The Brillo Pad

Robotic navigation set to guide arrhythmia treatment in SE Asia

2009-10-23T03:22:00.000-07:00

Medical Tribune October 2009 P4
David Brill

Cardiac arrhythmia patients can be treated faster, more safely and with less radiation exposure, following the unveiling of a cutting-edge robotic system at the National Heart Centre Singapore (NHCS).

The technology allows electrophysiological catheter ablation to be done by remote control, using magnets to guide the catheter to its target with dexterity that cannot be achieved by hand.

Cardiologists direct proceedings from a computer workstation – sparing them from neck and back pain that can result from manual ablation procedures, which last up to 6 hours. Procedural time is expected to drop to 2-3 hours with the magnetic navigation system.

Twelve patients have already been treated with the system, which is the first of its kind in Southeast Asia.

“The robotic magnetic navigation system can allow us to safely map the heart to 1 to 2 mm accuracy and precision without the use of fluoroscopy,” said Dr. Teo Wee Siong, director of electrophysiology and pacing and senior consultant cardiologist at NHCS.

“This precision cannot be achieved by conventional ablation with our hands manually, no matter how skilled we are. This will definitely improve patient outcome and safety, especially in complex arrhythmia cases such as atrial fibrillation and ventricular tachycardia,” he said.

The procedure eliminates physician radiation exposure and lowers patient exposure by 40 percent compared with conventional ablation. The new catheters are also softer and more flexible than manually operated versions, thereby reducing the risk of damaging the heart walls from 2-3 percent to less than 1 percent.

The feasibility of magnetic navigation systems for catheter ablation was first demonstrated 7 years ago in dogs and pigs. [Circulation 2002;106:2980] The intervening years have seen the technology evolve and progress to human usage, with centers in the US, Italy and Germany among the first to report their results. Some procedural times were initially longer than conventional ablation, but have shortened with growing experience.

Most recently, the Texas Cardiac Arrhythmia Institute, US, reported success in 164 of 193 robotic catheter ablations (85 percent), compared to 159 of 197 manual ablations (81 percent). Mean exposure to fluoroscopy was slightly increased for the first 50 procedures performed with the robotic system (61.8 minutes versus 58.4 minutes for conventional ablation), but dropped to 44.5 minutes over subsequent procedures. [J Cardiovasc Electrophysiol 2009 Jul 28; Epub ahead of print]

NHCS sees around 300 patients each year requiring catheter ablation and an implantable cardioverter-defibrillator. It estimates that around 60 percent of cases could be treated with the new magnetic navigation system.

Aspirin ineffective for primary CVD prevention

2009-10-23T03:20:00.001-07:00

Medical Tribune October 2009 P6

David Brill

Aspirin should not be used routinely for primary prevention of cardiovascular disease in people with asymptomatic atherosclerosis, results of a randomized trial suggest.

The Aspirin for Asymptomatic Atherosclerosis (AAA) study found that daily aspirin (100mg) did not significantly reduce vascular events compared to placebo, but increased rates of hemorrhage and gastrointestinal complications.

The trial involved 3,350 Scottish men and women aged 50 to 75 who had a low ankle brachial index (ABI; ≤ 0.95) – indicative of peripheral atherosclerosis. They were followed up for a mean of 8.2 years for primary outcomes of coronary events, stroke and revascularization.

A total of 357 study subjects experienced a vascular event: 181 in the aspirin group and 176 in the placebo group (hazard ratio 1.03, 95% CI 0.84 – 1.27). Secondary outcomes, including angina, transient ischemic attack and all-cause mortality, were also not significantly different between groups.

“There is no support for the routine use of aspirin for the prevention of vascular events in the context of ABI screening in the general population,” said study investigator Professor Gerald Fowkes of the University of Edinburgh, UK.

“It is possible that in the general population, aspirin could produce a smaller reduction in vascular events than this trial was powered to detect, but it is questionable whether such an effect, together with aspirin related morbidity, would justify the additional resources and health care requirements of an ABI screening program,” he said.

Fowkes noted that compliance is lower in the primary prevention setting, adding: “Whether aspirin is beneficial in clinical practice in a patient with a low ABI who was fully compliant with the medication is unknown, so our results cannot be extrapolated into that situation.”

Thirty four major hemorrhages occurred in the aspirin group and 20 in the placebo group (2 percent versus 1.2 percent; hazard ratio 1.71; 95% CI 0.99 – 2.97). There were 14 and eight cases, respectively, of gastrointestinal ulcers (0.8 versus 0.5 percent).

The efficacy of aspirin is well established for secondary prevention in patients with a history of cardiovascular disease, but the risk-benefit ratio for primary prevention in low-risk individuals remains less clear. A recent meta-analysis of six primary prevention trials found that aspirin reduced rates of serious vascular events by 12 percent, but increased major gastrointestinal and extracranial bleeds. [Lancet 2009;373:1849-60]

Recent studies have also questioned the use of aspirin for primary prevention in diabetic patients – a common practice which is advocated in international guidelines. [BMJ 2008;337:a1840]

New biomarker tests could slash heart attack diagnosis time

2009-10-23T03:18:00.001-07:00

Medical Tribune October 2009 P7
David Brill

New-generation tests can rapidly accelerate the diagnosis of acute myocardial infarction (MI) – saving time, improving convenience and reducing costs in the emergency department, studies show.

High-sensitivity cardiac troponin assays can now rule MI in or out in patients presenting within the first hours of chest pain onset, thereby removing the delays associated with conventional tests and allowing for earlier transfer and treatment.

Testing for stress marker copeptin, meanwhile, can exclude MI with 99 percent certainty, thus saving many patients from unnecessary further testing.

Professor Christian Müller, reviewing the data, said that the new tests could answer an unmet clinical need in the assessment of chest pain, since current troponin tests have an undetectable “blind interval” of 3-4 hours after the onset of MI. Even if patients follow recommendations and present within 2 hours of chest pain, the test will be negative and electrocardiography monitoring will be required for 6 to 8 hours.

“The current-generation troponin tests are important but have important limitations in [making an] early diagnosis. There seem to be two approaches to solve this problem: either use troponin in combination with copeptin, or perhaps the approach now favored by many is the use of sensitive troponin assays,” said Müller, of the University Hospital Basel, Switzerland.

The new troponin assays were tested in two European multicenter trials, published recently in the New England Journal of Medicine. [2009;361:858-67; 2009;361:868-77]

German investigators tested 1,818 consecutive patients at admission and 3 and 6 hours later. Diagnostic accuracy at admission was higher with a sensitive troponin I test, as compared to a conventional troponin T test (area under the receiver-operated-characteristic curve [AUC] 0.96 versus 0.85). The new test had a clinical sensitivity of 90.7 percent and specificity of 90.2 percent, with accuracy unaffected by the time of chest pain onset.

The second study, led by Müller and colleagues, involved 718 consecutive patients – 123 of whom were ultimately diagnosed with acute MI. Four high-sensitivity assays were tested: all were superior to a conventional test (AUCs 0.95 – 0.96 versus 0.90) when performed at presentation. The difference was most marked in patients presenting within 3 hours of chest pain onset (AUCs 0.92 – 0.94 versus 0.76).

In an earlier study, Müller and colleagues tested 487 potential MI patients for copeptin, the C-terminal section of the vasopressin prohormone, which denotes endogenous stress. Combination with a conventional troponin T test yielded an AUC of 0.97, compared to 0.86 for the troponin test alone (P<0.001). Low levels of both copeptin (<14 pmol/l) and troponin T (≤0.01 μg/l) correctly excluded MI in the majority of cases (sensitivity 98.8 percent; negative predictive value 99.7 percent). [J Am Coll Cardiol 2009;54:60-8]

ESC offers guidance on syncope workup

2009-10-23T03:15:00.000-07:00

Medical Tribune October 2009 P9

David Brill

The European Society of Cardiology has updated its guidelines to facilitate the diagnosis and management of syncope – a common clinical challenge for GPs and specialists alike.

A novel diagnostic workflow promotes early risk stratification – enabling prompt treatment for those who need it and avoiding unnecessary therapy for those who don’t.

New emphasis is also placed on prolonged monitoring for patients with benign but recurrent syncope, which can adversely affect quality of life.

The guidelines reflect a multidisciplinary collaboration and have been endorsed by leading European and American societies, ranging from emergency medicine to geriatrics and neurology.

The authors recommend that initial evaluation be performed to divide patients into syncope or non-syncopal loss of consciousness. Genuine cases of syncope should then be divided into certain and uncertain diagnosis – with risk stratification performed for the latter.

“In the vast majority of the population the cause of syncope is something very benign and it has no consequences for the patient. But in some, syncope can be the herald of a severe cardiac arrhythmia or even the first manifestation of a future sudden death, so it is important to recognize in which patients it is severe and in which patients it is benign,” said task force chairman Professor Angel Moya, of the University Hospital Vall d’Hebron in Barcelona, Spain.

The authors have also revised the definition of syncope itself, such that reduced cerebral blood flow is now a prerequisite for diagnosis. They define syncope as: “a transient loss of consciousness due to transient global cerebral hypoperfusion characterized by rapid onset, short duration and spontaneous complete recovery.”

“Without this diagnostic addition the definition of syncope becomes wide enough to include other disorders such as epileptic seizures and concussion. In fact [it] would be nothing more than ‘loss of consciousness,’ irrespective of mechanism and duration,” said Moya.

Syncope is a common problem, thought to affect up to 50 percent of people at least once in their lifetime. The three most common types identified in the guidelines are reflex syncope, orthostatic hypotension and cardiac syncope.

Reflex syncope results from an alteration of the cardiovascular reflexes that control circulation, leading to hypotension and reduced cerebral blood flow. Orthostatic hypertension is typically a recurring event resulting from circulatory abnormalities, which may also cause other symptoms such as dizziness and palpitations. Cardiac syncope is more serious, and is usually a sign of an underlying arrhythmia which should be treated.

The new guidelines – developed in collaboration with the European Heart Rhythm Association, the Heart Failure Association and the Heart Rhythm Society – were published online in the European Heart Journal. [2009 Aug 27; Epub ahead of print]

Experts back healthy lifestyle in battle against CVD

2009-10-23T03:13:00.000-07:00

Medical Tribune October 2009 SFV
David Brill

The drive to promote healthy living is gathering fresh momentum, with the publication of two major new studies suggesting substantial potential to tackle cardiovascular disease at a population-wide level.

Fourteen-year follow-up of over 83,000 healthy women in the Nurses’ Health Study showed that those who ate well, exercised and had lower BMI were considerably less likely to develop hypertension – the leading preventable contributor to death in women.

The Physicians’ Health Study, meanwhile, reported that keeping healthy significantly reduced the risk of developing heart failure over 22 years in a cohort of some 21,000 men. Those who followed at least four out of six healthy habits had a 10.1 percent lifetime risk of developing heart failure, compared to 21.2 percent for men who followed none of the six.

Both Asian and international experts are calling for a renewed focus on public health promotion in light of the data.

Dr. Goh Ping Ping, medical director of the Singapore Heart Foundation and chief of cardiology at Changi General Hospital, said that a lot of work remains to be done at the community level and urged doctors to “take a very proactive role”, particularly with opportunistic screening.

“Even if a patient comes in for a medical problem that is not directly related to the heart or to hypertension, [doctors] could also take the opportunity to check their blood pressure, or educate them on these very simple lifestyle principles,” she said, adding that further educational materials should be kept on hand for such cases.

An editorial accompanying the two papers noted that the “powerful simplicity” of the message begs a rethink on the very concept of lifestyle, which is often perceived to be an individual choice. Rather, it is an interaction between personal and societal factors that defines the approach to cardiovascular disease prevention, according to Dr. Véronique Roger of the Mayo Clinic, Minnesota, US. [JAMA 2009;302:437-439]

“The studies … underscore that healthy lifestyle will help prevent cardiovascular disease and greatly enhance health, which is a compelling reminder that health is the shared responsibility of individuals and communities. This in turn implies that public health policies and clinical care must join forces to achieve effective disease prevention,” she wrote.

The Nurses’ Health Study enrolled 83,882 women aged 27 to 44 in 1991, and followed them up until 2005. [JAMA 2009;302:401-11]

BMI, exercise, alcohol intake, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, use of non-narcotic analgesics and folic acid supplementation were all independently associated to risk of developing hypertension. Women who scored well on all six factors had a hazard ratio of just 0.22 (95% CI 0.10 – 0.51) for incident hypertension. Such healthy livers, however, comprised just 0.3 percent of the population.

The Physicians’ Health Study involved 20,900 men with a mean age of 53.6 at enrollment in 1982, with follow-up until 2008 (mean 22.4 years). [JAMA 2009;302:394-400]

Six lifestyle factors were also assessed: smoking, exercise, body weight, alcohol intake, consumption of fruits and vegetables, and consumption of breakfast cereals. Again, all factors were independently and jointly linked to an increased risk of heart failure.

Singapore’s Health Promotion Board welcomed the studies as “good evidence as to the importance of a healthy lifestyle,” given their size and robust data.

“A large proportion of chronic disease amongst the Asian population can be attributed to lifestyles, i.e. eating habits and lack of physical activity,” said Dr. Shyamala Thilagaratnam, director of the Healthy Ageing Division. “Therefore encouraging Singaporeans to lead a healthy lifestyle is likely to be useful in reducing the burden of chronic disease. Singaporean and other Southeast Asian doctors should use this as good evidence to promote the adoption of a healthy lifestyle amongst their patients.”

Goh added that it is important to adapt the messages of the studies to match local cultures and habits.

“Our dietary patterns are quite different – they talk about cereals for breakfast but that probably doesn’t apply too well here. It’s probably more about telling people not to have nasi lemak or roti prata, for example, and to substitute with something else,” she said.

Jury still out on clinical exams for breast cancer screening

2009-10-23T03:09:00.000-07:00

Medical Tribune October 2009 P12

David Brill

Controversy looks set to continue over the benefits of clinical breast examination (CBE) for cancer screening, following the publication of a large population-based study which could raise as many questions as answers.

Results from the Ontario Breast Screening Program show that adding CBE to mammography improves cancer detection rates, but considerably increases the number of false-positive results.

For every 10,000 women screened, the addition of CBE would detect four more cancers but expose 219 women to unnecessary further testing – along with its extra risks, costs and anxiety.

This risk-benefit ratio must be weighed up carefully, and women should be fully informed before consenting to CBE, wrote the researchers, led by Dr. Anna Chiarelli of Cancer Care Ontario, Toronto Canada. [J Natl Cancer Inst 2009 Aug 31; Epub ahead of print]

They screened 290,230 women aged 50 to 69 between 2002 and 2003, and followed them up for 12 months. Of these women, 232,515 received mammography plus CBE at 68 centers (nine regional and 59 affiliated), whereas 57,715 received mammography alone at 34 affiliated centers.

US experts called it “a steep price” for adding CBE to mammography but reserved judgment on how the findings should influence practice, concluding in an editorial that “more answers are needed on the role of CBE in breast cancer screening before definitive recommendations for or against its use can be made.”

“While we wait for those answers, the data presented by Chiarelli et al. suggest that CBE must be done well if it is to be done at all, with the acknowledgment that overall referrals and false-positive results will increase,” wrote Drs. Mary Barton and Joann Elmore, of the Agency for Healthcare Research and Quality, Rockville, and the University of Washington School of Medicine, Seattle, respectively. [J Natl Cancer Inst 2009 Aug 31; Epub ahead of print]

Barton and Elmore also called for the creation of universal standards for CBE, noting that inconsistency in the duration of examinations and the search pattern used can affect the accuracy of the test. They note that the highest-volume centers in the Ontario study also had the highest sensitivities and lowest false-positive rates – an observation which supports their case for standardization.

CBE has been advocated in some quarters since it can detect cancers which are missed by mammography – the gold standard for breast cancer screening. It has yet to be demonstrated conclusively, however, that addition of CBE to screening actually reduces mortality.

The practice is common in the US: one report found that 18 percent of screening centers surveyed performed CBE routinely alongside mammography, while another study found that 65 percent of women reported having CBE in the preceding 2 years. [Open Clin Cancer J 2008;2:32-43; AJR Am J Roentgenol 2005;184:433-8]

Breast cancer was traditionally less common in Asia than the West but rates are rising rapidly. In Singapore, the only Asian country with a national breast cancer screening program, it is now the number one cancer among women. The incidence rose 2.5-fold between 1968 and 2002, according to data from the national cancer registry.

First-line screening in the BreastScreen Singapore program is with mammography alone. CBE is included among possible follow-up tests, along with ultrasound, repeat mammography and biopsy.

Breast cancer has also become the leading cancer among women in Hong Kong – responsible for 21 percent of cancer cases in 2002. A self-referral, opportunistic mammography screening program at the Tung Wah Group of hospitals was shown to improve early detection and prognosis after 46,637 mammograms, with comparable results to Western programs. Screening was well received by the community, and the model has been proposed as a basis for a national program. [Hong Kong Med J 2007;13:106-13c]

Surveys in both Singapore and Hong Kong have shown, however, that public knowledge about breast cancer and screening is low, and myths and misconceptions are common. Only 57 percent of Singaporean women aged 40 and above had gone for a screening mammogram, while 58 percent of Hong Kong women had never even heard of mammographic screening. [Singapore Med J 2009;50:132-8; Breast J 2005;11:52-6]

Concerns grow over Cambodia’s “AIDS colony”

2009-10-22T00:09:00.000-07:00

The Lancet September 2009

The forced eviction of HIV-aff ected families from Phnom Penh has drawn criticism from human rights groups, amid fears for their health and access to treatment and care. David Brill reports.

On the outskirts of Phnom Penh stands a makeshift village of green metal shacks. There is little food, no clean water, and open sewers that flow alongside the buildings. More than 40 families live in the settlement, each occupying a space no bigger than 4 m by 5 m. All have one thing in common: each has at least one member who is HIV positive.

The residents of Tuol Sambo are just a few of the thousands of people who have been evicted from central Phnom Penh in recent years but their plight has captured international attention. Resettlement began in June, when 20 families were moved from the central Borei Keila neighbourhood to their new home outside the city. The eviction, to make way for a new Ministry of Tourism development, had been planned for some time, and went ahead despite appeals from the UN and other groups. The remainder of the families followed in July.

Far from the treatment and services they need, there are now fears that their health is declining amid the cramped, unsanitary conditions. Moreover, their isolation from nearby settlements has created a “de-facto AIDS colony” which promotes stigmatisation and discrimination, over 100 human rights and HIV/AIDS activists said in a recent open letter to Cambodian leaders. The letter called on the government to improve the “grossly inadequate” housing conditions at Tuol Sambo, guarantee access to medical services and stop moving people there.

Morale is already low among the residents of Tuol Sambo, according to Sara Colm of Human Rights Watch (HRW). Living conditions were no better in Borei Keila but people were close to medical care and had access to livelihoods, she said. “Some of them have a good fighting spirit…but it’s being whittled down by this sense that they’ve been banished out of town to this remote site. They don’t have much hope, and don’t know what their future is”, she said.

Medical care at Tuol Sambo is presently limited to mobile clinic visits every week from the Sihanouk Hospital Centre of Hope (SHCH) in Phnom Penh, which provides free antiretroviral therapy and treatment for opportunistic infections. Gerlinda Lucas, grants programme manager at SHCH, confi rmed that this arrangement will remain in place while funding is available presently until August next year. Residents have reported diarrhoea, fever, and cough since moving to Tuol Sambo, she added. Lucas also admitted concerns about the longer-term eff ect of the living conditions, particularly since temperatures can become stifling inside the metal shacks and could pose a problem for the storage of drugs. Some of the residents have already told HRW that their drugs are deteriorating in the heat.

The Cambodian Government, which has been praised in the past for its HIV/AIDS programmes, has told UN officials that disruption to treatment will be minimised and that a nearby health centre will be developed to provide antiretroviral therapy. The timeline and details of this, however, are unclear. The UN intends to visit Tuol Sambo shortly, along with government representatives, and will continue to “follow up vigorously on the treatment and broader health issues”, UNAIDS Cambodia coordinator Tony Lisle told The Lancet. Offi cials are also working
on the wider picture of evictions and resettlements in Cambodia, and pressing for the development of coherent national guidelines, he added.

Although continuity of treatment at Tuol Sambo has been discussed, other issues such as segregation remain unresolved. Set apart from nearby communities, the HIV-positive families have faced theft, discrimination from neighbours, and attacks from gangs, according to Prum Dalish of the Cambodian Community of Women Living with HIV and AIDS. “When the children go to school, the other children don’t want to play with the [HIV] positive children. These kinds of problems can make their health worse and worse”, she said.

HRW says it has yet to receive an official response to the letter decrying the conditions at Tuol Sambo, despite showing it to Cambodian minsters days before its public release. In the meantime, the families at Tuol Sambo face an uncertain future. “We’re heading into the rainy season now, which comes with flooding and disease”, said Colm.

New HIV strain came from gorillas

2009-10-20T03:22:00.002-07:00

Medical Tribune September 2009 P3

French scientists have identified a new strain of HIV, which appears to have evolved in gorillas before crossing the species divide.

The virus has a distinct lineage from other HIV strains – notably the one chiefly responsible for the current AIDS pandemic, which is thought to have reached humans from chimpanzees. The researchers, who found the virus in a 62-year-old Cameroonian woman living in Paris, propose calling the new strain HIV-1 group P.

“The discovery of this novel HIV-1 lineage highlights the continuing need to watch closely for the emergence of new HIV variants, particularly in western central Africa, the origin of all existing HIV-1 groups,” they wrote.

[Nat Med 2009 Aug;15(8):871-2]

New fears raised over hormone therapy cancer risk

2009-10-20T03:22:00.001-07:00

Medical Tribune September 2009 P3

A new study of almost a million people has strengthened the link between postmenopausal hormone therapy and the risk of developing ovarian cancer.

Danish researchers reviewed registry data from 909,946 women aged 50 to 79, over an average of 8 years of follow up. They found that hormone therapy users had an incidence rate ratio of 1.38 (95 percent CI 1.26 – 1.51) for all ovarian cancers, compared to women who had never used therapy. Cancer risk was increased “regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type and route of administration,” the authors wrote.

“Thus the risk of ovarian cancer is one of several factors to take into account when assessing the risks and benefits of hormone use,” they concluded.

[JAMA 2009 Jul 15;302(3):298-305]

Study flaws hinder review of TCM for stroke

2009-10-20T03:22:00.000-07:00

Medical Tribune September 2009 P3

The poor quality of published data prevents a proper assessment of the efficacy of traditional Chinese medicine (TCM) remedies for stroke, a study suggests.

Despite finding 11,234 journal articles on TCM post-stroke therapies, the researchers from Italy and China were unable to conduct a meta-analysis as intended. Thirty four randomized controlled trials (RCTs) were found, but wide variation in the studies prevented them from being pooled. Moreover, all but one RCT reported results in favor of TCM, prompting the authors to suggest a “strong publication bias.”

“The key to lead to evidence-based practices is establishing a consensus on standardized relevant outcome measures and then designing and conducting appropriate RCTs that adopt those standards,” they wrote.

[Stroke 2009 Aug;40(8):2797-804]

Famotidine protects against aspirin GI damage

2009-10-20T03:20:00.000-07:00

Medical Tribune September 2009 P6
David Brill

Histamine H2-receptor antagonists can limit the gastrointestinal side effects of low-dose aspirin and could offer a viable alternative to proton-pump inhibitors (PPIs), a recent study suggests.

The randomized, phase III FAMOUS* trial found that 12 weeks of treatment with famotidine significantly reduced the incidence of gastric ulcers, duodenal ulcers and erosive esophagitis compared to placebo.

The study, published in The Lancet, included 404 adults who were taking low-dose aspirin and had no ulcers or esophagitis at baseline. [2009;374:119-25]

Aspirin use continues to soar worldwide, yet there are few options for prevention of associated gastrointestinal complications. PPIs are known to be effective but have faced safety concerns – particularly over the risk of adverse interactions with clopidogrel.

“There is little doubt that aspirin and other anti-clotting drugs are very useful in the prevention of heart, brain, and other vascular diseases, hence their increasing use worldwide. Patients on such drugs should continue using them as advised by their family doctors or hospital specialists,” said the study’s lead author Dr. Ali Taha, of the University of Glasgow, UK.

“However, everybody should be aware that aspirin use can also be associated with a variety of gastrointestinal or digestive system problems, which sometimes can be serious. The results of this research widen the options for the prevention of such problems, particularly when more than one clotting drug is required,” he said.

Twelve weeks after randomization, 7 of 204 patients on famotidine had developed gastric ulcers, compared to 30 of 200 taking placebo (3.4 percent versus 15 percent; odds ratio 0.2; P=0.0002).

Just one patient developed a duodenal ulcer on famotidine, compared to 17 on placebo (0.5 percent versus 8.5 percent; OR 0.05; P=0.0045). Nine and 38 patients developed erosive esophagitis in the famotidine and placebo groups, respectively (4.4 percent versus 19 percent; OR 0.2; P<0.0001).>

Diabetic children often oblivious to hypoglycemia

2009-10-20T03:19:00.001-07:00

Medical Tribune September 2009 P7

David Brill

Almost one in three children with type 1 diabetes cannot tell when their blood sugar dips low, and could face serious consequences from slipping into hypoglycemia, a study suggests.

A survey of 656 Australian children found that 29 percent had impaired awareness of hypoglycemia – a deficit in the adrenergic symptoms that ordinarily serve as a warning sign.

Children with impaired awareness were over twice as likely to have experienced a severe hypoglycemic episode in the previous year, involving loss of consciousness or seizure.

The effect was even more pronounced in the very young: children under 6 with impaired awareness were almost six times as likely to have had a serious episode.

Senior author Dr. Tim Jones said that hypoglycemia unawareness has traditionally been considered to be an adult problem, but urged physicians to step up screening among younger patients in light of the new findings.

“Ask the child: ‘do you get your usual symptoms? Do you still feel shaky when you go low? Or is the first thing you notice about being low that you find a low reading when you test yourself?’ It only takes a minute if you know what to ask,” he said.

Hypoglycemia unawareness appears to be caused by hypoglycemia itself, with repeated episodes successively dampening the adrenergic response, added Jones, head of the department of endocrinology and diabetes at Princess Margaret Hospital for Children, Perth, Australia.

The good news, however, is that the problem seems to some extent to be reversible, he said. Once impaired awareness is identified, the patient should meticulously ensure that they avoid hypoglycemia for around a month, and the warning symptoms may begin to return.

Further testing can also be carried out – particularly using continuous glucose monitoring systems to track a child’s blood sugar over time. This can help to identify and avoid episodes of hypoglycemia, regardless of whether the child is aware of it.

The study involved type 1 diabetic children aged from 6 months to 19 years. All were taking insulin – ranging from twice-daily injections to four times a day with insulin analogs and subcutaneous infusion therapy. [Diabetes Care 2009 Jul 8; Epub ahead of print]

A total of 161 hypoglycemic episodes had occurred in the year leading up to the study. The rate of episodes among children with impaired awareness was 37.1 episodes per 100 patient-years, compared to 19.3 per 100 patient-years in children with normal awareness.

Patients with impaired hypoglycemia awareness tended to be younger, had an earlier onset of diabetes, and had lower mean HbA1C levels since diabetes onset.

MIMS.com hailed for excellence in technology

2009-10-20T03:18:00.000-07:00

Medical Tribune September 2009 P7
David Brill

Asia’s leading online drug database has been lauded for its innovative approach to digital technology at the recent Asian Multimedia Publishing Awards (AMPA).

MIMS.com – used by over 250,000 doctors and pharmacists in Asia – was named a runner-up in the ‘Use of Digital Technology’ category at the AMPA ceremony in Manila.

The award marks the 40th year of the directory, which is now used in 15 countries across the Asia-Pacific region and receives over 300,000 unique visitors each month. It was chosen out of 74 entries from 9 different countries.

Mr. Ben Yeo, Chief Executive Officer at CMPMedica Asia, publishers of MIMS and Medical Tribune, said: “This award commemorates the achievement that MIMS has attained in Asia at its 40th anniversary, further underscoring CMPMedica’s leading position in delivering drug information and scientific publishing in Asia. Our teams are keeping up their momentum in achieving the highest standards in the industry.”

