Medical Tribune November 2012 SG

November 2012
Step-off approach to LABA asthma therapy under scrutiny
FORUM Vaccination the key to global health
CONFERENCE Metformin can be used more widely
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November 2012
Step-off approach to LABA asthma therapy under scrutiny

Elvira Manzano
he approach of discontinuing long-acting 2-agonist (LABA) therapy (stepoff therapy) in patients who achieve control of their symptoms on a combination of LABA and inhaled corticosteroids (ICS) may lead to exacerbation of symptoms and reduce quality of life, according to new research. A meta-analysis of five randomized controlled trials comparing step-off therapy with continued use of LABA and inhaled ICS medications found that the LABA step-off approach was linked to a rise in asthma-related impairment. Compared with patients who continued combination therapy, those who stopped treatment had fewer symptom-free days (608 vs. 622) and lower scores on questionnaires assessing quality of life and overall asthma control. They also required an average of 0.71 (95% CI 0.29 to 1.14) more puffs per day of a rescue bronchodilator and had a non-significant increase in use of oral corticosteroids (RR 1.68, 95% CI 0.843.38). There were no deaths and too few exacerbations in the studies to evaluate safety outcomes. [Arch Intern Med 2012; DOI:10.1001/archinternmed.2012.3250] The findings contradict the US Food and Drug Administrations (FDA) black box warning that LABAs, when given with ICS, should be discontinued as soon as asthma control is achieved. In contrast to FDA recommendations, our analysis supports the continued use of LABAs to maintain asthma control, said study author Dr. Jan L. Brozek from the department
of clinical epidemiology and biostatistics and medicine, McMaster University, Hamilton, Ontario, Canada. Manufacturers of LABAs are conducting further large-scale safety studies of their products, however the results of these will not be available for 5 years. In the interim, the consistent trends that we identified for many asthma impairment factors, some of which were statistically significant, favor the continued use of LABAs, said Brozek. Brozek and his fellow investigators cautioned that the studies were of short duration and had high withdrawal rates. Nevertheless, our findings likely represent the current best evidence about stepping off LABA therapy in patients with asthma. While there is consensus that LABAs have no role in asthma monotherapy, the findings help shift the burden of proof in the debate over stepped-down withdrawal of LABAs, wrote Dr. Chee M. Chan and Dr. Andrew F. Shorr, from the division of pulmonary and critical care medicine at Washington Hospital Center, Washington D.C., US, in an accompanying commentary. Moreover, they called on the FDA to reconsider the black box warning for these agents based on the findings. We hope that this meta-analysis helps to lift some of the black clouds in the debate surrounding LABAs, they said. Similarly, physicians must now reevaluate the contents of the black box for LABAs, particularly in individuals whose asthma is well-controlled with combination LABA and ICS therapy.
November 2012
Forum
Vaccination the key to global health

Excerpted from a lecture by Edith L. Maes (Ph.D.), senior research fellow, Maastricht School of Management, the Netherlands, at a media briefing in Kuala Lumpur, Malaysia.
t has been shown by historical studies that there is a relationship between health and wealth, and that it really pays for governments to invest in health. Because of the dual relationship, there is a double dividend, especially in low- and middle-income countries. The reason is that healthy populations lead to economic growth. When people remain healthy, they also develop better physical and cognitive capabilities, so that in adulthood they become more energetic and active workers, which leads to higher incomes for their families, higher productivity and greater output, which is measured as gross domestic product (GDP) for the government. It is beneficial investing in health preventative measures that do not cost much or preventative measures which need an investment, but have a payoff in the short- and long-term. It is important at the individual level, family or household level, and the government level. Firstly, it is important at the individual level, especially to children, since they are vulnerable and contract diseases very easily because their immune system is not working well. If children are healthy, its better for the families because they will be able to develop their cognitive and physical abilities so parents will be able to continue working and generating an income. But if the child is sick often, the family incurs huge medical costs. In many countries, because of large out-ofpocket expenses, it also costs households a lot of savings, which indirectly has a long-term effect.
At government level, it is important because investing in health means actually investing in the workforce. So a healthy workforce is good for the country because it increases productivity and, as a consequence, its income. One measure to express health is life expectancy. Health can be defined in many ways, so epidemiologists and economists as well have taken one common measure, which is life expectancy, to express the benefits that accrue in a healthy population.
Health can be defined in many ways...
Life expectancy is a measure at the population level its an average among all individuals that survive in society. So, if large numbers of children die prematurely, the life expectancy will go down. In the early 1900s, most countries had low levels of income and life expectancy was 55 to 60 years. Gradually, especially in western countries, health improved because of better sanitation, potable water and preventive mea-
November 2012
Forum
programs, although sometimes it is only useful for certain target groups like travelers or healthcare workers.
sures like vaccines, and that increased the life expectancy in developed countries to 65 to 75. In 2010, when we cluster the countries, the high-income countries moved up to 70 to 82 years of age and their income also increased from US$14,000 to US$47,000, so their income increased accordingly to the increase in life expectancy. So that is how economies expressed the benefits of investing in health and tried to establish the relationship. Why is it that health in such nations and communities in general can improve? It is because the government decides to take measures, which can be very simple ie, educational programs to improve sanitation at home and building infrastructure to provide potable water for everyone. One of the measures that governments have been investing in is immunization for its short- and long-term benefits. In all the studies that have been done, the global community has recognized that vaccination is one of the worlds most important and cost-effective health interventions, with positive socioeconomic effects on society. [World Economics 2005;6:15-39] Key stakeholder benefits of vaccination include reduction in morbidity and mortality among individuals, which result in healthy families, a more productive workforce and herd immunity in society. It is in the interest of governments to invest in vaccination programs that are successful ie, that reach a coverage level of above 85 percent. When that level of protection is reached in the community, weaker and vulnerable people will also benefit from the decreased pool of pathogens. In the past 30 years, there has been a rapid increase in the number of vaccines. We are now at a point where we can prevent approximately 20 diseases through vaccination
...vaccination is one of the cost-effective health interventions
worlds most important and
Looking at the evolution of vaccines the very first vaccine, for smallpox, was actually experimentally tested in the 1800s. The person who tested the vaccine in farmers found that those who had been primed with pieces of the smallpox virus did not develop smallpox later in life. Gradually, the principle of priming the immune system started being recognized as being a very effective prevention method for certain diseases. The first few vaccines were developed for diphtheria, tetanus and polio those vaccines were based on simple technology and can still protect against those killer diseases. The latest vaccines are based on complex technologies against rotavirus, pneumococcal diseases and human papillomavirus. These vaccines have taken a long time to develop, and are complex and more expensive than those developed in the 1950s and 1960s. The Global Alliance for Vaccines and Immunisation (GAVI) was founded in 2000 to fund vaccines in very poor countries that cannot afford any immunization programs or expand it with newer vaccines, and are also lacking a proper health infrastructure to provide vaccines to children in rural areas. The GAVI Alliance is a public-private partnership built on international solidarity and it devised a very innovative way of financing through donor fronts from a number of coun-
November 2012
Forum
To be able to compare with other studies and to compare between diseases, the WHO has come up with a metrics called DALY (disability-adjusted life years), which is a measurement of the gap between current health status and an ideal health situation where the entire population lives to an advanced age, free of disease and disability. This common measure allows governments to compare across diseases and technologies. We have seen many success stories in governments adopting the hepatitis B, pneumococcal and Haemophilus influenzae type B childhood vaccines. Investing in vaccination gives a high return in the short- and long-term for both individuals and society as a whole, and is based on the principle that health is a human right, so why would we deny it to ourselves or to our children?
tries and foundations including the Bill & Melinda Gates Foundation. There are a number of Western countries that have been pledging millions of dollars every year to vaccination, which can be used in the low-income countries with incomes below US$1,500 per person per year to give them an incentive to start developing their programs. Through the GAVI Alliance, rigorous government policies, and strengthening of vaccination programs at the country level, over 5.5 million lives have been saved since 2000. [GAVI Alliance Progress Report 2011. www. gavialliance.org/results/gavi-progress-reports/ Accessed on 24 September] The assessment of costs and effectiveness is becoming an increasingly important factor for policymakers faced with decisions about adding a new vaccine to national immunization programs.
November 2012
Singapore Focus
TCM docs praise lifted berberine ban

