Uma nova perspectiva para a prevenção cardiovascular

No The Lancet, o cálculo da estratégia da polipílula para prevenção primária e secundária da doença cardiovascular. A proposta é administrar aspirina+estatina+hidroclorotiazida+enalapril a indivíduos com risco elevado de doença cardiovascular. Para aqueles que já sofreram infarto do miocárdio se acrescentaria o atenolol. O estudo apresentado é um simulação para países de baixa e e média renda, mas poderá ser também um bom exercício para uma política ampla de prevenção cardiovascular. Infelizmente, o texto no The Lancet é somente para assinantes. Prevention of cardiovascular disease in high-risk individuals in low-income and middle-income countries: health effects and costs Stephen S Lim, Thomas A Gaziano, Emmanuela Gakidou, K Srinath Reddy, Farshad Farzadfar, Rafael Lozano, Anthony Rodgers In 2005, a global goal of reducing chronic disease death rates by an additional 2% per year was established. Scaling up coverage of evidence-based interventions to prevent cardiovascular disease in high-risk individuals in low-income and middle-income countries could play a major part in reaching this goal. We aimed to estimate the number of deaths that could be averted and the fi nancial cost of scaling up, above current coverage levels, a multidrug regimen for prevention of cardiovascular disease (a statin, aspirin, and two blood-pressure-lowering medicines) in 23 such countries. Identifi cation of individuals was limited to those already accessing health services, and treatment eligibility was based on the presence of existing cardiovascular disease or absolute risk of cardiovascular disease by use of easily measurable risk factors. Over a 10-year period, scaling up this multidrug regimen could avert 17·9 million deaths from cardiovascular disease (95% uncertainty interval 7·4 million–25·7 million). 56% of deaths averted would be in those younger than 70 years, with more deaths averted in women than in men owing to larger absolute numbers of women at older ages. The 10-year financial cost would be US$47 billion ($33 billion–$61 billion) or an average yearly cost per head of $1·08 ($0·75–1·40), ranging from $0·43 to $0·90 across low-income countries and from $0·54 to $2·93 across middle-income countries. This package could effectively meet three-quarters of the proposed global goal with a moderate increase in health expenditure.

Quase tudo sobre tuberculose no Brasil

A Revista de Saúde Pública lançou edição especial sobre a tuberculose no Brasil. Com acesso livre (clique aqui) há quase tudo que “você-gostaria-de-saber-sobre-tuberculose-no-Brasil-mas-tem-vergonha-em-perguntar”. Abaixo, a apresentação dessa edição com o panorama histórico. A tuberculose (TB) afeta a humanidade há pelo menos cerca de 8.000 anos. Até a metade do século XIX o caráter infecto-contagioso da tuberculose não era reconhecido; a doença era atribuída a diversas causas como a hereditariedade, aos miasmas e a outros determinantes ambientais e sociais. Em 1882, Robert Koch identificou a Micobacteria tuberculosis, definindo assim a TB como uma doença infecciosa. Isto permitiu que a florescente pesquisa biomédica iniciasse a busca por vacinas e tratamentos medicamentosos. A vacina BCG foi, em 1921, usada pela primeira vez em humanos. Anos mais tarde, em 1944, a estreptomicina foi utilizada com sucesso no tratamento da TB, sendo o primeiro de uma série de medicamentos utilizados na terapêutica anti-TB. Essas descobertas trouxeram renovadas possibilidades para prevenção e tratamento da TB. Porém, não se deve esquecer que a mortalidade por esta doença na Europa no século XIX era mais alta do que é hoje na África. Entretanto, naquele continente, a mortalidade começou a declinar de maneira vertiginosa já no final do século XIX, portanto muitas décadas antes da existência dos modernos recursos preventivos e terapêuticos, possivelmente, em razão das mudanças ocorridas nas condições de vida da sua população. Na atualidade, nos países mais desenvolvidos a tuberculose continua sendo um problema quase restrito aos imigrantes dos países pobres e outras populações marginalizadas (desabrigados, alcoólatras, prisioneiros, e outros).

