sábado, 23 de agosto de 2008

Adiposidade e risco cardiovascular: razão cintura/altura

J Am Coll Cardiol. 2008 Aug 19;52(8):605-15.
Measures of obesity and cardiovascular risk among men and women.
Gelber RP, Gaziano JM, Orav EJ, Manson JE, Buring JE, Kurth T.
OBJECTIVES: This study examined associations between anthropometric measures (body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio [WHtR]) and risk of incident cardiovascular disease (CVD) (including nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death). BACKGROUND: Controversy exists regarding the optimal approach to measure adiposity, and the utility of body mass index has been questioned. METHODS: Participants included 16,332 men in the Physicians' Health Study (mean age 61 years in 1991) and 32,700 women in the Women's Health Study (mean age 61 years in 1999). We used Cox proportional hazards models to determine relative risks and 95% confidence intervals (CIs) for developing CVD according to self-reported anthropometric indexes. RESULTS: A total of 1,505 CVD cases occurred in men and 414 occurred in women (median follow-up 14.2 and 5.5 years, respectively). Although WHtR demonstrated statistically the strongest associations with CVD and best model fit, CVD risk increased linearly and significantly with higher levels of all indexes. Adjusting for confounders, the relative risk for CVD was 0.58 (95% CI: 0.32 to 1.05) for men with the lowest WHtR (<0.45)>/=0.69; vs. WHtR 0.49 to <0.53).>/=0.68; vs. WHtR 0.47 to <0.52).>

Diabetes e Linfoma

American Journal of Epidemiology 2008 168(5):471-480; doi:10.1093/aje/kwn160
Type 2 Diabetes Mellitus and Risk of Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis.
(e-mail: chun.r.chao@kp.org)
for publication February 19, 2008. Accepted for publication May 8, 2008.
Type 2 diabetes mellitus is associated with altered immune function and chronic inflammation. Both of these immune conditions are implicated in the pathogenesis of non-Hodgkin lymphoma. The authors performed a systematic review to summarize findings from the current literature on the association between history of type 2 diabetes mellitus and risk of non-Hodgkin lymphoma. Ten case-control studies and three prospective cohort studies were included in this review. Meta-analysis found that a history of type 2 diabetes mellitus was positively associated with overall non-Hodgkin lymphoma risk. However, there was significant heterogeneity between studies. Study design was an important source of heterogeneity. The rate ratio between type 2 diabetes mellitus and non-Hodgkin lymphoma was found to be 1.18 (95% confidence interval: 0.99, 1.42) among case-control studies and 1.79 (95% confidence interval: 1.30, 2.47) among the prospective cohort studies. Weaknesses were identified in some of the included studies in the areas of case and control selection, measurement of covariates and non-Hodgkin lymphoma, and confounding control. Although a positive association between type 2 diabetes mellitus and risk of non-Hodgkin lymphoma was suggested, the evidence is inconclusive because of methodological limitations of the included case-control studies. More prospective studies with improved control of confounding are needed to confirm these findings.
diabetes mellitus; diabetes mellitus, type 2; lymphoma; lymphoma, non-Hodgkin; meta-analysis

sexta-feira, 22 de agosto de 2008

ELSA no ano 1 saúda os 60 anos do "vovô" Framingham Heart Study

Em breve, o Framingham Heart Study completará 60 anos. Esse estudo iniciado em 1948 com mais de 5 mil pessoas na cidade do mesmo nome, próxima a Boston representa um dos grandes legados da epidemiologia à ciência e saúde pública. Impossível falar em fatores de risco cardiovascular sem os resultados de Framingham.
Essa semana, os quatros primeiros participantes terminaram os exames iniciais do Estudo Longitudinal de Saúde do Adulto, na sede paulista do projeto localizado no Hospital Universitário da USP. Na foto, a coordenadora, professora Isabela Benseñor e técnica Angelita trocam a placa no primeiro dia do estudo. O ELSA examinará 15 mil pessoas em SamPa (5 mil), BH (3 mil), Salvador (2 mil), Rio (2mil), PoA (2mil) e, Vitória (1 mil). Trará informações sobre os determinates do diabetes e da doença cardiovascular em uma população brasileira. Trata-se do grande empreendimento dos epidemiologistas brasileiros que aproveitam o momento para saudar o aniversário do "vovô" Framingham.

Vacina para o HPV: custo-benefício discutível

O PharmaBlog faz um resumo abaixo muito bom do artigo sobre a custo-efetividade da vacina para o HPV. Esse é recidivante nesse blogue, basta clicar aqui para ver o debate nos Estados Unidos a conduta do nosso Ministério da Saúde.
Eu volto a repetir o post de 19/01/07: "... quem precisará da vacina, não terá acesso e, fará uso quem tem risco mínimo de câncer de colo uterino. É o fenômeno descrito na Inglaterra por Julian Tudor- Hart chamado "inverse care law". O Ministério da Saúde precisa ser rigoroso e, impedir a liberalização total de venda da vacina? Sim, porque (1) somente o Ministério poderá comprar a vacina e, quem tomar em clínica particulares irá deduzir o valor pago no imposto de renda. Ou seja, por compra direta ou por renúncia fiscal, a conta será do erário; (2) existirá em breve, alternativa da Glaxo, que poderá ser mais barata e efetiva. Por isso, se o Ministério facilitar a venda do produto da Merck estará "matando" o concorrente que poderá ser ou não a melhor opção (não há dados confiáveis) entre as duas estratégias de prevenção.
No entanto, a prioridade de aplicação em termos de faixa etária, região e categoria social deveria ser do Ministério. Porque, se com certeza, a moça de 15 anos moradora em Brasília Teimosa em Recife se beneficiará mais da vacina, do que a senhora de 35 anos moradora no plano piloto de Brasília, não preciso ser advinho para saber quem terá e, quem não terá acesso à vacina, casos as "leis de mercado" prevaleçam."
Pharma Blog » 2008 » August » 21
Gardasil Isn’t Worth The Cost For Women Over 18
By Ed Silverman //
August 21st, 2008 // 8:05 am
That’s the conclusion of a new study that is going to make life much harder for Merck to wring needed sales out of its
controversial HPV vaccine. The study, which appears in the New England Journal of Medicine, comes as the drugmaker is already struggling to convince college-age and older women to get the vaccine, which costs about $360 for a three-dose regimen.
The vaccine, which is approved for girls and young women ages 9 to 26, makes economic sense for preteens because they are less likely to have the sexually transmitted virus that causes cervical cancer, according to
the study. But the cost-benefit depends on how long Gardasil’s protection will last, although Merck contends the vaccine is cost effective for women through age 24.
The analysis predicted that life expectancy gained by giving Gardasil to women older than 18 doesn’t outweigh the expense. “We aren’t saying older women can’t benefit. We are just saying that from a societal perspective there might be a better use of this investment in money,” Jane Kim, an author on the study and an assistant professor of health decision science at Harvard University, tells
Bloomberg News. “You are getting diminishing returns.”
The researchers compared the price of the vaccine and other expenses involved in getting the shot along with regular pap smears to the cost of pap smears. A pap smear, which detects abnormal cell change that could signify cervical cancer, costs about $38.68 and is recommended at least once every three years for women ages 21 through 64, according to the National Institutes of Health.
To wit, Gardasil cost about $43,600 per “quality-adjusted life year” gained when administered to 12- year-old girls. This falls below the $50,000 per QALY benchmark used by many researchers as a maximum for cost-effectiveness, although other researchers cite $100,000 per QALY.
It would cost $97,300 per QALY, however, to vaccinate girls and women through age 18; $120,400 per QALY for girls and women up to age 21, and $152,700 for girls and women up to age 26. However, the cost becomes more attractive when considering protection against genital warts - the cost per QALY when given to 12-year-olds falls 20 precent to $34,900, and to $133,600 for a program through age 26.
Current data has only looked at Gardasil’s ability to stop HPV for up to five years. It is unknown whether Gardasil can reduce overall rates of cervical cancer and deaths, Charlotte Haug, editor-in-chief of the Journal of the Norwegian Medical Association, wrote in a separate editorial also published in the New England Journal.
“There is good reason to be cautious about introducing large-scale vaccination programs,” Haug tells Bloomberg. “Instead, we should concentrate on finding more solid answers through research rather than base consequential and costly decisions on yet unproven assumptions.”
It is routine for vaccines to be used after five years of efficacy data and it would be unfair to patients keep the product off the market while researchers study its long-term effects, Rick Haupt, Merck’s executive director of Gardasil clinical research, tells Bloomberg. Merck may present data this year on the effects of the vaccine over nine years.
Gardasil protects against the HPV strains 16 and 18, which are responsible for 70 percent of cervical cancers, and HPV strains 6 and 11, which cause 90 percent of genital warts. While many of the sexually transmitted infections caused by HPV are resolved naturally, others develop into genital warts and cervical cancer. The CDC recommends girls be vaccinated at age 11 or 12.

