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

Arthroscopic Double-Row Repair for Acute Proximal Detachment of the Lateral Collateral Ligament in a Complex Ankle Sprain

Management of ankle sprains is still being discussed. For athletes, recent studies recommend surgical treatment for acute grade III rupture, because of better long-term ankle stability. The purpose of this technical note is to describe the arthroscopic acute double-row repair for proximal disinsertion of collateral lateral ligament ankle. With the patient in dorsal decubitus under spinal anesthesia, the foot and ankle are extended beyond the edge of the surgical table. The anteromedial portal is created inside the anterior tibial tendon in which the arthroscope is introduced. The anterolateral approach is simulated with a needle under arthroscopic control, in front and under the tip of the lateral malleolus. The anterior talofibular ligament (ATFL) is released from the capsule with a beaver blade. The tip of the lateral malleolus is sharpened, and a soft anchor is impacted there. ATFL is caught with a Mini-Scorpio plier, a Lasso loop is performed to improve tissue grasping. The ligament is pressed against the anchor, with the foot in maximum dorsiflexion and eversion. A knotless anchor is impacted 5 mm above and with the threads of the soft anchor, creating a double-row fixation. The arthroscopic acute double-row repair for proximal desinsertion of collatéral lateral ligament ankle can be done especially for athletes

Arthroscopic Modified Broström Repair with Suture-Tape Augmentation of the Calcaneofibular Ligament for Lateral Ankle Instability

Surgical repair of acute or chronic lateral instability of the ankle may be unsuccessful in the presence of associated anterior fibulotalar ligament (AFTL) and calcaneofibular ligament (CFL) injury. This Technical Note presents an arthroscopic double-row repair technique of the AFTL associated with suture tape augmentation of the CFL. The patient is in the supine position with the ankle hanging over the edge of the surgical table. The anteromedial portal is created inside the anterior tibial tendon, and the anterolateral portal is created under arthroscopic control. The ATFL is released from the capsule with a beaver blade. The calcaneal tunnel is created percutaneously at the footprint of the CFL. A soft anchor is impacted at the tip of the lateral malleolus with thread and tape. With the foot in the neutral position, the tape is then passed into the calcaneal tunnel and attached with an interference screw to strengthen the CFL. The ATFL is grasped with a Mini-Scorpion suture passer and pressed against the anchor with the foot in neutral position. A knotless anchor is impacted 5 mm above with the threads of the soft anchor, creating double-row fixation. This technique is indicated in proximal tears of the AFTL associated with a stretched CFL

Endoscopic Transfer of Gluteus Maximus and Tensor Fascia Lata for Primary Hip Abductor Deficiency

Complete avulsion of hip abductor muscles may cause severe gait dysfunction and pain. An open surgical procedure to transfer tendons of the gluteus maximus and the tensor fasciae latae to the greater trochanter to make up for the deficient hip abductor has been proposed. The purpose of this study was to describe an endoscopic procedure to transfer gluteus maximus and the tensor fasciae latae to the greater trochanter for hip abductor deficiency

The Middle Glenohumeral Ligament Test for the Diagnosis of Subscapularis Lesions

Arthroscopy has improved the diagnosis of subscapularis tendon lesions, and the outcomes of arthroscopic repair are satisfactory. Nonetheless, the diagnosis of some partial- and full-thickness subscapularis tears remains challenging. The middle glenohumeral ligament inserts distally into the articular surface of the subscapularis tendon and can be displaced when the subscapularis tendon is torn with retraction. This article describes the middle glenohumeral ligament test, which allows retracted lesions of the subscapularis tendon to be detected even if the superior edge is visible and normally placed. In addition, it allows control of the subscapularis tendon repair

Arthroscopic Shelf Acetabuloplasty in the Treatment of Acetabular Dysplasia Combined With Cam-Type Femoroacetabular Impingement

Acetabular dysplasia is a hip condition characterized by abnormal development of the acetabulum, which can be present from birth or develop during childhood and may persist into adulthood. Mild or borderline acetabular dysplasia frequently is associated with cam-type femoroacetabular impingement in adults. Over time, the association of impingement and abnormal contact can lead to hip pain, cartilage damage, labral tears, and an increased risk of developing hip osteoarthritis. Several surgical treatments have been proposed: arthroscopic capsular plication, periacetabular osteotomy, or shelf acetabuloplasty. As mini-invasive shelf acetabuloplasty procedure has already proven its effectiveness, an arthroscopic shelf acetabuloplasty represents a less-invasive, less-risky procedure and allows during the same procedure to perform intra-articular resection of the femoral cam, labrum repair and capsular plication. This Technical Note describes an original technique of arthroscopic shelf acetabuloplasty that combines an outside-in arthroscopic approach for the intra-articular procedure (labral repair, femoroplasty, capsular plication) and an endoscopic shelf acetabulopasty with a tricortical iliac crest autograft secure with a single cannulated screw

Arthroscopic ACL Reconstruction After Failed ACL Repair

For some authors, repair of the torn anterior cruciate ligament (ACL) in selected patients can be considered a valuable surgical treatment option. One of the main advantages is that it leaves all grafts available for any type of reconstruction in case the repair fails. This Technical Note describes arthroscopic ACL reconstruction after failure of an ACL repair

Lateral Meniscus Repair Using Posterolateral Portal: Suture Hook Technique

Lateral meniscus lesions result in loss of meniscus hoop stresses and can lead to lateral compartment overload and early degenerative changes. Arthroscopic suture repair provides good long-term results. However, posterior vertical tears in the peripheral area of the meniscus can be technically challenging to resolve. This Technical Note describes the suture hook technique using an accessory posterolateral portal. We believe it is a safe, effective method for repairing full vertical tears of the lateral meniscus

Posterior Oblique Ligament Repair Concomitant to Anterior Cruciate Ligament Reconstruction

The associated lesion of the posterior oblique ligament (POL) in the setting of anterior cruciate ligament rupture is quite frequent due to the same rotational mechanism. The diagnosis of POL lesions is challenging, and physical examination is delicate; moreover, they can be easily missed on magnetic resonance imaging. Once recognized, POL lesions must be repaired to restore posteromedial corner kinematics. The aim of this Technical Note is to present a safe and effective method for POL repair in the set of an anterior cruciate ligament reconstruction