Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

DS_10.1177_0363546518759540 – Supplemental material for Open Versus Arthroscopic Latarjet Procedure for Anterior Shoulder Instability: A Systematic Review and Meta-analysis

<p>Supplemental material, DS_10.1177_0363546518759540 for Open Versus Arthroscopic Latarjet Procedure for Anterior Shoulder Instability: A Systematic Review and Meta-analysis by Eoghan T. Hurley, Daren Lim Fat, Shane K. Farrington and Hannan Mullett in The American Journal of Sports Medicine</p

Postoperative Reoperations and Complications in 32,307 Ankle Fractures With and Without Concurrent Ankle Arthroscopic Procedures in a 5-Year Period Based on a Large U.S. Healthcare Database

Residual symptoms often persist even after successful operative reduction and internal fixation (ORIF) of ankle fractures. Concurrent ankle arthroscopic procedures (CAAPs) have been proposed to improve clinical outcomes; however, a dearth of evidence is available supporting this practice. The purpose of the present study was to investigate the reoperation and complication rates after ORIF of ankle fractures with and without CAAPs. Reoperations and complications after ORIF of ankle fractures were identified using the PearlDiver database from January 2007 to December 2011. The CAAPs included bone marrow stimulation, debridement, synovectomy, and unspecified cartilage procedures. Reoperation procedures consisted of ankle fracture repeat fixation, arthroscopic procedures, osteochondral autograft transfers, and ankle arthrodesis. Of the 32,307 patients who underwent ankle fracture fixation, 248 received CAAP and 32,059 did not. No significant difference was found in the reoperation rate between the 2 groups (7.7% versus 8.6%; odds ratio 0.89; 95% confidence interval 0.55 to 1.42; p = .61). Of the 248 patients in the CAAP group, 19 (7.7%) underwent reoperation, of which 13 (68.4%) were arthroscopic debridement and 6 were either ankle refixation or osteochondral autograft transfer. For the non-CAAP group, 3021 reoperation procedures were performed, consisting of ankle refixation in 83.2%, arthroscopic procedures in 14.3%, and ankle arthrodesis in 2.5%. The complication rate in the non-CAAP group included wound dehiscence in 2.4%, wound surgery in 0.4%, deep vein thrombosis in 0.8%, and pulmonary embolism in 0.4%. No complications were detected in the CAAP group. Ankle fracture fixation with CAAPs did not increase the postoperative reoperation rate compared with ankle fracture fixation without CAAPs

Sex-Based Differences in Outcomes of Tibial Tubercle Anteromedialization.

UNLABELLED: Bulletin of the Hospital for Joint Diseases 2022;80(4):252-6252 Bloom DA, Gonzalez M, Hurley ET, Kingery MT, Carter CW, Jazrawi LM, Strauss EJ. Sex-based differences in outcomes of tibial tubercle anteromedi- alization. Bull Hosp Jt Dis. 2022;80(4):252-6. Abstract Background: Previous research has demonstrated sex- based differences in patient-reported outcomes of orthopedic surgical procedures. The hypothesis of the current study was that females would have inferior patient-reported outcomes to their male peers following a tibial tubercle anteromedial- ization (AMZ) procedure for both patellofemoral instability and cartilage defects. METHODS: Patients who had undergone AMZ for isolated osteochondral defect or patellofemoral instability with a minimum follow-up time of 1 year were identified. They were then asked to complete several patient-reported outcome questionnaires that were then statistically analyzed. RESULTS: Overall, 109 patients were included in this study. Seventy-nine patients (72.5%) were female with a mean follow-up duration of 3.4 ± 2.0 years. Forty-seven females had AMZ for patellar instability while 32 females had AMZ for osteochondral defects. There were no statistically signifi- cant differences between sexes with respect to concomitant procedures performed, visual analog scale (VAS) pain score, or patient reported outcome (PRO) scores at follow-up (p \u3e 0.05). There was no statistically significant difference with respect to outcomes between the sexes for AMZ overall and when isolating the sexes based on indication. CONCLUSION: This study demonstrates that female patients undergoing AMZ have short-term clinical and functional outcomes that are not significantly different to those reported in males

Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis

Purpose: The purpose of this systematic review is to evaluate the effects of adipose derived mesenchymal stem cells (ADSCs) in the treatment of osteoarthritis (OA) in the clinical setting. Methods: A literature search was performed in the MEDLINE, EMBASE, and The Cochrane Library Database up to January 2017 for inclusion and exclusion criteria. Criteria for inclusion were clinical studies demonstrating the effects of ADSCs on OA, and written in English. The following variables were analyzed: donor site, volume of adipose tissue, preparation of ADSCs, clinical outcomes, and complication rate. Results: Sixteen studies (knee: 14 studies, multiple joints: 1 study, ankle: 1 study) were included in this systematic review. All of the studies prepared ADSCs in the form of the stromal vascular fraction (SVF). Inconsistencies between studies were found with regards to reported clinical variability, donor sites of SVF, and reported clinical outcomes. Nine studies used either platelet-rich plasma (PRP) (7/16) or fibrin (4/16) or both PRP and Fibrin (1/16), as an adjunct at time of SVF injection. All of the studies reported an improvement in clinical outcomes with the use of SVF. Five studies reported a 90% satisfaction rate, and no study reported any complications with liposuction. Five studies reported on complications, with a 5% incidence of swelling and pain. Conclusions: This systematic review demonstrated that ADSCs are currently used in the form of SVF. While SVF may produce favorable clinical outcomes with minimal risk of side effects on osteoarthritis, the variability in the data and the use of biological adjuvants have confounded the effectiveness of ADSCs. This study will help surgeons understand the limitations in the literature on ADSCs. Level of evidence: Level IV, systematic review of level IV studies

The statistical fragility of the management options for reverse shoulder arthroplasty: a systematic review of randomized control trial with fragility analysis

Reverse shoulder arthroplasty (RSA) is used in the treatment of traumatic and arthritic pathologies, with expanding clinical indications and as a result there has been an increase in clinical research on the topic. The purpose of this study was to examine the statistical fragility of randomized control trials (RCTs) reporting outcomes from RSA. A systematic search was undertaken to find RCTs investigating RSA. The Fragility Index (FI) was calculated using Fisher’s exact test, by sequentially altering the number of events until there was a reversal of significance. The Fragility Quotient (FQ) was calculated by dividing the FI by the trial population. Each trial was assigned an overall FI and FQ calculated as the median result of its reported findings. Overall, 19 RCTs warranted inclusion in the review, representing 1146 patients, of which 41.2% were male, with a mean age of 74.2 ± 4.3 years and mean follow-up of 22.1 ± 9.9 months. The median RCT population was 59, with a median of 9 patients lost to follow-up. The median FI was 4.5, and median FQ was 0.083, indicating more patients did not complete the trial than the number of outcomes which would have to change to reverse the finding of significance. This review found that the RCT evidence for RSA management may be vulnerable to statistical fragility, with a handful of events required to reverse a finding of significance