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...

Dietary inorganic nitrate supplementation causes physiological effects which may enhance exercise tolerance. However it is not known whether nitrate might alter cognitive function during exercise. In a double-blind, cross-over study, sixteen subjects ingested either nitrate-rich beetroot juice or a placebo and completed a continuous cycle exercise test involving 20min stages at 50% and 70% V˙O2peak and a final stage at 90% V˙O2peak until volitional exhaustion. Cognitive tasks were completed before, during and after exercise. In the dietary nitrate condition: plasma [nitrite] increased (p<0.01), systolic blood pressure decreased (p<0.05) and there was a trend for a reduced oxygen uptake at 50% V˙O2peak. Tissue oxygenation improved across exercise intensities and exercise tolerance was greater at 90% V˙O2peak (p<0.05). Rating of perceived exertion, energy levels and cognitive performance were similar between conditions with mental fatigue being evident from 70% V˙O2peak onwards (p<0.05). Dietary nitrate supplementation enhanced short-term endurance exercise performance with concomitant mental fatigue but did not improve cognitive performance post-fatigue.

Purpose:Previous literature has presented pacing data of groups of competition finalists. The aim of this study was to analyze the pacing patterns displayed by medalists and nonmedalists in international competitive 400-m swimming and 1500-m running finals.Methods:Split times were collected from 48 swimming finalists (four 100-m laps) and 60 running finalists (4 laps) in international competitions from 2004 to 2012. Using a cross-sectional design, lap speeds were normalized to whole-race speed and compared to identify variations of pace between groups of medalists and nonmedalists. Lap-speed variations relative to the gold medalist were compared for the whole field.Results:In 400-m swimming the medalist group demonstrated greater variation in speed than the nonmedalist group, being relatively faster in the final lap (P < .001; moderate effect) and slower in laps 1 (P = .03; moderate effect) and 2 (P > .001; moderate effect). There were also greater variations of pace in the 1500-m running medalist group than in the nonmedalist group, with a relatively faster final lap (P = .03; moderate effect) and slower second lap (P = .01; small effect). Swimming gold medalists were relatively faster than all other finalists in lap 4 (P = .04), and running gold medalists were relatively faster than the 5th- to 12th-placed athletes in the final lap (P = .02).Conclusions:Athletes who win medals in 1500-m running and 400-m swimming competitions show different pacing patterns than nonmedalists. End-spurtspeed increases are greater with medalists, who demonstrate a slower relative speed in the early part of races but a faster speed during the final part of races than nonmedalists.

Question: For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day noninferior to 70-90 mg/kg/day, and for 3 days noninferior to 7 days, with regard to the need for antibiotic retreatment? Findings: In this 2x2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic retreatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, respectively, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin.Meaning: Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day was noninferior to a dose of 70-90 mg/kg/day and for 3 days was noninferior to 7 days with regard to the need for later antibiotic retreatment.

The purpose of this study was to determine if inspiratory muscle training (IMT) alters the oxygen cost of breathing (Vo(2RM)) during voluntary hyperpnea. Sixteen male cyclists completed 6 wk of IMT using an inspiratory load of 50% (IMT) or 15% placebo (CON) of maximal inspiratory pressure (Pi(max)). Prior to training, a maximal incremental cycle ergometer test was performed to determine Vo(2) and ventilation (V(E)) at multiple workloads. Pre- and post-training, subjects performed three separate 4-min bouts of voluntary eucapnic hyperpnea (mimic), matching V(E) that occurred at 50, 75, and 100% of Vo(2 max). Pi(max) was significantly increased (P < 0.05) by 22.5 ± 8.7% from pre- to post-IMT and remained unchanged in the CON group. The Vo(2RM) required during the mimic trial corresponded to 5.1 ± 2.5, 5.7 ± 1.4, and 11.7% ± 2.5% of the total Vo(2) (Vo(2T)) at ventilatory workloads equivalent to 50, 75, and 100% of Vo(2 max), respectively. Following IMT, the Vo(2RM) requirement significantly decreased (P < 0.05) by 1.5% (4.2 ± 1.4% of Vo(2T)) at 75% Vo(2 max) and 3.4% (8.1 ± 3.5% of Vo(2T)) at 100% Vo(2 max). No significant changes were shown in the CON group. IMT significantly reduced the O(2) cost of voluntary hyperpnea, which suggests that a reduction in the O(2) requirement of the respiratory muscles following a period of IMT may facilitate increased O(2) availability to the active muscles during exercise. These data suggest that IMT may reduce the O(2) cost of ventilation during exercise, providing an insight into mechanism(s) underpinning the reported improvements in whole body endurance performance; however, this awaits further investigation.

BackgroundBoth fish oil and montelukast have been shown to reduce the severity of exercise-induced bronchoconstriction (EIB). The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH) in asthmatics.MethodsIn this model of EIB, twenty asthmatic subjects with documented hyperpnea-induced bronchoconstriction (HIB) entered a randomized double-blind trial. All subjects entered on their usual diet (pre-treatment, n = 20) and then were randomly assigned to receive either one active 10 mg montelukast tablet and 10 placebo fish oil capsules (n = 10) or one placebo montelukast tablet and 10 active fish oil capsules totaling 3.2 g EPA and 2.0 g DHA (n = 10) taken daily for 3-wk. Thereafter, all subjects (combination treatment; n = 20) underwent another 3-wk treatment period consisting of a 10 mg active montelukast tablet or 10 active fish oil capsules taken daily.ResultsWhile HIB was significantly inhibited (p<0.05) by montelukast, fish oil and combination treatment compared to pre-treatment, there was no significant difference (p>0.017) between treatment groups; percent fall in forced expiratory volume in 1-sec was −18.4±2.1%, −9.3±2.8%, −11.6±2.8% and −10.8±1.7% on usual diet (pre-treatment), fish oil, montelukast and combination treatment respectively. All three treatments were associated with a significant reduction (p<0.05) in FENO, exhaled breathe condensate pH and cysteinyl-leukotrienes, while the fish oil and combination treatment significantly reduced (p<0.05) urinary 9α, 11β-prostaglandin F2 after EVH compared to the usual diet; however, there was no significant difference (p>0.017) in these biomarkers between treatments.ConclusionWhile fish oil and montelukast are both effective in attenuating airway inflammation and HIB, combining fish oil with montelukast did not confer a greater protective effect than either intervention alone. Fish oil supplementation should be considered as an alternative treatment for EIB.Trial RegistrationClinicalTrials.gov NCT00676468

No abstract

These data suggest that IMT attenuates inspiratory muscle fatigue, reduces the perception of dyspnea, and increases exercise tolerance. These findings suggest that IMT may be a helpful adjunct to asthma management that has the potential to improve participation and adherence to exercise training in this group. However, the perception of breathlessness is also an important signal of bronchoconstriction, and thus, caution should be exercised if this symptom is abnormally low.