Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Causal and associational language in observational health research: A systematic evaluation.

This is the final version. Available from Oxford University Press via the DOI in this record. Data, data analysis code, and materials are available on the Open Science Framework project https://osf.io/jtdaz/.We estimated the degree to which language used in the high profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched and screened for 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, three reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as None (no causal implication) in 13.8%, Weak 34.2%, Moderate 33.2%, and Strong 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.Marie Skłodowska-Curie grantAustralian Research CouncilNational Institute of Mental HealthNational Institute of Mental HealthNational Institute of Biomedical Imaging and BioengineeringNational Center for Advancing Translational Sciences UCLA Clinical Translational Science InstituteBloomberg American Health InitiativeKaren Toffler Charity Trus

Self-Harm Thoughts Postpartum as a Marker for Long-Term Morbidity

Introduction: Postpartum depression predisposes to maternal affective and somatic disorders. It is important to identify which women are at an increased risk of subsequent morbidity and would benefit from an intensified follow-up. Self-harm thoughts (SHTs), with or without other depressive symptomatology, might have prognostic value for maternal health beyond the postpartum period. Aim: This study is to investigate the somatic and psychiatric morbidity of postpartum women with SHTs, with or without other depressive symptoms, over a 7-year follow-up period. Materials and methods: The subjects for this study are derived from a population-based Swedish cohort of women who gave birth at Uppsala University Hospital (May 2006–June 2007) and who answered the Edinburgh Postnatal Depression Scale (EPDS) at 5 days, 6 weeks, and 6 months postpartum. Three groups were included: women reporting SHTs (SHT group, n = 107) on item 10 of the EPDS; women reporting depressive symptoms, i.e., EPDS ≥ 12 at 6 weeks and/or 6 months postpartum, without SHTs (DEP group, n = 94); and randomly selected controls screening negatively for postpartum depression (CTL group, n = 104). The number of diagnostic codes for somatic and psychiatric morbidity according to the International Statistical Classification of Diseases and Related Health Problems system, and the number of medical interventions were retrieved from medical records over 7 years following childbirth and were used as the outcome measures, together with any prescription of antidepressants and sick leave during the follow-up. Results: The SHT group had the highest psychiatric morbidity of all groups and more somatic morbidity than controls. Affective disorders were more common in the SHT and the DEP groups compared with controls, as well as antidepressant prescriptions and sick leave. One-fifth of women with SHTs did not screen positive for depressive symptoms; nevertheless, they had more somatic and psychiatric morbidity than the control group. Conclusion: Women reporting thoughts of self-harm in the postpartum period are at an increased risk of somatic and psychiatric morbidity during a follow-up of 7 years after delivery, and this increased risk may not be fully attributed to depressive symptoms. Results underline the importance of screening for self-harm symptoms postpartum and point to a need for individualized follow-up. © Copyright © 2018 Iliadis, Skalkidou, Ranstrand, Georgakis, Axfors and Papadopoulos

Change in age distribution of COVID-19 deaths with the introduction of COVID-19 vaccination

Objectives: Most countries initially deployed COVID-19 vaccines preferentially in elderly populations. We aimed to evaluate whether population-level vaccine effectiveness is heralded by an increase in the relative proportion of deaths among non-elderly populations that were less covered by vaccination programs. Eligible data: We collected data from 40 countries on age-stratified COVID-19 deaths during the vaccination period (1/14/2021-5/31/2021) and two control periods (entire pre-vaccination period and excluding the first wave). Main outcome measures: We meta-analyzed the proportion of deaths in different age groups in vaccination versus control periods in (1) countries with low vaccination rates; (2) countries with age-independent vaccination policies; and (3) countries with standard age-dependent vaccination policies. Results: Countries that prioritized vaccination among older people saw an increasing share of deaths among 0-69 year old people in the vaccination versus the two control periods (summary proportion ratio 1.32 [95 CI% 1.24-1.41] and 1.35 [95 CI% 1.26-1.44)]. No such change was seen on average in countries with age-independent vaccination policies (1.05 [95 CI% 0.78-1.41 and 0.97 [95 CI% 0.95-1.00], respectively) and limited vaccination (0.93 [95 CI% 0.85-1.01] and 0.95 [95 CI% 0.87-1.03], respectively). Proportion ratios were associated with the difference of vaccination rates in elderly versus non-elderly people. No significant changes occurred in the share of deaths in age 0-49 among all 0-69 deaths in the vaccination versus pre-vaccination periods. Conclusions: The substantial shift in the age distribution of COVID-19 deaths in countries that rapidly implemented vaccination predominantly among elderly provides evidence for the population level-effectiveness of COVID-19 vaccination and a favorable evolution of the pandemic towards endemicity with fewer elderly deaths. Keywords: COVID-19; Death; Population data; Vaccination