The award makes CMPMedica the most highly decorated healthcare publisher at the Asian Publishing Convention, having previously picked up an award in 2007.

MIMS.com is used by doctors, pharmacists and healthcare professionals to access comprehensive drug information such as dosage, indications, safety and interactions. It is accessible online, and integrated within some hospital formularies.

Aspirin trial seeks to tackle colorectal cancer in Asia

2009-10-20T03:16:00.000-07:00

Medical Tribune September 2009 P8
David Brill

A major new trial is set to launch in Asia to establish whether aspirin can prevent recurrence of colorectal cancer.

The ASCOLT study will involve over 2,000 patients from centers across Southeast Asia, China and India, and will be led jointly by the National Cancer Centre Singapore (NCCS) and the University of Oxford, UK.

Patients will be randomized to aspirin (200mg/day) or placebo for 3 years, following surgery and adjuvant chemotherapy for high-risk stage II and III colorectal cancer. The primary endpoint will be disease-free survival over 5 years of follow-up.

A growing body of evidence suggests that aspirin is effective for primary prevention of colorectal cancer, but ASCOLT is thought to be the first prospective clinical study to investigate the drug in the adjuvant setting after chemotherapy.

If positive, the results could have a huge impact on the treatment of colorectal cancer in Asia and worldwide, according to Dr. Toh Han Chong, head of the department of medical oncology at NCCS and one of the ASCOLT lead investigators.

“It’s incredible how many people you could save from relapse with the addition of aspirin if this study is positive. If you go to a village in India you can’t really give costly [monoclonal antibodies], so there is compelling power of social responsibility here,” he told Medical Tribune.

“We have undervalued the power of simple drugs. It’s time to redress the balance – change the paradigm and go cheap.”

Recruitment for ASCOLT is already underway, with centers confirmed in Singapore, Hong Kong, Jakarta and several cities in India.

More study centers are still needed in order to reach the target of 2,000 patients however said Toh, who extended the invite to all Asian delegates at the recent ‘Best of ASCO’ conference in Singapore.

“It’s a drug trial that cannot be done in the West. Many people over the age of 50 in the US are popping aspirin over the counter for heart conditions or stroke prevention,” he said. “Fewer people are on aspirin in Asia. That’s why it’s a perfect study to do here.”

Colorectal cancer is the second leading cause of cancer death in North America, Europe and Australasia according to a 2007 global report from the American Cancer Society. In Southeast Asia, it is the third biggest killer (behind liver and lung cancer) – responsible for 7.9 percent of cancer deaths.

In Singapore, colorectal cancer is the leading cancer among men and the second most common among women, data from the national cancer registry show.

A recent study found that regular use of aspirin after a diagnosis of colorectal cancer was associated with lower overall mortality (hazard ratio [HR] 0.79; 95% CI 0.53 – 0.95) and cancer-specific mortality (HR 0.71; 0.53 – 0.95), after a median of 11.8 years of follow-up. [JAMA 2009;302(6):649-58]

A 2007 paper, meanwhile, reported that taking 300 mg/day or more of aspirin for 5 years was effective for primary prevention of colorectal cancer, according to pooled data from two large randomized trials (HR 0.74; 95% CI 0.56 – 0.97; P=0.02). [Lancet 2007;369(9573):1603-13] Earlier trials have also shown that aspirin can prevent colorectal adenomas – the precursors to cancer – both in patients with, and without, a prior history of cancer. [N Engl J Med 2003;348(10):883-90; N Engl J Med 2003;348(10):891-9]

“Why should oncologists do an aspirin trial? Because the epidemiological data is strong, the data on polyp reduction is very convincing, the retrospective observational studies are very compelling and remarkable in terms of hazard ratios, and the data preclinically is scientifically robust,” added Toh.

ASCO award set to boost Asian cancer research

2009-10-20T03:12:00.001-07:00

Medical Tribune September 2009 P8
David Brill

A Singapore oncologist has become the first Singaporean, and one of the first Asia-based recipients, to pick up a prestigious research award from the American Society of Clinical Oncology (ASCO).

Dr. Daniel Tan of the National Cancer Centre Singapore (NCCS) will receive a US$50,000 grant as part of the Young Investigator Award, bestowed by the ASCO cancer foundation.

The money will help fund his research on the molecular mechanisms of tyrosine kinase inhibitors (TKIs) in nasopharyngeal cancer. The work aims to understand why some patients respond better to targeted therapies than others – so as to improve patient selection and avoid unnecessary exposure to ineffective treatment and side effects.

“One of the challenges with any of these new-generation drugs is to find out how we can use them better – to get the right drug to the right patient. Understanding the reasons for response and resistance can also allow us to develop much more effective treatment strategies that hopefully translate to improved survival,” said Tan, who will work alongside his mentor Professor Teh Bin Tean, director of the NCCS-VARI laboratory – a joint project with the Michigan-based Van Andel Research Institute.

Tan’s ASCO proposal was borne out of clinical observations from a phase II trial of pazopanib, which saw a subset of nasopharyngeal cancer patients respond better to therapy than others. This trial is currently ongoing under principal investigator Dr. Darren Lim, a senior consultant at NCCS specializing in thoracic and head and neck cancers.

The goal now is to understand which proteins are targeted by the drug, and how this differs between patients and tumor types. Tan’s work will be done largely in a series of co-culture experiments and mouse xenograft models – allowing detailed analysis of how the drug affects each cellular compartment within a tumor.

Tan is also aiming to secure more local funding for his research, and hopes in the long term to help establish a comprehensive drug development program, which would also provide patients with access to novel therapeutic agents.

He added that he was pleased to receive the award, and is especially encouraged that the proposal was deemed to have sufficient scientific merit for further study.

“It is heartening to know that one’s ideas are being taken seriously by a highly regarded scientific body. Furthermore, the award is rarely given out to institutions outside of America, so it’s a nice endorsement of the research infrastructure at NCCS,” he said.

Cetuximab offers hope for Asian lung cancer patients

2009-10-20T03:12:00.000-07:00

Medical Tribune September 2009 P8
David Brill

A novel lung cancer therapy could be of particular benefit to Asian patients, results of a recent trial suggest.

The international FLEX* study reported that adding the monoclonal antibody cetuximab to chemotherapy prolonged survival of advanced lung cancer patients from 10.1 months to 11.3 months.

Further analysis revealed, however, that Asians treated with the drug survived for a median of 19.5 months, whereas non-Asians survived only 9.6 months.

The randomized trial involved 1,125 patients – 121 of whom were from Asian centers (predominantly in Hong Kong, Taiwan, Singapore and South Korea). [Lancet 2009;373(9674):1525-31]

There are several possible explanations for the ethnic discrepancy but also questions that remain unanswered, according to Professor Kenneth O’Byrne, one of the FLEX investigators, who spoke to Medical Tribune during the recent ‘Best of ASCO’ conference in Singapore.

Asian lung cancer patients are more likely to be women, non-smokers and have adenocarcinomas than non-Asian patients – all groups which tend to survive longer, he said. Moreover, epidermal growth factor receptor (EGFR) mutations are more common among Asians – a characteristic which not only improves prognosis in itself, but also makes patients eligible for first-line EGFR tyrosine kinase inhibitors which can further improve outcomes.

“So there is a combination of reasons as to why but it’s not just that – there may be some intrinsic sensitivity to treatment here that’s not present in the West,” said O’Byrne, adding that further study is needed to better understand these biological similarities and differences.

Cetuximab is presently licensed for use only in colorectal and head and neck cancers. An application for lung cancer licensing was recently rejected by the European Medicines Agency (EMEA), but is currently under appeal from the manufacturer, Merck Serono.

The verdict has also come as a surprise to many experts in the field and will face “a strong challenge,” said O’Byrne, a consultant medical oncologist at St. James’s Hospital and a clinical professor at Trinity College, Dublin, Ireland. The FLEX trial was published before the EMEA decision, with investigators concluding that cetuximab can be considered as standard first-line therapy for all patients with advanced non-small cell lung cancer (NSCLC).

“Cetuximab is the first drug to show a survival benefit in all histological types: adenocarcinoma, squamous carcinoma – across the board. Secondly, the toxicities are all very predictable – we know how to manage them and they’re straightforward. Thirdly, not only was the FLEX trial positive but when you take in all the other trials together … as a collective they show a positive result,” said O’Byrne. He added that US National Comprehensive Cancer Network guidelines already recommend that the drug be considered for lung cancer patients, and that many oncologists in Europe have begun off-label usage.

O’Byrne acknowledged that cetuximab therapy would be costly, but noted that around half of patients display a strong predictive marker in the form of a skin rash, which develops after one round of chemotherapy. These patients tend to survive for around an extra 5 months, which may justify the cost, he said. More work is needed to confirm whether cetuximab offers any benefit for those who do not develop a rash, but it appears likely that therapy could be discontinued after one cycle in these patients, he said.

---------------------------------------------
*FLEX: First-Line Erbitux in Lung Cancer

Low-salt diet offers key to treating stubborn high blood pressure

2009-10-20T03:09:00.000-07:00

Medical Tribune September 2009 P9

David Brill

Cutting down on salt can dramatically lower blood pressure (BP) in patients with resistant hypertension and could offer a genuine alternative to ramping up medications, a study suggests.

American researchers found that BP dropped by 22.7/9.1 mmHg after a week of a low-salt diet compared to a high-salt diet – a magnitude roughly equivalent to adding two more drugs.

This drop came on a background of heavy medication: patients in the study were already taking an average of 3.4 antihypertensive drugs per day.

Although small – just 12 patients took part – the study has been greeted enthusiastically by experts, who are calling for a renewed focus on salt reduction for patients whose BP remains uncontrolled.

Leading hypertension expert Dr. Lawrence Appel described the results as “striking,” particularly given that all study patients were taking hydrochlorothiazide. This volume-reducing therapy might have been expected to attenuate the effects of a low-salt diet, he wrote in an accompanying editorial. [Hypertension 2009 Jul 20; Epub ahead of print]

“The data presented … strongly suggest that persons with resistant hypertension are extremely sensitive to the BP-lowering effects of sodium reduction. The observed reductions in BP were huge – roughly equivalent to adding 2 antihypertensive medications,” wrote Appel, a Professor of Medicine at Johns Hopkins University, Baltimore, US.

“Although clinicians commonly focus on the next drug (e.g. aldosterone blocking therapy) and sometimes a device (e.g. Rheos systems that stimulate carotid baroreceptors), a renewed and aggressive emphasis on lifestyle modification, specifically sodium reduction, is warranted in patients with resistant hypertension and uncontrolled BP.”

Dr. Low Lip Ping, chairman emeritus of the Singapore Heart Foundation and founding president of the Singapore Hypertension Society, said: “This small but interesting study showed that among patients with medication-resistant hypertension, salt restriction has a substantial impact on lowering blood pressure by reducing intravascular fluid retention and improving vascular function.”

“Dietary salt restriction, ideally to less than 100 mEq of sodium/24 hours, should be recommended for all patients with resistant hypertension. With a low-salt diet these patients could have their blood pressure controlled with fewer medications,” said Low, also a private practitioner at the Low Cardiology Clinic, Mount Elizabeth Medical Center.

The study is the first to demonstrate that the benefits of salt reduction extend beyond patients with just mild or moderate hypertension, according to lead author Dr. Eduardo Pimenta.

“A low-salt diet is beneficial for all patients with hypertension but in patients with resistant hypertension the effect is stronger. Before prescribing another antihypertensive medication, doctors should spend more time with their patients explaining about low-salt diets and, if possible, refer the patient to a nutritionist,” said Pimenta, now a clinical research fellow at the Endocrine Hypertension Research Center, University of Queensland School of Medicine, Brisbane, Australia. The study itself was undertaken at the University of Alabama at Birmingham, US.

Study subjects had a mean office BP of 145.8/83.9 mmHg at baseline. All were randomized to either a high- or low-salt diet for 1 week, then a 2-week washout period, followed by a final week of the opposite diet. The low- and high-salt diets provided 50 and 250 mmol of sodium per day, respectively. [Hypertension 2009 Jul 20; Epub ahead of print]

All measures of BP were reduced by the low-salt diet as compared to the high-salt diet: systolic and diastolic; office and ambulatory; and daytime, nighttime and 24-hour.

The Singapore Heart Foundation and Hypertension Society have already been promoting the message about salt reduction – especially in light of National Nutrition Survey data suggesting that nine out of 10 Singaporeans exceed the recommended sodium intake of 2,000 mg/day.

In a joint statement to mark World Hypertension Day in May this year, the societies urged “all residents in Singapore to reduce their salt intake to reduce their risk of hypertension and hypertension-related diseases.” They also called on chefs and restaurants to lower the salt content of foods, and to avoid routinely providing soy sauce unless requested by the customer.

Cognitive rehab shows promise for stroke patients

2009-10-20T03:07:00.000-07:00

Medical Tribune September 2009 SFI
David Brill

A cognitive rehabilitation program used after traumatic brain injuries could also help stroke patients to overcome lingering attention deficits, a new study shows.

Stroke survivors who received Attention Process Training (APT) within 4 weeks were better able to concentrate on visual and auditory tasks 6 months later, New Zealand researchers reported in the journal Stroke.

It is the first study to test APT in an important but neglected area of stroke rehabilitation, the researchers say. Concentration problems are very common in stroke patients – affecting quality of life and contributing to poor functional outcomes – yet specific interventions remain largely unstudied.

Singapore stroke expert Dr. Nagaendran Kandiah, a consultant neurologist at the National Neuroscience Institute (NNI), said that APT could be a useful tool for local patients but that equivalent programs would need to be tailored to the language and culture. Researchers at the NNI are already “actively working on this”, he said.

Further research is also needed to better establish the local prevalence of post-stroke attention deficits, he added. Preliminary data from NNI suggest that about 15 to 20 percent of patients have cognitive difficulties, including poor attention, following a stroke.

“There is a significant amount of literature that shows that cognitive training is useful for post-stroke patients. The awareness that attention deficits and other cognitive deficits are common and can be potentially treated needs to be emphasized both to the public and medical community,” said Nagaendran.

The Stroke study researchers randomized 78 stroke patients to receive standard care alone or standard care plus up to 30 hours of APT (mean 13.5 hours). [2009 Jul 23; Epub ahead of print]

APT patients scored significantly better on the Integrated Visual Auditory Continuous Performance Test (IVA-CPT) Full-Scale Attention Quotient (FSAQ), at 5 weeks and 6 months after randomization. The test measures reaction times to auditory and visual stimuli, and can distinguish between genuine attention to the task and impulsive responding.

There were however no significant differences between the groups in other cognitive performance indicators, or broader outcome measures such as the Physical Component Score.

Lead author Dr. Suzanne Barker-Collo, a clinical psychologist and senior lecturer at the University of Auckland, said that she was disappointed that the intervention did not show benefit across other domains but was pleasantly surprised at the magnitude of effect on the primary outcome.

“We were expecting maybe half a standard deviation difference between the groups, and the effect we found was about four times that,” she said.

There are several cognitive rehabilitation packages available but very little evidence on how best to use them in stroke patients, added Barker-Collo, whose ongoing research seeks to better delineate the profile and time course of cognitive deficits after stroke. She is also reviewing the data from the present study to identify factors that could predict which patients will respond best to APT.

“I think cognition after stroke in general has been ignored to some degree,” she said. “A lot of rehabilitation time is spent on more physical tasks like walking, bathing and dressing – it’s very practical but very often the time spent on that means that not as much time is spent on other things like attention and memory, which are a bit less obvious but can still impact on other functional outcomes. Attention deficit in particular is a very, very common problem.”

Questions raised over vertebroplasty for osteo fractures

2009-10-20T03:06:00.001-07:00

Medical Tribune September 2009 P12
David Brill

Vertebroplasty performs no better than a placebo procedure for treating painful osteoporotic fractures, two major new studies have found.

Despite its widespread usage and recommendation in guidelines, vertebroplasty did not relieve pain, alleviate disability or improve quality of life compared to sham interventions, US and Australian researchers reported.

The studies are the first true randomized controlled trials to assess a procedure which has become a firmly established treatment for osteoporotic fractures. The number of vertebroplasties performed in the US, for example, almost doubled from 2001 to 2005. [JAMA 2007 Oct 17;298(15):1760-2]

The jury is still out as to how the findings will influence practice, according to an orthopedics expert whose editorial accompanies the papers in the New England Journal of Medicine. [2009 Aug 6;361(6):619-21]

“Although the trials by Kallmes et al. and Buchbinder et al. provide the best available scientific evidence for an informed choice, it remains to be seen whether there will be a paradigm shift in the treatment of vertebral compression fractures with vertebroplasty or similar procedures,” wrote Dr. James Weinstein, chair of the department of orthopedic surgery at Dartmouth-Hitchcock Medical Center, US.

Given the rise in the number of vertebroplasties and the questionable risk-benefit ratio, it is now essential that patients be well informed about the procedure, added Weinstein.

“When faced with several choices for which the evidence is less than clear, patients and doctors must thoroughly review the options together. Informed choice helps to educate patients about treatment options and allows them to recognize that a decision can be based on their values and preferences,” he wrote.

The larger of the two trials, led by Dr. David Kallmes of the Mayo Clinic, Rochester, US, followed 131 patients with osteoporotic vertebral compression fractures. They received either vertebroplasty or a simulation procedure in which cement was not injected into vertebrae. [N Engl J Med 2009;361:569-79.]

At 1 month there was no difference between groups on a pain scale ranking intensity from 0 to 10 (difference 0.7; 95% CI -0.3 to 1.7; P=0.19) or on the Roland-Morris Disability Questionnaire (difference 0.7; 95% CI -1.3 to 2.8; P=0.49). There was however a non-significant trend for more patients in the vertebroplasty group to report clinically meaningful improvements in pain (64 percent versus 48 percent; P=0.06).

Patients were subsequently allowed to cross over and receive the other intervention – still unaware of which they had already received. At 3 months, this option had been taken up by more control patients than vertebroplasty patients (43 percent versus 12 percent), but all patients who crossed over reported comparable or worse outcomes than those who received only the first intervention.

The second trial, led by Dr. Rachelle Buchbinder of Monash University, Australia, reported 6-month follow-up of 35 vertebroplasties and 36 placebo interventions. [N Engl J Med 2009 Aug 6;361(6):557-68]

Both interventions did relieve pain but to a comparable extent: at 3 months, the mean reductions (also measured on a 10-point scale) were 2.6 in the vertebroplasty group and 1.9 in the control group (adjusted between-group difference 0.6; 95% CI -0.7 to 1.8). This difference was also not significant at 1 week or 1 or 6 months; nor was there anything nothing to choose between groups on a range of secondary outcomes, including physical functioning and quality of life.

“It has been argued that performing a randomized, placebo-controlled trial of vertebroplasty is unnecessary and unethical in view of the published results of numerous studies that suggest a benefit of vertebroplasty. Our results show – not for the first time – the hazards of relying on the results of uncontrolled or poorly controlled studies to assess treatment efficacy,” the authors wrote.

Bacteria eradication holds hope for stomach cancer prevention

2009-10-20T03:03:00.001-07:00

Medical Tribune September 2009 P14

David Brill

A new study has renewed hopes for reducing the incidence of gastric cancer – a leading cause of death worldwide and a particular burden for Asia.

The link between Helicobacter pylori infection and gastric cancer is well known, but Italian researchers now provide some of the strongest evidence yet that eradicating the bacteria can actually reduce cancer risk.

In a meta-analysis of data from 6,695 participants, they report that H. pylori eradication reduced the relative risk of gastric cancer to 0.65 (95 percent CI 0.43 – 0.98) over up to 10 years of follow-up. [Ann Intern Med 2009;151:121-8]

The findings lend support to a recent Asia-Pacific consensus statement calling for H. pylori screening and eradication in high-risk populations.

Japan and China have the world’s highest rates of gastric cancer, with age-standardized incidences of 62.1 and 41.4, respectively, per 100,000 males and 26.1 and 19.2 per 100,000 females. [CA Cancer J Clin 2005;55:74-108]

Dr. Lorenzo Fuccio, lead author of the meta-analysis, stressed that the cancer risk reduction with H. pylori eradication was only marginally significant, but could prove vital in countries such as these.

“Even a small reduction in risk and incidence achieved with H. pylori treatment will probably give a huge advantage in terms of social health, especially in high-risk areas,” said Fuccio, of the department of internal medicine and gastroenterology at the University of Bologna, Italy.

“Furthermore, H. pylori eradication provides several other benefits: it reduces the risk of peptic ulcer development, it can resolve dyspeptic symptoms and it can resolve gastritis. Once H. pylori is detected, especially in high-risk areas, eradication is always advisable.”

Asia-Pacific experts released their consensus statement on gastric cancer prevention last year, concluding that “there is a definite causal link between H. pylori infection and gastric cancer, and it has come time to try and intervene to prevent this cancer at the population level.” [J Gastroenterol Hepatol 2008;23:351-65]

Lead author Professor Fock Kwong Ming said that H. pylori screening and treatment should be a complement to, not a replacement for, existing cancer surveillance strategies in high-risk countries.

Research is still ongoing to establish exactly who to screen in intermediate-risk countries such as Singapore and Malaysia, said Fock, a senior consultant gastroenterologist at Changi General Hospital (CGH), Singapore. The highest-risk group in Singapore appears to be Chinese males aged 45 to 50, he said.

Previous work showed that gastric cancer risk correlated with H. pylori infection in Chinese and Malay individuals but not Indians. Gastric cancer rates are known to be lower in the latter two groups. [J Gastroenterol Hepatol 2005 Oct;20(10):1603-9]

Two studies are currently underway in Singapore to identify risk factors for gastric cancer development.

The first – a 5-year, S$25 million project conducted across several institutions in the Singapore Gastric Cancer Consortium – will correlate endoscopy and biopsy findings to gastric cancer outcomes, with a view to understanding how cancer develops and improving early detection rates. The second study takes place at CGH, and involves narrow-band endoscopy – a more specialized technique which may be better able to detect precancerous lesions.

Fuccio noted that randomized, multicenter trials are needed to fully understand the impact of H. pylori eradication on cancer prevention, but that such studies would present considerable ethical, logistical and financial challenges. Achieving statistical power would require thousands of participants and decades of follow-up, he said.

He added that gastric cancer results from a complex combination of genetic and environmental factors, and that eradicating H. pylori does not completely abolish risk.

H. pylori eradication is typically achieved using two antibiotics combined with a proton-pump inhibitor.

No benefit to excessive BP lowering, study says

2009-10-20T03:01:00.000-07:00

Medical Tribune September 2009 P14
David Brill

Lower is not necessarily better when it comes to blood pressure (BP), a recent systematic review has found.

The analysis of seven randomized trials concluded that there was no clinical benefit to lowering BP beyond a currently recommended target of 140/90 to 160/100 mmHg.

Patients treated to lower targets did achieve significantly lower BPs (-4/-3 mmHg), but there were no differences in total mortality, major cardiovascular events, myocardial infarction or stroke rates compared to those treated to standard targets.

The review included data from a total of 22,089 patients, who had taken part in trials targeting various different diastolic BPs below 85 mmHg. No suitable trials of low systolic BP targets were identified. [Cochrane Database Syst Rev 2009;(3):CD004349]

“At present there is no evidence from randomized trials to support aiming for a BP target lower than 140/90 in the general population of patients with elevated blood pressure,” said lead author Dr. Jose Arguedas, of the University of Costa Rica, Costa Rica.

“Our research included patients with diabetes or chronic renal disease, and the evidence was slightly less robust for those subgroups of patients. We intend to carry out separate systematic reviews for those subgroups, especially because guidelines recommend even lower blood pressure targets for them,” he added.

There were also no significant differences in the incidence of congestive heart failure (relative risk [RR] 0.88, 95% CI 0.59 – 1.32) and end-stage renal disease (RR 1.01, 95% CI 0.81 – 1.27) between patients treated to low, as compared to standard, targets.

The full picture remains unclear with regard to safety, the authors note, since six of the seven trials did not provide complete information on serious adverse events and withdrawals.

Excessive BP lowering could cause unnecessary cost and inconvenience to patients, as well exposing them to a potential increased risk of adverse events if the number of antihypertensive medications is increased, they add.

Sunken treasure

2009-10-20T02:59:00.000-07:00

Medical Tribune September 2009 P18
David Brill

If Subic Bay seems unremarkable you may be looking in the wrong place. David Brill finds that attraction lies beneath the surface.

Looking out over Subic Bay, you could be forgiven for thinking you’d booked the wrong trip. Tankers float out at sea, cranes loom over the shoreline, and litter washes up at your feet. Far from the glorious beaches of Boracay or Palawan, Subic does not at first glance appear an obvious destination for visitors to the Philippines.

A look below the water, however, tells a different story. An entire fleet of shipwrecks sits silently at the bottom of the sea, oblivious to the trivial goings-on at the surface. Anemones sprout on deck, while lionfish lurk in twisted metal crannies below. Barracudas swim down gun turrets, emerging in ghostly loading chambers long disused and overgrown with rust. Subic is a sunken goldmine – entry only for those with a diving license.

Back on land, Subic Bay was home to a US naval base until forces withdrew in 1992. The area of the base remains enclosed as the Subic Bay Freeport Zone – the shipyards making way for hotels, restaurants and casinos. International access is via Clark airport, some 2 hours drive southeast of Subic, or from Manila, a further 3 or so hours south of Clark, depending on traffic.

Some of Subic’s shipwrecks date back to the Spanish-American war of 1898, but the majority sank during the years of World War II. Twenty-five ships from Japan alone are claimed to have gone down during the war but with salvage operations undertaken in the 1950s, no one is quite sure how many wrecks remain in the bay. Best guesses suggest that there are some 20 wrecks in still waters – 10 or so of which are suitable for recreational diving.

The main attraction at Subic Bay is the USS New York. Launched in 1891, she played a key role in the Spanish-American war before returning to action in World War I as the USS Saratoga. She was eventually decommissioned in the Philippines in the 1930s and remained moored at Subic Bay until 1941, when she was deliberately scuttled by retreating US forces to prevent her from falling into the hands of the Japanese.

The navy’s loss proved to be scuba divers’ gain, as the 120-meter-long USS New York came to rest on its side with its topmost point just 17 meters from the surface. This depth leaves the top of the wreck accessible for novice divers, with the inside and lower decks offering a variety of options for those seeking more challenging, technical dives. The engine rooms lie at the very bottom of the ship and remain largely unexplored.

Visibility was mediocre during a trip in late July but the wreck is eerily impressive nonetheless. Its sheer, hulking size is enough to leave you feeling insignificant by comparison, while the sight of its three giant gun barrels emerging ominously from the gloom offers another reminder of the vast power the ship once wielded. A variety of wildlife circulates the site: dive instructors list barracuda, rays, octopi, lobsters and spotted sweetlips among the wreck’s inhabitants, although not all were seen on our trip.

Other wrecks at Subic Bay include El Capitan, a shallow site which is easily accessible for all comers. Even fairly novice divers can swim through the hold, and poke their head up into a pocket of trapped, ancient air (attempting to breathe it is strongly not advised). Also of note is the infamous Oryoku Maru – a Japanese cruise liner used for transportation of prisoners of war from Manila to Japan. Later dubbed ‘The Hell Ship’ for the nightmarish conditions in which prisoners were kept, she was bombed and sunk at Subic by US navy planes in 1944. Several other vessels are accessible – including a largely intact Japanese patrol boat – along with various sites of debris, scattered metal, and even a few coral reefs.

Beyond the diving, a few activities are available at Subic, including horse riding, watersports, go-karting and, of course, gambling. Much of the area, however, feels run-down and seedy, and considerable regeneration will likely be needed if tourists are to come in large numbers. In the meantime, however, Subic offers an enjoyable and convenient weekend for divers, especially given the proximity of the wrecks to the shore and the relative ease of transport from abroad. Don’t be fooled by the cranes and tankers – Subic Bay is to be judged on what lies below.

Fears allayed over menopausal memory loss

2009-09-25T02:22:00.000-07:00

Medical Tribune August 2009 P8

David Brill

Women who experience memory loss as they approach the menopause can be reassured that the problem is only temporary, say US researchers.

