May 2012

www.medicaltribune.com

Dramatic blood sugar control with gastric surgery

FORUM Biobanks: Research dream or ethical nightmare?

IN PRACTICE Managing acute otitis media: Strategies for GPs

CONFERENCE Cardiac pacing reduces syncope recurrence

AFTER HOURS The science of food flavors

May 2012

Dramatic blood sugar control with gastric surgery

Radha Chitale
astric surgery controlled blood sugar better than intensive medical therapy among obese type 2 diabetics, according to the STAMPEDE trial, the results of which were presented at the 61st Annual Scientific Sessions of the American College of Cardiology meeting in Chicago, Illinois, US. Patients who underwent Roux-en-Y gastric bypass surgery or sleeve gastrectomy achieved HbA1c control below 6 percent within a year in 42 percent (P=0.002) and 37 percent of cases (P=0.008), respectively, compared with 12 percent who received intensive medical therapy alone. [N Engl J Med 2012 Mar 26. Epub ahead of print] Despite improvements in pharmacotherapy, fewer than 50 percent of patients with moderate-to-severe type 2 diabetes actually achieve and maintain therapeutic thresholds, particularly for glycemic control, said researchers from the Cleveland Clinic in Ohio, US, Veterans Affairs Boston Healthcare System and Brigham and Womens Hospital in Boston, Massachusetts, US. Observational studies have suggested that bariatric or metabolic surgery can rapidly improve glycemic control... The trial randomized 150 obese patients (mean age 49 years, mean body mass index 36 kg/m2, mean HbA1c 9.2 percent) with uncontrolled type 2 diabetes to receive intensive medical therapy alone, medical therapy

The STAMPEDE trial showed that gastric surgery significantly lowered HbA1c levels compared with intensive medical therapy alone in obese patients with type 2 diabetes.

plus Roux-en-Y gastric bypass surgery or medical therapy plus sleeve gastrectomy. Intense medical therapy followed the guidelines of the American Diabetes Association and included lifestyle counselling, weight management, and drug therapy. Patients randomized to surgery experienced significantly more weight loss compared with those receiving medical therapy after 12 months (-29.5 kg gastric bypass, -25.1 kg sleeve gastrectomy, -5.4 kg medical therapy, P<0.001 for both) and lead author Dr. Philip Schauer, of the Cleveland Clinic, said this, more than anything else, was the likely driver for glycemic control. Mean HbA1c was 6.4 percent in the gastric bypass group (P<0.001), 6.6 percent in the sleeve gastrectomy group (P=0.003) and

May 2012 tute, Melbourne, VIC, Australia, and Dr. K. George M. M. Alberti, Kings College Hospital, London, England, said surgery would not be the universal panacea for obese patients with type 2 diabetes and pointed out that the study duration was only 1 year and that surgery has inherent hazards. [N Engl J Med 2012 Mar 26. Epub ahead of print] There is also the problem of remission versus cure, they said. Type 2 diabetes is often progressive, and worsening of glycemic control over time is likely in many patients. However, some years of improved glycemia may well result in less microvascular disease. Both the researchers and commenters called for further studies on the long-term clinical effects of gastric surgery.

7.5 percent among patients receiving medical therapy. Patients who underwent surgery also significantly reduced or halted use of glucose control and cardiovascular medications. Reductions in the use of diabetes medications occurred before achievement of maximal weight loss, which supports the concept that the mechanisms of improvement in diabetes involve physiologic effects in addition to weight loss... the researchers said. No deaths or life threatening complications occurred although four patients required a second surgery for complications. In an accompanying comment, Dr. Paul Zimmet, Baker IDI Heart and Diabetes Insti-

May 2012

New guidelines urge tailored approach in hyperglycemia

Rajesh Kumar

he European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have issued joint guidelines, calling for a more patient-centred approach in the treatment of hyperglycaemia in people with type 2 diabetes. The wide range of pharmacological choices, conflicting data about some of those choices, and differences in how patients respond to medications makes it difficult to prescribe a single treatment that will work for everyone.

The document discusses in detail the available evidence on a growing number of pharmacological agents including metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, and different types of insulin, and calls for all patients with diabetes to receive personalized diabetes education, focused on dietary intervention and the importance of physical activity. The guidelines also recommend that comprehensive cardiovascular risk reduction be a major focus of therapy. Professor David Matthews, chairman of the EASD panel for overseeing guidelines and statements, said while pharmacological options are getting wider, the evidence base has become smaller. The consensus that we have come to [with the ADA] is that we need individualization of the [HbA1c] targets and it depends on the patients comorbidities and environments as to what the target should be, said Matthews, who works at the UK National Institute for Health Research (NIHR), Oxford Biomedical Research Centre, Oxford, UK. The new guidelines take a more holistic approach, focusing on treating the patient as an individual, added EASD president Professor Andrew Boulton. [The] approach will likely improve not only patient care, but also quality of life.

The consensus that we have come to

[with the ADA] is that we need individualization of the [HbA1c] targets

Therefore, physicians should consider individual patients needs, preferences and tolerances and consider that type 2 diabetes patients differ substantially in terms of age, disease progression and co-morbidities, the two organizations said in a position statement [Diabetologia 2012; DOI:10.1007/s00125012-2534-0, Diabetes Care 2012; Apr 19; DOI:10.2337/dc12-0413].

May 2012

Forum

Biobanks: Research dream or ethical nightmare?

Professor Alastair V. Campbell, Director of the Centre for Biomedical Ethics at the National University of Singapore, discussed the research potential of large-scale human health databases during the Asia-Pacific Research Ethics Conference, held recently in Singapore.

iobanks, large epidemiological cohorts, including past and present populations, that are associated with extensive samples of DNA and other biological materials, linked to health data, offer a rich source of information for public health research. Data capture health episodes affecting participants as they occur and are often followed up for decades. However, the possibility of information abuse or use for commercial gain is high. Creating and maintaining biobanks raises a number of major ethical questions that should be dealt with as we strive to define and defend the biocommons. Opportunities for research Biobanks warrant unusual consideration. The data they contain offer a broad range of possible research opportunities, mined from a broad range of future health information that will be captured. This is large-scale data, with many participants, making it somewhat impersonal. In addition, a range of researchers will have access to the data for a very long time. The major features that make a biobank enterprise different from a piece of research are the need for general consent, appropriate stewardship, and justified trust. Therefore, special measures are required for biobanks, rather than holding them to the

same standards of research protocol as other data sets. The UK Biobank is the worlds largest resource of genetic health and lifestyle data. It includes over 500,000 participants aged 4069 and has the unique advantage of gaining data from the comprehensive British National Health Service. This biobank took about 10 years of lead time in order to clarify the governance and ethical framework, in addition to public consultations. People would get a letter inviting them for an assessment at a clinic. A major part of the visit was spent explaining what they were giving consent to. Participants in the UK Biobank consented to access to medical records for the remainder of their lives and after their death, without feedback on the results of their testing, other

May 2012

Forum
This kind of data consolidation lends itself to growing into virtual biobanks. Virtual biobanks are gaining popularity as researchers push to share and use population information across regions. The issue of access is important in the face of pressure to link data sets internationally but it is complicated because there is no consistency in governance across international biobanks. Ethicists could discuss whether it is right to trust international entities with biobank data without international consistency. Security measures are important to have in place to prevent inappropriate access. Stewards must address who has access to the biobank data, to what extent access to other records is controlled and how easy it is to hack into the resource. Safeguards to prevent abuse One solution could be for a virtual biobanks to link registries with safeguards to prevent identification. A person would be assigned a serial number and the serial number is linked to the health data as a way to store data without compromising the safety of the subject. The link would be stored with an independent trusted third party and without their cooperation, no one can link the health information back to the original subject. Whatever the problems with broad consent, presumed consent is not sufficient. Biobanks are more than just a collection of tissue or data. Researchers have to see these as public property for the common good, uninfluenced by commercial or nationalist interests. The prospect for large-scale data sharing for health not profit could lead to greater information and more justice in healthcare.

than minor initial tests for basic things like blood pressure levels. Consent for use of participant data is rescindable but not conditional. That is, you cannot specify what type of research you are willing to allow your tissues to be used for. The big brother scenario The nightmare scenario would be that big brother is watching. How can we be sure such databases wont be used in ways other than what the participant signed up for? If, for example, stored genetic information could be accessed by court order in a society where authorities increasingly want access to citizens? In addition, if the commercial dominates, the whole purpose of the collection is in danger. This is where ethics in governance comes in. If the ethics governing body believes the participants trust was abused, they say so, acting as proxy for the people involved. The governance of the UK Biobank is independent, and they alone guard the ethics and governance framework. They advise on revisions, monitor the UK Biobank and report their findings publicly and provide general advice.

Creating and maintaining

biobanks raises a number of

major ethical questions that should be dealt with as we strive to define and defend the biocommons Biobanks can be built from the ground up, as the UK Biobank was, but they can also be created by linking existing collections of tissue and registry information.

May 2012

Hong Kong Focus

Noninvasive prenatal test for Downs syndrome

Christina Lau

oninvasive prenatal diagnosis of Downs syndrome is now available as a clinical service in Hong Kong, providing a safer and less stressful alternative for pregnant women. The test, called safeT21 (sensitive analysis of fetal DNA for T21 screening), is the result of 15 years of research at the Chinese University of Hong Kong (CUHK). Using highthroughput DNA sequencing technology, the test analyzes millions of DNA fragments in maternal blood to determine if there is an elevation in chromosome 21 DNA molecules, which suggests the presence of a fetus with Downs syndrome, said Professor Dennis Lo of the Department of Chemical Pathology. The test is based on Los discovery in 1997 that cell-free fetal DNA is present in maternal plasma as short fragments among primarily maternally derived DNA fragments. [Lancet 1997;350:485-487] Subsequently, the research team found that the entire fetal genome is indeed present in maternal plasma. [Sci Transl Med 2010;2:61ra91] The findings led to the development of a groundbreaking sequencing technology that enabled the researchers to construct a genome-wide genetic map and determine the mutational status of the fetus from the maternal plasma DNA sequences and from information about the paternal genotype and maternal haplotype. The safeT21 test accurately detects 99.1 percent of fetuses affected by Downs syndrome. The false positive rate is 0.1 percent, said Lo. The diagnostic accuracy has been

Prof. Lo introducing the test

validated by us in a large cohort of samples, and in a large number of clinical studies conducted by other groups around the world. The test is currently available at prenatal diagnostic units at CUHK, Hong Kong Sanatorium & Hospital, Union Hospital, Hong Kong Baptist Hospital, and a number of obstetric group practices. Downs syndrome is conventionally diagnosed by analyzing genetic material obtained directly from the fetus through invasive procedures, such as amniocentesis and chorionic villus sampling. However, these invasive procedures are associated with a miscarriage rate of 0.5 to 1 percent, explained Lo. Its envisioned that the noninvasive technology will be increasingly used by centers around the world, leading to substantial reductions in the number of invasive prenatal diagnostic procedures required. Further information on the safeT21 test may be obtained by calling 2632 1192.

