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Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale. To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies. We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years. The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually. Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.

Hazard ratios for cause-specific death were calculated according to baseline diabetes status or fasting glucose level. In addition to its association with vascular disease, diabetes was associated with premature deaths from a number of diseases and disorders, independent of several major risk factors. The presence of diabetes mellitus approximately doubles the risk of a wide range of vascular diseases. 1 Evidence is also emerging that diabetes is associated with nonvascular conditions, including positive associations with certain cancers (e.g., liver cancer) and negative associations with other cancers (e.g., prostate cancer). 2 – 4 However, a joint consensus statement of the American Diabetes Association and the American Cancer Society indicated that it is unclear whether such associations are direct (e.g., due to hyperglycemia) or indirect (e.g., due to diabetes as a marker of underlying biologic factors such as insulin resistance or hyperinsulinemia that alter the risk of cancer) . . .

We tested the hypothesis that underrepresented students in active-learning classrooms experience narrower achievement gaps than underrepresented students in traditional lecturing classrooms, averaged across all science, technology, engineering, and mathematics (STEM) fields and courses. We conducted a comprehensive search for both published and unpublished studies that compared the performance of underrepresented students to their overrepresented classmates in active-learning and traditional-lecturing treatments. This search resulted in data on student examination scores from 15 studies (9,238 total students) and data on student failure rates from 26 studies (44,606 total students). Bayesian regression analyses showed that on average, active learning reduced achievement gaps in examination scores by 33% and narrowed gaps in passing rates by 45%. The reported proportion of time that students spend on in-class activities was important, as only classes that implemented high-intensity active learning narrowed achievement gaps. Sensitivity analyses showed that the conclusions are robust to sampling bias and other issues. To explain the extensive variation in efficacy observed among studies, we propose the heads-and-hearts hypothesis, which holds that meaningful reductions in achievement gaps only occur when course designs combine deliberate practice with inclusive teaching. Our results support calls to replace traditional lecturing with evidence-based, active-learning course designs across the STEM disciplines and suggest that innovations in instructional strategies can increase equity in higher education.

Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology. A genome-wide association study performed in 1,126,563 individuals identifies seven new loci associated with Alzheimer’s disease and implicates microglia and immune cells in late-onset disease.

The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Bill & Melinda Gates Foundation.

AbstractObjectiveTo evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD).DesignProspective cohort study.Setting21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China).Participants116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years.Main outcome measuresThe main outcome was development of IBD, including Crohn’s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals.ResultsParticipants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn’s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn’s disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD.ConclusionsHigher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods.Study registrationClinicalTrials.gov NCT03225586.

Bottom trawling is the most widespread human activity affecting seabed habitats. Here, we collate all available data for experimental and comparative studies of trawling impacts on whole communities of seabed macroinvertebrates on sedimentary habitats and develop widely applicable methods to estimate depletion and recovery rates of biota after trawling. Depletion of biota and trawl penetration into the seabed are highly correlated. Otter trawls caused the least depletion, removing 6% of biota per pass and penetrating the seabed on average down to 2.4 cm, whereas hydraulic dredges caused the most depletion, removing 41% of biota and penetrating the seabed on average 16.1 cm. Median recovery times posttrawling (from 50 to 95% of unimpacted biomass) ranged between 1.9 and 6.4 y. By accounting for the effects of penetration depth, environmental variation, and uncertainty, the models explained much of the variability of depletion and recovery estimates from single studies. Coupled with large-scale, high-resolution maps of trawling frequency and habitat, our estimates of depletion and recovery rates enable the assessment of trawling impacts on unprecedented spatial scales.

Objective: No recent meta-analysis has examined the effects of cognitive-behavioural therapy (CBT) for adult depression. We decided to conduct such an updated meta-analysis. Methods: Studies were identified through systematic searches in bibliographical databases (PubMed, PsycINFO, Embase, and the Cochrane library). We included studies examining the effects of CBT, compared with control groups, other psychotherapies, and pharmacotherapy. Results: A total of 115 studies met inclusion criteria. The mean effect size (ES) of 94 comparisons from 75 studies of CBT and control groups was Hedges g = 0.71 (95% CI 0.62 to 0.79), which corresponds with a number needed to treat of 2.6. However, this may be an overestimation of the true ES as we found strong indications for publication bias (ES after adjustment for bias was g = 0.53), and because the ES of higher-quality studies was significantly lower (g = 0.53) than for lower-quality studies (g = 0.90). The difference between high- and low-quality studies remained significant after adjustment for other study characteristics in a multivariate meta-regression analysis. We did not find any indication that CBT was more or less effective than other psychotherapies or pharmacotherapy. Combined treatment was significantly more effective than pharmacotherapy alone (g = 0.49). Conclusions: There is no doubt that CBT is an effective treatment for adult depression, although the effects may have been overestimated until now. CBT is also the most studied psychotherapy for depression, and thus has the greatest weight of evidence. However, other treatments approach its overall efficacy.

To clarify and quantify the influence of video game violence (VGV) on aggressive behavior, we conducted a metaanalysis of all prospective studies to date that assessed the relation between exposure to VGV and subsequent overt physical aggression. The search strategy identified 24 studies with over 17,000 participants and time lags ranging from 3 months to 4 years. The samples comprised various nationalities and ethnicities with mean ages from 9 to 19 years. For each study we obtained the standardized regression coefficient for the prospective effect of VGV on subsequent aggression, controlling for baseline aggression. VGV was related to aggression using both fixed [β = 0.113, 95% CI = (0.098, 0.128)] and random effects models [β = 0.106 (0.078, 0.134)]. When all available covariates were included, the size of the effect remained significant for both models [β = 0.080 (0.065, 0.094) and β = 0.078 (0.053, 0.102), respectively]. No evidence of publication bias was found. Ethnicity was a statistically significant moderator for the fixed-effects models (P ≤ 0.011) but not for the random-effects models. Stratified analyses indicated the effect was largest among Whites, intermediate among Asians, and nonsignificant among Hispanics. Discussion focuses on the implications of such findings for current debates regarding the effects of violent video games on physical aggression.

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1 , 2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3 – 7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease. A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.