In a recent study of over 2,000 women, they found that verbal memory and processing speed appear to drop during perimenopause, but typically return to normal upon reaching postmenopause.

The findings confirm a problem which is reported by up to 60 percent of women but has been addressed by very few quantitative studies, say the authors. [Neurology 2009;72:1850-7]

Lead author of the Study of Women’s Health Across the Nation (SWAN) report, Dr. Gail Greendale, said that physicians can now use the findings to reassure concerned women and “validate their experience.”

“Women who are experiencing memory difficulties during the menopause transition often find this experience frightening. They do not know what to expect and worry that their memory will worsen over time,” said Greendale, of the David Geffen School of Medicine at the University of California, Los Angeles, US.

“The SWAN results provide women with a frame of reference … and show that the memory problems are temporary. Also, if women are having memory problems of a greater degree than that which we observed, then their physician should not ascribe the problem to menopause and should dig deeper,” she said.

The SWAN study involved 2,362 women with a mean age of 45.9. They were classified as premenopausal, perimenopausal or postmenopausal, and followed for 4 years with regular testing in domains of processing speed, verbal memory and working memory.

The decline in cognition over the menopause transition was particularly marked for processing speed: pre- and postmenopausal women showed significant improvements with repeated testing, whereas late perimenopausal women scored worse over time. A similar effect was seen for verbal memory, but there was no difference in working memory between groups.

The paper also points to cognitive benefits of early initiation of hormone therapy: women who had already begun therapy before their final menstruation scored 4 to 6 percent higher on tests than those with no prior therapy.

Estrogen has a range of effects on the brain and is thought to influence mood, higher cognitive function and motor skills. Estrogen receptor density is particularly high in the prefrontal cortex and hippocampus – hence it has been postulated that the fluctuation in estrogen levels during perimenopause could adversely influence brain function. [J Appl Physiol 2001;91:2785-801]

Only two previous longitudinal studies however have measured cognitive performance over the menopause transition, according to Greendale and colleagues. The more recent of the two, a study of 694 women from a rural community in Taiwan, found that verbal memory declined during the menopause transition. The other study found no cognitive effects of the transition on working memory or perceptual speed. [Maturitas 2006;53:447-53; Neurology 2003;61:801-6]

Knee replacements cost-effective, say US researchers

2009-09-25T02:20:00.000-07:00

Medical Tribune August 2009 SFI
David Brill

Total knee arthroplasty (TKA) is cost-effective, especially when performed in high-volume centers, according to a US study.

The findings will prove valuable for informing both policy and practice as the number of TKAs performed each year continues to spiral upward, the authors say. Some 500,000 TKAs were performed in the US in 2005, at a cost of over US$11 billion, and the number of procedures is projected to reach 3.5 million by 2030.

The study found that the incremental cost-effectiveness ratio of TKA was US$18,300 per quality-adjusted life year (QALY) – a figure that meets most commonly used definitions of cost-effectiveness. The UK National Institute for Health and Clinical Excellence, for example, sets its cost-effectiveness threshold between £20,000 and £30,000 (around US$33,000 to US$49,000) per QALY.

The researchers, led by Dr. Elena Losina of the Brigham and Women’s Hospital, Boston, developed a computer model using Medicare claims data and outcomes data of people with end-stage knee osteoarthritis. [Arch Intern Med 2009 Jun 22;169(12):1113-21]

Quality-adjusted life expectancy increased from 6.8 to 8.0 QALYs in people who underwent TKA. Procedures performed at low-volume centers cost more and were less effective than in high-volume centers, regardless of whether patients were at high or low risk.

TKA is widely accepted as an effective procedure but assessing cost-effectiveness has proven difficult, due in part to the ethical and logistical constraints that prohibit a randomized controlled trial.

Despite the insights from the new study, however, policymakers still face many difficulties in evaluating established medical technologies such as TKA, according to an accompanying editorial by Assistant Professor Stephen Lyman, director of the epidemiology and biostatistics core at Weill Cornell Medical College, New York, and colleagues.

“At least in the US, even well-performed cost-effectiveness analyses do not influence either payers or physicians directly. Payers do not use the results to make coverage determinations nor do physicians use them to make treatment decisions. How we move from this current state to a system in which cost-effectiveness of procedures affects medical practice is unclear,” they wrote. [Arch Intern Med 2009 Jun 22;169(12):1102-3]

Demand for TKAs is also expected to rise in parts of Asia, where populations are ageing rapidly. An analysis of 1,663 procedures from a high-volume center in Singapore found that patients were typically Chinese females in their mid-60s. Ninety six percent had osteoarthritis and four percent had rheumatoid arthritis. [Ann Acad Med Singapore 2008 Nov;37(11):924-8]

Average length of stay decreased between 2000 and 2005 – due, in part, to an increase in the number of same-day admissions. Overall complication rates were 2 percent and mortality less than 1 percent, the group from Tan Tock Seng Hospital reported.

Questions raised over childhood antibiotics

2009-09-25T02:17:00.000-07:00

Medical Tribune August 2009 SFV

David Brill

Using antibiotics to treat acute otitis media (AOM) in young children could increase their risk of recurrent infection, a recent study suggests.

Children who received amoxicillin for AOM were 2.5 times more likely to have a recurrent episode within the following 3.5 years, reported Dutch researchers, who are calling for more conservative use of antibiotics in this setting.

Senior author Dr. Maroeska Rovers said that up to 80 percent of children with mild, uncomplicated AOM will recover spontaneously, and that a 2 to 3 day “wait and see” policy is justified in such cases. Close observation by parents is required, since acute mastoiditis can result if AOM worsens and goes untreated, she said.

The British Medical Journal study included follow-up surveys from 168 children who had presented to Dutch GPs with AOM between the ages of 6 months and 2 years, and been randomized to amoxicillin or placebo. It is one of the first studies to look at the long-term effects of antibiotics in pediatric AOM, the authors say. [2009 Jun 30;338:b2525]

Sixty three percent of antibiotic-treated children had an AOM recurrence, compared to 43 percent of placebo-treated children (risk difference 20 percent; 95% CI 5-35%). Antibiotic-treated children were, however, less likely to undergo ear, nose and throat (ENT) surgery (21 percent versus 30 percent; risk difference 9 percent; 95% CI 4-23%).

Singapore expert Associate Professor Lynne Lim cautioned that more research is needed before practice should be changed, particularly given the small size of the study, the width of the reported confidence intervals and the different ethnicity and geographical location of patients.

“The debate on antibiotics use in AOM is continuing worldwide. It is definitely important to use antibiotics judiciously to avoid bacterial resistance and worse outcomes, if any, but until we are able to comcommitantly answer in the same study the complication rates and other problems associated with no antibiotic use, we cannot answer the question fully,” said Lim, head of the pediatric ENT service and senior consultant ENT surgeon at the National University Health System Singapore.

“The study suggests that more large, population-based, randomized clinical trials should be done to determine the cost-benefit of antibiotic use in AOM. I will continue treating as normal until more data are out,” she said, adding that that she typically follows US guidelines when treating AOM, and prescribes high-dose oral amoxicillin or amoxicillin/clavulanate potassium (80-90 mg/kg per day) for 7 to 10 days for children under 2.

Rovers, a clinical epidemiologist at University Medical Center Utrecht in the Netherlands, stressed that the “wait and see” policy should only apply to mild, unilateral AOM. Children under 2 years who have bilateral AOM or AOM with otorrhea should receive antibiotics without delay, she said, citing a meta-analysis of 1,643 children which found that antibiotics were of greatest benefit in these subgroups. [Lancet 2006 Oct 21;368(9545):1429-35]

“We now know which children benefit most from antibiotics but we also know that there is some harm. The next step for me will be to try to study the benefit and risk. Then we can say whether the guidelines should be changed or should not be changed,” she said.

Rovers and Lim both added that analgesics should be given to all children with AOM, regardless of whether antibiotics are prescribed.

NHG ups ante on manpower training budget

2009-09-25T02:14:00.000-07:00

Medical Tribune August 2009 SFIX
David Brill

The National Healthcare Group (NHG) is to invest an additional $1.3 million in training fellowships this year, the group’s chairman announced recently.

The funding boost will see 189 staff undergo specialist placements through the Health Manpower Development Plan (HMDP) awards – up from 138 recipients last year.

This year’s awardees comprise 75 doctors, 77 nurses, 23 health sciences professionals and 14 healthcare administrators.

“With the bar for healthcare being raised consistently, we need to relentlessly improve our healthcare delivery, to become the preferred healthcare provider in Singapore and the region. HMDP is, and will continue to be, one of the key anchors for NHG’s staff training and development efforts,” said NHG Chairman Madam Kay Kuok, who presented the awards in a ceremony at the Institute of Mental Health (IMH).

Recipients of the HMDP award undergo training fellowships – often overseas – in skills and specialist areas which are not easily found in Singapore. The focus of this year’s awards is on health services and outcomes research, multi-disciplinary training, the ageing population and mass disasters and emergencies.

Previous winners “have done us proud,” said Kuok, highlighting the example of Dr. Sung Min, consultant in the department of child and adolescent psychiatry at IMH. Sung established Singapore’s first public autism clinic at IMH in April 2006, having spent a month studying in the UK as part of her HMDP award the previous year. The clinic has now seen more than 650 patients.

The total budget for this year’s awards is S$5.7 million – co-funded by NHG and the Ministry of Health (MOH).

The HMDP was launched in 1980 by MOH, but administration has since been devolved to NHG and SingHealth.

The unsung heroes of healthcare: Part I

2009-09-25T02:12:00.000-07:00

Medical Tribune August 2009 SFXII

David Brill

Born in 2004 from the legacy of SARS, the annual Healthcare Humanity Awards are given to those who go above and beyond the call of duty to improve the care and wellbeing of patients. David Brill spoke to two of this year’s recipients about their achievements, challenges and hopes for the future.

The children’s champion: Ensuring a bright future for Singapore

Some doctors continue their medical education by reading journals and taking exams. Others brush up by attending conferences or participating in workshops.

Dr. Ong Say How is different. He keeps up to date by watching cartoons and listening to pop music. Unlikely sources of information for most specialists, but an important part of the routine for this dedicated child and adolescent psychiatrist. Following popular culture helps him better relate to his patients, he says. And few would question his approach: in 2005, Ong received the Best Psychiatrist Award from the prestigious Columbia University in New York, US, for his volunteer work in Caring@Columbia – a program for underprivileged and at-risk children. Other accolades have followed since returning to Singapore, culminating in his recent Healthcare Humanity Award.

Engaging troubled children would be a daunting task for most, but Ong is completely relaxed around youngsters. This, he says, is his strength – allowing him to break down the formality of a clinic setting using humor, anecdotes and roleplays. “I think like a kid sometimes, so we can talk on the same page and be on the same wavelength. Most of the time when kids come to me they have already seen their teachers, seen their school counselors, talked at length with their parents, and nothing has helped. So I have to take a different approach to get them to confide in me,” he says.

As a consultant and deputy head of child and adolescent psychiatry at the Institute of Mental Health, Ong has spent much of his career engaging with the youth of Singapore. He also runs an outpatient clinic at the Child Guidance Clinic and is involved with various workgroups and committees, including the national Pediatrics Services Review Committee. His caseload is wide and varied, but most commonly involves anxiety, depression, stress-related conditions and attention deficit hyperactivity disorder.

Progress has been made but child psychiatry remains a “high-need medical area” for Singapore, he says. Surveys point to a fairly high number of undiagnosed psychiatric disorders among schoolchildren, suggesting that screening is one of the areas in need of strengthening. Improving step-down facilities and access to treatment in the community are also amongst the most pressing challenges, he says.

“Some kids fall through the gaps because they are not very aware of the services available to them, or sometimes still face a stigma about seeking psychiatric help. And parents alike … a lot of families are still stricken with fear when it comes to seeking help for their mental health. Rather they will bring the kids to see a non-professional, or a temple medium or a traditional healer, and in the end they suffer.

“Recently I lost a kid because the parents were not keen to bring the child forward and refused to seek help in the community setting. Someone so young and intelligent and with so many good things going for him – it’s just sad that the parents or the child himself refused to seek proper help.”

Despite the tragic stories such as this, Ong remains upbeat about the future of Singapore’s youth. New outreach programs are underway in schools, bringing psychiatrists closer to counselors and teachers, and opening up new avenues for screening and prevention. Mental wellbeing, Ong hopes, will one day be entrenched in the national curriculum. In the meantime he will continue to champion for the children through his tireless work in the clinics and community.

“Seeing them open up and let you into their thoughts and feelings is the first step to building that rapport and to making the first change. It’s very rewarding when they start to trust me that I will help see them through and see them smile again. The children are our future, and in order to secure a future for Singapore we must make sure that they are well taken care of,” he says.

The Unsung Heroes of Healthcare: Part II

2009-09-25T02:07:00.000-07:00

Medical Tribune August 2009 SFXII
David Brill

Born in 2004 from the legacy of SARS, the annual Healthcare Humanity Awards are given to those who go above and beyond the call of duty to improve the care and wellbeing of patients. David Brill spoke to two of this year’s recipients about their achievements, challenges and hopes for the future.

A picture of health: Putting patients at the center

Associate Professor Chia Sing Joo is designing a hospital. It’s his biggest project to date, yet he works on it alone. There are no meetings, no paperwork and no phone calls – he’s been doing it for years and no one even knows about it.

The blueprints, for now at least, are in Chia’s mind. He refines them constantly, hoping one day for the opportunity to put them to use. “I would like to build a hospital which is totally patient-focused,” he explains. “Patients don’t have to wait for a long time, and they don’t have to worry about unforeseen outcomes because the process is so transparent. The doctors all share the same values and are not for profit. Every patient would want to come here, and every doctor would want to train here.”

This vision may sound ambitious, but Chia is already striding toward it. As chairman of the division of surgery at Tan Tock Seng Hospital (TTSH), Singapore, he has worked hard to improve processes of care and ensure that the welfare of patients remains the primary focus. Day surgery is up; unnecessary inpatient stays are down. Increased collaboration with GPs has freed up hospital beds and reduced waiting times, and the establishment of a multidisciplinary surgical oncology group has improved quality of care and outcomes for cancer patients. The list goes on, and many more projects lurk in the pipeline.

Communication is a theme that surfaces repeatedly in conversation with Chia, and would form a central pillar in the ethos of his patient-centric hospital. As a member of TTSH’s mediator team he is often on the front line against complaints, and has come to believe that the majority could be avoided simply by spending more time talking to patients and their relatives. Misinformation can lead to misunderstandings, and anxiety and stress typically follow, he says. And nowhere is this need for openness greater than when advising patients on surgery.

“First I explain the options to the patient and the complications of each,” says Chia, who is also a senior consultant urologist. “Second, I tell them what I would choose if they were my uncle or auntie. Finally, I let them know that there is no guaranteed surgery in this world. Expectations are important – patients have to understand that we are only human and a lot of things are beyond our control. If you do these things, there are very few patients who will not trust you. If complications arise, 99 percent will understand that you have done your best and this was something unavoidable and unpredictable.”

Chia’s quest to improve patient-doctor communication, however, does not end in the clinic or the operating theatre. He speaks in public forums, has recently published a book entitled Male Urological Problems: The Essential Guide for Every Man & Couple, and is now working on another layman-orientated book about “how to spice up your sex life”. He also gives out his home and hand phone numbers to patients, and encourages them to call if they have any concerns or questions. And, it seems, they don’t hesitate: he estimates that his phone rings every 5 or 6 minutes on a typical working day.

Even by doctors’ standards, Chia is a busy man. In between the phone calls, books and surgery, he also spends one day a week as a visiting consultant at KK Women’s and Children’s Hospital, works on several research papers, oversees the development of a new training center at TTSH, raises three sons – none of whom want to be doctors – and still finds the time to run for an hour before dinner. Citing “every day” as his career highlight, however, it is clear that he wouldn’t change a thing. Except, of course, for the long-awaited chance to roll out those imaginary blueprints. “If I really had the opportunity to build my own hospital, that would be a great challenge for me,” he says.

Urine test could allow for lung cancer risk prediction

2009-09-25T01:59:00.001-07:00

Medical Tribune August 2009 P12
David Brill

A simple urine test could one day reveal which smokers are at greatest risk of developing lung cancer, according to a team of Singaporean, Chinese and American scientists.

The group recently reported the first link between elevation of certain urinary metabolites – total NNAL* – and increased lung cancer risk in humans. Cigarette smokers with the highest total NNAL levels were over twice as likely to develop lung cancer.

A commercially available test remains at least 5 years off, but the identification of these urinary biomarkers raises “an exciting possibility,” say the researchers.

“Such a test would enable doctors to screen more frequently for lung cancer in smokers with high levels of biomarkers, and provide a strong incentive for these smokers to quit smoking,” said study authors Associate Professor Yuan Jian-Min of the University of Minnesota, US, and Associate Professor Koh Woon-Puay of the National University of Singapore, in a joint statement to Medical Tribune.

“With the identification of new biomarkers, we could ultimately develop an assay that simultaneously quantifies a panel of tobacco carcinogens or their metabolites to best predict the risk of lung cancer for an individual smoker,” they said.

The work goes some way towards explaining why some smokers develop lung cancer while others do not. With over 60 established carcinogens in cigarette smoke, it may be that individual differences in the uptake and metabolism of particular chemicals play an important role in the development of cancer, the authors say.

One such carcinogen, NNK**, has been strongly linked to lung cancer but an epidemiological link had only been shown in animal studies.

Yuan, Koh and colleagues instead investigated levels of NNAL – a metabolite of NNK – in a nested case-control study using data on 63,257 men and women from the Singapore Chinese Health Study, and 18,244 men from the Shanghai Cohort Study. They identified 246 cases of incident lung cancer, and 245 matched controls. [Cancer Res 2009;69:2990-5]

The odds ratio of developing lung cancer was 2.11 for smokers who were in the highest tertile of urinary total NNAL before cancer diagnosis, compared to those in the lowest tertile (95% CI 1.25 – 3.54; P for trend = 0.005).

Combination with cotinine, a nicotine metabolite, further increased the predictive value of NNAL: the odds ratio for developing cancer was 8.47 for smokers in the highest tertile for both markers, compared to those in the lowest tertile (95% CI 3.69 – 19.46; P for trend – 0.005).

“Biomarkers for prediction of cancer risk are useful as proxy measures of outcome in interventional studies. Nevertheless, for smokers, the best intervention for the reduction of lung cancer risk is still to quit smoking,” added Yuan and Koh.

------------------------------------------------------------------------------------------------
* NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Total NNAL is the sum of NNAL and its glucuronides.
**NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

New CV risk score could replace Framingham in UK

2009-09-25T01:59:00.000-07:00

Medical Tribune August 2009 P13

David Brill

The long-established rules for cardiovascular risk assessment could be overhauled in the UK, following calls for the Framingham risk score to be abandoned in favor of a newer model.

An independent analysis found the QRISK score to be superior to Framingham on all measures – identifying a higher proportion of people who went on to develop cardiovascular disease.

The findings prompted a resounding endorsement of QRISK in a British Medical Journal editorial, recommending its routine adoption. Reports have since emerged that QRISK is under review at the UK National Institute for Health and Clinical Excellence (NICE), and is set to be integrated into software packages used by GPs.

University of Oxford statisticians validated QRISK using an independent cohort of 1.07 million patients from 274 UK general practices. There were 43,990 cardiovascular events over a median of 4.9 years’ follow-up. [BMJ 2009 Jul 7;339:b2584]

QRISK under-predicted cardiovascular risk by 12 percent (13 percent for men and 10 percent for women) but was considerably more accurate than the Anderson Framingham algorithm, which overestimated risk by 23 percent (32 percent for men and 10 percent for women).

“We believe this formula has the potential to save many thousands of lives, by helping clinicians to more accurately predict those at risk of developing cardiovascular disease – the nation’s biggest killer,” said Professor Julia Hippisley-Cox of the University of Nottingham, who led the team which developed the QRISK score.

“It will arm doctors with all the information they need to decide how best to target patients with preventative measures such as lifestyle advice and cholesterol-lowering treatments. We are delighted to receive another strong endorsement of the value of QRISK in assessing the risk of heart disease in the UK population,” she said.

QRISK includes most of the traditional risk factors seen in the Framingham equations but also includes family history, social deprivation, body mass index and use of antihypertensive treatments. It was first developed and validated in 2007, using data from 1.28 million patients from 318 UK general practices. [BMJ 2007 Jul 21;335(7611):136]

Further refinements to the model – QRISK2 – were published last year to include ethnicity and other conditions such as type 2 diabetes, hypertension, atrial fibrillation, renal disease and rheumatoid arthritis. The updated version, however, has yet to receive independent validation. [BMJ 2008 Jun 28;336(7659):1475-82]

The external validation of the original QRISK was commissioned by the UK Department of Health to compare the model against the Anderson Framingham algorithm, which is presently recommended by NICE as the basis for deciding on whether to prescribe statins.

The incidence rate of cardiovascular events was 30.5 per 1,000 person years among men who were classed as high risk by QRISK, compared to 23.7 per 1,000 person years among men classed as high risk by the Anderson Framingham score. In high-risk women, the incidence rates were 26.7 per 1,000 person years for those identified with QRISK, and 22.2 per 1,000 person years for those identified by Anderson Framingham.

Despite the improvements with QRISK, the data provide “a sobering message about the current state of cardiovascular risk prediction,” according to the authors of the accompanying editorial. Increased usage, improved data collection and further refinements to the system could however increase the accuracy of risk prediction in future, wrote Professor Rod Jackson of the University of Auckland, New Zealand, and colleagues. [BMJ 2009 Jul 7;339:b2673]

Fertility preservation guidelines overlooked by oncologists

2009-09-03T03:09:00.000-07:00

Medical Tribune July 2009 P4
David Brill

The majority of US oncologists do not follow recommendations on discussing fertility preservation with cancer patients, a survey shows.

Although seventy nine percent of respondents reported broaching the subject with patients, less than 25 percent referred them to a specialist or provided educational materials.

Just 38 percent were even aware of the existence of the guidelines, issued by ASCO in 2006. [J Clin Oncol 2006 Jun 20;24(18):2917-31]

The findings could prompt the development of new training programs for physicians and nurses, said study author Dr. Gwendolyn Quinn of the H. Lee Moffitt Cancer Center and Research Institute, Miami, US.

“We send patients to get wigs before they lose their hair during chemotherapy. We give medications to prevent nausea. Discussing fertility preservation should be something else that we do early in a patient’s care, rather than waiting until infertility occurs,” she said.

The survey was mailed to 1,979 oncologists – 613 of whom completed it. Those working in gynecological oncology and hematological/medical oncology were the most comfortable with having fertility preservation conversations. Physicians’ views of fertility preservation were also a key factor: those with a favorable attitude towards preservation were nearly five times as likely to discuss the options.

The main reason given for avoiding the discussion was that patients were too ill to delay treatment. Of greater concern, however, was physicians who skipped it because they did not believe that the patient was going to survive their cancer, said Quinn.

“It’s the patient’s right. It’s their choice. They may never pursue it, and some of them can’t afford it, but just to be given that information is important, and it’s perhaps not the role of the physician to make decisions. The guidelines say all patients – they don’t specify the healthiest of patients or the ones most likely to survive,” she said.

Even those who do not survive may wish to review their options for “posthumous parenting,” she added, noting that many US couples cryopreserve embryos or sperm for this purpose before beginning treatment.

Quinn acknowledged, however, that there can be many barriers to discussing fertility preservation, including financial constraints for the patient, or a lack of physician resources in certain geographic areas.

“It’s important to bring it up very near to the time of diagnosis, but we understand that it’s an emotional time,” she said. Future training could move the emphasis towards nurses, who may be better placed to have an in-depth discussion with the patient, she added.

Statins could boost prostate health, studies show

2009-09-03T03:06:00.000-07:00

Medical Tribune July 2009 P4

David Brill

Evidence is growing to suggest that statins could help to maintain a healthy prostate – protecting against both benign and malignant disease.

Recent studies have found that statins lowered the risk of developing prostate cancer, reduced the aggressiveness of cancers, and reduced the risk of cancer recurrence after surgery.

Other reports have suggested that the drugs can protect against lower urinary tract (LUT) symptoms, benign prostatic hyperplasia (BPH) and even erectile dysfunction.

Researchers, however, are urging caution, saying that further studies are needed before firm conclusions can be drawn.

Six key studies were presented recently at the annual meeting of the American Urological Association (AUA) in Chicago, US. Three come from a single cohort of 2,447 men aged 40 to 79, who have been followed since 1990 by researchers at the Mayo Clinic, Minnesota, US.

The first study found that men who were taking statins were three times less likely to develop prostate cancer than non-users. Just 6 percent of statin users developed cancer over a median of 14.1 years of follow-up – a considerable reduction compared to the US national average, which sees around 17 percent of all men diagnosed with prostate cancer in their lifetime.

The second study, which included only 1,480 of the men, found that statins reduced the risk of erectile dysfunction in those aged over 60. This apparent protective effect increased over time – men who had been taking statins for 9 years or more were 64 percent less likely to develop the condition than men not taking statins, whereas those taking statins for less than 3 years were equally as likely.

A third analysis of the Mayo Clinic cohort, meanwhile, reported that statin users had a 57 percent reduction in risk of developing BPH, and a 63 percent risk reduction for developing LUT problems.

"If you are taking a statin for a heart condition or to lower cholesterol, these studies suggest that statins could have other benefits," said one of the study authors Dr. Jennifer St. Sauver, an epidemiologist at the Mayo Clinic. "However, it's very clear we need more information before men are advised to start taking statins for their urological health."

The fourth study presented at the AUA meeting found that men taking statins at the time of radical prostatectomy for prostate cancer were 30 percent less likely to have a recurrence. They also had lower prostate-specific antigen levels than non-users, and were more likely to have T1-stage disease. The study included 1,325 men, of whom 237 were taking statins at the time of surgery.

“Our findings suggest that statins may slow prostate cancer progression after radical prostatectomy," said study author Dr. Robert Hamilton, of the University of Toronto, Canada.

“Although the results of these studies are exciting, they need to be confirmed,” he added. “At this point we cannot say with confidence that statins reduce the risk of prostate cancer recurrence after radical prostatectomy."

The fifth study, led by Johns Hopkins University, US, found that prostate cancer was less aggressive in statin users than non-users. Of 1,282 men who underwent radical prostatectomy over 5 years, the 418 who were taking statins had lower tumor volume, lower prevalence of positive surgical margins, and lower percentage of cancer in their prostatectomy specimens.

The final study, meanwhile, suggests that statins might exert their beneficial effects by reducing inflammation within prostate tumors. Researchers from Duke University Medical Center, US, examined specimens from 254 men who had undergone radical prostatectomy, and found that inflammation was reduced by 72 percent in statin users compared to non-users.

Despite the positive results presented at the AUA, not all studies have shown benefits of statins of prostate cancer outcomes. One paper published earlier this year found that statin usage had no effect on progression-free survival after radiotherapy for prostate cancer. [Urology 2009 Jan;73(1):158-62. Epub 2008 Aug 22]

Some researchers have even suggested that statins could actually increase prostate cancer, and have called for further attention to be given to the issue. [Cancer Epidemiol Biomarkers Prev 2008 Feb;17(2):459]

Gemcitabine improves safety for adjuvant pancreatic cancer therapy

2009-09-03T03:04:00.000-07:00

Medical Tribune July 2009 P8
David Brill

Gemcitabine is a safer option than 5-fluorouracil/folinic acid (5-FU/FA) for the adjuvant treatment of pancreatic cancer, results of a phase III trial suggest.

Investigators from the European Study Group for Pancreatic Cancer (ESPAC) found that there was no difference in survival between the two therapies, but fewer side effects with gemcitabine.

The study included 1,088 patients who were randomized to one of the two therapies following resection of pancreatic ductal adenocarcinoma. It is the largest adjuvant trial ever carried out in this patient population and the first to directly compare gemcitabine against 5-FU/FA in the adjuvant setting, the researchers say.

“This study is important because it shows no difference between these treatments in prolonging survival,” said lead author Professor John Neoptolemos, head of surgery and oncology at the University of Liverpool, UK.