May 2012

Hong Kong Focus

Early, intensive disease control advocated in RA

Naomi Rodrig

requent monitoring and therapy adjustment in the early stage of rheumatoid arthritis (RA) can reduce disease activity and improve patients physical function, according to a pilot study at the Queen Elizabeth Hospital. [Hong Kong Med J 2012; 18:108-114] Twenty patients with RA onset of <2 years who attended the hospitals tight control RA clinic were enrolled. Patients were followed up every 3-6 weeks to assess Disease Activity Score 28 (DAS28). Disease-modifying antirheumatic drug (DMARD) treatment was stepped up according to a preset protocol and patient tolerance, with the objective of achieving DAS28 3.2. The study subjects were compared to matched historical controls in the rheumatology clinic. The majority of patients were started on methotrexate (MTX) as first-line DMARD; only one patient was started on suphasalazine due to hepatitis B infection. At baseline, more patients in the control group were receiving steroids due to higher disease activity and less aggressive DMARD step-up therapy. After 1 year, the mean MTX dose was 13.0 mg/week in the intensive care group, and 11.3 mg/week among the historical controls. At 1-year follow-up, patients in the intensive care group had significantly greater improvements in DAS28 scores (mean score, 2.7 vs 4.2 for historical controls) and in physical function assessed by the health assessment questionnaire (HAQ) score (0.2 vs 1.3,

respectively). While both patient groups experienced a reduction in DAS28 scores, the difference between the groups was sustained throughout the study. Patients in the tight control group also had significantly greater improvements in disease activity variables such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), swollen and tender joint counts, early morning stiffness and patient global assessment (PGA). Authors Kitty Kwok and MH Leung remarked that such treat-to-target strategy involving tight control in early disease was previously shown in overseas studies to achieve favorable disease activity. Moreover, our treatment target was low disease activity, ie, DAS28 of 3.2. With earlier diagnosis of RA based on the EULAR/ ACR 2010 classification criteria, and by adhering to a protocol-driven approach, nowadays remission is a realistic goal, they wrote. Notably, the study treatment protocol did not include biological therapy, although there is evidence that early biological use can achieve better disease control and better radiological outcomes. Since some studies reported radiographic progression occurring despite good clinical response to MTX therapy, the authors suggest that radiographs of the hands and feet should be included in all evaluations of patients with early RA. Though the tight control approach entails an increase in manpower and hospital costs, earlier achievement of good disease activity control should eventually ease the disease burden, they concluded.

May 2012

Hong Kong Focus

Molecular studies highlight hazards of TCM use

wo recently published molecular studies reveal that ingredients used in traditional Chinese medicine (TCM) preparations are often dangerous as well as illegal. Data reported in PNAS last month showed that exposure to aristolochic acid a common component of various TCM products is a primary cause of urothelial carcinoma of the upper urinary tract (UUC). The researchers, led by Dr. Arthur Grollman of Stony Brook University, New York, USA, conducted a molecular epidemiologic study of UUC in Taiwan, where its incidence is the highest reported anywhere in the world and where Aristolochia herbal remedies have been used extensively for many years. [Doi: 10.1073/ pnas.1119920109] Following metabolic activation, aristolochic acid reacts with DNA to form aristolactam (AL)-DNA adducts. These lesions concentrate in the renal cortex, where they serve as a sensitive and specific biomarker of exposure, and are found also in the urothelium, where they give rise to a unique mutational signature in the TP53 tumor-suppressor gene. Sequencing of tumor samples (151 UUC and 25 renal cell carcinomas) revealed that among patients with the characteristic TP53 mutations, 83 percent also showed the unique molecular signature of exposure to aristolochic acid. We conclude that exposure to aristolochic acid contributes significantly to the incidence of UUC in Taiwan, a finding with significant implications for global public health, the authors wrote.

In the second study, investigators at Murdoch University, Perth, Australia used highthroughput DNA sequencing technology to analyze 15 TCM samples (powders, tablets, capsules, flakes, and herbal teas) seized by Australian customs officials. [Doi: 10.1371/ journal.pgen.1002657] In total, we found 68 different plant families in the medicines they are complex mixtures of species, reported lead investigator, Dr. Michael Bunce. Some of the TCMs contained plants of the genus Ephedra and Asarum. These plants contain chemicals that can be toxic if the wrong dosage is taken, but none of them actually listed concentrations on the packaging. We also found traces from trade-restricted animals that are classified as vulnerable, endangered, or critically endangered, including the Asiatic black bear and Saiga antelope. Another concern is the mislabelling of TCMs, meaning that consumers are unaware of the presence of some ingredients, including animal DNA and potential allergens such as soy or nuts. Incorrect labelling also makes it difficult to enforce legislation and to prosecute cases of illegal trade. It is hoped that this new approach will help to genetically audit medicinal products and bring about a new level of regulation to the area of complementary and alternative medicine, said Bunce. TCMs have a long cultural history, but today consumers need to be aware of the legal and health safety issues before adopting them as a treatment option. -NR

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May 2012

Hong Kong Focus

Beware of biosimilars, professionals and authorities told

Christina Lau

ealthcare professionals and authorities in Hong Kong need to be watchful of biosimilars as more are anticipated to enter the market following patent expiry of a few biologics in the near future. Many new-generation biologics will be offpatent soon, including at least one monoclonal antibody for cancer [trastuzumab] and one biologic for rheumatoid arthritis [etanercept] in the next 2 to 3 years, said Associate Professor Vivian Lee of the School of Pharmacy, Chinese University of Hong Kong. As partial disclosure of the manufacturing procedure is required after patent expiry, emergence of biosimilars is anticipated in the near future so that patients can benefit from lower-priced replicated drugs. However, Lee cautioned that due to the complexity of biologics production, and the key differences in how biosimilars and biologics are manufactured, biosimilars are only similar rather than identical to the original biologics. Biologics are produced with top-notch biotechnology and involve more than 5,000 critical steps. Even slight deviations can lead to farreaching consequences on drug efficacy and safety, she explained. For example, 175 cases of pure red cell aplasia [PRCA] were reported in France, Canada, UK and Spain in 1998-2004 with the use of epoetinum alfa, a biologic for anemia in patients with kidney failure. In affected patients, epoetinum alfa led to cessation rather than boosting of red blood cell production. [N Engl J Med 2004;351:1403-1408] Scientists suspected that the PRCA was due to slight deviations in the manufacturing process of epoetinum alfa, said Lee. In Hong Kong, no

PRCA was reported, but the drug was completely recalled later to ensure patient safety. Production of biologics starts with the creation of a unique cell line, which is exclusively owned by the original innovator. Manufacturers of biosimilars can only use a similar cell line, she explained. The complex molecules or gene extraction involved in the production of biologics also make replication very difficult. Furthermore, as the end products are highly susceptible to changes in pressure, temperature, oxygen level, storage and transportation, drug efficacy and safety maybe affected if any of these factors are not well controlled. In the past, phase III clinical data and postregistration pharmacovigilance were not required of biosimilars. Close monitoring in these areas is needed to ensure the efficacy and safety of biosimilars in the long term, stressed Lee. International health authorities have indeed realized the importance and urgency of imposing strict monitoring on biosimilars. The WHO, US FDA and European Medicines Agency (EMA) have either released or started formulating guidelines and regulations on the research and quality data, safety, purity, potency, and pharmacovigilance required of biosimilars. Compared with chemical drugs that have been used for years, the efficacy and safety of biosimilars are relatively less familiar to the pharmaceutical industry and the Hong Kong government, pointed out Lee. Local authorities should catch up with the global trend and start formulating guidelines on the approval of biosimilars in Hong Kong. Phase III clinical study and pharmacovigilance should be required.

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May 2012

Hong Kong Focus

Thrombolysis treatment was also associated with shorter hospital stay (mean, 25 days vs 35 days in the non-thrombolysis group; p=0.034). Twenty-nine percent of patients in the thrombolysis group were discharged home directly vs 6 percent in the non-thrombolysis group (p<0.001). The proportion of patients discharged to nursing homes was similar. According to the authors, the study suggests that use of IV tissue plasminogen activator for acute ischemic stroke in Hong Kong is as safe and efficacious as demonstrated in Western population-based studies. A fledging stroke thrombolysis service in Hong Kong for predominantly Chinese patients seemed safe and efficacious, they wrote. From a clinical perspective, thrombolysis is the standard of care for eligible stroke patients. In a real world where health resource is limited, improving thrombolysis coverage remains one of the top challenges for stroke physicians. However, further studies on the economics of stroke thrombolysis in Hong Kong are needed.

Enhancing stroke services: A priority

Christina Lau

mplementation of territory-wide 24-hour stroke thrombolysis service should be a priority for the local health authority as the intervention is safe and associated with better outcomes, a new study suggests. In the historical cohort study, researchers from the Chinese University of Hong Kong and Prince of Wales Hospital compared the outcome of acute ischemic stroke patients treated with IV tissue plasminogen activator between October 2008 and May 2011 (n=48) with those admitted during the same period who were thrombolysis-eligible, but treated conservatively due to unavailability of thrombolysis service after-hours (n=63). [Hong Kong Med J 2012;18:92-98] At 3 months, 52 percent of patients in the thrombolysis group achieved functional independence vs 24 percent in the non-thrombolysis group (p=0.003). There was no significant increase in mortality (15 vs 13 percent) or symptomatic intracranial hemorrhage (4 vs 2 percent).

New centers at PWH

ew cardiovascular intervention and urological treatment centers have opened officially at the Prince of Wales hospital (PWH) recently. The CUHK-PWH-Lee Quo Wei Cardiovascular Intervention Center serves a population of 1.3 million in the New Territories East Cluster and is a referral center for cardiovascular diseases for the rest of Hong Kong. According to director Professor Cheuk-Man Yu, it is the only public center providing renal sympathetic denervation and implantation of left atrial appendage

occluder and cardiac contractility modulation device. The center runs the largest percutaneous coronary intervention (PCI) and electrophysiology service in Hong Kong, and has the largest volume of complex radiofrequency ablation and chronic total occlusion PCI cases. The Youth Urological Treatment Center provides urological assessment and treatment to those aged <30 years who suffer from urinary tract dysfunction as a result of psychotropic substance abuse. A hotline is available for fasttrack appointment across the territory. CL

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May 2012

Hong Kong Focus

(H3N2) detections increased from 117 to 316 for the same period. In early April, the main circulating influenza viruses were the influenza A (H3N2) virus (64.4 percent), followed by the influenza B (35.2 percent) and influenza A (H1N1) 2009 (0.4 percent) viruses. Furthermore, between January and April 2012, there were 115 cases of ICU admissions with laboratory-confirmed influenza, including 66 deaths. During the corresponding period in the winter flu season in 2011, there were 123 cases, including 34 deaths. While most of the deaths were among vulnerable groups such as the elderly, young children and those with chronic medical conditions, the high mortality rate underscores the need for expanding flu vaccination coverage, which may offer protection against influenza-related complications in these patient groups.