Radha Chitale
pecialists in traditional Chinese medicine (TCM) say the Singapore Health Sciences Authority (HSA) move to lift a 35-year ban on Chinese proprietary medicines containing berberine is long overdue and is a mark of respect towards their practice. The Ministry of Health prohibited the use of berberine, an alkaloid with some antibiotic properties found in the roots and woody parts of plants such as Chinese goldthread and turmeric, in 1978 after research showed it was linked to jaundice and brain damage in babies deficient in glucose-6-phosphate dehydrogenase (G6PD), which can cause anemia. At that point [the ban] was accepted because TCM wasnt regulated... and people would give herbs indiscriminately, said Dr. Yong Peng Swee, a family physician and Traditional Chinese Medicine Practitioner and Acupuncturist at Parkway Healths Integrative Medical Clinic in Singapore.
No safety concerns with berberine have been found by an HSA Berberine Expert Panel.
Berberine has been a doctors
sore point among TCM
However, TCM practice has come under review in recent decades and regulations for safety and standards of care have been put in place. Practitioners are required to complete accredited coursework and registration. The HSA said periodic literature reviews by a Berberine Expert Panel showed no safety concerns for appropriate berberine use, though it should still be avoided in babies and G6PD deficient individuals.
The ban lifts on 1 January, 2013 and allows TCM practitioners to use CPM capsules, oral liquid preparations, powders and granules containing berberine. This is the correct thing... because you can expect a certain standard from TCM, Swee said. The HSA will continue to monitor for adverse reactions and plans to implement educational programs for TCM practitioners about berberine uses and to share patient results from berberine medications. Barring more negative outcomes, the HSA may consider further lifts on Chinese herbs containing berberine by 2015. But Swee said uptake of berberine-containing medications will be slow because many current TCM practitioners would have earned
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November 2012
Singapore Focus
Swee believes they will incorporate it into their repertoires. Berberine has been a sore point among TCM doctors and is brought up at every regulatory meeting, Swee said. By taking this one small step to acknowledge that we [TCM practitioners] have done so much, the government concedes that they will also loosen control.
their degrees after the ban and have not used the compound in practice. In TCM, berberine is a heat clearing or dampness drying therapy known to have antibacterial, antiviral and antipyretic activity. Therefore, it is used to combat fever, infection and general inflammation. As younger physicians find that berberine works better than their current therapies,
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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.
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November 2012
Singapore Focus
Free eye checks, spectacles for senior citizens
t least 250 senior citizens in Singapore recently received free eye checks and eyeglasses in an eye-screening event organized by the Optometry Giving Sight (OGS), an international non-government organization helping to eliminate preventable blindness around the world. Many people take healthy sight for granted, said Dr. Stan Isaacs, chairman, Optometry Giving Sight in Singapore. Underprivileged senior citizens may not have the financial means or do not understand the importance of regular checks to maintain eye health. As a result, many are suffering from vision impairment and other preventable eye health problems. The WHO estimates that over 29,000 Singaporeans have uncorrected refractive er-
ror at distance which is the leading cause of preventable blindness and impaired vision in the world. Uncorrected refractive error is diagnosed through eye checks and corrected with eyeglasses. The eye screening program was part of World Sight Day celebrations and the Vision 2020 declaration of eliminating avoidable blindness by the year 2020.
HPB starts health-focused school clubs
o get children involved in making healthy lifestyle choices, Singapores Health Promotion Board (HPB) will partner with schools around Singapore to include Health Promotion Clubs as part of students co-curricular activity (CCA) choices. The Canberra Secondary School in Sembawang was the first to set up a Health Promotion CCA. Topics covered will include physical activity, nutrition, mental health, tobacco control and current health issues. Officials hope that participating students will help encourage healthy behaviors
among their classmates, family and community. HPB aims to start 20 similar programs at secondary schools across Singapore by 2015. To develop youth leaders and advocates in health promotion, HPB is also teaching club members the basics of running health promotion outreach activities, honing their skills in project management, planning and communication as well as offering them the opportunity to take part in national health campaigns, said Mr. Ang Hak Seng, HPB chief executive officer.
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November 2012
Singapore Focus
ClinicalKey search tool launched

new search engine, which uses clinical definitions of medical terms to sort through peer-reviewed, evidence-based content to find the most relevant answers to search queries, has been launched. Elseviers ClinicalKey search tool sorts through over 900 textbooks and 500 medical journals, including Lancet, Gastroenterology and the Journal of the American College of Cardiology, and offers relevant content as well as expert commentary, videos, MEDLINE abstracts and some third-party journals. The search tool has some unique features such as the ability to click straight to content and a presentation maker. It has access to Elseviers entire library of resources including practice guidelines, drugs, and patient education materials. Since ClinicalKey uses clinical terms to
search, it returns relevant content more quickly and may catch content that a general search engine might overlook. The results could improve and streamline workflow.
Opthalmology award helps identify AMD subtypes

ifferentiating subtypes of age-related macular degeneration (AMD) can be tricky but Dr. Gemmy Cheung, consultant ophthalmologist at the Singapore National Eye Centre, is attempting to improve the process. With a US$25,000 research award from Bayer HealthCare, Cheung plans to develop a simple algorithm based on a variety of physical characteristics of the eye to determine whether a patient suffers from polypoidal choroidal vasculopathy (PCV), a type
of AMD that benefits from laser treatments, not injections like normal AMD. PCV occurs in about half the AMD population and a special screen for everyone is expensive, Cheung said. Gauging response to AMD injections before screening for PCV can delay diagnosis or miss patients. Cheung and colleagues have collected the initial data and she said the award funds will help them analyze it, test their algorithm, and validate it in Japanese and UK populations.
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November 2012
Singapore Focus
Kids race against rotavirus

lose to 100 children under 12 raced around Bishan-Ang Mo Kio Park last month to raise awareness of rotavirus infection. The Human Race Against Rotavirus Bike Hike 2012 was organized by the Singapore Paediatric Society (SPS). SPS president Professor Anne Goh said many parents underestimate the potential severity of rotavirus infection which is the leading cause of severe gastroenteritis in young children. In Singapore, up to 40 percent of diarrhea-related hospitalizations are caused by rotavirus. The children suffer from prolonged diarrhea, vomiting, fever, abdominal pains and a loss of appetite. The most common com-
plication is dehydration. In severe cases, the child is put on a drip which adds to the trauma and suffering. Severe dehydration can be fatal in rare cases. Goh urged parents to consider vaccination of infants and young children and to take necessary precautions, such as hand washing, to control the spread of the infection.
Doctors wave for arthritis

octors across Singapore marked their support for a World Arthritis Day with a wave for arthritis encouraging people to actively prevent arthritis. The Sanofi Knee Pain Survey results, which were released to coincide with the event, revealed that 73 percent of Singaporeans are at risk of knee osteoarthritis (OA). Knee OA starts as knee pain and stiffness, but it can become a very serious condition. If left untreated, joint deformities can start to develop leading to limited mobility and even disability, said Dr. Yoon Kam Hon, rheumatologist at El Shaddai arthritis and rheumatism specialist medical centre, and consultant rheumatologist at Changi General Hospital, adding that young adults can also be affected. Early detection is critical in delaying disease progression, and waiting too long to seek treatment could adversely affect the quality of life, said Yoon.
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November 2012
Singapore Focus
No pain more important than longer life

Radha Chitale
ingaporeans would trade a year of their life to avoid dying in pain or away from home, according to a community-based local survey. Findings from a Duke-NUS Graduate Medical School and Lien Centre for Palliative Care survey of over 500 adults aged 50 and older indicated that people are willing to spend S$24,000 per year to avoid pain at the end of their lives, Survey respondents said they would spend S$13,200 to die in a home setting versus in a hospital or other institution but only S$9,100 to extend their lives by 1 year. Lead researcher Dr. Chetna Malhotra, an assistant professor at the Lien Centre, noted that as treatment options for advanced illness expand and as overall lifespan increases, patients are living longer with end-stage disease. Malhotra said the survey was meant to determine patients priority issues when faced with end-of-life care decisions and the results have significant policy implications and suggest a stronger role for palliative care, and indicate that extending life at high cost is not an attractive option. Is there a rationale for the government to provide subsidies on [expensive end-stage] therapies when people are not willing to pay for it? she said. We think end-of-life care can be improved and its not by focusing on treatments that extend life but its by focusing on these other things that people seem to be telling us they value even more, said Dr. Eric Finkelstein, an associate professor at Duke-NUS and a collaborator on the survey .
Survey findings suggest that people are willing to spend more to avoid pain than extend their lives.
The value estimates reported in the study may be even more conservative, Malhotra pointed out, because they were given by healthy individuals who could change their minds when faced with care decisions during end-stage disease.
Singaporeans would trade a year of their life to avoid dying in pain
Individuals were likely to under-insure and under-invest in their Medisave or make advanced care planning decisions that would suggest too little end-of-life care, she said. Cost was the most important deciding factor for care in 23 percent of respondents, who always chose the cheaper treatment option. Not burdening family and friends with end-of-life care, either by the number of hours per day spent caring for the patient or by providing out-of-pocket or Medisave financial
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November 2012
Singapore Focus
they near death is critical because people do value avoiding pain and their quality of health care much more than extending life... so palliative care should play a role, Malhotra said. The survey findings were presented during the recent Lien Centre for Palliative Care conference.
support was important to respondents, but not as much as issues surrounding pain, place of death or survival. Respondents also indicated the importance of quality of care but Malhotra said it was unclear was weather patients assumed that a better healthcare meant more positive outcomes. Educating people about their options as
National science awards recognize robotics and infection research

