Medical Tribune June 2012 HK

June 2012
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More intensive dialysis improves patient outlook
FORUM Smoke-free cities A step towards healthy environments
IN PRACTICE Low back pain: Current concepts
CONFERENCE Personalize CVD prevention for women
NEWS Lutein crucial for early cognitive development
June 2012
More intensive dialysis improves patient outlook

Elvira Manzano
ncreasing dialysis frequency and duration may improve overall health and survival in patients with renal failure compared with conventional dialysis, four studies have found. In one study involving 11,000 patients, the risk for all-cause mortality was 13 percent lower in patients who received daily home hemodialysis compared with those on traditional thrice weekly in-center regimens (HR 0.87, 95% CI 0.78-0.97). [J Am Soc Nephrol 2012; DOI:10.1681/ASN.2011080761] The finding was supported by another study demonstrating a 45 percent reduction in mortality for patients receiving intensive dialysis (five sessions a week, each session lasting 7 hours) compared with those on conventional dialysis (HR 0.55, 95% CI 0.340.87). [J Am Soc Nephrol 2012; DOI:10.1681/ AS.2011070676] In the 420-patient study, 6.1 deaths per 100 person-years were seen in the intensive group versus 10.5 deaths per 100 person-years in the conventional group. We found that intensive home dialysis is associated with markedly improved patient survival compared with conventional incenter dialysis, said study author Dr. Gihad Nesrallah, from the London Health Sciences Center in London, Ontario, Canada. But whether this relationship is causal remains unknown. The authors noted that patients may find home dialysis more appealing because of less
Several studies suggest that increasing the frequency and duration of dialysis may improve the prognosis of patients with renal failure.
dietary restriction, flexible scheduling and lower cost. Meanwhile, another study of 2,800 patients showed that maintaining the thrice a week schedule but extending the sessions to a mean of 7.85 hours during overnight clinic stays provided better mortality outcomes than conventional dialysis. Patients who opted for nocturnal hemodialysis showed a 25 percent reduction in 2-year mortality risk compared with matched controls. (HR 0.75, 95% CI 0.61-0.91; P=0.004). [J Am Soc Nephrol 2012; DOI:10.1681/ASN. 2011070674] Overnight dialysis also resulted in reduced weight, lower systolic blood pressure and blood phosphorous levels. Conversion to in-center nocturnal hemodialysis (INHD) was associated with favorable laboratory markers with significantly lower serum phosphorus despite improved
June 2012 with many benefits, but the association with improved survival requires further analysis. Daily hemodialysis is more efficient with respect to solute clearance and better blood pressure control. Of note, increased clearance of waste products from the blood has not been shown to improve survival in a key landmark study on dialysis patients (HEMO study). Compared with conventional dialysis, frequent or longer dialysis is however more efficient at removing phosphate, she said. Patients can benefit from reduced pill burden and superior phosphate control. Oei noted that despite growing demand, hemodialysis remains a limited resource. She said frequent dialysis is not routinely prescribed due to lack of dialysis resource and unfavorable response from patients with regard to increasing time attached to the machine. The procedure is expensive and currently, there is no support for subsidized home dialysis programs. Despite government support, dialysis is still a significant burden to patients who elect to suffer the complications of untreated end stage renal failure than burden their family with long term hefty medical bills, Oei said. Until we can meet the basic dialysis requirements of the underprivileged, frequent and prolong dialysis may be regarded as a luxury rather than a necessity, she concluded.
or stable nutritional status, said the authors, led by Dr. Eduardo Lacson, Jr. from the Fresenius Medical Care North America, Massachusetts, US. This study supports the notion that therapy with INHD is a viable alternative dialysis regimen. In the final study, Dr. John Daugirdas from the University of Illinois, Chicago, US and colleagues, showed that six times a week of dialysis decreased patients serum phosphorous levels compared with standard dialysis treatment. High-frequency dialysis also reduced patients need for phosphorous lowering medications. [J Am Soc Nephrol 2012; DOI:10.1681/ASN.2011070688] Frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorous binders, the authors said. Thrice-a-week dialysis, lasting 4 hours per treatment, is the standard protocol for endstage renal disease at most dialysis centers. Extended intervals between dialysis sessions maybe preferred by patients. However, this poses risks as the less frequent the dialysis sessions, the greater the gradient between peak and trough solute and water levels. Commenting on the studies, Dr. Elizabeth Oei, associate consultant at the department of renal medicine, Singapore General Hospital, said frequent or longer dialysis is associated
June 2012
Forum
Smoke-free cities A step towards healthy environments

Excerpted from a presentation by Mr. Chris Gray, senior director, International Public Affairs, Pfizer, during the World Congress of Cardiology Scientific Sessions 2012, held recently in Dubai, UAE. ubai, host of the 2012 World Congress of Cardiology, has zero-tolerance policies on drink-driving and drugs, but not for smoking. Though smoking is banned in many public offices and places such as shopping malls, there are designated smoking areas all over the city. The ban is not difficult to observe even for the most addicted smokers. That is the situation in Dubai, and in many cities around the world. A report by the World Health Federation showed that over half of the worlds total population of 6.7 billion lives in an urban setting. Three out of five people will live in cities by 2030. While city living offers more opportunities, greater access to health care facilities, and governance, the conditions in an urban setting can also amplify problems. Many of todays sprawling cities face a triple burden of infectious diseases, waves of accidents, injuries and violence, and chronic diseases with the globalization of unhealthy lifestyle practices such as heavy drinking, physical inactivity and smoking. Interestingly, smoking prevalence is highest in urban areas. An estimated 600,000 individuals worldwide died from second-hand smoke in 2011, and 75 percent of these deaths were among women and children. We see the impact of second-hand smoke as people live together in closer environments. According to Dr. Sidney Smith, World Health Fed-
eration president, where a person lives intrinsically affects their health and life options. The harmful effects of smoking heart attack, stroke and preventable deaths speak for themselves in many ways. What can we Dubai, like many cities around the world, has do to advocate banned smoking in public places. for smokefree cities around the world? We should raise public awareness to bring statistics to a much broader audience. Urban areas can be built, organized, managed, retrofitted and governed in ways that promote health. The number of people protected by comprehensive smoke-free laws has doubled from 2008 to 2010. Nearly 3.8 billion people live in countries with some kind of antismoking measure; 11 percent of the worlds population are protected by national smokefree laws. Some cities have taken incremental steps and acted as catalyst for developing smoke-free environments. Restaurants
June 2012
Forum
smoke in homes, workplaces and on public transportation. A city with a tobacco plantation and 400,000 inhabitants succeeded in instituting anti-tobacco measures. China, home to one-third of the worlds smokers, outlawed smoking in buses, restaurants and bars starting in May 2011. Russia plans to implement a similar measure beginning in 2015. In the Middle East, where waterpipe tobacco smoking is a concern, heart experts have emphasized the need to direct resources to prevention strategies to fight heart disease. Saudi Arabia has long-declared the holy cities of Mecca and Medina as smokefree. Last February, Kuwait imposed a blanket ban covering all forms of smoking in all indoor public places, except in shisha parlors, to protect public health. Acknowledging the ill-effects of tobacco on health, heart societies in Asia went a step further and took on the challenge to become leaders in tobacco control at the recent World Conference on Tobacco or Health 2012 (WCTOH) held recently in Singapore. Twentyone country representatives and 16 heart foundations established advocacy priorities all targeted at making Asia Pacific smokefree by 2040. The move is a major step forward and adds momentum to the growing smoke-free movement across the globe. Tobacco use is not just a problem for individual people or nations; it is a collective health responsibility for mankind, said Dr. Wael Al Mahmeed, board member, Emirates Cardiac Society, which collaborated on the bid to host the 2015 World Congress in Abu Dhabi. In years to come, we want Abu Dhabi 2015 to be remembered as the place where the world collectively said: enough is enough.
worldwide are going smoke-free. We can see it in the Americas and in Southeast Asia. Article 8 of the WHO Framework Convention on Tobacco Control (FCTC) has become the basis for cities developing smoke-free legislation. Moscow has no national smoke-free legislation and sub-national jurisdictions have no authority to adopt and implement smokefree laws. While Manila has national laws regulating smoking in public places, strict implementation remains a problem. Mexico City set an example for the world when it enforced a comprehensive smoke-free law in 2008. The hospitality industry restaurants and bars went up against it and argued that the smoking ban will harm economic interests, employment and productivity. However Mexicos experience, as well as Hong Kongs, suggest otherwise. New York City made a tremendous move when it raised the tobacco tax in 2002 and instituted a smoking ban in all bars, clubs and restaurants in the city in 2003. As a result, the number of smokers dropped by 300,000 a reduction that could save 100,000 lives. The ban has been extended to include public golf courses, sports grounds, beaches and plazas. So far, in 2012, 108 tickets have been issued for smoking violations. In the UK, the Liverpool City Council voted to pursue a local act of Parliament to make the city smoke-free became instrumental in the passage of a national smoking legislation in 2006. This demonstrates the strong role municipal leaders play to drive national agendas and policies. Activism really has a profound impact on government. In Nueva Vizcaya, a province in the north of Philippines, serious implementation of smoke-free ordinances dramatically reduced tobacco use and exposure to second hand-
June 2012
Hong Kong Focus
Subretinal microchip implant restores vision

Naomi Rodrig
he Eye Institute of the University of Hong Kong (HKU) successfully performed a subretinal microchip implantation in a local patient who was legally blind due to retinitis pigmentosa (RP). According to the researchers, this is the first such procedure performed in Asia, kicking off a phase III international trial of this technology. The microchip, developed by a German company that produces subretinal implants for the visually impaired, was subdermal cable successfully tested in phase I and II clinical trials in Germany, as reported in the Proceedings of the Royal Society B. [DOI: 10.1098/ rspb.2010.1747]
chip
(a)
subdermal cable
chip
extracorporal cable plug
power suppy and transmitter/receiver
su
(b)
bipolar cells ganglion cells nerve fibres
degenerated layer of photoreceptors pigmentepithelium DSelectrodes amplifier light light sensitive microphotodiode
The early result of the surgery is highly plug sight, satisfactory and our patient has gained including seeing light and dark and being able to read letters projected on a screen, power suppy and transmitter/receiver reported Institute Director Professor David Wong, who is the lead investigator of the study. After months of careful preparation, we are very excited to carry out the first implantation in a Chinese patient, marking the first such procedure outside Germany. We are particularly excited by the amazing early results, which prove that patients with this previously incurable condition can in fact regain at least some sight. The procedure involves placing a 1500-electrode light-sensitive, externally powered microchip in the macular region below the retina. Visual scenes are projected naturally
extracorporal cable
MPDA electrodes subretinal implant polyimide foil, power line
(a) The cable from the implanted chip connects with a wirelessly operated power control unit. (b) Microphotodiode arrays (MPDA) amplifiers and electrodes in relation to retinal neurons and pigment epithelium. Adapted from Proc Ro Soc B. DOI: 10.1098/rsbp 2010.1747
through the eyes lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 x 40 pixels, each releasing light intensity-dependent electric stimulation pulses.
June 2012
Hong Kong Focus

tients, and we thank the patient group Retina Hong Kong that helped us identify those patients who might be suitable for this treatment. The investigators are now refining the procedure and following up two patients for physiological and neurological changes in response to sight restoration. We will observe them with great interest in the coming months, he said. Looking forward, they are planning to perform it in patients who are totally blind to further establish its effectiveness. We prefer to operate on patients who have no light perception or those who cannot utilize what light they see for navigational purposes, Wong pointed out.
Post implantation, the microchip is turned on this is when the evaluation of sight restoration begins, he explained. Having been blind for 15 years, the patient has to learn to see once again, she has to practice handeye coordination and learn to control her eye movement in order to focus her sight at appropriate targets. Furthermore, as patients must develop new internal processes for interpreting the images they see, it typically takes several weeks to fully realize their new sight capabilities. I have always believed that subretinal chip implant offers the best chance of success in our quest for artificial vision, noted Wong. In Hong Kong, there are more than 2,000 RP pa-
June 2012
Hong Kong Focus

clinical trials in infectious diseases, hepatology, gastrointestinal diseases, and HIV / AIDS. The hospitals dedicated research center for phase II/III trials operates according to standard procedures with oversight by an internal independent quality control program. At present we are focusing mainly on liver diseases. The 1,000-bed hospital, with 27,000 admissions and nearly 100,000 outpatients per year, offers a huge pool of subjects for clinical research in hepatitis B and C, hepatocellular carcinoma [HCC], and other liver diseases, said Karlberg. Hepatitis accounts for 72,000 outpatients and over 18,000 admissions, while nearly 6,000 patients are hospitalized for HCC annually at the 302 Hospital. The agreement benefits both parties, as most investigators and administrators in China lack adequate experience in large-scale international clinical trials. H&H has the expertise in conducting such trials according to ICH GPC guidelines [International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice Guidelines], stressed Karlberg. We will help the 302 Hospital with the development of clinical research infrastructure, education in clinical research methodology, and the establishment of an Institutional Review Board and Ethics Committee, so it will become a leading center for clinical trials conducted to international standards. Having taken part in numerous clinical trials for major global pharmaceutical companies, the H&H team is hoping to attract trial sponsors who can benefit from their wide experience and the large pool of liver disease patients at the 302 Hospital.
Tapping into Chinas potential for clinical trials

Naomi Rodrig
ith the ongoing trend towards globalization of clinical research, China is the next hot destination with a huge, untapped potential in this area, according to Dr. Johan Karlberg, CEO of a Hong Kong company aiming to facilitate clinical trials at Chinas top clinical centers. The past few years have seen a decline in the proportion of phase II/III trials in Europe, North America and South America against a corresponding increase in Asia. While India has declined slightly, the main increase was in South Korea, China, Taiwan and Japan, accounting together for 1.2 percent growth, remarked Karlberg, who is the Founder and Editor of Clinical Trial Magnifier. [http://www. ctmagnifier.org/2011/M2011_4_01.aspx; http:// www.ctmagnifier.org/2011/M2011_4_02.aspx, accessed on May 17, 2012] As for Hong Kong, the interest from trial sponsors has diminished. Although our hospitals have good infrastructure and extensive expertise in conducting clinical trials, the number of patients they can enroll is relatively small, he added. Humanity & Health International Holdings Ltd. (H&H) was established last year by a group of local investors and physicians as a clinical research management organization focusing on site management for sponsors of clinical trials. The company has signed an 8-year collaborative agreement with the 302 Military Hospital in Beijing, one of the largest and leading infectious disease facilities in China, and the first to be accredited by the State Food and Drug Administration (SFDA) to conduct registration
June 2012
Hong Kong Focus
Magnetic rods revolutionize scoliosis treatment

