Indapamide Prevents Stroke (PROGRESS) in post stroke patients (N=6105)

f/u 3.9y RRR - 28% ARR -3.7% NNT 27

Placebo P<0.0001 Perindopril Indapamide

Figure 3: Perindopril/Indapamide reduces All-cause Mortality in type 2 Diabetes (ADVANCE); (N=11,140)6

HR 0.86 (95% CI 0.75-0.98), P=0.025 Placebo

European Respiratory Society Annual Congress, 1-5 September, Vienna, Austria

Long-distance running raises pulmonary edema risk