Radha Chitale
even researchers from Singapore were selected to receive the 2012 Presidents Science and Technology Awards for their contributions to knowledge in their fields. Among the winners were researchers who pioneered a novel minimally invasive surgical technique and researchers who characterized the virulence mechanism of a common infectious fungus.
expected to take over open surgery and laparoscopic surgery as the most common surgical procedure moving forward Professors Lawrence Ho of the Department of Gastroenterology and Hepatology at the National University Hospital (NUH) and Associate Professor Louis Phee of the School
Endoscopic surgery is
of Mechanical and Aerospace Engineering at Nanyang Technological University (NTU) received the Presidents Technology Award for developing the first ever robotic flexible endoscope in which tiny claws attached to the end of a flexible tube inserted into the mouth that performs no holes surgery. So far, the novel endoscopic surgery technique has been used to successfully remove small tumor masses in the stomach in a number of trial patients but the researchers said the implications of the device are huge. Instead of cutting through skin and muscle tissue to access organs, the endoscope may be able to perform stomach surgeries or even access organs in the peritoneal cavity through a small hole in the stomach itself, which would significantly reduce hospital stays and possibly surgical costs. Endoscopic surgery is expected to take over open surgery and laparoscopic surgery as the most common surgical procedure moving forward, Phee said. We are going
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November 2012
Singapore Focus
infectious, the master regulatory gene that controls how benign C. albicans transform into their virulent state, and identified molecules in the blood required to activate the transformation. By doing this we solved a 50-year mystery, Wang said. C. albicans is very common in intensive care units of hospitals and the number of immunocompromised patients is large... This is great inspiration and encouragement for us to do even better in the future so we can make more important discoveries that will be useful for diagnosis and treatment. Professor Dim-Lee Kwong, executive director of the Institute of Microelectronics at A*STAR, received the Presidents Science and Technology medal, for his research on semiconductors and microelectronics and as recognition for his initiatives to involve Singapore in the global research community. Three other researchers from NUS, NTU and A*STAR won Young Scientist Awards.
into a paradigm shift and we strongly believe that our robotic system is the platform to go into this next shift.
This is great inspiration and encouragement for us to do even better in the future...
The Presidents Science Award was presented to Professor Wang Yue of the Institute of Molecular and Cell Biology at the Agency for Science, Technology and Research (A*STAR) for his body of research to characterize the virulence mechanism of the human fungal pathogen Candida albicans that may lead to new therapies for this and other infectious agents that account for many hospital-acquired infections. In the past decade alone, Wang and his team have identified the key virulence gene without which C. albicans cannot become
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cushion between joint bones wears away, resulting in painful bone-on-bone contact during movement. Non-surgical treatments include non-steroidal anti-inflammatory drugs, corticosteroids or viscosupplementation with injectable materials such as hyaluronic acid that provide temporary cushioning in the joint area to reduce pain and prolong time until surgery. Knee surgery can still be an eventuality but 45 percent of survey respondents were unwilling to go for surgery because of the costs, the time necessary for rehabilitation and the pain involved. The number of knee replacement surgeries per year in Singapore has more than doubled over the past decade, up from 700 in 2000 to 2,000 in 2011, Lee said. Lee is conducting a trial to compare the effects of hyaluronic acid injections on osteoarthritic knees undergoing microfracture to attempt to repair some of the cartilage versus the effects of a combination of hyaluronic acid and mesenchymal stem cell injections. I dont think anything can regenerate cartilage, but [injectable treatments] do alleviate pain and may improve quality of life, he said.
Knee pain sufferers often avoid treatment

Radha Chitale
lmost half of elderly Singaporeans suffer from knee pain, according to a small local survey, but a significant proportion avoid seeking treatment, citing pain as one of the side effects of age or the cost of medical care. Patients choosing to limp around and delay treatment can worsen their condition, said Dr. Kevin Lee, medical director for the Centre for Joint and Cartilage Surgery and the Singapore Sports Orthopaedic Surgery Centre. The survey included 210 Singaporeans aged 50-69 years, of which 42 percent experienced knee pain, many for 5 years or more. Of the 53 percent who sought treatment, most said they consulted their general practitioner while others consulted polyclinic doctors, Chinese physicians or private specialists. The most common self-treatment methods were pain relieving creams or oils and herbs. The most common prescribed treatments were painkillers, nutritional supplements like glucosamine, and traditional Chinese medicines. However, advanced knee pain may be the result of osteoarthritis, in which the cartilage
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November 2012
Singapore Focus
Sutureless valve replacement a novel option in aortic stenosis

Elvira Manzano
ardiac surgeons at the National University Hospital Singapore have successfully performed sutureless aortic valve replacement using a new generation bovine pericardial device (Perceval S, Sorin). Two patients with severe aortic stenosis who had a diseased native valve and one with an old prosthetic valve have so far benefited from the procedure. One of the patients had an old valve that was broken and had to come out, so we performed redo operation using the Perceval S valve, said Associate Professor Theodoros Kofidis, senior consultant, Department of Cardiac, Thoracic, and Vascular Surgery, National University Heart Centre, Singapore (NUHCS). This was the first time Perceval S was used in the region in redo setting, which is riskier and requires longer surgery. Through an incision in the chest, the diseased aortic valve was excised and three guiding sutures were placed beneath the leaflet insertion line to ensure accurate positioning of the new prosthetic valve within the aortic annulus. Unlike conventional aortic valve replacement that uses several interrupted sutures to secure the valve, the Perceval S valve does not need surgical fixation. Once the prosthesis is released, annular sealing is obtained with brief low-pressure balloon dilation. Sutureless heart valves are just one milestone in our journey to continuously improve the quality and safety of patient care
Surgeons conduct a post-implantation check.
in NUHCS, said Dr. Kristine Teoh, consultant at the Department of Cardiac, Thoracic and Vascular Surgery, NUHCS who trained with Kofidis on the new surgical technique. Patients who require more complex cardiac surgery (eg, combined valve and coronary bypass surgery) and those at risk for routine aortic valve surgery would benefit the most from Perceval S valve. The device is made of animal tissue and mounted with nitinol, a combination of nickel and titanium. As it is self-anchoring, no sutures are required, thus minimizing surgical time and operative risks, said Kofidis. With advancing technology, a rich spectrum of implants and devices is at hand to allow the surgeon to adapt therapy according to the individual patients requirements. Sutureless valves promise to have a stake in the heart surgeons armamentarium. Although new in Singapore, the Perceval S valve has been around for the last 4 years and used in more than 700 patients around the world, with excellent results.
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Singapore Focus
21/11/12 GP-CME Child Psychiatry Case Examples
Info : National Healthcare Group (NHG) Polyclinics Tel : +65 6353 2461 Website : www.nhg.com.sg/events.asp?eventgroup=4
Singapore Events
6/11/12 GP-CME Clinical Management of Bronchial Asthma
7/11/12 GP-CME Updates in COPD Management

23/11/12 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
8/11/12 GP-CME Overview of Problem and Pathological Gambling

23/11/12 GP-CME Approach to Patient with Psychosis

19/11/12 GP-CME Hand Conditions

28/11/12 GP-CME Clinical Management of Bronchial Asthma

21/11/12 GP-CME Managing Allergies in Children

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November 2012
Conference Coverage
48th Annual Meeting of the European Association for the Study of Diabetes, 1-5 October, Berlin, Germany
EASD/ADA promote individualized therapeutic goals in T2DM

Leonard Yap
he European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have released a new joint position statement on the treatment of type 2 diabetes mellitus (T2DM). [Diabetes Care 2012;35:1364-1379; Diabetologia 2012;55:1577-1596] Designed to be less prescriptive than previous guidelines, the new statement advocates more patient involvement and gives guidance on the rational approach to the choice of therapy. This choice will now combine the best available evidence from the literature with the clinicians expertise and the patients own inclinations. Given the uncertainties in terms of type and sequence of therapies, this approach is particularly appropriate in T2DM, said EASD president Professor Andrew Boulton from the University of Manchester School of Medicine and consultant physician at the Manchester Royal Infirmary in the UK. Ultimately, it is the patients who make the final decisions on their lifestyle choices and, to some degree the pharmacological interventions they use, said Boulton, adding that implementation of therapy occurs in the context of the patients real lives and relies on the consumption of resources. The overarching goal should be to reduce blood glucose concentrations safely to a range that will substantially minimize long-term
The new statement focuses on the individual patient rather than one fits all therapy.
complications, but always keeping in mind the potential adversities with treatment burden, particularly in the elderly who are more often exposed to multiple drug treatments, Boulton said. The new recommendations of EASD and ADA called for individualized interventions in T2DM but also individualized goals for different patients. In the past, general recommendations regarding the intensiveness of glycemic therapy focused on a HbA1c target of below 7 percent. The statement emphasized the need to be pragmatic and to keep goals individualized.
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November 2012
Conference Coverage
sess the effectiveness of T2DM interventions. How this might translate to actual effects on the quantity and quality of our patients lives remains largely unknown.
The long-term effects of T2DM reveal themselves over the course of decades, which makes distinguishing the effects of medical interventions difficult, said Dr. Silvio Inzucchi, co-chair of the position statement and professor of medicine, Yale University School of Medicine, New Haven, Connecticut, US. Clinical investigators have been forced to use biochemical surrogates such as HbA1c to as-
This approach is in T2DM
particularly appropriate
Key points from the position statement:

