sábado, 24 de maio de 2008

Uma "doença" que se esvai....a síndrome metabólica

In today's Lancet, Naveed Sattar and co-workers put yet another nail in the coffin of the metabolic syndrome. (VER POST ANTERIOR) Their analysis of longitudinal data from two independent population-based cohorts, which document the incidence of cardiovascular events or diabetes in elderly patients, shows that a fasting plasma glucose test is as good as or potentially better than a diagnosis of the metabolic syndrome for predicting diabetes. They also show that a diagnosis of the metabolic syndrome has negligible association with risk of cardiovascular disease; and that the whole is not greater than the sum of the parts. Thus diagnosis of the metabolic syndrome has no apparent clinical value. In the joint statement from the American Diabetes Association and the European Association for the Study of Diabetes on the metabolic syndrome, eight major concerns were identified. Since then, other commentaries support the concept of the metabolic syndrome or, conversely, provide additional perspectives that concerns raised in the statement were justified.Panel. Summary of concerns about the metabolic syndrome2 • Criteria are ambiguous or incomplete; rationale for thresholds is ill-defined • Value of including diabetes in definition is questionable • Insulin resistance as unifying cause is uncertain • No clear basis for including or excluding other cardiovascular risk factors • Cardiovascular risk value is variable and dependent on specific risk factors present • Cardiovascular risk associated with the syndrome seems to be no greater than sum of its parts • Treatment of syndrome is no different from treatment for each of its components • Medical value of diagnosing the syndrome is unclear
Importantly, critics of the metabolic syndrome do not question or doubt the evidence that many risk factors of cardiovascular disease are found more often in combination than chance would dictate. Thus identification of one risk factor for cardiovascular disease in a patient should prompt the search for others—even those not in the syndrome's construct. Moreover, there is no argument that results from many studies show that metabolic syndrome factors by themselves, or in any combination, portend cardiovascular disease and many other adverse outcomes. It is well known that elevated blood glucose, obesity, increased blood pressure, or dyslipidaemia are serious. Substantial evidence also shows that insulin resistance plays an important part in risk-factor clustering, and probably contributes in some way to many of the untoward outcomes attributed to the metabolic syndrome. Indeed, nearly everyone agrees that lifestyle modification is a helpful intervention for those who have one or any combination of the syndrome's components and other risk factors for cardiovascular disease or diabetes (eg, raised LDL cholesterol, smoking). On the other hand, sceptics of the usefulness of the metabolic syndrome's construct would like evidence that diagnosis of an individual with the syndrome somehow focuses attention on the need for lifestyle therapy that would otherwise be ignored or missed. They would also like evidence that such a diagnosis informs clinicians that cardiovascular disease is a multiple risk-factor model of a form they would otherwise not know, or that the diagnosis conveys the seriousness of obesity in a way not currently appreciated. They would also like evidence that the diagnosis inspires patients to take action and be more adherent to therapy than if they were diagnosed with one or more risk factors, but not the metabolic syndrome. And that the diagnosis results in a treatment that would otherwise not be recommended for modifiable risk factors, and that the construct is a valuable risk-assessment method to identify patients at increased risk of cardiovascular disease or diabetes. More than a decade since its formal introduction and thousands of papers later, these six propositions—promulgated by the proponents of the syndrome—remain no more than intriguing thoughts. However, the last argument—ie, metabolic syndrome is valuable for risk assessment and therefore its identification will improve patients' outcomes—is often considered as the syndrome's greatest strength. That people with metabolic syndrome are at increased risk of cardiovascular disease events or diabetes does not mean that the construct is useful for risk prediction in itself or compared with other approaches. First, as reviewed by Pepe and colleagues, odds ratios or relative risks regarded as giving strong associations in observational studies (eg, odds ratios of 1·2–2·5) are inadequate to distinguish between people who do (will) or do not (will not) have the outcome of interest. Much stronger associations are needed (eg, ≥4·0). Second, many reports compare metabolic syndrome with much simpler risk-assessment tests for cardiovascular disease, and those risk-assessment tests are significantly better. and Additionally, a simple fasting plasma glucose measurement is a much better predictor of future diabetes than the expense and inconvenience necessary to diagnose the syndrome.] What seems to make most sense is for clinicians to focus on global risk assessment that takes into account all the well-established cardiometabolic risk factors (and then to treat each abnormality appropriately. Also, more research is needed to understand the cause of risk-factor clustering and the pathogenesis of insulin resistance. Both actions would better serve the health of those at risk of diabetes and cardiovascular disease than seeking a diagnosis of the metabolic syndrome.