Christina Lau
ew magnetically-controlled growing rods (MCGRs) can eliminate the need for repeated surgery in children with scoliosis, as a local study shows that frequent noninvasive lengthening of the rods is possible in outpatient settings. This is the first report on the efficacy and safety of MCGRs in early-onset scoliosis. [Lancet 2012, e-pub 19 Apr; DOI:10.1016/S01406736(12)60112-3] According to authors from the Department of Orthopedics and Traumatology, University of Hong Kong, scoliosis in skeletally immature children is often treated by implantation of a rod to straighten the spine. Traditional growing rods need to be lengthened (distracted) under general anesthesia every 6 months to maintain normal spine growth, but the procedure is associated with wound complications and substantial healthcare costs. In contrast, MCGRs are remotely distractible, allowing frequent non-invasive distractions as outpatient procedures. The investigators implanted the MCGR in five children with severe scoliosis, followed by monthly outpatient distractions. In the two patients with 24 months follow-up, the mean degree of scoliosis, measured by Cobb angle, was 67 before implantation and 29 at 24 months. Length of the instrumented segment of the spine increased by a mean of 1.9 mm with each distraction in congruence with the childrens normal growth, wrote the authors. Throughout follow-up, both patients had
no pain, had good functional outcome, and were satisfied with the procedure. No MCGR-related complications were noted. According to the authors, these preliminary results suggest that the procedure is effective and safe. Whether MCGR leads to significantly better outA magnetically-controlled growing comes than tradi- rod fixed to a spine model Adapted tional growing rods from Lancet 2012. DOI:10.1016/ is not yet known, S0140-6736(12)60112-3. but early results are positive and the avoidance of open distractions is a great improvement, they noted. This new technology represents a giant leap forward and new hope in the management of children with severe scoliosis, co-author Dr. Dino Samartzis told Medical Tribune. It completely eliminates the need for repeat surgeries, and the traumatic experience associated with that process for the parent and child. He noted that the concept of using magnetism for lengthening growing rods was developed about a decade ago and the technology evolved throughout the years. The particular device used in our study was developed in
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Hong Kong Focus

indications and patient selection criteria for its use, and taking part in an international multicenter trial to further assess the safety and efficacy of MCGR. Furthermore, the team is designing new applications for MCGR in other disorders in which slow, progressive change to bone structures is needed, such as correction of limb abnormalities, thoracic insufficiency syndrome or limb lengthening.
the US, allowing both lengthening and shortening of the rod by an external hand-held controller. Our spine team in Hong Kong played a role to further refine the protocol and assess this device in patients, said Samartzis. Our study was the first to report on the initial experience using the MCGR in young children with severe scoliosis. The researchers are currently evaluating the long-term effects of this technology, refining
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June 2012
Hong Kong Focus
Hong Kong College of Cardiology 20th Annual Scientific Congress 2012 Sue Mulley reports
Dual therapy stent may cut duration of antiplatelet therapy
he Combo Dual Therapy Stent, which combines an abluminal biodegradable sirolimus elution with the endothelial progenitor cell (EPC) capture technology, may potentially reduce the need for antiplatelet therapy, according to Dr. Michael Haude, Director of Medical Clinic I, Lukas-krankenhaus, Neuss, Germany. Haude noted that current guidelines specify drug-eluting stents (DES) as the default devices to limit restenosis. However, the drugs used in DES also inhibit the natural healing of the vessel, he said. This prolonged recovery of the vessel wall, or lack of re-endothelialization, may lead to late stent thrombosis and has emerged as a limiting factor in the application of DES. Although we prescribe prolonged dual antiplatelet therapy [DAPT] to prevent stent thrombosis, it is unlikely or impossible for a significant number of patients to continue it for >12 months, he emphasized. In the Combo stent, sirolimus controls neointimal proliferation, while the EPCs are captured by a layer of anti-CD 34 antibodies and then mature into endothelial cells, playing a key role in wound healing. The Combo stent was shown to be as effective as the TAXUS Liberte paclitaxel-eluting stent in the REMEDEE study (Randomized Evaluation of an Abluminal Sirolimus Coated Bio-engineered Stent), based on the studys primary endpoint of in-stent late lumen loss at 9 months. The international study included 183 patients with symptomatic, ischemic heart dis-
ease due to a stenotic lesion located in a native coronary artery. The in-stent late lumen loss for the Combo stent was 0.39 0.45 mm compared with 0.44 0.56 mm for the TAXUS DES. Using intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging, homogenous coverage of the Combo stent struts was observed at 9 months, vs less extensive coverage with TAXUS, noted Haude. There was no significant difference in major cardiovascular events between the two stents. Although the study was not powered to establish statistical significance for secondary endpoints, their rates at 9 months were lower among patients treated with the Combo stent vs the conventional DES (risk reduction of 45 percent for clinically driven target lesion revascularization, 43 percent for binary restenosis, and 21 percent for major adverse cardiac events). Interim results from the REMEDEE OCT study further established the healing profile of the Combo stent. Based on an analy-
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Hong Kong Focus

With this homogenous coverage of the Combo stent, our goal is to document shorter DAPT probably <6 months, said Haude. For patients at high risk of developing thrombosis who cannot tolerate 1 year of antithrombotic therapy, the Combo stent would be the most balanced device.
sis of 60,069 struts, endothelial coverage approached 70 percent in <50 days and 100 percent by 140 days. At 12 months follow-up, only one patient of the 61 enrolled had non-ischemic target driven lesion revasculariztion. There was no stent thrombosis, MI or death.
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June 2012
Hong Kong Focus
Addressing the antiplatelet dilemma

hile several effective antiplatelet agents are now available, tailoring therapy to the individual patient remains challenging, according to Dr. Ze-Ning Jin, Consultant Cardiologist at Beijing Anzhen Hospital, China. You have to balance the risk of bleeding against possible thromboembolic complications, taking into account the patients history, Jin said. Using a clinical case to demonstrate the challenges, he described a middle-aged male patient who presented with rheumatic heart disease 4 years ago. The patient received a prosthetic mechanical valve and a lifelong prescription of warfarin. Recently, the patient suffered an acute MI and underwent percutaneous coronary intervention and stenting with a first-generation drug-eluting stent (DES). He was prescribed dual antiplatelet therapy (aspirin and clopidogrel). On discharge, the patient was receiving triple antiplatet therapy (warfarin 3 mg QD, aspirin 100 mg QD, clopidogrel 75 mg QD), and a calcium channel blocker, an angiotensin II receptor blocker, and a proton-pump inhibitor. Unfortunately, triple antiplatelet therapy is known to significantly increase the risk of intracranial and gastrointestinal bleeding. This patient also had a history of gastric ulcer, Jin noted. During follow-up, he complained of upper abdominal discomfort, as well as frequent nose bleeds and petechiae. What is the rationale for deciding the ideal antiplatelet therapy in such patients? he asked. Once patients receive a DES, they have to take dual antiplatelet therapy for 3-6 months;
this significantly increases the risk of bleeding, and has been associated with higher mortality rates, Jin said, explaining that he would have opted for a bare-metal stent (BMS) with a shorter period of triple antiplatelet therapy. Jin set out a rationale for individualizing the approach to patients with indications for triple therapy. [Netherlands Heart Journal 2010; 18:444-450] In patients with atrial fibrillation or a true indication for oral anticoagulant therapy (and higher bleeding risks), the surgeon should consider stenting via the radial artery. A DES is only indicated for patients with long lesions (>20 mm), a small vessel, diabetes, a complex lesion and high restenosis risk; otherwise a BMS is preferred. Patients with an acceptable bleeding risk (<80 years of age, glomerular filtration rate >30, no history of gastrointestinal or intracranial bleeding, no thrombocytopenia, no existing anemia) should receive clopidogrel for 3 months minimum, and continuous aspirin and anticoagulant therapy. Patients receiving BMS with an acceptable bleeding risk can take at least 1 months clopidogrel and continuous aspirin and oral anticoagulant therapy. However, for high-risk patients, BMS, balloon angioplasty, and continuous aspirin and oral anticoagulant therapy is preferable. Jin also stressed the importance of continuity of care. Overseas, patients are followed up by the same cardiologist but in China, patients travel to Beijing for surgery but are then followed up by a local cardiologist. They dont come back to us until they have a problem, he said.
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June 2012
Hong Kong Focus
HKU Bachelor of Pharmacy program gets accreditation

Naomi Rodrig
he Bachelor of Pharmacy (BPharm) program of the University of Hong Kong (HKU), launched in 2009, has recently obtained full accreditation from the Hong Kong Pharmacy and Poisons Board, allowing the first batch of graduates to start their pharmacy internship training this summer. Following the accreditation, graduates will be exempted from the Boards written examinations to register as pharmacists in Hong Kong after successfully finishing the 1-year internship. This is an important milestone in the development of both the Department of Pharmacology and Pharmacy and the Faculty. With full confidence, we will continue to recruit and train young talents for the pharmacy profession to meet the ever-escalating needs of the society, remarked Dean of Medicine, Professor Sum-Ping Lee. According to Professor Ian Wong, Head of HKUs Department of Pharmacology and Pharmacy, the current demand for pharmacists is extremely high and many employers have found it challenging to recruit pharmacists. In 2009, the estimated per-population ratio of Hong Kong pharmacists was 1:3,700, which is unsatisfactory in view of the WHOrecommended ratio of 1:2,000, he said. With the aging population, the demand is expected to increase as pharmacists will play vital roles in managing medicines for the elderly and those with chronic illnesses. Wong noted that the BPharm program provides comprehensive student training, in-
cluding considerable clinical exposure at the Queen Mary Hospital, which is home to the biggest pharmacy department among all public hospitals in Hong Kong. Furthermore, exchange programs with Kings College London, Sojo University in Japan and University Joseph Fourier in France offer students the opportunity for international exposure through a 4-week attachment to these institutions. Study tours to China and other countries are also part of the curriculum, enhancing student exposure to the practice of pharmacy and the operation of pharmaceutical companies in other countries. A career in pharmacy offers many diverse options, including positions in community pharmacies, pharmaceutical companies producing Western and Chinese medicines, hospital pharmacies and the academia. We work very closely with the Hospital Authority, private hospitals, the pharmaceutical industry and universities to ensure that there are adequate training positions for our graduates, noted Wong.
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June 2012
Hong Kong Focus

subnanomolar concentrations, corresponding to over 10-fold higher potency than maraviroc. Besides inhibiting HIV-1 entry, it also blocked cell-mediated viral transmissions with similar potency, which is over 1,000-fold better than the reverse transcriptase inhibitor, tenofovir, emphasized Chen. Importantly, TD-0680 was also active against a TAK-779/ maraviroc-resistant variant of HIV-1. Moreover, he reported that a vaginal microbicide gel containing TDF-0680 was recently shown to reduce HIV-1 infection rates by 39 percent. Chen noted that an effective anti-HIV vaccine, which would be an ideal solution for HIV infection prevention, remains elusive despite decades of research and development efforts. Unprotected sexual contact is the major risk factor for the spread of HIV/AIDS among general populations in China and elsewhere. In 2011, it resulted in a record high number of HIV infections in Hong Kong. It is urgently needed to discover a biomedical means to prevent HIV sexual transmission, he argued. Our findings have implications for drug design and developing TD-0680 as an antiretroviral and/or as a microbicide against HIV1, the authors wrote. According to Chen, the agent may be formulated into vaginal or rectal microbicide gels, therefore offering people, especially women, an alternative method of protection in addition to condoms. The research project was conducted in collaboration with Shanghai Targetdrug Co. Ltd, Nanjing University and City University of Hong Kong, and supported by the National 11th Five-Year Research Project and HKU Development Fund.
Novel anti-HIV agent developed in Hong Kong

Naomi Rodrig
esearchers at the AIDS institute of the University of Hong Kong (HKU) discovered a novel molecular mechanism that prevents the human immunodeficiency virus (HIV-1) from entering the host cells, and identified a potent anti-HIV-1 drug candidate based on this approach. The agent dubbed TD-0680 is an antagonist of CCR5, a co-receptor involved in sexually transmitted HIV-1 infection. HIV1 enters human cells by binding to the human receptor CD4 and the co-receptor CCR5. Since sexually transmitted HIV-1 strains bind mainly to CCR5, a CCR5 antagonist can effectively block the interaction between the virus and the receptor, thus preventing the virus from entering human cells and thereby avoiding persistent and latent infection, explained Dr. Zhiwei Chen, Director of the Institute and principal investigator of the study. The newly discovered distinct mechanism of action of TD-0680 involves the blockade of two functional regions on the CCR5, accounting for its enhanced potency as compared with maraviroc, the only FDA-approved CCR5 antagonist to date. The clinical utility of maraviroc may be diminishing due to emergence of maraviroc-resistant HIV-1 strains after nearly 5 years of use. The study is the first discovery of a CCR5 antagonist with such a unique mechanism of action. Our findings, reported in the Journal of Biological Chemistry, indicated that TD-0680 is currently the most potent CCR5 antagonist. [DOI: 10.1074/jbc.M112.354084. Epub ahead of print] TD-0680 demonstrated antiviral activity in
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June 2012
Hong Kong Focus
HPV vaccination for males: Uptake still low