Diet, exercise and education remain the foundation of any type 2 diabetes treatment program Unless there are prevalent contraindications, metformin is the optimal firstline drug A fter metformin, combination therapy with an additional one or two oral or injectable agents is reasonable, aiming to minimize side effects where possible Ultimately, many patients will require insulin therapy alone or in combination with other agents to maintain glucose control Comprehensive cardiovascular risk reduction must be a major focus of therapy
The precise glycemic target takes into account several factors including patients attitude and expected treatment efforts, risks associated with hypoglycemia and other adverse effects, disease duration, life expectancy, other co-morbidities, established vascular complications, and the patients own resources and support system. For example, some patients may feel that the weight gain associated with a particular diabetes therapy is unacceptable, and want other options to be considered. Older patients with multiple comorbidities will have different issues compared with a younger newly-diagnosed person that is otherwise healthy. The position statement pointed out that there is a need for numerous studies in specific subgroups of people of different ages and with different stages of diabetes, in order to assess the various possible combinations of glucose-lowering therapies.
23
November 2012
Conference Coverage
Enterovirus may be linked to type 1 diabetes

Leonard Yap
n enterovirus infection may be a cause of type 1 diabetes (T1D) in some patients, says an expert. Evidence suggests that an infection of pancreatic islet beta-cells with one or more serotypes of enterovirus may contribute to the development of autoimmunity in some patients with T1D, said Professor Noel G. Morgan from the University of Exeter Medical School, UK. The evidence has arisen from various sources, ranging from large-scale epidemiological studies undertaken across populations, to the isolation of productive virus strains from individual pancreas samples [in rare cases], Morgan said. However, despite the increasing weight of evidence, the hypothesis that an enteroviral infection might play a role in the etiology of T1D remains unproven. Morgans research team studied a collection of pancreas samples recovered post-mortem from patients who died soon after a diagnosis of T1D. This cohort was used to study both viral protein expression and the establishment of anti-viral response mechanisms at the level of individual islet cells. The teams aim was to determine whether individual islet endocrine cells displayed evidence of viral infection in human T1D and to establish, at the molecular level, how the cells responded to such infection.
The progression of human type 1 diabetes may be influenced by beta-cell enteroviral infection.
By monitoring expression of the enteroviral capsid protein, VP1, as a marker of infection, it was revealed that more than 60 percent of the pancreatic samples tested positive for enteroviral infection. However, within any given patient, only about 20 percent of insulin-containing islets expressed immunoreactive VP1 and the overall proportion of available -cells that expressed VP1 was small (about 5 percent). A similar prevalence of immunopositivity was confirmed in a smaller, but more contemporary, cohort from within the Juvenile Diabetes Research Foundation (JDRF) nPOD series from the US. Morgan and co-workers also monitored the expression of various other proteins, including protein kinase R (PKR) and myeloid cell leukemia-1 (Mcl-1), in concert with VP1.
24
November 2012
Conference Coverage
ated with the mounting of an active antiviral response. The data are consistent with the hypothesis that the progression of human type 1 diabetes may be influenced by beta-cell enteroviral infection. Morgan believes that it is entirely possible that additional mechanisms beyond enteroviral infection can act as triggers leading to islet autoimmunity. It is also probable, however, that enteroviruses may be able to maintain a low-level persistent infection of islet cells under conditions when they produce minimal amounts of viral protein, he added. Hence, the failure to detect them by analysis of protein production in tissue sections does not necessarily mean they are not there.
PKR is an enzyme responsible for the activation of antiviral cascades within cells and is known to be induced during enteroviral infection. It is activated by the presence of viral dsRNA and leads to the rapid arrest of global protein synthesis by virtue of increased phosphorylation of the initiation factor eIF2. Mcl1 is an anti-apoptotic protein which is subject to rapid turnover in cells, such that it is degraded quickly during the translational arrest that ensues following the activation of PKR. Collectively, our data imply that enteroviral infection can be detected within a small proportion of -cells in the majority of patients with recent-onset type 1 diabetes, said Morgan. Moreover, this infection is associ-
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November 2012
Conference Coverage
Stroke risk high in diabetes patients

Alexandra Kirsten
ype 2 diabetes is associated with an increased risk of stroke in the long term, suggests new research. A recent large-scale study involving 1,334 patients with type 2 diabetes found a cumulative stroke incidence of 12 percent over a 10year follow-up period. The morbidity and mortality due to stroke in persons with type 2 diabetes mellitus is 3 to 4 times higher than in the general population, explained study author Dr. M. Bernas from the department of internal diseases and diabetology at Warsaw Medical University, Warsaw, Poland. The study patients, who were all attending the same outpatient diabetic clinic, included 597 men and 737 women, and had an average age of 62.6 years and a mean duration since diabetes diagnosis of 9.4 years. Clinical determinants such as BMI, blood pressure, fasting and postprandial glycemia, cholesterol, triglycerides, creatinine, albuminuria, and co-existing complications and co-morbid states, were recorded at baseline and every year during the 10-year study period. Morbidity and mortality due to stroke were determined and correlated with potential risk factors every year separately and as a cumulative value for the whole period. At baseline, 62 patients (4.6 percent) had a previous history of stroke. In the 10-year period, 135 new episodes of stroke (in 7.5 percent
Type 2 diabetes has been shown to be a long-term risk factor for stroke.
of patients) were observed. The cumulative incidence of stroke was 12.1 percent, which equated to 10.8 cases per 1,000 patient-years. The cumulative mortality due to stroke was 11.0 percent. Statistically significant risk factors included age (95% Cl 1.03-1.07; P<0.001), fasting glycemia (95% Cl 1.17-3.39; P<0.05), daily albuminuria (95% Cl 1.02-4.06; P<0.05), atrial fibrillation (95% Cl 1.39-6.09; P<0.01) and smoking (95% Cl 1.17-3.00; P<0.01). These are the main objectively established clinical risk factors for stroke, summarized Bernas. This information should be taken under consideration in building up an individual plan of stroke prevention since the efficacy of the prevention of stroke stands up as the hot problem in diabetes mellitus care, she concluded.
26
November 2012
Conference Coverage
Insulin infusions beneficial in diabetics post-stroke

Alexandra Kirsten
atients with type 2 diabetes who experience an acute episode of stroke seem to benefit more from continuous intravenous insulin infusions than from intermittent subcutaneous injections. Hyperglycemia is associated with [a] worse outcome in stroke patients, said Leonid G. Professor Strongin from the State Medical Academy, Nizhny Novgorod, Russia. The benefits of intravenous infusions for blood glucose control in patients with stroke and type 2 diabetes mellitus are proved at a target glucose level less than 7 mmol/L, but it is not so obvious for the more acceptable range of 7.8-10 mmol/L, he explained. Strongin and colleagues conducted a clinical study to compare the efficacy and safety of the two different insulin delivery methods in patients with type 2 diabetes who had experienced a stroke. A total of 73 patients were subdivided into two comparable groups within 24 hours of the stroke event, with one group assigned to receive continuous insulin infusions and the other intermittent subcutaneous insulin injections, in order to achieve blood glucose levels between 7.8 and 10 mmol/L. Overall, 97 percent of the patients in the insulin infusion group achieved the glucose target compared with only 71 percent
of those in the injection group (P=0.012). The mean daily glycemia level was 8.7 mmol/L in the infusion group and 9.7 mmol/L in the comparison group (P=0.025). Additionally, the infusion group reached the target glucose levels faster (2-3h vs. 3-6h, P=0.0019) and showed a smaller amplitude of fluctuations of glycemia (0.95 mmol/L vs. 5.3 mmol/L, P<0.01). The frequency of hypoglycemia was significantly lower in the infusion group than in the comparison group (9 percent vs. 22 percent, P=0.037). Patients in the basal group presented with better scores in the Barthel Activities of Daily Living Index (BADLI) at the time of discharge (45 vs. 20 points P<0.01) and after 6 months (62 vs. 47, P=0.006). However, there were no significant differences in hospital mortality between the groups: in the infusion group 25 percent of the patients died, in the control group 32.4 percent died (P=0.32). Glucose control using continuous intravenous insulin infusions has advantages in regressing neurological deficit, improving functional recovery and decreasing risk of hypoglycemia, concluded Strongin. But, the impact of routes of insulin administration on 6-month survival could not be proved.
27
November 2012
Conference Coverage
Exercise lowers CV risk in diabetics