quinta-feira, 21 de agosto de 2008

terça-feira, 19 de agosto de 2008

Arsênico e diabetes

Arsenic Exposure and Prevalence of Type 2 Diabetes in US Adults
Ana Navas-Acien, MD, PhD; Ellen K. Silbergeld, PhD; Roberto Pastor-Barriuso, PhD; Eliseo Guallar, MD, DrPH
JAMA. 2008;300(7):814-822.
Context High chronic exposure to inorganic arsenic in drinking water has been related to diabetes development, but the effect of exposure to low to moderate levels of inorganic arsenic on diabetes risk is unknown. In contrast, arsenobetaine, an organic arsenic compound derived from seafood intake, is considered nontoxic.
Objective To investigate the association of arsenic exposure, as measured in urine, with the prevalence of type 2 diabetes in a representative sample of US adults.
Design, Setting, and Participants Cross-sectional study in 788 adults aged 20 years or older who participated in the 2003-2004 National Health and Nutrition Examination Survey (NHANES) and had urine arsenic determinations.
Main Outcome Measure Prevalence of type 2 diabetes across intake of arsenic.
Results The median urine levels of total arsenic, dimethylarsinate, and arsenobetaine were 7.1, 3.0, and 0.9 µg/L, respectively. The prevalence of type 2 diabetes was 7.7%. After adjustment for diabetes risk factors and markers of seafood intake, participants with type 2 diabetes had a 26% higher level of total arsenic (95% confidence interval [CI], 2.0%-56.0%) and a nonsignificant 10% higher level of dimethylarsinate (95% CI, –8.0% to 33.0%) than participants without type 2 diabetes, and levels of arsenobetaine were similar to those of participants without type 2 diabetes. After similar adjustment, the odds ratios for type 2 diabetes comparing participants at the 80th vs the 20th percentiles were 3.58 for the level of total arsenic (95% CI, 1.18-10.83), 1.57 for dimethylarsinate (95% CI, 0.89-2.76), and 0.69 for arsenobetaine (95% CI, 0.33-1.48).
Conclusions After adjustment for biomarkers of seafood intake, total urine arsenic was associated with increased prevalence of type 2 diabetes. This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence. Prospective studies in populations exposed to a range of inorganic arsenic levels are needed to establish whether this association is causal.

segunda-feira, 18 de agosto de 2008

Jejum versus não jejum: perfil lipídico

Fasting Compared With Nonfasting Lipids and Apolipoproteins for Predicting Incident Cardiovascular Events . Circulation on line first
Samia Mora MD, MHS*, Nader Rifai PhD, Julie E. Buring ScD, and Paul M Ridker MD, MPH
From the Donald W. Reynolds Center for Cardiovascular Research (S.M., J.E.B., P.M.R.), Leducq Center for Molecular and Genetic Epidemiology (S.M., P.M.R.), and Center for Cardiovascular Disease Prevention (S.M., P.M.R.), Division of Preventive Medicine (S.M., J.E.B., P.M.R.), and Division of Cardiovascular Medicine (S.M., P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Department of Epidemiology, Harvard School of Public Health, Boston, Mass (J.E.B., P.M.R.); and Department of Laboratory Medicine, Children's Hospital and Harvard Medical School, Boston, Mass (N.R.).
* To whom correspondence should be addressed. E-mail:
smora@partners.org
Background—Although guidelines recommend measuring fasting lipids for initial screening of adults without cardiovascular disease (CVD), recent studies suggest that nonfasting triglycerides may be superior to fasting. Whether fasting status alters associations of nontriglyceride lipids with CVD is unclear.
Methods and Results—In a prospective study of 26 330 healthy women (19 983 fasting; 6347 nonfasting), associations of baseline lipids with incident CVD (754 fasting; 207 nonfasting) were examined over an 11-year follow-up. Except for triglycerides, lipid concentrations differed minimally (<5%) for fasting versus nonfasting. However, stronger associations with CVD were noted for fasting total cholesterol (adjusted fasting hazard ratio [HR], 1.22 per 1-SD increment; 95% CI, 1.14 to 1.30; nonfasting HR, 1.07; 95% CI, 0.93 to 1.21), low-density lipoprotein (LDL) cholesterol (fasting HR, 1.21; 95% CI, 1.13 to 1.29; nonfasting HR, 1.00; 95% CI, 0.87 to 1.15), apolipoprotein B-100 (fasting HR, 1.36; 95% CI, 1.27 to 1.45; nonfasting HR, 1.20; 95% CI, 1.05 to 1.36), non–high-density lipoprotein (HDL) cholesterol (fasting HR, 1.29; 95% CI, 1.21 to 1.38; nonfasting HR, 1.15; 95% CI, 1.01 to 1.31), and apolipoprotein B-100/A-1 ratio (fasting HR, 1.39; 95% CI, 1.30 to 1.48; nonfasting HR, 1.18; 95% CI, 1.09 to 1.27). Compared with fasting levels, nonfasting HDL cholesterol, apolipoprotein A-1, and total/HDL cholesterol ratio had similar associations, and triglycerides had a stronger association, with CVD. Significant interactions were seen for LDL cholesterol and apolipoprotein B-100/A-1 ratio with fasting status (P for interaction=0.03 and <0.001, respectively).
Conclusions—This study demonstrates that HDL cholesterol, triglycerides, total/HDL cholesterol ratio, and apolipoprotein A-1 predict CVD when measured nonfasting. By contrast, total, LDL, and non-HDL cholesterol, in addition to apolipoprotein B-100 and B-100/A-1 ratio, provide less useful CVD risk information when nonfasting, despite small changes in their concentrations. Guidelines for lipid screening may need to consider these differences.

O fim dos nomogramas

The Nomogram Epidemic: Resurgence of a Medical Relic David A. Grimes, MD
Annals of Internal Medicine 19 August 2008 Volume 149 Issue 4 Pages 273-275
The obsolete calculators known as nomograms have become epidemic in recent medical literature. The frequency of articles in PubMed retrieved with this search term nearly doubled between 1990 to 1999 and 2000 to 2007. Popular in medicine from about 1925 to 1975, a nomogram is a crude graphical means for solving an equation by placing a straightedge across several scales. Today, most reported nomograms are inconsistent with both established definitions and half a century of clinical use. The need for nomograms disappeared with the advent of personal computing. Instead of constructing nomograms, authors should develop software, such as prediction models, that can either be downloaded to personal digital assistants or be used on the Internet. Modern computing features both accuracy and speed; nomograms offer only the latter

Caso Vioxx: ver o post anterior. Aqui, o editorial do The Annals of Internal Medicine