Sue Mulley
here is growing evidence that the human papilloma virus (HPV) vaccine provides significant benefits to males by reducing their risks of developing anal cancer and genital warts. However, according to local physicians, uptake of the vaccine is still low among Hong Kong males. The incidence of genital warts is high among local adults, estimated at 203.7 per 100,000 person-years vs 120 per 100,000 person-years in Europe and North America, according to Dr. Nelson Siu of the Department of Obstetrics and Gynecology, Prince of Wales Hospital. Genital warts have become a special problem in recent years with an increasing number of young people seeking casual sexual encounters via the Internet, pointed out Dr. Daniel Chiu, Vice President of the Hong Kong Pediatric Society. Around 50 percent of Internet sex cases are males arranging casual sexual encounters in public lavatories. An increasing number of teenage boys are asking for money in return for sex. Despite accumulating evidence on the benefits of HPV vaccination, it is not included in the school-based immunization platform in Hong Kong, which may account for the low coverage. We vaccinate about 30-40 girls a month, but not too many boys ... probably less than 10 [aged <18] in the past year, Chiu noted. However, the probability that a sexually active male will acquire a new genital HPV infection is about 0.35 per 1,000 person-
months over 12 months, similar to estimates for females. [N Engl J Med 2011;364:401-411] Although most HPV infections are asymptomatic and resolve within 2 years without complications, persistent infection has been linked to numerous cancers, including cervical, vaginal, vulvar, anal, penile, and head and neck cancer, as well as recurrent respiratory papilloma and genital warts. Previously, the main argument for vaccinating males has been to stop the virus spreading to females because women present with most of the HPV-related diseases. However, a greater role for HPV vaccination is indicated because men present with a significant share of HPV 16- and 18-associated cancers. In the US, about one third of the cases occur in men. [MMWR Morb Mortal Wkly Rep 2011;60:17051708] A large international trial (n=4,065) confirmed that the quadrivalent HPV vaccine protected against infection with HPV 6, 11, 16 and 18, and the development of external genital lesions in healthy males aged 16-26 years. [N Engl J Med 2011;364:401-411] In a sub-study of 602 healthy men having sex with men (who run higher risks of developing anal
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Hong Kong Focus
cancer than heterosexual men), the quadrivalent HPV vaccine reduced the rates of anal intraepithelial neoplasia, including grade 2 or 3. [N Engl J Med 2011;365:1576-1585] These results suggest that vaccinating males will likely lead to reduced HPV transmission and infection through herd immunity. The quadrivalent HPV vaccine is indicated for males aged 9-26 years and females aged 9-45 years. It is currently recommended for males and females in countries such as US, Australia and Austria. In Australia, the number of high-grade cervical abnormalities in girls aged <18 years has halved since a national HPV vaccination program was launched in 2007 for females aged 12-26 years. [Lancet 2011;377:2085-2092] Furthermore, the number of new cases of genital warts fell by 59 percent in young women and by 28 percent in heterosexual men. [Lancet Infect Dis 2011;11:39-44] The question for many family physicians is how to bring up HPV vaccination during a consultation, according to private practitioner Dr. Francois Fong. Sexual issues are often avoided in general practice. Physicians feel embarrassed and concerned about what their patients might think of them. But 40 percent of our male patients are asymptomatic HPV carriers, said Fong, advising GPs to present the facts on HPV rather than launch into a discussion of sexual behavior. Patients need to be told that HPV can be transmitted both sexually and non-sexually, so their partners and children may be at risk. This should convince men to think about vaccination, said Fong, pointing out that men in Hong Kong have an average of 16 sexual partners one of the highest rates in Asia, upping their HPV risk.
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Hong Kong Focus
Survey: AF patients know little about their condition

Christina Lau
atients with atrial fibrillation (AF) know little about their condition and its potential danger, which may impair disease control and increase their stroke risk, according to Professor Vivian Lee of the School of Pharmacy, Chinese University of Hong Kong (CUHK). Lee presented the results of a CUHK survey at the recent inauguration of the Hong Kong Atrial Fibrillation Alliance.In the survey, 70 patients with AF for more than 5 years were interviewed between February and April 2011. Results showed that their knowledge of AF was much poorer than their Western counterparts interviewed in similar surveys. [Lee WY, et al; International Congress of Cardiology 2012] For instance, none of the respondents were able to point out that they had AF, although 65 percent were aware of having heart disease. Half of the respondents were unaware of the symptoms of AF, while 74 percent were unaware of its risk factors. Importantly, only 33 percent of local AF patients knew that they are at increased risk of thromboembolism and stroke, pointed out Lee, who serves as Expert Consultant to the Alliance. Only 34 percent knew that monitoring of vitamin K intake is required during warfarin therapy.
In contrast, in similar surveys overseas, nearly 50 percent of UK patients were able to point out that they had AF, while 80-90 percent of Finnish patients were aware of the symptoms of the condition. Furthermore, more than half of UK patients knew that they are at increased risk of thromboembolism and stroke, while nearly all US patients understood the importance of monitoring vitamin K intake during warfarin therapy. Poor understanding of AF is associated with delayed treatment and poorer treatment outcomes, said Dr. Wing-Hong Fung, Specialist in Cardiology and Deputy Convener of the Alliance. [J Adv Nurs 2008;61:5161] AF patients should learn more about their condition and take medications to prevent stroke. New-generation anticoagulants such as dabigatran are more effective than warfarin in this regard. [Ann Intern Med 2007;146:857-867; Thromb Haemost 2010;104:1106-1115] The Alliance is formed by cardiologists, neurologists, family physicians and pharmacists to provide multidisciplinary educational support for AF patients and healthcare professionals. Our goal is to help prevent AFrelated stroke and reduce the burden of AFrelated hospitalizations, said Dr. Bernard Wong, Specialist in Cardiology and Convener of the Alliance.
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June 2012
Hong Kong Focus
Higher obstetric fees for non-residents

Naomi Rodrig
ttempting to stem the flow of mainland women coming to give birth in Hong Kong, the Hospital Authority (HA) had recently raised fees for obstetric services for non-eligible persons (NEP). As of May 12, the new charges for an obstetric package for non-booked cases in public hospitals have nearly doubled, from HK$48,000 to $90,000. The HA spokesman reiterated that the fee hike was applied to complement the stepped-up border control and law enforcement by the government to deter the undesirable and high-risk behavior of seeking last-minute hospital admission before delivery through Accident & Emergency Department [AED]. He explained that the revision has taken into consideration the relevant factors, such as the complexity and intensity of care for non-booked cases, price comparability with the private market; and the affordability factor. Under the new government regulations, all patients who deliver or receive delivery care services in public hospitals, clinics or AED without prior booking arrangement and/or without any antenatal attendance at a HA spe-
cialist outpatient clinic during the concerned pregnancy will be charged a minimum rate of $90,000. This minimum rate covers the charges for the delivery and the first 3 days of hospitalization in general wards (ie, a 2-night stay) for the concerned delivery, he said. If the woman is admitted to general wards for a further period, the prevailing NEP rate for general wards will be charged for the extra days, while other inpatient charges for public wards and outpatient charges will apply separately.
20
June 2012
Hong Kong Focus
Survey reveals extent of drug dependence in HK

Christina Lau
ealthcare professionals should be aware of the abuse potential of common drugs, as a large-scale epidemiological survey shows that dependence on these drugs is quite common in the community. The Hong Kong Mental Morbidity Survey 20102013 aims to investigate the prevalence of mental disorders in Hong Kong. Supported by a HKD 7 million fund from the Food and Health Bureau, the project involves interviews with 5,700 randomly selected adults (age, 16-75 years) and is a joint effort by the Department of Psychiatry, Chinese University of Hong Kong; Department of Psychiatry, University of Hong Kong; and several psychiatric service units of the Hospital Authority. Interim results in 2,500 respondents showed that 2.7 percent were dependent on analgesics, while 0.8 percent were dependent on sleeping pills. Dependence on cough medicines was less common, at a rate of 0.08 percent. The researchers thus called for attention to the abuse potential of analgesics, sleeping pills and cough medicines, as they were most commonly used by the respondents in daily life. In the survey, 66.4 percent, 5.2 percent and 32.6 percent of the respondents reported use
of these medicines in the past year, respectively. The survey also looked into substance abuse. Among 1,670 respondents aged 16-54 years, the lifetime prevalence of substance abuse was 4 percent. Half of the abusers were aged 16-34 years. While cannabis and ketamine were the most commonly abused substances (62.5 and 48.5 percent, respectively), nearly half of the abusers reported using more than one drug. The most commonly used combination was cannabis and ketamine. In the survey, 14.5 percent of respondents were found to have significant levels of neurotic symptoms. The prevalence of mixed anxiety and depressive disorder, generalized anxiety disorder, and depression was 6.6, 4.7 and 4.2 percent, respectively. Notably, 2.4 percent of the respondents were found to have more than one mood disorder.
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June 2012
Hong Kong Focus

Hong Kong Events
2nd IDKD Intensive Course in Hong Kong Diseases of the Abdomen and Pelvis 16/6-19/6
Info: Swire Travel Limited Tel: 852 (0) 315 188 19 Fax: 852 (0) 315 463 24 E-mail: idkd-hk2012@swiretravel.com www.idkd.org
Live 3D TTE/TEE Practical Training Course Division of Cardiology, Department of Medicine & Therapeutics, CUHK 8/6-9/6
Tel: (852) 2647 6639 Fax: (852) 2144 5343 E-mail: cardiacsec@cuhk.edu.hk
Pain Genetics Symposium: From Basic Science to Clinical Applications Department of Anesthesiology, HKU; Hong Kong Pain Society 9/6
Tel: (852) 2559 9973 Fax: (852) 2547 9528 E-mail: pgs@icc.com.hk www.anaesthesia.hku.hk/PGS2012.htm
2nd Practical Workshop Diagnostic and Therapeutic Endoscopic Ultrasound Department of Surgery, CUHK 26/6-27/6
Tel: (852) 2632 2644 Fax: (852) 2632 4708 E-mail: info@hkmisc.org.hk www.hkmisc.org.hk
Annual Scientific Meeting 2012 Hong Kong Society of Dermatology and Venereology 9/6-10/6
Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 / 3153 4374 Fax: (852) 2559 6910 E-mail: meeting.hk@ubm.com
12th Asian Conference on Clinical Pharmacy Department of Pharmacy, CUHK 7/7-9/7

Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 / 3153 4374 Fax: (852) 2559 6910 E-mail: info@accp2012.org www.accp2012.org
Primary Care Innovations, Developments and Evidence (PRIDE) 2012 Conference CUHK; Primary Care Office, Department of Health 9/6-10/6
Info: Mr. CC Lee Tel: (852) 2252 8433 Fax: (852) 2145 8517 E-mail: cclee@cuhk.edu.hk www.gp-pride.com/index.php?option=com_ content&view=article&id=1
Chinese Medicine in Geriatrics Hong Kong International Integrative Medicine Conference 2012 Hospital Authority; Hong Kong Association for Integration of Chinese-Western Medicine 7/7-8/7
Tel: (852) 2871 8898 E-mail: hkiic2012@hkam.org.hk
Alzheimers Disease Conference 2012: From Public Health, Basic and Clinical Sciences to Therapeutic Insights The Alzheimers Disease Research Network (HKUADR Network); SRT Healthy Aging, HKU 15/6-16/6
Tel: (852) 2255 4689 Fax: (852) 2974 1171 E-mail: hkuadrn@gmail.com www.med.hku.hk/hbha/adc2012
2012 Conference of Asia Oceania Research Organization on Genital Infection and Neoplasia (AOGIN 2012) Department of Obstetrics and Gynecology, HKU 13/7-15/7
Info: PC Tour and Travel Tel: (852) 2734 3315 Fax: (852) 2367 3375 E-mail: conference@pctourshk.com www.ogshk.org/2011/AOGIN_2012.pdf
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June 2012
Hong Kong Focus
Hong Kong Surgical Forum Summer 2012 Department of Surgery, HKU 14/7
Tel: (852) 2819 9691 / 2819 9692 Fax: (852) 2818 9249 E-mail: hksf@hku.hk www.surgery.hku.hk/forum.php
3rd Oncology Forum of Hong Kong Hong Kong College of Radiologists; Hong Kong Society of Clinical Oncology 21/7
Info: PC Tour and Travel Tel: (852) 2734 3312 / 2734 3315 Fax: (852) 2367 3375 / 2367 3375 E-mail: veronica@pctourshk.com / cachel@pctourshk.com www.hkcr.org
Annual Scientific Meeting and Workshop Hong Kong Institute of Musculoskeletal Medicine 21/7-22/7
Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 / 3153 4374 Fax: (852) 2559 6910 E-mail: meeting.hk@ubm.com www.hkimm.hk
5th International Infection Control Conference Hong Kong Infection Control Nurses Association; HKU; Hong Kong College of Radiologists 24/8-26/8
Info: MV Destination Management Ltd. Tel: (852) 2735 8118 Fax: (852) 2735 8282 E-mail: hkicna@mvdmc.com www.mvdmc.com/hkicna/index.html
2012 FDI Annual World Dental Congress FDI World Dental Federation 29/8-1/9
Tel: (852) 2528 5327 Fax: (852) 2529 0755 E-mail: congress@fdiworldental.org www.fdiworldental.org
Transcatheter Renal Denervation (TREND) 2012 Asia-Pacific 29/9

Info: cme4u GmbH Congresses, Meetings and Education Tel: (49) 69 25 61 28 55 Fax: (49) 69 25 62 86 58 E-mail: info@cme4u.org / trend@cvcfrankfurt.de www.csi-trend.org
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June 2012
Conference Coverage
World Congress of Cardiology Scientific Sessions 2012, 18-21 April, Dubai, UAE
Personalize CVD prevention for women

Radha Chitale
Cardiovascular disease prevention is important among women but the ideal approach, which includes personalized risk stratification and assessment, is not reflected in current risk assessment models. The global risk assessment tools that we use today they dont care about the dynamic nature of risk factors within individuals and populations, said Dr. Dilek Ural, Department of Cardiology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey. It is impossible with these tools to evaluate temporal lifelong changes in individuals. More than 8.6 million women die of CVD yearly but their risk of cardiac morbidity or mortality is underestimated. Women often present with heart disease differently than men do. While major risk factors for heart disease and stroke are similar between men and women, many of the nonmajor risk factors differ. Hypertension, diabetes, psychological stress and lack of physical activity are more important determinants of CVD in women. Additionally, these risk factors are distributed with significant differences throughout the world. For example, high cholesterol is a major problem among women in North America, Europe and Australia. High blood pressure is a common contributor to CVD among African women, and diabetes and obesity are the culprits among women in the Middle East.
Over 8.6 million women die of CVD each year around the world.
The American Heart Association made an important amendment to their guidelines in 2011 by changing the criteria for risk status from a 10-year coronary heart disease event risk of 20 percent to a 10-year cardiovascular disease event risk of 10 percent. This change was the result of studies showing women are more prone to stroke as a result of heart disease and may present with disease about 10 years later than male counterparts. Ideally, Ural said cardiovascular prevention and assessment tools should incorporate genetic factors, vascular age, lifelong exposure to multiple risk factors and countrybased socioeconomic factors in order to personalize risk stratification and management for women.
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June 2012
Conference Coverage
Salt tax lowers CV mortality