“On the basis of the safety profile, however, this trial shows that gemcitabine is likely to be the preferred adjuvant therapy. We are now also looking at combining the two treatments to see if we get a better response, because the drugs have different mechanisms of action,” he said.

After a median of 34 months follow up, overall survival times were 23.6 months for patients receiving gemcitabine and 23 months for those receiving 5-FU/FA.

Ten percent of 5-FU/FA patients experienced treatment-related hospitalization, compared to 3.5 percent of gemcitabine patients. Other adverse events which were more common in the 5-FU/FA group included stomatitis (10 percent versus 0 percent; P<0.001) and diarrhea (13 percent versus 2 percent; P<0.001). Some gemcitabine patients, conversely, experienced a drop in platelet count which was not seen in the 5-FU/FA group (1.5 percent versus 0 percent; P=0.0034).

Gemcitabine is typically used in the US for the adjuvant treatment of pancreatic cancer, whereas 5-FU/FA is the standard in some parts of Europe. It was previously unclear which treatment offered a better prognosis.

The trial, known as ESPAC-3, included patients from 16 countries, who were randomized between 11 July 2000 and 12 Jan 2007. Ages ranged from 31 to 85, with a median of 63.

The results will also help to reinforce the design of the upcoming ESPAC-4 trial, added Neoptolemos. The study is set to compare gemcitabine alone against gemcitabine plus capecitabine – a prodrug which is converted to 5-FU in tumors.

No change needed for anal cancer treatment

2009-09-03T03:01:00.001-07:00

Medical Tribune July 2009 P8

David Brill

Radiotherapy combined with 5-fluorouacil (5-FU) and mitomycin-C should remain the standard of care for anal cancer, say UK investigators.

Pull quote: “We recommend that radiotherapy with 5-FU and mitomycin-C remains the standard of care for this condition.”Results of the largest-ever trial for anal cancer showed no benefit from switching mitomycin-C for cisplatin, or from adding maintenance chemotherapy to the regimen.

The Second UK Phase III Anal Cancer Trial (ACT II) included 940 patients (median age 58), followed up for a median of 3 years. Those who relapsed or failed to respond to therapy were treated with surgery.

The results of the trial provide good news, despite the lack of benefit shown by the alternative treatment regimens, said lead investigator Dr. Roger James, a consultant radiation oncologist at Maidstone Hospital, Kent, UK.

“Overall the outcome for patients in this study is excellent, with a 95 percent complete response rate at 6 months and an 85 percent survival at 3 years. These are very good results relative to the international trials published so far. We recommend that radiotherapy with 5-FU and mitomycin-C remains the standard of care for this condition,” he said.

Patients were recruited from 2001 to 2008. All were given radiotherapy and 5-FU, and were randomized to receive either additional mitomycin-C or cisplatin. They were then further randomized: half received an extra round of maintenance chemotherapy, comprising two cycles of cisplatin and 5-FU at weeks 11 and 14, and half did not.

Six-month response rates were 94.5 percent for mitomycin-C and 95.4 percent for cisplatin (P=0.53). Non-hematological toxicity was comparable between the groups, affecting 60.2 percent of mitomycin-C patients, compared to 64.6 percent of cisplatin patients (P=0.17). There was, however, more hematological toxicity in the mitomycin-C group (24.7 percent) compared to the cisplatin group (13.4 percent; P<0.001).>

Maintenance chemotherapy had no impact on 3-year recurrence-free survival rates, which were 75 percent for both groups. Overall survival at 3 years was also not significantly different between those who received maintenance therapy (85 percent) and those who didn’t (84 percent).

The ACT II trial results bring another blow to hopes that cisplatin would prove beneficial in anal cancer. Early data had shown anal tumors to be sensitive to a combination of cisplatin and fluorouacil, but a trial of 682 patients, published last year, found that it offered no survival benefits over mitomycin-based therapy. Moreover, cisplatin-treated patients were almost twice as likely to undergo colostomy as those treated with mitomycin (19 percent versus 10 percent; P=0.02), the US Gastrointestinal Intergroup trial Radiation Therapy Oncology Group reported. [JAMA. 2008;299(16):1914-1921]

Hypertension study named ‘Trial of the Year’

2009-09-03T02:58:00.000-07:00

Medical Tribune July 2009 P9

David Brill

The Hypertension in the Very Elderly Trial (HYVET) has been named as 2008’s Trial of the Year, reflecting its potential to change healthcare and “improve the lot of mankind.”

The study found that antihypertensive treatment reduced the risk of cardiovascular events, death from stroke, and death from any cause in over-80s.

The largest clinical trial of its kind, HYVET was carried out against a backdrop of uncertainty about the benefits of blood pressure (BP) lowering in the very elderly.

The award was bestowed recently by the Society for Clinical Trials (SCT) and Project ImpACT (Important Achievements of Clinical Trials). HYVET was also voted Medscape’s most important clinical trial of the year, and named in the American Heart Association’s top 10 advances in stroke and heart disease research for 2008.

“The results of HYVET will have important implications for the generation of future guidelines and mean that very elderly individuals with sustained systolic BPs of 160 mmHg or more should now be appropriately assessed and treated in accordance with these findings,” said trial coordinator Dr. Nigel Beckett, from the Care of the Elderly group at Imperial College London, UK.

Dr. Deepak Bhatt, director of the Integrated Interventional Cardiovascular Program at Brigham and Women’s Hospital, US, added: “HYVET is a landmark study that challenges current paradigms which question the risk to benefit of treating hypertension in patients older than 80 years of age. The results of this study should encourage practitioners to treat elevated systolic BP in the very elderly.”

HYVET involved 3,845 patients from 13 centers in Europe, China, Tunisia and Australasia, who had a sustained systolic BP of 160mmHg or more. They were randomized to placebo or sustained release indapamide (1.5 mg), with perindopril (2 or 4mg) to be added if the BP target of 150/80 mmHg could not be reached. [N Engl J Med 2008 May 1;358(18):1887-98]

After a median of 1.8 years of follow-up, treatment reduced the risk of death from stroke by 39 percent (unadjusted hazard ratio [HR] 0.61; P=0.046), death from any cause by 21 percent (unadjusted HR 0.79; P=0.02), risk of any cardiovascular event by 34 percent (unadjusted HR 0.66; P<0.001)>

There were also non-significant risk reductions for outcomes of any stroke (unadjusted HR 0.70; P=0.06) and death from cardiovascular cause (unadjusted HR 0.77; P=0.06) in the treatment group.

The SCT / Project ImpACT awards are given to trials which are deemed, among other criteria, to “have improved the lot of mankind,” and “provided the basis for a substantial, beneficial change in health care.”

Hong Kong symposium: Facing up to the diabetes epidemic

2009-09-03T02:51:00.000-07:00

Medical Tribune July 2009 P10
David Brill

The global diabetes epidemic has transcended medical specialties and become a priority for all healthcare professionals, say the organizers of this year’s Hong Kong Diabetes and Cardiovascular Risk Factors – East Meets West (EmW) symposium.

The meeting, to be held in September, will bring attendees up to speed on the latest research into the twin burdens of diabetes and cardiovascular disease (CVD).

With topics ranging from lifestyle interventions and nutrition to the management of diabetes in pregnancy, the symposium promises to deliver a host of practical insights for day-to-day patient care. Leading cardiologists will review strategies for assessing cardiovascular status in people with diabetes, while other sessions will address the crucial importance of good glycemic control, particularly in light of major recent studies such as ACCORD*, ADVANCE** and VADT***.

Other highlights include cutting-edge sessions on the pathogenesis of type 2 diabetes, including pancreatic beta-cell pathology, the developmental-origins hypothesis of diabetes and the role of lipid metabolism in insulin resistance.

“The rate of diabetes is now rampant in Asia, especially in young to middle-aged people. In some countries, the prevalence can be as high as 10 percent,” said Dr. Gary Ko, chairman of the organizing committee for the EmW symposium, now entering its eleventh year.

“The economic burden of diabetes to governments, and the health impact to individuals, cannot be overemphasized. Diabetes can be linked to all systems and specialties. We believe that a good and up-to-date understanding of diabetes is essential for all practicing doctors, be they family physicians, specialists or from other fields,” he said.

“We hope to arouse the attention of our clinicians, particularly those working in Asia, to the increasing epidemic of diabetes, its devastating morbidity and mortality, and what needs to be done to minimize the impact of diabetes and CVD on society.”

Managing weight and diet in type 2 diabetics is just one of the many challenging areas which will be addressed in depth at the EmW symposium, said Professor Ronald Ma, chairman of the EmW scientific committee. He highlighted a presentation by world-renowned endocrinologist Professor Harold Lebovitz, who will introduce a new gastrointestinal ‘pacemaker’ known as Tantalus, which can regulate appetite and help patients to lose weight. Leading Hong Kong nutritionist Ms. Lorena Cheung will offer a different angle – providing insights on how to advise patients on glycemic index and glycemic load.

US obesity expert Professor John Foreyt will also share his knowledge and experience as an investigator on the Look-AHEAD (Action for Health in Diabetes) trial – a successful lifestyle intervention study which helped overweight diabetics to lose an average of 8.6 percent of their weight, improve fitness, reduce medications and lower HbA1C by 0.7 percent, after just one year. [Diabetes Care 2007 Jun;30(6):1374-83]

The ACCORD, ADVANCE and VADT trials have shown the critical need to balance the benefits of blood glucose lowering against potential drug-related side effects, notably weight gain and hypoglycemia. In this session, Professor Brian Frier, of the University of Edinburgh, UK, will give an overview of hypoglycemia: its impact on cardiovascular events and the underlying mechanisms.

Hong Kong expert Professor Terrence Lao, meanwhile, will provide an Asian perspective on the ever-growing problem of gestational diabetes, while Professor Edwin Lee will probe the link between anti-psychotic medications and metabolic disorders. Finally, world expert Professor Edward Fisher will share his wisdom on the rationale and evidence for peer support in the management of diabetes.

Over 600 attendees from all over the world are expected at the EmW symposium, which will take place at the Hong Kong Convention and Exhibition Centre from 30 September to 1 October 2009.

The event is jointly organized by the Hong Kong Institute of Diabetes and Obesity at the Chinese University of Hong Kong, CMPMedica Pacific Limited, the Hong Kong Atherosclerosis Society, the Hong Kong Association for the Study of Obesity and the Hong Kong Foundation for Research and Development in Diabetes, with support from the Hong Kong Dietitians Association.

For more information, see: http://www.eastmeetswest.org.hk/

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*ACCORD: Action to Control Cardiovascular Risk in Diabetes
**ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
***VADT: Veterans Affairs Diabetes Trial

Singapore moves center stage in childhood vaccine manufacturing

2009-09-03T02:47:00.000-07:00

Medical Tribune July 2009 SFI

David Brill

Singapore is set to produce GlaxoSmithKline (GSK)’s new pediatric pneumococcal conjugate vaccine, following the opening of a S$600 million manufacturing plant in Tuas.

Commercial production of the vaccine, which protects against diseases such as bacteremic pneumonia, meningitis and acute otitis media, is expected to begin in 2011.

The new plant is GSK’s first primary vaccine manufacturing facility in Asia, and only the second site in the world to manufacture the pneumococcal vaccine, after Belgium.

It is also one of the first centers in Singapore to produce biologic drugs – a considerably more complex process than manufacture of non-biologic agents. Four other biologics production plants are under construction in Singapore, and five more have been announced.

“The burden of childhood pneumococcal diseases is considerable and every year around 1 million children under 5 years of age die from pneumococcal infections,” said Mr. Emmanuel Amory, vice president, global industrial operations, GSK Biologics. “This plant is part of GSK’s commitment to ensure maximum availability of this life-saving vaccine.”

The pneumococcal vaccine protects children against Streptococcus pneumoniae and Nontypeable Hemophilus influenza – two of the major pathogens responsible for pediatric illnesses, particularly in developing countries.

The opening of the plant in June by Prime Minister Lee Hsien Loong marked the 50th anniversary of GSK’s business in Singapore – an investment which now exceeds S$1.5 billion and sees over 1,000 staff employed here. The company already has two other production and supply centers in the city-state.

GSK’s Chief Executive Officer Mr. Andrew Witty also announced the establishment of a S$30 million endowment fund to support graduate students in healthcare policy and green chemistry. Singapore’s Economic Development Board will add a further S$20 million, bringing the total fund to S$50 million.

Voglibose prevents diabetes in high-risk Asians

2009-09-03T02:38:00.000-07:00

Medical Tribune July 2009 SFII
David Brill

Alpha-glucosidase inhibitors could play an important role in preventing, as well as treating, the growing epidemic of type 2 diabetes in Asia.

A recent trial found that adding voglibose to diet and exercise counseling almost halved the risk of developing diabetes in Japanese patients with impaired glucose tolerance (IGT).

The study extends similar findings from Western populations, where acarbose has been shown to reduce the progression from IGT to diabetes – notably in the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial. [Lancet 2002;359(9323):2072-7] Equivalent studies in Asian populations, however, were previously lacking.

The researchers, led by Professor Ryuzo Kawamori, Juntendo University School of Medicine, Tokyo, randomized subjects to placebo or voglibose (0.2 mg three times a day). The trial was terminated early, following an interim analysis. [Lancet 2009;373(9675):1607-14]

At a mean of 48 weeks of treatment, 50 of 897 patients taking voglibose had developed diabetes, compared to 106 of 881 who took placebo (hazard ratio 0.595, 95 percent CI 0.43 – 0.82; P=0.0014). More people achieved normoglycemia in the voglibose group: 559 of 897, versus 454 of 881 in the placebo group (P<0.0001).

Singapore diabetes expert Dr. Kevin Tan said that alpha-glucosidase inhibitors offer a good option in cases which need more aggressive intervention than lifestyle therapies alone.

“The results of this study mirror those of acarbose in STOP-NIDDM and demonstrate the efficacy of this group of alpha-glucosidase inhibitors in preventing type 2 diabetes – now in an Asian population as well,” said Tan, vice president of the Diabetic Society of Singapore and a private practitioner at Mount Elizabeth Medical Centre.

“Lifestyle interventions remain central as they are simple and available to all and, moreover, their effects are sustainable. However, lifestyle interventions are notoriously difficult to maintain at the same intensity over time and therefore safe and effective medications to complement them are needed as well. Alpha-glucosidase inhibitors are amongst the safest of compounds as there is minimal absorption into the body and no interference with the metabolism of other drugs,” he said.

The epidemic of type 2 of diabetes continues to boom in Asia, with total numbers predicted to increase from some 114 million patients in 2007 to 180 million in 2025. The prevalence of IGT is expected to rise from 157 million to 213. [JAMA 2009 May 27;301(20):2129-40]

The worst-affected countries appear to be those undergoing significant economic and dietary changes: the overall prevalence in China, for example, rose from 1 percent in 1980 to 5.5 percent in 2001. For affluent urban areas such as Hong Kong and Taiwan, the figure is as high as 10 percent. [Diabetes Res Clin Pract 2006 Aug;73(2):126-34]

Adverse events in the Japanese study were more common with voglibose than placebo (P<0.0001) – mostly comprising gastrointestinal symptoms such as flatulence, abdominal distention and diarrhea. There were also six serious advents in the voglibose group, consisting of colonic polyp, cholecystitis, inguinal hernia, liver dysfunction, rectal neoplasm and subarachnoid hemorrhage. Two placebo patients experienced serious events – one cerebral infarction and one case of cholecystitis.

Alpha-glucosidase inhibitors could feasibly be given in combination with metformin, which has also shown good results in diabetes prevention studies, wrote Dr. André Scheen of the University of Liège, Belgium, in an accompanying commentary. This dual approach, using acarbose, is currently being trialed in Canada. [Lancet 2009 May 9;373(9675):1579-80; Diabetes Obes Metab 2006;8(5):531-7]

Stockings ineffective for DVT prevention after stroke

2009-09-03T02:36:00.000-07:00

Medical Tribune July 2009 SFIV

David Brill

Compression stockings do not reduce the risk of deep vein thrombosis (DVT) in stroke patients, despite their widespread usage for this purpose, a major international study shows.

The multicenter CLOTS* 1 trial, involving 2,518 patients, found that stockings were not only ineffective, but increased the risk of ulcers, blisters and skin necrosis.

The results have prompted calls for revision of guidelines, as experts point to substantial cost and time savings from abandoning the practice. Some hospitals in Asia are already reviewing the findings, and may stop using stockings for stroke patients in the near future.

The trial was carried out across 64 centers in the UK, Australia and Italy. DVT occurred in 10 percent of patients who were randomized to thigh-length stockings, and 10.5 percent who were randomized to no stockings. [Lancet 2009 Jun 6;373(9679):1958-65]

All patients were immobile and had been admitted to hospital within a week of acute stroke. They were assessed for DVT at 7 to 10 days, and again at 25 to 30 days.

“In this study, we have shown conclusively that compression stockings do not work for stroke patients,” said study author Professor Martin Dennis of the University of Edinburgh, UK. “National guidelines need to be revised and we need further research to establish effective treatments in this important group of patients.

“Given that most national guidelines recommend stockings in at least some patients, the results of our study will affect the treatment of millions of patients each year. Abandoning this ineffective and sometimes uncomfortable treatment will free up significant health resources – both funding and nurse time – which might be better used to help stroke patients,” he said.

DVT is thought to be less common among Asians than Western populations, but compression stockings are nonetheless commonly used for prophylaxis in stroke patients with lower limb weakness. [Ann Acad Med Singapore 2007 Oct;36(10):815-20]

Dr. Lee Sze Haur, senior neurology consultant at the National Neuroscience Institute (NNI), Singapore, said, however, that this practice “will likely change” in light of the new data.

“Based on the CLOTS trial, there is good reason to consider discontinuing the use of graded compression stockings for prevention of DVT in patients with acute stroke, as this will save cost and time as well as reduce the incidence of skin complications,” said Lee.

National University Hospital, meanwhile, is currently reviewing the evidence before changing its use of compression stockings, according to senior neurology consultant Dr. Bernard Chan. He noted that stockings remain effective for DVT prevention in post-surgical patients, but said that the usage for stroke has been “a long-standing practice without good clinical evidence.”

Two other studies are in progress to establish alternatives for post-stroke DVT prevention. CLOTS 2 compares thigh-length and below-knee stockings, but is now expected to finish early in light of CLOTS 1. The third trial is testing the effects of intermittent pneumatic compression, and is scheduled for completion in 2013.

Blisters, ulcers, skin breaks and necrosis were reported in 64 of the 1,256 patients given stockings in CLOTS 1 (5 percent), compared to just 16 of 1,262 control patients (1 percent; odds ratio 4.18; 95 percent CI 2.40 – 7.27).

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*CLOTS: Clots In Legs Or Stockings After Stroke

Tumor compartments: A ‘revolution’ in cancer surgery

2009-09-03T02:34:00.000-07:00

Medical Tribune July 2009 SFIV
David Brill

A novel approach to treating cervical cancer may signal the end of the radical hysterectomy and could one day revolutionize the field of surgical oncology, says a pioneering team of German surgeons.

By removing only the embryologically defined ‘compartments’ in which tumors are most likely to spread, the surgeons can spare surrounding tissues and minimize collateral damage.

The technique reduces complications and recurrence rates, removes the need for radiotherapy, and could improve survival rates by as much as 20 percent compared to conventional hysterectomy, the group reported recently in The Lancet Oncology.

Research is already underway to extend the concept to vulvar and endometrial cancers, said lead researcher Professor Michael Höckel, chairman of the department of obstetrics and gynecology at the University of Leipzig, Germany.

“We have found that the tumor is confined for a long time in its natural course to a defined tissue compartment – it’s not like an explosion infiltrating all tissues around the tumor,” said Höckel.

“This new perspective in surgical anatomy enables you to see and operate on the tissue in which the tumor is spreading, irrespective of the tumor entity. This is a general principle which could really revolutionize surgical treatment for malignant disease,” he said.

The cervical cancer procedure – total mesometrial resection (TMMR) – targets only the non-distal part of the Müllerian compartment. Surgeons remove the proximal vagina, uterus and extra-cervical mesenchyme but spare nearby non-Müllerian tissues, including the nerves which supply the vagina, bladder and rectum.

Results from 212 women who underwent TMMR without radiotherapy at the University of Leipzig show an overall 5-year survival rate of 96 percent, and recurrence-free survival of 94 percent. The study was conducted prospectively from October 1999 to July 2008 on women with early-stage cancers: International Federation of Gynecology and Obstetrics (FIGO) stages IB, IIA and selected IIB. [Lancet Oncol 2009 May 29; Epub ahead of print]

Sixty two percent of procedures were complication-free at a median of 41 months’ follow-up; 35 percent of patients had grade one complications and 9 percent had grade two. Three patients had developed pelvic cancer recurrence, five developed distant recurrences, and two developed both pelvic and distant recurrence.

Höckel and colleagues developed the principle of TMMR by studying uterovaginal development in embryos and fetuses – enabling discrimination of tissue compartments on the basis of their embryological origin. Previous work showed that early cervical tumors grow largely along these lines. [Lancet Oncol 2005 Oct;6(10):751-6]

Singapore surgeon Adjunct Associate Professor Yam Kwai Lam said that he would be “open to any new technique” as long as it provided “substantial overall benefit to the patient.”

“The published results look impressive, but lacking in long-term survival data. In order for the technique to replace conventional hysterectomies, validation would require a large randomized controlled trial to provide the answer,” said Yam, head and senior consultant in the department of gynecological oncology at KK Women’s and Children’s Hospital.

Höckel has previously presented TMMR to surgeons in Southeast Asia – performing live demonstrations in Hong Kong in December 2006, and Bangkok in August 2008.

A multicenter trial is due to launch soon in Germany, with a view to comparing results of 200 TMMRs against 200 conventional hysterectomies. Publication is expected in around 4 years, said Höckel, who has not performed a standard hysterectomy since first developing TMMR some 10 years ago.

“The conventional techniques have no right to exist any longer because they are wrong. Now that we know how a tumor is spreading … it’s no longer acceptable to use these sub-prime concepts and techniques,” he said.

Pain perception: Personality goes a long way

2009-09-03T02:20:00.000-07:00

Medical Tribune July 2009 P12

David Brill

Personality has a major influence on the way people perceive headaches, and should be considered when assessing patients, say Italian researchers.

In a recent study they found that ‘emotionally overwhelmed’ people report a greater affective dimension to their pain than those with other personality types, yet score the same on a simple measure of pain intensity.

The other personality types – conversive, depressive and copers – did not differ significantly in their perception of pain.

The findings should encourage physicians to routinely consider a patient’s personality and emotions before simply prescribing medications, said lead researcher Professor Franco Mongini, of the Headache and Facial Pain Unit at the University of Turin.

Moreover, presentation with a headache or migraine could be a warning sign of an underlying personality disorder or mental health problem, he said, adding that early recognition could facilitate referral to a specialist before the pain gets worse.

“I keep seeing patients with chronic migraine and chronic tension-type headache together, and they have been receiving new drugs. But very often the patient’s personality and the consequences of this personality have not been considered,” said Mongini, who typically questions new patients on their history of phobias, panic attacks and sleep disturbances, among others, before considering whether to treat with cognitive behavioral therapy.

“I’m convinced after years and years of work that the approach to the problem of chronic head pain should be remodeled and widened. I’m not saying that drugs should not be prescribed – I prescribe a lot of medications myself – but other factors should be considered and treated also with non-pharmacological methods,” he said.

Mongini and colleagues assessed 317 patients with migraine and/or tension-type headache with myogenic facial pain. They performed two types of pain assessment: the verbal MacGill Pain Questionnaire (MPQ), which classifies pain in a range of dimensions, and the visual analog scale (VAS), which measures pain intensity alone. [Pain 2009 Jul;144(1-2):125-9]

Personalities, meanwhile, were classified using 10 scales of the Minnesota Multiphasic Personality Inventory (MMPI). ‘Copers’ score normally across all domains, whereas ‘depressive’ and ‘conversive’ personalities show various elevation in scores of depression, hypochondria and hysteria. The ‘emotionally overwhelmed’ personality has elevation in all three of these scores, plus one other MMPI dimension.

The affective dimension of the MPQ was significantly higher in emotionally overwhelmed than in coper (P=0.003), depressive (P=0.027) and conversive (P=0.002) people, regardless of sex, age and type of pain. VAS score did not vary significantly between groups.

Mongini and colleagues also recently reported on a successful intervention to reduce head and neck pain in the office place. A combined educational and physical program reduced the frequency of headaches by 41 percent and the use of analgesics by 50 percent, when tested in a study of 384 civil servants in Turin. [Cephalalgia 2008 May;28(5):541-52]

Breast cancer prediction and prevention could start younger

2009-09-03T02:17:00.000-07:00

Medical Tribune July 2009 P13
David Brill

Risk assessment for breast cancer could one day start in girls as young as 15, according to a recent paper which may open up new opportunities for early disease prevention.

Canadian researchers found that breast tissue composition – a known risk factor in middle age and above – begins to vary at a much younger age, and could provide a quantifiable way to predict risk.

It is the first extensive study to look at breast tissue composition in young women, say the authors, who used MRI in order to avoid the radiation exposure of mammography.

Percent breast water was found to decrease with age (P=0.04) – a finding which could explain why breast tissue is thought to be most susceptible to carcinogens at a young age.

The researchers also found strong correlations to height and weight – suggesting that breast composition could be influenced by factors relating to growth and development. Percent breast water was also strongly linked to mammographic density in the subjects’ mothers – lending support to a hereditary component to breast formation.

“What [this study] suggests is that prevention is going to be most effective if started earlier in life, and that measurement of breast tissue characteristics might be one way of modifying and monitoring prevention,” said lead author Professor Norman Boyd, of the Campbell Family institute for Breast Cancer Research, Toronto, Canada.

Further research is needed before risk assessment could be practiced routinely in young girls, said Boyd, noting two key areas of uncertainty. First would be to establish the most appropriate method for assessing breast composition in young women, and second would be to be determine which interventions would be appropriate and safe in those found to be at high risk.

“The long-term vision would be that we would have a method of assessing breast tissue composition as soon as the breast forms, essentially. MRI is what we’ve used, but MRI is clearly not the answer to this because it’s so expensive and there are so few machines,” he said.

“It’s difficult to know how technology is going to advance but at the moment, ultrasound looks very appealing. It can be done quickly, it can be done quantitatively, it can give us measurements of tissue volumes, which mammography does not do, it can be done very, very quickly… and it’s completely free of risk.”

Boyd and colleagues measured levels of water and fat in the breasts of 400 women aged 15 to 30, and their mothers. The percentage of water on MRI correlated strongly with mammographic density in a randomly selected subset of 100 of the mothers (r=0.85). [Lancet Oncol 2009 Apr 29; Epub ahead of print]

Height, weight and maternal mammographic density were all strongly associated with per cent breast water in young women (P<0.0001). Height and weight also correlated strongly to total breast fat, and maternal mammographic density correlated strongly to total breast water (P<0.0001).

The association between weight and percent breast water was inverse – suggesting that heavier young women are at lower risk of breast cancer. Previous studies have also shown similar findings but the mechanisms for the association remain unclear, said Boyd. The authors did, however, report an association between percent breast water and serum levels of growth hormone – a finding which could underlie the associations with height and weight, they say.

Further research is already ongoing to better understand the genetic factors that influence breast composition, added Boyd.

Dieticians call for action on overweight mothers-to-be

2009-09-03T02:12:00.000-07:00

Medical Tribune July 2009 P16

David Brill

Overweight women should receive nutrition counseling before, during and after pregnancy, leading US dietitians have advised.

With the global obesity epidemic showing no signs of slowdown, the health of mothers and babies alike is at risk unless eating habits improve, cautions a recent joint statement from the American Dietetic Association (ADA) and the American Society of Nutrition (ASN).

Studies show that obese mothers are more likely to experience preeclampsia, gestational diabetes mellitus (GDM), gestational hypertension, postpartum anemia and cesarean delivery than women of normal weight. Their offspring, meanwhile, face an increased risk of birth defects, fetal macrosomia, childhood obesity and even perinatal death.