Seeding Trials: Just Say "No" Harold C. Sox, MD, Editor, and Drummond Rennie, MD
Annals of Internal Medicine 19 August 2008 Volume 149 Issue 4 Pages 279-80
The public has lacked convincing documentary evidence of a long-suspected drug company practice: promoting a new drug by sponsoring a randomized trial in which participating physicians use the drug as they follow the trial protocol. This practice—a seeding trial—is marketing in the guise of science. The apparent purpose is to test a hypothesis. The true purpose is to get physicians in the habit of prescribing a new drug.
Why would a drug company go to the expense and bother of conducting a trial involving hundreds of practitioners—each recruiting a few patients—when a study based at a few large medical centers could accomplish the same scientific purposes much more efficiently? The main point of the seeding trial is not to get high-quality scientific information: It is to change the prescribing habits of large numbers of physicians. A secondary purpose is to transform physicians into advocates for the sponsor's drug. The company flatters a physician by selecting him because he is "an opinion leader" and incorporates him in the research team with the title of "investigator." Then, it pays him good money: a consulting fee to advise the company on the drug's use and another fee for each patient he enrolls. The physician becomes invested in the drug's future and praises its good features to patients and colleagues. Unwittingly, the physician joins the sponsor's marketing team. Why do companies pursue this expensive tactic? Because it works
(1, 2).
It works, but it may endanger the unwary physician. The tide is turning against the physician who accepts emoluments from drug companies. Academic institutions and professional organizations are issuing ethical guidelines that proscribe transactions in which drug companies pay physicians an amount that is disproportionate to the services that the physician provides
(3, 4). The office of the U.S. Inspector General has issued guidance about which transactions are legal. Although its guidance focuses on gifts, it also states that payments for participation in research "should be fair market values for legitimate, reasonable, and necessary services" (5). Moreover—and most ominously for the future of seeding trials—"postmarketing research activities should be especially scrutinized to ensure that they are legitimate and not simply a pretext to generate prescriptions of a drug" (5).
Several years ago, Annals published a seeding trial
(6). Merck & Co. (Whitehouse Station, New Jersey) sponsored ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness), a large, community-based, randomized comparison of a cyclooxygenase-2 inhibitor (Vioxx [rofecoxib]) and a nonselective cyclooxygenase inhibitor (naproxen). At the end of the 3-month follow-up, the proportion of patients who discontinued naproxen was larger (8.1% vs. 5.9%) than that of those who discontinued Vioxx. We published the study because we thought that physicians would be interested in the low discontinuation rates for both drugs and the small difference between them.
No one told Annals the true purpose of ADVANTAGE. We learned about it when we received a letter to the editor from Dr. David Egilman, who was a consultant to the plaintiffs' attorneys in the civil suits against Merck
(7). He had access to publicly accessible trial documents, which included Merck employees' e-mail messages that disclosed the true intent of the ADVANTAGE trial. These messages are the meat of the article about seeding trials published in this issue by Hill and colleagues (8). To our knowledge, this article is the first to provide documentary evidence that proves the existence of seeding trials. Other than an excerpt from a single industry document cited in an article by Kessler and colleagues (9), we have not had "smoking gun" evidence, in which the perpetrators are on public record about why they conducted a trial like ADVANTAGE. The article provides clear evidence that the intent of ADVANTAGE was to increase prescriptions of Vioxx (the study outcome of greatest interest to Merck seems to have been Vioxx prescribing rates). However, despite the large body of documents searched by the authors, they discovered few details about exactly how Merck's marketing division carried out ADVANTAGE.
The documents do tell us that deception is the key to a successful seeding trial. That information—once it becomes general knowledge—could be the fatal blow for seeding trials. Institutional review boards, whose purpose is to protect humans who participate in research, would probably not likely approve an action that places patients in harms' way in order to influence physicians' prescribing habits. If they knew, few established clinical researchers would participate as coinvestigators. Few physicians would knowingly enroll their patients in a study that placed them at risk in order to provide a company with a marketing advantage, and few patients would agree to participate. Seeding trials can occur only because the company does not disclose their true purpose to anyone who could say "no."
It is also true that seeding trials exist only because physicians say "yes" to a deal that seems too good to be true. Academic physicians agree to be on the byline of an article that someone else wrote about a study that someone else designed and paid for because there is considerable prestige, little effort, and low risk
(10). A practicing physician says, "Why not?" when he learns that he has been selected to participate in an important clinical trial and receives inducements designed to make it an offer he will not refuse. Our parents prepared us for this moment when they warned us to ask questions when someone offers us easy money. We owe it to them and especially our patients to ask if we are being recruited to participate in a seeding trial.
How can people with decisional responsibility—institutional review boards, researchers, physicians, and patients—identify a seeding trial? They could ask the about the intent of the trial. If the answer was "It's a seeding trial," most would say no, and seeding trials would soon fade away; but this scenario is a fairy tale, because sponsors would probably ascribe a scientific purpose to the trial and proving otherwise would be difficult. Nonetheless, institutional review boards could routinely ask, "Is this a seeding trial?" Sponsors would think twice about lying to an institutional review board, an institution that has so much legal and public support, especially in an era in which e-mail messages seem to live on forever, awaiting discovery by a curious someone.
Asking about intent may be the wrong approach. Does the goodness of a trial inhere in its intent or in something else? An adequately powered trial is good if it tries to answer an important scientific question on which patients should be in equipoise, even though participating physicians will become familiar with a new drug and be more likely to prescribe it. Is the same trial bad if its main purpose is to increase drug sales by habituating trial physicians to prescribing a new drug? Couldn't the answer to this question depend on the scientific importance of the question that it addresses? The trial would be bad if it addressed a question that lacked merit but good, despite its intent, if the question had intrinsic merit. Does the motivation for the trial make it wrong to participate in it, or does addressing an important, unsettled question make the study worthwhile, despite its intent? Perhaps physicians should focus less on intent and more on the scientific question. The ADVANTAGE physicians should have been asking whether the trial addressed an issue that previous trials had already answered—or should have answered.
This line of reasoning suggests that institutional review boards, researchers, physicians, and patients should be asking about the study hypothesis and whether it addresses a settled question. Physicians have a fiduciary obligation to ask these questions on behalf of their patients, as do institutional review boards and researchers, which have the skill set and personnel to judge whether a trial is asking an already-answered question. They could look for other clues, such as a study with an open-label design, no control group, a very large projected enrollment relative to the importance of the question, a short-term study of a chronic disease, a study of an already approved drug, and so forth (
1, 8, 9). None of these clues is highly specific, but institutional review boards should start asking questions when a study has several of them.
A bureaucratic solution, such as relying on institutional review boards, could help to rid us of seeding trials, but simply shining a bright light on their existence may have already sown the seeds of their destruction. The next step would be a societal consensus that it is wrong to deceive institutional review boards and participants about the true purpose of a trial. Therein lies the importance of Hill and colleagues' article
(8).

Por dentro do caso Vioxx

The ADVANTAGE Seeding Trial: A Review of Internal Documents
Kevin P. Hill, MD, MHS; Joseph S. Ross, MD, MHS; David S. Egilman, MD, MPH; and Harlan M. Krumholz, MD, SM
Annals of Internal Medicine 19 August 2008 Volume 149 Issue 4 Pages 251-8
Background: Seeding trials, clinical studies conducted by pharmaceutical companies that are designed to seem as if they answer a scientific question but primarily fulfill marketing objectives, have not been described in detail.
Purpose: To describe a known seeding trial, ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness), through documents of the trial sponsor, Merck & Co. (Whitehouse Station, New Jersey).
Data Sources: Merck internal and external correspondence, reports, and presentations elicited to inform legal proceedings of Cona v Merck and Co., Inc., and McDarby v Merck and Co., Inc. The documents were created between 1998 and 2006.
Data Extraction: An iterative case-study process of review, discussion, and re-review of documents to identify themes relevant to the design and conduct of ADVANTAGE. To supplement the case-study review, the authors did a systematic review of the literature to identify published manuscripts focused on seeding trials and their conduct.
Data Synthesis: Review of the documents revealed 3 key themes: The trial was designed by Merck's marketing division to fulfill a marketing objective; Merck's marketing division handled both the scientific and the marketing data, including collection, analysis, and dissemination; and Merck hid the marketing nature of the trial from participants, physician investigators, and institutional review board members. Although the systematic review of the literature identified 6 articles that focused on the practice of seeding trials, none provided documentary evidence of their existence or conduct.
Limitations: The legal documents in these cases provide useful, but limited, information about the practices of the pharmaceutical industry. This description of 1 company's actions is incomplete and may have limited generalizability.
Conclusion: Documentary evidence shows that ADVANTAGE is an example of marketing framed as science. The documents indicate that ADVANTAGE was a seeding trial developed by Merck's marketing division to promote prescription of Vioxx (rofecoxib) when it became available on the market in 1999

Vitamina D e fraturas ósseas

Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures
Jane A. Cauley, DrPH; Andrea Z. LaCroix, PhD; LieLing Wu, MS; Mara Horwitz, MD; Michelle E. Danielson, PhD; Doug C. Bauer, MD; Jennifer S. Lee, MD; Rebecca D. Jackson, MD; John A. Robbins, MD; Chunyuan Wu, MS; Frank Z. Stanczyk, PhD; Meryl S. LeBoff, MD; Jean Wactawski-Wende, PhD; Gloria Sarto, MD; Judith Ockene, PhD; and Steven R. Cummings, MD
Annals of Internal Medicine 19 August 2008 Volume 149 Issue 4 Pages 242-250
Background: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear.
Objective: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women.
Design: Nested case–control study.
Setting: 40 clinical centers in the United States.
Participants: 400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from 39 795 postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture.
Measurements: Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures.
Results: Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD, 20.28] vs. 59.60 nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption.
Limitations: Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis.
Conclusion: Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture

Angina do peito: critérios para coronariografia.