Radha Chitale
educing daily salt intake via voluntary salt reduction in industrially processed foods or through a tax on high-salt foods may help cut cardiovascular disease mortality, according to preliminary research conducted in the US. Elevated blood pressure is the leading risk factor for death globally, said lead researcher Dr. Thomas Gaziano of the Harvard School of Medicine, Boston, Massachusetts, US. Salt is associated with increased blood pressure in cardiovascular disease. Gaziano and colleagues also sought to reduce the economic burden of hypertension while improving quality and quantity of life through low-cost salt reduction methods. This type of approach could be important in low- and middle-income countries and the fast-developing BRIC (Brazil, Russia, India, China) nations where hypertension is poorly controlled, if it is diagnosed at all. The World Health Organization and other global agencies recommend a daily salt intake of 5 grams or less. The mean daily salt intake in BRIC countries is 10 grams. In some countries, daily salt intake exceeds 16 grams. The researchers modelled the efficacy and financial viability of reduced salt intake through a voluntary 9.5 percent decrease in the salt content of manufactured foods and a 40 percent tax on salty foods, similar to a tobacco tax. Similar models have been used in the UK. Both methods reduced daily sodium intake but voluntary salt reduction was more effective with a 10 percent decrease in sodium in-
take. The salt tax led to a 6 percent decrease. Although some mean daily salt intake remained over the recommended value, Gaziano said both approaches would lead to about a 3 percent reduction in the rate of cardiovascular death and save costs by reducing the number of treatments for heart attacks and stroke. For example, the incidence of heart attacks and strokes would fall by 1.7 percent and 4.7 percent in China, respectively, and by 1.47 percent and 4 percent in India. The total cost for either method of salt reduction was less than US$50 per person over their lifetime. Gaziano estimated that high blood pressure accounts for about 10 percent of the global healthcare expenditure about US$450 billion with up to a trillion USD expected over the next 10 years in new blood pressurerelated events such as stroke and heart attack, not including the cost of lost productivity due to absence from work or early death. Even modest reductions in salt consumption could lead to improvements in CVD mortality and save overall healthcare costs, he said. A separate model emphasizing improved screening and treatment for high-risk hypertensives whose systolic blood pressure was over 140 and whose 10-year cardiovascular event risk was over 20 percent proved to be a more expensive but still cost effective method of reducing cardiovascular fatalities by about 3 percent in low- and middle-income countries. The results of this preliminary study are expected to be published later this year.
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June 2012
Conference Coverage
Personal Perspectives
My favorite topic at WCC was echocardiography during intervention. I was surprised that the session was ticketed because it was not mentioned on the website. It would have been better if ticketed sessions were highlighted on the website beforehand. Dr. Amuthan Vivekanandan, cardiologist, India
There were a variety of presentations at this WCC from basic science to interventional cardiology. Many sessions that I was interested in were concurrent and that made it difficult for me to attend.
Dr. Abdulwasea Derhim Alduais, cardiologist, Yemen
This is a well-organized conference, with lectures presented from many topics. It would have been more interesting if greater emphasis was given to yoga and its ability to reduce stress.
Amandah Hoogbruin, professor of nursing, Kwantlen Polytechnic University-Surrey, British Columbia, Canada
This is my first time attending the WCC. It has been very rewarding, both from the point of view of content and meeting people. Im into public health and prevention, so Ive been going to sessions on physical activity, tobacco control and nutrition.
Trevor Shilton, director of cardiovascular health, Heart Foundation of Australia, Perth, Australia
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June 2012
Conference Coverage
India becoming CVD capital of the world

Rajesh Kumar
ndia is acquiring the dubious distinction of being known as the diabetes and cardiovascular disease (CVD) capital of the world, according to a US expert. Professor Prakash Deedwania of the University of California, San Francisco, US, was commenting on the findings of the Indian Heart Watch (IHW) study that assessed the countrys growing CVD epidemic and identified reasons behind it. The study found that lifestyle (physical activity, diet and smoking) and biological (obesity, diabetes, high blood pressure and elevated cholesterol) risk factors for CVD were at higher levels in India than in developed regions such as the US and Western Europe. Conducted between 2006 and 2010 and involving 6,000 men and women from 11 cities across India, it is the largest ever study probing CVD risk factors in the country. It was led by Deedwania and Dr. Rajeev Gupta of Fortis Escorts Hospital, Jaipur, India. While 79 percent of the polled men and 83 percent of the women were found to be physically inactive, 51 percent of men and 48 percent of women were found to have high-fat diets. About 60 percent of men and 57 percent of women were found to have a low intake of fruit and vegetables, and 12 percent of men and 0.5 percent of women smoked. These resultsmust prompt the [Indian] government to develop public health strategies that will change lifestyles, if these risk factors are to be controlled, said Deedwania. As for the biological and metabolic risk factors, the IHW also found overweight and obesity in 41 percent of men and 45 percent of women. High blood pressure was reported
in 33 percent of men and 30 percent of women, while high cholesterol was found in onequarter of all men and women. Diabetes or metabolic syndrome was also reported in 34 percent of men and 37 percent of women. Urban development is playing a role in the development of CVD risk factors, the IHW found. Smoking, high fat intake and low fruit/vegetable intake were shown to be more common in less developed cities, while physical inactivity was seen to be more prevalent in highly-developed cities with their better transport networks. Accordingly, metabolic risk factors such as obesity, high blood pressure and high cholesterol were seen to be more prevalent in highly developed cities that had easy access to cheaper fast foods/refined foods. Even literate middle-class urban Indians had a low awareness and control of the CVD risk factors, the IHW study results showed. Of the approximately one-third of study participants found to have hypertension, only 57 percent were aware of their status, 40 percent were on treatment and only 25 percent had adequate blood pressure control. In contrast, more than 75 percent of people with hypertension in high and middle-income countries are aware of their health status and more than 5060 percent actually have their blood pressure under control. These results show that improving urban planning and overall living conditions are critical to curb the CVD epidemic in India, said Gupta, adding that basic amenities, healthcare facilities and health literacy also needed to improve so people could take responsibility for their own actions.
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June 2012
Conference Coverage
High-dose nicotine patch safe for heavy smokers

Rajesh Kumar
mokers who have been smoking more than 40 cigarettes daily can be safely treated with a high-dose nicotine patch, according to Professor Richard Hurt, professor of medicine and director of nicotine dependence center at Mayo Clinic in Rochester, Minnesota, US. Current dosing recommendations based on patients smoking rate suggest a dose of 7-14 mg/day for those smoking less than 10 cigarettes daily, 14-21 mg/day for those on 10 to 20 cigarettes daily, and 21-42 mg/day for smokers of 21 to 40 cigarettes daily. [Mayo Clin Proc 2000;75:1311-1316] Hurt said the initial dose can be estimated on the basis of either the patients smoking rate or blood cotinine levels, and the adequacy of the nicotine replacement therapy (NRT) can be assessed either by patient response or by the replacement rate of blood cotinine. A higher percentage of blood cotinine replacement may increase patch therapys efficacy and improve withdrawal symptoms. Nicotine gum, patch, lozenge, inhaler, bupropion, varenicline and the combinations thereof can be used as first-line pharmacotherapy, while clonidine and nortriptyline are suitable for second-line. Of these, the patch and varenicline and/or bupropion can be used as floor medications, along with short acting NRT products for withdrawal symptoms, said Hurt.
Smokers who have been smoking more than two packs of cigarettes a day may be safely treated with high-dose nicotine patches.
Patient involvement is the key to tobacco cessation and the selection of medicines and their doses should be guided by cardiologists clinical skills and knowledge of pharmacotherapy, he added. One study comparing 24-week extended therapy of transdermal nicotine patch dose of 21 mg/day with 8-week standard therapy showed a dose-response to patch therapy. [Ann Int Med 2010;152:144-151]
28
June 2012
Conference Coverage
In this 568-patient study, smoking abstinence was the same in the two groups by week 8. However, the extended therapy achieved a delayed relapse to smoking. At week 24, extended therapy produced higher rates of point-prevalence abstinence (31.6 percent vs. 20.3 percent; [95% CI, 1.23 to 2.66]; P=0.002), prolonged abstinence (41.5 percent vs. 26.9 percent; [95%CI, 1.38 to 2.82]; P=0.001), and continuous abstinence (19.2 percent vs. 12.6 percent; [95% CI, 1.04 to 2.60]; P=0.032) versus standard therapy. Extended therapy also reduced the risk for lapse (hazard ratio, 0.77 [95% CI, 0.63 to 0.95]; P=0.013) and increased the chances of recovery from lapses (hazard ratio, 1.47 [95% CI, 1.17 to 1.84]; P=0.001). At week 52, extended therapy produced higher quit rates for prolonged abstinence only (P=0.027). No differences in side effects and adverse events between groups were found at the extendedtreatment assessment. In a randomized placebo-controlled trial involving varenicline therapy in 714 smokers with stable cardiovascular disease, patch therapy achieved 47 percent abstinence, compared to 14 percent on placebo (95% CI 4.188.93). [Circ 2010;121:221-229] Citing the case study of a 58-year-old smoker with chest pain who was put on two 21mg patches every morning, Hurt said a follow-up phone call 2 weeks later revealed he was experiencing cravings for cigarettes in the evenings, which had increased his use of reliever nicotine inhaler. A 14mg patch at 4pm resolved the issue and the patient was encouraged to use high-dose patches until he could comfortably abstain, and then reduce the morning dose. For smokers with coronary heart disease, stopping smoking decreases all cause mortality by 36 percent, he concluded.
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June 2012
Conference Coverage
Omega-3 fatty acids may reduce CV risk in smokers

Elvira Manzano
mega-3 polyunsaturated fatty acids (PUFA) perform better than placebo in reversing the endothelial damage caused by smoking, according to a small study conducted in Greece. Adult smokers treated with 2 grams of omega-3 fatty acids daily for 12 weeks had significant improvements in endothelial function and arterial stiffness, with a parallel anti-inflammatory effect. This was matched by improvements in flow mediated dilatation (FMD; P<0.05), augmentation index (ALX; P<0.001) and carotid-femoral pulse wave velocity (PWV; P<0.01) values. [Int J Cardiol 2011 Epub ahead of print] These suggest that omega-3 fatty acids inhibit the detrimental effects of smoking on arterial function, which is an independent prognostic marker of cardiovascular risk, said lead study author Dr. Gerasimos Siasos, from the University of Athens Medical School, 1st Department of Cardiology, Hippokration Hospital in Greece. He said the cardioprotective effects of omega-3 fatty acids may be due to a synergism between multiple, intricate mechanisms involving anti-inflammatory and anti-atherosclerotic effects. Siasos and his fellow researchers evaluated the effects of short-term treatment with omega-3 PUFAs in 20 healthy smokers at baseline, day 28 and day 84. At the end of the study period, omega-3 PUFAs decreased endothelial dysfunction
and improved arterial elasticity or distensibility in this cohort of patients. Endothelial dysfunction is Omega-3 fatty acids improve arterial elasticity in healthy smokers. an early marker for atherosclerosis and can be detected before structural changes to the vessel wall become apparent (on angiography or ultrasound). Reduced arterial distensibility contributes to a disproportionate increase in systolic pressure and arterial pulsatility and is associated with cardiovascular morbidity and mortality. Commenting on the study, Dr. Kathryn Taubert, chief science officer of the World Heart Federation, said the only way to protect the body from the harmful effects of tobacco is to stop smoking. We encourage all people, both smokers and non-smokers, to eat healthy diets which include foods rich in omega-3 fatty acids. The American Heart Association (AHA) recommends consumption of at least two servings of fish, especially those rich in omega-3 fatty acids such as salmon, sardines, herring, tuna and halibut, per week. Other good sources of omega-3 fatty acids are dark green leafy vegetables and nut oils, though the body cannot process these as easily as the docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) omega-3 fatty acids found in fish.
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June 2012
Conference Coverage
Daily exercise may help hypertensive patients live longer

Elvira Manzano
ven low levels of daily physical activity could reduce the risk of death in individuals with high blood pressure, according to a new study. In a cohort of 416,175 adult individuals in Taiwan, those who exercised an average of 15 minutes a day or 90 minutes a week were found to have a 14 percent lower risk of dying from cardiovascular disease (CVD) and all causes compared with those who did not exercise. Life expectancy was also longer by 3 years in the physically active group. Every additional 15 minutes of exercise (beyond the minimum 15-minute duration) further reduced all-cause mortality by 4 percent (95% CI 2.5-7). [Lancet 2011;378:1244-1253] These benefits applied to all age groups and both sexes, including those with CVD risks, said study author Dr. Chi-Pang Wen, from the Institute of Population Health Sciences, National Health Research Institute in Zhunan, Taiwan.The reduction in mortality risk was equivalent to a permanent reduction of 50 mmHg in blood pressure, over and above any anti-hypertensive medications. In their prospective cohort study, Wen and colleagues compared the all-cause and CVD mortality risks of men and women participating in standard medical screening programs in Taiwan from 1996 to 2008. They found that inactive individuals had a 17 percent greater risk of mortality (HR 1.17, 95% CI 1.10-1.24) than active individuals.
The study was the first to quantify the impact of exercise on the risk profile of people with high blood pres- Exercise has permanent beneficial effects on CVD. sure. Appreciating this relationship will hopefully help to motivate inactive hypertensive patients to exercise, said Wen. At least 31 percent of the worlds population does not get sufficient exercise. Two out of five adults have hypertension. Clinicians would normally concentrate on treating hypertension as patients do not see the relevance of physical activity with blood pressure. Medications can lower blood pressure, but are temporary, costly and have side effects. Exercise is cost-free and with permanent [beneficial] effect, Wen said. Doctors should also discuss the importance of physical exercise as a means to manage the CVD and all-cause mortality risks, he concluded. Studies have shown that a sedentary lifestyle is one of the major risk factors for CVD, the others being uncontrolled hypertension, hypercholesterolemia, obesity and smoking. Modifying these risk factors through regular exercise, healthy eating and smoking cessation can reduce the risks of a future heart attack, stroke or premature death.
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June 2012
In Practice
Low back pain: Current concepts

