Publications

Publication selection bias undermines the systematic accumulation of evidence. To assess the extent of this problem, we survey over 68,000 meta-analyses containing over 700,000 effect size estimates from medicine (67,386/597,699), environmental sciences (199/12,707), psychology (605/23,563), and economics (327/91,421). Our results indicate that meta-analyses in economics are the most severely contaminated by publication selection bias, closely followed by meta-analyses in environmental sciences and psychology, whereas meta-analyses in medicine are contaminated the least. After adjusting for publication selection bias, the median probability of the presence of an effect decreased from 99.9% to 29.7% in economics, from 98.9% to 55.7% in psychology, from 99.8% to 70.7% in environmental sciences, and from 38.0% to 29.7% in medicine. The median absolute effect sizes (in terms of standardized mean differences) decreased from d = 0.20 to d = 0.07 in economics, from d = 0.37 to d = 0.26 in psychology, from d = 0.62 to d = 0.43 in environmental sciences, and from d = 0.24 to d = 0.13 in medicine.

Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Missed, delayed, or incorrect diagnosis can lead to inappropriate patient care, poor patient outcomes, and increased cost. This systematic review analyzed evaluations of interventions to prevent diagnostic errors. Searches used MEDLINE (1966 to October 2012), the Agency for Healthcare Research and Quality's Patient Safety Network, bibliographies, and prior systematic reviews. Studies that evaluated any intervention to decrease diagnostic errors in any clinical setting and with any study design were eligible, provided that they addressed a patient-related outcome. Two independent reviewers extracted study data and rated study quality. There were 109 studies that addressed 1 or more intervention categories: personnel changes (n = 6), educational interventions (n = 11), technique (n = 23), structured process changes (n = 27), technology-based systems interventions (n = 32), and review methods (n = 38). Of 14 randomized trials, which were rated as having mostly low to moderate risk of bias, 11 reported interventions that reduced diagnostic errors. Evidence seemed strongest for technology-based systems (for example, text message alerting) and specific techniques (for example, testing equipment adaptations). Studies provided no information on harms, cost, or contextual application of interventions. Overall, the review showed a growing field of diagnostic error research and categorized and identified promising interventions that warrant evaluation in large studies across diverse settings.

Routers built around a single-stage crossbar and a centralized scheduler do not scale, and (in practice) do not provide the throughput guarantees that network operators need to make efficient use of their expensive long-haul links. In this paper we consider how optics can be used to scale capacity and reduce power in a router. We start with the promising load-balanced switch architecture proposed by C-S. Chang. This approach eliminates the scheduler, is scalable, and guarantees 100% throughput for a broad class of traffic. But several problems need to be solved to make this architecture practical: (1) Packets can be mis-sequenced, (2) Pathological periodic traffic patterns can make throughput arbitrarily small, (3) The architecture requires a rapidly configuring switch fabric, and (4) It does not work when linecards are missing or have failed. In this paper we solve each problem in turn, and describe new architectures that include our solutions. We motivate our work by designing a 100Tb/s packet-switched router arranged as 640 linecards, each operating at 160Gb/s. We describe two different implementations based on technology available within the next three years.

Abstract ὠφελέειν, ἢ μὴ βλάπτειν (Primum non nocere) – Hιppocrates’ principle should still guide daily medical prescribing. Therefore, assessing evidence of psychopharmacologic agents’ safety and harms is essential. Randomised controlled trials (RCTs) and observational studies may provide complementary information about harms of psychopharmacologic medications from both experimental and real-world settings. It is considered that RCTs provide a better control of confounding variables, while observational studies provide evidence from larger samples, longer follow-ups, in more representative samples, which may be more reflective of real-life clinical scenarios. However, this may not always hold true. Moreover, in observational studies, safety data are poorly or inconsistently reported, precluding reliable quantitative synthesis in meta-analyses. Beyond individual studies, meta-analyses, which represent the highest level of ‘evidence’, can be misleading, redundant and of low methodological quality. Overlapping meta-analyses sometimes even reach different conclusions on the same topic. Meta-analyses should be assessed systematically. Descriptive reviews of reviews can be poorly informative. Conversely, ‘umbrella reviews’ can use a quantitative approach to grade evidence. In this editorial, we present the main factors involved in the assessment of psychopharmacologic agents’ harms from individual studies, meta-analyses and umbrella reviews. Study design features, sample size, number of the events of interest, summary effect sizes, p -values, heterogeneity, 95% prediction intervals, confounding factor adjustment and tests of bias (e.g., small-study effects and excess significance) can be combined with other assessment tools, such as AMSTAR and GRADE to create a framework for assessing the credibility of evidence.

Abstract Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10−5) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10−5; female effect = −0.007 and p = 3.3 × 10−2), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10−8) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.

Objectives Immortal time bias (ITB) occurs when a period during which, by design, participants cannot experience the outcome (like death) is incorrectly included in the treatment group’s follow-up, artificially making the treatment look better than it truly is. We aimed to identify a systematic sample of cases of ITB in the literature of studies using survival analysis and assess the impact of ITB on the results. Design Meta-epidemiological study (PROSPERO[CRD42022356073]). Setting We searched PubMed/MEDLINE, Embase and Cochrane Database of Systematic Reviews from database inception to August 2024. Systematic reviews with quantitative syntheses that allowed subgroup analysis by the presence of ITB for any available exposure-outcome pairs (‘topics’) were eligible for inclusion. Participants Participants included in the systematic reviews. Main outcome measures Information on ITB and effect sizes (ESs) with 95% confidence interval for individual studies in forest plots were extracted to run re-analysis using generic inverse variance fixed- and random-effects methods. After extracting data, we conducted subgroup analysis by the presence of ITB for all available topics and assessed the impact of ITB on the heterogeneity ( I 2 ), vulnerability of evidence (or conclusion), statistical significance of the finding, and altering ES in favour of intervention/exposure. Results The median (interquartile range (IQR)) number of studies included for a topic was 6 (4–10). Across 25 topics (including 182 studies), 44.0% of the eligible studies (80 studies) were affected by ITB. Among the 21 topics where both studies with ITB and studies without ITB were available (four topics only had studies unaffected by ITB), 57.1% (12/21) demonstrated statistically significant results only in studies with ITB ( n = 11 topics) or only in studies without ITB (one topic). In 23.8% (5/21), the overall summary results changed from statistically significant to non-statistically significant or vice versa after excluding studies with ITB. The ratio of ES – summary ES from studies with ITB relative to summary ES from studies without ITB – was 0.71 (95% CI, 0.66-0.78), suggesting that the ES from studies with ITB was larger by an average of 29% in favour of the intervention/exposure. Excluding studies involving ITB reduced between-study heterogeneity ( I 2 ) by 21.4% on average. Conclusions ITB can be common among studies in some medical areas, and its presence may substantially inflate the ESs and lead to misleading, exaggerated evidence.