Appropriateness Criteria for Coronary Angiography in Angina: Reliability and Validity Harry Hemingway, MBBChir; Ruoling Chen, MD; Cornelia Junghans, PhD; Adam Timmis, MBBChir; Sandra Eldridge, PhD; Nick Black, MD; Paul Shekelle, MD; and Gene Feder, MD
19 August 2008 Volume 149 Issue 4 Pages 221-231
Background: Evaluated criteria for tailoring the decision to perform coronary angiography in specific clinical scenarios are lacking.
Objective: To determine the reliability and prognostic validity of patient-specific appropriateness criteria for coronary angiography among patients with suspected angina pectoris.
Design: Prospective observational study. Two independent panels of clinicians scored 2400 patient-specific indications for coronary angiography as inappropriate, uncertain, or appropriate. Using a simple computer algorithm, patients were matched to 1 of these indications.
Setting: 6 urban ambulatory care clinics in the United Kingdom.
Patients: 9356 consecutive patients with recent-onset chest pain in whom stable angina was suspected.
Measurements: Appropriateness ratings and clinical outcomes (coronary death and acute coronary syndrome events) over a median of 3 years of follow-up.
Results: 660 coronary deaths or acute coronary syndrome events occurred. Agreement between the 2 panels (reliability) on appropriateness category was moderate (weighted = 0.58; P < 0.001). Use of subsequent angiography was strongly related to appropriateness category (P for linear trend <0.001) according to scores from either panel. Among patients judged as appropriate candidates for angiography, underuse was common (57% according to panel A and 71.3% according to panel B), and not undergoing coronary angiography was associated with higher coronary event rates than was undergoing the procedure. The hazard ratio after adjustment for age, sex, exercise electrocardiography result, and secondary prevention medication was similar according to panel A (2.78 [95% CI, 1.77 to 4.37]) and panel B (2.47 [CI, 1.72 to 3.55]).
Limitation: The study was too small to assess the relationship of angiography with coronary death and did not assess the reasons why patients did not receive angiography.
Conclusion: Appropriateness scores offer prognostically valid criteria for judging which specific patients might benefit from coronary angiography. Patient-specific appropriateness scores help pinpoint areas where judgments diverge and are a promising tool for making guidelines more effective.

Começa o maior estudo epidemiológico em doenças cardiovasculares e diabetes do hemisfério sul

Hoje, às 12:15, no Hospital Universitário da USP, a primeira participante do Estudo Longitudinal de Saúde do Adulto completou o questionários e os diversos exames do maior estudo epidemiológico em doenças crônicas do hemisfério sul. Restam 14 999 pessoas entre 35-74 anos, funcionários das universidades federais da Bahia, Espírito Santo, Minas Gerais, Rio Grande do Sul, da FIOCRUZ-Rio de Janeiro e, da USP. O financiamento é do Ministério da Saúde e do Ministério de Ciência e Tecnologia.
Maiores informações com a coordenadora do Elsa-SP, profa Isabela Bensenor, em isabensenor@hu.usp.br.

Radiação UV e diabetes tipo 1

S. B. Mohr1, C. F. Garland1 , E. D. Gorham1 and F. C. Garland1
(1) Diabetologia - Clinical and Experimental Diabetes and Metabolism, 06/23/08
Abstract
Aims/hypothesis This study is an analysis of the relationship between ultraviolet B (UVB) irradiance, the primary source of circulating vitamin D in humans, and age-standardised incidence rates of type 1 diabetes mellitus in children, according to region of the world.
Methods The association of UVB irradiance adjusted for cloud cover to incidence rates of type 1 diabetes in children aged <14 years during 1990–1994 in 51 regions worldwide was assessed using multiple regression. Incidence data were obtained from the Diabetes Mondial Project Group.
Results Incidence rates were generally higher at higher latitudes (R 2 = 0.25, p < 0.001). According to multiple regression, UVB irradiance adjusted for cloud cover was inversely associated with incidence rates (p < 0.05), while per capita health expenditure (p < 0.004) was positively associated (overall R 2 = 0.42, p < 0.0001).
Conclusions/interpretation An association was found between low UVB irradiance and high incidence rates of type 1 childhood diabetes after controlling for per capita health expenditure. Incidence rates of type 1 diabetes approached zero in regions worldwide with high UVB irradiance, adding new support to the concept of a role of vitamin D in reducing the risk of the disease.
Keywords Epidemiology - Type 1 diabetes - Ultraviolet rays - Vitamin D

Vertigem e tontura: aumento de procura a pronto-socorro

Dizziness Presentations in U.S. Emergency Departments, 1995–2004
Kevin A. Kerber MD, William J. Meurer MD, Brady T. West MA, A. Mark Fendrick MD
From the Department of Neurology (KAK, WJM), the Department of Otolaryngology (KAK), the Department of Emergency Medicine (WJM), and the Department of Internal Medicine (AMF), University of Michigan Health Systems, Ann Arbor, MI; and the Center for Statistical Consultation and Research (BTW) and the Department of Health Management and Policy (AMF), University of Michigan, Ann Arbor, MI.
Address for correspondence and reprints: Kevin A. Kerber, MD; e-mail:
kakerber@umich.edu.
ACADEMIC EMERGENCY MEDICINE 2008; 15:744–750 ABSTRACT
Objectives: The objectives were to describe presentation characteristics and health care utilization information pertaining to dizziness presentations in U.S. emergency departments (EDs) from 1995 through 2004.
Methods: From the National Hospital Ambulatory Medical Care Survey (NHAMCS), patient visits to EDs for "vertigo-dizziness" were identified. Sample data were weighted to produce nationally representative estimates. Patient characteristics, diagnoses, and health care utilization information were obtained. Trends over time were assessed using weighted least squares regression analysis. Multivariable logistic regression analysis was used to control for the influence of age on the probability of a vertigo-dizziness visit during the study time period.
Results: Vertigo-dizziness presentations accounted for 2.5% (95% confidence interval [CI] = 2.4% to 2.6%) of all ED presentations during this 10-year period. From 1995 to 2004, the rate of visits for vertigo-dizziness increased by 37% and demonstrated a significant linear trend (p < 0.001). Even after adjusting for age (and other covariates), every increase in year was associated with increased odds of a vertigo-dizziness visit. At each visit, a median of 3.6 diagnostic or screening tests (95% CI = 3.2 to 4.1) were performed. Utilization of many tests increased over time (p < 0.01). The utilization of computerized tomography and magnetic resonance imaging (CT/MRI) increased 169% from 1995 to 2004, which was more than any other test. The rate of central nervous system diagnoses (e.g., cerebrovascular disease or brain tumor) did not increase over time.
Conclusions: In terms of number of visits and important utilization measures, the impact of dizziness presentations on EDs is substantial and increasing. CT/MRI utilization rates have increased more than any other test

sábado, 16 de agosto de 2008

Hemoglobina glicada ou glicemia: ADAG study

A1C or Average Glucose: Take your pickThe results of the A1C-Derived Average Glucose study (ADAG), published in Diabetes Care this month, have affirmed the existence of a linear relationship between A1C and average blood glucose levels. Prior studies using limited numbers of meter glucose readings primarily in type 1 Caucasian populations had been used in the past to estimate average glucose. The international ADAG study clarified the very close linkage using about 2700 glucose readings per subject per A1C measurement, and verified that the relationship holds in people with type 1 and type 2 diabetes, of all ages, of both genders, and across ethnic/racial groups. The “new numbers” are somewhat different than those in the old tables of A1C vs. average glucose.In light of the study results, health care providers can confidently report A1C results to patients using the same units (mg/dl or mmol/l) that patients see routinely in blood glucose measurements. For more information about the ADAG study, a table of A1C and the corresponding estimated average glucose, an eAG calculator, and other materials, go to http://professional.diabetes.org/glucosecalculator.aspx

