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

Pediatric Clavicle Fractures and Congenital Pseudarthrosis Unraveled

Clavicle fractures are commonly seen in the pediatric and adolescent populations. In contrast, congenital pseudarthrosis of the clavicle is rare. Although both conditions may present with similar signs and symptoms, especially in the very young, clear differences exist. Clavicle fractures are often caused by trauma and are tender on palpation, while pseudarthrosis often presents with a painless protuberance on the clavicle, which becomes more prominent as the child grows. Its presence may only become apparent after trauma, as it is usually asymptomatic. The diagnosis is confirmed on plain radiography, which shows typical features to distinguish both entities. Both clavicle fractures and congenital pseudarthrosis are generally treated conservatively with a high success rate. Operative treatment for a fracture can be indicated in the case of an open fracture, severely displaced fracture, floating shoulder, neurovascular complications or polytrauma. Congenital pseudarthrosis requires operative treatment if the patient experiences progressive pain, functional limitation and late-onset thoracic outlet symptoms, but most operations are performed due to esthetic complaints

Pediatric Clavicle Fractures and Congenital Pseudarthrosis Unraveled

Clavicle fractures are commonly seen in the pediatric and adolescent populations. In contrast, congenital pseudarthrosis of the clavicle is rare. Although both conditions may present with similar signs and symptoms, especially in the very young, clear differences exist. Clavicle fractures are often caused by trauma and are tender on palpation, while pseudarthrosis often presents with a painless protuberance on the clavicle, which becomes more prominent as the child grows. Its presence may only become apparent after trauma, as it is usually asymptomatic. The diagnosis is confirmed on plain radiography, which shows typical features to distinguish both entities. Both clavicle fractures and congenital pseudarthrosis are generally treated conservatively with a high success rate. Operative treatment for a fracture can be indicated in the case of an open fracture, severely displaced fracture, floating shoulder, neurovascular complications or polytrauma. Congenital pseudarthrosis requires operative treatment if the patient experiences progressive pain, functional limitation and late-onset thoracic outlet symptoms, but most operations are performed due to esthetic complaints

Model development for evidence-based prioritisation of policy action on emerging chemical and microbial drinking water risks

While the burden of disease from well-studied drinking water contaminants is declining, risks from emerging chemical and microbial contaminants arise because of social, technological, demographic and climatological developments. At present, emerging chemical and microbial drinking water contaminants are not assessed in a systematic way, but reactively and incidence based. Furthermore, they are assessed separately despite similar pollution sources. As a result, risks might be addressed ineffectively. Integrated risk assessment approaches are thus needed that elucidate the uncertainties in the risk evaluation of emerging drinking water contaminants, while considering risk assessors’ values. This study therefore aimed to (1) construct an assessment hierarchy for the integrated evaluation of the potential risks from emerging chemical and microbial contaminants in drinking water and (2) develop a decision support tool, based on the agreed assessment hierarchy, to quantify (uncertain) risk scores. A multi-actor approach was used to construct the assessment hierarchy, involving chemical and microbial risk assessors, drinking water experts and members of responsible authorities. The concept of value-focused thinking was applied to guide the problem-structuring and model-building process. The development of the decision support tool was done using Decisi-o-rama, an open-source Python library. With the developed decision support tool (uncertain) risk scores can be calculated for emerging chemical and microbial drinking water contaminants, which can be used for the evidence-based prioritisation of actions on emerging chemical and microbial drinking water risks. The decision support tool improves existing prioritisation approaches as it combines uncertain indicator levels with a multi-stakeholder approach and integrated the risk assessment of chemical and microbial contaminants. By applying the concept of value-focused thinking, this study addressed difficulties in evidence-based decision-making related to emerging drinking water contaminants. Suggestions to improve the model were made to guide future research in assisting policy makers to effectively protect public health from emerging drinking water risks