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

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

“Digging Deeper” Advocate Researchers’ Views on Advocacy and Inclusive Research

We are the Clare Inclusive Research Group (CIRG) a group of advocates with a learning disability, funded by the Irish support agency the Brothers of Charity (B.O.C.), Clare Services. As a long-established inclusive research group we were approached to reflect on our journey as advocates and researchers. In this article we talk about our work, challenging and helping repeal discriminating Irish law regarding intimate relationships. We then talk about our understanding of advocacy and inclusive research and make recommendations to make this work more effective. Method: As a group of members of CIRG, with the coordinator of the group, we developed this article using online Zoom discussion calls to identify themes, circulating online explanations of drafts followed by Zoom reflections and finally responding to academic reviews. The direct comments made by us as advocate researchers have been retained as they were expressed. Conclusions, Limitations and recommendations: One of our team remarked “advocacy and inclusive research are twins”. We concluded that they are very close but not identical. Our work together on this article led us to create a discussion paper, Manifesto for Inclusive Research. This was adopted as a touchstone for presentations at the first webinar roundtable of the newly formed Inclusive Research IASSID Special Interest Research Group in March 2022. In it we set out guidelines for creating inclusive research which require accessible information and valuing our input in terms that match our status as experts by experience in inclusive research. We challenge academic inclusive researchers who explore the world of intellectual disability to stand shoulder to shoulder with advocate inclusive researchers. Through our work together, we aim to create more fulfilling lives for us all

“Digging Deeper” Advocate Researchers’ Views on Advocacy and Inclusive Research

We are the Clare Inclusive Research Group (CIRG) a group of advocates with a learning disability, funded by the Irish support agency the Brothers of Charity (B.O.C.), Clare Services. As a long-established inclusive research group we were approached to reflect on our journey as advocates and researchers. In this article we talk about our work, challenging and helping repeal discriminating Irish law regarding intimate relationships. We then talk about our understanding of advocacy and inclusive research and make recommendations to make this work more effective. Method: As a group of members of CIRG, with the coordinator of the group, we developed this article using online Zoom discussion calls to identify themes, circulating online explanations of drafts followed by Zoom reflections and finally responding to academic reviews. The direct comments made by us as advocate researchers have been retained as they were expressed. Conclusions, Limitations and recommendations: One of our team remarked “advocacy and inclusive research are twins”. We concluded that they are very close but not identical. Our work together on this article led us to create a discussion paper, Manifesto for Inclusive Research. This was adopted as a touchstone for presentations at the first webinar roundtable of the newly formed Inclusive Research IASSID Special Interest Research Group in March 2022. In it we set out guidelines for creating inclusive research which require accessible information and valuing our input in terms that match our status as experts by experience in inclusive research. We challenge academic inclusive researchers who explore the world of intellectual disability to stand shoulder to shoulder with advocate inclusive researchers. Through our work together, we aim to create more fulfilling lives for us all

Prophylactic biological mesh reinforcement versus standard closure of stoma site (ROCSS): a multicentre, randomised controlled trial

Background: Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site. Methods: In this randomised controlled trial (ROCSS) done in 37 hospitals across three European countries (35 UK, one Denmark, one Netherlands), patients aged 18 years or older undergoing elective ileostomy or colostomy closure were randomly assigned using a computer-based algorithm in a 1:1 ratio to either biological mesh reinforcement or closure with sutures alone (control). Training in the novel technique was standardised across hospitals. Patients and outcome assessors were masked to treatment allocation. The primary outcome measure was occurrence of clinically detectable hernia 2 years after randomisation (intention to treat). A sample size of 790 patients was required to identify a 40% reduction (25% to 15%), with 90% power (15% drop-out rate). This study is registered with ClinicalTrials.gov, NCT02238964. Findings: Between Nov 28, 2012, and Nov 11, 2015, of 1286 screened patients, 790 were randomly assigned. 394 (50%) patients were randomly assigned to mesh closure and 396 (50%) to standard closure. In the mesh group, 373 (95%) of 394 patients successfully received mesh and in the control group, three patients received mesh. The clinically detectable hernia rate, the primary outcome, at 2 years was 12% (39 of 323) in the mesh group and 20% (64 of 327) in the control group (adjusted relative risk [RR] 0·62, 95% CI 0·43–0·90; p=0·012). In 455 patients for whom 1 year postoperative CT scans were available, there was a lower radiologically defined hernia rate in mesh versus control groups (20 [9%] of 229 vs 47 [21%] of 226, adjusted RR 0·42, 95% CI 0·26–0·69; p<0·001). There was also a reduction in symptomatic hernia (16%, 52 of 329 vs 19%, 64 of 331; adjusted relative risk 0·83, 0·60–1·16; p=0·29) and surgical reintervention (12%, 42 of 344 vs 16%, 54 of 346: adjusted relative risk 0·78, 0·54–1·13; p=0·19) at 2 years, but this result did not reach statistical significance. No significant differences were seen in wound infection rate, seroma rate, quality of life, pain scores, or serious adverse events. Interpretation: Reinforcement of the abdominal wall with a biological mesh at the time of stoma closure reduced clinically detectable incisional hernia within 24 months of surgery and with an acceptable safety profile. The results of this study support the use of biological mesh in stoma closure site reinforcement to reduce the early formation of incisional hernias. Funding: National Institute for Health Research Research for Patient Benefit and Allergan