Long influenza season takes heavy toll

Naomi Rodrig
he 2011/2012 influenza season in Hong Kong, which continued with high activity well into April, was characterized by changing infection trends and a high mortality rate, according to surveillance data from the Center for Health Protection (CHP). By April this year, the number of influenza detections at the Public Health Laboratory Center remained high, at around 500 cases per week. While there was a decrease in the number of influenza B detections, the number of influenza A (H3N2) detections showed a rising trend. For example, the weekly number of influenza B detections decreased from 339 to 173 between mid-March and early April, whereas the weekly number of influenza A

More $ for Samaritan Fund

Secretary for Food and Health, Dr. York Chow, announced recently that the government plans to inject HK$10 billion into the Samaritan Fund, benefitting another 2,300 people. The Fund assists patients in need by providing full or partial subsidies for self-financed drugs and medical items required for medical treatment. The 2011/12 projected expenditure of the Fund is $295 million, representing a 30 percent increase from $227 million in 2010/11. The increase is attributable to higher demand due to population aging, particularly an increasing number of patients suffering from heart diseases. Furthermore, the government may add some drugs and medical equipment to the list of items the Fund currently covers, and extend the indications of existing drugs supported by the Fund, he added. The projected total expenditure on nondrug items in 2011/12 is $95 million. The projected total expenditure on drug items in 2011/12 is $200 million. The extra funding would provide adequate provision for the Funds operation over the next 10 years, and would be closely monitored, noted Chow. The major sources of its income are government grants, reimbursement from the Social Welfare Department, and donations. - NR

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May 2012

News

World Sepsis Day to highlight global emergency

Rajesh Kumar

he acute care community has designated 13 September 2012 as World Sepsis Day to highlight a global medical emergency that kills more than 10,000 people worldwide every day more than from prostate cancer, breast cancer and HIV/ AIDS combined. Sepsis arises when the bodys response to an infection injures its own tissues and organs. If not recognized and treated promptly, it can lead to shock, multiple organ failure or death. With hospital mortality rates of 30 to 60 percent, sepsis remains the primary cause of death from infection in both the developed and developing world despite advances in modern medicine, including vaccines, antibiotics, and acute care. According to the Global Sepsis Alliance (GSA), which represents about 250,000 intensive and critical care physicians around the world, the prevalence of sepsis has increased dramatically over the last decade, by 8 to 13 percent annually in the developed world alone. The GSA attributes this trend largely due to ageing populations and the increased use of high-risk interventions, alongside the development of drug resistance and more virulent varieties of pathogens. It has also been suggested that the way sepsis interventions are being delivered is haphazard, with less than one in five patients receiving appropriate or adequate care according to international guidelines. Rapid initiation of simple, timely interventions can halve the risk of dying. Early sepsis treatment is cost effective and reduces hospital and critical care bed days for patients. Unfortunately,

sepsis is still mostly overlooked and recognized too late, said Dr. Ron Daniels, Chairman of the UK Sepsis Group and executive director of GSA. Professor Younsuck Koh of the department of pulmonary and critical care medicine at University of Ulsan College of Medicine in Seoul, Korea, cited an Asian observational study which showed the basic principles of giving fluid on time, taking blood culture samples to detect pathogen, and administering antibiotics on time were closely related to patient outcomes. The three components could be followed even in resource limiting countries. However, we found that blood cultures and broad spectrum antibiotics on time were performed in around two-thirds of the patients, and the central venous pressure measurement as an index for fluid resuscitation was performed only around onethird, said Koh. The study involved 1,285 adult patients with severe sepsis admitted in 150 intensive care units in 16 Asian countries in July 2009. The main outcome measure was compliance with the Surviving Sepsis Campaigns resuscitation (6 hours) and management (24 hours) components. High income countries, university hospitals, intensive care units with an accredited fellowship program and surgical intensive care units were more likely to be compliant with the resuscitation component. The situation is not much better in developed countries. World Sepsis Day aims to change that through education and active engagement of physicians, decision makers and the general public all over the world.

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May 2012

News

Bergamot orange a natural supplement for cholesterol control

Rajesh Kumar
An Australian cardiologist has found a natural ally in his fight against metabolic disorders an extract of the bergamot orange, an Italian citrus fruit which has long been believed to possess heart health benefits. Dr. Ross Walker, who runs a private practice in Sydney, said he has successfully used the extract in about 700 of his registered patients who are overweight with dyslipidemia and elevated blood sugar levels. Within a few weeks of starting the supplement, some of those patients have totally avoided the need for statins while others have reduced their statin dose to control dyslipidemia. As a bonus outcome, their blood glucose and middle obesity have also significantly reduced, said Walker. His findings are consistent with those of an unpublished clinical study conducted in Italy involving more than 200 patients with hyperlipidemia. In the study, 1 months supplementation with bergamot reduced LDL cholesterol by 39 percent and blood sugar by 22 percent, and raised HDL cholesterol by 41 percent. Bergamot contains extremely large amounts of polyphenols, as compared to other citrus species. Two of these, Brutelidin and Metilidin, directly inhibit cholesterol biosynthesis in a similar way to statins and they are not found in any other citrus derivatives, said lead study author Dr. Vincenzo Mollace, professor in the faculty of pharmacology at the University of Cantanzaro in Italy. Bergamot extract blocks the HMG CoA reductase enzyme at a different level than statins. As a result, myalgia and other side effects typically associated with statins can be avoided because bergamot does not block the component that depletes the muscular co-enzyme q10, said Walker. Bergamot extract (BergametTM) also inhibits cholesterol absorption in the gut, the same way plant sterols do. Thats why I ask my patients to take it 15 minutes before meal twice a day, in the afternoons and evenings, to block cholesterol absorption from food, he said. The unique and most important action of bergamot, due to which cardiologists (like me) are supporting this, is that it affects metabolic syndrome as a whole: raising HDL cholesterol, lowering LDL and blood sugar and reducing arterial stiffness and middle obesity. Could patients be advised to consume bergamot juice as part of a healthy diet to prevent metabolic syndrome, rather than taking its extract in a pill form? Walker said it is not that easy since bergamot orange is extremely bitter/sour and large amounts of its juice would be needed to get the desired benefit. [Bergamot extract] is not a replacement for statins. Patients who have had a heart attack or have vascular disease do need to take statins. [But] the extract can be useful in preventing metabolic syndrome, correcting it in early stages and as a supplement to reduce statin dose, he said.

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May 2012

News

Omega-3 fatty acids help slow aging of the brain

Rajesh Kumar

he status of omega-3 fatty acids as brain food is well established. However, research now suggests a diet lacking in these fatty acids may cause brain to age faster and lose some of its memory and thinking abilities. The finding has prompted a study author to recommend that physicians should remind patients to regularly consume fatty fish or other food sources of omega-3 as part of a balanced diet. [In the study] people with lower blood levels of omega-3 fatty acids had lower brain volumes that were equivalent to about 2 years of structural brain aging, said lead researcher Dr. Zaldy Tan of the Easton Center for Alzheimers disease research and the division of geriatrics at the University of California at Los Angeles, California, US. A total of 1,575 people with an average age of 67 and free of dementia underwent MRI brain scans for the study. They were also given tests that measured mental function, body mass and omega-3 fatty acid (comprising docosahexaenoic acid or DHA, and eicosapentaenoic acid, EPA) levels in their red blood cells. [Neurology 2012;78: 658-664]. Fatty acid composition of red blood cells (RBC) reflects dietary fatty acid intake averaged over the RBC lifespan of up to 120 days, whereas plasma concentrations reflect intake over only the last few days. The researchers found that people whose

The regular consumption of fatty fish or other food sources of omega-3 fatty acids is well known to be part of a balanced diet.

DHA levels were among the bottom 25 percent of the participants had lower brain volume compared to people who had higher DHA levels. Similarly, participants with levels of all omega-3 fatty acids in the bottom 25 percent also scored lower on tests of visual memory and executive function, such as problem solving and multi-tasking and abstract thinking. Lower DHA levels are associated with smaller brain volumes and a vascular pattern of cognitive impairment, even in persons free of clinical dementia, concluded the researchers. It may be premature for physicians to advise their patients to consume adequate amounts of food rich in omega-3 specifically for their brain health, without evidence from a large randomized control trial. But Tan said there is already ample evidence supporting the benefits of this fatty acid in cardiovascular and overall health and such an advice could only be beneficial.

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May 2012

News

Even mild hearing loss increases risk of falling

Rajesh Kumar

dults aged 60 and older should be routinely screened for hearing loss and treated according to best practice guidelines, according to Dr. Frank Lin, assistant professor of otolaryngology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health in Baltimore, Maryland, US. The advice follows research findings that link even mild hearing loss to a three-fold risk of falls. Hearing loss among the elderly is already associated with a range of social and cognitive problems, including dementia. But the researchers feel the latest finding could help in the development of new ways to prevent falls and resulting injuries that cost billions of dollars in health care. We still do not know if treating hearing loss can reduce falls. But hearing loss treatment entails no risks and could potentially only lead to benefits for cognitive, social and physical functioning, said Lin, adding that hearing loss was only one of many potential risk factors for falls. To determine whether hearing loss and falling are connected, Lin and colleagues used data from the 2001 to 2004 cycles of the US National Health and Nutrition Examination Survey. A total of 2,017 participants aged 40 to 69 had their hearing tested and answered questions about whether they had fallen over the past year. [Arch Intern Med 2012;172:369371] They also collected demographic information, including age, sex and race, and tested

participants vestibular function, a measure of how well they kept their balance. They found that people with a 25-decibel hearing loss, classified as mild, were nearly three times more likely to have a history of falling. Every additional 10-decibels of hearing loss increased the chances of falling by 1.4 fold (95% CI, 1.3-1.5).

Gait and balance are ... actually very cognitively demanding

The finding held true even when researchers accounted for other factors linked with falling, including age, sex, race, cardiovascular disease and vestibular function. Excluding participants with moderate to severe hearing loss from the analysis also didnt change the results. Among the possible explanations for the link is that people who cant hear well might not have good awareness of their overall environment, making tripping and falling more likely, said Lin. Another reason hearing loss might increase the risk of falls is cognitive load, in which the brain is overwhelmed with demands on its limited resources. Gait and balance are things most people take for granted, but they are actually very cognitively demanding. If hearing loss imposes a cognitive load, there may be fewer cognitive resources to help with maintaining balance and gait, he said.

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White rice link to diabetes stirs debate

Rajesh Kumar
recent meta-analysis linking regular white rice consumption to significantly elevated risk of type 2 diabetes has stirred up some controversy. The analysis, conducted by researchers from the Harvard School of Public Health in Boston, Massachusetts, US, included data from four primary prospective cohort studies, two of which were conducted in Asia (China and Japan) and the other two in the West (USA and Australia). [BMJ 2012; DOI:10.1136/bmj.e1454] The results showed that higher white rice intake is associated with a significantly elevated risk of type 2 diabetes. Assuming a serving size of white rice of 158 grams, the researchers estimated that the risk of type 2 diabetes is increased by 10 percent with each additional serving. Dr. Daphne Gardner, associate consultant in the department of endocrinology at Singapore General Hospital, cautioned physicians against a simplistic interpretation of the study data, saying the methods used to quantify white rice consumption in the primary studies were very imprecise, which made the analysis based on their pooled summary data also imprecise. Asian diets are known to rely on white rice as a staple food, with some studies reporting white rice contributing to nearly three-quarters of the glycemic load. Should Western diets contain equivalent amounts of carbohydrates (glycemic load), but of an alternative form (eg, bread or potatoes), would the same effect be seen? asked Gardner.