quinta-feira, 14 de agosto de 2008

Medidas de adiposidade

J Am Coll Cardiol, 2008; 52:605-615, doi:10.1016/j.jacc.2008.03.066
Measures of Obesity and Cardiovascular Risk Among Men and Women
Rebecca P. Gelber, MD, DrPH*,**, J. Michael Gaziano, MD, MPH*,,¶, E. John Orav, PhD,, JoAnn E. Manson, MD, DrPH,, Julie E. Buring, ScD*,,,# and Tobias Kurth, MD, ScD*,,,*
* Reprint requests and correspondence: Dr. Tobias Kurth, Brigham and Women's Hospital, Division of Aging, 1620 Tremont Street, Boston, Massachusetts 02120. (Email: tkurth@rics.bwh.harvard.edu
Objectives: This study examined associations between anthropometric measures (body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio [WHtR]) and risk of incident cardiovascular disease (CVD) (including nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death).
Background: Controversy exists regarding the optimal approach to measure adiposity, and the utility of body mass index has been questioned.
Methods: Participants included 16,332 men in the Physicians' Health Study (mean age 61 years in 1991) and 32,700 women in the Women's Health Study (mean age 61 years in 1999). We used Cox proportional hazards models to determine relative risks and 95% confidence intervals (CIs) for developing CVD according to self-reported anthropometric indexes.
Results: A total of 1,505 CVD cases occurred in men and 414 occurred in women (median follow-up 14.2 and 5.5 years, respectively). Although WHtR demonstrated statistically the strongest associations with CVD and best model fit, CVD risk increased linearly and significantly with higher levels of all indexes. Adjusting for confounders, the relative risk for CVD was 0.58 (95% CI: 0.32 to 1.05) for men with the lowest WHtR (<0.45) and 2.36 (95% CI: 1.61 to 3.47) for the highest WHtR (0.69; vs. WHtR 0.49 to <0.53). Among women, the relative risk was 0.65 (95% CI: 0.33 to 1.31) for those with the lowest WHtR (<0.42) and 2.33 (95% CI: 1.66 to 3.28) for the highest WHtR (0.68; vs. WHtR 0.47 to <0.52).
Conclusions: The WHtR demonstrated statistically the best model fit and strongest associations with CVD. However, compared with body mass index, differences in cardiovascular risk assessment using other indexes were small and likely not clinically consequential. Our findings emphasize that higher levels of adiposity, however measured, confer increased risk of CVD.

ITB melhora o Framingham Risk Score

Ankle Brachial Index Combined With Framingham Risk Score to Predict Cardiovascular Events and Mortality
A Meta-analysis Ankle Brachial Index Collaboration
JAMA. 2008;300(2):197-208.
Context Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.
Objective To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.
Data Sources Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.
Study Selection Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.
Data Extraction Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.
Results Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480 325 person-years of follow-up of 24 955 men and 23 339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women.
Conclusion Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Genética do fibrinogênio

Linkage Study of Fibrinogen Levels: The Strong Heart Family Study
Lyle G. Best , Kari E. North , Xia Li , Vittorio Palmieri , Jason G. Umans , Jean MacCluer , Sandra Laston , Karin Haack , Harald Goring , Laura Almasy , Elisa T. Lee , Russell P. Tracy and Shelley A. Cole
BMC Medical Genetics 2008, 9:77doi:10.1186/1471-2350-9-77
Published: 12 August 2008
Abstract (provisional)
Background
The pathogenesis of atherosclerosis involves both hemostatic and inflammatory mechanisms. Fibrinogen is associated with both risk of thrombosis and inflammation. A recent meta-analysis showed that risk of coronary heart disease may increase 1.85 fold for each 1g/L of increased fibrinogen, independent of traditional risk factors. It is known that fibrinogen levels may be influenced by demographic, environmental and genetic factors. Epidemiologic and candidate gene studies are available; but few genome-wide linkage studies have been conducted, particularly in minority populations. The Strong Heart Study has demonstrated an increased incidence of cardiovascular disease in the American Indian population, and therefore represents an important source for genetic-epidemiological investigations.
Methods
The Strong Heart Family Study enrolled over 3,600 American Indian participants in large, multi-generational families, ascertained from an ongoing population-based study in the same communities. Fibrinogen was determined using standard technique in a central laboratory and extensive additional phenotypic measures were obtained. Participants were genotyped for 382 short tandem repeat markers distributed throughout the genome; and results were analyzed using a variance decomposition method, as implemented in the SOLAR 2.0 program.
Results
Data from 3535 participants were included and after step-wise, linear regression analysis, two models were selected for investigation. Basic demographic adjustments constituted model 1, while model 2 considered waist circumference, diabetes mellitus and postmenopausal status as additional covariates. Five LOD scores between 1.82 and 3.02 were identified, with the maximally adjusted model showing the highest score on chromosome 7 at 28cM. Genes for two key components of the inflammatory response, i.e. interleukin-6 and "signal transducer and activator of transcription 3" (STAT3), were identified within 2 and 8 Mb of this 1 LOD drop interval respectively. A LOD score of 1.82 on chromosome 17 between 68 and 93cM is supported by reports from two other populations with LOD scores of 1.4 and 1.95.
Conclusion
In a minority population with a high prevalence of cardiovascular disease, strong evidence for a novel genetic determinant of fibrinogen levels is found on chromosome 7 at 28cM. Four other loci, some of which have been suggested by previous studies, were also identified

Hemoglobina glicada, internação, mortalidade na insuficiência cardíaca

The Hemoglobin A1c Level as a Progressive Risk Factor for Cardiovascular Death, Hospitalization for Heart Failure, or Death in Patients With Chronic Heart Failure. An Analysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program
Hertzel C. Gerstein, MD, MSc; Karl Swedberg, MD, PhD; Jonas Carlsson, MSc; John J. V. McMurray, MD; Eric L. Michelson, MD; Bertil Olofsson, PhD; Marc A. Pfeffer, MD, PhD; Salim Yusuf, DPhil; for the CHARM Program Investigators

Arch Intern Med. 2008;168(15):1699-1704.
Background A progressive relationship between hemoglobin A1c (HbA1c) levels and cardiovascular (CV) events has been observed in persons with and without diabetes. To our knowledge, the nature of such a relationship in patients with symptomatic chronic heart failure (HF) has not been studied.
Methods A total of 2412 participants (907 with prior diabetes) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program with at least 1 HbA1c level were followed up for a median of 34 months. The incidence of the primary outcome (CV death or HF hospitalization), CV death, and total mortality was calculated according to eighths of the usual HbA1c level ranging from 5.8% or less to greater than 8.6%. Adjusted and unadjusted hazard ratios per 1% rise in HbA1c levels were also calculated.
Results A total of 99.6% of eligible participants were followed up until they developed an outcome or the study finished. The risk of the primary composite outcome, CV death, hospitalization for worsening HF, and total mortality rose progressively with higher levels of usual HbA1c (P for trend <.001). After age and sex were adjusted for, hazards of these outcomes per 1% higher HbA1c level were 1.25 (95% confidence interval [CI ],1.20-1.31), 1.24 (95% CI, 1.17-1.31), 1.25 (95% CI, 1.19-1.31), and 1.22 (95% CI, 1.16-1.29), respectively. This relationship was evident in patients with and without diabetes and with reduced or preserved ejection fraction and persisted after adjustment for diabetes, other risk factors, and allocation to candesartan.
Conclusion In diabetic and nondiabetic patients with symptomatic chronic HF, the HbA1c level is an independent progressive risk factor for CV death, hospitalization for HF, and total mortality.

quarta-feira, 13 de agosto de 2008

Como as taxas de fecundidade foram diminuindo

Absolutamente, totalmente, imperdível, a leitura desse artigo de Suzana Cavenaghi com acesso gratuito. Torna-se claro que os resultados da PNDS não foram tão "inesperados"..

As verdades da vida são sem prazos.

