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...

Deficiency of vitamin B12 produces protean effects on the nervous system, most commonly neuropathy, myelopathy, cognitive and behavioural symptoms, and optic atrophy. Involuntary movements comprise a relatively rare manifestation of this readily treatable disorder. Both adults and infants deficient in vitamin B12 may present with chorea, tremor, myoclonus, Parkinsonism, dystonia, or a combination of these, which may precede diagnosis or become apparent only a few days after parenteral replacement therapy has begun. The pathogenesis of these movement disorders shows interesting parallels to certain neurodegenerative conditions. The clinical syndrome responds well to vitamin B12 supplementation in most cases, and an early diagnosis is essential to reverse the haematological and neurological dysfunction characteristic of this disorder. In this article, we elucidate the association of vitamin B12 deficiency with movement disorders in adults and in infants, discuss the pathogenesis of this association, review previously reported cases, and present a young adult male with severe generalized chorea that showed a salutary response to vitamin B12 supplementation.

Despite positive economic forecasts, stable democracies, and reduced regional conflicts since the turn of the century, Africa continues to be afflicted by poverty, poor infrastructure, and a massive burden of communicable diseases such as HIV, malaria, tuberculosis, and diarrheal illnesses. With the rising prevalence of chronic kidney disease and kidney failure worldwide, these factors continue to hinder the ability to provide kidney care for millions of people on the continent. The International Society of Nephrology Global Kidney Health Atlas project was established to assess the global burden of kidney disease and measure global capacity for kidney replacement therapy (dialysis and kidney transplantation). The aim of this second iteration of the International Society of Nephrology Global Kidney Health Atlas was to evaluate the availability, accessibility, affordability, and quality of kidney care worldwide. We identified several gaps

ObjectiveThe aim of this study was to report the prevalence of peritonitis and mortality in patients with end-stage kidney disease (ESKD) treated with chronic peritoneal dialysis (PD) in Africa.DesignSystematic review.SettingAfrica.ParticipantsPatients with ESKD in Africa.InterventionsPD in its varied forms.Primary and secondary outcomesPD-related peritonitis rate (primary outcome), time-to-discontinuation of PD, mortality.Data sourcesFour databases, including PubMed, Embase, Web of Science and Africa Journal Online were systematically searched from 1 January 1980 to 31 December 2019.Eligibility criteriaStudies conducted in Africa reporting peritonitis rate and mortality in patients treated with PD.Data extraction and synthesisTwo reviewers extracted and synthesised the data using Microsoft Excel. The quality of included data was also assessed.ResultsWe included 17 studies from seven African countries representing 1894 patients treated with PD. The overall median age was 41.4 years (IQR: 38.2–44.7) with a median time on PD of 18.0 months (17.0–22.6). An overall median peritonitis rate of 0.75 (0.56–2.20) episodes per patient-year (PPY) was observed and had declined with time; peritonitis rate was higher in paediatric studies than adult studies (1.78 (1.26–2.25) vs 0.63 (0.55–1.87) episodes PPY). The overall median proportion of deaths was 21.1% (16.2–25.8). Culture negative peritonitis was common in paediatric studies and studies that reported combined outcomes of continuous ambulatory PD and automated PD. Both 1-year and 2-year technique survival were low in all studies (83.6% and 53.0%, respectively) and were responsible for a high proportion of modality switch.ConclusionsOur study identifies that there is still high but declining peritonitis rates as well as low technique and patient survival in PD studies conducted in Africa. Sustained efforts should continue to mitigate factors associated with peritonitis in patients with ESKD treated with PD in Africa.PROSPERO registration numberCRD42017072966.