She suggested that the main question ought to be: How much of the diet (ie, proportion of macronutrient) should consist of carbohydrates and what implications does this have for the increased risk of type 2 diabetes? Dr. Cho Li Wei, consultant in the department of endocrinology at Changi General Hospital agreed, saying the observational nature of the study limited the ability to state cause and effect and controlled studies were needed to determine if white rice indeed increases the risk of type 2 diabetes. Gardner said the study had few immediate implications for physicians, patients or public health authorities. It should certainly not support large scale action to change the dietary habits of Asian populations which have been present for centuries. In order to determine the contribution of white rice to developing type 2 diabetes, one would need a prospective large-scale randomized controlled trial, with the intervention group having modified white rice consumption. However, such a trial is unlikely to happen. The important take home message is: more fiber is always beneficial. And this may take the form of increased consumption of vegetables or less-processed foods (raw oats rather than processed cereal). In addition, portion control of calorie intake (whether this is protein, carbohydrate or fat) is important in maintaining a healthy weight and reducing the overall risk of developing type 2 diabetes, she said.

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

PARTNER: 2-year study supports use of catheter-placed heart valves

Elvira Manzano
atheter-placed heart valves performed well over 2 years in patients with symptomatic severe aortic stenosis at high risk of requiring traditional open heart surgery, according to the updated results of the PARTNER* trial. At 2 years, the primary endpoint of death from any cause was not statistically different between patients who underwent transcatheter aortic valve replacement (TAVR) and those who underwent surgical aortic valve replacement (AVR) 33.9 percent with TAVR and 35 percent with AVR, P=0.41. The rates of death from cardiovascular causes also remained comparable between the two groups (21. 4 percent with TAVR and 20.5 with surgery; P=0.80). Based on the results of the PARTNER Cohort A, TAVR should be considered as an alternative surgery with similar mortality and clinical benefits, said study author Dr. Susheel K. Kodali, from Columbia University Medical Center in New York City, New York, US. One-year results comparing TAVR with AVR, presented at last years ACC meeting, showed similar death rates and treatment benefit between the two groups. The trial was extended to determine the long-term outcomes following TAVR and assess valve performance. A total of 699 high-risk patients were randomly assigned to TAVR (N=348) or AVR (N=351). Patients who received TAVR either had transapical or transfemoral access. The

transapical approach appeared to have a higher mortality rate at 2 years compared with a transfemoral approach, however Kodali said the study was not designed for this comparison. Symptom improvement was similar in both groups and was maintained over the course of follow-up. Strokes were more frequent with TAVR in the first 30 days, however no significant differences were seen between the two groups at 2 years (hazard ratio [HR]=1.22, 95% CI 0.67 to 2.23; P=0.52). Periprocedural stroke concerns after TAVR have diminished with longer follow-up and TAVR hemodynamic performance was maintained, with no evidence of structural valve deterioration. Kodali said. However, paravalvular regurgitation was more common after TAVR than surgery. Interestingly, the authors found that even mild paravalvular regurgitation was associated with increased mortality in TAVR patients. Kodali however said the finding is not going to dampen the enthusiasm for TAVR, instead this will motivate us to improve on these procedures and devices. Now we know what to fix in the future. TAVR is already comparable with surgery in the most experienced surgeons hands. If we can reduce these leaks, theres a good chance we can reduce mortality with TAVR even more, he concluded.
*PARTNER: Placement of Aortic Transcatheter Valves

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

Cardiac pacing reduces syncope recurrence

Elvira Manzano

ctive pacemaker therapy can reduce episodes of syncope or fainting in patients with neurally mediated syncope (NMS), according to a recently reported study. In the randomized controlled ISSUE- 3 study*, which involved 77 patients, 57 percent of patients who had pacemakers set to the off mode had a recurrence of syncope within 2 years compared with only 27 percent of those in the on mode (P=0.039). The point is no therapy has been proven effective for NMS syncope, said principal study investigator Dr. Michele Brignole, head of the department of cardiology, Arrhythmologic Centre, Ospedali del Tigullio, Lavagna, Italy. Now, we have evidence that cardiac pacing works for this form of syncope. NMS, also called reflex syncope, is one of the most common forms of syncope. The condition is characterized by peripheral vasodilation, hypotension and bradycardia. Brignole said reflex syncope is benign regarding mortality but it increases the risk of secondary trauma. Patients in the study were >40 years old, with severe NMS identified through an implantable loop recorder (ILR) that did not respond to more conservative interventions. Half of them had diabetes and had a history of injuries related to fainting. Patients were

randomized to receive dual-chamber pacemakers with one lead in the atrium and another in the ventricle that was switched on (N=38) or off (N=39). The primary endpoint was fainting recurrence. There was no difference in treatment outcomes between women and men. Procedure-related complications included right atrium lead dislodgement in two patients, right ventricular lead dislodgement in two patients and subclavian vein thrombosis in one patient. Brignole said the observed 32 percent absolute and 57 percent relative syncope reduction rate support the use of dual-chamber pacemaker for relatively benign NMS. He added that the overall strategy of using an ILR to determine which patient needs pacing likely contributed to the success of ISSUE-3. We found that approximately one out of three pacemaker patients will benefit from pacing therapy within the subsequent 2 years, Brignole said. The efficacy of pacing therapy has been established in the study. However, he said that the fact that pacing is effective does not mean that it is always necessary. Cardiac pacing should be a last choice in highly selected patients affected by severe NMS. He added that other patients who suffer a more benign form of NMS may respond to less drastic treatments.
ISSUE 3*=International Study on Syncope of Uncertain Etiology 3

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

CT angiography reduces hospital waiting times

Radha Chitale
ardiac computed tomography (CT) angiograms are effective at scanning patients presenting to emergency departments with chest pain for coronary blockages and allows those not at risk for cardiovascular events to go home within just a few hours, according to the results of two US-based studies. Up to 85 percent of chest pain cases presenting to emergency departments are not heart-related. Ruling out the risk of heart attack or other cardiac event typically involves a 24-hour hospital stay plus a stress test and may include imaging. Subsequent tests can include cardiac catheterization to determine the extent of coronary blockage. Tests can be costly, time consuming and uncomfortable for the patient. Discharge criteria is a less than 1 percent risk of heart attack or heart-related death over 30 days. Risk is determined by 50 percent or more blocked coronary arteries. The ACRIN PA* trial randomized 1,393 patients to standard rule out care (N=462) or CT scans (N=908). Further care was determined by individual healthcare providers. [N Engl J Med 2012 Mar 26. Epub ahead of print]

No deaths occurred in the 640 patients who were discharged. CT was a better indicator of coronary artery disease than stress tests (9 percent versus 3.5 percent, respectively). CT was also superior to standard care in the number of discharged patients (50 percent vs. 23 percent), median hospital stay (18 hours vs. 25 hours) and median hospital stay for patients whose CT or stress test results were negative (12 hours vs. 25 hours). Since low-to-intermediate-risk patients account for 50 to 70 percent of presentations with a possible acute coronary syndrome, we believe that a [CT]-based strategy can safely and efficiently redirect many patients home who would otherwise be admitted, the ACRIN PA researchers said. ROMICAT II*, a separate but related trial, included 1,000 patients presenting to emergency departments with chest pain randomized to standard care or CT scan. CT scans reduced average time spent in the hospital by 18 hours (24 vs. 36 hrs, P=0.0002). Lead author Dr. Udo Hoffmann, from Massachusetts General Hospital in Boston, Massachusetts, US, also reported 50 percent of patients were discharged within 8 hours when assessed with CT scans. It took 28 hours to discharge half the patients with standard care.

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Conference Coverage
standard evaluation takes much longer to assess whether the symptoms stem from blockages in their arteries, he said. Patients benefit from an earlier diagnosis and can safely go home from the ER earlier.
*ACRIN PA: American College of Radiology Imaging Network *ROMICAT II: Rule Out Myocardial Infarction Using Computer Assisted Tomography II

He said the overall costs to the hospital and patients were similar between assessment methods and that using CT scans could help already crowded emergency departments better distribute resources. Physicians benefit because they can discharge many patients from the overcrowded ER very quickly, with solid reassurance that theyre not having a heart attack, while the

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

Rivaroxaban tops standard PE treatment

Naomi Rodrig

ivaroxaban, an oral Factor Xa inhibitor, has demonstrated comparable efficacy and superior safety to standard therapy for pulmonary embolism (PE), in a large phase III multinational study. The EINSTEIN-PE study enrolled 4,833 patients with PE, 25 percent of whom also had deep vein thrombosis (DVT). Patients were randomized to rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg once daily (N=2,419), or to standard therapy enoxaparin 1.0 mg/kg for 5 days until International Normalized Ratio (INR) was 2.0 for 2 consecutive days, plus warfarin or acetocoumarol started within 48 hours of randomization, with dose adjustment to maintain INR of 2.03.0 (N=2,413). Patients were treated for 3, 6 or 12 months as deemed appropriate by the attending physician. The primary efficacy outcome was first recurrent VTE; principal safety outcome was first major or non-major clinically relevant bleeding. [N Engl J Med 2012; DOI:10.1056/NEJMoa1113572] The trial set out to show non-inferiority of rivaroxaban and succeeded. Furthermore, it also showed a significant reduction in bleeding, reported Professor Harry Buller of the Academic Medical Center, Amsterdam, The Netherlands, who is chair of the EINSTEIN clinical trial program. Previously, the EINSTEIN-DVT study led to the approval of rivaroxaban as the only oral anticoagulant for DVT prevention in patients undergoing knee or hip replacement. [N Engl J Med 2010;363:499-

2510] Rivaroxabans efficacy was highly significant for non-inferiority, with 2.1 percent recurrent DVT events vs 1.8 percent in the standard therapy arm [P=0.0026], reported Buller. On safety measures, rivaroxaban demonstrated a non-significant trend towards reduction in clinically significant bleeding with a hazard ratio [HR] of 0.9 (P=0.23). Importantly, there was a 50 percent lower rate of major bleeding, particularly intracranial hemorrhage and retroperitoneal bleeding (HR=0.49; P=0.0032). The biggest advantage was seen in patients over 75 years of age, with a HR of 0.19 for major bleeding.