Alexandra Kirsten
new study has reported that leisure-time physical activity (LTPA) can significantly reduce the risk of cardiovascular (CV) events in patients with type 2 diabetes. Dr. Bjrn Zethelius and colleagues from Uppsala University in Uppsala, Sweden reviewed data on leisure-time physical activity from 15,462 patients with type 2 diabetes registered in the Swedish National Diabetes Register (NDR). In their study, patients were grouped as either low physical activity (no regular exercise or exercise once per week) or regular exercise (between three times per week and daily exercise). If a patient died during the course of the study, his or her last recorded physical-activity level was used for the analysis. The yearly recorded data showed that regular exercisers were significantly less likely to have a cardiovascular event or to die either from cardiovascular disease or any other cause. The level of LTPA was related to fatal CV outcomes and all-cause mortality independently of conventional CV risk factors in type 2 diabetes. An increased LTPA level during the follow-up seemed to lower both CV risk and mortality in diabetic patients. Those in the study who reported doing little or no physical activity at baseline but who managed to increase their regular exercise to at least three times per week by the end of the study period (average 4.8 years) had even greater benefits. Compared with individuals who did not improve their exercise hab-
its, the number of CV-related deaths among diabetics who increased their exercise levels fell by 67 percent (95% CI 0.17-0.60). Rates of all-cause mortality were reduced by almost the same degree (95% CI 0.25-0.49). In general, Its never too late to increase your physical diabetics are activity, a recent study suggests considered to be less likely to engage in a regular exercise program than the general population, stated the researchers. However, approximately 1,800 patients moved from a low physical-activity category into a higher physical-activity level over the course of the study. We consider physical activity and dietary advice as the basal treatment for diabetes, and when it fails, different types of pharmacological treatment are added, Zethelius explained. But what this study shows is that its never too late to increase your physical activity. Even when you are on medication, if you increase your physical activity, you will lower your risk for cardiovascular diseases.
28
November 2012
Conference Coverage
Metformin can be used more widely, study suggests

Alexandra Kirsten
he effectiveness and overall benefits of the antidiabetic drug metformin far outweighs its risks, even in patients with renal impairment, according to a Swedish study. The long-term effectiveness and safety of glucose-lowering medications are under debate, said lead study author Dr. Nils Ekstrm from the Sahlgrenska University Hospital in Sweden. Metformin in particular is normally not prescribed for patients with reduced kidney function because the risk of adverse effects is widely regarded as unacceptably high. Ekstrm and his colleagues evaluated the risks of cardiovascular disease, lactic acidosis, serious infections and mortality in 51,675 patients with type 2 diabetes registered in the Swedish National Diabetes Register (NDR). The patients were grouped according to their medication (ie, metformin monotherapy, insulin monotherapy and therapy with other oral hypoglycemic agents). The researchers analysed risks of fatal/non-fatal cardiovascular disease (CVD), acidosis/serious infection and all-cause mortality in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. The mean follow-up of the study was 3.9 years equivalent to more than 200,000 patient-years at risk. After adjusting for clinical characteristics, risk factors and treatments, insulin monother-
apy was associated with an increased risk of fatal and non-fatal CVD and all-cause mortality compared with metformin monotherapy (95 % CI 1.07-1.29 and 95% CI 1.19-1.50, respectively). In subgroup analyses, metformin was not associated with an increased risk of any of the outcomes in patients with eGFR 3045, 45-60, or >60 mL/min/1.73 m2 compared with all other hypoglycemic agents. Of note, on a subgroup of patients with renal impairment (eGFR 45-60 mL/min/1.73 m2), metformin showed a reduced risk of any acidosis/serious infection and all-cause mortality. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects. These results support the less strict approach to metformin use in patients with renal impairment advocated in most guidelines, the researchers said. Thus, the drug can be prescribed for many more patients with diabetes than is currently the case. According to Ekstrm, a number of other countries already recommend metformin for patients with mild kidney impairment. Nevertheless, it is important to keep in mind that the results are for patients with mild to moderate kidney impairment, he pointed out. Metformin still cannot be recommended for patients with severe kidney impairment and should be prescribed with great caution for those patients.
29
November 2012
Hepatitis
Children or young adults with CHB may benefit from earlier treatment
Radha Chitale
reating chronic hepatitis B (CHB) in younger patients before they begin to show signs of liver damage could help to control or clear the disease better than starting treatment later, researchers said. When patients are young, from children up to young adults, the disease is not very aggressive, said lead researcher Professor Antonio Bertoletti, director of the Infection and Immunity Programme at Singapores Institute for Clinical Sciences at the Agency for Science, Technology and Research (A*STAR). The assumption that has always been present is that these patients dont have any strong immune response against the hepatitis B virus. In the first study to compare young patients and adult patients, who were infected at birth or in the first year of life and had similar disease profiles, the researchers isolated T-cells from CHB patients of various ages and measured levels of inflammatory cytokines and the number of HBV-specific Tcells. [Gastroenterology 2012;143:637645] Their analysis showed that inflammation levels in younger patients were similar to those of healthy control subjects and that their immune systems were primed with higher levels of T-cells that fight off HBV infection than adults with CHB. International guidelines recommend delaying treatment for CHB until the liver begins to deteriorate as a result of the increased immune response to the virus. But the results did not support the theory that younger patients with CHB existed in a state of asymptomatic immune tolerance,
Study results do not support the international guidelines recommending delayed treatment for CHB in children.
in which the immune system does not recognize or attack a disease target, until they grew older. Young patients have an immune response against the virus that is better than adults that work to keep the level of virus down, but it is not sufficient to clear it, Bertoletti said. Typically, adults show signs of liver damage after the age of 30, by which time their Tcells have become fatigued and are no longer performing optimally. Control rates for HBV drugs are about 20 percent. Cure rates are significantly lower, about 2-3 percent, Bertoletti said. Positive therapeutic effects are often temporary and viral levels increase once patients think the virus has cleared and stos taking medication. CHB infections can lead to cirrhosis of the liver, liver cancer and liver failure. The implication is that young patients have an immune reaction against HBV, perhaps they should be monitored when they are young and not just when they become adults, Bertoletti said. It could be that treating patients when they are younger could yield a better response.
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31
November 2012
Hepatitis
Hep C therapy just as effective for prisoners

Elvira Manzano
rison inmates infected with hepatitis C virus (HCV) are just as likely to benefit from cornerstone antiviral treatment with combination pegylated interferon (PEG-INF) and ribavirin as community patients, a recent US study has shown. In the study, rates of sustained viral response (SVR) did not differ between the two groups 42.9 percent for incarcerated patients and 38 percent for non-incarcerated patients (P=0.304). [Hepatology 2012; DOI:10.1002/hep.25770] Given that a history of intravenous drug use is more frequent among inmates, there is a higher prevalence of HCV infection in the prison population, said lead study author Dr. Michael Lucey, chief of the Division of Gastroenterology and Hepatology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, US. HCV treatment during incarceration provides an opportunity to make a significant improvement to public health. Previous studies have shown that inmates were 156 times more likely to acquire hepatitis C, compared with at-risk individuals in the community. In the US, up to 31 percent of inmates have chronic hepatitis C infection compared with only 2 percent in the general population, yet inmates are among the most
difficult population to reach with critical health information and treatment. The researchers compared antiviral therapy between incarcerated and non-incarcerated patients at an academic center in the US between January 2002 and December 2007. Ninety-seven (out of 234) inmates achieved SVR compared with 115 (out of 319) in community patients. All patients in the study have non-genotype 1 virus and are not co-infected with HIV. The same number of patients from both groups completed full treatment. SVR, or undetectable HCV load in the blood 6 months after completion of treatment, is almost synonymous to a cure. Patients who achieve that status experience slower progression of liver disease, however, a portion of patients relapse shortly after therapy is stopped. Our findings highlight the effectiveness of antiviral therapy in HCV-infected prisoners and show that it is as successful as treatment for HCV patients in the general population, Lucey said. A correctional setting may be an optimal setting for treatment that will help curb the hepatitis C public health crisis. The research was funded by the American Cancer Society Research Scholar Grant and the National Institutes of Health.
32
November 2012
News
lie Minogues breast cancer, which led to an increase in unscreened women in the target age range having mammography, but also to an increase in young women at very low risk seeking mammograms and thus being exposed to unnecessary radiation and falsepositive investigations. The ambivalence about this effect reflects the debate about the wisdom of breast cancer screening, he said, but it should not blind us to the potential value of celebrity engagement in important causes. In response to Chapmans comments, Dr. Geof Rayner, former chair of the UK Public Health Association and Honorary Research Fellow at City University London, England, said he remains concerned about the influences of celebrities who dabble in the public health arena. While celebrities might help to boost campaigns in the short term, Rayner said they must tread a cautious path of support because of the risk that the celebrity becomes the story, not the campaign. [BMJ 2012;345 DOI: http:// dx.doi.org/10.1136/bmj.e6362] Certainly celebrities help shift products, but according to Rayner this has become mainstream marketing strategy across society, even in politics. Rather than relying on media stunts, modern health campaigners need to go on the offensive against junk food, alcohol, gambling, and other often celebrity linked, commercial propaganda. Rayner postulated new measures to promote public health, for example campaign groups that bring together the lobbying power of thousands of ordinary people through the internet. Some celebrities might help, but lets not look for saviours, buoyed by the happy thought that the work is done when a celebrity is involved. Thats a lie too, Rayner concluded.
Do celebrities help public health campaigns?