Ms. Ximena Jimenez, a consultant dietitian and national ADA spokesperson, said that healthcare professionals across the spectrum should work together to promote healthy eating and physical activity in women who are pregnant or planning to conceive. Physicians, for example, can play “a big role” in reinforcing the advice given by dietitians and other specialists, she said.

“A lot of the time it takes more than one type of counseling to get these women to change their lifestyle. I would encourage any healthcare professional to encourage these women to seek nutrition counseling,” she said.

“The principles are that you want them to increase whole grains and decrease refined carbohydrates like cakes, pastries and white breads. We also want them to replace saturated fat with healthy fats like omega-3 fats or fats from olive oil, canola oil or avocado, and also to increase their intake of fruits and vegetables. We also want them to be physically active,” she added.

Some 52 percent of women aged 20 to 39 in the US are overweight or obese (BMI 25 or above), according to data from the National Health and Nutrition Examination Survey of 2003-2004. Twenty-nine percent are obese (BMI 30 or above) and 8 percent are extremely obese (BMI 40 or above). Among adolescent girls aged 12 to 19, almost 32 percent are overweight or at risk of being overweight. [JAMA 2006 Apr 5;295(13):1549-55]

Despite the scale of the task, Jimenez remains optimistic that overweight women can be successfully counseled.

“I think it’s a very realistic target. There has to be promotion of healthy eating among women,” she said. “Imagine the benefits. As a society we are all going to benefit because we are going to have healthy women and healthy children.”

Jimenez highlighted studies showing the success of dietary interventions in overweight mothers, such as the Nurses’ Health Study, which found that risk of GDM was approximately halved by following a low-glycemic, high-cereal fiber diet. [Diabetes Care 2006 Oct;29(10):2223-30] The risk of preeclampsia can also be halved by taking calcium supplements, a meta-analysis of 12 studies shows. [Cochrane Database Syst Rev 2006 Jul 19;3:CD001059]

The new ADA / ASN position statement also reviews the literature on the prevalence of various pregnancy outcomes for overweight mothers and their babies. [J Am Diet Assoc 2009 May;109(5):918-27]

The risk of developing GDM, for example, is reported to double in overweight women, and increase over eightfold in the extremely obese. [Diabetes Care 2007 Aug;30(8):2070-6] Preeclampsia risk is around three times higher in pregnant women who are obese than those of normal weight. [Obstet Gynecol 2007 Feb;109:419-33]

The offspring of obese mothers are around twice as likely to have neural tube defects such as spina bifida, according to the US National Birth Defects Prevention Study. [Arch Pediatr Adolesc Med 2007 Aug;161(8):745-50] Oral clefts, hydrocephaly and cardiac abnormalities were also found to be more common in these infants than those born to normal-weight mothers.

Stroke prevention under-used in the elderly

2009-09-01T02:11:00.000-07:00

Medical Tribune June 2009 P1&6
David Brill

Elderly patients are missing out on life-saving stroke prevention drugs in primary care, according to a report in the British Medical Journal.

Stroke patients aged 80 to 89 were almost half as likely to be receiving secondary prevention treatments as those aged 50 to 59, the researchers found.

This discrepancy in treatment was not justified by outcomes, however – receipt of the drugs halved mortality risk, regardless of age.

The study of 12,380 patients took place in England but carries an important message for Singapore, according to stroke expert Associate Professor Lee Kim En, senior consultant and head of the department of neurology at the National Neuroscience Institute, Singapore.

“We do not have local figures, but similar findings are expected in Singapore. This is a timely article serving as a reminder that social support must include ensuring the elderly receive their medications,” he said.

“As doctors, we have a responsibility to motivate our elderly patients to continue with treatment regardless of challenges, constraints and limitations. All primary care physicians must share this responsibility.”

The researchers reviewed data from 113 general practices to identify over-50s who had a stroke between 1995 and 2005 and survived the first 30 days. Therapy had to be initiated within 90 days of the stroke to be included in the study as secondary prevention. [BMJ 2009 Apr 16;338:b1279]

Overall treatment rates were low: 25.6 percent of men and 20.8 percent of women were receiving secondary prevention. Mortality within one year of stroke was 5.7 percent for patients receiving treatment, compared to 11.1 percent among those receiving no such therapy.

Treatment rates did not vary by socioeconomic status but dropped markedly with age – from 26.4 percent of patients aged 50 to 59, to 15.6 percent of those aged 80 to 89. Just 4.2 percent of over-90s were receiving treatment.

Lipid lowering drugs were particularly under-used in the elderly – the odds ratio for receipt of these therapies was 0.44 for 80 to 89 year-olds, compared with 50 to 59 year-olds (95 percent CI, 0.33 to 0.59; P<0.001).

The study did not explore the reasons for the observed age bias, but lead researcher Professor Rosalind Raine speculated that responsibility could lie with both patients and prescribers.

“We can’t leave an attack of clinical bias on the doors of the clinicians until we’ve really excluded all of the other explanations,” said Raine, professor of health care evaluation at University College London. “Patients are increasingly more informed, and so there is also a balance about what they’re asking for.”

Some experts have suggested that GPs may be unsure about the efficacy of secondary prevention drugs in the elderly since they are often excluded from clinical trials, she said. She noted, however, that there is a growing body of evidence – particularly from meta-analyses – to support the benefits of this practice. The mortality findings from the present study further underscore this point in a real-world, general practice population, she added.

Raine also ruled out the possibility that prescribers may be worried about adherence in the elderly, since the discrepancy was only evident for lipid lowering drugs and not for cheaper therapies such as antihypertensive and antithrombotic drugs. She expressed her concern that it could be the relative cost of the drugs which is driving this particular effect.

“It does make you wonder if lay beliefs about values of people in society are actually being transposed into the clinical situation. But I do not have evidence on which to base that – it’s only by exclusion of some of the other likely explanations,” she said.

Rifts widen in prostate screening debate

2009-09-01T02:05:00.000-07:00

Medical Tribune June 2009 P1&9
David Brill

American and European experts have diverged in their stances on prostate cancer screening, as debate intensifies over the benefits of prostate-specific antigen (PSA) testing.

The subject has held center stage since the publication of two major studies in March: one showed that PSA testing every 4 years reduced mortality by 20 percent but carried a high risk of overdiagnosis; the other showed that annual screening had no impact on death rates.

The American Urological Association (AUA) has since aligned itself with the first study – recommending PSA testing in all well-informed men, and lowering the age for a first test from 50 to 40. It has also adjusted its criteria for proceeding to biopsy.

The European Association of Urology (EAU), meanwhile, has advised against population screening until more data are available – warning of the dangers of overtreatment and calling for urgent development of new diagnostic markers and screening algorithms.

Singapore experts are taking a similar stance to their European counterparts, although they note that the lower incidence of prostate cancer in Asia makes screening less worthwhile than in Western populations.

The Singapore Urological Association (SUA) nonetheless intends to downplay the role of PSA screening in this year’s upcoming Prostate Awareness Month, according to Professor Kesavan Esuvaranathan, SUA president and senior consultant, department of urology, National University Hospital.

“I wouldn’t be in a hurry to recommend screening. We don’t know for sure whether there is a benefit,” he said.

“My feeling is that it’s too early to say that PSA screening is inappropriate, but I also think that it is probably wrong to unconditionally recommend PSA screening. I think we have to wait for the long-term results of these studies.”

Associate Professor Weber Lau, senior consultant, department of urology, Singapore General Hospital, also urged caution in the use of PSA testing, stressing the need to select the right patients.

“We are quite clear that screening is not a goal for Singapore at this juncture. For people who are asking to be tested, the key words are risk stratification,” he said.

“PSA can be used as a tool for early detection of prostate cancer in the right patients. But on the other hand it can be harmful too if used in health screening without understanding the risks of the patient group and the general health of the patient.”

The 20 percent mortality reduction with PSA screening was reported in the European Randomized Study of Screening for Prostate Cancer, which included 162,387 men aged 55 to 69 from seven countries. They were assigned to PSA screening every 4 years on average, or to no screening. [N Engl J Med 2009 Mar 26;360(13):1320-8]

After a median of 9 years’ follow-up, the adjusted rate ratio for prostate cancer death in the screening group was 0.80, as compared to the control group (95 percent CI, 0.65 – 0.98; P=0.04). The absolute risk difference was 0.71 deaths per 1,000 men – meaning that to prevent one death from prostate cancer, 1,410 men would need to be screened and an additional 48 cases would need to be treated.

The second study – the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial – included 76,693 men aged 55 to 74, recruited at 10 US centers. Men were randomized to annual screening – with PSA for 6 years and digital rectal exam for 4 years – or to the control group. [N Engl J Med 2009 Mar 26;360(13):1310-9]

After 7 years’ follow-up, there were 50 prostate cancer deaths in the screening group and 44 in the control group (rate ratio 1.13; 95 percent CI, 0.75 – 1.70). Ten-year data showed similar patterns but follow-up was only complete for 67 percent of patients at the time of publication.

Despite the lack of national recommendations, PSA tests are commonly offered in Singapore as part of executive health screens, according to Kesavan. This situation need not change in light of the studies, he said, but he emphasized the importance of explaining the potential consequences before testing.

“It would place the patient in a quandary if it was not explained properly and then he had an abnormal test. Then to put that worry to rest it would require him to undergo a biopsy.”

Building bridges: A new dawn of collaboration for the pharmaceutical industry

2009-09-01T01:57:00.000-07:00

Medical Tribune June 2009 P2

Pharmaceutical companies must branch out and forge new collaborations if they are to survive the global economic crisis, says Mr. Abhijit Ghosh, life sciences leader, PricewaterhouseCoopers Services LLP, Singapore.

The pharmaceutical industry is entering a challenging era of uncertainty. The global economic crisis has intensified the strain on a marketplace which was already struggling to come to terms with soaring costs, the drying up of drug pipelines, and the pricing pressures created by the emergence of generic medications. We predict that by 2020 the current business model will become unsustainable, and a new landscape will arise for companies, healthcare providers and patients alike.

Pharmaceutical companies must adapt quickly if they are to survive these challenges and emerge stronger in the new marketplace. The days of ‘blockbuster’ drugs are coming to an end, and companies can no longer rely on a strategy of making huge investments to single-handedly develop and market their most promising molecules. Public expectations, too, are changing: as patients become better informed they demand a more holistic approach to healthcare, shifting the balance away from universal, one-size-fits-all treatments and into the realms of prevention and personalized medicine. Moreover, by 2020, medicines will be paid for on the basis of results, not products, and companies will be forced into offering broader health management services to ensure that they achieve the best outcomes.

Few companies will be able to meet these daunting goals on their own. In an industry where ‘profiting alone’ has long been the mantra, it is now ‘profiting together’ that offers the key to survival.

We predict that pharmaceutical companies will join forces with a range of external organizations in future: from hospitals and academic centers to companies which offer physiotherapy, stress management, nutritional advice and health screening. Many of these collaborations will be unconventional, as an increasing number of non-pharmaceutical companies enter the arena. The technology sector in particular is one where partnerships with the pharmaceutical industry will be beneficial, as drug providers team up with manufacturers of portable devices and implants.

Two models are proposed for the strategy of collaboration. The first is the federated model, which would see a network of separate entities coming together with a common goal and a shared supporting infrastructure. Each partner could play to their strengths and expertise: for example, the pharmaceutical company could focus on drug development while other players worked on improving patient compliance and encouraging them to lose weight. One such example of federated collaboration is already underway in Spain, where Vodafone has joined forces with Aerotel Medical Systems, a device manufacturer, and Medcronic Salud, a telemedicine provider, with a view to providing wireless home monitoring services. Bringing clinics and hospitals into such partnerships in future could even provide medical companies with access to outcomes data, allowing them to monitor the long-term effects of treatment outside the clinical setting.

The second approach to collaboration is the fully diversified model, in which a pharmaceutical company expands to provide related products and services. This enables them to spread their risk away from reliance on blockbuster drugs and into other market areas. Johnson & Johnson, for example, has branched out from drugs into medical devices and diagnostics, and has recently begun building a web-based wellness and prevention platform. GlaxoSmithKline (GSK) and Novartis have both invested heavily in vaccines, while Roche is translating its expertise in molecular diagnostics into consumer products for measuring allergen levels indoors. These diversification approaches, however, require substantial investment, and may detract from the core business and create risks which might even alienate investors.

Besides the financial and commercial benefits of increased collaboration, there are also obvious public health implications, particularly as the global burden of chronic disease continues to rise. Research by the RAND corporation shows that the US alone could save some US$28 billion if all diabetes, asthma, pulmonary disease and congestive heart failure patients enrolled in disease management programs – not to mention the considerable economic benefits in terms of working days saved.

Pharmaceutical companies will need to make their own decisions on how to move forwards, depending on their individual circumstances. Some are already exploring collaborations which previously may have seemed unlikely. In April this year, for example, GSK and Pfizer announced the joint formation of a new firm for HIV drug development, with 11 existing products and a further 17 in the drug-discovery pipeline. It is hoped that this combined venture will offer a broad and sustainable approach, with potential for growth in future.

Some companies, however, will find it harder than others to survive the current economic crisis, and it is small biotech firms that may face the roughest ride. Those with one or two promising molecules in the pipeline will most likely need to collaborate with big companies for their development, or seek to sell their stake entirely and join the ever-growing number of mergers and acquisitions.

Despite the current crisis there is optimism in the industry: in a recent survey we found that CEOs of pharmaceutical companies were more confident about their prospects for growth than their peers in other industries. It remains to be seen how the landscape will evolve and whether this optimism will be justified, but it is clear that the industry cannot stand still. Profiting alone is no longer an option, and the sector must branch out into new partnerships if it is to continue to move forward.

New risk tool allows prediction of dementia in elderly

2009-09-01T01:54:00.000-07:00

Medical Tribune June 2009 P3

David Brill

A new algorithm could help physicians to stratify elderly patients according to their risk of developing dementia.

The late-life dementia risk index was developed using data from 3,375 subjects with a mean age of 76. Just 4 percent of those classified as low risk developed dementia over 6 years, compared to 23 percent of moderate-risk and 56 percent of high-risk subjects.

"This new risk index … could be used to identify people at high risk for dementia for studies on new drugs or prevention methods,” said lead author Dr. Deborah Barnes, University of California, San Francisco, US. “The tool could also identify people who have no signs of dementia but should be monitored closely, allowing them to begin treatment as soon as possible." [Neurology 2009 May 13; Epub ahead of print]

Laughter: The best medicine for cardiovascular disease?

2009-09-01T01:53:00.001-07:00

Medical Tribune June 2009 P3
David Brill

Watching comedy shows can improve cardiovascular risk factors, researchers have reported in the journal Psychosomatic Medicine.

The study of 18 healthy people found that arterial stiffness and central hemodynamics improved after watching a 30-minute section from the movie Naked Gun. Cortisol and von Willebrand factor levels also decreased with laughter, reported the team from Athens Medical School, Greece.

Watching stressful scenes, however, had the opposite effect: carotid-femoral pulse wave velocity increased after watching a 30-minute clip from Saving Private Ryan. Stressful viewing also lowered interleukin-6 levels, but did not affect fibrinogen or soluble CD40 ligand levels. [Psychosom Med 2009 Feb 27]

Gene variants point to East Asian health risks

2009-09-01T01:51:00.000-07:00

Medical Tribune June 2009 P3
David Brill

Korean scientists have identified East Asian-specific gene variants which play a role in obesity, blood pressure, bone density and pulse rate.

The group, led by the National Institute of Health, Seoul, conducted the first large-scale genome-wide association study of an East Asian population. They analyzed 8,842 samples from Korean population-based cohorts.

Besides identifying novel East Asian gene variants, they also found that many genetic markers are shared with Europeans, including several which play a role in height, body mass index, type 2 diabetes, obesity, heart disease and osteoporosis. [Nat Genet 2009 May;41(5):527-34]

Alcohol ‘flush’ signals cancer risk in Asians

2009-09-01T01:37:00.000-07:00

Medical Tribune June 2009 P4

David Brill

East Asians who ‘flush’ when drinking alcohol could be at increased risk of esophageal cancer if they do not drink responsibly, a recent study has warned.

The characteristic red cheeks and nausea are a well-recognized phenomenon, but few people are aware that the underlying enzyme deficiency also predisposes heavy drinkers to squamous cell esophageal carcinoma, say the researchers.

With some 36 percent of East Asians displaying the flush response, there is potential to save “a substantial number of lives” by counseling affected individuals against heavy drinking. [PLoS Med 2009 Mar 24;6(3):e50]

"Cancer of the esophagus is particularly deadly, with 5-year survival rates ranging from 12 to 31 percent throughout the world,” said lead researcher Dr. Philip Brooks, of the US National Institute on Alcohol Abuse and Alcoholism. “And we estimate that at least 540 million people have this alcohol-related increased risk for esophageal cancer.

"We hope that by raising awareness of this important public health problem, affected individuals who drink will reduce their cancer risk by limiting their alcohol consumption," he said.

Flushing is caused by a deficiency in aldehyde dehydrogenase 2 (ALDH2) – an enzyme which breaks down acetaldehyde, a carcinogenic by-product of ethanol metabolism. People with normal ALDH2 function can convert acetaldehyde safely into acetate, but in ALDH2-deficient individuals it accumulates in the body, leading to facial redness, nausea and tachycardia.

In people who are homozygous for the ALDH2-deficiency gene, the response to alcohol is so unpleasant that they cannot consume large quantities, and are thereby protected from the associated risk of esophageal cancer.

Heterozygotes, however, can develop tolerance to acetaldehyde and may become heavy drinkers. Studies from Japan and Taiwan have shown that ALDH2-deficient heterozygotes who drink heavily are over ten times as likely to develop esophageal cancer, [Jpn J Clin Oncol 2003 Mar;33(3):111-21; Int J Cancer 2008 Mar 15;122(6):1347-56]

Dr. Michael Wang, a radiation oncology consultant at the National Cancer Centre Singapore, agreed that the link between flushing and esophageal cancer is not likely to be common knowledge among doctors.

“From the article, it is fair to comment that there is a causative relation between deficiency of the gene and increased risk of esophageal cancer,” he said.

“However, there has been a lot of material published since the 1970s regarding this condition. This relationship may be confounded by smoking, which is also related to esophageal cancer. Before we say something drastic like ‘people who flush when drinking have a higher risk of contracting esophageal cancer,’ we should research all the previously published articles first.”
Wang added that all heavy alcohol drinkers should be counseled, since drinking also predisposes to other medical conditions and to drink-driving.

The study authors advise clinicians to determine whether East Asian patients are ALDH2 deficient by asking simple questions about their history of flushing when drinking alcohol. Identified flushers should then be advised of their cancer risk and encouraged to moderate their consumption, they say.

Fatty fish and fish oils could lower HF risk in men

2009-09-01T01:29:00.000-07:00

Medical Tribune June 2009 P5
David Brill

Moderate consumption of fatty fish and marine omega-3 fatty acids may help to protect against heart failure (HF), a study of Swedish men has found.

Eating fatty fish once a week reduced the chances of developing HF over 6 years by 12 percent, while consuming around 0.3 grams a day of marine omega-3 fatty acids reduced the risk by 33 percent (adjusted hazard ratios 0.88, 95 percent CI 0.68 – 1.13; and 0.67, 05 percent CI 0.50 – 0.90).

The apparent protective effect did not grow stronger with increasing consumption, however. Eating more than moderate amounts, in fact, restored HF risk almost to that of men who did not consume any fatty fish or marine omega-3 fatty acids.

The researchers conducted food questionnaires in 39,367 men aged 45 to 75, and followed them up in inpatient and cause-of-death registries from 1998 to 2004. A total of 597 men developed HF in this time, 34 of whom died. [Eur Heart J 2009 Apr 21; Epub ahead of print]

“Our study shows that a moderate intake of fatty fish and marine omega-3 fatty acids is associated with lower rates of HF in men, but that the men did not gain a greater benefit by eating more of these foods,” said lead author Dr. Emily Levitan, a cardiology research fellow at Harvard Medical School, US.

“This study reinforces the current recommendations for moderate consumption of fatty fish. For example, the Swedish National Food Administration recommends consuming fish two to three times per week, with one of those portions being fatty fish. Similarly, the American Heart Association recommends eating fish, preferably fatty fish, twice a week,” she said.

Omega-3 fatty acids, which are found in fish oil, have been previously shown to reduce blood pressure, triglycerides and platelet aggregation, and to benefit heart rate and endothelial function. Consumption of fatty fish, such as salmon, herring and mackerel, has also been shown to confer cardiovascular benefits: one such study found that moderate consumption reduced the risk of coronary death by 36 percent and total mortality by 17 percent. [JAMA 2006 Oct 18;296(15):1885-99]

The reason for the U-shaped association between consumption and HF risk in the present study is unclear, said Levitan, although she speculated that men with poor health may be eating more fish in an attempt to improve their wellbeing.

“It will be important to replicate these findings in other populations, particularly those including women, as our study was conducted in men only,” she added.

Omega-3 fatty acids may also have a protective effect against age-related macular degeneration (AMD), a recent study of elderly Australians suggests. One serving of fish per week reduced AMD risk by 31 percent, with a similar magnitude observed for consumption of long-chain omega-3 polyunsaturated fatty acids. [Arch Ophthalmol 2009 May;127(5):656-65]

The OMEGA (Randomized trial of omega-3 fatty acids on top of modern therapy after acute myocardial infarction) trial, however, found that daily consumption of omega-3 fatty acids had no benefit for preventing sudden cardiac death after acute myocardial infarction, in a cohort of 3,851 patients with 1-year follow-up. The results were presented recently at the Annual Scientific Session of the American College of Cardiology.

End-of-life discussions reduce costs and relieve suffering

2009-09-01T01:26:00.000-07:00

Medical Tribune June 2009 P7

David Brill

The decision to prolong life in advanced cancer patients presents an ethical, emotional, and financial challenge. Buying time can be costly, and a heavy legacy is often left for families and healthcare providers alike.

A new study suggests that physicians can play a major role in relieving this burden, simply by talking patients and families through their options and helping them to make plans in advance. Patients who had these end of life discussions received fewer aggressive interventions and had substantially lower medical costs, researchers found.

Economics aside, these discussions could also be in the patient’s best interests: the study found that high medical costs in the last week of life correlated to increased physical and psychological distress, and a worse quality of death. Moreover, survival was not significantly longer in patients who received aggressive therapies – raising questions as to whether the expense is justified.

Senior author Dr. Holly Prigerson said that patients ultimately have the right to choose, but that physicians can help to ensure that they make an informed decision.

“We’re not saying you should or you shouldn’t [prolong llfe], but you should at least realize what you’re buying with this more aggressive care. There is not improved quality of life,” she said.

“Whether they want to endure that pain is up to the patient to decide, but at least they should have the information to know that when they’re resuscitated, the likelihood that they’re going to survive an extra week really isn’t that much greater.”

Prigerson, director of the Center for Psychosocial Oncology and Palliative Care Research at the Dana-Farber Cancer Institute, Harvard Medical School, US, said that the study was born out of a belief among some oncologists that having end of life conversations would make patients “needlessly hopeless and depressed.” With data now showing that these discussions actually improve quality of life, she hopes that the study will bolster the confidence of physicians to address these “very difficult” subjects in future.

Singapore palliative care expert Dr. Cynthia Goh agreed that these conversations are important but stressed the need to approach them correctly. Physicians should listen to what patients and families want and guide them through their options, rather than pushing them towards a decision, she said.

“When talking about, for example, ‘do not resuscitate’ orders, the wrong way of doing things is to say: ‘do you want us to save your father or not?’” said Goh, director of the Lien Centre for Palliative Care at Duke-NUS Graduate Medical School, Singapore.

“What they’re talking about in this paper is a different kind of end of life conversation, which is certainly not initiated in the hospital corridor. It’s not about ‘do you want this or do you want that’ – really it’s a conversation to say what is important for the patient. People go bankrupt for this kind of treatment, so having the chance to reflect on whether it is likely to fulfill their life goals is a very good thing.”

Prigerson and colleagues interviewed advanced cancer patients from several US institutions, and followed them up until death. Of 603 patients, 188 (31.2 percent) reported having had an end of life conversation with a physician at baseline. [Arch Intern Med 2009; 169(5):480-8]

The mean cost of care for these patients was US$1041 (35.7 percent) lower than in those who did not have such conversations (P=0.002). Medical costs did not correlate to survival time (P=0.70) but were associated with worse quality of death, as assessed by caregivers and family members (P=0.006).

Another recent study led by Prigerson found that cancer patients who used religion to cope with the advent of death were more likely to receive intensive life-prolonging care. [JAMA 2009; 301(11):1140-7]

The explanation remains unclear but the effect appears to be driven by be a subset of patients who are not lifelong believers but rather turn to religion as death approaches, she said. Their new-found beliefs could therefore be a proxy for psychological distress, which manifests in a desire to remain alive for longer.

Goh, who is also honorary secretary of the Asia Pacific Hospice Palliative Care Network and co-chair of the newly formed Worldwide Palliative Care Alliance, said that the findings were very interesting but may not be applicable to Asian populations since the study patients were all American Christians. She added, however, that religion is an important factor in end of life decisions, and said that physicians should take these beliefs into account on a patient-by-patient basis.

Swine flu: The view from the Asia Pacific region

2009-09-01T01:24:00.000-07:00

Medical Tribune June 2009 P7

Age no barrier to continued cervical screening

2009-09-01T01:12:00.000-07:00

Medical Tribune June 2009 P9

David Brill

Cervical cancer screening should not stop at age 50, even in women who have had several all-clears in the past, new evidence suggests.

An analysis of national data from the Netherlands found that older women were just as likely to develop cancer after three negative smear tests as younger women.

Previous studies had found that pre-invasive disease is rare in well-screened over-50s, prompting calls for screening to be stopped at this age.

The Dutch study, however, focused instead on the incidence of full-blown cancers. It included data from 445,382 women aged 30 to 44 at the time of their third negative smear, and 218,847 women aged 45 to 54. [BMJ 2009 Apr 24;338:b1354]

After 10 years of follow-up the cumulative incidence of cancer was similarly low: 41 per 100,000 in the younger age group, and 36 per 100,000 in the older age group (P=0.48).

The findings suggest that age should not be the decisive factor for early cessation of screening in well-screened women, said lead author Dr. Matejka Rebolj. They do not, however, provide a definitive answer as to whether it will ultimately prove worthwhile to continue universal screening after three negative tests.

“We cannot really say with these data whether you should continue screening or not. However we can say that if you’re screening younger women, then in order to make your policy consistent you should continue screening women above the age of 50,” said Rebolj, a postdoctoral researcher at the University of Copenhagen, Denmark.

“The next logical step would be to do a proper cost-effectiveness analysis to determine whether this low absolute level of risk does warrant further screening. Until then we should encourage women to continue screening at the regular interval recommended in each particular country.”

Singapore oncologist Dr. Francis Chin praised the quality of the data, and said that the findings support Singapore’s policy of continuing screening up to age 69.

“This study confirms the importance of screening in the age group over 50 years old, because the risk of cervical cancer after several negative smears is similar in older versus younger patients,” said Chin, consultant radiation oncologist at the National Cancer Centre Singapore.

“The predilection of doctors has always been that screening and early detection is better than treating cancer in the later stages. These data confirm and validate this policy,” he said.

Singapore’s Health Promotion Board (HPB) agreed that the study supports the current guidelines of its CervicalScreen Singapore initiative, implemented in 2004. The program, which promotes screening every 3 years, will continue to focus on increasing its coverage of eligible women, said Dr. Shyamala Thilagaratnam, director, Healthy Ageing Division, HPB.

Several previous studies have proposed that cervical screening should stop at 50, notably a 1997 paper which found that only 1 percent of 23,440 previously screened over-50s had significant cytological abnormalities. The authors concluded that ending screening in this group could reduce anxiety and enable better allocation of resources to targeting higher-risk women. [Br J Obstet Gynaecol 1997 May;104(5):586-9]

The case against this argument, however, could be furthered strengthened by another recent paper, supporting the findings of the Dutch study. UK researchers, reviewing National Health Service screening records for 2 million women, found that two thirds of all the lesions detected in over-50s were found in women who had had previously had negative smears results. Discontinuation of screening would therefore lead to the majority of important abnormalities being missed, the researchers say. [Br J Cancer 2009 May 5; Epub ahead of print]

Singapore physician Dr. Siew Wei Fong concurred with the conclusion that screening should continue beyond the age of 50, in light of the recent evidence. She added that she does not expect any change in screening practices at the Singapore Polyclinics, where she is senior family physician.

