Stroke prevention under-used in the elderly

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

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

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

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?

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

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

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.