Physicians want to know rivaroxaban was highly

about major bleeding, and

significantly superior. This was our most astonishing finding Bleeding rates start to separate very early in the treatment. Physicians want to know about major bleeding, and rivaroxaban was highly significantly superior. This was our most astonishing finding, he remarked. These data are pretty convincing. Rivaroxaban is as good as standard treatment for PE with an oral-only approach, which makes treatment very simple. The reason people look for alternatives to the standard treatment is because its a nightmare to give, with

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Conference Coverage
ogy, probably because the clot is closer to the heart, he said. He added that the investigators are planning a subgroup analysis of the 8,200 subjects of the EINSTEIN-PE and EINSTEIN-DVT trials to identify a risk profile for patients who are likely to have bleeding problems.

the subcutaneous injections and constant INR monitoring. Buller speculated that rivaroxaban will likely increase cost effectiveness by reducing hospitalization time for PE. While patients with DVT are usually treated outside the hospital, with PE its a different psychol-

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

Vorapaxar reduces post-MI CV mortality risk, but bleeding an issue

Radha Chitale

reatment with the experimental antithrombotic agent vorapaxar reduced the risk of cardiovascular death and ischemic events among patients with a history of heart attack or stroke, but significantly increased the risk of bleeds and intracranial hemorrhage, according to a study. This benefit and risk emerged early and continued to accrue throughout follow-up, said researchers from Brigham and Womens Hospital in Boston, Massachusetts, US. Vorapaxar reduced the relative risk of the TRA 2P-TIMI 50* trial primary endpoints cardiovascular death, myocardial infarction or stroke by 20 percent after 3 years of follow up. [N Engl J Med 2012 Mar 24. Epub ahead of print] The researchers reported the rate of the primary endpoints as 9.3 percent and 10.5 percent among patients treated with vorapaxar or placebo, respectively (P<0.001). However, the corresponding rates of moderate-to-severe bleeding and intracranial hemorrhage was 4.2 percent and 1.0 percent, respectively, among vorapaxar-treated patients compared with 2.5 percent and 0.5 percent among those given placebos (P<0.001 for both). The large, international trial included

26,449 patients with atherosclerosis, evidenced by prior myocardial infarction (MI), stroke or peripheral arterial disease who were on standard therapy, typically aspirin, randomized to daily vorapaxar or placebo. Patients at risk for stroke were removed from the trial following evaluation after 2 years of follow up due to the increased risk of bleeding. At 3 years, patients without a history of stroke reached the primary endpoint in 8.3 percent of cases among the vorapaxar group and 9.6 percent of the placebo group (P<0.001). The group that benefited the most were those included in the trial due to a prior heart attack. The researchers said the overall trial cohort showed no significant between-group difference in the pre-specified net clinical outcome including thrombotic end points and bleeds. If vorapaxar were to become clinically available, it is not an agent for all patients with atherosclerosis, said lead author Dr. David Morrow, of Brigham and Womens Hospital. We need to select patients where we think theres an appropriate balance of the potential benefit versus the risk.
*Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2P)Thrombolysis in Myocardial Infarction (TIMI) 50 trial

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

Elective angioplasty safe without surgical backup

Elvira Manzano
lective angioplasty, or percutaneous coronary intervention (PCI), performed at hospitals without on-site cardiac surgery units, was no riskier than the same procedure done at hospitals with surgical backup, according to the C-PORT E* study. Patient mortality rates at 6 weeks and major adverse cardiac events at 9 months were similar regardless of the hospitals on-site cardiac capabilities. There were also no significant differences in rates of bleeding and renal failure between the two groups. The short-term safety outcomes of elective angioplasty are the same regardless of the hospital type, said lead study investigator Dr. Thomas Aversano, associate professor of cardiology at Johns Hopkins University in Baltimore, Maryland, US. The study shows that under certain circumstances, non-primary angioplasty can be performed safely and effectively at hospitals without onsite-cardiac surgery. Aversano and colleagues compared the 9-month outcomes of 4,718 patients who received elective PCI at hospitals with on-site cardiac surgery with 14,149 patients who had the procedure at hospitals without cardiac surgery units but which were staffed with interventionalists who met strict criteria for proficiency and experience. No significant differences in the primary composite endpoints of death and heart at-

tack were observed between the two groups, but there was a small increase in the need for target vessel revascularization or repeat procedure in patients who received PCI without surgical backup (8.5 percent vs 7 percent, P<0.01). The difference in repeat procedure rates was small, between 11 to 17 additional procedures for every 1,000 patients, which may be due to the more conservative approach to treating the blockage at hospitals without cardiac surgery capability, Aversano said. However, he said the findings should be interpreted with caution. Not every community hospital should perform elective angioplasty. Hospitals and cardiologists that participated in the study met the strict criteria they went through a detailed angioplasty development program and had to perform 200 PCI procedures a year. Aversano also clarified that the trial was not performed to indiscriminately expand the number of hospitals doing angioplasty but to give health care policy makers information on which to base their decisions on quality and cost of angioplasty in their state so patients can have access to highest quality of care. Study discussant, Dr. Loren Hiratzka, from the Bethesda North and Good Samaritan Hospitals in Cincinnati, Ohio, US, said the findings are important but there could be unintended consequences of moving elecTurn to page 27>>

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Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

Bypass offers better survival than PCI in some patients

Rajesh Kumar
oronary artery bypass graft (CABG) surgery may provide higher long-term survival in some patients, compared to the lessinvasive percutaneous coronary intervention (PCI) including stenting and balloon angioplasty, according to the largest study comparing the two. Researchers compared the health outcomes of 86,244 CABG and 103,549 PCI patients aged over 65 years across the US who underwent treatment from 2004 to 2008. At 1 year postintervention, they found no difference in adjusted mortality rates between the two groups 6.24 percent and 6.55 percent, respectively. However, by 4 years, PCI was associated with a higher rate of mortality than CABG (20.80 percent vs. 16.41 percent, respectively; risk ratio 0.79, 95% CI 0.76-0.82). Similar results were noted for multiple subgroups and with several different analytic methods. Our study is the most general one ever done because it uses data from across the whole country. It is also much larger than any other study, said lead researcher Dr. William Weintraub, chair of cardiology at Christiana Care Health System in Wilmington, Delaware, US. Some previous studies have suggested the two treatments have similar long-term outcomes, while others have shown better outcomes with bypass surgery. When both treatments are an option, patients and doctors tend

to choose the less-invasive PCI. Although the latest study found survival is better with surgery, this does not mean bypass surgery is the best for every patient, Weintraub cautioned. It does push the needle toward coronary surgery, but not overwhelmingly so. When were recommending coronary surgery to patients, even though it is a bigger intervention than PCI, we can now have a little more confidence that the decision is a good one. A major limitation of observational studies such as the current one is that the groups may not have the same level of risk, and so it is possible that the worse outcomes in the PCI patients were related to these patients being sicker overall, said Weintraub. The large number of cases allowed the researchers to compare results across many subgroups and found the data was consistent across all subgroups, no matter what analytic approach they used. They found the long-term advantage for CABG was independent of age, sex, diabetes, renal function, and lung disease and was evident even among patients whose propensity scores were most consistent with selection for PCI. Survival was better with coronary surgery for all patient subgroups. This study should help inform decision making concerning the choice of revascularization in patients with stable ischemic heart disease, he said, adding, but there may be differences between the two groups that we could not account for.

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

Similar outcomes seen with different CABG pump techniques

Rajesh Kumar

he largest ever randomized control trial to compare on-pump and off-pump coronary artery bypass grafting (CABG) has found not much difference in the 30-day outcomes for both techniques. Long-term outcomes are not yet evident. About 4,700 patients (mean age 67.6 years) from 79 centers in 19 countries, with coronary artery disease, were randomized to undergo either off-pump or on-pump CABG by an expert cardiac surgeon, experienced in at least 100 cases of the allocated technique over 2 or more years. [N Engl J Med 2012; DOI 10.1056/ nejmoa1200388] Primary composite endpoint including death, myocardial infarction, stroke, or new renal failure requiring dialysis was similar in the two groups (9.8 percent 10.3 percent; 95% CI 0.79-1.14 P=0.59). However, the use of offpump CABG (beating heart surgery) resulted in reduced rates of transfusion, reoperation for perioperative bleeding, respiratory complications, and acute kidney injury.

The latter group also had fewer grafts performed and had more revascularizations (0.7 percent vs. 0.2 percent; hazard ratio 4.01; 95% CI, 1.34-12.0; P=0.01). The co-primary outcome involves checking for all of the above at 5 years. The efficacy of off-pump CABG is not well established. A previous trial and Cochrane Review have shown its benefits to be only marginal, raising the need for a randomized trial of this magnitude to better understand the issue, said lead author Dr. Andre Lamy of the Population Health Research Institute at McMaster University in Hamilton, Ontario, Canada. The findings on 30-day outcomes prompted Lamy to suggest that surgeons train in both methods and decide on which one to use according to clinical parameters of the individual patient in question, until long term outcomes become available. The long-term results of the primary outcomes and neurocognitive outcomes will have a determinant influence on the interpretation of this trial, he said.

>>From page 25 tive PCI into the community. The real question is: Can these results be reproduced in general community practice? The study is the first randomized controlled trial to investigate elective angioplasty in US community hospitals. Long-term outcomes are expected to be released next year.
*C-PORT E: Cardiovascular Patient Outcomes Research Team Elective

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May 2012

Conference Coverage

61st Annual Scientific Sessions of the American College of Cardiology, 24-27 March, Chicago, Illinois, US

Lowering cholesterol in childhood reduces CVD risk later

Rajesh Kumar

igh LDL-cholesterol (LDL-C) in children needs to be controlled early on as a US study showed that doing so could be three times better at reducing the subsequent risk of cardiovascular disease (CVD), than treatment with a statin later in life. The findings do not suggest that everyone should start taking statins from childhood. Instead, preventing high LDL-C and lowering its raised levels through healthy diet and exercise early on could make a big difference to public health in terms of CVD prevention, said lead author Dr. Brian Ference of the Wayne State University School of Medicine, Detroit, Michigan, US. By the time most people begin treatment to lower their LDL-C levels, coronary atherosclerosis has often been silently developing for many decades. Researchers hypothesized that lowering LDL-C at a younger age, or reducing prolonged exposure to raised LDL-C, may produce even greater reductions in their risk of CVD. A randomized control trial (RCT) to check this hypothesis would have required monitoring a very large number of young and healthy people for many decades. Instead, they employed the Mendelian RCT, which is often referred to as the natural RCT. Using genetic data from over 1 million patients, they studied the effects of nine single-nucleotide polymorphisms (SNPs, or single-letter changes in DNA sequence), each of which is associated with lower levels of LDL-C, on CVD risk.

Samples with 1 SNP were classed as the treatment arm while those with no SNPs were categorized as the usual care group. Each of the nine SNPs was associated with LDL-C levels that were lower by 2.6 to 16.9 mg/ dL and coronary heart disease risks that were lower by a relative 6 percent to 27 percent. After adjusting the analyses for each unit of lower LDL-C, each 38.7 mg/dL lower lifetime exposure to LDL was associated with a more consistent relationship with CVD risk, which was 51 percent to 59 percent lower. Combining non-overlapping data from 325,000 participants showed lifetime exposure to lower LDL-C was associated with a 54 percent relative risk reduction of CVD per mmol/L lower LDL-C. This effect is approximately 3-fold greater per unit decrease in LDL-C than that observed during treatment with a statin started later in life, the researchers wrote. Previous meta-analyses have suggested that lowering LDL-C by 1 mmol/L with statins at the average age of 63 years reduces the CVD risk by only 24 percent, while lowering the levels by 3mmol/L through statins could achieve relative risk reduction of up to 54 percent in the older population. The results of our study demonstrate that the clinical benefit of lowering LDL-C can be substantially improved by initiating therapies to lower LDL-C beginning early in life[and], diet and exercise are probably as effective as statins or other pharmacologic interventions early in life, said Ference.