Smokers more likely to drop oral contraceptives

2009-09-01T00:59:00.001-07:00

Medical Tribune June 2009 P12
David Brill

Young women who smoke are more likely to stop taking oral contraceptives (OCs), a recent study suggests.

After 6 months of follow-up, only 26 percent of smokers were still taking OCs, compared to 46 percent of non-smokers (P<0.0001).

The study included 1,598 inner-city women aged under 25 – 198 of whom were smokers. After adjustment for confounding factors, smokers were 40 percent less likely to still be taking OCs (odds ratio 0.6; 95 percent CI, 0.4 – 1.0). [Contraception 2009 May;79(5):375-8]

“The take-home message is that smokers may be risk takers and thus more likely to discontinue contraceptives,” said lead author Dr. Carolyn Westhoff, professor of obstetrics and gynecology at Columbia University, New York, US.

The findings also serve as a reminder of the need to promote the right public health messages about smoking and OC use, say the researchers. Smoking while taking OCs is widely considered to be dangerous, but evidence so far is only conclusive for women over 35.

“The public health message and package labeling that birth control pills and smoking are incompatible is a bit over-simplified. While smoking is always a bad thing, the adverse interaction with OCs doesn't apply to our youngest patients,” said Westhoff. Pushing the same message to younger women could encourage them to quit OCs rather than quit smoking, she noted.

Study subjects were enrolled at three publicly funded family planning clinics. They reported smoking status at baseline, and OC continuation at 3 and 6 months. Twelve percent of the cohort were smokers.

“Whether public health messages or clinician messages about the risk of smoking and OC use are driving the excessive discontinuation rates seen in this study deserves further study,” the researchers wrote.

“In the meanwhile, these data indicate that young smokers may be a high-risk group for premature discontinuation of OCs. Clinicians need to clarify the appropriate health messages and find ways to support young smokers in avoiding pregnancy.”

The study is a secondary analysis of a previously published trial, which found that initiating OCs in the clinic, under observation, improved short-term compliance compared to a conventional, delayed start. [Obstet Gynecol 2007 Jun;109(6):1270-6]

In search of paradise

2009-09-01T00:59:00.000-07:00

Medical Tribune June 2009 P18

David Brill

Halong Bay is a haven of spectacular natural beauty – once you run the tourist gauntlet to get there. David Brill seeks out the tranquility at the end of the conveyor belt.

The clues, in hindsight, were there from the start. Bundled from one minibus to another at 8 a.m., trying desperately to keep track of our luggage as it piled up on the sidewalk, it was clear that this trip was not going to be relaxing. We eventually squeezed into uncomfortable seats to be reassured by our unfailingly cheerful tour guide, over the death throes of the air conditioning system, that we were just a short trip away from one of the most beautiful places on earth. Suitcases loaded, we set off – joining an ever-lengthening convoy of vehicles on the bumpy pilgrimage to paradise.

This is the road to Halong Bay, where travelers flee the chaotic streets of Hanoi in search of the moped-free serenity of a cruise junk. One of Vietnam’s top attractions, the bay draws locals and tourists alike in their thousands all year round. In 1994 the area was designated a UNESCO World Heritage site – offering an extra level of attraction for the box-ticking Lonely Planet followers.

For most travelers, the experience begins at the hotels and high-street tour operators of Hanoi, where a disorientating selection of cruise packages is on offer to those who can successfully navigate a path through the traffic. Boats range from the basic to the seriously luxurious, and neither families nor students will find themselves short of choices. US$15 should cover a budget day trip, while 3-day, 2-night cruises start at around US$80 and extend anywhere up to US$600 for a deluxe double room at the top end of the scale.

The journey from Hanoi lasts around 4 and a half hours, complete with toilet stops at custom-built tourist traps. Weary-looking backpackers wander through aisles of paintings, wood carvings and conical hats, before rejecting it all in favor of an ice cream and a bottle of water. Many simply sit outside – eager to re-board the bus and reach the utopia they have been promised.

The prospects of relaxation and tranquility seem even more distant upon finally disgorging from the bus in the midday sun of Halong City. Tourists mill around in their hundreds, awaiting directions from their guides, who scurry frantically from office to boat and back, clutching papers, passports and money. Hawkers work their way through the increasingly restless crowd, selling t-shirts and hats to those who missed the earlier opportunity to buy them. Eventually the guides return to disperse the group, leading their followers into the armada of junks floating patiently in the harbor. Other boats lie further offshore, and some passengers must take a choppy connecting ride before finally putting their suitcases to rest.

For passengers on the luxury cruises, the tranquility of Halong Bay presumably begins as they step on board to be welcomed with a glass of champagne and a porter to carry their luggage. Those of us on the lesser boats had to wait a little longer, as we tucked into a disappointing lunch still moored against the backdrop of hotels and traffic. Our tour guide informed us that we had arrived and would shortly be free to relax, just as soon as we had visited a cave, gone kayaking, and explored a floating village. Definitions of paradise vary, but I had not expected it to run to such tight schedules.

It took some time yet to find the real Halong Bay, but there were no regrets upon arrival. As the boats escape the clutches of the harbor, it quickly becomes obvious why it draws so many visitors. A maze of limestone islands – some 1,600 in all – rises up from the sea, lining the horizon in every direction. Some are faceless, rocky outcrops, offering a surreal feeling of desolation, while others are overgrown with vibrant greenery that extends right down to the water. All shapes and sizes are present – from those resembling ancient volcanoes, to those no bigger than boulders poking their heads above water. One pair of miniature islands even appears locked in a stand-off, and is known either as the Fighting Roosters or the Kissing Rocks, depending on one’s romantic perspective.

The personal highlight of Halong Bay was to simply unwind and enjoy the beautiful surroundings. There are, however, several activities available for those seeking a distraction from the sunbathing. The caves were impressive, and there are many others to be explored if time allows. Kayaking is also enjoyable, offering the chance to find your own, quieter alcove if you have the inclination to paddle away from the crowd. Some islands have beaches – although a longer cruise may be required to reach those which can claim to be secluded – while swimming off the boat is also an excellent option when anchors are dropped for the night (a running jump from the top deck is highly recommended for those in a hurry to cool off).

For all its nooks and crannies, however, there are few places to hide in Halong Bay. The junks spread out as they leave the port, but the sheer weight of numbers ensures that they are never far apart. Moor up too close at night and you may even have trouble sleeping over the blare of music from next door. Add to this the regular appearance of small boats selling snacks, drinks and other tourist-friendly goodies, and you’ll begin to realize just how beaten the track really is.

Our overnight cruise ended in much the same spirit as it had begun: rushed off in a hurry as the cabin crew scrambled to prepare for the arrival of the next guests. Even the consolation hope of avoiding another disappointing meal proved unfounded, as we were herded into a restaurant at the harbor for a mass-produced set lunch, before embarking on the sweat-inducing return to Hanoi.

In spite of the prepackaged nature of the pilgrimage, I was left wishing that our trip had been longer. Halong Bay is spectacular, and truly deserving of its UNESCO acclaim, but it can scarcely be enjoyed in a whirlwind 24 hours. Take an extra day or two, explore the islands, and you should begin to shake the feeling that you’re doing the exact same thing as everyone else. Venture far enough from the mainland, and you might even find that tranquility you had hoped for.

Enter the dragon

2009-08-31T02:13:00.000-07:00

Medical Tribune May 2009 P18
David Brill

It may have taken 2,000 years but dragon boating is finally going global. David Brill finds out what makes paddling so popular.

Four p.m. on a Saturday afternoon an unlikely-looking crowd begins to gather. Twenty year-olds chat idly with 50-somethings – locals mingle with expatriates. Some look ready for combat, sporting Rambo-style bandanas with oiled biceps to match. Others look ready for bed, reluctantly stretching uncooperative muscles and swapping stories of last night’s excess.

Ten minutes later their connection becomes obvious. Armed with large wooden paddles and bright red lifejackets they squeeze into long, narrow boats and take to the water. The coach shouts the command and they move off – arms rising and falling in unison as the individuals blend into a synchronized propulsion unit.

The team is paddling a dragon boat, and it is their love of the sport that brings them together each week. This group represents the British Chamber of Commerce – just one of the many teams which make up the now-thriving dragon boating community in Singapore. The local scene wasn’t always so healthy, however.

“Two years ago there were some weeks we couldn’t even put the boat in the water because there weren’t enough people to carry it,” says Mr. Paul Robinson, captain of the British team. “Then suddenly it shot up. Now we’re putting out three boats a week – around 50 or 60 people.”

There are currently some 7,000 regular dragon boaters in Singapore and the numbers continue to rise. From one-off corporate events through to teams that paddle at international level, there is a full spectrum of competition that makes the sport feel welcoming to all comers. This accessibility is one of the main forces behind its rising popularity, according to Mr. Jason Chen, a former member of the Singapore national team and now a professional dragon boat coach. What first began as a hobby at school has now developed into a full time career as sales and marketing manager of SAVA – a Singapore-based private company which aims to develop and promote the sport.

“Dragon boating is very easy to learn – it’s not a sport that requires years of training,” he says. “Satisfaction is high and there is that sense of teamwork, of trying to achieve a common goal.

“The sport is really growing. If you go into a shopping center now you’ll probably see someone walking around carrying a paddle. It’s becoming a trend that people will at least paddle a dragon boat once or twice in their lifetime, or be in a team for some time,” says Chen.

Dragon boating originated in China around 2,000 years ago and the country continues to dominate the scene today with some 50 million paddlers, according to the International Dragon Boat Federation (IDBF). The appeal of the sport, however, is rapidly spreading: there are presently over 300,000 dragon boaters in Europe and nearly 100,000 in the US and Canada. The IDBF, formed in 1991, now comprises 61 member countries, representing all the different continents and a wide range of socioeconomic backgrounds.

Hong Kong has one of Asia’s most vibrant dragon boat scenes and plays host to one of the world’s best-known events – the Stanley International Dragon Boat Championships. Up to 20,000 people turn up each year to compete, cheer on the teams and sip champagne aboard the flotilla of corporate junks that line the harbor.

“It’s a tremendous spectacle … like nothing I’ve ever experienced,” says Mr. John Pache, who coached the Royal Hong Kong Yacht Club men’s team to gold in last year’s Stanley tournament. He describes the win as an “amazing feeling,” but feels that for many of the new recruits to dragon boating, it’s the fun of taking part that counts.

“I think there are a lot of people who do dragon boating who don’t necessarily do a lot of other sports. It appeals to people who want to do something as part of a team but don’t necessarily want to do ball sports or a lot of running, or anything high-impact,” he explains. “People also like the social aspect of it. You can meet up with your friends and become part of a wide community that all turns up regularly, and enjoy all the events that go along with that.”

Pache believes the popularity of dragon boating will continue to rise naturally but says that much will depend on the sport’s ability to gain inclusion in the Olympic Games. The IDBF is working towards this goal but without definitive success so far. In the meantime the major international event remains the annual world championship, to be held this year in Prague, Czech Republic. Thousands have already registered for the event, and many more are expected to do so by the time the boats hit the water in August.

Back in Singapore there are plenty of opportunities to compete locally as well as internationally, with a constant spread of events throughout the year. Robinson and his team are currently training for the annual Singapore Dragon Boat Festival, to be held on the last weekend in June.

New starters to dragon boating may wish to dip their toe in the water with a training session, but it is the grandstand experience of these race days that will keep them coming back for more. The cheers from the crowd, the beat of the drums – everything combines to create a nerve-wracking yet exhilarating day out.

“It’s a hell of a shock to the system when the buzzer goes off,” says Robinson. “It’s all going to be over within minutes so you just go for it with everything you’ve got. You’re becoming tired with every stroke but you have to keep your mind focused and keep going. As soon as you cross the finish line you absolutely think you’re going to die. If you don’t then you haven’t paddled hard enough.”

For some, it is the camaraderie and social aspect that attract them to dragon boating; for others it is the intensity of a good upper-body workout. Robinson acknowledges all of these things, but ultimately it’s a simple desire to compete which drives him to take out his bandana every weekend.

“It’s a great rush of adrenaline and testosterone. I’m addicted to it. It’s like going to war. I’m friends with all the other captains but as soon as my foot gets in that boat I want to destroy them,” he says.

For more information on dragon boating, see: http://www.idbf.org/ and http://www.sava.com.sg/.

Study heralds dawn of the cardiovascular polypill

2009-05-25T04:07:00.000-07:00

Medical Tribune May 2009 P1&6

David Brill

A five-drug combination tablet could cut the risk of coronary heart disease by more than 60 percent and nearly halve the risk of stroke, results of the first major ‘polypill’ trial suggest.

The Indian Polycap Study (TIPS) found that combining the medications did not hinder their potency – offering effective blood pressure (BP) and lipid control with a simple once-daily capsule.

The study paves the way for further trials to see whether the pill improves clinical outcomes on a wide scale, say the researchers.

The Polycap formulation used in TIPS contains low doses of aspirin (100 mg), simvastatin (20 mg), thiazide (12.5 mg), atenolol (50 mg) and ramipril (5 mg).

It was tested in a double-blind randomized controlled trial of 2,053 people aged 45 to 80 who had one existing risk factor but no history of cardiovascular disease (CVD).

Lead researcher Dr. Salim Yusuf stressed the need for further trials but called the potential to lower CVD risk with a single pill “a huge step in the management of patients.” He said that the Polycap has “definite” applicability for secondary prevention, and would lower costs and improve compliance in CVD patients who are already taking the individual drugs.

“The big question … is whether you take the whole world at large, over a certain age group, don’t measure anything, and then give them all a polypill. I will withhold judgment on whether that’s the right thing to do or not right now,” he said at a press conference.

TIPS was presented at the 58th Annual Scientific Session of the American College of Cardiology and published online in The Lancet. [2009 Mar 30; Epub ahead of print]

The study, carried out at 50 centers in India, comprised nine groups: 412 patients took the Polycap, while around 200 each were assigned to one of eight different permutations of the drugs alone and in combination.

After 12 weeks of Polycap therapy, mean systolic and diastolic BPs decreased by 7.4 mmHg and 5.6 mmHg, respectively, as compared to people taking no BP-lowering drugs. This magnitude was similar to that achieved with three BP-lowering drugs, either with or without aspirin.

LDL cholesterol was reduced by 0.70 mmol/L in Polycap users – a slightly lesser reduction than with simvastatin alone (0.83 mmol/L; P=0.04) but still highly significant compared to people who did not take a statin (P less than 0.0001).

The Polycap, manufactured by Cadila Pharmaceuticals, India, was well tolerated: discontinuation rates were similar to other treatment groups and largely attributable to social reasons.

The projected risk reductions for taking the Polycap were 62 percent for coronary heart disease events and 48 percent for stroke. These were calculated using the methods of Drs. Wald and Law, who first proposed the polypill concept in a seminal British Medical Journal paper. [2003 Jun 28;326(7404):1419]

Yusuf, director of the Population Health Research Institute at McMaster University, Canada, said that clinical event-driven trials of polypills could be published within 6 months to a year.

He acknowledged concerns that polypills could promote the wrong message if marketed incorrectly, stressing that lifestyle modification is the “the crux and the fundamental basis of CVD prevention.” He rejected, however, the suggestion that widespread medication could be a difficult idea to promote.

“There’s something inherently repulsive to most of us to say we’re medicalizing the whole population. Just think of the millions of people in the world taking multivitamins with no evidence.

“The concept of taking a pill to improve your health is really not new – it is embedded in most cultures, whether it is Asian, Western or wherever else,” he said.

Guidelines grow but offer opinions, not evidence

2009-05-25T04:04:00.000-07:00

Medical Tribune May 2009 P4
David Brill

The complexity of cardiology guidelines is growing but new recommendations are often unsupported by scientific evidence, a recent study has found.

The analysis of American College of Cardiology (ACC) / American Heart Association (AHA) clinical practice guidelines shows that the number of recommendations has risen considerably in the past 24 years.

The balance of recommendations, however, has shifted towards ‘class II’ – those that reflect a conflict of evidence or a divergence of opinion. The proportion of class I recommendations has remained largely unchanged.

Just 11 percent of all recommendations in the most recent guidelines are based on evidence level A. Almost half are based on level C – the lowest level – comprising expert opinion, case studies or standards of care.

The study, published in the Journal of the American Medical Association, was accompanied by an editorial calling for guidelines to be abolished unless the present system can be overhauled. [2009;301(8):831-41; 2009;301(8):868-9]

“Unfortunately, too many current guidelines have become marketing and opinion-based pieces, delivering directive rather than assistive statements,” wrote Drs. Terrence Shaneyfelt and Robert Centor from the University of Alabama, US.

“If all that can be produced are biased, minimally applicable consensus statements, perhaps guidelines should be avoided completely. Unless there is evidence of appropriate changes in the guideline process, clinicians and policy makers must reject calls for adherence to guidelines.”

Dr. Pierluigi Tricoci, lead author of the study, was more cautious in his response – acknowledging room for improvement with the format of guidelines but saying that they remain “important and useful” documents.

“The main message of our paper is that in cardiology, which we believe is one of the most advanced and evidence-based fields in medicine, we have a huge gap in knowledge,” said Tricoci, a cardiologist at Duke University, US. “In most situations that we find in clinical practice we don’t have enough supporting evidence that helps us make clinical decisions on what’s best for the patient.

“We hope that [this study] gives out the right message because we are not in a very good situation right now. Institutions and the government have to understand that there is a lot of research that is not well funded … we want to improve our current situation to close those gaps.”
Tricoci and colleagues reviewed 53 separate guidelines covering 22 topics. Excluding those which were never revised or updated, the number of recommendations has risen by 48 percent from the first to the latest editions of each document. The total number of recommendations rose from 1,330 in 1984 to 1,973 in 2008.

The levels of evidence vary widely between diseases. More than 20 percent of recommendations in heart failure and ST-segment elevation myocardial infarction guidelines, for example, have evidence level A. For valvular heart disease guidelines, however, just one of 320 recommendations is based on level A.

The ACC and the AHA welcomed the study’s findings in a joint statement, calling it a “valuable and important message” about the need to invest more in research.

“There are gaps in the evidence base for patient care, gaps that could be eliminated if more clinical research were funded, especially comparative effectiveness research that specifically compares one kind of diagnostic procedure or treatment with another,” said ACC president Dr. Douglas Weaver.

“Improving our evidence base can lead to even greater improvements in treatment and in saving lives.”

Statin ‘reloading’ improves PCI outcomes

2009-05-25T04:01:00.000-07:00

Medical Tribune May 2009 P8

David Brill

Topping up a patient’s statin levels before percutaneous coronary intervention (PCI) could improve outcomes in long-term statin users, a new study suggests.

The ARMYDA*-RECAPTURE trial found that “reloading” with high-dose atorvastatin before PCI reduced the relative risk of major adverse cardiac events by 48 percent at 30-day follow-up.

Treating seventeen patients with this strategy would prevent one such adverse event, the investigators reported.

The study, which involved 352 chronic statin users, extends the findings of the earlier ARMYDA trial which demonstrated the benefits of a statin loading dose in statin-naïve patients undergoing PCI.

“These findings may support a strategy of routine reload with high-dose atorvastatin early before intervention, even in the background of chronic therapy,” said lead investigator Dr. Germanio Di Sciascio, of the University of Rome, Italy.

“If confirmed by future studies, the results of ARMYDA-RECAPTURE may influence practice patterns, particularly for the acute care of non-ST elevation acute coronary syndromes [ACS].”

The researchers randomized 175 patients to placebo and 177 to atorvastatin reloading, which comprised an 80mg dose 12 hours before angiography, followed by a further 40mg dose 2 hours before.

Just 3.4 percent of statin-treated patients reached the primary endpoint – a composite of cardiovascular death, myocardial infarction and target vessel revascularization – as compared to 9.1 percent of those in the placebo group (P=0.045).

This effect was driven largely by patients who presented with ACS, rather than those presenting with stable angina. In a separate analysis of ACS patients alone, the relative risk reduction with atorvastatin was 87 percent and the number needed to treat was 9.

Atorvastatin reloading also significantly reduced the proportion of patients with elevation of creatine kinase-MB and troponin-I following PCI, and non-significantly reduced the proportion with elevated C-reactive protein. These findings suggest that a rapid LDL-independent effect may underlie the cardioprotective phenomenon, said Di Sciascio.

Dr. Robert Harrington, director of the Duke Clinical Research Institute, US, said that ARMYDA-RECAPTURE adds to the literature supporting early, intensive statin therapy both before and after ACS.

“The trial was very carefully done and it adds to the totality of the data. It is, however, small, and it does have borderline P values with very broad confidence intervals, suggesting a high degree of uncertainty as to the true estimate of effect.

“The limitations of the trial, I believe, warrant replication or validation before recommending widespread adoption of statin reloading,” he said. “Efforts to reduce periprocedural MI should absolutely explore options other than anti-thrombotic therapy, and inflammation certainly is a reasonable target.”

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*Atorvastatin for Reduction of Myocardial Damage during Angioplasty

Japanese CPR success could light the way for Asia

2009-05-25T03:57:00.000-07:00

Medical Tribune May 2009 P10
David Brill

Japan’s “impressive” success at tackling out-of-hospital cardiac arrests could inspire other Asian countries to improve their own survival rates, according to the chairman of the Singapore Heart Foundation (SHF).

One-month survival after a witnessed ventricular fibrillation episode has risen from 15 to 31 percent since a program was implemented in Osaka in 1998, researchers reported recently in Circulation. [2009;119:728-734] Neurologically-intact 1-month survival has risen from 6 to 16 percent.

The initiative has also reduced delays in calling for medical services, initiating cardiopulmonary resuscitation (CPR), and delivering a first shock, the study shows.

In Singapore, just 2.7 percent of people currently survive following an out-of-hospital cardiac arrest (OHCA), according to the SHF, which launched its own CPR initiative last year.

“This is a very encouraging study because it inspires us to put more effort into CPR training and providing defibrillators,” said SHF chairman Associate Professor Terrance Chua.

“What is most impressive is that they were able to improve survival rates. Having this clear documentation is good for morale because otherwise you can commit a lot of resources without knowing how much benefit you are getting from it,” he said. “We really take our hats off to them for having done this in a prospective registry so that they can monitor the improvements.”

The Utstein Osaka Project focuses on a four-step “chain of survival,” comprising activation of emergency medical services, CPR, defibrillation and advanced life support measures given by healthcare providers. The survival benefits were driven largely by improvements in the first three links of the chain, suggesting that the program’s public education component has had a significant impact.

Some 120,000 citizens per year have been trained in conventional CPR since the introduction of the program in Osaka, covering an area with a population of 8.8 million.

“This study proves that improvement in the chain of survival results in increased survival from out-of-hospital cardiac arrest in the real world,” said Dr. Taku Iwami, an assistant professor at Kyoto University Health Service, who led the research.

“We need to increase the number of automated external defibrillators [AEDs] in public places as well as train people in not only CPR but in the use of AEDs,” he said. “In many areas of the world, there are serious delays in the use of CPR and AEDs. We hope this study encourages other emergency medical service systems to start or continue their efforts to improve based on objective data.”

The study included 42,873 OHCAs in which resuscitation was attempted, occurring from May 1998 to December 2006. The median time from collapse to call for medical attention dropped from 4 to 2 minutes, and the time from collapse to first CPR dropped from 9 to 7 minutes. Median time from collapse to first shock decreased from 19 to 9 minutes.

In Singapore the public response to learning CPR has so far been “pretty positive,” according to Chua, who noted that despite the improvements in Osaka’s survival rates the study still highlights that there is further room for improvement.

The SHF launched its 3A (Anyone, Anytime, Anywhere) program in November 2008. The project includes the provision of CPR kits which include a mannequin, DVD and other reference materials, all of which can be used at home with the intention of creating a ”multiplier effect” whereby CPR skills are passed on to friends and family.

Thailand and Indonesia have also expressed an interest in adopting similar programs, Chua said.

The SHF has already trained some 2,000 students from seven schools using the CPR kits, which are on sale at a subsidized price of S$20 for students and S$50 for corporations and communities.

Several commercial facilities, including Suntec City and VivoCity shopping centers, have already installed their own AEDs since the launch of the 3A program, according to Chua. Changi Airport has also backed the project, and is currently in the process of developing and implementing its own AED installation program.

A 2002 study from three airports in Chicago, US, reported that 11 out of 18 patients who arrested with ventricular fibrillation over a 2-year period were successfully resuscitated using AEDs. Ten were alive and neurologically intact a year later. Six of the 11 rescuers had never used an AED before, although three were medically trained. [N Engl J Med 2002 Oct 17;347(16):1242-7]

Vaccinate the young against HPV, says Nobel Laureate

2009-05-25T03:55:00.000-07:00

Medical Tribune May 2009 SFIII

David Brill

Countries should “seriously consider” offering widespread human papillomavirus (HPV) vaccinations, according to the Nobel Prize-winning scientist who first linked the virus to cervical cancer.

Professor Harald zur Hausen, addressing the media on a recent visit to Singapore, said that boys and girls alike would benefit from the vaccine, but stressed that it should be given prior to the onset of sexual activity.

For older women who are already sexually active, it should be a personal decision whether or not to be vaccinated, he said.

zur Hausen also rejected the argument that effective screening programs can be superior to widespread vaccination.

“I think that’s a mistake because screening and vaccination do something different,” he said. “In screening you discover lesions which need to be removed. In vaccination you prevent the lesions, and therefore you don’t [need] surgical intervention.”

Vaccination has been shown to be safe and highly effective for preventing HPV infections but opinions remain divided about who, when and how to vaccinate. Australia, for example, has approved vaccination of women aged 10 to 45, whereas the US FDA limits approval to 9 to 26 year-olds.

“It would really be something which one should seriously consider – to vaccinate everyone,” said zur Hausen, winner of the 2008 Nobel Prize in Physiology or Medicine.

“[But] let me be quite clear about it – the vaccine is really only protective in preventing the infection. If there has [already] been an infection the vaccine has no effect whatsoever.

“Up to the onset of sexual activity, yes, you can clearly say it’s worthwhile. But subsequently it’s more difficult to make a statement along those lines.”

Neither of the HPV vaccines is presently approved for use in males, but zur Hausen outlined several supporting arguments. Firstly, it would protect women from cervical cancer by reducing HPV transmission. Secondly, men themselves would gain protection from genital warts and other HPV-positive cancers, including anal and oropharyngeal cancers. Upcoming data from the first clinical studies in boys “look very promising,” he said.

zur Hausen also called for reductions in the price of HPV vaccines, which are presently “unaffordable” for parts of the developing world. This would pave the way for global vaccination programs, offering “the theoretical chance to eradicate some of these infections which lead to cervical cancer.”

Professor zur Hausen delivered the 6th Humphrey Oei Distinguished Lecture at the National Cancer Center, Singapore, and the second opening lecture at the Asian Oncology Summit 2009.

Singapore to wait and see on HPV vaccination

2009-05-25T03:52:00.000-07:00

Medical Tribune May 2009 SFIII
David Brill

Singapore will not rush to make human papillomavirus (HPV) vaccination part of its national immunization program.

Insteady, the city-state will await the outcomes of vaccination programs in other countries before making its own decision, said Dr. Balaji Sadasivan, senior minister of state, Ministry of Foreign Affairs.

In the meantime, the nation will continue strengthening its Pap smear screening coverage. The HPV vaccine will remain available on an optional basis, giving individual parents the right to choose whether to vaccinate their daughters.

“As a country with a lower incidence of cervical cancer, the risk-benefit ratio will be lower in Singapore. We should therefore be cautious in making any national recommendation with regard to vaccination,” said Balaji at the recent Asian Oncology Summit 2009.

“If we put it in our national immunization program almost every young girl will get vaccinated. That’s a very, very major step, and sometimes … it’s not necessarily the wisest thing to be the first to try something out because you’re basically the guinea pig. It may just be safer to wait and see how other countries proceed with this.”