Big Pharma ameaçada pelos genéricos

The Wall Street Journal apresenta hoje uma reportagem bem objetiva, acompanhada de quadro mostrando que todos os grandes produtos da Big Pharma em cinco anos poderão ser vendidos como genéricos. Entende-se a nova linha de "pesquisa-marketing" de remédios combinados, p.ex. hipertensão e dislipidemia, como um jeito de aumentar o período de patente.

Big Pharma Faces Grim Prognosis Industry Fails to FindNew Drugs to ReplaceWonders Like Lipitor By BARBARA MARTINEZ and JACOB GOLDSTEIN

December 6, 2007; Over the next few years, the pharmaceutical business will hit a wall. Some of the top-selling drugs in industry history will become history as patent protections expire, allowing generics to rush in at much-lower prices. Generic competition is expected to wipe $67 billion from top companies' annual U.S. sales between 2007 and 2012 as more than three dozen drugs lose patent protection. That is roughly half of the companies' combined 2007 U.S. sales. At the same time, the industry's science engine has stalled. The century-old approach of finding chemicals to treat diseases is producing fewer and fewer drugs. Especially lacking are new blockbusters to replace old ones like Lipitor, Plavix and Zyprexa. The coming sales decline may signal the end of a once-revered way of doing business. "I think the industry is doomed if we don't change," says Sidney Taurel, chairman of Eli Lilly & Co. Just yesterday, Bristol-Myers Squibb Co. announced plans to cut 10% of its work force, or about 4,300 jobs, and close or sell about half of its 27 manufacturing plants by 2010. Between 2011 and 2012, annual industry revenue will decline, estimates Datamonitor, a research and consulting firm. That would be the first decline in at least four decades. Patent expirations are a big problem. Drugs are granted 20 years of patent protection, although companies often fail to get a product to market before half of that period has elapsed. Once it hits the market, however, the patent-protected drug is highly profitable: Typical gross margins are 90% to 95%. When patents expire, generic makers offer the products at a price much closer to the cost of production. Pfizer Inc. will be particularly hard-hit when the patent expires as early as 2010 on Lipitor, the cholesterol-lowering blockbuster that ranks as the most successful drug ever. Pharmacists and managed-care companies will aggressively fill prescriptions with generics, reducing annual Lipitor sales to a fraction of last year's $13 billion.

Como é difícil aceitar que a poção mágica não é mágica

Somente nosso pensamento é mágico. A natureza segue seu rumo, com lógicas próprias que deixo para Edward Wilson, Stephen Jay Gould, Richard Dawkins e outros discutirem. Destaco hoje, pesquisa publicada em JAMA que avalia informações oriundas de estudos observacionais: vitamina E e doença cardiovascular, beta-caroteno e câncer e estrógeno e doença de Alzheimer. Todas essas associações não se comprovaram em ensaios clínicos, porém a maioria dos artigos abordando o tema, ainda consideram que vitamina E, beta-caroteno e estrógeno têm utilidade na prevenção da doença cardiovascular, do câncer e da demência, respectivamente. Persistence of Contradicted Claims in the Literature Athina Tatsioni, MD; Nikolaos G. Bonitsis, MD; John P. A. Ioannidis, MD JAMA. 2007;298(21):2517-2526. Context Some research findings based on observational epidemiology are contradicted by randomized trials, but may nevertheless still be supported in some scientific circles. Objectives To evaluate the change over time in the content of citations for 2 highly cited epidemiological studies that proposed major cardiovascular benefits associated with vitamin E in 1993; and to understand how these benefits continued being defended in the literature, despite strong contradicting evidence from large randomized clinical trials (RCTs). To examine the generalizability of these findings, we also examined the extent of persistence of supporting citations for the highly cited and contradicted protective effects of beta-carotene on cancer and of estrogen on Alzheimer disease. Data Sources For vitamin E, we sampled articles published in 1997, 2001, and 2005 (before, early, and late after publication of refuting evidence) that referenced the highly cited epidemiological studies and separately sampled articles published in 2005 and referencing the major contradicting RCT (HOPE trial). We also sampled articles published in 2006 that referenced highly cited articles proposing benefits associated with beta-carotene for cancer (published in 1981 and contradicted long ago by RCTs in 1994-1996) and estrogen for Alzheimer disease (published in 1996 and contradicted recently by RCTs in 2004). Data Extraction The stance of the citing articles was rated as favorable, equivocal, and unfavorable to the intervention. We also recorded the range of counterarguments raised to defend effectiveness against contradicting evidence. Results For the 2 vitamin E epidemiological studies, even in 2005, 50% of citing articles remained favorable. A favorable stance was independently less likely in more recent articles, specifically in articles that also cited the HOPE trial (odds ratio for 2001, 0.05 [95% confidence interval, 0.01-0.19; P < .001] and the odds ratio for 2005, 0.06 [95% confidence interval, 0.02-0.24; P < .001], as compared with 1997), and in general/internal medicine vs specialty journals. Among articles citing the HOPE trial in 2005, 41.4% were unfavorable. In 2006, 62.5% of articles referencing the highly cited article that had proposed beta-carotene and 61.7% of those referencing the highly cited article on estrogen effectiveness were still favorable; 100% and 96%, respectively, of the citations appeared in specialty journals; and citations were significantly less favorable (P = .001 and P = .009, respectively) when the major contradicting trials were also mentioned. Counterarguments defending vitamin E or estrogen included diverse selection and information biases and genuine differences across studies in participants, interventions, cointerventions, and outcomes. Favorable citations to beta-carotene, long after evidence contradicted its effectiveness, did not consider the contradicting evidence. Conclusion Claims from highly cited observational studies persist and continue to be supported in the medical literature despite strong contradictory evidence from randomized trials.

