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 and purposeThere is debate as to the relative merits of unicompartmental and total knee arthroplasty (UKA, TKA). Although the designer surgeons have achieved good results with the Oxford UKA there is concern over the reproducibility of these outcomes. Therefore, we evaluated published long-term outcomes of the Oxford Phase 3 UKA.Patients and methodsWe searched databases to identify studies reporting ≥10 year outcomes of the medial Oxford Phase 3 UKA. Revision, non-revision, and re-operation rates were calculated per 100 component years (% pa).Results15 studies with 8,658 knees were included. The annual revision rate was 0.74% pa (95% CI 0.67–0.81, n = 8,406) corresponding to a 10-year survival of 93% and 15-year survival of 89%. The non-revision re-operation rate was 0.19% pa (95% CI 0.13–0.25, n = 3,482). The re-operation rate was 0.89% pa (95% CI 0.77–1.02, n = 3,482). The most common causes of revision were lateral disease progression (1.42%), aseptic loosening (1.25%), bearing dislocation (0.58%), and pain (0.57%) (n = 8,658). Average OKS scores were 40 at 10 years (n = 3,417). The incidence of medical complications was 0.83% (n = 1,443).InterpretationVery good outcomes were achieved by both designer and non-designer surgeons. The PROMs, medical complication rate, and non-revision re-operation rate were better than those found in meta-analyses and publications for TKA but the revision rate was higher. However, if failure is considered to be all re-operations and not just revisions, then the failure rate of UKA was less than that of TKA.

Liposomal bupivacaine at the surgical site does appear to reduce postoperative pain compared to placebo, however, at present the limited evidence does not demonstrate superiority to bupivacaine hydrochloride. There were no reported drug-related serious adverse events and no study withdrawals due to drug-related adverse events. Overall due to the low quality and volume of evidence our confidence in the effect estimate is limited and the true effect may be substantially different from our estimate.