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

Development and validation of a prediction model for adenoma detection during screening and surveillance colonoscopy with comparison to actual adenoma detection rates

OBJECTIVE: The adenoma detection rate (ADR) varies widely between physicians, possibly due to patient population differences, hampering direct ADR comparison. We developed and validated a prediction model for adenoma detection in an effort to determine if physicians' ADRs should be adjusted for patient-related factors. MATERIALS AND METHODS: Screening and surveillance colonoscopy data from the cross-sectional multicenter cluster-randomized Endoscopic Quality Improvement Program-3 (EQUIP-3) study (NCT02325635) was used. The dataset was split into two cohorts based on center. A prediction model for detection of >/=1 adenoma was developed using multivariable logistic regression and subsequently internally (bootstrap resampling) and geographically validated. We compared predicted to observed ADRs. RESULTS: The derivation (5 centers, 35 physicians, overall-ADR: 36%) and validation (4 centers, 31 physicians, overall-ADR: 40%) cohort included respectively 9934 and 10034 patients (both cohorts: 48% male, median age 60 years). Independent predictors for detection of >/=1 adenoma were: age (optimism-corrected odds ratio (OR): 1.02; 95%-confidence interval (CI): 1.02-1.03), male sex (OR: 1.73; 95%-CI: 1.60-1.88), body mass index (OR: 1.02; 95%-CI: 1.01-1.03), American Society of Anesthesiology physical status class (OR class II vs. I: 1.29; 95%-CI: 1.17-1.43, OR class >/=III vs. I: 1.57; 95%-CI: 1.32-1.86), surveillance versus screening (OR: 1.39; 95%-CI: 1.27-1.53), and Hispanic or Latino ethnicity (OR: 1.13; 95%-CI: 1.00-1.27). The model's discriminative ability was modest (C-statistic in the derivation: 0.63 and validation cohort: 0.60). The observed ADR was considerably lower than predicted for 12/66 (18.2%) physicians and 2/9 (22.2%) centers, and considerably higher than predicted for 18/66 (27.3%) physicians and 4/9 (44.4%) centers. CONCLUSION: The substantial variation in ADRs could only partially be explained by patient-related factors. These data suggest that ADR variation could likely also be due to other factors, e.g. physician or technical issues

Microdrilling Resulted in Less Subchondral Bone Destruction Than a Traditional Microfracture Awl for Articular Cartilage Defect Bone Marrow Stimulation

Purpose: The purpose of this study was to compare bone marrow stimulation using micro-computed tomography (micro-CT) analysis of an abrasion arthroplasty technique, drilling k-wire technique, traditional microfacture awl, or a microdrill instrument for subchondral bone defects. Methods: Eleven cadaveric distal femoral specimens were obtained and divided into 3 common areas of osteochondral defect: trochlea and weightbearing portions of the medial and lateral femoral condyles. Each area of interest was then denuded of cartilage using a PoweRasp and divided into quadrants. Each quadrant was assigned either a 1.6 mm Kirschner wire (k-wire), 1.25 mm microfracture awl, 1.5 mm fluted microdrill, PowerPick, or a curette (abrasion arthroplasty) to create 4 channels into the subchondral bone sing the same instrument. Subchondral bone and adjacent tissue areas were then evaluated using micro-CT to analyze adjacent bone destruction and extension into the bone marrow. Results: Overall, there was a significantly decreased area of bone destruction or compression using the microdrill (0.030 mm) as compared to the microfracture awl (0.072 mm) and k-wire (0.062 mm) (P < .05). Within the trochlea and the medial femoral condyle, there was significantly decreased bony compression with the microdrill as compared to the awl and k-wire (P < .05); however, when stratified, this was not significant among the lateral femoral condylar samples (P = .08). Conclusion: Bone marrow stimulation causes bony compression that may negatively impact subchondral bone and trabecular alignment. It is important to understand which tools used for bone marrow stimulation cause the least amount of damage to the subchondral bone. Clinical Relevance: This study demonstrates the decreased subchondral bony defects seen with the microdrill versus the traditional microfracture awl indicating that when performing bone marrow stimulation, the microdrill may be a less harmful tool to the subchondral bone