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News

Study shows how smoking causes COPD

Dhenuka Ganesh
ew light has been shed on how chronic obstructive pulmonary disease (COPD) develops in association with long-term smoking. Our findings have important implications for understanding the etiology of COPD and suggest that pharmaceuticals designed to reduce leukocyte recruitment through the bronchial circulation may be a potential therapy to treat COPD, said the study authors, led by Dr. Ryan P. Davis of the UC Davis School of Medicine, Davis, California, US. Their research revealed that tobacco smoke exposure stimulates neutrophils to migrate from the bronchial blood vessels, due to the production of adhesion molecules and chemokines, and accumulate in the lung tissues. Although neutrophils help repair tissues, excessive numbers of activated neutrophils can release enzymes that kill cells and accelerate inflammation. In this study, a highly reproducible animal model of COPD was used to show that the equivalent of approximately 10 years of onepack-a-day smoking completely damages the bronchial airways by accelerating inflammation, obstructing airflow, and reducing normal lung function. [PLoS One 2012;7:e33304. Epub 2012 Mar 21] The researchers studied rats having a genetic defect that made them react to smoke exposure much like humans with smoking-related diseases. The animals developed all the physiological and anatomical traits of COPD. A smoking machine was used to automatically load, light, and puff on cigarettes, and the rats were exposed to amounts that a

COPD is the fourth leading cause of death worldwide, according to the WHO.

two-pack-a-day smoker would be exposed to, for 6 hours a day, 3 days a week. After 4 weeks, their physiological changes reflected those of a 10- to 20-year smoker with complications of wheeze and cough and reduced respiratory function. After 12 weeks, they were reflective of a 30- to 40-year smoker having severe limitations in breathing and COPD. The UC Davis team is now testing whether statin drugs may prevent COPD development in this model. The model appears to be ideal for screening drugs to treat early COPD, but the ultimate test comes when a treatment is transitioned from the lab to COPD patients, said the lead author, Dr. Benjamin Davis. Our primary goal is to save lives. According to the WHO, COPD is the fourth leading cause of death worldwide. In India, around 15 million people suffer from COPDthis number is expected to increase. Dr. Aloke Gopal Ghoshal, director of the National Allergy Asthma Bronchitis Institute, Kolkata, India, stressed the importance of COPD management and treatment. [In India], people who are more exposed to biomass fuel and smoke are at a greater risk of having COPD this number is around 578 million.

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News

Potential new target identified for treating infectious diseases, cancer

Dhenuka Ganesh
novel T-cell activation pathway though which dendritic cells become highly specialized to fight Mycobacterium leprae, the causative agent of leprosy, may be a potential therapeutic target for a range of infectious diseases and cancer, according to new research. Dendritic cells, which deliver key information about an invading pathogen for T-cell activation, have been known to be important for eliciting a strong immune response and their numbers at the infection site are positively correlated with this robust reaction. However, it was poorly understood how dendritic cells become more specialized to address specific types of infections. The research found that a protein called NOD2 triggers the cell-signaling molecule interleukin-32 that induces general immune cells monocytes to become specialized information-carrying dendritic cells. [Nat Med 2012 Mar 25;18:555-63] This is the first time that this potent infection-fighting pathway with dendritic cells has been identified, and demonstrated to be important in fighting human disease, said the studys lead author Mirjam Schenk, postdoctoral scholar, division of dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, US. The scientists used monocytes from the blood of healthy donors and leprosy patients and incubated the cells with M. leprae or specific parts of the bacterium known to trigger NOD2 and TLR2, both associated with immune system activation.

The objective was to investigate how these proteins might trigger mechanisms that activate different immune receptors that recognize specific parts of the microbe in an infection. They found that the NOD2 interleukin-32 pathway was the most effective and caused the monocytes to differentiate into dendritic cells. The team also studied the gene expression profiles of the protein-triggered pathways and then examined how the monocytes of leprosy patients responded to NOD2. The protein induced the monocytes to develop into dendritic cells in tuberculoid leprosy, a milder infection that is more easily contained. The NOD2 pathway was inhibited and could not be activated in lepromatous leprosy, which is more serious and causes widespread infection throughout the body. We were surprised to find the high potency of the dendritic cells in triggering certain specific T-cell responses, which may be useful in developing new therapeutic strategies for infectious diseases and cancer, said senior investigator Dr. Robert Modlin, UCLAs Klein professor of dermatology and chief of dermatology at the Geffen School of Medicine. Modlin added that leprosy is a good model to study immune mechanisms in host defense since it presents as a clinical spectrum that correlates with the level and type of immune response of the pathogen. The next stage of research will involve trying to further understand how to manipulate the innate immune system to induce a potent immune response in human infections and possibly for cancer immunotherapy as well.

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News

Breast cancer survivors can learn to handle hot flushes, night sweats
Radha Chitale
ognitive behavioral therapy (CBT) is effective at reducing the hot flushes and night sweats (HFNS) that are common following treatment for breast cancer, according to a study. HFNS, which the study researchers reported affect up to 85 percent of women after breast cancer treatment, are sources of distress and negatively impact patient quality of life. Hormone replacement therapy for HFNS, used among affected women who are menopausal, is contraindicated or undesirable in cancer patients. Previous research has shown reductions in HFNS with paced breathing and the researchers reported pilot trials showed promise for CBT. The improvement in social functioning after CBT is relevant because women report finding hot flushes especially difficult to deal with at work and in other social situations, the researchers said. Additionally, group CBT provided sustained benefits to depressed mood and sleep and some improvements in dimensions of quality of life. Women from breast clinics in the UK who had at least 10 HFNS episodes per week after breast cancer treatment were randomized to receive usual care (N=49) or usual care plus one 90-minute session per week of group CBT (N=47). [Lancet Oncol 2012 Mar;13:309-318] Usual care included follow-up visits to oncologists or clinical nurse specialists ev-

ery 6 months and as needed, telephone support from a cancer survivorship program, information leaflets, and advice about HFNS and treatment options, including symptoms management, paced breathing and relaxation. The CBT program was based on the causal and maintaining factors of HFNS, including anxiety, stress, embarrassment, negative beliefs and catastrophic thoughts, and the resultant behaviors, which can impact patient outcomes, such as avoidance activities. Women receiving CBT spent 6 weeks in structured, interactive group classes where they were given information about the physiology of HFNS, taught paced breathing, relaxation techniques and behavioral strategies to manage HFNS. The weekly plan included discussions on topics including handling HFNS, the role of stress, and what cognitive factors might contribute to it. Women were given the opportunity to describe their own experiences with HFNS as a result of breast cancer, their triggers and outline their treatment goals. CBT significantly reduced HFNS after 9 weeks and the results were maintained at 26 weeks compared with usual care (adjusted mean difference in HFNS problem rating [1-10 scale] -1.67 and -1.76, respectively; P<0.0001). Women reported sustained benefits to mood, sleep and quality of life. Current treatments for HFNS are nonhormonal drugs such as selective serotonin

32

May 2012

News
pausal when they had breast cancer, the researchers said. However, treatment options are still restricted for these women the most cost effective method of delivering the group CBT would probably be to include it as part of survivorship support program, delivered by trained and supervised breast-care nurses.

reuptake inhibitors (SSRIs) or gabapentin that result in moderate reductions in HFNS frequency about 37 percent across trials, the researchers reported, but with few improvements in quality of life. We do not know whether HFNS were caused by breast cancer treatments or whether women were naturally meno-

Website: www.ensure.com.hk

33

May 2012

News

Minimally invasive technique safe, effective for ruptured aneurysms

Dhenuka Ganesh
minimally invasive interventional radiology treatment for ruptured abdominal aortic aneurysms (AAAs) resulted in significantly fewer hospital deaths after treatment as compared to open surgery, according to a new study. People with peripheral arterial disease are at risk of an aneurysm, which is a weakening and abnormal bulging of a major artery. Once this area of bulge ruptures, this can lead to fatal internal hemorrhage, explained study co-author Dr. Prasoon Mohan, from the department of diagnostic and interventional radiology at Saint Francis Hospital in Evanston, Illinois, US. Once an AAA reaches a particular size, treatment is recommended to prevent its rupture. Conventional open surgery involves making a large abdominal incision and then replacing the dilated portion of the aorta with a synthetic blood vessel. In contrast, the less-invasive endovascular aneurysm repair (EVAR) technique involves a small incision made in the groin for a thin wire catheter to be guided through the femoral artery to the dilated aorta. Once in place, a stent graft compressed into the catheter is opened up and the edges of the stent push against the aortic wall, holding it in place. Blood flows through the stent graft instead of the abnormally dilated aorta and prevents it from rupturing. In their retrospective study, the researchers mined the National Inpatient Sample data-

base for all cases of ruptured AAA from 2001 to 2009, treated by one of the two techniques. Of the 32,069 patients who received open surgery, 39.7 percent died in the hospital, compared with 28.2 percent of the 6,790 EVAR patients (P<0.001). The mean hospital stay associated with EVAR was also significantly shorter than that with open surgery (10.7 vs. 13.8 days, respectively; P<0.001). Additionally, a significantly higher proportion of those who underwent EVAR were discharged home without requiring further in-patient rehabilitation compared with open surgery recipients (35.3 vs. 21.7 percent, respectively; P<0.001). [Proceedings of the 37th Annual Scientific Meeting of the Society of Interventional Radiology, San Francisco, California, US, 2012; Abstract 178] Endovascular aortic repair involves less recovery time and fewer discharges to in-patient care facilities, potentially saving insurers, institutions and individuals money, said Mohan. EVAR has been one of the great innovations in interventional radiology that has helped the field make significant contributions to modern medicine, he added. I believe endovascular aortic repair will be the procedure of choice for emergency treatment of ruptured aneurysms in the future. Mohan said that a majority of the elective aneurysm repairs are being done using the endovascular technique. Its only a question of getting clinicians and institutions to use the technique in emergency settings for ruptured aneurysms.

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34

May 2012

In Practice

Managing acute otitis media: Strategies for GPs

Dr. Eng Soh Ping
Consultant ENT Surgeon Ascent Ear Nose Throat Specialist Group Mount Elizabeth Medical Centre Singapore

Disease of childhood Acute otitis media (AOM) inflammation of the middle ear is the second most common disease of childhood after upper respiratory tract infection (URTI). Most children have at least one or two episodes during childhood; many have repeated episodes with the peak incidence occurring between ages 2 and 5. Obstruction of the Eustachian tube is the most important antecedent event linked to this condition. Children are particularly susceptible because they have shorter and more horizontal Eustachian tubes than adults which are not fully developed and are more difficult to drain. With age, however, part of the tube ossifies to bone and the horizontal angle descends, increasing the downward flow of fluid.

Surgery takes only 10 minutes but recovery takes a few days.

A bulging erythematous tympanic membrane.

Otitis media with effusion resolves without surgery.