Dr. Eugene Wong
Consultant Spine & Orthopedic Surgeon Kuala Lumpur
Low back pain (LBP) is a common and challenging health problem in primary care. There is a point prevalence of 15 to 30 percent and a lifetime prevalence of between 50 and 85 percent. [Spine (Phila Pa 1976) 2001;26(22):250413; discussion 2513-4] Nonspecific low back pain (NSLBP) comprises approximately 85 percent of all back pain diagnoses and affects 80 percent of adults. It is associated with enormous expense in terms of healthcare expenditures, and work- and disability-related losses. Mean direct and indirect costs for LBP care are twice as high for patients with chronic LBP when compared with acute LBP. The severity of LBP (high disability and moderate-to-severe limitations in daily living) and depression are the two most important predictors of costs. Currently, there is a shift in the clinical model of LBP from a biomedical injury to a multifactorial biopsychosocial pain syndrome which erupts periodically over the course of a lifetime of an individual. The consensus of clinical guidelines suggests that acute NSLBP patients should be reassured of a good prognosis, educated in selfcare, remain active and use over-the-counter medications as a first line of symptom control. Many patients with low back pain have at least one red-flag sign. Red-flag signs have a
poor test specificity. Thus, the evaluation of LBP should take into account the whole clinical presentation of the patient. The key is to have a high index of suspicion in high-risk patients or when more than one red flag is present. (Table 1) Diagnostic and therapeutic management of LBP vary tremendously among GPs. A recommended approach to diagnosis and treatment is provided in Tables 2 and 3. An ideal approach in managing LBP patients should be multidisciplinary and inter-professional. GPs could focus on pain management through medication, red-flag screening, encouragement to stay active and reassurance. Physical therapy could focus on pain management, general exercise and encouragement to stay active. Occupational therapy could focus on disability prognosis, yellow-flags management (Table 4) and return to activity parameters. Patients with yellow flag signs require cognitive behavioral therapy, the aim of which is to change patients thoughts and beliefs about their pain. Adequate information and good communication between the primary care physician and patient is a prerequisite for a successful psychosocial intervention, but this will not guarantee a change in the way patients behave and how they deal with their pain problem. The key to treatment success is that patients become active processors of information, and not passive reactors. Patients should be active collaborators when changing misconceived thoughts and behaviors (Table 5). [Spine (Phila Pa 1976) 2008;33(1):81-9]
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June 2012
In Practice
brings us to the question: is there a need for such a guideline to address the issue of LBP in the local population? LBP can be managed successfully in the primary care setting through a program of activity modification, reassurance, shortterm symptom control and alteration of inappropriate beliefs about the correlation between back pain and impairment. Multiple evidence-based guidelines exist, but a fundamental concern is the current lack of knowledge on the best ways to change the behavior of clinicians.
A high proportion of patients recover from acute back pain. Reductions in pain and disability have to be more than 50 percent to be consistent with recovery from LBP. [Spine (Phila Pa 1976) 2011;36(26):2316-23] When should LBP cases be referred to a spine surgeon? Indications would include patients with no response after 6 weeks of conservative treatment, patients with radicular syndrome, presence of nerve root tension signs, suspicion of a pathologic change, cauda equina syndrome and MRI showing disc protrusion or prolapse. To rationalize the approach of LBP and to take account of emerging scientific evidence, clinical guidelines on the management of LBP have been issued in various countries. This
Table 1: Red flags Cancer
Age >50 or <17. History. U nexplained weight loss of >10 kg within 6 months. Failure to improve with therapy. P ain persists for more than 6 weeks. Pain at rest or at night. P rogressive neurologic deficit. Major motor weakness. Major sensory deficit.
Table 3: Recommendations for treatment of LBP Acute or Subacute Pain

Reassure patients (favorable prognosis). Advise to stay active. P rescribe medication if necessary paracetamol, nonsteroidal anti-inflammatory agents, muscle relaxants or opioids. D iscourage bed rest. D o not advise back-specific exercises.
Chronic Pain
Refer for exercise therapy.
Significant herniated nucleus pulposus

M ajor muscle weakness (strength 3 of 5 or less). Foot drop.
Table 4: Yellow Flags Psychiatric disorders

Anxious, depressed, social withdrawal. Misconception of danger of back disorders. Somatization; poor sleep because of back pain.
Infection

Severe pain. P ersistent fever. History of intravenous drug abuse. Recent bacterial infection. U rinary tract infection or pyelonephritis. Pneumonia. W ound (eg, decubitus ulcer) in spine region. Immunocompromised state. Systemic corticosteroids. Organ transplant. Diabetes mellitus. H uman Immunodeficiency Virus (HIV). P ain at rest.
Vertebral fracture
Prolonged use of corticosteroids. Age greater than 70 years. History of osteoporosis. Mild trauma over age 50 (or with osteoporosis). Recent significant trauma at any age.
Socioeconomic issues
O ccupation related (heavy lifting, unsociable working hours, high mental workload, prolonged time off work, dissatisfaction with work, lack of work support, problems with claims or compensation, and no economic gain from resuming work). Economic/ social hardships (eg, death in the family, divorce or loss of income).
Abdominal Aortic Aneurysm

Abdominal pulsating mass. Atherosclerotic vascular disease. Pain at rest or nocturnal pain.
Behavior
Inappropriate or limited belief of improvement or ability to work. E xpectation that passive treatment (physical agents, extended bed rest) is better than active participation (exercise, walking, working). High fear-avoidance behavior scale score. H igh kinesiophobia scale score.
Gastrointestinal/ Genitourinary
Abdominal tenderness. Rebound tenderness. Diarrhea/constipation. Anuria, oliguria, polyuria. Abnormal menses, dyspareunia.
U rinary incontinence or retention. S addle anesthesia. Anal sphincter tone decreased or fecal incontinence. B ilateral lower extremity weakness or numbness.
Cauda Equina Syndrome
Miscellaneous
Confusion about diagnosis and prognosis. M isunderstandings about the cause of pain. Negative experience with previous intervention for back pain.
General (weak test specificity)

Vertebral tenderness. Limited spine range of motion.
Table 5: Aims of a cognitive behavioral approach Table 2: Recommendations for diagnosis of LBP
History taking and physical examination to exclude red flags. Diagnostic triage (nonspecific LBP, radicular syndrome, specific pathologic change). Physical examination for neurologic screening. Radiographs not useful for nonspecific LBP. Consider psychosocial factors if there is no improvement. C ombat demoralization by assisting patients to change their view of their pain from overwhelming to manageable. Assist patients to reconceptualize themselves as active, resourceful and competent. H elp patients in coping strategies and techniques to help them adapt and respond to pain and the resultant problems. T each patients how to anticipate problems proactively and generate solutions. Attribute successful outcomes to their own efforts.
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June 2012
News
Large doses of vitamin C good for hypertension

Elvira Manzano
aking extra doses of vitamin C may help reduce hypertension in adults, according to a meta-analysis. Patients taking an average of 500 mg of vitamin C a day roughly five times the recommended daily requirement for a median duration of 8 weeks, reduced systolic blood pressure (SBP) by 3.84 mm Hg (P<0.01) and diastolic blood pressure (DBP) by 1.48 mm Hg (P=0.04). Among patients with hypertension, the drop in SBP was nearly 5 mm Hg (P<0.01). [Am J Clin Nutr 2012; 95(5):1079-1088] The researchers however said it is still too early to recommend extra loading of vitamin C. Although our research suggests a modest blood pressure-lowering effect with vitamin C supplementation we really need more research to understand the implications of taking them, said lead study author Dr. Edgar Pete R. Miller III, associate professor, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, US. Miller and colleagues analyzed data from 29 randomized controlled trials culled from three US databases (Medline, EMBASE, and Central) from 1966 to 2011 that examined the effects of oral vitamin C supplementation on blood pressure. The trials involved a total of 1,400 adult participants. BP effects were pooled by random-effects models, with trials weighted by inverse variance. Our review found only a moderate impact on blood pressure, but if the entire US
population lowered blood pressure by 3 mm Hg, there would be a lot fewer strokes, he said. Miller however cautioned that A meta-analysis has shown that extra vitamin none of the C intake has a modest blood pressure-lowering 29 studies has effect in patients with hypertension. shown that vitamin C directly prevents cardiovascular disease, including stroke. People love to take vitamins regardless of the evidence or lack of it, he said. Were trying to raise the bar and provide evidencebased guidance about whether supplements help or actually do harm. With respect to vitamin C, the jury is still out, Miller added. He said that in observational studies, increased vitamin C intake, vitamin C supplementation, and higher serum vitamin C are associated with lower BP. However, evidence of BP-lowering effects of vitamin C in clinical trials is inconsistent. In short term trials, vitamin C supplementation reduced SBP and DBP. Long term trials are however needed, the authors concluded. Research showed that vitamin C has a diuretic effect which helps the body get rid of excess sodium and water, thus lowering blood pressure. Other studies also suggested that vitamin C, acting as an antioxidant, can slow down the progression of atherosclerosis.
34
June 2012
News
Oral bacteria can trigger blood clots

Elvira Manzano
ral bacteria that enter the bloodstream through poor oral hygiene or during dental procedures can cause blood clots and life-threatening endocarditis, research has found. A pre-clinical study by scientists from the US, UK and Ireland showed that the bacterium Streptococcus gordonii, a normal inhabitant of the mouth, produces a molecule that mimics the human protein fibrinogen and tricks the platelets into recognizing the bacteria as vascular injury, resulting in platelet aggregation and clot formation in the blood vessels. [Infect Immun 2010;78:413-422] Both mechanisms are important in the development of infective endocarditis, said study author Dr. Helen Petersen from the University of Bristol, UK. A crucial step is the bacteria sticking to the heart valve and activating the platelets to form a clot, leading to inflammation and valve dysfunction. Despite modern antibiotics and surgical therapy, mortality rates from infective endocarditis remain as high as 30 percent with deaths resulting primarily from central nervous system complications and congestive heart failure. The researchers are now studying other oral bacteria that may have similar effects as S. gordonii, in the hope of developing new drugs that could prevent unwanted blood clots and infective endocarditis. We are getting closer to design new compounds that would inhibit it we are also trying to determine how widespread this phenomenon is, Petersen said.
Commenting on the study, Dr. Mark Chan, consultant at the cardiac department, National University Heart Centre, Singapore, said increased platelet clumping and thrombus formation arising from invasion of S. gordonii may be a possible mechanism through which poor dental hygiene leads to an increased risk of heart attack. However, he cautioned that clinical studies are needed to confirm the true clinical impact of Petersens findings. If platelets indeed play an important role in infective endocarditis, it further supports recommendations that anti-platelet therapy [should] not be stopped during routine dental procedures. Studies have shown that discontinuation of anti-platelet therapy during dental or surgical procedures increases the risk of heart attacks during the peri-operative period.
35
June 2012
News
Teen drug abuse linked to brain network

Leonard Yap
pecific brain networks have been found to predispose teenagers to drug and alcohol abuse, a large US study reports. Researchers from the University of Vermont (UVM) in Burlington found that diminished activity in a network involving the orbitofrontal cortex is associated with a higher probability of experimentation with alcohol, cigarettes and illegal drugs in early adolescence. Dr. Robert Whelan and Dr. Hugh Garavan, of UVM, along with a large group of international colleagues, reported that differences in these networks provided strong evidence that some teenagers were at higher risk for drug and alcohol experimentation because their brains work differently, causing them to be more impulsive. This was the largest imaging study of the human brain ever conducted. It involved 1,896 teenagers and the study findings were presented online in Nature Neuroscience. [doi:10.1038/nn.3092] The differences in these networks seem to precede drug use, said Garavan, Whelans colleague in UVMs psychiatry department, who also served as principal investigator of the Irish component of a large European research project called IMAGEN. These networks are not working as well for some kids as for others, said Whelan, thus making them more impulsive. A 14-year-old teenager with a less functional impulse regulating network faced with a choice about smoking or drinking, will
more likely say, yeah, gimme, gimme, gimme! said Garavan, and the more functional kid is more likely to say, no, Im not going to do that. Testing for lower function in this brain network, and perhaps other networks, could someday Function in particular be used as a risk factor or brain networks of teenagers could be used as a biomarker for potential biomarker to assess risk drug use, Garavan said. of drug abuse. The researchers also found that other newly discovered networks were connected with attention-deficit hyperactivity disorder (ADHD) symptoms. These networks are distinct from those associated with early drug use. Both ADHD and early drug use are associated with poor inhibitory control, a problem that plagues impulsive people. This strengthens the idea that the risk of ADHD is not necessarily a full-blown risk for drug use, as some recent studies suggest. Dr. Edythe London, a professor of addiction studies and director of the University of California Los Angeles Laboratory of Molecular Pharmacology, described the study as outstanding and substantially advances our understanding of the neural circuitry that governs inhibitory control in the adolescent brain. The take-home message is that impulsivity can be decomposed, broken down into different brain regions, and the functioning of one region is related to ADHD symptoms, while the functioning of other regions is related to drug use, Garavan said.
36
June 2012
News
Lutein crucial for early cognitive development

Rajesh Kumar
illions of children under five years of age fail to reach their full cognitive potential each year, mainly due to lack of adequate nutrition essential for development during the early years of life. While the role of iron, iodine, choline, zinc and omega-3 fatty acids is well established, lutein is now being acknowledged as another important nutrient crucial in the early cognitive development, said Dr. Elizabeth Johnson, research scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, US. Johnson cited her study involving the examination of brain tissues of 30 healthy infants who had died in the first year of their lives due to sudden infant death syndrome (SIDS) and other reasons. We found that lutein is not only present in all the four regions of the infant brain (frontal cortex, hippocampus, auditory cortex and occipital cortex), but it is there in preference to other carotenoids, she said. Lutein is an integral part of the eyes retina too. Also, 60 percent of all carotenoids in the infant brains turned out to be in the form of lutein. This proportion was double than what earlier studies have found in the adult brains. Researchers found this level of concentration surprising, considering only a sixth of all the carotenoids found in the human diet are usually in the form of lutein. If the brain is soaking it up from across the blood-brain barrier and accumulating it, clearly it is needed for something, said profes-
sor Sanja Kolaek, professor of pediatrics at the Childrens Hospital Zagreb, Croatia and the vice-president of the Croatian Pediatric Society. Lutein is only available through dietary sources and cannot be made by the body. Therefore, women of child bearing age and expectant and breastfeeding mothers should be encouraged to eat a wide variety of foods as part of a balanced diet, including luteinrich foods such as green, leafy vegetables and eggs, said Kolaek. For infants, breast milk is the best source of lutein and breast feeding exclusively for up to six months can prevent a lot of problems in them, including growth issues such as the child growing too fast, or not growing fast enough. Supplementing breast feeding with other foods is usually recommended no earlier than four months and no later than six. Where mothers need to provide a formula at any age during the first year of the childs life, [fortified formula] is the right option compared to cows milk, she added. Cows milk should not be the infants basic diet as it does not provide all the nutrients necessary for the childs physical and cognitive development. Kolaek said doctors should never recommend elimination diet to prevent a disease. If a woman or child needs to eliminate nuts, dairy products, fish or eggs due to a health condition, they should try to substitute the nutrients they might be missing out on. Both Johnson and Kolaek were recently hosted in Singapore by Abbott Nutrition.
38
June 2012
News
Feeding difficulties can persist into adulthood