Alexandra Kirsten
elebrities can help to promote public health and are effective in doing so, says a public health expert in Australia. While celebrities are not always health experts, unlike many health experts, they often speak personally and bring compelling authenticity to public discourse, wrote Dr. Simon Chapman, professor of public health at the University of Sydney, Australia, in a recent editorial published in the British Medical Journal. [BMJ 2012;345 DOI: http://dx.doi. org/10.1136/bmj.e6364] Critics of celebrities in health campaigns point to examples which have gone badly wrong. They focus on celebrity endorsement of flaky complementary medicine and quack diets or incidents where celebrities have veered away from the message. On the contrary, Chapman suggests there are many examples of celebrity engagement that have amplified news coverage about important neglected problems or celebrity involvement in campaigns to promote evidence-based health policy reform. Talking about the case of Australian cricketer Shane Warne, who accepted a six-figure sum to use nicotine replacement therapy to quit smoking, Chapman said we should not expect perfect outcomes after celebrity engagement and need to be realistic about the need to sustaining public campaigns beyond their first burst. When photographs appeared of the sportsman smoking again, many experts failed to exploit the important message about the risks of relapsing, said Chapman, instead climbing on a cynical populist bandwagon about his alleged motives. He also mentioned Australian singer Ky-
33
November 2012
News
Self-harmers at increased risk of premature death

Malvinderjit Kaur Dhillon
eople who intentionally harm themselves are more than three times as likely to die prematurely as the general population from natural and external causes. The risk of premature death is also much higher for individuals living in socially disadvantaged areas, according to a UK study. The study, published in The Lancet, looked at 30,000 individuals who were attended to at emergency departments in Oxford, Manchester and Derby following attempts of self-poisoning or self-injury between 2000 and 2007. The causes of premature death and years of life lost (YLL) were assessed and compared with the general population. Links to socioeconomic deprivation were drawn using residential postcodes. [The Lancet doi:10.1016/ S0140-6736(12)61141-6] The study found that 6 percent (1,832) of these patients died during the median 6-year course of follow up. Death from natural and external causes including suicides, accidental poisonings and accidents other than poisoning was markedly increased for both sexes, equating to an average of 30 YLL for each individual. Accidental poisoning was the most common cause of premature death, followed by suicide. However, the researchers found that deaths from natural causes were 2.0 to 7.5 times greater than expected, with diseases of the digestive and circulatory systems, and mental and behavioral disorders (largely due
to psychoactive substance abuse) the largest contributors. The researchers also found that the risk of early death from natural causes was closely linked with socioeconomic status, with the risk increasing with greater economic deprivation. Our study confirms that the increase in premature death among people who selfharm is not limited to suicide or other external causes, but includes dying prematurely from a wide variety of natural causes such as diseases of the circulatory and digestive systems which accounted for a third of deaths in our study, said Professor Dr Keith Hawton, a consultant psychiatrist at Oxfordshire and Buckinghamshire Mental Health NHS Foundation Trust and professor of psychiatry at Oxford University. Our findings have significant public health implications, and emphasise the importance of assessing physical health as well as psychosocial problems as part of standard checks when individuals present with self-harm, he said.
34
November 2012
News
Keep older drivers on the road, says expert

Alexandra Kirsten
andatory medical screening of older drivers which has been imposed in some European countries and is proposed in the UK is not evidencebased and may have dangerous consequences, a gerontologist has said. Age-related medical screening should be abolished, said Professor Desmond ONeill, consultant physician in geriatric and stroke medicine at Trinity College, Dublin, Ireland, recently in the British Medical Journal. [BMJ 2012;345 DOI: 10.1136/bmj.e6371] Older drivers not only have an enviable crash record, but they also raise traffic safety among other generations, explained ONeill. The risk of serious injury to children is halved if driven by grandparents rather than parents, he said, yet the belief that older drivers pose a disproportionate risk to other road users refuses to die. His suggestion that medical screening for older drivers be abolished does not imply professional neglect of their medical fitness to drive, he added. ONeill said a recent report from a UK parliamentary charity that overstates the risk of older drivers and recommends training for them was disappointing and an unnecessary measure of dubious value. According to him, several practitioners are confusing increased risk of death because of fragility with crash risk. In addition, they may lack sufficient gerontological training to understand that the positive aspects of ag-
It is a misnomer that older drivers pose high risk to other road users.
ing, such as wisdom and strategic thinking, help in adaptation and compensation to the vicissitudes of later life. Previous studies on medical screening showed a hazardous shift from protected to unprotected road user, explained ONeill. When the Danish government added a cognitive screening test to the medical screening test for older drivers, it did not reduce the rate of older people dying in car crashes but significantly increased the risk these people had of being injured as pedestrians. We need flexible transportation options responsive to the needs of older people and car safety features designed with the elderly in mind, he said. The emergence of better guidelines for doctors dealing with opportunistic screening among older patients in the clinical setting is of enormous value. Rather than mass screening, we should focus on evidence based innovations, such as restricted licensing and rehabilitation, for people with agerelated illness.
35
November 2012
Research Reviews
Reconstructive surgery for female genital mutilation
n the last 10 years female genital mutilation (FMG) has affected 130-140 million girls worldwide, with 92 million in Africa. Now surgeons in France have reported the results of genital reconstructive surgery on 2,938 women between 1998 and 2009. The mean age at FMG was 6.1 years and the mutilative procedures had been performed mainly in Mali, Senegal, and the Ivory Coast, but 564 had been done in France. Reasons given for requesting reconstructive surgery were recovery of identity (99 percent), improvement in sex life
(81 percent) and pain reduction (29 percent). Only 866 women (29 percent) attended the 1-year follow-up but most of them reported improvement in pain and sexual satisfaction. Women may benefit from reconstructive surgery after FMG. A multidisciplinary approach is needed to deal with nonsurgical issues.
Folds P et al. Reconstructive surgery after female genital mutilation: a prospective cohort study. Lancet 2012;380:13441; Abdulcadir J et al. Reconstructive surgery for female genital mutilation. Ibid: 902 (comment).
Maraviroc to prevent visceral GVHD
hemokine (C-C motif) receptor 5 (CCR5) promotes lymphocyte recruitment to tissues involved in acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation and, in animal experiments, giving anti-CCR5 antibody protects against GVHD. Maraviroc is a non-competitive, slowly reversible small-molecule antagonist of CCR5. Now US researchers have shown that maraviroc may provide protection against GVHD. In vitro, maraviroc inhibited CCR5 internalization and lymphocyte chemotaxis but did not impair T-cell function or the formation of hematopoietic-cell colonies. Among 35 patients treated with oral maraviroc from 2 days before to 30 days after transplantation plus standard anti-GVHD prophylaxis,
the cumulative rate of grade II to IV acute GVHD was low (14.7 percent by day 100 and 23.6 percent by day 180). The cumulative incidence of grade III or IV GVHD by day 180 was only 5.9 percent, there being no liver or gut GVHD before day 100 and little before day 180. The rate of death without disease relapse at 1 year was 11.7 percent and rates of relapse or infection were not excessive. Serum from treated patients prevented CCR5 internalization by chemokine (C-C motif) receptor ligand 5 (CCL5) and blocked T-cell chemotaxis in vitro. Maraviroc shows promise as prophylaxis against visceral acute GVHD.
Reshef R et al. Blockade of lymphocyte chemotaxis in visceral graftversus-host disease. NEJM 2012;367:13545.
36
November 2012
Research Reviews
Antiretroviral prophylaxis for at-risk women

study in Kenya, South Africa, and Tanzania has assessed the prophylactic use of combined tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) in women at increased risk of HIV-1 infection, with negative results. The trial included 2,120 sexually active HIV-negative women aged 1835 years. Randomization was to TDF-FTC or placebo once daily for 52 weeks and follow-up was every 4 weeks for 60 weeks. HIV infection occurred in 33 women in the prophylaxis group and 35 in the placebo group (incidence 4.7 vs. 5.0 per 100 personyears, a nonsignificant difference). Prophylaxis was associated with higher rates of nausea,
vomiting and raised alanine amino-transferase levels. Drug discontinuation for kidney or liver function abnormalities was significantly more frequent in the TDF-FTC group (4.7 percent vs. 3.0 percent). Plasma drug level testing suggested that drug adherence was low. Prophylaxis with TDF-FTC was not effective in this study but rates of adherence were probably low.
Van Damme L et al. Preexposure prophylaxis for HIV infection among African women. NEJM 2012;367:41122; Cohen MS, Baden LR. Preexposure prophylaxis for HIV where do we go from here? Ibid: 45961 (editorial); Abdool Karim SS et al. Pre exposure prophylaxis for HIV prevention. Ibid: 4625 (clinical decisions).
37
November 2012
Research Reviews
Racial differences in HIV infection in MSM

