Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...
Key Points Question Is the prevalence of depression in pregnancy increasing across 2 generations of the Avon Longitudinal Study of Parents and Children? Findings In this 2-generation cohort study, evidence was found showing that depression in young pregnant women is higher today than in the 1990s. Meaning The findings highlight the need for increased support for young pregnant women to minimize the potentially far-reaching effects of depression on mothers, their children, and future generations.
BackgroundSome studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic-pituitary-adrenal function and potentially of stress reactivity.AimsTo investigate whether salivary cortisol, particularly the cortisol awakening response, is associated with subsequent depression in a large population cohort.MethodYoung people (aged 15 years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC) collected salivary cortisol at four time points for 3 school days. Logistic regression was used to calculate odds ratios for developing depression meeting ICD-10 criteria at 18 years.ResultsWe found no evidence for an association between salivary cortisol and subsequent depression. Odds ratios for the cortisol awakening response were 1.24 per standard deviation (95% CI 0.93-1.66, P = 0.14) before and 1.12 (95% CI 0.73-1.72, P = 0.61) after adjustment for confounding factors. There was no evidence that the other cortisol measures, including cortisol at each time point, diurnal drop and area under the curve, were associated with subsequent depression.ConclusionsOur findings do not support the hypothesis that elevated salivary cortisol increases the short-term risk of subsequent depressive illness. The results suggest that if an association does exist, it is small and unlikely to be of clinical significance.
SummaryBackgroundPrevious research has suggested that deliberate self-harm is associated with contemporary goth subculture in young people; however, whether this association is confounded by characteristics of young people, their families, and their circumstances is unclear. We aimed to test whether self-identification as a goth is prospectively associated with emergence of clinical depression and self-harm in early adulthood.MethodsWe used data from the Avon Longitudinal Study of Parents and Children, a UK community-based birth cohort of 14 541 pregnant women with expected delivery between April 1, 1991, and Dec 31, 1992. All children in the study were invited to attend yearly follow-up visits at the research clinic from age 7 years. At 15 years of age, participants reported the extent to which they self-identified as a goth. We assessed depressive mood and self-harm at 15 years with the Development and Wellbeing Assessment (DAWBA) questionnaire, and depression and self-harm at 18 years using the Clinical Interview Schedule-Revised. We calculated the prospective association between goth identification at 15 years and depression and self-harm at 18 years using logistic regression analyses.FindingsOf 5357 participants who had data available for goth self-identification, 3694 individuals also had data for depression and self-harm outcomes at 18 years. 105 (6%) of 1841 adolescents who did not self-identify as goths met criteria for depression compared with 28 (18%) of 154 who identified as goths very much; for self-harm, the figures were 189 (10%) of 1841 versus 57 (37%) of 154. We noted a dose–response association with goth self-identification both for depression and for self-harm. Compared with young people who did not identify as a goth, those who somewhat identified as being a goth were 1·6 times more likely (unadjusted odds ratio [OR] 1·63, 95% CI 1·14–2·34, p<0·001), and those who very much identified as being a goth were more than three times more likely (unadjusted OR 3·67, 2·33–4·79, p<0·001) to have scores in the clinical range for depression at 18 years; findings were similar for self-harm. Associations were not attenuated after adjustment for a range of individual, family, and social confounders.InterpretationOur findings suggest that young people identifying with goth subculture might be at an increased risk for depression and self-harm. Although our results suggest that some peer contagion operates within the goth community, our observational findings cannot be used to claim that becoming a goth increases risk of self-harm or depression. Working with young people in the goth community to identify those at increased risk of depression and self-harm and provide support might be effective.FundingWellcome Trust, Medical Research Council Programme.
Background This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization. Methods A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of <60 ml/min/1.73 m2. Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included. Results Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg/m2. Conclusions Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.
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