Homenagem a meu ex-aluno e co-autor do livro abaixo citado:
Felipe Montenegro Carneiro da Cunha Kumamoto (1977 - 2007).
O seu exemplar de autor foi entregue hoje aos pais em cerimonia no Hospital Universitário.
As verdades da vida são sem prazos
G.Rosa, Tutaméia

ITB e risco cardiovascular

Different Calculations of Ankle-Brachial Index and Their Impact on Cardiovascular Risk Prediction
Christine Espinola-Klein MD*, Hans J. Rupprecht MD, Christoph Bickel MD, Karl Lackner MD, Savvas Savvidis MD, Claudia M. Messow , Thomas Munzel MD, Stefan Blankenberg MD, for the AtheroGene Investigators
Background—An ankle-brachial index (ABI; ratio of ankle and brachial systolic blood pressure) <0.9 indicates peripheral arterial disease (PAD) and is a strong predictor of cardiovascular events. The aim of the present study was to address the prognostic value of different methods of ABI calculation.
Methods and Results—In 831 patients admitted with chest pain for diagnostic heart catheterization, blood pressure of both anterior and posterior tibial arteries was measured. ABI was calculated for each leg with the higher of the 2 ankle pressures (current definition of the American Heart Association) or with the lower of the 2 ankle pressures (modified definition) in relation to the higher of the left or right brachial systolic blood pressure. For each patient, the lower ABI from both legs was used for further evaluation. Fifteen patients (1.8%) with ABI >1.5 were excluded. We compared patients with ABI <0.9 according to the current definition (with PAD, n=204 [25.0%]), those with ABI 0.9 according to the modified definition (without PAD, n=524 [64.2%]), and those with ABI <0.9 according to the modified definition and 0.9 according to the current definition (suspected PAD, n=88 [10.8%]). Follow-up data (median 6.6 years) were available for 812 patients (99.5%); 157 patients (19.3%) experienced cardiovascular events (cardiovascular death, myocardial infarction, or stroke). Patients without PAD had the lowest cardiovascular event rate, whereas event rates were comparable for patients with PAD and those with suspected PAD (14.8% versus 28.4% versus 25.0%, respectively). In a fully adjusted Cox regression analysis that included patients without PAD as the reference group, the hazard ratio (95% CI) was 1.56 (0.97 to 2.53) for patients with suspected PAD and 1.67 (1.16 to 2.40) for patients with PAD.
Conclusions—When the higher ankle pressure is used for ABI calculation, a group of patients at high risk for cardiovascular events is overlooked. With a simple modification of ABI (use of the lower instead of the higher ankle pressure), more patients at risk could be identified.

Prevenção Primária e AVC

Primary Prevention of Stroke by Healthy Lifestyle
Stephanie E. Chiuve ScD*, Kathryn M. Rexrode MD, MPH, Donna Spiegelman ScD, Giancarlo Logroscino MD, PhD, JoAnn E. Manson MD, DrPH, and Eric B. Rimm ScD

Background—The combination of healthy lifestyle factors is associated with lower risk of coronary heart disease, diabetes, and total cardiovascular disease. Little is known about the impact of multiple lifestyle factors on the risk of stroke.
Methods and Results—We conducted a prospective cohort study among 43 685 men from the Health Professionals Follow-up Study and 71 243 women from the Nurses' Health Study. Diet and other lifestyle factors were updated from self-reported questionnaires. We defined a low-risk lifestyle as not smoking, a body mass index <25 kg/m2, 30 min/d of moderate activity, modest alcohol consumption (men, 5 to 30 g/d; women, 5 to 15 g/d), and scoring within the top 40% of a healthy diet score. We documented 1559 strokes (853 ischemic, 278 hemorrhagic) among women and 994 strokes (600 ischemic, 161 hemorrhagic) among men during follow-up. Women with all 5 low-risk factors had a relative risk of 0.21 (95% confidence interval [CI], 0.12, 0.36) for total and 0.19 (95% CI, 0.09, 0.40) for ischemic stroke compared with women who had none of these factors. Among men, the relative risks were 0.31 (95% CI, 0.19, 0.53) for total and 0.20 (95% CI, 0.10, 0.42) for ischemic stroke for the same comparison. Among the women, 47% (95% CI, 18 to 69) of total and 54% (95% CI, 15 to 78%) of ischemic stroke cases were attributable to lack of adherence to a low-risk lifestyle; among the men, 35% (95% CI, 7 to 58) of total and 52% (95% CI, 19 to 75) of ischemic stroke may have been prevented.
Conclusion—A low-risk lifestyle that is associated with a reduced risk of multiple chronic diseases also may be beneficial in the prevention of stroke, especially ischemic stroke

Apnéia do sono e AVC

Increased Risk of Stroke in Patients With Coronary Artery Disease and Sleep Apnea. A 10-Year Follow-Up
Fredrik Valham MD, Thomas Mooe MD, PhD, Terje Rabben MD, Hans Stenlund PhD, Urban Wiklund PhD, and Karl A. Franklin MD, PhD*
* To whom correspondence should be addressed. E-mail: Karl.Franklin@Lung.umu.se
Background—The effect of sleep apnea on mortality and cardiovascular morbidity is mainly unknown. We aimed to study whether sleep apnea is related to stroke, death, or myocardial infarction in patients with symptomatic coronary artery disease.
Methods and Results—A total of 392 men and women with coronary artery disease referred for coronary angiography were examined by use of overnight sleep apnea recordings. Sleep apnea, defined as an apnea-hypopnea index 5, was recorded in 54% of the patients. All patients were followed up prospectively for 10 years, and no one was lost to follow-up. Stroke occurred in 47 (12%) of 392 patients during follow-up. Sleep apnea was associated with an increased risk of stroke, with an adjusted hazard ratio of 2.89 (95% confidence interval 1.37 to 6.09, P=0.005), independent of age, body mass index, left ventricular function, diabetes mellitus, gender, intervention, hypertension, atrial fibrillation, a previous stroke or transient ischemic attack, and smoking. Patients with an apnea-hypopnea index of 5 to 15 and patients with an apnea-hypopnea index 15 had a 2.44 (95% confidence interval 1.08 to 5.52) and 3.56 (95% confidence interval 1.56 to 8.16) times increased risk of stroke, respectively, than patients without sleep apnea, independent of confounders (P for trend=0.011). Death and myocardial infarction were not related to sleep apnea. Intervention in the form of coronary artery bypass grafting or percutaneous coronary intervention was related to a longer survival but did not affect the incidence of stroke.
Conclusions—Sleep apnea is significantly associated with the risk of stroke among patients with coronary artery disease who are being evaluated for coronary intervention.
Key words: sleep apnea syndromes • coronary disease • stroke • prognosis • risk factors • myocardial infarction

terça-feira, 12 de agosto de 2008

Lançamento de livro: Clínica Médica

Mais um livro da coleção Medicina Ciência e Arte, da Sarvier reunindo as experiências de profissionais dos Hospitais das Clínicas e Universitário: Clínica Médica: Diagnóstico e Tratamento.
Os autores Itamar Santos, Leonardo Borges, Isabela Bensenor e esse blogueiro.
Lançamento no HU: quarta-feira, dia 13 de agosto, às 11 hs.
Lançamento no HC: quarta-feira, dia 20 , às 11 hs

Checando o Check-up

Mais uma vez o questionamento aos famigerados "check-ups" em um síntese no blog do WSJ.
Why Cancer Screening Isn’t Always a Good Idea
Cancer screening sounds like the kind of the thing we should all be behind — “Go out there and get tested!” And some screenings, such as pap smears and colonoscopies, are indeed a great way to catch cancers and stop them before they turn deadly.
But the wrong kind of cancer screening can actually do more harm than good. Last week, a panel of experts convened by the federal government suggested that, for men 75 and older, the risks of prostate cancer screening outweigh the benefits.
Prostate cancer is often a slow-growing disease that doesn’t wind up causing any problems. So screening often leads to treatments (and side effects) for conditions that wouldn’t have caused any harm if they’d been left alone. For older men, the panel concluded, these risks outweigh the benefits of catching tumors that would have caused health problems — including death — if left alone.
But as this morning’s New York Times reminds us, it can be difficult to communicate the subtleties of this message. “We’re uncomfortable with the notion that some screening tests work and others don’t,” Peter Bach of Memorial Sloan-Kettering tells the NYT. “That seems mystifying to people.”
In Japan, the NYT notes, a screening program for neuroblastoma in infants was abandoned after it became clear the program wasn’t saving lives, but was causing risky treatments of tumors that weren’t life-threatening.
Screening smokers for lung cancer is another one that sounds good but remains unproved. And the risk-benefit balance for screening middle-aged men for prostate cancer remains unclear, the panel said last week. Some clarity on that question should be coming soon, though, when the evidence from a huge, federally funded trial is reported.