We cannot predict which

patients will go on to develop

complications. Thus, we should be aggressive, but a little cautious, when managing AOM

What causes AOM? Otitis media is caused by viral and bacterial inA grommet tube in position. fections. The most common bacteria responsible are Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Moraxella catarrhalis. Among older children, the most common cause is Haemophilus influenzae. The vast majority of AOM episodes are

35

May 2012

In Practice
accurate visualization of the tympanic membrane may lead GPs to the diagnosis of acute otitis media one of the three presentations of otitis media (OM), the other two being recurrent otitis media and otitis media with effusion (OME) or glue ear. A direct examination of the middle ear with an otoscope will reveal erythema, bulging and apparent opacity. The normal tympanic membrane moves in response to pressure changes. In AOM, mobility is reduced or absent with pneumatic otoscopy. An accurate clinical diagnosis is possible in most cases, but this is a challenge to physicians as the canal is small and the view may be obscured by earwax. Crying may also distend the small blood vessels in the eardrum, mimicking the redness associated with AOM. Another useful but lost skill among physicians is the use of tuning fork. If the child is cooperative, tuning fork tests both Weber and Rhine tests may be performed to distinguish between conductive and sensorineural hearing loss. Clinical guidelines for AOM GPs can refer to the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) guidelines when diagnosing and treating AOM. In the EENT circle, we use the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) clinical practice guidelines. The guidelines support the use of antibiotics, but an initial observation period of 48 to 72 hours is recommended for select cases to determine if the infection will resolve on its own. Current guidelines tend to be less aggressive although some parents may push for more active treatment due to anxiety and distress from seeing their children suffer.

triggered by URTIs. Eustachian tube dysfunction is a major risk factor. If the Eustachian tube becomes blocked, fluid can build up and lead to infection. Other risk factors for acute ear infections are attending daycare, changes in altitude or climate, recent ear infection and genetic factors. The childs position during bottle-feeding, for example lying down, also predisposes the child to AOM. For this reason, breast-feeding position semi-Fowlers may be good for normal Eustachian function. Signs and symptoms to watch out for When the middle ear which is normally sterile becomes acutely infected, pressure builds up behind the eardrum, resulting in otalgia. The tissues surrounding the tubes swell and fluid accumulates in the middle ear. Pyrexia, with or without co-existing URTI, is a common symptom in children of any age. Aside from earache, older children may complain of fullness in the ear and conductive hearing loss, which is usually transient. In young children, complaints of ear pain can be muted and only represented by crying, irritability and sleeping or feeding difficulties. Severe infections or untreated cases may cause the eardrum to rupture, causing the pus to drain from the middle ear to the ear canal. The condition usually resolves with pharmacological treatment. However, what we are worried about are those cases that do not rupture and have become complicated. More commonly, it would lead to mastoiditis which requires emergency surgery. Untreated, the infection can spread to surrounding structures, affecting the brain and the facial nerves. Diagnosing AOM The presence of the above symptoms, combined with a complete clinical history and

36

May 2012

In Practice
than 10 minutes although it takes a few days to fully recover. The tube will also self-extrude in 3 to 6 months. Take home message for GPs GPs, being at the heart of the community, have an important role to play in managing AOM. A sharp clinical acumen may not be enough to arrive at a good diagnosis. Paying attention to detail definitely has an added value. Rubbing of the ear, for example, may not mean anything, but it is a significant symptom in young children with AOM. Finally, it takes a sound judgment and due diligence to be able to spot early signs of complications. The infection can spread beyond the mucosal structures of the middle ear resulting in mastoiditis, facial nerve palsy, chronic otitis media, meningitis or brain abscess. Sagging of the posterior canal wall and swelling of post auricular areas with loss of skin crease usually signal danger signs that should alert clinicians and lead to ENT referral.

Treating AOM Most children with uncomplicated AOM recover fully without intervention, which is why some clinicians adopt the wait-and-see approach. However, we cannot predict which patients will go on to develop complications. Thus, we should be aggressive, but a little cautious, when managing AOM. AOM is treated just like any URTIs. Amoxicillin is the initial treatment of choice. Analgesics and antipyretics may be used for symptomatic management. If symptoms do not resolve after 48 hours and there is abscess, refer. Instrumentation and support may be limited under primary care setting. It helps to be on the careful side. Do not underestimate the problem. When in doubt, refer.

It takes a sound judgment and due diligence to be able to spot early signs of complications

Otitis media with effusion usually resolves without surgery. Complex cases that have not responded to antibiotic therapy however require tympanocentesis puncture of the tympanic membrane to aspirate fluid or to facilitate delivery of medication directly to the middle ear. In chronic cases with effusions, we do myringotomy with insertion of tympanostomy tube, called grommet, to allow ventilation and drainage. Surgery often takes less

Online Resources:
American Academy of Pediatrics www.aap.org American Academy of Otolaryngology, Head and Neck Surgery www.entnet.org Pediatrics pediatrics.aappublications.org/ content/113/5/1451.long

37

May 2012

Urology

Odor may help signal UTI in children

Elvira Manzano

oul-smelling urine may predict urinary tract infection (UTI) in children with unexplained fever, according to a leading pediatrician. Dr. Marie Gauthier, from the department of pediatrics, Sainte-Justine University Hospital Center, Montreal, in Quebec, Canada, cited the results of her own study which showed that malodorous urine was associated with UTI (odds ratio [OR] 2.83, 95% CI 1.54 to 5.20). [Pediatrics 2012; DOI:10.1542/peds.2011-2856] The association persisted despite adjustment for other UTI risk factors such as gender and the presence of vesicoureteral reflux abnormal flow of urine from the bladder to the upper urinary tract (OR 2.73, 95% CI 1.46 to 5.08). Parental reporting of malodorous urine increased the probability of UTI among young children, Gauthier said. However, she cautioned that the association is not strong enough to definitely rule in or out a diagnosis of UTI. In this prospective consecutive cohort study, Gauthier and colleagues surveyed the parents of 331 children, aged 1 to 3, tested in the emergency department of a hospital in Canada for suspected UTI, about their childs past medical history and symptoms. Of eight questions, two were on whether their childs urine smelled stronger than normal. Of the 331 children, 51 met the UTI diagnosis criteria. Bad-smelling urine was the risk factor most strongly linked to UTI 57 percent of the children who tested positive for a UTI had malodorous urine, while only 32

A study conducted in Canada suggests that malodorous urine may predict UTI in children.

percent of children who tested negative had pungent urine. Patients with UTI also had a fever of unknown origin as did 92 percent of those without. Gauthier suspects that the foul odor may be due to the production of ammonia from bacteria. She said the study findings are more useful for doctors than parents who, very often, would not ask about urine odor when a child is assessed in the ER for non-specific symptoms such as unexplained fever or irritability. It should make the clinician more suspicious of this type of infection, Gauthier concluded. The bacterium Escherichia coli causes the vast majority of UTIs in children. Throughout childhood, the risk of having a UTI is 2 percent for boys and 8 percent for girls. Most cases respond to antibiotics but serious infections may cause kidney scarring or blood poisoning if left untreated.

38

May 2012

Hong Kong Focus

Cranial acupuncture relieves major depression

Christina Lau
novel acupuncture technique known as dense cranial electroacupuncture stimulation (DCEAS) may represent an additional treatment option for patients with major depressive disorder (MDD), according to a new study. DCEAS involves stimulating the acupoints Bai Hui and Yin Tang that are traditionally used to treat depression, together with other acupoints including Si Shen Cong, Tou Lin Qi, Tai Yang, Shuai Gu and Tou Wei. This technique is believed to stimulate the release of serotonin and other chemicals in the brain more effectively, resulting in better treatment outcomes, explained Dr. Zhang-Jin Zhang of the School of Chinese Medicine, University of Hong Kong, who developed the technique. In a randomized controlled trial, Zhang and colleagues tested DCEAS vs placebo acupuncture (noninvasive electroacupuncture) in 73 MDD patients aged 25 to 65 years. Treatment was given in nine sessions over 3 weeks, each session lasting 45 minutes. Patients continued their current antidepressant (fluoxetine) throughout the study. Results showed that DCEAS rapidly reduced the severity of depressive symptoms, with improvement seen in the DCEAS group as early as day 3. According to Zhang, the improvement lasted till the end of the study, with no significant adverse events being observed. On day 21 post treatment, patients in the DCEAS group had greater reductions in the

17-item Hamilton Depression Rating Scale scores (between-group difference, 2.39 points) and Self-rating Depression Scale scores (between-group difference, 4.68 points) than those in the control group. Clinical response rate was 19.4 percent in the DCEAS group vs 8.8 percent in the control group. The findings suggest that DCEAS is a safe and effective additional treatment option for patients with MDD, said Zhang. The study was conducted jointly with the Department of Psychiatry, Kowloon Hospital. Another clinical trial is ongoing to explore the mechanisms of the antidepressant effects of DCEAS using of PET and functional MRI imaging techniques. [http://www3.hku.hk/ chinmed/PET-RCT.html]

39
May

May 2012

Calendar
The International Digestive Disease (IDD) Forum Institute of Digestive Disease, CUHK 9/6-10/6 Info: Swire Travel Tel: (852) 3151 8900 Fax: (852) 2590 0099 E-mail: iddf2012@swiretravel.com www.iddforum.com Annual Scientific Meeting 2012 Hong Kong Society of Dermatology and Venereology 10/6 Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 / 2116 4348 Fax: (852) 2559 6910 E-mail: meeting.hk@ubm.com 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 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

17th Hong Kong Medical Forum Department of Medicine, HKU; Queen Mary Hospital 12/5-13/5 Tel: (852) 2255 4607 Fax: (852) 2855 1143 www.hku.hk/medicine/hkmf 9th Hong Kong International Orthopedic Forum Orthopedics and Pain Department of Orthopedics & Traumatology, HKU 26/5-27/5 Info: Ms. Chang Tel: (852) 2255 4257 www.hku.hk/ortho/forum2012 Advanced Laparoscopic Urology Workshop Department of Surgery, Pamela Youde Nethersole Eastern Hospital; Hong Kong Urological Association 28/5 Tel: (852) 2595 6362 Fax: (852) 2505 7101 E-mail: pyneh_mastc@ha.org.hk www.ha.org.hk/mastc

June
Advances in Medicine 2012 Department of Medicine & Therapeutics, CUHK 2/6-3/6 Info: Ms. Priscilla Chu / Ms. Flora Lo Tel: (852) 2632 3593 / 2632 3307 Fax: (852) 2637 3852 E-mail: priscillachu@cuhk.edu.hk / floralo@cuhk.edu.hk www.mect.cuhk.edu.hk/AIM2012/index.htm Hong Kong Primary Care Conference Hong Kong College of Family Physicians 2/6-3/6 Info: Ms. Crystal Yung / Ms. Priscilla Li Tel: (852) 2861 0220 Fax: (852) 2866 0981 E-mail: hkpcc@hkcfp.org.hk www.hkcfp.org.hk/

July
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

40

May 2012

Calendar
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

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 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 3rd Oncology Forum of Hong Kong Hong Kong College of Radiologists; Hong Kong Society of Clinical Oncology 21/7 Info: PC Tour and Travel Ms. Veronica Cheng / Miss Rachel Lee 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 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