Rajesh Kumar
eeding difficulties can have a lasting impact on a childs physical and mental development and the condition can persist into adolescence and adulthood if not treated early, according to an expert. Dr. Glenn Berall, chief of pediatrics at North York General Hospital in Toronto, Ontario, Canada and a leading expert on the subject, cited a study that looked at children diagnosed with feeding difficulties at age one or two, followed them up at nine About 20 to 30 percent of all children have some level of feeding difficulty. years of age and compared tal or emotional and behavioral. Studies have them with their classmates shown that children who have feeding probwho did not have such prior diagnosis. lems have a higher prevalence of depression, The researchers found that prevalence of anxiety and delinquency, Berall said. feeding difficulties was three times as high in About 20 to 30 percent of all children are children with prior diagnosis. Recent studies believed to have some level of feeding diffialso support the idea that the condition perculty, and the rate is up to 80 percent in those sists if not addressed early, said Berall. He with autism and other neuro-developmental was hosted in Singapore recently by Abbott problems. Nutrition and spoke to GPs and pediatriBeing the first line of care, GPs will be the cians about his experiences. first ones to encounter these cases. They usuWhile habitually picky eaters who are ally check the level of severity, sub-category otherwise well nourished are not a concern, that the condition falls into and the level of eating difficulties become troublesome when parental anxiety associated with the childs they cause consequences, be they nutritional feeding problems, Berall said. (iron and calcium deficiency), developmen-
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June 2012
News
The food rules
T he parent decides where, when, and what the child eats, but the child decides how much is eaten. A void distraction at mealtime. Use a high chair to help confine the toddler to the feeding environment. Avoid juice and milk and provide only water for thirst D o not get overly excited or animated (eg, flying airplanes into the mouth). E ating should begin within 15 minutes of the start of the meal and last no longer than 30-35 minutes. o not cook at short notice to pander D to the childs whim. R espect the childs tendency to neophobia and offer a food repetitively before giving up on it. ncourage independent feeding: The E toddler should have his or her own spoon.
Some doctors use the diagnostic toolkit called Identification and Management of Feeding Difficulties (IMFeD) to identify and manage the condition themselves or to refer the child to a specialist. The kit classifies common feeding difficulties as: limited appetite, sensory food aversion, underlying medical condition, fear of feeding, neglect and undue caregiver concern. Berall said common caregiver styles (controlling, responsive, neglectful and indulgent) also need to be understood before deciding on the right treatment approach. Some children will do well with the food rules (see box). The highly selective eaters are afraid of trying new foods and can respond well to spicy foods, whereas the more serious ones will require a longer work up. While parents and GP work together to resolve the issue, adding a balanced supplement such as PediaSure to the childs diet wont suppress their appetite or interfere with feeding, added Berall. Instead, it could help recover their growth and relieve the parents anxiety by providing reassurance that their child is getting better nutrition. That will help parents follow the food guidelines to make sure the whole treatment package is a success, he said. Children with high selectivity and fear of feeding also take a long time to respond. Adding a supplement to their diet, given at the end of the day, will help balance their nutrition in the meanwhile.
40
June 2012
News
Healthcare system overhauls needed, say experts

Radha Chitale
edical experts and government officials said coordinated government efforts across Southeast Asia, as well as fundamental changes in value systems, are necessary to improve awareness of chronic diseases and access to care, during a gathering to discuss the state of healthcare in the Asia Pacific region. Its a mix of what individuals need to do and how one can influence their behaviors towards a certain set of values, and how to support the initiative towards achieving [health] objectives, said Dr. Anil Kapur, managing director of the World Diabetes Foundation, at a summary roundtable during the Economist Healthcare in Asia conference, held recently in Singapore. Activity from local governments to initiate policy is important to understanding the importance of chronic disease, said Professor Garry Jennings, director of the Baker IDI Heart and Diabetes Institute, a cardiovascular and metabolic research centre in Australia. Dr. Gilberto Lopes, senior consultant medical oncologist and assistant director for Clinical Research at the Johns Hopkins Singapore International Medical Centre, noted that coordinated programs such as the Global Alliance Vaccine Immunization (GAVI) program have successfully created funds and generated new markets for low-cost drugs in the developing world.
Lopes said such networks that increase access to vaccines in poor countries could be useful models for increasing access to oncology medications. It is clear today we do have a large population of patients that we cannot cure, who have pain and discomfort, and can be palliated with simple, cheap medications, he said. Coordination and funding at the national level can help relieve patient suffering [in palliative care or survivorship care].
Coordination and funding at the national level can help relieve patient suffering
Other government initiatives such as subsidies to make food affordable, contracts between governments and health non-governmental organizations, bulk-purchasing medications to bargain prices down and taking advantage of corporate social responsibility programs may also improve patient outcomes. But even when a country has funds or guidelines for improving access to care, Dr. Mary Gospodarowicz, president-elect of the Union for International Cancer Control and medical director of the Cancer Programme at Princess Margaret Hospital in Toronto, Canada, said
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June 2012
News
Kapur said harnessing technology would be critical when reaching out to the developing world, particularly using mobile technology, to bring advanced equipment to primary care settings. He also said schools are key environments for improving awareness of health. Emphasizing healthy eating and physical activity among children will help prevent diabetes in the future. People behave in a certain way because those are the values that society accepts, Kapur said. If we have to bring about a change in outcomes, then we have to adjust the values society has for certain behaviors.
those resources may lie unused because governments may lack metrics and specific measurable goals to evaluate progress. While everyone wants to show decreased mortality and [improved] survival from cancer, you need interim surrogate measures that can be shown to be making progress, she said. Continual lack of access to primary and specialist care, accurate diagnoses, and the ablity to follow through from diagnosis to treatment may be prevalent due to distance from care, poor insurance coverage or even cultural factors that might keep patients from following screening or treatment recommendations.
42
June 2012
News
Stem cells prevent organ rejection better than antibodies

Radha Chitale
one marrow-derived mesenchymal stem cells (MSCs) prevented organ rejection better than antibody induction therapy in patients with end-stage renal disease who received new kidneys. Antibody induction therapy is routine in organ transplant procedures to prevent the host from attacking and destroying the foreign tissue, but it can be toxic due to the effects of the calcineurin inhibitors (CNIs) used in conjunction with the antbodies, as well as leaving patients vulnerable to infection. Patients with end-stage renal disease require dialysis or a kidney transplant. [MSCs] inhibit T-cell proliferation, monocyte differentiation to dendritic cells, modulate B-cell functions, and suppress natural killer cytotoxic effects, said researchers from the Organ Transplat Institute at Fuzhou General Hospital and Xiamen University in China. Thus, MSCs offer new therapeutic opportunities to prevent transplant rejection. The trial included 159 patients with endstage-renal disease who had undergone a kidney transplant from a living-related donor. Treatments were administered at kidney reperfusion and at 2 weeks. [JAMA 2012;307:1169-1177] Patients were randomized to receive either autologous MSCs plus a standard dose of immunosuppressive CNIs (N=53), MSC plus a low-dose of CNIs (N=52), or anti-IL-2 recep-
tor antibody plus standard dose CNI (N=51; controls). We found that autologous MSC recipients had faster renal function recovery during the first month, displayed fewer adverse events, and had reduced opportunistic infections than controls, the researchers said. Thus, autologous MSCs may replace anti-IL-2 receptor antibodies and may allow for using lower CNI maintenance doses without compromizing patient safety and graft outcome. Survival was similar between groups at 1330 months but 21.6 percent of control patients showed acute organ rejection at 6 months compared with 7.5 percent (P=0.04) and 7.7 percent (P=0.046) of MSC-treated patients in the standard and low-dose CNI arms, respectively. Creatinine tests showed that MSC-treated patients had improved renal function in the month following surgery compared to the control arm. Patients maintained this outcome at a 1-year follow up, which the researchers noted was encouraging as renal allograft function is a good indicator of long-term outcomes. A combined analysis during the 1-year follow up of both MSC-treated groups showed a significantly decreased risk of opportunistic infection compared to the antibody-treated group (P=0.02). Extended monitoring of study participants will allow assessment of the long-term effects of autologous MSCs on renal allograft function, survival, and safety, the researchers said.
43
June 2012
News
BPA may increase future risk of heart disease

Leonard Yap
ealthy people with prolonged exposure to a widely used chemical in plastics may have an increased risk of developing heart disease later in life, a study shows. Researchers at Peninsula College of Medicine and Dentistry, the University of Exeter and the European Centre for the Environment and Human Health found that healthy people with higher urine concentrations of bisphenol A (BPA) had a higher probability of eventually developing heart disease. [Circulation 2012; Feb 21 Epub ahead of print] This recent study utilized data from the European Prospective Investigation of Cancer (EPIC) in Norfolk, UK, a long-term population investigation led by the University of Cambridge. It is the first time that data have been used to establish a link between BPA exposure and future onset of cardio vascular disease. The analysis was funded by the British Heart Foundation (BHF). The study compared urine BPA levels of 758 initially healthy EPIC study respondents who later developed cardiovascular disease, and 861 respondents who did not develop heart disease over a period of 10 years. The findings of the study showed that those who developed heart disease tended to have higher urinary BPA concentrations at the start of the 10-year period. Professor David Melzer, of Peninsula Medical School, who led the team, said: This study strengthens the statistical link between BPA and heart disease, but we cant be certain
that BPA itself is responsible. It is now important that government agencies organize drug style safety trials of BPA in humans, as much basic information about how BPA behaves in the human body is still unknown. If BPA itself is directly responsible for this increase in risk, the size of effect is difficult to estimate. However, it adds to the evidence that BPA may be an additional contributor to heart disease risk alongside the major risk factors, such as smoking, high blood pressure and high cholesterol levels, said Professor Tamara Galloway, of the University of Exeter and senior author of the study. We dont believe there is any cause for the public or heart patients to be concerned by BPA. While this study suggests a possible link between BPA and heart disease, its clear that even if there is a link, the risk is very small. The saturated fat, salt and sugar in pre-packaged foods are far more harmful than anything youll find in the packaging, said Professor Jeremy Pearson, BHFs associate medical director. Despite important limitations in its methods, this study adds to suspicion of a possible hazard from BPA, and should be an encouragement to further research. A stronger study design would use results from several repeated urinary measurements in each subject, and a different method of statistical analysis. The findings are not sufficiently strong to warrant additional controls on BPA at this stage, said Dr. David Coggan, professor of occupational and environmental medicine at the University of Southampton.
44
June 2012
News
Higher risk of stroke in older women diagnosed with AF

Rajesh Kumar
lderly women had a higher risk of stroke than men following a recent diagnosis of atrial fibrillation (AF), regardless of their other risk factors and use of warfarin, a study has found. The findings suggest that current anticoagulant therapy to prevent stroke might not be sufficient for older women, the researchers said while urging clinicians to apply new strategies to effectively prevent stroke equally in men and women. [JAMA 2012;307:19521958] All patients with AF have a 5-fold increase in the risk of stroke compared with the general population; therefore, antithrombotic agents are prescribed to reduce this risk. Under-utilization of these agents in elderly women is believed to contribute to an even higher risk in these patients. Researchers used administrative databases linking to hospital discharge summaries, physicians records and prescription drug claims database for 39,398 men (47.2 percent) and 44,115 women (52.8 percent) aged 65 years or older, who were admitted to hospital with recently diagnosed AF in Quebec, Canada from 1998 to 2007. At admission, women were older and had a higher CHADS2 (congestive heart failure, hypertension, age 75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 vs. 1.74, P<0.001). At discharge, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P<0.001) and adher-
Elderly women with AF should be the target of more effective stroke prevention therapy.
ence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs. 1.61 per 100 person-years (95% CI, 1.541.69) in men (P<0.001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P<0.001), even after adjusting for baseline comorbid conditions, individual components of the CHADS2 score, and warfarin treatment. Analysis indicated that women had a 14 percent higher risk of stroke than men, after adjusting for various factors. But the authors could not figure out why. [It] may be attributable to physiology (such as uncontrolled hypertension), vascular biology, genetic factors, hormonal or thromboembolic factors, or psychosocial factors that differ between men and women. We were
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June 2012
News
and director of clinical trials at the National Heart Centre Singapore, agreed saying the recent European AF management guidelines already advocate the use of a new stroke risk score (CHA2DS2-VASc) that assigns higher risk to female patients with AF, compared with males. This current study confirms the observation in several prior studies that stroke rates are higher in women with AF. In addition, it demonstrates that the increased risk in women is most pronounced in elderly patients aged 75 years or more, regardless of their risk profile and use of anticoagulation, said Tan.
not able to identify these factors with our database, said author Dr. Meytal Avgil Tsadok of the McGill University Health Center, Montreal, Canada, and colleagues. Although epidemiologic studies have investigated sex differences in stroke occurrence, little is known about warfarin effectiveness between men and women in the real-world clinical setting. Our results suggest that elderly women with AF may need to be targeted for more effective stroke prevention therapy. Associate Professor Tan Ru San, senior consultant in the department of cardiology
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46
June 2012
News
Fish oil-flavored yoghurt more than a pick-me-up

Pank Jit Sin
he combination of fish oil with yoghurt may help consumers achieve the recommended amount of n-3 fatty acids (also known as omega-3 fatty acids), reveals a study. According to scientists at Virginia Polytechnic Institute and State University (Virginia Tech), US, many consumers find it difficult to consume the recommended amounts of n-3 fatty acids. As a solution, the researchers said the consumption of a single serving of savoryflavored yoghurt would be sufficient to achieve this aim. [J Dairy Sci 2012;95:1690-1698] Lead author Professor Susan E. Duncan, professor and director of the macromolecular interfaces with life sciences program, Food Science and Technology, Virginia Tech, said yoghurt, being an internationally popular and healthy drink, could be an excellent vehicle for the delivery of n-3 fatty acids. With the recent introduction of exotic yoghurt flavors, Duncan said it is now possible to incorporate fish oil into a chili- and limeflavored yoghurt (to hide the smell of fish oil). As little as 1 percent concentration of fish oil is sufficient to provide more than the recommended daily intake of this heart-healthy oil. This advancement could make it more acceptable to a large proportion of the general population and could find its place among healthconscious consumers, she said. Duncans team carried out two studies to determine consumer reaction towards savory
flavored yoghurts. In the first study, which had two panels of tasters, it was found that one panel could not differentiate between low levels of fish and butter oils in unflavored yoghurt. However, they could taste oxidized fish oil as it had a strong fishy taste. The second panel underwent 6 hours of training so that they were able to accurately describe and measure lime, sweet, heat, acid and oxidized flavor attributes. These tasters found the fish flavor to be more pronounced than the lime and acid characteristics in a lime-chili flavored yoghurt with 1 percent oxidized fish oil. This was in comparison to yoghurts that contained 0.43 percent or 1 percent fresh fish oil. The second study took 100 untrained consumers who were nutritionally motivated and aware of the health benefits of n-3 fatty acids and evaluated their overall acceptance and flavor acceptance of chili-lime yoghurt enriched with butter oil or fish oil. This study found that 50 percent of this group rated chili-lime flavored yoghurt enriched with 1 percent butter oil or fish oil between liked extremely to neither liked nor disliked. Of this number, 39 percent said they would highly likely or likely consume the chili-lime flavored yoghurt on a regular basis. The researchers said the low acceptance of the chili-lime yoghurt in the remaining 50 percent of the group might have been caused by the flavor itself or the lack of sweetness.
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June 2012
News
Popcorn, the unexpected super-snack?