Avandia: agora osteoporose

Quando uma empresa força demais a indicação de um medicamento, ocorre uma reação inversa, que muitas vezes é desproporcional ao potencial dano do medicamento. Um exemplo é o relatado abaixo pela Associated Press e, repetido em todos os jornais do planeta. Apesar, da empresa reconhecer a possibilidade de aumento de fraturas, o objeto de discussão - osteoporose - não é objeto de preocupação em termos clínicos. Primeiro, os dados foram obtidos em animais. Segundo, o risco cardíaco é mais importante do que o aumento de risco de osteoporose. Por último, notem que o pesquisador que identificou o mecanismo em ratos de forma súbita já indica ações médicas a longo prazo.

Popular Diabetes Drug May Increase Osteoporosis Associated PressDecember 2, 2007 1:29 p.m. WASHINGTON -- The popular diabetes drug marketed as Avandia may increase bone thinning, a discovery that could help explain why diabetics can have an increased risk of fractures. New research raises the possibility that long-term treatment with rosiglitazone, as Avandia is also called, could lead to osteoporosis. The diabetes drug is used to improved response to insulin. While bones seem solid, they constantly are being broken down and rebuilt by the body. Researchers found that in mice, the drug increased the activity of the cells that degrade bones, according to a report in this week's online issue of Nature Medicine. Avandia recently was labeled with warnings about the risk of heart failure in some patients. GlaxoSmithKline, which markets the drug, already has acknowledged that a study found a higher risk of fractures among women who take the drug. But this report is the first to attempt to explain the link between the drug and fractures. The finding "has led to a better understanding of the challenges associated with long-term treatment of patients with Type II diabetes," said Ronald M. Evans of the Salk Institute for Biological Studies in La Jolla, Calif., lead author of the report. "It also provides a basis for the development of a "next generation" of drug that can specifically dial out this side effect and a new insight into a previously unrecognized aspect of bone physiology that has important medical consequences," he said in an interview via e-mail. Nearly 21 million people in the United States have diabetes. Rosiglitazone is widely used in people with Type II, or adult onset diabetes, the most common form of the disease. Evans said the discovery was fortuitous. Researchers were looking at different aspects of the diabetic mice and did not realize they would be able to change the bone-removing activity. The assumption had been that more brittle bones in diabetics were the result of a reduced bone-building activity, not increased bone removal. "Considering the widespread use of these drugs and the known action in people it is surprising that such a key observation had been missed," he said. "The long-term use of rosiglitazone should be cautious in patients with higher risk of fractures such as older women," he added. Using it in combination with anti-osteoporosis drugs could be beneficial, he said. The research was funded by the Howard Hughes Medical Institute and the National Institutes of Health.