sexta-feira, 23 de maio de 2008

Diabetes e Sindrome Metabólica

Na edição do The Lancet dessa semana, http://www.thelancet.com para quem se inscrever e, com acesso livre para assinantes do Science Direct vários artigos de folego sobre diabetes e a tal da síndrome metabólica.Vale o passeio nesse final de feriado.
Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies Background: Clinical use of criteria for metabolic syndrome to simultaneously predict risk of cardiovascular disease and diabetes remains uncertain. We investigated to what extent metabolic syndrome and its individual components were related to risk for these two diseases in elderly populations. Methods We related metabolic syndrome (defined on the basis of criteria from the Third Report of the National Cholesterol Education Program) and its five individual components to the risk of events of incident cardiovascular disease and type 2 diabetes in 4812 non-diabetic individuals aged 70–82 years from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). We corroborated these data in a second prospective study (the British Regional Heart Study [BRHS]) of 2737 non-diabetic men aged 60–79 years. Findings :In PROSPER, 772 cases of incident cardiovascular disease and 287 of diabetes occurred over 3·2 years. Metabolic syndrome was not associated with increased risk of cardiovascular disease in those without baseline disease (hazard ratio 1·07 [95% CI 0·86–1·32]) but was associated with increased risk of diabetes (4·41 [3·33–5·84]) as was each of its components, particularly fasting glucose (18·4 [13·9–24·5]). Results were similar in participants with existing cardiovascular disease. In BRHS, 440 cases of incident cardiovascular disease and 105 of diabetes occurred over 7 years. Metabolic syndrome was modestly associated with incident cardiovascular disease (relative risk 1·27 [1·04–1·56]) despite strong association with diabetes (7·47 [4·90–11·46]). In both studies, body-mass index or waist circumference, triglyceride, and glucose cutoff points were not associated with risk of cardiovascular disease, but all five components were associated with risk of new-onset diabetes. Interpretation: Metabolic syndrome and its components are associated with type 2 diabetes but have weak or no association with vascular risk in elderly populations, suggesting that attempts to define criteria that simultaneously predict risk for both cardiovascular disease and diabetes are unhelpful. Clinical focus should remain on establishing optimum risk algorithms for each disease

segunda-feira, 19 de maio de 2008

Doenças negligenciadas: Big Pharma não se dá tão mal quanto seus defensores brasileiros alegam