Leonard Yap
elieve it or not, popcorn, the staple food in cinemas, has higher levels of antioxidants than fruits or vegetables, say US scientists. Scientists from the University of Scranton, Pennsylvania, found that popcorn has more antioxidant compounds, called polyphenols, than fruits and vegetables. The outcome of their study was presented at the 243rd National Meeting and Exposition of the American Chemical Society in San Diego, California. The new study found that the amount of polyphenols in popcorn was up to 300 mg a serving compared to 114 mg for a serving of sweet corn and 160 mg for all fruits. In addition, one serving of popcorn provides 13 percent of an average intake of polyphenols a day per person in the US. Fruits provide 255 mg per day of polyphenols and vegetables 218 mg per day to the average US diet. This surprising discovery has given popcorn new-found respect as a healthy snack. Dr. Joe Vinson, a pioneer in analyzing the healthy components in chocolate, nuts and other common foods, said the concentration of polyphenols is much higher in popcorn, which averages only about 4 percent water. Polyphenol content in many fruits and vegetables are typically diluted in 90 percent water. In another surprising discovery, the researchers found that the hull of the popcorn, the part that has a tendency to get stuck between the teeth, has the highest concentration of polyphenols and fiber. Those hulls deserve more respect, said Vinson, They are nutritional gold nuggets.
Popcorn is a healthy snack when prepared without butter, sugar and salt.
Popcorn may be the perfect snack. Its the only snack that is 100 percent unprocessed whole grain. All other grains are processed and diluted with other ingredients, and although cereals are called whole grain, this simply means that over 51 percent of the weight of the product is whole grain. One serving of popcorn will provide more than 70 percent of the daily intake of whole grain. The average person only gets about half a serving of whole grains a day, and popcorn could fill that gap in a very pleasant way, Vinson said. But the way popcorn is prepared and served can quickly dent its healthful image. Cook it in oil, butter or fake butter (as used in cinemas), and loading it with salt and sugar will make popcorn a nutritional nightmare loaded with fat and calories. Furthermore, popcorn cannot replace fresh fruits and vegetables in a healthy diet, Vinson cautioned.
49
June 2012
News
Hepatitis E widespread in Asia and Africa

Pank Jit Sin
n estimated 20.1 million persons in nine regions of the world are infected with the hepatitis E virus (HEV), reveals new research funded by the WHO. In 2005, 3.4 million symptomatic cases, 70,000 deaths and 3,000 stillbirths were attributed to HEV in Asia and Africa. [Hepatology 2012;55:988-997] HEV infection is acute, much like hepatitis A, and follows a different infection path than hepatitis B and C. The genotypes studied were types 1 and 2 as these are known to specifically infect humans and are involved in large outbreaks in developing countries due to poorer sanitary conditions. Although an effective HEV vaccine exists, the vaccine is not widely available and is out of reach for most people in these regions. The study found that the pattern of HEV spread was consistent across the study regions, and that the largest incidence increase was in the 5 to 20 years age group. Of the total 20.1 million people infected with HEV, 61 percent were in East and South Asia. These re-
gions also accounted for 65 percent of deaths from HEV. North Africa, on the other hand, registered 14 percent of global HEV infections, but only 8.3 percent were symptomatic cases and 8 percent resulted in death. The authors attributed this relatively low mortality rate to the younger average age of infected individuals in that region. According to lead author Dr. David Rein, of the social science research organization NORC, University of Chicago, US, the study is the first attempt to estimate the annual global impact of HEV. The estimated figures were determined through modeling based on published data of the disease burden of HEV genotypes 1 and 2 in the nine selected regions. These regions represent 71 percent of the worlds population. A limitation to the study was leaving out genotype 3, as it was more prevalent in Europe and US, and genotype 4. Rein suggested further studies to include these two genotypes to paint a clearer picture of the global burden of HEV.
50
June 2012
Diabetes
Doctors have exaggerated fears when starting patients on insulin

Elvira Manzano
hysicians may be more concerned about side effects and slower to start insulin therapy than patients themselves, according to a meta-analysis. In a review of randomized controlled trials involving insulin-nave patients, the barriers to insulin initiation perceived by physicians, for example, fear of hypoglycemia and weight gain, were amplified compared with patient perception. Doctors were also more concerned about injection-related pain and anxiety than their patients. [CMAJ 2012. DOI:10.1503/cmaj.110779] Insulin is effective in lowering blood sugar, said lead study author Dr. Catherine Yu, a researcher at the Keenan Research Center, St. Michaels Hospital in Toronto, Canada. But there are no clear recommendations on the safest and most effective way to start patients on it, so physicians are often hesitant to do so. Yu and colleagues analyzed past studies examining the effects of insulin on glycemic control, weight gain, risk of hypoglycemia and other adverse effects in outpatients with type 2 diabetes and found that insulin is safe and effective in reducing glycosylated hemoglobin (HbA1c). Insulin use is associated with weight gain, but not with an increased risk of hypoglycemia. When some physicians think of the side effects of insulin and the barriers to starting it, theyre often thinking about the older types [of insulin] and older delivery systems, Yu
said. So a lot of the hesitation may be that their way of thinking about the drug has not changed along with the new types of insulin that are used. She added that new insulin is better and used in smarter ways, thus there is less risk of hypoglycemia and weight gain. Everyone knows that insulin works, but the key point here is that its safe and can be straightforward to use, too. The researchers used their findings to develop recommendations for physicians and healthcare providers on how to start patients on insulin.
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June 2012
Diabetes
in patients with type 2 diabetes. Canadian guidelines recommend insulin as a first-line therapy in patients with HbA1c value of 9.0 percent or greater in those with newly-diagnosed diabetes. US and European guidelines recommend basal insulin as a second-line agent if the HbA1c value is >7.0 percent after metformin monotherapy. For patients taking antihyperglycemic agents, the authors recommend continuation of medications with insulin. The combination therapy reduces weight gain, insulin dose and risk of hypoglycemia compared with insulin therapy alone, the authors concluded.
Insulin initiation should be considered early in the course of type 2 diabetes. A basal regimen is an ideal one to start with given its simplicity and favorable safety profile, the authors advised. In the meta-analysis, patients treated with pre-mixed and basal-bolus regimens had greater HbA1c reduction compared with patients who received basal insulin. However, both regimens were associated with more weight gain, and in the case of pre-mixed regimen, an increased risk of hypoglycemia. Current guidelines vary as to the recommended criteria for the initiation of insulin
52
June 2012
Clinical Reviews
CARDIOLOGY
Niacin for patients with low HDL cholesterol and on intensive statin therapy: Not effective
he results of several studies have suggested that adding niacin to statin therapy to raise high-density lipoprotein (HDL) cholesterol levels in patients who have achieved low low-density lipoprotein (LDL) cholesterol levels but still have low HDL cholesterol levels might be effective. Now, a large multicentre trial in the US and Canada has shown no benefit from the addition of niacin. A total of 3,414 patients aged at least 45 years with established cardiovascular disease (coronary, cerebrovascular, or peripheral arterial disease) on treatment with a statin were randomized to niacin 1,5002,000 mg daily or placebo, as well as statin treatment (simvastatin 4080 mg daily) plus ezetimibe if needed, to maintain an LDL cholesterol level of 1.032.07 mmol/L. All patients had low levels of HDL cholesterol (< 1.03 mmol/L for men and < 1.29 mmol/L for women), raised triglycerides and low LDL cholesterol levels (< 4.65 mmol/L if not on statins at entry). The trial was stopped after a mean follow-up of 3 years because of lack of clinical efficacy of niacin. After 2 years of niacin treatment, median HDL cholesterol levels had increased from 0.91 to 1.08 mmol/L, and median triglyceride levels
had fallen from 1.85 to 1.34 mmol/L and LDL cholesterol from 1.91 to 1.60 mmol/L. The primary end point (death from coronary disease, non-fatal myocardial infarction, ischemic stroke, hospital admission for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization) had occurred in 16.4 percent (niacin) vs 16.2 percent (placebo). The addition of niacin to treatment improved levels of LDL and HDL cholesterol and triglycerides but did not improve clinical outcomes.
The AIM-HIGH investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. NEJM 2011; 365: 22552267; Giugliano RP. Niacin at 56 years of age time for an early retirement? Ibid: 23182320 (editorial).
53
June 2012
Clinical Reviews
CARDIOLOGY
Dronedarone in high-risk permanent atrial fibrillation: Negative trial
ronedarone, a new antiarrhythmic drug, has been shown to reduce the risks of death, hospital admission, stroke, and acute coronary syndrome requiring hospital admission, in patients with paroxysmal atrial fibrillation. Now, it has been tried unsuccessfully for patients with high-risk permanent atrial fibrillation. In a trial at 489 sites in 37 countries, a total of 3,236 patients with atrial fibrillation lasting for 6 months or more and at high risk (age 65 or older and at least one other risk factor such as coronary disease, previous stroke or transient ischaemic attack, symptomatic heart failure leading to admission in the last year, left ventricular ejection fraction not > 40%, peripheral arterial disease, or age at least 75 with hypertension and diabetes) were randomized to dronedarone or placebo. The study was stopped after this number of patients had been enrolled because of poor results in the dronedarone group. Median follow-up was for 3.5 months. The first co-primary outcome (stroke, myocardial infarction, systemic embolism, or cardiovascular death) occurred in 43 patients (dronedarone) vs 19 (placebo), giving rates of 8.2 vs 3.6 per 100 patient-years, a highly significant 2.3-fold increase in the dronedarone group. For the second co-primary outcome (unplanned hospital admission with a cardiovascular cause, or death), there were 127 vs 67 events with rates of 25.3 vs 12.9 per 100 patient-years, also a highly significant difference. The difference in mortality from any cause (25 vs 13 deaths; 4.7 vs 2.4
deaths per 100 patient-years) was just within the limits of significance (P=0.049). Stroke was significantly more common in the dronedarone group (23 vs 10 patients; 4.4 vs 1.9 per 100 patient-years) as was hospital admission for heart failure (43 vs 24 events; 8.3 vs 4.6 per 100 patient-years). These researchers conclude that dronedarone should not be used for patients with these features. Why dronedarone appears to be beneficial in paroxysmal atrial fibrillation and detrimental in permanent atrial fibrillation in high-risk patients is unclear.
Connolly SJ et al. Dronedarone in high-risk permanent atrial fibrillation. NEJM 2011; 365: 22682276; Nattel S. Dronedarone in atrial fibrillation Jekyll and Hyde? Ibid: 23212322 (editorial).
54
June 2012
Clinical Reviews
CARDIOLOGY
Cardiac arrest in marathons

ong-distance races have become more popular. In the last decade, participation in marathons and half-marathons in the USA has doubled from 1 million to 2 million participants. The occurrence of sudden death among the competitors has attracted media attention. Now, a US study has shown a cardiac arrest rate of 0.54 per 100,000 runners. The study included 10.9 million runners who took part in marathon or half-marathon races between January 1, 2000 and May 31, 2010. There were 59 cases of cardiac arrest (51 men, 8 women; mean age, 42 years), 0.54 per 100,000 participants (1.01 per 100,000 in marathons, 0.27 per 100,000 in half-marathons; a significant difference). Men were at greater risk than women (0.90 vs 0.16 per 100,000). The risk to male marathon runners increased during the later years of the study (0.71 per 100,000 in 20002004, and 2.03 per 100,000 in 20052010). Cardiac arrest was fatal in 71 percent of cases. Among 31 cases with adequate data, the strongest factors predicting survival after cardiac arrest were cardiopulmonary resuscitation by bystanders and a diagnosis other than hypertrophic cardiomyopathy. The most common underlying cases of cardiac ar-
rest were hypertrophic cardiomyopathy and ischaemic heart disease. Cardiac arrest occurred at an overall rate of 0.54 per 100,000 runners. It was more likely in marathons rather than half-marathons, and in men rather than women. The most common underlying causes were hypertrophic cardiomyopathy and coronary disease. The rate of cardiac arrest has increased in male marathon r unners, possibly because more at-risk men have been tempted to participate.
Kim JH et al. Cardiac arrest during long-distance running races. NEJM 2012; 366: 130140.
55
June 2012
Clinical Reviews
CARDIOLOGY
Antihypertensive treatment at age 80 or older
trial in Eastern and Western Europe, China, and Tunisia (the HYVET trial) showed that antihypertensive treatment for people aged 80 years or older with a sustained systolic blood pressure of at least 160 mm Hg provided benefit. A 1-year extension of that trial has been reported. In the main trial, hypertension was treated with indapamide sustained-release 1.5 mg with added perindopril 24 mg as necessary. In the 1-year extension trial, all patients received open-label indapamide with target blood pressures of < 150 mm Hg systolic and < 80 mm Hg diastolic. Of the 1,712 patients in the extension trial, 924 had been taking indapamide and 788 placebo in the main trial. After
6 months of the extension trial, blood pressure were similar in these two groups. Throughout the extension trial, there were no significant differences between the two groups in rates of stroke, cardiovascular events, or heart failure. Overall and cardiovascular mortality rates, however, were significantly better in patients who had taken indapamide in the main part of the study. Antihypertensive treatment for people aged 80 or older may be beneficial within a year.
Beckett N et al. Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial. BMJ 2012; 344: 16 (2011; 343 [Jan 14]: d7541); Mancia G. Antihypertensives in octogenarians. Ibid: 8 (2011; 343: d7293) (editorial).
Lifetime cardiovascular risks