Diabetes e Cognição

Association of Duration and Severity of Diabetes Mellitus With Mild Cognitive Impairment
Rosebud O. Roberts, MBChB, MS; Yonas E. Geda, MD; David S. Knopman, MD; Teresa J. H. Christianson, BS; V. Shane Pankratz, PhD; Bradley F. Boeve, MD; Adrian Vella, MD; Walter A. Rocca, MD, MPH; Ronald C. Petersen, MD
Arch Neurol. 2008;65(8):1066-1073.
Background It remains unknown whether diabetes mellitus (DM) is a risk factor for mild cognitive impairment (MCI).
Objective To investigate the association of DM with MCI using a population-based case-control design.
Design Population-based case-control study.
Setting Academic research.
Participants Our study was conducted, among subjects aged 70 to 89 years on October 1, 2004, who were randomly selected from the Olmsted County (Minnesota) population.
Main Outcome Measure We administered to all participants a neurologic examination, the Clinical Dementia Rating Scale, and a neuropsychological evaluation (including 9 tests in 4 cognitive domains) to diagnose normal cognition, MCI, or dementia. We assessed history of DM, DM treatment, and DM complications by interview, and we measured fasting blood glucose levels. History of DM was also confirmed using a medical records linkage system.
Results We compared 329 subjects having MCI with 1640 subjects free of MCI and dementia. The frequency of DM was similar in subjects with MCI (20.1%) and in subjects without MCI (17.7%) (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.85-1.57). However, MCI was associated with onset of DM before age 65 years (OR, 2.20; 95% CI, 1.29-3.73), DM duration of 10 years or longer (OR, 1.76; 95% CI, 1.16-2.68), treatment with insulin (OR, 2.01; 95% CI, 1.22-3.31), and the presence of DM complications (OR, 1.80; 95% CI, 1.13-2.89) after adjustment for age, sex, and education. Analyses using alternative definitions of DM yielded consistent findings.
Conclusion These findings suggest an association of MCI with earlier onset, longer duration, and greater severity of DM.

Vitamina D e Mortalidade: NHANES III

25-Hydroxyvitamin D Levels and the Risk of Mortality in the General Population
Michal L. Melamed, MD, MHS; Erin D. Michos, MD, MHS; Wendy Post, MD, MS; Brad Astor, PhD
Arch Intern Med. 2008;168(15):1629-1637.
Background In patients undergoing dialysis, therapy with calcitriol or paricalcitol or other vitamin D agents is associated with reduced mortality. Observational data suggests that low 25-hydroxyvitamin D levels (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown.
Methods We tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the Third National Health and Nutrition Examination Survey (NHANES III) linked mortality files. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000.
Results In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8>

Dislipidemia e Disfunção Endotelial: Apo CIII

Circulation. 2008;118:731-742.)
Apolipoprotein CIII Links Hyperlipidemia With Vascular Endothelial Cell Dysfunction
Akio Kawakami, MD; Mizuko Osaka, BS; Mariko Tani, PhD; Hiroshi Azuma, PhD; Frank M. Sacks, MD; Kentaro Shimokado, MD; Masayuki Yoshida, MD
. E-mail kawakami.vasc@tmd.ac.jp
Background— Apolipoprotein CIII (apoCIII) is a component of some triglyceride-rich very-low-density and low-density lipoprotein and is elevated in dyslipidemia with insulin resistance and the metabolic syndrome. We previously reported that apoCIII directly activates proinflammatory and atherogenic signaling in vascular endothelial cells through protein kinase C-β (PKCβ). Because PKCβ impairs the response of vascular endothelial cells to insulin, we tested the hypothesis that apoCIII affects insulin signaling in vascular endothelial cells and its function in vitro and in vivo.
Methods and Results— ApoCIII inhibited insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), decreasing phosphatidylinositol 3-kinase (PI3K)/Akt activation in human umbilical vein endothelial cells. These effects of apoCIII led to reduced endothelial nitric oxide synthase (eNOS) activation and NO release into the media. ApoCIII activated PKCβ in human umbilical vein endothelial cells, resulting in IRS-1 dysfunction via serine phosphorylation. ApoCIII also activated mitogen-activated protein kinase through PKCβ. The impaired insulin signaling was restored by PKCβ inhibitor or MEK1 inhibitor. ApoCIII-rich very-low-density lipoprotein and apoCIII impaired insulin signaling in the aorta of C57BL/6J mice and in human umbilical vein endothelial cells, which was recovered by PKCβ inhibitor. They also inhibited endothelium-dependent relaxation of the aortas of C57BL/6J mice. In summary, apoCIII in very-low-density lipoprotein impaired insulin stimulation of NO production by vascular endothelium and induced endothelial dysfunction in vivo. This adverse effect of apoCIII was mediated by its activation of PKCβ, which inhibits the IRS-1/PI3K/Akt/eNOS pathway.
Conclusion— Our results suggest that apoCIII is a crucial link between dyslipidemia and insulin resistance in vascular endothelial cells with consequential deleterious effects on their atheroprotective functions.

domingo, 10 de agosto de 2008

Esterilização: a crueldade e cinismo da elite dirigente

Abaixo transcrevo na íntegra reportagem do JB sobre laqueadura e vasectomia em unidades básicas de saúde. A esterilidade cirúrgica é um tema que a elite dirigente e intelectualizada discute muito, traça planos e sempre a considera como "última alternativa". Apesar das diretrizes dos donos da política reprodutiva, o "povo" pratica a esterilização há décadas. Inclusive, escondidos em unidades básicas de saúde. Parte dos partos cesáreos são na verdade laqueaduras. Quem trabalha na periferia de São Paulo conhece muito o termo "Credi-Laq", o pagamento em prestações ao médico durante a gravidez para garantir a esterilização tubárea.
Pior são os planos de saúde e seguradoras que não cobriam a esterilização.
Bem, acima descrevi a crueldade da elite intelectualizada. O cinismo é comprovado pela prática rotineira nesse segmento tanto da vasectomia como da laqueadura. No debate abaixo, há um candidato que afirma que a vasectomia é cara. Em hospital chique de primeira linha em São Paulo, não sai por mais de mil reais, tudo incluído.
Candidatos debatem sobre proposta de laqueadura em postos de saúde e Planejamento Familiar (PF) http://jbonline.terra.com.br/extra/2008/08/09/e090826464.html Marcelo Migliaccio, Pedro Vieira e Renata Victal, Jornal do Brasil RIO - A proposta do candidato à prefeitura do Rio Marcelo Crivella (PRB-PR-PSDC-PRTB) de que, caso seja eleito, fará os postos de saúde municipais atenderem jovens com 18 anos ou mais que optem pela laqueadura ou vasectomia como métodos para evitar novos filhos abriu o debate sobre o planejamento familiar na cidade. – É preciso que o povo tenha consciência de que há esses métodos. Podemos fazer uma ampla distribuição de camisinhas e o controle das doenças – afirmou Crivella. O petista Alessandro Molon classificou como “infeliz” a proposta de seu adversário. – Não se resolve problema social com cirurgia, mas com informação e planejamento familiar para garantir a maternidade e a paternidade responsáveis. Laqueadura e vasectomia as são as últimas opções. O tema é mesmo polêmico e costuma ser evitado pelos candidatos. Motivos para isso não faltam. Na última campanha para o Senado, Jandira Feghali (PCdoB) liderava todas as pesquisas de intenção de voto com ampla margem. Mas, faltando apenas 10 dias para o pleito, uma série de mensagens ressaltando que a deputada tinha sido uma das principais promotoras da lei que eliminaria do Código Penal todos os artigos que definiam o aborto como um delito contribuiu para que perdesse a eleição.. Precavida, a comunista prefere não comentar o assunto. Favorável ao aborto, o candidato Eduardo Serra (PCB) acredita que a vasectomia e a laqueadura não podem ser feitas por imposição e que é melhor legalizar o aborto a ver jovens morrerem em clínicas ilegais. – Alguns hospitais têm estrutura para realizar laqueaduras e vasectomias, mas são necessários mais postos de saúde, com uma rede hierarquizada, espalhados pelo município – explica Serra. – Sou favorável a colocar os meios contraceptivos para a população. Também sou a favor de se legalizar o aborto, mas como última opção.. Atualmente, muita gente morre ao usar clínicas clandestinas. Chico Alencar (PSOL) acredita que criminalizar o aborto é “tão errado quanto incentivá-lo”. – Defendo a educação sexual desde a escola e o apoio ao pré-natal da gestante pobre. Nem a mais insensível das mulheres faz um aborto sem traumas, sem sofrimento. O candidato não concorda com a proposta de Crivella.. – Pensei que o Crivella, como bispo, considerasse a vida humana um bem. A laqueadura é um método agressivo à dignidade e à consciência da mulher, que é percebida como um mero objeto reprodutivo. O que ele está propondo é um controle de natalidade induzido ou compulsório. Eduardo Paes (PMDB) também não concorda com Crivella. – Há outros métodos de planejamento familiar. Laqueadura e vasectomia são os limites. O candidato verde Fernando Gabeira prefere não entrar no tema da legalização ou não do aborto. Para ele esta é uma discussão “equivocada”. – O nosso objetivo maior não deveria ser o aborto, e sim evitar a gravidez indesejada por falta de informação – ressalta Gabeira. O candidato do PV diz que o serviço prestado pela prefeitura será mantido, mas tem ressalvas: – Recebi uma queixa de uma mulher que engravidou depois da laqueadura. Mais conservadora, a candidata Solange Amaral (DEM) disse não ser favorável à proposta de Crivella. Para ela, reduzir a idade mínima da laqueadura de 25 para 18 anos seria um erro e mais uma prova do preconceito contra as mulheres. – Não sou favorável à mudança na lei, que já permite a laqueadura para mulher com mais de 25 anos e dois filhos – enfatiza Solange. – O que vejo nessas propostas é o preconceito contra a mulher, que acaba tendo o ônus de uma gravidez. Para a candidata, a melhor saída a ser adotada é investir no planejamento familiar: – É preciso pensar em soluções como o incentivo à paternidade responsável – acredita Solange. – Além disso, vou criar um programa de atenção à saúde reprodutiva. Paulo Ramos (PDT) compartilha da mesma opinião. Apesar de ser favorável à esterilização, ele acha que uma mulher aos 18 anos é muito jovem para perder o direito de ter filhos. – Sou a favor da esterilização, mas tem de estabelecer idade mínima e número de filhos. Não pode ser aos 18 anos. É absurdo. Tem que estudar e debater com a sociedade esses limites. A cirurgia é cara

