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...

AimsThe aim of this study was to compare the variability and sensitivity of impulse oscillometry (R5, X5 and RF), plethysmography (Raw and sGaw) and spirometry (FEV 1 , FVC and MMEF) in order to determine the most powerful technique for assessing bronchodilation in COPD clinical trials. MethodsTwenty-four patients with COPD had impulse oscillometry, plethysmography and spirometry measured twice 30 mins apart, to determine variability. Then ascending doses of salbutamol (20, 50, 100, 200, 400 and 800 m g) were given and the same measurements made after each dose. Significant changes greater than variability were determined for each performed measurement (expressed as mean percentage improvement with 95% CI). ResultsSignificant effects ( P < 0.05) were detected after 20 m g by X5 (18.5% CI 9.8-27.2) RF (11.1% CI 7.2-15.0) and sGaw (21.5% CI 10.1-32.9), and after 50 m g by R5 (16.7% CI 10.8-22.5) and . FEV 1 was less sensitive, detecting significant bronchodilation at 100 m g (10.2% CI 7.4-12.9). ConclusionsWe conclude that impulse oscillometry and plethysmography should be considered the preferred techniques for measuring bronchodilation in COPD clinical trials.

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Increasingly, exhaled breath condensate (EBC) is being used to sample airway fluid from the lower respiratory tract. EBC pH may be a biomarker of airway inflammation in chronic obstructive pulmonary disease (COPD). In this study, the reproducibility of EBC pH in COPD was investigated.A total of 36 COPD patients and 12 healthy nonsmoking subjects participated in several investigations: duration of argon deaeration, within-sample variability, effect of freezing, leaving samples at room temperature, nose-peg use, within-(WD) and between-day (BD) variability. Analysis of repeated measurements was performed using the Bland-Altman method with limits of agreement (LOA; mean difference¡2SD). Wider LOA indicate greater variability.EBC pH became significantly higher with argon deaeration for f5 min. Variability during sample analysis was minimal; LOA of within-sample variability, freezing for 3 months and leaving at room temperature for 3 h were -0.29-0.45, -0.37-0.42 and -0.13-0.09, respectively. In contrast, variability due to nose-peg use (LOA -1.46-1.99), WD (LOA -1.50-2.48) and BD variability (LOA -2.52-3.02) were higher in COPD. In healthy nonsmoking subjects, nose-peg use (LOA -0.27-0.23), WD (LOA -0.33-0.40) and BD variability (LOA -0.46-0.44) were more reproducible.In conclusion, the variability of exhaled breath condensate pH in chronic obstructive pulmonary disease patients is mainly due to changes in airway pH over time, which are not seen in healthy nonsmoking subjects. Reasons for these fluctuations in exhaled breath condensate pH are unclear and require further investigation.