lack men who have sex with men (MSM) make up about 1 percent of the US population, yet in 2009 nearly a quarter of all new HIV infections were in this group. A meta-analysis was conducted to explain the extent and causes of this disparity. The meta-analysis included 174 studies from the US, 7 from Canada and 13 from the UK. In all three countries, the rates of serodiscordant unprotected sex were similar in black MSM and other MSM. In the US and Canada, black MSM were less likely than other MSM to have a history of substance abuse. In the US and the UK, black MSM were more likely than other MSM to be HIV-positive, but HIV-positive black MSM in both countries were less likely than other HIV-positive men to start combination antiretroviral therapy (cART). In the US, black HIV-positive MSM were less likely than other HIV-positive MSM to have health insurance or a high CD4 cell count, to adhere to cART, or to be virally suppressed. US black MSM were more likely to report preventive behavior against HIV infection despite being twice as likely to have HIV risk factors such as unemployment, low income, previous imprisonment, and low level of education, compared with other US MSM. Racial differences in HIV and sexually transmitted infections and in cART initiation are common to the US and the UK.
Millett GA et al. Comparisons of disparities and risks of HIV infection in black and other men who have sex with men in Canada, UK, and USA: a meta-analysis. Lancet 2012;380:3418; Koblin BA et al. Disparities in HIV/AIDS in black men who have sex with men. Ibid: 3168 (comment).
38
November 2012
Research Reviews
Antiretroviral prophylaxis for HIV-1-negative partner
study at nine centers in Kenya and Uganda has shown that antiretroviral prophylaxis given to the HIV-1-negative partner of an HIV-1-serodiscordant couple may prevent acquisition of the infection. The trial included a total of 4,747 serodiscordant heterosexual couples. The seronegative partners were randomized to tenofovir disoproxil fumarate (TDF) 300 mg daily, the same dose of TDF plus emtricitabine 200 mg daily (TDF-FTC), or placebo and followed up monthly for up to 36 months. The seropositive partners were not eligible for antiretroviral treatment on enrolment but were referred for treatment if they became eligible. During the study 82 seronegative partners became seropositive: 17 in the TDF group, 13 in the TDF-FTC group, and 52 in the placebo group, giving incidence rates of 0.65, 0.50, and 1.99 per 100 personyears, respectively. Both treatments were significantly better than placebo in both men and women but there was no significant difference between TDF and TDF-FTC. Adverse event rates were similar in the three groups. Both TDF and TDF-FTC were effective prophylaxis for the seronegative partner of HIV-1 serodiscordant heterosexual couples.
Baeten JM et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. NEJM 2012;367:399410; Cohen MS, Baden LR. Preexposure prophylaxis for HIV-where do we go from here: Ibid: 45961 (editorial); Abdool Karim SS et al. Preexposure prophylaxis for HIV prevention. Ibid: 4625 (clinical decisions).
39
November 2012
In Practice
Managing HFMD in primary care

Dr. K. Vijaya
Director, Youth Health Division Singapore Health Promotion Board
The Singapore Health Promotion Board (HPB) advocates eight target areas for effective hand washing (Box). Diagnosing HFMD Primary care physicians need to pay close attention to symptoms to ensure that patients are diagnosed early so that infected children are prevented from spreading disease to others in the school. The burden of HFMD is likely to be concentrated within young, school-going children, but rates may vary. For example, the number of HFMD cases in Singapore reached a record high of 1,687 in May 2012, which far exceeded the epidemic level of 780 cases a week. The incubation period of HFMD lasts approximately 1 week and patients may only present with a sore mouth or throat. Therefore, symptoms may not be apparent initially and early symptoms may be mistaken for other illnesses. In addition to looking out for symptoms, physicians can also check if there are other cases of HFMD within the family or in the school the child attends. A child with HFMD usually presents with the following symptoms: Fever for 2-3 days Sore throat and runny nose Rash (flat or raised red spots, some with blisters) on the hands (especially the palms), feet, and occasionally on the buttocks, arms and legs Mouth ulcers Vomiting and diarrhea Tiredness and weakness A child is infectious throughout the duration of the illness.
and, foot and mouth disease (HFMD) is a common viral infectious disease that affects all age groups, but young children are especially susceptible. HFMD can be easily spread through direct contact with saliva, nasal discharge, feces or fluid from the blisters of an infected person. Generally, it is a mild self-limiting illness that resolves in 7-10 days. HFMD rarely recurs or persists, and serious complications are also rare. Although HFMD affects all age groups, children under the age of 5 are highly prone to infection because they interact closely with one another, in the classroom or on the playground, for example, at preschools. Human contact is one of the most common causes for infections to spread person to person. Individual cases of HFMD occur constantly but these can spiral into outbreaks affecting many children rapidly. For example, HFMD has become more prevalent in Singapore of late. Cases of HFMD infection have risen from 20,687 in 2011 to 31,590 as of September 2012. Education for prevention Primary care physicians are in the ideal position to educate parents and caregivers on the importance of hygiene and help prevent the spread of infection. Simple messages teaching parents and children the proper way to wash their hands is an effective method of preventing outbreaks.
40
November 2012
In Practice
gency department. In most cases, patients do not require follow up care. Physicians should closely monitor young children (especially infants) for development of dehydration. Rarely, patients with central nervous system manifestations of HFMD such as encephalitis or aseptic meningitis may require hospitalization. HFMD is highly contagious. A child is also susceptible to getting other infections when they have HFMD. Physicians can advise parents the following: Keep the child away from public places. Get everyone at home to wash their hands frequently with soap. Keep childs toys, books, eating utensils, towels and clothes separate from others, and disinfect them regularly Inform the school, kindergarten or child care center as soon as possible. They can monitor other children closely and take additional precautions to prevent the spread of HFMD. Keep the child at home until he or she is fully recovered, after the expiry of the medical certificate (MC) given by the family doctor. Ensure that any siblings are well before sending them to the school, kindergarten, or child care center. Conclusion Primary care physicians need to educate parents and caregivers about keeping their child away from public places and schools during the infection period to avoid creating an outbreak. HFMD is present all year round in Southeast Asia, with seasonal outbreaks every year. Parents and caregivers should closely monitor their children to help prevent such outbreaks in childcare centers, kindergartens and schools.
Laboratory testing is available to isolate and identify the causative agent. However, testing is usually not necessary because HFMD diagnosis is typically based on clinical grounds. Treating HFMD There is no specific treatment for the infection other than relief of symptoms. Treatment with antibiotics is not effective or indicated as HFMD is a viral infection. Easing the patients discomfort and helping them recover is the priority. Physicians should ask parents and caregivers to: Encourage the child to drink plenty of fluids Change to a soft diet (eg, porridge, pureed fruit) if the mouth ulcers are a problem Medications can be provided to ease the discomfort, such as paracetamol syrup to relieve fever and pain Keep the child at home to allow plenty of rest In most cases, HFMD is mild. However, a few children who are infected with the EV71 strain of the virus can become very ill, with signs and symptoms such as: Disorientation, drowsiness and/or irritability Fits Severe headache, dizziness or neck stiffness Breathlessness or turning blue Dehydration this can happen due to continuous vomiting, diarrhea or pure fluid intake as a result of painful mouth ulcers. The child will be very tired, have a dry tongue and may pass very little urine. A child with any of these symptoms should be immediately referred to a hospital emer-
The Changing Panorama Of Womens Health:
Navigating New Frontiers

