Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Influence of acute endurance activity on isokinetic strength

The purpose of the investigation was to determine whether low-intensity continuous (LSD) or high-intensity interval (INT) endurance activity prior to isokinetic strength assessment reduced torques generated 0.52 rad (30°) prior to horizontal (T30). T30was measured at 10 contractile speeds (0.52-5.20 rad s-1) prior to and following the LSD and INT exercise bouts. Six males (23.2 ±3.3 yrs, 74.9 ±6.8 kg, 177.6 ±5.4 cm) with a mean peak cycle ergometer oxygen consumption (PCE VO2) of 3.85 (±0.33) Lmin-1completed 150 min cycling at 35% PCE VO2in the LSD challenge. The 5 females and 3 males (20.8 +4.6 yrs, 63.2 ±12.0 kg, 168.8 ±8.5 cm, 2.51 ±0.78 L min-1) of the INT condition completed five 5-min repetitions in which the work rate was progressively increased from 40 to 100% PCE VO2. Both the LSD and INT regimens reduced T30at all contractile speeds. The reduction in T30was similarly small for the LSD and INT conditions when expressed as percentage of preintervention values and effect sizes. Small, acute reductions in strength as a result of temporally proximal endurance activity may partially explain the inhibition in strength development that has followed some concurrent strength and endurance training investigations

Changes in surface EMG of biceps brachii with increasing velocity of eccentric contraction in women

Twelve physically active women underwent a 3-week program involving eccentric, isotonic arm flexion at 120 to 180% of their maximal isometric arm flexion strength (MVC). They then performed 5 trials at 120, 140, 160, and 180% MVC. High-speed video ascertained the mean eccentric angular velocity of each trial. Bipolar surface electrodes recorded mean integrated electromyographic activity (IEMG), mean frequency and peak amplitude of electromyographic activity (EMG), and rate of occurrence of isolated, high-amplitude spikes to identify differences in recruitment patterns at different angular velocities. A one-way MANOVA suggested that all variables responded differently to the increasing loads, thus two-way ANOVAs were conducted for each variable. Mean angular velocity increased significantly from 120 to 140% MVC and then tended to plateau. Peak amplitude was significantly greater for 120% MVC than for the 3 higher load categories. Mean IEMG, mean frequency, and rate of spike occurrence did not differ significantly across conditions. These results were equivocal as to whether there were significant differences in recruitment patterns for maximal eccentric arm flexions for speeds between 0.18 and 0.25 rad·s-1

Characteristics of titin in strength and power athletes

The purpose of this investigation was to identify characteristics of the muscle protein titin in different athletic populations with increased levels of strength and power relative to non-athletes. Subjects fell into one of four groups: (1) non-athletes (NA) (n = 5), (2) weightlifters (WL) (n = 5), (3) powerlifters (PL) (n = 5), (4) sprinters (S) (n = 5). A one repetition maximum in the squat exercise was performed to assess strength. In addition, countermovement vertical jump trials were performed to assess power capabilities. Peak power (W) was calculated for the vertical jumps from force plate measurements. From gel electrophoresis analyses of muscle samples, titin-1 (T1) and titin-2 (T2) protein bands were identified, quantified and expressed relative to each other. In addition the relative mobility (R) of T1 and T2 was determined as an estimate of molecular weight. The NA group [%T1 = 47.8 (5.1), %T2 = 52.2 (5.1), mean (SE)] had lower T1 and higher T2 percentages than WL [%T1 = 62.3 (6.6), %T2 = 3 7.7 (6.6)], PL [%T1 = 66.8 (5.0), %T2 = 33.2 (5.0)] and S [%T1 = 65.9 (4.9), %T2 = 34.1 (4.9)] groups (P ≤ 0.10, preliminary investigation into titin and exercise justifies more liberal alpha level). No significant differences were found in R of T1 or T2 between the groups. This investigation has shown that there is a differential expression of titin protein bands in competitive athletes with increased levels of strength and power in comparison to untrained non-athletic individuals. Some relationships between titin characteristics and athletic performance were observed; however, no conclusions can be made based on these data as to the contribution of titin to strength or power capabilities

Does visual-perceptual training augment the fielding performance of skilled cricketers?

This study examined the effectiveness of visual-perceptual training for improving fielding performance in cricket. Twelve highly-skilled cricket players completed a video-based decision-making test and an in-situ fielding test before and after a six-week training intervention. During this period, all participants completed the same on-field training program, but seven players completed three additional perceptual training sessions per week (TRAIN). The remaining five players acted as a control (CON). Despite no group differences at pre-test, TRAIN scored significantly higher than CON at post-test for decision accuracy within the video-based test. For the in-situ fielding test, TRAIN demonstrated greater improvements in fielding success following the intervention compared to CON. The results indicate that six weeks of on-field training combined with visual-perceptual training can lead to improvements in the fielding performance of skilled cricketers above those of on-field training alone. Findings are discussed from empirical and applied coaching perspectives