Balaji singled out the UK in particular as one “for us to watch,” following the September 2008 introduction of a national HPV immunization program for girls aged 12 to 13. “If it turns out to be safe to do it on a national scale then I think it would make sense for us to consider doing the same thing,” he said, adding that it would be “a few years” before any conclusions could be made.

Balaji also expressed clinical concerns about the vaccine, notably that it remains unclear whether immunity is long-lasting. It is also unknown whether other strains of HPV could become dominant if current strains are contained.

“From an ethical standpoint, there is also the issue of consent, which has to be viewed in the local context, where the community’s moral viewpoint is that offering such a vaccination program sends out the wrong message – that teenage sex is condoned by the community,” he said.

“Pap smear screening is one of the most effective ways of reducing the risk of cervical cancer, and we have pretty good coverage of about 60 to 70 percent. We should continue to build on that program and not neglect [it] because of the possibility of vaccination. That is a reasonable alternative while waiting to have better data,” he concluded.

Dr. Balaji delivered the opening address at the Asian Oncology Summit 2009, and spoke directly with the media.

Folic acid-vitamin combo cuts AMD risk in women

2009-05-25T03:48:00.000-07:00

Medical Tribune May 2009 P11
David Brill

Taking folic acid with vitamins B6 and B12 could help to prevent age-related macular degeneration (AMD) in women at high risk of cardiovascular disease (CVD).

Women who took daily supplements for 7 years reduced their relative risk of AMD by around a third, a recent trial reported.

The analysis included 5,205 women aged over 40 who had a history of CVD and a minimum of three CVD risk factors but no AMD at baseline. There were 55 cases of AMD in the treatment group and 82 in the placebo group at trial’s end. [Arch Intern Med 2009 Feb 23;169:335-41]

Lead author Dr. William Christen, an associate professor at Brigham and Women’s Hospital and Harvard Medical School, US, said that the intervention is safe and inexpensive and could, theoretically, be applied on a wide scale. However, he stressed the need for more research before making any specific recommendations.

“This is the first trial to suggest a possible benefit so I think it’s important at this point to corroborate the findings in other populations,” he said.

“Other than avoiding cigarette smoking we have no means to prevent the early stages of AMD so these findings, if they’re corroborated … will be particularly important from a public health perspective.”

AMD is the leading cause of blindness in European and US over-60s and is thought to be on the rise in Asia.

The Singapore Malay Eye Study found that in its early stages the condition affects 3.5 percent of Malays aged 40 to 80 – a comparable figure to that reported in the Australia. The prevalence of late-stage AMD among Malays was 0.34 percent. [Ophthalmology 2008;115(10):1735-41]

For elderly Singaporeans in general the prevalence of AMD could be as high as 27 percent, according to a study of 574 over-60s. Awareness of the condition however seems to be low – for every AMD patient with a confirmed diagnosis there were 154 who did not know they had the condition. [Singapore Med J 1997;38(4):149-55]

Vitamins are not currently recommended for primary AMD prevention but have been shown to delay progression in those who already have intermediate-stage disease. A combination of high-dose antioxidants (vitamins C, E and beta carotene) and zinc reduced the odds of developing advanced AMD by 28 percent, as compared to placebo, in a trial of 3,640 patients with an average of 6.3 years of follow up. [Arch Ophthalmol 2001 Oct;119(10):1417-36]

Christen et al. randomized participants to placebo or a regimen of 2.5 mg/day folic acid, 50 mg/day vitamin B6 and 1 mg/day vitamin B12 – higher dosages than typically given over the counter. The relative risk in the treatment group was 0.66 for AMD (95 percent CI 0.47-0.93; P=0.02) and 0.59 for visually significant AMD (95 percent CI 0.36-0.95; P=0.03). Mean follow-up was 7.3 years.

The study could also provide important new insights into the much-debated role of homocysteine in vascular disease. The marker has been strongly linked to atherosclerosis, CVD and AMD, but trials have yet to show that homocysteine-lowering therapies, notably folic acid and B vitamins, significantly improve outcomes.

“If these findings are real for AMD then one possible explanation would be … that there may be a difference between small vessel and large vessel disease in the response to homocysteine lowering. At this point we can only speculate,” said Christen.

New jab shows promise for CMV prevention

2009-05-25T03:45:00.000-07:00

Medical Tribune May 2009 P12

David Brill

American researchers have scored “a home run” in the quest to prevent congenital cytomegalovirus (CMV) infections – a leading cause of birth defects in newborns.

In a recent phase II trial they found that a new vaccine was 50 percent effective at preventing CMV infection among women, after a minimum of 1 year follow-up.

Just 18 of 234 women who were vaccinated went on to develop CMV infection, compared to 31 of 230 women in the placebo group. [N Engl J Med 2009 Mar 19;360(12):1191-9]

Further trials are now needed to confirm whether immunizing mothers will actually translate to a reduction in congenital infections, said lead researcher Dr. Robert Pass.

With phase III trials also required it is likely to be at least 5 years before the vaccine is licensed, he said. It also remains unclear whether CMV immunity persists or would need boosters.

Successful CMV vaccines have so far proved elusive: none are currently licensed despite more than 30 years of research and a ‘top priority’ listing by the US Institute of Medicine in 2001.

“CMV is a very complex virus which has a long-standing relationship with its host,” said Pass, who is professor of pediatrics at the University of Alabama at Birmingham, US.

“When this trial was initiated most people did not think we would find any efficacy for prevention of maternal infection. So to find that the vaccine was actually able to prevent infection in women was essentially a home run.”

Around 0.7 percent of babies are born with a congenital CMV infection – 11 percent of whom are symptomatic at birth. Fetal damage typically occurs in cases where the infection is acquired during pregnancy: around 0.5 percent of such babies die and up to 20 percent have permanent disabilities. [N Engl J Med 2009 Mar 19;360(12):1250-2]

CMV is endemic in Singapore – the virus was present in 87 percent of antental women screened at KK Women’s and Children’s Hospital (KKH) from 1997 to 1998. [Singapore Med J 2000 Apr;41(4):151-5]

Dr. Lai Fon Min, a consultant and head of the antenatal risk assessment unit at KKH, said that there is an important need for CMV vaccines since there are limitations to both maternal and fetal screening, and no accepted therapy for congenital infections.

“If a highly effective vaccine for CMV is developed there may be justification in introducing it in Singapore as we have a high prevalence rate,” he said, but added that it “remains to be seen” whether routine vaccination would be cost effective.

The vaccine tested by Pass and colleagues comprises 0.02 mg of CMV envelope glycoprotein B, along with 13.25 mg of a squalene-in-water emulsion known as MF59. The rights are owned by Sanofi Pasteur.

The study was not designed to assess outcomes among newborns but the findings appear promising: just one of 81 babies born to vaccinated mothers had CMV, whereas three of 97 babies born to placebo-group mothers were infected.

The trial enrolled CMV-seronegative women who had given birth within the previous year. They were vaccinated at 0, 1 and 6 months, and tested quarterly for CMV infections over 42 months.

Injection-site reactions were more common in the vaccinated women but overall adverse event rates were not significantly different to placebo.

Pass added that vaccination could either be performed in pre-teen girls – potentially in combination with the human papillomavirus vaccine – or in very young children, since they are the main source of CMV infections for pregnant women.

Picking and choosing: No way to lose weight

2009-05-25T03:40:00.001-07:00

Medical Tribune May 2009 P13
David Brill

Weight loss diets which promote one particular food group may not be the best way to shed the kilos, a recent study suggests.

In one of the longest trials of its kind, US researchers found that there was ultimately little difference in weight loss whether diets emphasized carbohydrates, protein or fat.

Nor did waist circumferences differ significantly after 2 years of following the diets, the study of 811 overweight adults showed.

"This is important information for physicians, dieticians and adults, who should focus weight loss approaches on reducing calorie intake," said lead author Professor Frank Sacks, Harvard School of Public Health, US.

Participants were randomized to one of four diets. The compositions varied, but all targeted a 750 kcal decrease in daily intake. [N Engl J Med 2009;360(9):859-73]

Weight loss peaked at 6 months – when participants had lost an average of 6 kg, or 7 percent of their initial weight. Weight regain began after 12 months: those who completed the study had lost an average of 4 kg at its conclusion.

The researchers also found that people who attended the most group counseling sessions lost the most weight – an average of 0.2 kg per weekly session.

"These findings suggest that continued contact with participants to help them achieve their goals may be more important than the macronutrient composition of their diets," said Sacks.

Singapore’s Health Promotion Board (HPB) welcomed the study as an informative, but not definitive, addition to the literature.

“The study was limited in that the differences in the macronutrient content of the different diets was not as substantial as originally planned, hence the resultant diets did not fully replicate the macronutrient distribution of popular ‘low-carb’ or low-fat diets,” said Mr. Benjamin Lee, manager and nutritionist, adult health division, HPB.

The HPB advocates a holistic approach to weight loss including exercise and stress management, added Lee. Specific dietary recommendations are to focus on calorie reduction while maintaining a diet which covers four food groups: rice and alternatives, fruit, vegetables, and meat and alternatives (including dairy foods).

Ms. Jamie Liow, a nutritionist and member of the Singapore Nutrition and Dietetics Association, said that carbohydrate intake is typically a concern among Asians who diet.

“Most would either have a low-carbohydrate, high-protein diet, or no carbohydrates at all. Crash dieting seems to be popular among younger girls as well,” she said.

Liow also emphasized the importance of getting nutrients from “a whole spectrum of foods,” adding that doctors should refer their patients to dieticians for specific advice on the best way to lose weight.

The four diets tested by Sacks et al. comprised: 20 percent fat, 15 percent protein and 65 percent carbohydrate; 20 percent fat, 25 percent protein and 55 percent carbohydrate; 40 percent fat, 15 percent protein and 45 percent carbohydrate; or 40 percent fat, 25 percent protein and 35 percent carbohydrate.

The lowest-fat and the highest-carbohydrate diets brought about the greatest reduction in LDL cholesterol levels, whereas the lowest-carbohydrate diet yielded the biggest increase in HDL cholesterol. Triglyceride levels dropped similarly for all diets.

Dieters were also encouraged to exercise for 90 minutes per week, and received weekly group counseling sessions and 8-weekly individual sessions.

Despite this intensive encouragement, dieters did not meet their nutrient intake targets when questioned at 6 months and 2 years. This appears to be a common problem in weight-loss trials, say the authors, noting that many previous studies have also found that adherence declines after a few months.

Simple online tool predicts type 2 diabetes risk

2009-05-25T03:40:00.000-07:00

Medical Tribune May 2009 P14
David Brill

A simple new tool could allow GPs to identify patients at high risk of developing type 2 diabetes without the need for laboratory tests.

The QDScore, developed with electronic medical record data from some 2.5 million patients, is quick and easy to use and is freely available online.

It is the first prediction algorithm to include ethnicity and social deprivation alongside conventional diabetes risk factors, and is intended for routine use in primary care.

The QDScore performed well in a recent study – accurately predicting 10-year diabetes risk in a diverse patient population drawn from 176 UK general practices. [BMJ 2009 Mar 17;338:b880]

“There is good evidence that lifestyle changes and medical intervention at an early stage can prevent type 2 diabetes in up to two-thirds of high-risk cases and that early diagnosis is likely to improve outcomes,” said lead researcher Professor Julia Hippisley-Cox, professor of clinical epidemiology and general practice at the University of Nottingham, UK.

“As the number of people diagnosed with diabetes in the UK continues to rise, this new algorithm will be an invaluable tool to help doctors identify those at greatest risk who are most likely to benefit from interventions.”

The QDScore calculates risk using age, sex, ethnicity, family diabetes history, personal cardiovascular disease history, hypertension medications, steroid usage, smoking status and body mass index. It was derived from a cohort of more than 2.5 million 25 to 79 year-olds – over 78,000 of whom developed type 2 diabetes over 10 years of follow up.

There were considerable differences in diabetes risk between ethnic groups. Bangladeshi men were the most likely to develop diabetes, with an adjusted hazard ratio (HR) of 4.53 as compared to Caucasian men. The subsequent male risk hierarchy was: Pakistani, Indian, Other Asian, Black African, Chinese and Black Caribbean (adjusted HRs 2.54, 1.93, 1.89, 1.67, 1.41 and 0.80 respectively).

The risk patterns were similar for women, although Chinese ethnicity conferred a greater risk than in men. Bangladeshi women were the most likely to develop diabetes, followed by those of Pakistani, Chinese, Indian, Other Asian, Black African and Black Caribbean origin (adjusted HRs 4.07, 2.15, 1.96, 1.71, 1.26, 0.81 and 0.80, respectively).

The QDScore was tested on records from more than 1.2 million patients – over 37,500 of whom developed diabetes. It scored highly on validation statistics, out-performing the Cambridge risk score in all domains for both men and women. It is available at: http://www.qdscore.org/.

Sputum testing offers key to improving asthma therapy

2009-05-25T03:37:00.000-07:00

Medical Tribune May 2009 P15

David Brill

Individualizing therapy on the basis of sputum cell counts could help to improve the treatment of severe asthma, new research suggests.

A recent small-scale randomized study found that patients treated in this way had significantly fewer exacerbations and were able to safely reduce their prednisone doses.

The trial involved a rare subset of patients with high levels of eosinophils in the sputum, but the same principles could be extended to other types of asthma, the researchers say.

“Our philosophy ... has been to measure bronchitis by a simple processing of sputum. Identify the type of bronchitis and treat it accordingly based on the type of cell. It’s a very simple message,” said lead author Dr. Parameswaran Nair, an associate professor of medicine at McMaster University, Ontario, Canada.

“Most patients with eosinophilia are easy to treat and can be controlled with small or moderate doses of inhaled corticosteroids. But in the severe patients people [should] take a step back if the patient is not getting better with prednisone and think ‘what is the type of bronchitis? Should we not understand what’s going on here before we increase or add new treatments?’”

The study, which lasted 26 weeks in total, included only patients whose sputum eosinophilia had persisted despite prior prednisone treatment. Nine received five monthly infusions of mepolizumab (750 mg) – a monoclonal antibody which disrupts the activation of eosinophils by targeting interleukin-5 – and 11 received placebo. [N Engl J Med 2009 Mar 5;360(10):985-93]

There was only one asthma exacerbation in the mepolizumab group and this was associated with sputum neutrophilia rather than eosinophilia. Placebo patients, in contrast, experienced a total of 12 exacerbations – nine associated with eosinophilia and three with neutrophilia (P=0.002).

Patients taking mepolizumab reduced their prednisone dosage by a mean of 83.4 percent of the maximum possible reduction, compared to 47.7 percent for patients on placebo (P=0.04).

The accumulation of eosinophils in the airway is thought to be an important event in the pathogenesis of asthma but the exact role of the cells remains unclear. Previous studies have failed to show any benefit of anti-interleukin-5 antibodies as a therapy for asthma, but these trials did not tailor the therapy to specific patients.

“We argued that if we give it to every patient with asthma it’s not going to work – it’s only going to work if you’ve got eosinophilia to begin with,” said Nair.

The McMaster respiratory group, led by Professor Freddy Hargreave, has already demonstrated the benefits of individualizing therapy in an earlier randomized trial of 117 asthma patients. The number and severity of eosinophilic exacerbations were both reduced using the sputum-based approach, as compared to standard treatment according to Canadian guidelines. [Eur Respir J 2006 Mar;27(3):483-94]

Nair hopes that latest new study will raise awareness of the benefits of sputum testing for asthma, admitting that he is “very frustrated” that such a simple procedure has not caught on more widely.

“A rheumatologist would aspirate fluid from a joint to look at inflammation before giving anti-inflammatories, and a gastrointestinal surgeon would take a rectal biopsy for colitis before giving corticosteroids.

“But we in respiratory medicine are giving bucketloads of corticosteroids and anti-inflammatory drugs without measuring inflammation. Most physicians all over the world only measure forced expiratory volume in 1 second (FEV1), which is just a measure of airway caliber and not of bronchitis,” he said.

The results of another study, published in the same edition of the journal, lend further support to the theories of Nair et al. In a randomized double-blind trial of 61 patients, UK researchers showed that mepolizumab, compared to placebo, reduced severe exacerbations and improved quality of life in patients with refractory eosinophilic asthma. [N Engl J Med 2009 Mar 5;360(10):973-84]

A separate study, meanwhile, is already underway at McMaster to assess the effects of blocking neutrophils, which are typically found in asthma patients who have bronchitis caused by an infection.

Conquering Kinabalu

2009-05-19T04:41:00.000-07:00

Medical Tribune April 2009 P18
David Brill

Mount Kinabalu is widely promoted as a straightforward climb for the everyday tourist. David Brill wonders whether Superman has been writing travel books in his spare time.

Pulling myself up a sheer cliff face in the pitch black at 4 a.m. I realized I’d been misled. With my hands slipping on the wet rope, the cramp aching in my legs and the insidious cold penetrating four layers of clothing, it began to dawn on me that climbing Mount Kinabalu was not going to be as simple as I’d been led to believe. When I saw a grown adult burst into tears, my worst suspicions were confirmed.

Rising to 4,095 meters above sea level, Mount Kinabalu is the highest mountain in Borneo although not, as often claimed, the highest in Southeast Asia (Myanmar and Indonesia boast loftier peaks). With 47,848 climbers in 2008 alone –26,595 of them non-Malaysians –it is considered to be one of the world’s most accessible mountains, and no specialist climbing skills are required.

Armed with a personal assurance that conquering the peak would be “easy,” we had arrived in the town of Kota Kinabalu on Friday night and travelled straight to the Kinabalu National Park, the UNESCO World Heritage site where the mountain is located. The drive usually takes around 2 hours but with heavy rain, thick fog and herds of cows mysteriously crossing the road, our progress was a little slower than might be expected. We arrived in the small hours of Saturday and, 5 hours sleep in a freezing dormitory later, were ready to begin the climb.

Only the bravest attempt to ascend and descend Mount Kinabalu in a single day, and the majority of tourists spend a night at Laban Rata –an accommodation compound situated around 3,000 meters up. With the mountain entirely shrouded in mist, it was left to our imaginations as to how high this might actually be, and we set off with the blissful optimism that accompanies blind ignorance.

Stage one of the climb is straightforward but cannot be described as easy. Five hours on a steep, meandering path, clambering over boulders and slipping in the mud, was achievable but not an experience I’d wish to repeat. When cramp set in it became genuinely challenging, and the need for effective hydration was a lesson learned the hard way. Cramp does not seem to be a problem for the porters, however, who regularly ferry supplies and equipment back and forth up the slopes, hardly breaking a sweat as they do so. There can be few experiences in life more demoralizing than struggling your way up a mountain, only to be overtaken by a man running full pelt with a dishwasher strapped to his back.

The relief upon arriving at Laban Rata was palpable. Accommodation here must be reserved before beginning the climb and is often booked up as far as 6 months in advance. There are a few different options within the compound, which can hold a total of 146 climbers on any single night, but the Laban Rata Rest House is promised as offering the greatest level of luxury. However with ice-cold showers and an electric radiator that struggled to generate heat but succeeded in unleashing a torrent of sparks during the night, I can only imagine what comforts await in the other buildings. The wisdom of reserving early was firmly reinforced.

Any last lingering hopes of a relaxing weekend break were finally shattered by the 2:30 a.m. wake up on the Sunday morning. Half an hour later we were on our way to Low’s Peak –an ironic title dedicated to British Explorer Sir Hugh Low who in 1851 became the first documented person to reach the summit. The warmth that was enjoyed at 3,000 meters quickly plummets along this stretch, and it is here that the rewards of a sensible packing list are reaped. A good pair of waterproof gloves and a head torch are extremely useful for sections where a rope is required, and a warm, windproof jacket will come in handy throughout. As the temperature drops so too does the vegetation –the lush greenery of the lower slopes giving way to sweeping expanses of bare rock that offer little shelter from the wind.

With altitude sickness, fatigue and depression setting in, we finally reached the peak around 2 hours after leaving Laban Rata. We did not have to wait long for the mood to lift, however. As the sun crept up over the horizon sometime after 5 a.m. the misery of all that had gone before was forgotten, replaced with a delirium-heightened wave of elation which swiftly swept through
the group. Aches and pains were put on hold as we reveled in the collective sense of achievement – 13 members of our motley crew had set off from Singapore and 13 were now sitting at the peak of Mount Kinabalu.

The view, as expected, is breathtaking. And as the sun began to provide some warmth, so the urgency to descend diminished. For the first time on the trip we were able to take in our surroundings without the sense of impending dread at what was to follow, leaving us free to return to Laban Rata in a more relaxed fashion than that in which we left. The rocks are significantly easier to traverse with the benefit of daylight, and we were breakfasting at the hostel around an hour after leaving the peak.

The rest of the descent is no simple task, and is considered by some to be the hardest part of the journey. Stiffness sets into the muscles and the height of the steps places considerable strain on the knees and calves. Buoyed by the knowledge that the worst was over, however, the pain became bearable and personally I came dangerously close to enjoying myself. Descending at a leisurely pace brought us back to base camp within 4 hours, while quicker members of the group made it inside 3. The porters, needless to say, sprinted past like Olympic mountain goats.

Climbing Mount Kinabalu is a physical and emotional rollercoaster. It took me a week to regain the full use of my legs, but it’s a small price to pay to know that I made it. Easy? No. Worth every second? Undoubtedly.

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For details of accommodation and climbing fees for Mount Kinabalu, see: www.suterasanctuarylodges.com.my/climbing_mt_kinabalu.php

Urine test shows promise for prostate cancer detection

2009-05-19T04:39:00.000-07:00

Medical Tribune April 2009 P4

David Brill

A prototype urine test has been shown to be highly specific for detecting prostate cancer and could even help to reduce the number of unnecessary biopsies, US researchers suggest.

Moreover the results showed some correlation to disease severity markers, suggesting that the test could be used to distinguish between mild and aggressive forms of cancer.

The urine test detects the presence of a fusion between the TMPRSS2 (T2) and ERG genes, which is found in around 50 percent of prostate cancers.

“Many cancers detected at biopsy are low volume, low grade. There is a real need for tests that can help determine which of those men should receive aggressive treatment such as prostatectomy, and which could potentially be monitored more conservatively,” said lead researcher Dr. Jack Groskopf, who presented the results at the recent Genitourinary Cancers Symposium in Orlando, US.

“The key next steps here are to follow up and confirm the results that we have generated to date and, perhaps more importantly, to start looking at the correlation between the urine test and pathologic features in prostatectomy tissues, such as tumor volume stage and grade,” he said.

Commenting on the results, Dr. Howard Sandler, chair of radiation oncology at Cedars-Sinai Medical Center, Los Angeles, said: “The fact that this gene fusion is related to the progression and development of prostate cancer in half of all men who develop prostate cancer has major implications for diagnosis but hopefully for therapy as well. This unique fusion protein might become a therapeutic target at some point in the future.”

In a preliminary study of 556 men due to undergo prostate biopsy the urine test was 84 percent specific, reported Groskopf, a senior research scientist at Gen-Probe Incorporated, the San Diego-based company which is developing the test. For serum prostate-specific antigen (PSA) testing this figure is just 27 percent, he said, adding that the other current screening method – digital rectal exam – is also hampered by its low specificity.

“As a result the majority of prostate biopsies are negative, and you could argue that we are doing too many biopsies,” he said.

The sensitivity of the urine test was 42 percent – a favorable result considering that with only half of cancers containing the T2:ERG gene fusion, the theoretical maximum would be 50 percent, Groskopf added.

The urine test showed significant correlations to aggressiveness indicators such as the Gleason Score, the percentage positive prostate cores and the Epstein criteria.

Researchers from the University of Michigan, who are collaborating with Gen-Probe on the test, recently published another research paper linking sarcosine, a glycine derivative, to more aggressive forms of prostate cancer. This metabolite and its pathways could not only serve as a disease severity marker but also as a target for therapeutic intervention in future, they suggest. [Nature 2009 Feb 12;457:910-4]

CRT holds promise for atrial fibrillation in heart failure

2009-05-19T04:32:00.000-07:00

Medical Tribune April 2009 P9
David Brill

The benefits of cardiac resynchronization therapy (CRT) for heart failure could extend to those sicker patients who have atrial fibrillation (AF), according to a leading Hong Kong cardiologist.

Although more randomized controlled studies are needed, observational data so far appear to support the use of CRT for these patients said Dr. Jeffrey WH Fung, director of cardiac electrophysiology and pacing services at the Prince of Wales Hospital, Chinese University of Hong Kong.

Fung estimated that up to 30 percent of heart failure patients have AF, but noted that guidelines currently exclude this group from the class I indications for CRT. This top-level recommendation is presently reserved for those who are in sinus rhythm, while AF patients are grouped under class IIa indications – reflecting a lower level of evidence in support of the treatment.

Fung, however, pointed to a recent paper from the Multicentre Longitudinal Observational Study (MILOS) group – the largest study so far to address the use of CRT in AF patients. After a median of 34 months following CRT, all-cause and cardiac mortality were similar between the 243 AF patients and the 1,042 sinus rhythm patients. [Eur Heart J 2008 Jul;29(13):1644-52]

Further support for these findings comes from a meta-analysis of 5 observational studies involving 1,164 patients, which showed that AF and sinus rhythm patients had similar mortality 1 year after CRT initiation. Improvements in New York Heart Association functional class were also comparable for the two groups. [J Am Coll Cardiol 2008 Oct 7;52(15):1239-46]

“It seems that sinus rhythm and AF patients behave similarly after receiving CRT,” Fung summarized. He noted that sinus rhythm patients appear to fare better on quality of life measurements, but said that this finding is “consistent with other heart failure studies which show that AF patients are much sicker than those who remain in sinus rhythm, no matter what therapies they receive.”

Besides the clinical benefits, CRT also seems to offer comparable improvements between the two patient groups when it comes to echocardiographic parameters, he added.

The jury is still out, however, on whether AF patients should undergo atrio-ventricular junction (AVJ) ablation alongside CRT, said Fung. The MILOS study found that ablation improved survival compared to CRT alone but other studies have produced inconsistent results, he said, cautioning that AVJ ablation renders patients device-dependent for the rest of their lives and should not be done unless necessary.

“I think we need a properly randomized study to try to ascertain the merits of ablation or pharmacological rate control and understand which one is really preferred in patients with heart failure and permanent AF,” he said.

“We should try to maximize drugs and sometimes maybe if there is a very low percentage of pacing you may ask the patient to undergo AVJ ablation. But looking in our database it seems that most of the patients are doing fine with more than 90 percent pacing just with drugs,” he concluded.

Healthcare technology saves lives, boosts care

2009-05-19T04:21:00.002-07:00

Medical Tribune April 2009 SFI

David Brill

Adopting the latest healthcare information technologies can save lives, reduce complications and cut costs, a new report from 41 US hospitals shows.

It is one of the first studies to provide generalizable, empirical evidence that technology actually improves outcomes, the researchers say.

Inpatient mortality dropped by 15 percent in hospitals with the most highly automated notes and record systems. Complication rates were reduced by 16 percent in those with the highest levels of electronic decision support. [Arch Intern Med 2009;169:108-14]

Lead author Dr. Ruben Amarasingham, assistant professor of medicine at the University of Texas Southwestern Medical Center, said that the study “provides good news and caution” as governments worldwide debate healthcare stimulus packages.

The findings were welcomed in Singapore, where the upgrading of electronic systems across the healthcare clusters continues apace (inset).

Dr. Chong Yoke Sin, group chief information officer at SingHealth, said: “This study is reassuring for the people who invest in information technology for hospitals. There is now evidence to prove that it is indeed useful.”

Although happy with progress so far Chong stressed the importance of performing “meticulous” checks to ensure the integrity of new systems.

“When you use any kind of technology you have got to do it right, otherwise you are propagating the wrong faster and more pervasively. If a human being writes a wrong prescription you have only got that one wrong prescription, whereas if technology is not performing correctly it’s systemic,” she said. “At SingHealth we are always improving with constant feedback from clinical staff on the ground, which enables us to review workflow for better efficiency.”

Amarasingham agrees. “Our results suggest that investment in information technology is a necessary part to improving healthcare. But it’s clearly not sufficient – there needs to be a lot of other action taken.