eople who are considered to be at low risk of cardiovascular disease in the short term (10 years) may be at considerable lifetime risk. Lifetime risks have been estimated by pooling data from US studies over the past 50 years. A meta-analysis included 18 cohort studies with a total of 257,384 men and women and risk factors assessed at ages 45, 55, 65, and 75. At age 55, the estimated risk of death from cardiovascular disease up to the age of 80 was 4.7 percent for men and 6.4 percent for women among people with a good risk-factor profile (total cholesterol < 4.7 mmol/L, blood pressure < 120/80 mm Hg, non-smoking, no diabetes). Among people with two or more major risk factors, the corresponding estimates were 29.6 percent for men and 20.5 percent for women.
The difference in risk between the two risk factor groups among men was 3.6 percent vs 37.5 percent for coronary death or myocardial infarction, and 2.4 percent vs 8.3 percent for stroke. Among women, the differences were < 1 percent vs 18.3 percent for coronary death or myocardial infarction, and 5.3 percent vs 10.7 percent for stroke. Race and birth cohort made little difference to the trends within risk-factor strata. Risk-factor profiles can distinguish between very different lifetime cardiovascular risks.
Berry JD et al. Lifetime risks of cardiovascular disease. NEJM 2012; 366: 321329.
56
June 2012
Clinical Reviews
GENERAL MEDICINE
Reporting of clinical trials: Missing data and effect on meta-analyses
he January 7, 2012 issue of the BMJ includes six papers about the reporting, misreporting, or non-reporting of clinical trials. Forty-two meta-analyses of drug trials (nine drugs, six drug classes, 41 efficacy outcomes, one harm outcome) were reanalysed after the inclusion of previously unpublished data obtained from the US Food and Drug Administration (FDA). The reanalyses showed less drug efficacy in 19 cases, greater drug efficacy in 19, and unchanged drug efficacy in three. The absence of unpublished data from drug trial meta-analyses may affect the conclusion in either direction. In 2005, prior registration of all trials became a condition for later publication. A study of 635 trials funded by the US National Institutes of Health and registered within ClinicalTrials.gov has shown that the results of many trials are not published promptly. Only 294 (46 percent) were published in a Medline-indexed, peer-reviewed, biomedical journal within 30 months of trial completion. After a median follow-up of 51 months, 432 (68 percent) had been published and the median time to publication was 23 months. There is some evidence, though, that things are improving since the proportion of trials published within 30 months of study completion was 36 percent for trials completed before 2007 and 54 percent for trials completed in 2007 or 2008. The US Food and Drug Administration amendments Act of 2007 makes it necessary to
publish a results summary on ClinicalTrials. gov, but the law is not being complied with. Of 738 trials completed in 2009 and subject to mandatory reporting, only 163 (22 percent) had reported results within a year. Among trials not subject to mandatory reporting, the number reported was even less (76/727; 10 percent). Trials funded by industry were more likely to have been reported (40 percent vs 9 percent), as were later-phase studies. Meta-analyses using individual patient data may be subject to biases in publication, availability, and selection, and these may falsely increase the impression of positive treatment effects. A review of 31 recent metaanalyses of drug trials showed that only nine
57
June 2012
Clinical Reviews
tion of the studies. Of 268 studies examined, details were published in journals for 72 percent, in registry reports for 29 percent, and in study reports submitted to regulatory authorities for 38 percent. The highest quality of reporting was in study reports for regulatory authorities where complete information was provided for 90 percent of items considered necessary. By contrast, journal publications and registry reports provided complete information for only 46 percent and 51 percent of items, respectively. Changes are needed in the functioning and monitoring of systems for the reporting of clinical trials. Concealment of data must be regarded as serious professional misconduct, subject to disciplinary action by professional organizations.
Hart B et al. Effect of reporting bias on meta-analysis of drug trials: reanalysis of meta-analyses. BMJ 2012; 344 (Jan7): 13 (d7202); Ross JS et al. Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis. Ibid: 14 (d7292); Prayle AP et al. Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study. Ibid: 15 (d7373); Ahmed I et al. Assessment of publication bias, selection bias, and unavailable data in meta-analyses using individual participant data: a database survey. Ibid: 16 (d7762); Wieland LS et al. Understanding why evidence from randomised clinical trials may not be retrieved from Medline: comparison of indexed and non-indexed records. Ibid: 17 (d 7501); Wieseler B et al. Impact of document type on reporting quality of clinical drug trials: a comparison of registry reports, clinical study reports, and journal publications. Ibid: 18 (d8141); Chan AW. Out of sight but not out of mind: how to search for unpublished clinical trial evidence. Ibid: 1922 (d8013) (research methods and reporting); Lehman R, Loder E. Missing clinical trial data. Ibid; 78 (d8158) (editorial).
included individual patient data from grey literature (such as unpublished studies) in the primary meta-analysis and only 10 (32 percent) discussed the potential for publication bias. In 16 of the 31 metaanalyses, not all of the individual patient data requested had been provided, but only 11 of the 16 mentioned this as a potential problem and only six discussed how the trial conclusion could be affected by absent data. In nine of the 231 metaanalyses, the identification of relevant trials was either not explained or based on a selective, non-systematic approach, raising the possibility of reviewer selection bias. The potential for all of these biases is a cause of concern about the reliability of some metaanalyses. Even use of Medline may have its problems. Between 1994 and 2006, the Cochrane Collaboration and the US National Library of Medicine collaborated to retag records of randomized controlled trials that were not indexed with RCT[PT]. It has been found that, since the retagging project ended in 2006, anybody relying on RCT[PT] to search for randomized controlled trial data may miss important evidence. It is estimated that at least 3,000 records describing randomized controlled trials but not indexed as such may have been entered into Medline between 2006 and 2011. Use of validated search strategies is essential. Finally, three types of reporting have been examined, and two of them have been found to be potentially inadequate. Reports in trial results registries and in journals may provide insufficient information for complete evalua-
58
June 2012
Clinical Reviews
GENERAL MEDICINE
When does cognitive decline begin?
here is uncertainty about the age at which cognitive decline begins in the population. Much of the evidence is based on crosssectional data that may not be reliable for this purpose. The Whitehall II prospective cohort study began in 19851988 and included 10,308 civil servants in London. Cognitive testing began in 19971999 when there were 9,250 people still in the study. Cognitive testing (memory, reasoning, vocabulary, phonemic and semantic fluency) was performed on 7,390 people aged 4570 at the start of 10 years of follow-up. Testing was done three times, in 19971999, 20022004, and 20072009. Over a period of 10 years, there was significant decline in test scores for all modalities except vocabulary, and this decline occurred in all age groups including those aged 4549 at the first testing session. Decline was greater at older ages.
The belief that cognitive decline does not occur until after the age of 60 was derived mainly from evidence based on cross-sectional studies. This longitudinal study shows that cognitive decline may begin in the late 40s or even earlier.
Singh-Manoux A et al. Timing of onset of cognitive decline: results from Whitehall II prospective cohort study. BMJ 2012; 344 (Jan 21): 18 (2011; 343: d7622); Grodstein F. How early can cognitive decline be detected: Ibid: 10 (d7652) (editorial).
59
June
June 2012
Calendar
10th International Conference of the Asian Clinical Oncology Society

13/6/2012 to 15/6/2012 Location: Seoul, Korea Tel: (82) 2 3476 7700 Fax: (82) 2 3476 8800 Email: office@acos2012.org Website: www.acos2012.org
15th World Congress of Pain Clinicians

27/6/2012 to 30/6/2012 Location: Granada, Spain Info: Kenes International Tel: (41) 22 908 0488 Fax: (41) 22 9069140 Email: wspc2012@kenes.com Website: www.kenes.com/wspc
15th International Congress of Infectious Diseases

13/6/2012 to 16/6/2012 Location: Bangkok, Thailand Tel: (617) 277 0551 Fax: (617) 278 9113 Email: info@isid.org Website: www.isid.org/icid/
ESMO 14th World Congress on Gastrointestinal Cancer

27/6/2012 to 30/6/2012 Location: Barcelona, Spain Info: European Society of Medical Oncology Tel: (770) 751 7332 Fax: (770) 751 7334 Email: meetings@imedex.com Website: www.worldgicancer.com
International Society for Stem Cell Research

13/6/2012 to 16/6/2012 Location: Yokohama, Japan Tel: (847) 509 1944 Fax: (847) 480 9282 Email: isscr@isscr.org Website: www.isscr.org/annual_meeting_home.htm
July
30th International Congress of Psychology
22/7/2012 to 27/7/2012 Location: Cape Town, South Africa Tel: (27) 11 486 3322 Fax : (27) 11 486 3266 E-Mail: info@icp2012.com Website: www.icp2012.com
World Conference on Interventional Oncology

14/6/2012 to 17/6/2012 Location: Chicago, Illinois, US Tel: (1) 202 367 1164 Fax: (1) 202 367 2164 Email: info@wcioonline.org Website: www.wcio2012.org
17th World Congress on Heart Disease 2012

27/7/2012 to 30/7/2012 Location: Toronto, Ontario, Canada Info: International Academy of Cardiology Tel: (1) 310 657 8777 Fax : (1) 310 659 4781 E-Mail: Klimedco@ucla.edu Website: www.cardiologyonline.com
67th Annual Meeting of the Canadian Urological Association

23/6/2012 to 27/6/2012 Location: Banff, Alberta, Canada Info: Canadian Urological Association Tel: (1) 450 550 3488 Fax: (1) 514 227 5083 Email: info@iseventsolutions.com Website: www.cuameeting.org
60
June 2012
Calendar
Upcoming
European Society of Cardiology Congress 2012
25/8/2012 to 29/8/2012 Location: Munich, Germany Info: European Society of Cardiology Tel: (33) 4 9294 7600 Fax: (33) 4 9294 7601 E-Mail: ascoregistration@jspargo.com Website: www.escardio.org/congresses/esc-2012
15th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2012)
3/10/2012 to 6/10/2012 Location: Florence, Italy Tel: (41) 22 908 0488 Fax: (41) 22 732 2850 Email: esid@kenes.com Website: www.kenes.com/esid
42nd Annual Meeting of the International Continence Society

15/10/2012 to 19/10/2012 Location: Beijing, China Tel: (41) 22 908 0488 Fax: (41) 22 906 9140 Email: ics@kenes.com Website: www.kenes.com/ics
National Diagnostic Imaging Symposium

2/12/2012 to 6/12/2012 Location: Orlando, Florida, US Info: World Class CME Tel: (1) 980 819 5095 Email: office@worldclasscme.com Website: www.cvent.com/events/national-diagnostic-imaging-symposium-2012/event-summaryd9ca77152935404ebf0404a0898e13e9.aspx
Asian Pacific Digestive Week 2012

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

6/12/2012 to 9/12/2012 Location: Hyderabad, India Info: World Allergy Organization Tel: (1) 414 276 1791 Fax: (1) 414 276 3349 E-mail: WISC@worldallergy.org Website: www.worldallergy.org
61
June 2012
After Hours
One doctor tells of his evolving culinary creations at home in addition to crafting healthy traditional meals for the whole family. Rajesh Kumar reports.
r. Poh Beow Kiong is a diehard foodie. His day job as a urology consultant at Singapores Changi General Hospital keeps him quite busy. But on occasional weekday evenings and the weekends, Poh takes on the role of a kitchen maestro, whipping up quick, healthy dinners for the family. Some find cooking to be a chore, he says, But I find it therapeutic. It relaxes me after a long day at work. Besides, the family doesnt like to eat out. Occasionally, when we do, it is on days when our kids go for swimming lessons. We buy takeouts rarely, said Poh. While he has not developed a signature style, Poh said his cooking has undergone a sort of evolution over the years. Ten years ago, we used to eat a lot of fried food and used more oil in our cooking. Now, we are more health conscious and tend to steam our fish, vegetables and even chicken, rather than fry them. While healthy eating is the norm, Poh occasionally indulges in fatty food and believes certain traditional recipes shouldnt be altered, no matter how calorie dense the dish may be.
62
June 2012
After Hours
is and rolled up like a sushi roll after dabbing it with sweet sauce, hot chilli paste and stuffing the fillings before cutting the rolls into pieces. Pohs culinary skills have endeared him to his family and the mother-in-law. He encourages his fellow physicians to try their hand at cooking and offers to share the recipe for a healthy snack, which anyone with negligible cooking skills can master: Take a chunk of egg tofu. Pan fry it, drain the excess oil on kitchen paper and cut into pieces. Chop and fry some garlic to pleasant golden brown color, sprinkle on tofu pieces and, voila! The natural sweetness of the egg tofu and light pungency of the fried garlic work so well together that you may not need a dipping sauce. Just make sure not to overcook the garlic, or it will taste bitter. The cooking process continues even after you turn off the heat. As the garlic turns light brown, turn the heat off and drain out the excess oil before it overcooks. Its not easy to brown the egg tofu. Pat it dry with kitchen paper, drizzle oil on a really hot pan and leave it to sizzle on one side for several minutes before turning it over.
Chinese fatty pork cooked in duck soya sauce, for example. That is an extremely greasy but sumptuous dish. And trying to cook it with anything other than fatty pork is pointless, he said. Obviously, you dont eat such food regularly and need to burn off the extra calories through vigorous exercise. Else, the coronary arteries will clog up, cautioned Poh. But many special dishes, and the way they are cooked, are a part of our cultural heritage that needs preserving You ask your mum how these are cooked, write down the recipes, add your tweaks over the years and pass them on to the next generation. That should never be lost! Is there a favorite dish he likes more over others? My mothers home cooked popiah is the best, Poh said excitedly. Like chilly crab, popiah is among Singapores iconic dishes and that is prepared by wrapping a choice of cooked fillings in paper thin crepe, usually bought ready made from the market. Dried shrimps and cooked pork, vegetables, mushrooms, crab meat and other ingredients can be mixed with boiled radish to make different fillings. The crepe is used as it
Photo credits: Changi General Hospital
63
June 2012
Humor
I have good news and bad news. The bad news is that the DNA tests showed that it was your blood they found at the crime scene. The good news is your cholesterol is down to 120!
I've terrible news. You are not a hypochondriac!
You're a very lucky man Harry, you could have broken your nose!
I thought you told me to go on a diet just to be mean!
I'm sick of being sick Doctor. Is there an illness other than the one I have that I might enjoy?
The place is empty. Everybody called in sick!
Enjoy your vacation. I'll tell you the bad news when you get back!
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June 2012

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