Vacinação para gripe e redução das desigualdades: pesquisa da USP no IJE

Professores da USP publicam no International Journal of Epidemiology pesquisa mostrando o impacto da vacinação para gripe na cidade de São Paulo. Mais um dado que vai contra os famosos detratores do SUS, aqueles da "falência da saúde pública", "má utilização de recursos" etc etc

Effectiveness of influenza vaccination and its impact on health inequalities de José Leopoldo F. Antunes, Eliseu A. Waldman, Carme Borrell and Terezinha M. Paiva. O artigo completo pode ser solicitado a leopoldo@usp.br , o resumo é apresentado abaixo.

Background Since 1998, annual publicly funded campaigns for mass vaccination against influenza of the population aged 65 years or older have been performed in the city of São Paulo, Brazil. The effectiveness of the intervention was not assessed for its contribution to the reduction of influenza-attributable mortality. This study sought to compare the age-specific mortality (65 years or older) before and after the onset of yearly vaccination, and to assess the impact of the intervention on health inequalities in relation to inner-city areas. Methods Official information on deaths and population allowed assessment of overall pneumonia and influenza mortality. Monitoring of outbreaks and the estimation of mortality attributable to influenza peaks used Serfling and ARIMA models. Rates were compared between 1998 and 2002, when vaccination coverage ranked higher than 60% among individuals aged 65 years or older, and 1993–97 (prior to vaccination). Results Overall mortality due to pneumonia and influenza fell by 26.3% after vaccination. An even higher reduction was observed for mortality specifically attributable to influenza epidemics; the number of peaks of influenza mortality also decreased. Deprived areas of the city had a higher decrease of mortality by pneumonia and influenza during the vaccination period. Conclusions Influenza vaccination contributed to reduce influenza-attributable mortality in this age group, and was associated with the reduction of inequalities in the burden of the disease among social groups. The concurrent promotion of health and social justice is feasible when there is political will and commitment to implement public health interventions with prompt and effective universal access.

Os precursores da epidemiologia moderna

Abaixo, os comentários de MichaelMarmot publicados no The Lancet sobre o livro mostrado ao lado.

