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...

Based on responses of ordering physicians, the CCP report adds meaningful new information to risk assessment for localized prostate cancer patients. Test results led to changes in treatment with reductions and increases in interventional treatment that were directionally aligned with prostate cancer risk specified by the test.

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In patients undergoing video-assisted thoracoscopic surgery, is paravertebral block (PVB) superior to epidural analgesia (EP) in terms of pain control and its postoperative complication rates? Altogether, 153 papers were found using the reporting search, of which 4 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. At present, there are a limited number of studies directly comparing pain control and postoperative outcomes between PVB and EP, and no large-scale randomized trials have been reported. Three of the 4 papers are small prospective randomized trials, with a small cohort study featuring as the final piece of literature. There is no conclusive body of evidence to recommend either route as more efficacious from a pain control perspective; one study demonstrated significantly lower levels of pain with EP (P = 0.01), with a second study demonstrating significantly better pain control with PVB (P < 0.01) and a third failing to demonstrate any significant difference (P = 0.899). The frequency of requiring supplemental analgesia was similar between the PVB and EP cohorts (56% vs 48%, P = 0.26). PVB is associated with lower rates of postoperative complications compared to EP, specifically urinary retention (64% vs 34.6%, P = 0.0036) and hypotension (32% vs 7%, P = 0.0031; 21% vs 3%, P = 0.02). In summary, PVBs appear to offer an equivalent level of analgesic effect following video-assisted thoracoscopic surgery, with a more favourable side-effect profile, compared to EP. This does need to be contextualized in light of the scarcity of published material, with the available studies each containing a small number of participants.

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