Em tradução livre: pântano ou mina de ouro? Aquilo que seria custoso e sem sentido para os interesses da Big Pharma pode ser uma fonte rentável: o mercado de países como Brasil, China e Índia, por exemplo, mesmo com quebra de patentes. Pela importância, reproduzo na íntegra o texto do The Economist.
PS: destaco a volta do senhor Yamada, agora na Gates Foundation, já motivo de comentários nesse blogue.
Quagmire to goldmine? May 15th 2008 NEW YORK From The Economist print edition The rapid growth in developing countries prompts a rethink by drugs companies Illustration by David Simonds BRAZIL has long been a thorn in the side of the global drugs companies. The country's vibrant generics industry has often trampled over their patents. As recently as last year, its government threatened to invoke compulsory licensing (a legal mechanism that, in effect, legitimises such trampling) to browbeat a foreign drugs firm into offering huge discounts. And Brazil's state-funded researchers have devised some impressive drugs, including a new therapy for malaria (see article). Small wonder, then, that big drugs firms have remained leery of this market. Indeed, they have been cautious about developing countries in general, which they have regarded as the source of many headaches and few profits. A decade ago Britain's GlaxoSmithKline (GSK) got a bloody nose in South Africa when it tried too vigorously to defend patents on an HIV drug. More recently Novartis, a Swiss firm, lost a bitter battle in India over patent protection for Gleevec, a profitable cancer drug. In Thailand the government has invoked compulsory licensing for some drugs. And next week the industry can expect another drubbing over patents harming “innovation for the poor” at the World Health Organisation's annual assembly. But consider the story of Moksha8, a new drugs firm launched last month with money from Texas Pacific Group, a private-equity outfit. It aims to capitalise on Big Pharma's neglect of many emerging economies by striking licensing deals for branded drugs which it, in turn, intends to market to affluent customers in those countries. It already has some two dozen drugs under licence for Brazil from Roche and Pfizer. Fernando Reinach of Votorantim, a Brazilian firm that also invested in Moksha8, expects its annual sales to top $1 billion within a year or two. All of which suggests that the situation is ripe for change. For much of its history, the industry has focused chiefly on the diseases that afflict people in rich countries, while largely neglecting research into diseases of the poor. But as growth slows in developed markets, and the twin threats of generic drugs and price controls advance even in pharma-friendly America, drugs companies are thinking again. That is not simply because governments in developing countries are wielding the big stick of busting patents: their expanding middle classes also provide a tantalising carrot. McKinsey, a consultancy, estimates that the value of the Indian drugs market will grow from $6.3 billion in 2005 to $20 billion in 2015. China's market is expected to soar even more spectacularly. Given such prospects for growth, says Mark Feinburg of Merck, an American drugs giant, “you've got to be in these markets—it's a great opportunity.” G.V. Prasad, vice-chairman of Dr Reddy's, a successful Indian drugs firm that is evolving from copycat to innovator, is convinced that the thinking at Western firms is changing, and cites a recent reorganisation at GSK as evidence. Andrew Witty, who takes over as the firm's chief executive on May 22nd, wants to combine all its little divisions that deal with developing countries into one emerging-markets group, to be run by Abbas Hussain, whom he has just poached from Eli Lilly, a rival American firm. Serving these markets will mean building up local expertise and research efforts. Where drugs firms have set up shop in developing markets, it has generally been to cut costs, rather than to cater to the needs of locals. But that is changing. Novartis has opened a research centre in Shanghai and has another outpost in Singapore focused on tropical diseases. Merck has struck several deals with firms in emerging markets to do early-stage research. The drugs giants argue that this new approach allows them to tap a global network of innovation, and also provides insights into local markets. Paul Herrling of Novartis points out that virally induced cancers are rare in Europe but common in China. Terry Hisey of Deloitte, a consultancy, notes that Asians and Europeans can respond differently to anaesthesia. “We see China and India as research-and-development partners, and partnerships can help us learn how to do business there,” says Robert Court of GSK. New thinking is also needed when deciding how to sell drugs in developing countries. In the past Western firms either ignored such countries or saw them as charity cases. But now, says Tachi Yamada of the Gates Foundation, who was at GSK when the firm faced the South African backlash over HIV drugs, “pharma companies can't possibly survive without recognising their responsibilities to the poor.” Some firms have adopted “differential pricing” schemes that use formulas, based on average income per head, to set lower prices in poor countries. Merck, for example, recently launched Januvia, a blockbuster diabetes drug, in India for a fraction of the price it charges in America. But in future, says Prashant Yadav of the Massachusetts Institute of Technology, firms must “price differentially not between OECD and developing-country markets, but within each developing-country market.” In other words, middle-class Indian patients will pay more than the rural poor. Both Novartis and GSK say they are thinking along these lines. But is there not a danger that cheap drugs intended for the poorest will be pilfered and sold at a profit to the urban middle classes, or shipped overseas to rich countries? This has been the standard argument against differential pricing from the drugs companies. Once again attitudes are shifting. Some diversion will happen, but firms that have tried tiered pricing have found ways to reduce it. Just changing the colour of a pill can help. So too can after-market checks on distributors and pharmacists by drugs companies: those selling looted products may be cut off from future distribution. Nan Wang of Sinovac Biotech, a Chinese vaccine firm, says her company has long sold the same vaccine at lower prices in poor parts of China than in rich cities; the two versions have different packaging. But not everyone is convinced. “In the absence of competition, differential pricing is a hoax,” scoffs Yusuf Hamied, chairman of Cipla, an Indian generics firm. In his view, only generics-makers like his firm provide genuine competition to Big Pharma, which he insists should have no patent rights in poor countries. Even if the drugs giants really have changed their approach to the developing world, the arguments over their rights and responsibilities will continue to rage.