September
Transcatheter Renal Denervation (TREND) 2012 Asia-Pacific 29/9 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

October
14th Hong Kong Diabetes and Cardiovascular Risk Factors East Meets West Symposium 1/10-2/10 Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 / 2116 4348 Fax: (852) 2559 6910 E-mail: info@eastmeetswest.org.hk www.eastmeetswest.org.hk Annual Scientific Meeting 2012 Hong Kong Society of Pediatric Respirology 8/10 Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 / 2116 4348 Fax: (852) 2559 6910 E-mail: meeting.hk@ubm.com www.hkspr.org

August
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

November
23rd Video Urology World Congress 2012 Hong Kong Urological Association 8/11-11/11 Tel: (852) 2632 2644 Fax: (852) 2632 4708 E-mail: info@videourology2012.com www.videourology2012.com/default.asp

41

May 2012

Calendar

7th International Huaxia Congress of Endocrinology Hong Kong Society of Endocrinology, Metabolism and Reproduction 30/11-2/12 Info: Ms. Veronica Cheng Tel: (852) 2734 3312 Fax: (852) 2367 3375 E-mail: huaxia2012@pctourhk.com www.endocrine-hk.org/huaxia2012poster.jpg

December
4th Asian Preventive Cardiology & Cardiac Rehabilitation Conference Hong Kong College of Cardiology 1/12-2/12 Info: Ms. Lynn Lam / Ms. Queenie Wong Tel: (852) 2911 7902 / 2911 7923 Fax: (852) 2893 0804 E-mail: apccrc@mci-group.com www.hkcchk.com/scientificcongress.php 3rd HK-UK Joint International Conference Mental Health for All Hong Kong College of Psychiatrists; Royal College of Psychiatrists (UK) 8/12-10/12 Tel: (852) 2734 3312 Fax: (852) 2367 3375 E-mail: conference@pctourshk.com www.psychconference.org.hk 17th Congress of the APSR Hong Kong 2012 Hong Kong Thoracic Society 14/12-16/12 Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 / 2116 4348 Fax: (852) 2559 6910 E-mail: info@apsr2012.org www.apsr2012.org/

GO DEEP. DO MORE.

42
May

May 2012

Calendar
19th WONCA Asia Pacific Regional Conference 24/5/2012 to 27/5/2012 Location: Jeju, Korea Tel: (82) 2 566 6031 Email: admin@woncaap2012.org Website: www.woncaap2012.org

5th European Clinam Conference for Clinical Nanomedicine 7/5/2012 to 9/5/2012 Location: Basel, Switzerland Info: Clinam, European Foundation for Clinical Nanomedicine Tel: (11) 41 61 695 9395 Fax: (11) 41 61 695 9390 Email: clinam@clinam.org Website: www.clinam.org 19th European Congress on Obesity 9/5/2012 to 12/5/2012 Location: Lyon, France Info: European Association for the Study of Obesity Tel: (44) 20 8783 2256 Fax: (44) 20 89796700 Email: enquiries@easo.org Website: www.eco2012.org American Thoracic Society International Conference 2012 18/5/2012 to 23/5/2012 Location: San Francisco, California, US Tel: (1) 212 315 8652 Email: conference@thoracic.org Website: www.thoracic.org/go/international-conference American Society of Hypertension 19/5/2012 to 22/5/2012 Location: New York, New York, US Info: American Society of Hypertension Tel: (1) 212 696 9099 Fax: (1) 212 696 0711 Email: symposia@ash-us.org Website: www.ash-us.org/Scientific-Meetings/FutureMeetings.aspx Digestive Diseases Week 2012 19/5/2012 to 22/5/2012 Location: San Diego, California, US Info: American Society of Gastrointestinal Endoscopy Tel: (1) 301 272 0022 Fax: (1) 301 654 3978 Email: nmurphy@gastro .org Website: www.ddw.org

June
2012 American Society of Clinical Oncology Annual Meeting 1/6/2012 to 5/6/2012 Location: Chicago, Illinois, US Tel: (1) 571 483 1300 Email: membermail@asco.org Website: chicago2012.asco.org 10th Royal College of Obstetricians and Gynecologists International Scientific Congress 5/6/2012 to 8/6/2012 Location: Kuching, Malaysia Tel: (60) 3 6201 1858 Email: info@rcog2012.com Website: www.rcog2012.com 15th International Congress of Infectious Diseases 13/6/2012 to 16/6/2012 Location: Bangkok, Thailand Tel: (1) 617 277 0551 Fax: (1) 617 278 9113 Email: info@isid.org Website: www.isid.org/icid 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

43

May 2012

Calendar

Upcoming
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 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 World Allergy Organization International Scientific Conference (WISC 2012) 6/12/2012 to 9/12/2012 Location: Hyderabad, India Info: World Allergy Organization Tel: (1) 414 276 1791 Fax: (1) 414 276 3349 E-mail: WISC@worldallergy.org Website: www.worldallergy.org

44

May 2012

After Hours

The Science of Flavors in Food

Radha Chitale

he harmony of a delicious meal is often called a labor of love, but it is also the evolutionary product of history, culture and good chemistry. Chefs and scientists have long tried to describe the underlying patterns of tasty dishes. Within the last decade, a theory of flavor pairings has emerged stating that ingredients sharing flavor compounds are more likely to taste good together than ingredients that dont, which can lead to unexpected combinations. For example, analysis of shared compounds landed white chocolate and caviar together on upscale menus around the world the two shared the fishy chemical trimethylamine, among others. But new research using flavor networks has shown that the food pairing principle is both true and not true, and is significantly linked to region. Such studies expand scientific understanding about what tastes good. Harnessing patterns in how people combine foods could help develop new products that benefit health without compromising the palate. An amateur interest in molecular gastronomy led Dr. Sebastian Ahnert, a fellow in the Theory of Condensed Matter Group of the Cavendish Laboratory at University of Cambridge in the UK, to apply the theory of complex networks to flavor compounds, one of the basic components of flavor, besides odor

45

May 2012

After Hours
quent use of beef, ginger, pork, cayenne, chicken and onion. They also identified a handful of authentic ingredients that instantly bind a flavor to a cuisine soy sauce, sesame oil, rice and ginger instantly skew a dish Asian. Paprika, onion and lard would, on the other hand, be a signature of Hungarian food. Although food scientists do not cite health benefits as the primary driver of cuisine evolution, rather emphasizing the importance of history, economics, climate and regional habits, Ahnert said the flavor network approach could be used to predict novel flavor combinations to create a wider, more attractive variety of health options. Food and medicine already intersect in some cuisines Many flavor ingredients [such as curcumin in turmeric or ginseng] have antioxidant properties or a bioactive component, said Dr. Liu Sho Quan, of the Food Science and Technology Programme and the department of chemistry at the National University of Singapore, though large randomized trials investigating their effects are rare. A central component of traditional Chinese medicine (TCM) is the use of heating and cooling foods to balance the bodys energy that together may have a synergistic effect for health, Liu added. Dr. Christopher Loss, director of the depart-

and freshness, to uncover the patterns behind how people combine ingredients. Ahnert and colleagues at Harvard University and Indiana University in the US mined 56,498 recipes from the US recipe database sites Allrecipes. com and Epicurious.com and the Korea-based site menupan.com, to compile a list of 381 basic ingredients and 1,021 flavor compounds found in them. [Sci Rep 2011;1:196. Epub 2011 Dec 15] Statistical analysis yielded a bipartite flavor network that shows the connectedness of any two ingredients based on how many flavor compounds they share. Fruits are connected to each other and share many flavor compounds with wine and tea, while mushrooms inhabit a flavor island of their own. But when the researchers grouped the ingredients by cuisine, the principle of flavor pairing proved to be untrue for Asian food. In North American [and Western European] recipes, the more compounds are shared by two ingredients, the more likely they appear in recipes. By contrast, in East Asian cuisine the more flavor compounds two ingredients share, the less likely they are to be used together, they said. The researchers found that the iconic harmony or dissonance, respectively, of the regional foodscape is dominated by ingredients including milk, butter, cocoa, vanilla, cream, eggs and peanut butter in North American cuisine, while East Asian cuisine makes fre-

46

May 2012

After Hours
director of Client Insights and Sensory Science at the culinary consultancy In4mation Insights in Boston, Massachusetts, suggested that food networks could be used to create combinations with specific functions, such as weight loss or sugar free/diabetic. Food combinations could also be modelled to fit a nutritional profile. An elderly person may need a diet that focuses on soluble fiber, calories, B vitamins, omega-3 fatty acids, iron and phytosterols. Incorporating human behavior when building the flavor network can help identify the foods consumers will like that also fulfil the desired nutritional profile. These network approaches, for the first time are able to attempt to explain extremely complex patterns in how people consume food that previously we were unable to model because we didnt know how, Nestrud said.

ment of menu research and development at the Culinary Institute of America in Hyde Park, New York, US, said Ahnert and colleagues approach could be used in reverse by beginning with ingredient combinations known to be healthful and mining the flavor network to find combinations that make them taste better. It does not provide a formula per se, but can help catalyze the ideation process at the front end of research and development, he said. Developing positive hedonic flavor quality is the forte of the chef. Dr. Michael Nestrud, a food scientist and

47

May 2012

Humor

Smile, youre on Candid Camera!

If you think these pills are too expensive, we will be more than happy to operate!

Sorry folks, Im running a little behind today!

Forget about possible damage to my liver. Will it make my skin smoother?

Nurse, theres a fly in my IV!

In order to qualify for medical benefits you have to be 65, not feeling like 65!

Publisher

: Ben Yeo

Korea

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: K  evin Yi Tel: (822) 3019 9350 Email: inquiry@kimsonline.co.kr : I rene Lee, Lee Pek Lian, Sumitra Pakry, Grace Yeoh Tel: (603) 7954 2910 Email: enquiry.my@ubmmedica.com : M  arian Chua, Julie Mariano, Philip Katipunan Tel: (632) 886 0333 Email: enquiry.ph@ubmmedica.com : J  ason Bernstein, Carrie Ong, Elijah Lee, Reem Soliman Tel: (65) 6223 3788 Email: enquiry.sg@ubmmedica.com : W  ipa Sriwijitchok Tel: (662) 741 5354 Email: enquiry.th@ubmmedica.com : N  guyen Thi Lan Huong, Nguyen Thi My Dung Tel: (848) 3829 7923 Email: enquiry.vn@ubmmedica.com

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Medical Tribune is published 12 times a year (23 times in Malaysia) by UBM Medica, a division of United Business Media. Medical Tribune is on controlled circulation publication to medical practitioners in Asia. It is also available on subscription to members of allied professions. The price per annum is US$48 (surface mail) and US$60 (overseas airmail); back issues at US$5 per copy. Editorial matter published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great effort has been made in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The information contained within should not be relied upon solely for final treatment decisions. 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Philippine edition: Entered as second class mail at the Makati Central Post Office under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Bldg, 28 Lee Chung Street, Chai Wan, Hong Kong. ISSN 1608-5086

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