“It has to be done carefully and thoughtfully over a prolonged period of time with careful outcome measures. If [investment] is not accompanied by a deliberative, strategic approach within hospitals and clinics then you may end up with worse systems, or at least a waste of money,” he said.

Over at the National Healthcare Group Mr. Ho Khai Leng, information technology director, said that new technology “improves care” by giving clinicians quicker and more accurate access to medical information. New systems also “facilitate the seamless transfer of patient information between care providers,” he said.

The digitization of x-rays has been particularly successful – cutting turnaround time from 2 or 3 days down to an hour or less, and saving “significant costs” for NHG and patients alike, he said. Tan Tock Seng Hospital alone saved $16,000 on films and chemicals between January and March 2006, following implementation of the project.

Amarasingham and colleagues reviewed data from 167,233 over-50s who were admitted to urban Texas hospitals between December 1 2005 and May 30 2006. They graded hospitals using the Clinical Information Technology Assessment Tool (CITAT), which measures the level of computerization in four clinical areas.

Average patient costs were reduced by US$538 ($816), US$132 ($200) and US$110 ($167) in hospitals with high scores on decision support, CPOE and test results, respectively. Costs were not significantly different within the notes and records domain.

Amarasingham acknowledged a “generational gap” with technology use, but said that all opinions must be considered when implementing new systems.

“If there are physicians who are reluctant or scared of using it then we need to reach out to them and involve them in the process. They are sometimes our best physicians with enormous experience that they can bring to the table,” he said.

Singapore center set to tackle childhood cancer in Asia

2009-05-19T04:21:00.001-07:00

Medical Tribune April 2009 SFIV

David Brill

A new Singapore center could help raise childhood cancer survival rates across Asia, thanks to a recent $24 million funding boost.

The money will expand treatment facilities and strengthen research at the Viva-University Children’s Cancer Centre, which has already treated some 40 overseas children and begun training visiting specialists.

Around four out of five children with leukemia are cured in Singapore but in nearby countries this figure can be as low as one in 20.

“There is an urgent need for us to respond to the cries of children with cancer in Singapore and the whole region,” said Mrs. Jennifer Yeo, director and secretary of Singapore-based Viva Foundation for Children with Cancer.

“We are confident that with the support of all our donors, volunteers and strategic partners we can save many young lives,” she said.

The center, known as VUC3, has been operational for a year but was officially opened last month. Two specialists from the Philippines have already trained there, and one each from Myanmar and Brunei are currently in training.

The new funding comprises a $12 million gift from the Goh Foundation – a nonprofit private group – matched like-for-like by the Singapore government.

Four main research programs will be established, comprising bone marrow transplantation, childhood leukemia, bone cancer and ‘after completion of therapy,’ which focuses on the long-term impact of cancer treatment. This research will have a strong translational clinical focus with a view to raising cure rates, lowering treatment costs and minimizing side effects, said Associate Professor Allen Yeoh, medical director of VUC3.

“This will provide us with a quantum leap in the care of childhood cancer in Singapore, and help ensure that no child dies in the dawn of life. In the current severe recessionary climate, we are truly grateful to the Goh Foundation for their generosity,” said Yeoh, also a consultant at the University Children’s Medical Institute, National University Hospital, which houses VUC3.

Pediatric cancer survival is “dismal” in low-income countries, according to a study published last year. Five-year survival in the Philippines was estimated at 10 percent and in Vietnam just 5 percent. [Lancet Oncol 2008 Aug;9:721-9]

Between 120 and 140 new pediatric cancer cases are diagnosed in Singapore each year – some 40 percent of which are leukemia. Around 40 local children have been treated at VUC3 so far.

The center has already installed five new bone marrow transplant rooms and raised the number of inpatient beds from 12 to 17. The funding has also helped establish the Viva-Goh Foundation Professorship in Pediatric Oncology.

VUC3, built at a cost of $5 million from the Singapore Tote Board and Viva Foundation, is working closely with the St. Jude Children’s Research Hospital in Memphis, US – one of the world’s leading childhood cancer centers.

Statin-associated adverse events under-appreciated, experts say

2009-05-19T04:21:00.000-07:00

Medical Tribune April 2009 P11

David Brill

The potential hazards of taking statins may be under-appreciated by the medical community, with adverse reactions often overlooked and sometimes even dismissed, according to US researchers.

Attention has largely focused on the most commonly-reported issue of muscle problems but the full side effect profile is wider than typically thought, they warn.

Cognitive problems are the second most common reaction to statins, followed by peripheral neuropathy-type symptoms, such as numbness and burning, said Dr. Beatrice Golomb, an associate professor of medicine at the University of California, San Diego (UCSD).

Rarer reports have also linked statins to a range of other conditions including sexual dysfunction, glucose elevation and vision problems.

Golomb is head of the Statin Study Group at UCSD, which is currently conducting an observational study looking at the adverse effects of the drugs. She also recently co-authored a literature review which, with almost 900 references, she believes to be the most comprehensive look at the subject to date. [Am J Cardiovasc Drugs 2008;8(6):373-418]

“In clinical trials, adverse events look rare. But for those of us who see real-world patients they’re a really big problem,” she told Medical Tribune.

Golomb highlighted a French observational study reporting that 10.5 percent of patients experienced muscle symptoms, and a Danish population-based study which showed that current statin users had a roughly 16-fold increased risk of polyneuropathy compared to non-users. [Cardiovasc Drugs Ther 2005 Dec;19(6):403-14; Neurology 2002 May 14;58(9):1333-7] She noted, however, that adverse event rates vary between different studies and populations, making it difficult to provide definitive overall figures.

Meta-analyses, meanwhile, have yielded significant odds ratios of 1.4 and 1.44 for any adverse event on statins (the latter with intensive therapy), although both also recorded substantial clinical benefits. [Clin Ther 2006 Jan;28(1):26-35; Clin Ther 2007 Feb;29(2):253-60]

“I think there is a lack of awareness of these problems from physicians,” added Golomb, pointing to an earlier survey of 650 patients which found that doctors were “more likely to deny than affirm a connection” in cases of adverse statin reactions. [Drug Saf 2007;30(8):669-75]

“Even for patients who met literature criteria for probable or definite causality of their problems, the physicians denied the possibility of a connection about 50 percent of the time for each of the top three best known and most reported symptoms. And when we asked who initiated the conversation it was overwhelmingly the patients, even though it should be the physician who is aware of the connection of those specific symptoms to statins,” said Golomb.

Golomb believes that the most of the problems are class effects, and largely relate to the dose and potency of the statin rather than to any particular brand. Her literature review also notes that mitochondrial mechanisms are implicated in several adverse effects and proposes that this may be a common underlying factor behind a wide range of the problems.

She added that muscle problems occurring with statins are not always associated with a rise in creatine kinase levels, and that this can sometimes cause them to be overlooked.

Other academic authors have reached different conclusions about the risk profile of statins. The most recent such review paper in The Lancet, for example, concluded that statins are “a well-tolerated and extensively studied group of drugs.” [2007; 370:1781-90]

“With a few caveats, and while awaiting good-quality randomized data for the newer drugs, statins seem to be a remarkably safe group of drugs when used at their usual doses,” wrote Dr. Jane Armitage, of the University of Oxford, UK.

Golomb added, however, that the side effects reported so far could be just “the tip of the iceberg,” cautioning that even more problems could ultimately be shown to be related to statins.

“We’ve had reports from patients who have developed accelerated hearing loss or tinnitus with onset of statins. We don’t have data to demonstrate an association but that’s one of the domains in which I predict an association will likely be found in future,” she said.

Orbit of JUPITER extends to stroke prevention

2009-05-19T04:17:00.000-07:00

Medical Tribune April 2009 P12
David Brill

The benefits of rosuvastatin for patients with elevated high sensitivity C-reactive protein (hsCRP) could include a reduction in the risk of stroke, according to new data from the JUPITER* trial.

The relative risk of any stroke was reduced by 48 percent among patients taking the drug, the study’s investigators reported recently at the International Stroke Conference in San Diego, US.

This finding appears to have been driven largely by a reduction in ischemic stroke rates – just 23 of the 8,901 patients in the treatment group experienced this outcome compared to 47 in the equally-sized placebo group (hazard ratio 0.49; P=0.004). Rates of hemorrhagic stroke, conversely, were not significantly different – six events occurred in the intervention group and nine in the placebo group (hazard ratio 0.67; P=0.44).

The new stroke data bring fresh fuel to the debate about the role of hsCRP in risk stratification and the use of statins for primary prevention – questions that have risen to prominence since the presentation of the original JUPITER study at the American Heart Association’s annual Scientific Sessions in November last year. [N Engl J Med 2008 Nov 20;359(21):2195-207]

“The bottom line is that we now have conclusive evidence for the efficacy of statins specifically for primary prevention of stroke,” said Dr. Robert Glynn of Brigham and Women’s Hospital in Boston, US, one of the JUPITER investigators who presented the latest findings.

LDL cholesterol is not typically considered as a risk factor for stroke in patients without established vascular disease, said Glynn, noting that CRP, however, has been shown to be a valid predictor of stroke risk. Statin therapy, which lowers levels of both biomarkers, could therefore be particularly beneficial for stroke prevention in patients with elevated CRP, he added.

The ARIC** study implicated hsCRP as a risk marker for stroke. The study, which involved 12,762 middle-aged men and women followed up for around 6 years, showed that those with an hsCRP level above 3 mg/L had an adjusted hazard ratio for ischemic stroke of 2.7 when compared to those with an hsCRP level below 1 mg/L. [Arch Intern Med 2005 Nov 28;165(21):2479-84]

The SPARCL*** study, meanwhile, demonstrated the benefits of atorvastatin (80 mg daily) for secondary stroke prevention in a population of 4,731 patients with a recent history of stroke or transient ischemic attack. After a median follow up of 4.9 years, overall stroke risk was reduced by 16 percent in the statin group compared to placebo (adjusted hazard ratio 0.84; P=0.03) with comparable mortality between the two groups. There was, however, an increase in the number of hemorrhagic strokes: 55 events occurred in the atorvastatin group and 33 in the placebo group. [N Engl J Med 2006 Aug 10;355(6):549-59]

The original JUPITER trial found that after a median of 1.9 years of follow up rosuvastatin (20 mg daily), as compared to placebo, reduced the relative risk of major cardiovascular events by 44 percent in a cohort of 17,802 overtly healthy subjects with baseline hsCRP levels above 2 mg/L and LDL cholesterol levels below 130 mg/dL (hazard ratio 0.56; P<0.00001). Over the course of the study hsCRP levels were reduced by 37 percent and LDL cholesterol levels by 50 percent. *JUPITER: Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin **ARIC: Atherosclerosis Risk in Communities *** SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels

Declining heart attack severity drives drop in CHD deaths

2009-04-13T04:17:00.000-07:00

Medical Tribune March 2009 P1
David Brill

A decrease in the severity of heart attacks is fuelling the decline in coronary heart disease (CHD) deaths in the US, new research suggests.

The study – an analysis of 10,285 myocardial infarction (MI) cases hospitalized over 15 years – showed significant declines across almost all indicators of severity.

This trend, which appears to be mirrored by data from some parts of Asia, was independent of either gender or ethnicity.

“This landmark study suggests that better prevention and better management in the hospital have contributed to the reduction in deaths,” said Dr. Merle Myerson, principal investigator of the Atherosclerosis Risk in Communities (ARIC) study, published in Circulation. [2009 Jan 19; Epub ahead of print]

“Better control of risk factors for heart disease, such as blood pressure and cholesterol, as well as improvements in hospital management, may lessen the severity if somebody has a heart attack,” he said.

The time between symptom onset and arrival at hospital remained constant throughout the study, period with only around a third of patients arriving at the hospital within 2 hours of an attack.

Dr. Adrian Low, a consultant at the National University Heart Centre Singapore, stressed the importance of raising public awareness in order to further improve MI outcomes.

“While this study is reassuring, it also emphasizes that we still have room for improvement. A significant percentage of patients still present late to us for treatment,” he said.

“We know that early presentation and appropriate management can result in better outcomes. This will only be achieved with enhanced public education and a better evaluation of how we can overcome our shortcomings,” he added.

The ARIC investigators reviewed MI discharge data from 1987 to 2002, taken from hospitals across four communities in North Carolina, Maryland, Mississippi and Minnesota. The analysis was limited to white and African-American patients, aged 35 to 74.

Previous studies had shown that CHD mortality in the US was dropping but that the incidence of MI remained unchanged – prompting the researchers to investigate whether declining MI severity might be the driving force behind the bigger-picture CHD effect.

In-hospital deaths from acute MI in Singapore have also dropped over a similar period, according to data from the National Heart Center, where overall inpatient mortality declined from 20.6 percent in 1988 to 14.7 percent in 2002. [Ann Acad Med Singapore 2007 Dec;36(12):974-9] A study published last year by the Singapore’s National University Hospital, meanwhile, showed that the use of evidence-based medications for MI has significantly reduced 1-year mortality in both elderly and young patients. [Am J Geriatr Cardiol 2008 Jan-Feb;17(1):21-6]

Low added that the ARIC study “reinforces our current understanding that cardiovascular risk factors, treated aggressively, can impact on subsequent development and outcome of acute MI,” but noted that there are several limitations to the research. The generalizability to other populations is not clear, nor is it known which specific measures led to the improved outcomes, he said. He also added that some of the severity indicators used by the researchers are proxies for disease severity, while more direct measures such as left ventricular ejection fraction were unavailable.

Twenty MI severity indicators were used in the ARIC study, including the proportion of cases having major ECG abnormalities. For ST-segment elevation, for example, the proportion of cases dropped by 1.9 percent per year (P = 0.002), while the percentage of cases with any major Q wave dropped by 4.5 percent per year (P<0.001).>

Greater awareness needed on childhood anxiety disorders

2009-04-13T03:59:00.005-07:00

Medical Tribune March 2009 P5
David Brill

Pediatric anxiety disorders are “under-recognized and under-treated” and could be contributing to depression, drug abuse and educational underachievement in later life, a leading US psychiatrist has warned.

As many as 20 percent of children have some sort of anxiety problem but few are likely to be receiving optimal therapy, Professor Graham Emslie wrote in a recent New England Journal of Medicine editorial. [2008 Dec 25;359(26):2835-6]

Specialists at KK Women’s and Children’s Hospital (KKH) in Singapore, where referrals for pediatric anxiety disorders are low but rising, agreed that the problem is under-recognized and called for greater awareness among medical practitioners.

Emslie, a professor of psychiatry and pediatrics at the University of Texas Southwestern Medical Center, said that children often develop avoidance or coping strategies which can mask the true extent of the problem and contribute to the diagnosis being missed. Genuine anxiety disorders may also be dismissed as “normal, developmentally appropriate worries, fears and shyness,” he said.

The success of the CAMS* study, published in the same edition of the journal, highlights that the treatment options for pediatric anxiety are now more effective than ever before, Emslie said. The researchers found that 81 percent of children showed significant improvements in their anxiety levels when cognitive behavioral therapy (CBT) was combined with the selective serotonin-reuptake inhibitor sertraline. [N Engl J Med 2008 Dec 25;359(26):2753-66]

CBT is typically employed as the first line treatment at KKH but may also be combined with medications in severe cases, according to principal psychologist Ms. Frances Yeo. The number of children with anxiety disorders seen at the hospital rose from 26 in 2007 to 48 in 2008.

Yeo noted that the under-recognition of pediatric anxiety disorders may result from children’s inability to vocalize their worries and fears, which may subsequently manifest themselves as behavioral problems and lead to the child being wrongly labeled as lazy or difficult.

“Children usually show signs of their anxiety through physical symptoms such as stomachaches, headaches, hyperventilation, heart palpitations and tightness in the chest. These symptoms are rather vague and can overlap with many other disorders which make it difficult to distinguish,” she added.

“The first step for the medical community is awareness. GPs need to be alert for children with vague physical symptoms which cannot be explained by medical illnesses,” she said.

Pediatric anxiety disorders comprise a spectrum of conditions including social phobias, separation anxiety disorder, and generalized anxiety disorder. Children who are affected at ages 14 – 16 are more likely to have poor educational, mental health and social role outcomes at ages 16 – 21, a study of 1,265 New Zealand adolescents showed. [J Am Acad Child Adolesc Psychiatry 2001 Sep;40(9):1086-93]

Emslie noted that the exposure component seems to be the most effective part of CBT for children with avoidance strategies, suggesting that they should be encouraged to tackle their phobias head on. Doctors have an important role to play in this, he said, adding that they can unwittingly “collude” with avoidance coping by writing medical notes which give anxious children an excuse to miss school.

Dr. Ng Koon Hock, visiting consultant psychiatrist to the Mental Wellness Service at KKH, said that parents may be failing to recognize anxiety disorders because they tend to downplay a child’s emotions and focus overly on their behavior as a disciplinary issue. “There is less tendency to look at things from the child’s perspective,” he said.

Ng believes that doctors are generally reluctant to liberally grant medical leave to children who regularly makes suspicious-looking health complaints, but noted that this can be a difficult balancing act.

“If the child is very stressed and wants to escape from the problem then in the long-term it’s not helpful, but sometimes it does allow them to get by in the short term,” he said.

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*CAMS: Child-Adolescent Anxiety Multimodal Study

FDA warns on skin anesthetic dangers

2009-04-13T03:59:00.004-07:00

Medical Tribune March 2009 P6
David Brill

The US FDA has issued a new public alert on skin-numbing drugs, warning of “potentially serious and life-threatening” consequences if products are misused.

Absorption of topical anesthetics from the skin to the bloodstream can cause seizures, arrhythmias, coma and even death, the organization said in a recent news release.

The warning specifically highlights creams, gels and ointments containing lidocaine, prilocaine, tetracaine and benzocaine – products which are available over the counter or by prescription in the US. These are often used in cosmetic and medical procedures, as well as for general relief of pain and itching.

Two women, aged 22 and 25, are already reported to have died in the US from using skin anesthetics prior to laser hair removal. They wrapped their legs in plastic to increase the pain-relieving effects of the creams but developed seizures and died from the toxic effects, the FDA said in a 2007 statement, which first warned about the use of these products.

Consumers should avoid heavy usage across large areas of skin, select products with the lowest possible amount of anesthetic, and avoid applying to broken or irritated skin, the latest warning advises. They are also advised to refrain from wrapping recently-treated skin in plastic or applying heating pads to the area.

Healthcare professionals, meanwhile, “should determine whether adequate pain relief can be safely achieved with a topical anesthetic, or whether a different treatment would be more appropriate,” the health advisory adds.

Dr. Melvin Ee, a consultant dermatologist at the National Skin Centre, Singapore, stressed that the adverse events highlighted by the FDA are rare but said that the warning serves as a timely reminder of the increasing use of skin numbing products in cosmetic and aesthetic procedures.

“I think the warning is important but the context must be taken into consideration,” he said.

“Topical anesthetics within the hospitals are prescribable medications and it is the onus of the prescribing doctor to adhere to safe prescribing. I personally think that if a doctor adheres to safe prescribing and according to the formulary of the medication, these are useful and safe drugs to use. The public should be made aware of the possible side effects of the medication but it must not be sensationalized.”

Ee advised physicians to consider the suitability of a patient’s age and check for allergies, potential interactions with any other medications, and a history of blood disorders or G6PD deficiency before using the products. They should also look for breaks in the skin and assess the required dosage.

Topical anesthetics reduce painful sensations by interfering with sodium and potassium currents in neuronal membranes, thereby preventing depolarization and inhibiting transmission of the signal. Excessive levels in the bloodstream can lead to systemic toxicity, the effects of which are usually manifested through the central nervous and cardiovascular systems.

Ee added, however, that this is outcome is rare and likely only to happen in the context of an overdose. The more common side effects tend to include transient local reactions at the application site, such as edema, paleness, erythema and a mild burning sensation, he said. In very rare circumstances – less than 0.1 percent of cases – application of topical anesthetics in children can result in allergic reactions leading to shock and methemoglobinemia, he added.

The FDA also expressed concerns over a recent trial which reported that lidocaine gel reduced discomfort and improved patient satisfaction when applied ahead of mammography screening. Despite these positive findings and a lack of adverse events there is potential for harm if the technique becomes used more widely, the FDA said, acknowledging the relatively small size of the 418-women study. [Radiology 2008 Sep;248(3):765-72]

Simple surgical checklist cuts deaths and complications

2009-04-13T03:59:00.003-07:00

Medical Tribune March 2009 P7
David Brill

Using a simple checklist for surgical procedures could dramatically reduce mortality and complication rates across the globe, the “unprecedented” results of a new study show.

Implementation of the WHO-developed list saw post-surgical death rates drop from 1.5 percent to 0.8 percent (P=0.003), and inpatient complications fall from 11 percent to 7 percent (P<0.001)> over 11 months.

The checklist was trialed at hospitals in eight diverse cities, ranging from London to Manila to Ifakara in Tanzania. Data were collected from 3,733 procedures conducted before implementation of the list, and 3,955 after. [N Engl J Med 2009 Jan 29;360(5):491-9]

“The concept of using a brief but comprehensive checklist is surprisingly new to us in surgery. Not everyone on the operating teams was happy to try it,” said Dr. Atul Gawande, senior author of the study. “But the results were unprecedented. And the teams became strong supporters.

“These findings have implications beyond surgery, suggesting that checklists could increase the safety and reliability of care in numerous medical fields. The checklists must be short, extremely simple, and carefully tested in the real world. But in specialties ranging from cardiac care to pediatric care, they could become as essential in daily medicine as the stethoscope,” added Gawande, an associate professor of surgery at Harvard Medical School, US, and team leader for the WHO project.

The checklist was first launched in 2008 as part of new “safe surgery” guidelines from the WHO. It comprises 19 items, and is used at three “critical junctures” in care: before anesthesia, before incision, and before the patient is taken from the operating room.

Rates of surgical site infection also dropped following implementation of the list – from 6.2 to 3.4 percent (P<0.001)> – and unplanned reoperation rates decreased from 2.4 to 1.8 percent (P=0.047).

Dr. Sophia Ang, patient safety officer and associate chairman of the medical board at National University Hospital (NUH), Singapore, said that similar checklists are already in use at NUH.

“Some of these have been in place for a long time, such as an instrument count, sponge count and needle count,” she said.

“There is no deliberate effort on our part to do this as a scientific research so we have no findings to conclusively show that the changes have brought about improved outcomes. Some of the elements were introduced in phases and over time and we are continually reviewing and improving on them to enable us to meet our patient safety needs,” she added.

Some 234 million operations are performed worldwide each year, according to Gawande and his colleagues. At least half of all complications arising from surgery are thought to be avoidable, they add.

The study, which was conducted between October 2007 and September 2008, included only patients aged over 16 who underwent noncardiac surgery. The other cities where the checklist was tested were New Delhi, India; Toronto, Canada; Amman, Jordan; Auckland, New Zealand; and Seattle, US.

Everolimus shows promise for advanced stomach cancer treatment

2009-04-13T03:59:00.002-07:00

Medical Tribune March 2009 P9
David Brill

Everolimus could provide a viable new treatment option for advanced gastric cancer, Japanese investigators said recently, following the conclusion of a phase II trial of the drug.

After 8 weeks of therapy everolimus halted tumor growth in 55 percent of patients, with 45 percent showing signs of tumor shrinkage.

A phase III trial involving some 500 patients will open for enrollment later this year, the drug’s manufacturer, Novartis, announced following the presentation of the new data at an American Society of Clinical Oncology symposium in January.

The multicenter, open-label study involved 54 Japanese patients of Asian descent who had previously undergone heavy treatment with chemotherapy.

"There are very limited treatment options for patients who progressed despite the standard treatment for this aggressive cancer," said lead researcher Dr. Atsushi Ohtsu, director of the Research Center for Innovative Oncology at the National Cancer Center Hospital East, Chiba, Japan. "The results from this study demonstrate that [everolimus] has the potential to provide an effective new option for these patients."

Patients in the study took 10 mg oral everolimus daily for an average of 57 days. The overall rate of adverse events – including anorexia, vomiting and stomatitis – was around 10 percent, with serious adverse events occurring in some 3 percent.

The median progression-free survival with everolimus was 83 days. At 4 months, around 30 percent of patients were still progression-free.

Everolimus inhibits the mammalian target of rapamycin (mTOR) – a cell signaling protein which is implicated in the development of several cancers. The drug has already shown promise for advanced renal cancer carcinoma and is currently under regulatory review in Europe and the US for this indication. A phase III randomized controlled trial, published last year, found that the drug prolonged progression-free survival by a median of 2.1 months over placebo in patients with metastatic renal cell carcinoma. [Lancet 2008 Aug 9;372(9637):449-56]

Gastric cancer is the most common type of cancer in East Asia, accounting for 18.9 percent of new cases in 2007, according to data from the American Cancer Society. Globally, it is the second leading cancer and is responsible for some 866,000 deaths worldwide each year, according to the WHO.

The risk of gastric cancer is thought to be increased by eating a diet high in salted, pickled and smoked foods, and by long-term infection with Helicobacter pylori. Male gender, smoking and age above 50 are also important risk factors.

Preventive antibiotics cut ICU death rates

2009-04-13T03:59:00.001-07:00

Medical Tribune March 2009 P10
David Brill

Adopting a widespread preemptive approach with antibiotics could save lives in the Intensive Care Unit (ICU), Dutch researchers have recently reported.

Absolute mortality at 28 days was reduced by 3.5 percent in patients who received intravenous cefotaxime along with a cocktail of antibiotics applied topically to the stomach and orophyarynx. A simpler regimen – applying antibiotics only to the oropharynx – reduced mortality by 2.9 percent, as compared with standard care.

The findings are likely to prove contentious in the era of rising antibiotic resistance rates and hospital-associated infections. A Singapore infectious disease expert, who recently called for tighter regulation of the nation’s antibiotic usage, said that a similar approach could be adopted here but expressed his concern that resistance levels would increase in the long term.

The study, conducted across 13 ICUs in the Netherlands, randomized 5,939 patients to standard care or one of the two antibiotic regimens. Patients were only eligible if they were expected to be intubated for more than 48 hours or to remain in the ICU for more than 72 hours. [N Engl J Med 2009 Jan 1;360(1):20-31]

Lead researcher Dr. Anne Marie de Smet, of the University Medical Center Utrecht, said that the trial demonstrates that the benefits of preventive antibiotics outweigh the disadvantages.

“There are very few interventions in the ICU which can lower mortality on their own. These are not patients who come in for surgery and leave the next day – these people are really ill,” she said.

Antibiotic resistance rates did not rise significantly over the course of the 6-month study but longer follow-up data are needed, said de Smet. She added that The Netherlands has unusually low rates of resistance due to its strict regulations on antibiotic usage.

Dr. Hsu Li Yang, an infectious disease consultant at National University Hospital, Singapore, said that he would be “very concerned that resistance rates would increase” were the strategy to be adopted here, but added that is “for society as a whole to decide” whether such a move would be beneficial given the obvious short-term advantages.

“Doctors should not ‘allow’ patients to die so that future patients may be better or more easily treated. What we try to do is to retard the rise of resistance while preventing any increased mortality that may arise from inadequate use of antibiotics … minimize the use of antibiotics for those who do not need them and prescribe appropriate but not excessive antibiotics for those patients who do,” he said.

“Similar strategies might be adopted [here] in the future following the results of this study,” said Hsu, adding that the trial was very well conducted and one of the few in this field with adequate statistical power to demonstrate a significant mortality reduction.

The researchers used an antibiotic paste containing colistin, tobramycin and amphotericin B for both strategies. In the more comprehensive approach – selective digestive tract decontamination – the paste was applied topically to the stomach and oropharynx, and intravenous cefotaxime was given for the first 4 days. In the simpler strategy – selective orophyarygeal decontamination – the paste was just applied to the oropharynx.

Hsu added that that a different combination of antimicrobial agents would probably be necessary were the approach to be adopted in Singapore hospitals, where resistance rates are considerably higher than in the Netherlands.

Hsu recently co-authored a position paper calling for more data to be gathered on the use of antibiotics in Singapore and for the Ministry of Health to take a greater role in regulating usage. [Singapore Med J 2008 Oct;49(10):749-55]