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...

Background: Children comprise a large proportion of the population in sub-Saharan Africa. The burden of paediatric surgical disease exceeds available resources in Africa, potentially increasing morbidity and mortality. There are few prospective paediatric perioperative outcomes studies, especially in low-and middle-income countries (LMICs). Methods: We conducted a 14-day multicentre, prospective, observational cohort study of paediatric patients (aged <16 yrs) undergoing surgery in 43 government-funded hospitals in South Africa. The primary outcome was the incidence of in-hospital postoperative complications. Results: We recruited 2024 patients at 43 hospitals. The overall incidence of postoperative complications was 9.7% [95% confidence interval (CI): 8.4e11.0]. The most common postoperative complications were infective (7.3%; 95% CI: 6.2e8.4%). In-hospital mortality rate was 1.1% (95% CI: 0.6e1.5), of which nine of the deaths (41%) were in ASA physical status 1 and 2 patients. The preoperative risk factors independently associated with postoperative complications were ASA physcial status, urgency of surgery, severity of surgery, and an infective indication for surgery. Conclusions: The risk factors, frequency, and type of complications after paediatric surgery differ between LMICs and high-income countries. The in-hospital mortality is 10 times greater than in high-income countries. These findings

Background The prevalence of anemia in the South African pediatric surgical population is unknown. Anemia may be associated with increased postoperative complications. We are unaware of studies documenting these findings in patients in low‐ and middle‐income countries (LMICs). Aim The primary aim of this study was to describe the association between preoperative anemia and 26 defined postoperative complications, in noncardiac pediatric surgical patients. Secondary aims included describing the prevalence of anemia and risk factors for intraoperative blood transfusion. Method This was a secondary analysis of the South African Paediatric Surgical Outcomes Study, a prospective, observational surgical outcomes study. Inclusion criteria were all consecutive patients aged between 6 months and <16 years, presenting to participating centers during the study period who underwent elective and nonelective noncardiac surgery and had a preoperative hemoglobin recorded. Exclusion criteria were patients aged <6 months, undergoing cardiac surgery, or without a preoperative Hb recorded. To determine whether an independent association existed between preoperative anemia and postoperative complications, a hierarchical stepwise logistic regression was conducted. Results There were 1094 eligible patients. In children in whom a preoperative Hb was recorded 46.2% had preoperative anemia. Preoperative anemia was independently associated with an increased risk of any postoperative complication (odds ratio 2.0, 95% confidence interval: 1.3‐3.1, P = .002). Preoperative anemia (odds ratio 3.6, 95% confidence interval: 1.8‐7.1, P < .001) was an independent predictor of intraoperative blood transfusion. Conclusion Preoperative anemia had a high prevalence in a LMIC and was associated with increased postoperative complications. The main limitation of our study is the ability to generalize the results to the wider pediatric surgical population, as these findings only relate to children in whom a preoperative Hb was recorded. Prospective studies are required to determine whether correction of preoperative anemia reduces morbidity and mortality in children undergoing noncardiac surgery.

The use of modern and electronic resources is relatively common, but traditional educational resources are still preferred. This study illustrates an opportunity for greater integration of online resources and social media in educational activities to enhance multimodal and self-directed learning. Specific training in the use of these resources and how to appraise them may further improve their utility.

Background.Currently there is little information on the identification, management and outcomes of patients with sepsis in developing countries. Simple cost-effective measures such as accurate identification of patients with sepsis and early antibiotic administration are achievable targets, within reach without having to make use of unsustainable protocols constructed in developed countries. Objectives. To assess the ability of clinicians at a district-level hospital to identify and manage sepsis, and to assess patient outcome in terms of in-hospital mortality and length of hospital stay given the above management. Methods. A retrospective descriptive study design was used, analysing data from the routine burden of disease audit done on a 3-monthly basis at Karl Bremer Hospital (KBH) in the Western Cape Province, South Africa. Results. The total sample size obtained was 70 patients, of whom 18 (25.7%) had an initial triage blood pressure indicative of sepsis-induced hypotension. However, only 1 (5.5%) of these 18 patients received an initial crystalloid fluid bolus of at least 30 mL/kg. The median time that elapsed before administration of antibiotics in septic shock was 4.25 hours. Furthermore, a positive delay in antibiotic administration (p=0.0039) was demonstrated. The data also showed that 8/12 patients (66.7%) with septic shock received inappropriate amounts of fluids. The in-hospital mortality rate for sepsis was 4/24 (16.7%), for severe sepsis 11/34 (32.3%) and for septic shock a staggering 9/12 (75.0%). Conclusions. The initial classification process and management of sepsis by clinicians at KBH is flawed. This inevitably leads to an increase in in-hospital mortality.