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...
Objectives To assess whether late surfactant treatment of extremely low gestational age newborn (ELGAN) infants requiring ventilation at 7–14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Study design ELGAN infants (≤ 28 0/7 weeks) who required mechanical ventilation at 7–14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide (INO) and either surfactant (calfactant/Infasurf®) or sham instillation every 1–3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, evaluated by physiologic oxygen/flow reduction. Results Between January 2010 and September 2013, 511 infants were enrolled. There were no differences between treatment groups in mean birth weight (701±164 g), gestational age (25.2±1.2 weeks), percentage <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or co-morbidities of prematurity. Survival without BPD was not different between treated vs. controls at 36 weeks PMA (31.3% vs. 31.7%; relative benefit 0.98 (95% CI: 0.75, 1.28 p=0.89) or 40 weeks (58.7% vs. 54.1%; relative benefit 1.08:0.92, 1.27 p=0.33). There were no differences between groups in serious adverse events, co-morbidities of prematurity, nor in the severity of lung disease to 36 weeks. Conclusions Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving iNO was well tolerated but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing.
Staff training, specialist equipment and new service models for the delivery of domiciliary care are required.
AMS is a common problem among adolescents. There are increasing numbers of adolescents traveling to high altitudes, and there appears to be a lack of information about the prevalence of AMS in this age group. Motivated adolescents seemed capable of self-monitoring for AMS using the Lake Louise questionnaire. Combined with an appropriate ascent profile and support, we feel this approach may contribute to safety in the mountains and merits further study.
These results emphasise the importance of ongoing inflammation in the development of BPD; ETCO levels, rather than lung function test results, were the more accurate predictor of BPD development.
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