Dealing with heterogeneity of treatment effects: is the literature up to the challenge?

<p>Abstract</p> <p>Background</p> <p>Some patients will experience more or less benefit from treatment than the averages reported from clinical trials; such variation in therapeutic outcome is termed heterogeneity of treatment effects (HTE). Identifying HTE is necessary to individualize treatment. The degree to which heterogeneity is sought and analyzed correctly in the general medical literature is unknown. We undertook this literature sample to track the use of HTE analyses over time, examine the appropriateness of the statistical methods used, and explore the predictors of such analyses.</p> <p>Methods</p> <p>Articles were selected through a probability sample of randomized controlled trials (RCTs) published in <it>Annals of Internal Medicine</it>, <it>BMJ</it>, <it>JAMA</it>, <it>The Lancet</it>, and <it>NEJM </it>during odd numbered months of 1994, 1999, and 2004. RCTs were independently reviewed and coded by two abstractors, with adjudication by a third. Studies were classified as reporting: (1) HTE analysis, utilizing a formal test for heterogeneity or treatment-by-covariate interaction, (2) subgroup analysis only, involving no formal test for heterogeneity or interaction; or (3) neither. Chi-square tests and multiple logistic regression were used to identify variables associated with HTE reporting.</p> <p>Results</p> <p>319 studies were included. Ninety-two (29%) reported HTE analysis; another 88 (28%) reported subgroup analysis only, without examining HTE formally. Major covariates examined included individual risk factors associated with prognosis, responsiveness to treatment, or vulnerability to adverse effects of treatment (56%); gender (30%); age (29%); study site or center (29%); and race/ethnicity (7%). Journal of publication and sample size were significant independent predictors of HTE analysis (p < 0.05 and p < 0.001, respectively).</p> <p>Conclusion</p> <p>HTE is frequently ignored or incorrectly analyzed. An iterative process of exploratory analysis followed by confirmatory HTE analysis will generate the data needed to facilitate an individualized approach to evidence-based medicine.</p

Análise epidemiológica do suicídio no Brasil entre 1980 e 2006 Epidemiological analysis of suicide in Brazil from 1980 to 2006

OBJETIVO: O objetivo deste estudo foi realizar uma análise epidemiológica dos índices de suicídio registrados entre 1980 e 2006 nas regiões e capitais estaduais. MÉTODO: Dados referentes à taxa de mortalidade devido ao suicídio foram coletados do Departamento de Informática do Sistema Único de Saúde. RESULTADOS: Entre 1980 e 2006, foi registrado um total de 158.952 casos de suicídio, excluindo-se os casos nos quais os indivíduos tinham menos de 10 anos de idade (n = 68). No período estudado, o índice total de suicídio cresceu de 4,4 para 5,7 mortes por 100.000 habitantes (29,5%). Os índices médios mais altos foram registrados nas regiões Sul (9,3) e Centro-Oeste (6,1). Os homens são os que têm a maior probabilidade de cometer suicídio. Os índices mais altos de suicídio foram registrados na faixa etária de 70 anos ou mais, enquanto que os maiores aumentos aconteceram na faixa etária dos 20 aos 59 anos. As principais características sociodemográficas das pessoas que cometeram suicídio durante o período estudado foram baixo nível educacional e estado civil solteiro. Os métodos mais comuns de suicídio foram por enforcamento, armas de fogo e envenenamento. CONCLUSÃO: Embora o índice brasileiro tenha crescido 29,5% em 26 anos, o índice nacional ainda é considerado baixo se comparado aos índices de suicídio mundiais (média de 4,9 por 100.000 habitantes). Os índices de suicídio nas regiões brasileiras variam muito, ou seja, estão entre 2,7 e 9,3.<br>OBJECTIVE: The objective of this study was to carry out an epidemiological analysis of the suicide rates found in Brazilian regions and state capitals between 1980 and 2006. METHOD: Data on mortality rates due to suicide were collected from the Departamento de Informática do Sistema Único de Saúde (Information Technology Department of the Brazilian Public Health System - DATASUS). RESULTS: A total of 158,952 suicide cases were registered between 1980 and 2006, excluding those cases in which the individual was less than 10 years old (n = 68). In the period under study, the total suicide rate in Brazil increased from 4.4 to 5.7 deaths per 100,000 inhabitants (29.5%). Higher average rates were found in the South (9.3) and Central-West (6.1) regions. Men were more likely to commit suicide. The highest suicide rates were found in the 70-years or above age range while the highest increases were found in the 20 to 59 year age bracket. The most dominant social-demographic characteristics of the persons who committed suicide in the period under study were low educational level and singlehood. The most common methods of suicide were hanging, fire arms and poisoning. CONCLUSION: Although in Brazil the rate increased 29.5% in 26 years, the national rate is still considered to be low when compared to worldwide suicide rates (average of 4.9 per 100,000 inhabitants). Suicide rates in Brazilian regions vary broadly, ranging from 2.7 to 9.3

Sperm production in an extremophile fish, the cave molly (Poecilia mexicana, Poeciliidae, Teleostei)

A prominent trade-off in life history theory and evolution balances the costs of reproduction with those of basic somatic needs. Hence, reproductive efforts may be reduced in environments where additional energy is required for somatic maintenance. Here, we investigated male sperm stores in Atlantic mollies (Poecilia mexicana) from a sulfidic cave and several sulfidic and non-sulfidic surface habitats. We found significant differences among populations in the number of sperm stripped per male, which was also correlated with differences in gonad weights. The largest sperm stores were detected in males from non-sulfidic surface creeks, while males from a partially sulfidic surface system had lower sperm counts, and males from completely sulfidic systems, surface as well as subterranean, had even fewer available sperm. We conclude that the extreme environmental conditions in sulfidic habitats appear to constrain male sperm production, since hydrogen sulfide as a naturally occurring toxin requires energy-demanding adaptations. Furthermore, we examined sperm counts of lab-reared cave and surface mollies in response to energy limitation. Males from stock populations were placed under high and low food treatments for a 2-week period and then stripped of sperm. Sperm counts of surface mollies tended to be reduced by low food availability, whereas sperm counts of cave mollies did not significantly vary between food treatments, which likely points towards a higher starvation resistance in cave mollies