When I joined Epidemiology at the London School of Hygiene and Tropical Medicine, in 1976, I was told: this School is run by upper-class Englishmen and lower-class Scotsmen—my informant was a Scotsman. He went on: it reflected the old Colonial Medical Service; the Englishmen went to the tropics to run the empire, and the Scots to escape their lousy weather. In the USA, I had been told, it was surprising how many of the older generation of epidemiologists had a father who was a preacher, or were of Jewish background. It reflected their social concern. Of course, the London School has Hygiene as well as Tropical Medicine in its title and there were motivations, other than noblesse oblige or the weather, that brought people into epidemiology. One of the attractions of The Development of Modern Epidemiology is the insight it gives into these motivations. It brings together contributions from many who have been centrally involved in the International Epidemiology Association (IEA) during the 50 years of its existence. So many of the key figures came to epidemiology because they wanted to improve health in society. John Pemberton, the co-founder of the IEA, was a member of the Socialist Medical Association that was started in 1930. Many of their members believed that poverty was an important cause of ill-health and that some solutions to health problems required political action. In the same vein, Mervyn Susser was aroused to hope and commitment to a socially useful occupation. He, and Zena Stein, saw the practice of socially oriented medicine as an important form of activism. As always, such commitment does not arise, prosper, or otherwise in a vacuum. The pioneers of this approach in South Africa, among them Sydney Kark, as well as Susser and Stein, had to leave because they fell foul of the political regime promoting apartheid. Jerry Morris, in the UK, stated it clearly: “Society largely determines health; ill-health is not a personal misfortune due often to personal inadequacy but a social misfortune due, more commonly, to social mismanagement and social failure.” The commitment to improving health for the whole of society runs through many of the contributions in this volume. Ian Prior's great grandfather was a missionary in Fiji whose public-health contribution was to convince his parishioners to give up cannibalism. Henry Blackburn, the master of the ECG in epidemiology, was influenced by experiences in Cuba, in 1949, that taught him of the limitations of medicine to deal with mass disease due mainly to poverty and ignorance. Lester Breslow, slightly coy, says that friendly advice was that “with my ideology, I consider public health”. Public Health is grateful that he heeded this advice. I am in awe of these pioneers. Today, rightly, we expect our students to do Master's degrees and PhDs, to get accredited, pass exams. That is as it should be. But it does not stop me worshipping at the shrine of these founders of our discipline who had none of these qualifications. It may be social concern that motivated these pioneers of epidemiology, but they brought methodological rigour to their enquiries and they had to make it up as they went along. Richard Doll, in a characteristically pithy piece, does not suggest that he chose to go into “epidemiology” as such. Rather, he used his mathematical bent to help a distinguished clinician, Avery Jones, to investigate variations in the occurrence of peptic ulcer. A short course in medical statistics with Bradford Hill (what, no PhD!) and he was put to work to figure out why lung cancer was on the rise. He reports that there were a few early case-control studies of cancer that had come in for methodological criticism. Doll and Hill, therefore, designed their case-control study of lung cancer and smoking to be better. They published in 1950, concluding, with no messy understatement or qualification: “that cigarette smoking is an important cause of cancer of the lung”. The pioneers developed their investigations with rigour and, in part because of shortage of funds, with precision. Archie Cochrane is justly famous for effectiveness and efficiency and has been immortalised in the Cochrane collaboration. He also did so much to develop observational epidemiology. Nearly 30 years ago I made a pilgrimage to south Wales to see Archie at work, then in his 80s. He drove me in his little car out into the Rhondda where he was still following a cohort of miners. We called on a miner's cottage and a woman took a death certificate off the mantelpiece with the words that her husband had died 3 years previously and she kept the certificate because she knew that Professor Cochrane would call. We then drove back to Cardiff. “That's it”, I asked, “just the death certificate, no questionnaire to the widow?” “What would you want to ask?”, said Archie, “I got all the information I needed.” Archie Cochrane's personal contribution sums up another theme running through the volume: the different uses of epidemiology, to borrow Jerry Morris' 1957 phrase. Breslow and Detels are clear: epidemiology is the basic science of public health. Richard Heller and Kerr White are equally clear: epidemiology can be used to improve clinical practice and the evaluation and, hence, operation of health services. When we discover that some non-infectious diseases are infectious in origin it makes clear that there should not be two epidemiologies—infectious and non-infectious. There is surprisingly little whingeing in this volume. There is the occasional allusion to sneering reactions from the medical establishment to the pursuit of epidemiology. These pioneers cannot have had it easy, yet they focus on getting the job done rather than dwelling on their critics. Richard Doll says simply: “epidemiology has contributed more than any other branch of science to our knowledge of the causes of cancer”. There is some allusion to the political nature of a concern with the health of populations. Adapting this to contemporary debates, a critic, exercising his prejudices, might read the accounts by John Pemberton and others of their social concerns and see not a group motivated by the highest ideals but a bunch of do-gooders who are out to provide ammunition to the nanny state to control people's lives. Rodolfo Saracci puts this another way. In a thoughtful chapter he suggests that, in the period 1945–75, the rise in epidemiology reflected the impulse of postwar reconstruction and a sense of social solidarity. Accepting health as the right of everybody meant that epidemiology with its focus on whole populations had a ready political acceptance and results had some chance of influencing policy. At the start of the millennium, says Saracci, a neoliberal climate will pay more attention to economics than to a political desire to improve the lot of all sectors of society. Saracci's implications are plain: we need high-quality epidemiological research and we need the political commitment to implement findings to improve population health. In: Walter W Holland, Jørn Olsen and Charles du V Florey, Editors, The Development of Modern Epidemiology: Personal Reports From Those Who Were There, Oxford University Press (2007) ISBN 0-19856-954-8 Pp 472. US$110·00