sábado, 9 de agosto de 2008

Dieta, Ferro e Pressão Arterial

Published 15 July 2008, doi:10.1136/bmj.a258Cite this as: BMJ 2008;337:a258
Research

Relation of iron and red meat intake to blood pressure: cross sectional epidemiological study
Ioanna Tzoulaki, lecturer in epidemiology1, Ian J Brown, research assistant1, Queenie Chan, senior research officer1, Linda Van Horn, professor of preventive medicine2, Hirotsugu Ueshima, professor of medicine3, Liancheng Zhao, professor of epidemiology4, Jeremiah Stamler, professor emeritus2, Paul Elliott, professor1, for the International Collaborative Research Group on Macro-/Micronutrients and Blood Pressure
Correspondence to: I Tzoulaki I.Tzoulaki@imperial.ac.uk
Objective To investigate associations of dietary iron (total, haem, and non-haem), supplemental iron, and red meat with blood pressure.
Design Cross sectional epidemiological study.
Setting 17 population samples from Japan, China, the United Kingdom, and the United States participating in the international collaborative study on macro-/micronutrients and blood pressure (INTERMAP).
Participants 4680 adults aged 40-59.
Main outcome measure Average of eight blood pressure readings.
Results In multiple linear regression analyses dietary total iron and non-haem iron were consistently inversely associated with blood pressure. With adjustment for potential non-dietary and dietary confounders, dietary total iron intake higher by 4.20 mg/4.2 MJ (2 SD) was associated with –1.39 mm Hg (P<0.01) lower systolic blood pressure. Dietary non-haem iron intake higher by 4.13 mg/4.2 MJ (2 SD) was associated with –1.45 mm Hg (P<0.001) lower systolic blood pressure. Differences were smaller for diastolic blood pressure. In most models haem iron intake from food was positively, non-significantly associated with blood pressure. Iron intake from combined diet and supplements yielded smaller associations than dietary iron alone. Red meat intake was directly associated with blood pressure; 102.6 g/24 h (2 SD) higher intake was associated with 1.25 mm Hg higher systolic blood pressure. Associations between red meat and blood pressure persisted after adjustment for multiple confounders.
Conclusion Non-haem iron has a possible role in the prevention and control of adverse blood pressure levels. An unfavourable effect of red meat on blood pressure was observed. These results need confirmation including in prospective studies, clinical trials, and from experimental evidence on possible mechanisms.

Epidemiologia das citocinas

Epidemiology of Cytokines
The Women On the Move through Activity and Nutrition (WOMAN) Study Eric Wong1, Matthew Freiberg1,2, Russell Tracy3 and Lewis Kuller1
kullerl@edc.pitt.edu
American Journal of Epidemiology 2008 168(4):443-453; doi:10.1093/aje/kwn132
Using multiplex technology, the authors investigated the laboratory and biologic variation of a panel of cytokines (interleukin (IL)-1a, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, interferon-inducible protein-10, monocyte chemoattractant protein-1, and tumor necrosis factor-) over 18 months and their relations to cardiovascular disease risk factors, hormone therapy, and weight loss. Data were obtained from the Woman On the Move through Activity and Nutrition (WOMAN) Study, a randomized clinical trial investigating the effect of nonpharmacologic interventions on subclinical atherosclerosis among overweight, postmenopausal women in Pennsylvania. The present analysis (February 2002–August 2005) comprised 290 women aged 52–62 years (mean age = 57 years). Most of the cytokines were detectable in a majority of the samples, and the between-individual biologic variation was greater than the within-individual biologic and laboratory variation. There was little association between use of hormone therapy at baseline or change in hormone therapy by 18 months and cytokine levels. Weight loss was associated with a decrease in levels of IL-1 receptor antagonist, IL-6, and C-reactive protein. The results suggest that a wide panel of cytokines may be measured simultaneously from one sample. There is large unexplained variability in cytokine levels that is probably due to genetic-environmental associations.
cytokines; hormones; inflammation; obesity; weight loss; women

sexta-feira, 8 de agosto de 2008

Demência na América Latina

The Lancet 2008; 372:464-474 DOI:10.1016/S0140-6736(08)61002-8
Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey
Prof Juan J Llibre Rodriguez MD a, Cleusa P Ferri PhD b, Daisy Acosta MD c, Mariella Guerra PhD d, Prof Yueqin Huang PhD e, Prof KS Jacob PhD f, Prof ES Krishnamoorthy PhD g, Aquiles Salas MD h, Ana Luisa Sosa MSc i, Isaac Acosta Lic i, Michael E Dewey PhD b, Ciro Gaona MD j, AT Jotheeswaran MSc g, Prof Shuran Li MD e, Diana Rodriguez PhD k, Guillermina Rodriguez Lic l, P Senthil Kumar MSW f, Adolfo Valhuerdi MD m and Prof Martin Prince MD b , for the 10/66 Dementia Research Group
Background
Studies have suggested that the prevalence of dementia is lower in developing than in developed regions. We investigated the prevalence and severity of dementia in sites in low-income and middle-income countries according to two definitions of dementia diagnosis.
Methods
We undertook one-phase cross-sectional surveys of all residents aged 65 years and older (n=14960) in 11 sites in seven low-income and middle-income countries (China, India, Cuba, Dominican Republic, Venezuela, Mexico, and Peru). Dementia diagnosis was made according to the culturally and educationally sensitive 10/66 dementia diagnostic algorithm, which had been prevalidated in 25 Latin American, Asian, and African centres; and by computerised application of the dementia criterion from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). We also compared prevalence of DSM-IV dementia in each of the study sites with that from estimates in European studies.
Findings
The prevalence of DSM-IV dementia varied widely, from 0·3% (95% CI 0·1–0·5) in rural India to 6·3% (5·0–7·7) in Cuba. After standardisation for age and sex, DSM-IV prevalence in urban Latin American sites was four-fifths of that in Europe (standardised morbidity ratio 80 [95% CI 70–91]), but in China the prevalence was only half (56 [32–91] in rural China), and in India and rural Latin America a quarter or less of the European prevalence (18 [5–34] in rural India). 10/66 dementia prevalence was higher than that of DSM-IV dementia, and more consistent across sites, varying between 5·6% (95% CI 4·2–7·0) in rural China and 11·7% (10·3–13·1) in the Dominican Republic. The validity of the 847 of 1345 cases of 10/66 dementia not confirmed by DSM-IV was supported by high levels of associated disability (mean WHO Disability Assessment Schedule II score 33·7 [SD 28·6]).
Interpretation
As compared with the 10/66 dementia algorithm, the DSM-IV dementia criterion might underestimate dementia prevalence, especially in regions with low awareness of this emerging public-health problem.