22-24 August 2013 Visit www.Sicog2013.com for more details soon!
42
November 2012
After Hours
tanding atop St Pauls Hill, facing the sea, you just need to close your eyes and get whisked away by the gentle breeze to a time not very long ago when Malacca was a bustling port with ships, sailors and traders from the far corners of the world. Nestled strategically between the Indian Ocean and the South China Sea, protected from winds, earthquakes and volcanoes, it is little wonder why Malacca was an international trading port. It is precisely because of Malaccas status as an international harbor that so many pow-
ers tried to conquer it. Today, as one strolls through the streets of Malacca town, it is easy to spot the various influences of the colonists who came and went over the centuries. Of course, it helps that there are little plaques inserted into the walls, signs and fences to indicate when the structures were built and what they served as. At the foot of St Pauls Hill, you can see A Famosa, the landmark fort that was built by the Portuguese. Also a remnant of those times is the chapel on St Pauls Hill. In Malaccas town square, the Stadthuys, easily distinguishable by its red walls, sits beside Christ
43
November 2012
After Hours
Church, also built by the Dutch. In the town square, tourists mill around, snapping pictures of the red buildings as colorful trishaws wait for passengers. At the riverbank, one cannot ignore the large ship that appears to have docked there. The Malacca Maritime Museum is a replica of the Flora de La mar, a Portuguese trading vessel that sank off the coast of Malacca while en route to Portugal with loot plundered from Malacca. Inside, visitors can get a peek into the trading history of Malacca, from the time of the Sultanate and through the years of Portuguese, Dutch and British dominance. Malacca has turned some of its historic buildings into museums housing precious relics of its past. The Stadthuys, once a Dutch administrative building, now houses historical artifacts, guiding visitors through the history of Malacca from its humble beginnings to its height of glory as a trading destination and onwards through the years of colonization by the European powers.
Everything in Malacca is within walking distance. From the AFamosa to the Stadthuys, it is just a few minutes walk. In between are many attractions for tourists to feast their eyes on. And right by the town square is the famed Jonker Street. Jonker Street is a delight for anyone who loves antiquities or just finds joy looking at curios. One of the shops is a cobblers, who still makes shoes worn by the ancient Chinese women with bound feet and authentic Nyonya beaded slippers. While wandering about these streets, you may also be accosted by the wonderful smells of nyonya cuisine wafting from the little coffeeshops. The beauty and charm of Malacca must be experienced first-hand. Just a 2-hour drive from Kuala Lumpur, its the perfect place for a weekend getaway. With good food and a rich culture, one leaves Malacca feeling sated in both body and mind, already longing for another round of ayam pongteh and chicken rice balls.
44
November 2012
After Hours
Crater culture
Yen Yen Yip investigates the music and magic of Lake Toba in North Sumatra, Indonesia.
he Batak man sits in front of a multihued display of souvenir T-shirts and ulos, the traditional cloth of North Sumatran Bataks. A two-stringed mandolin is cradled in his arms. He opens his mouth to sing and reveals a row of broken teeth. With one hand clasping, moving and pressing down on alternate string positions, he strums, coaxing a twanging melody out of the mandolin to accompany his hoarse voice. The song is harsh and strangely elemental; it conjures up images of men sitting around a fire at night, drinking palm fruit toddy after a day of fishing on Lake Toba. One of the most famous features of Lake Toba is a caldera a crater lake that was formed when a super-volcano erupted more than 69,000 years ago. The eruption blew up about 2,800km3 of material and created a colossal hole about 906m above sea level, which gradually filled with water. Tens of thousands of years later, the Austronesian people traveled to Sumatra, made their way inland and found a beautiful lake ringed with forested dusky-blue silhouettes of mountains. The ones who settled on the surrounding mountainous regions and Samosir, the island in the middle of the lake, became known as the Toba Bataks. Accounts of Batak traditions date back to the 1200s. Some customs have survived the test of
time. For instance, traditional music played with Batak instruments such as the two-stringed mandolin, flute and drums is still used during ceremonies and festivities. At these events, ulos cloth weaved with Batak designs are folded lengthwise and draped over a shoulder. Some Bataks on Samosir continue to live in houses called rumah adat, built with distinctive roofs that sweep upwards on either end like buffalo horns, the gables adorned with elaborate carvings of thumbprint-like whorls and lines. Other tribal rituals, such as cannibalism, have died out. Early accounts of the Bataks predilection for human flesh came from the European explorer Marco Polo, who traveled to Sumatra in the 1290s and wrote about stories told to him of man-eaters who eat humans stump and rump. In the 1800s, Sir Stamford Raffles and other colonialists studied cannibalistic rituals of the Bataks and reported that human flesh was typically eaten when tribes waged war against neighboring villages and captured prisoners, or if a tribe member was accused of legal infringements such as murder, rape or theft. In Samosir, these grisly details can be recounted in full at Ambarita, a tribal village in Samosir which features a set of historic stone chairs where a judicial council would have sat to decide the fate of a
45
November 2012
After Hours
which the bones are exhumed and cleaned, to be reinterred in a bone house that is elevated above ground to be closer to the heavens. The tomb of the Batak rajah Sidabutar rests on a hill in Tomok, a village in southern Samosir, past about half a kilometre of souvenir stalls lining a narrow meandering lane. His sarcophagus is carved in stone and sits out in the sun, bleached and silent. Legend has it that the monarch was a just and wise ruler whose affections were spurned by a Batak beauty, Anting Malela. In vengeance, the rajah cursed the woman and drove her insane through black magic. The rajahs unrequited love persisted at his deathbed: he had a statue of Anting Malela carved to adorn his tomb. Today, the sarcophagus is the object of tourist fascination and camera clicks.
prisoner. If the prisoner was condemned to execution, he would be beheaded; the body would be disposed in the lake, but the blood collected and the liver extracted for consumption. The Bataks believed that all humans possess a tondi, or a life-soul, which can affect his or her physical well-being: a weakened tondi can lead to illness and even death. The blood and the liver, considered to be rich in tondi, were consumed to heal and strengthen the eaters spiritual self. In 1890, the Dutch colonial government passed a law banning cannibalism. Rumors of cannibalism among the Bataks persisted until the early 20th century. Todays Toba Bataks have mostly converted to Christianity. Brightly colored churches with steeples glinting in the sun are frequently spotted in the middle of rice paddies and agricultural fields along the dusty, empty roads of Samosir. Before the advent of Christianity, however, the Batak religious worldview was animistic. Divination and magic were commonly practised. Datuks animistic shamans recorded magic spells, healing charms, prophecies and other mystical notes in arcane Batak characters on pushtahas, books made of tree bark, folded and opened in concertina style. Certain burial practices have endured until today. At death, the Bataks are buried twice. It was traditionally believed that the tondi of a deceased person will vanish from the body; however, the begu, or the death-soul, remains. A priest is required to perform rituals at the first funeral to advise the begu to leave the family and the village. Reburial typically takes place about 8 years after death, during
Getting There
Lake Toba is a five hour drive from Medan, the largest city in North Sumatra. Tourists can fly in to Medan through Polonia International Airport.
What to Do
D ive into the delicious cool waters of the crater lake Dance with the locals in a traditional Batak performance Hike the peaceful, rolling hills of Samosir and drink in the scenery Take a sip of palm fruit toddy
46
November 2012
Humor
Give it to me straight doctor, should I start dating?
I sent your brown suit to the cleaners. It will match the mahogany casket perfectly!
He likes his steak and mashed potatoes intravenously!
I didnt expect to still be constipated up here!
At our hospital we either perform a Cesarian, or the Heimlich maneuver. Which one do you prefer?
This here? I cut myself shaving!
I wouldn't worry about it. He won't get far without lungs!
47 November 2012 Calendar

November
012 Scientific Sessions of the American Heart 2 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
December
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-diagnostic-imagingsymposium-2012/event-summary-d9ca77152935404ebf0404a0898e13e9.aspx
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
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
3rd Annual Meeting of the American Association 6 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
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
9th International Diabetes Federation-West Pacific Region Congress 25/11/2012 to 27/11/2012

Location: Kyoto, Japan Info: Japan Convention Services, Inc. Tel: (81) 6 6221 5931 Fax: (81) 6 6221 5939 E-mail: JCS-9idfwpr-4aasd@convention.co.jp Website: www2.convention.co.jp/idfwpr2012
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
48 November 2012 Calendar

Upcoming
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
23rd Conference of the Asia Pacific Association for the Study of the Liver 7/3/2013 to 10/3/2013
Location: Singapore Info: Gastroenterological Society of Singapore, The Asian Pacific Association for the Study of the Liver Tel: (65) 6292 4710 Fax: (65) 6292 4721 Email: apaslconference@kenes.com Website: www.apaslconference.org
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
62nd American College of Cardiology (ACC) Annual Scientific Session 9/3/2013 to 11/3/2013
Location: San Francisco, California, US Info: American College of Cardiology Foundation Tel: (415) 800 699 5113 Email: accregistration@jspargo.com Website: www.accscientificsession.org/Pages/home.aspx
International Meeting on Emerging Diseases and Surveillance (IMED 2013) 15/2/2013 to 18/2/2013
Location: Vienna, Austria Info: International Society for Infectious Diseases Tel: (617) 277 0551 Fax: (617) 278 9113 Email: info@isid.org Website: www.isid.org/imed/Index.shtml
4th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association 27/3/2013 to 30/3/2013

Location: Shanghai, China Info: Asian Pacific Hepato-Pancreato-Biliary Association Tel: (86) 21 350 30066 Fax: (86) 21 655 62400 Email: secretariat@aphpba2013shanghai.org Website: www.aphpba2013shanghai.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: www2.kenes.com/apsc2013/pages/home.aspx
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November 2012

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