Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...

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Objectives To systematically review published studies to identify the characteristics that distinguish fractures in children resulting from abuse and those not resulting from abuse, and to calculate a probability of abuse for individual fracture types.Design Systematic review.Data sources All language literature search of Medline, Medline in Process, Embase, Assia, Caredata, Child Data, CINAHL, ISI Proceedings, Sciences Citation, Social Science Citation Index, SIGLE, Scopus, TRIP, and Social Care Online for original study articles, references, textbooks, and conference abstracts until May 2007.Study selection Comparative studies of fracture at different bony sites, sustained in physical abuse and from other causes in children <18 years old were included. Review articles, expert opinion, postmortem studies, and studies in adults were excluded.Data extraction and synthesis Each study had two independent reviews (three if disputed) by specialist reviewers including paediatricians, paediatric radiologists, orthopaedic surgeons, and named nurses in child protection. Each study was critically appraised by using data extraction sheets, critical appraisal forms, and evidence sheets based on NHS Centre for Reviews and Dissemination guidance. Meta-analysis was done where possible. A random effects model was fitted to account for the heterogeneity between studies.Results In total, 32 studies were included. Fractures resulting from abuse were recorded throughout the skeletal system, most commonly in infants (<1 year) and toddlers (between 1 and 3 years old). Multiple fractures were more common in cases of abuse. Once major trauma was excluded, rib fractures had the highest probability for abuse (0.71, 95% confidence interval 0.42 to 0.91). The probability of abuse given a humeral fracture lay between 0.48 (0.06 to 0.94) and 0.54 (0.20 to 0.88), depending on the definition of abuse used. Analysis of fracture type showed that supracondylar humeral fractures were less likely to be inflicted. For femoral fractures, the probability was between 0.28 (0.15 to 0.44) and 0.43 (0.32 to 0.54), depending on the definition of abuse used, and the developmental stage of the child was an important discriminator. The probability for skull fractures was 0.30 (0.19 to 0.46); the most common fractures in abuse and non-abuse were linear fractures. Insufficient comparative studies were available to allow calculation of a probability of abuse for other fracture types.Conclusion When infants and toddlers present with a fracture in the absence of a confirmed cause, physical abuse should be considered as a potential cause. No fracture, on its own, can distinguish an abusive from a non-abusive cause. During the assessment of individual fractures, the site, fracture type, and developmental stage of the child can help to determine the likelihood of abuse. The number of high quality comparative research studies in this field is limited, and further prospective epidemiology is indicated.