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...

Parent carers of children with Autism Spectrum Disorder (ASD) often report increased levels of stress, depression, and anxiety. Unmet parent carer mental health needs pose a significant risk to the psychological, physical, and social well-being of the parents of the child affected by ASD and jeopardize the adaptive functioning of the family as well as the potential of the child affected by ASD. This systematic review identifies key qualities of interventions supporting the mental health of parent carers and proposes practitioner-parent carer support guidelines. A search of four databases (Medline, PubMed, PsycINFO, and Social Science Data) was conducted to identify studies that met the following criteria: (1) an intervention was delivered to parent carers of a child with ASD under the age of 18 years; (2) the research design allowed for a comparison on outcomes across groups; and (3) outcome measures of the parent carers’ mental health were used. A total of 23 studies met the inclusion criteria. A critical interpretive synthesis approach was used to produce an integrated conceptualization of the evidence. Findings suggest practitioner guidelines to support the mental health and wellbeing of parent carers should include addressing the parent’s self-perspective taking and skill for real time problem-solving.

We have tested the hypothesis that airway infiltration by inflammatory cells reflects the severity of asthma by comparing the inflammatory cell infiltrates in fatal severe asthma and in subjects with mild to moderate asthma who died of unrelated causes. Sections of lung tissue from 25 fatal asthma cases and eight asthmatics who died of unrelated causes were immunostained by monoclonal antibodies (mAbs) using streptavidin-biotin peroxidase technique. The following cells were identified: mast cells (AA1:tryptase), eosinophils (EG1:stored cationic protein and EG2: secretory form of cationic protein), monocytes/macrophages (CD68), neutrophils (elastase), CD3+ and CD8+ T cells (CD3 polyclonal Ab and CD8+ mAb, respectively). Positive cells were counted in the epithelium and airway wall. The airways were divided into two groups: larger airways with internal perimeter (Pi) > 2 mm and smaller airways with Pi < 2 mm. All airways together were studied first, followed by larger and smaller airways examined separately. The numbers of intraepithelial CD3+ T cells were significantly lower in fatal asthma than in mild-moderate asthma both when all airways were considered (0.35 versus 0.86 cells/mm, p = 0.034) and in the larger airways alone (0.08 versus 1.05 cells/mm, p = 0.039). The numbers of EG1- and EG2-positive eosinophils infiltrating the airway wall of the larger airways were greater in fatal asthma than in mild-moderate asthma (78.2 versus 22.8 cells/mm2, p = 0.012 and 138.1 versus 31.7 cells/mm2, p = 0.022). In the smaller airways no significant difference was found between the two groups. We conclude that in fatal asthma there is a redistribution of CD3+ T cells away from the epithelium and proximal enhancement of the eosinophil inflammatory infiltrate. These findings have implications for the pathophysiology of asthma that results in death.

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The prognostic significance of histologic tumor grade has been evaluated in 1537 women entered into the Ludwig Trials I-IV of adjuvant therapy for node-positive breast cancer. Tumor grade was determined on histologic review of primary tumor sections by two central review pathologists using a modification of the Bloom and Richardson grading system. The 5-year overall survival rates (+/- SE) were: Grade 1, 86% +/- 2; Grade 2, 70% +/- 2; and Grade 3, 57% +/- 2 (P less than 0.0001). This survival difference was seen in both premenopausal (P less than 0.0001) and postmenopausal (P less than 0.0001) women. Significant differences in disease-free survival (DFS) by tumor grade were also observed (P less than 0.0001). The tumor grade determined by the 75 contributing local clinic pathologists was also highly significant for predicting DFS and overall survival. Tumor grade remained a statistically significant prognostic factor for DFS (P less than 0.0001) and overall survival (P less than 0.0001) in multivariate analyses controlling for nodal status, tumor size, estrogen receptor status, menopausal status, age, peritumoral vessel invasion, and treatment assigned. In postmenopausal patients for whom adjuvant treatment was compared with no adjuvant therapy, the prognostic significance of tumor grade was modified by the effect of treatment. The presence of vessel invasion by primary tumor cells was a stronger predictor of early recurrence than was increasing tumor grade in postmenopausal patients who received no adjuvant therapy. The higher failure rates for patients with high-grade tumors was due to a larger number of failures in regional and visceral sites. Tumor grade can be determined by any pathologist and allows for selection of a subpopulation of breast cancer patients at high risk for early mortality.