Self-Harm Thoughts Postpartum as a Marker for Long-Term Morbidity

Introduction: Postpartum depression predisposes to maternal affective and somatic disorders. It is important to identify which women are at an increased risk of subsequent morbidity and would benefit from an intensified follow-up. Self-harm thoughts (SHTs), with or without other depressive symptomatology, might have prognostic value for maternal health beyond the postpartum period. Aim: This study is to investigate the somatic and psychiatric morbidity of postpartum women with SHTs, with or without other depressive symptoms, over a 7-year follow-up period. Materials and methods: The subjects for this study are derived from a population based Swedish cohort of women who gave birth at Uppsala University Hospital (May 2006-June 2007) and who answered the Edinburgh Postnatal Depression Scale (EPDS) at 5 days, 6 weeks, and 6 months postpartum. Three groups were included: women reporting SHTs (SHT group, n = 107) on item 10 of the EPDS; women reporting depressive symptoms, i.e., EPDS &gt;= 12 at 6 weeks and/or 6 months postpartum, without SHTs (DEP group, n = 94); and randomly selected controls screening negatively for postpartum depression (CTL group, n = 104). The number of diagnostic codes for somatic and psychiatric morbidity according to the International Statistical Classification of Diseases and Related Health Problems system, and the number of medical interventions were retrieved from medical records over 7 years following childbirth and were used as the outcome measures, together with any prescription of antidepressants and sick leave during the follow-up. Results: The SHT group had the highest psychiatric morbidity of all groups and more somatic morbidity than controls. Affective disorders were more common in the SHT and the DEP groups compared with controls, as well as antidepressant prescriptions and sick leave. One-fifth of women with SHTs did not screen positive for depressive symptoms; nevertheless, they had more somatic and psychiatric morbidity than the control group. Conclusion: Women reporting thoughts of self-harm in the postpartum period are at an increased risk of somatic and psychiatric morbidity during a follow-up of 7 years after delivery, and this increased risk may not be fully attributed to depressive symptoms. Results underline the importance of screening for self-harm symptoms postpartum and point to a need for individualized follow-up.Stavros I. Iliadis and Alkistis Skalkidou contributed equally to this work</p

Medical journal requirements for clinical trial data sharing: Ripe for improvement

: Florian Naudet and co-authors discuss strengthening requirements for sharing clinical trial data

Preferences for Gender Affirming Treatment and Associated Factors Among Transgender People in Sweden

Introduction Gender affirming surgery of primary and/or secondary sex characteristics has been shown to alleviate gender dysphoria. A descriptive snapshot of current treatment preferences is useful to understand the needs of the transgender population seeking health care. This study aimed to describe preferences for gender affirming treatment, and their correlates, among individuals seeking health care for gender dysphoria in Sweden after major national legislative reforms. Methods Cross-sectional study where transgender patients (n = 232) recruited from all six Gender Dysphoria centers in Sweden 2016-2019, answered a survey on treatment preferences and sociodemographic, health, and gender identity-related information during the same time-period. Factors associated with preferring top surgery (breast augmentation or mastectomy), genital surgery, and other surgery (e.g., facial surgery) were examined in univariable and multivariable regression analyses in the 197 people without prior such treatment. Main study outcomes were preferences for feminizing or masculinizing hormonal and surgical gender affirming treatment. Results The proportion among birth assigned male and assigned female patients preferring top surgery was 55.6% and 88.7%, genital surgery 88.9% and 65.7%, and other surgery (e.g., facial surgery) 85.6% and 22.5%, respectively. Almost all participants (99.1%) wanted or had already received hormonal treatment and most (96.7%) wished for some kind of surgical treatment; 55.0% wanted both top and genital surgery. Preferring a binary pronoun (he/she) and factors indicating more severe gender incongruence were associated with a greater wish for surgical treatment. Participants with somatic comorbidities were less likely to want genital surgery, while aF with lacking social support were less likely to want internal genital surgery, in the multivariable analyses. Conclusions In this sample of Swedish young adults seeking health care for gender dysphoria, preferences for treatment options varied according to perceived gender identity. Policy Implications The study findings underline the need for individualized care and flexible gender affirming treatment options. The role of somatic comorbidities should be further explored, and support should be offered to transgender people in need. There is an unmet need for facial surgery among aM

Psychometric properties and concurrent validity of the Transgender Congruence Scale (TCS) in the Swedish setting

The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n=135) and controls (n=443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD