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Concept: The Canon of Medicine

836

Background Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. Methods We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses' Health Study (1980-2010) and 42,498 men in the Health Professionals Follow-up Study (1986-2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Results During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. Conclusions In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. (Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation.).

Concepts: Medicine, Epidemiology, Disease, Diseases and disorders, Death, Hypertension, Diabetes mellitus, The Canon of Medicine

472

To the Editor: Zika virus (ZIKV) is currently spreading widely, while its clinical spectrum remains a matter of investigation. Evidence of a relationship between ZIKV infection and cerebral birth abnormalities(1),(2) is growing.(3) An increased incidence of some peripheral nervous syndromes among adults was reported during outbreaks in French Polynesia(4),(5) and Brazil,(1),(2) but no formal link with ZIKV infection was shown. We describe a case of central nervous system infection with ZIKV that was associated with meningoencephalitis in an adult. An 81-year-old man was admitted to the intensive care unit (ICU) 10 days after he had been on . . .

Concepts: AIDS, Central nervous system, Nervous system, Psychology, Brain, The Canon of Medicine, Intensive care medicine, Peripheral nervous system

420

To reanalyse SmithKline Beecham’s Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine.

Concepts: The Canon of Medicine, Systematic review, Randomized controlled trial, Avicenna, Major depressive disorder, Paroxetine, GlaxoSmithKline, Beecham

358

The predominant etiology for erectile dysfunction (ED) is vascular, but limited data are available on the role of diet. A higher intake of several flavonoids reduces diabetes and cardiovascular disease risk, but no studies have examined associations between flavonoids and erectile function.

Concepts: Medicine, Nutrition, Death, The Canon of Medicine, Obesity, Cardiovascular disease, Erectile dysfunction, Diabetic diet

328

Aging is variably but inevitably accompanied by declines in health; concomitantly, in men, circulating sex-steroid levels fall with age.(1) To what extent these two processes are causally linked and whether testosterone therapy can prevent or ameliorate important age-related problems have been major issues in men’s health. In 2003, a committee assembled by the Institute of Medicine (IOM) found a paucity of randomized, placebo-controlled clinical trials involving older men and noted a lack of definite evidence that testosterone therapy conferred benefits.(2) The committee recommended that clinical trials be initiated, first to evaluate the efficacy of testosterone supplementation in older men and . . .

Concepts: Health care, Medicine, Clinical trial, Death, The Canon of Medicine, Randomized controlled trial, Avicenna, Placebo

316

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

Concepts: Pharmacology, Nutrition, Insulin, Diabetes mellitus, The Canon of Medicine, Obesity, Randomized controlled trial, Carbohydrate

246

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

Concepts: Alzheimer's disease, Pharmacology, Medicine, Epidemiology, Clinical trial, The Canon of Medicine, Avicenna, Clinical research

240

Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS.

Concepts: Lymphocyte, Medicine, Clinical trial, The Canon of Medicine, Leukemia, Fibromyalgia, Fatigue, Chronic fatigue syndrome

199

Mortality from coronary heart disease (CHD) remains at quite notable levels. Research on the risk factors and the treatment of CHD has focused on physiological factors, but there is an increasing amount of evidence connecting mental health and personality traits to CHD, too. The data concerning the connection of CHD and dispositional optimism and pessimism as personality traits is relatively scarce. The aim of this study was to investigate the connection between optimism, pessimism, and CHD mortality.

Concepts: Psychology, Epidemiology, Death, Heart, The Canon of Medicine, Avicenna, Heart disease, Optimism

190

Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality.

Concepts: Experimental design, Epidemiology, Clinical trial, Medical statistics, The Canon of Medicine, Randomized controlled trial, Pharmaceutical industry, Clinical research