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 COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44–45 weeks) between the first and second dose, and response to a third dose as a booster given 28–38 weeks after the second dose. Methods In this substudy, volunteers aged 18–55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 10 10 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44–45 weeks after first dose) or a third dose of the vaccine (28–38 weeks after second dose). Data from volunteers aged 18–55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 10 10 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov , NCT04324606 , and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov , NCT04400838 , and ISRCTN, 15281137, and both are continuing but not recruiting. Findings Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8–12 weeks: 267 [83%] of 321; 15–25 weeks: 24 [7%]; or 44–45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8–12 weeks: 115 [44%] of 261; 15–25 weeks: 116 [44%]; and 44–45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44–45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83–91·08] vs 1·75 EUs [1·60–1·93]). 32 participants received a late second dose of vaccine 44–45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525–1764] with an 8–12 week interval; 1860 EUs [917–4934] with ...

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Background: Epidural steroid injection is the most frequently performed pain procedure. This study of epidural steroid "control" injections aimed to determine whether epidural nonsteroid injections constitute a treatment or true placebo in comparison with nonepidural injections for back and neck pain treatment. Methods: This systematic review with direct and indirect meta-analyses used PubMed and EMBASE searches from inception through October 2012 without language restrictions. Study selection included randomized controlled trials with a treatment group receiving epidural injections of corticosteroids or another analgesic and study control groups receiving either an epidural injection devoid of treatment drug or a nonepidural injection. Two reviewers independently extracted data including short-term (up to 12 weeks) pain scores and pain outcomes. All reviewers evaluated studies for eligibility and quality.Results: A total of 3,641 patients from 43 studies were included in this systematic review and meta-analysis. Indirect comparisons suggested epidural nonsteroid were more likely than nonepidural injections to achieve positive outcomes (risk ratio, 2.17; 95% CI, 1.87-2.53) and provide greater pain score reduction (mean difference, −0.15; 95% CI, −0.55 to 0.25). In the very limited direct comparisons, no significant differences were noted between epidural nonsteroid and nonepidural injections for either outcome (risk ratio Conclusion: Epidural nonsteroid injections may provide improved benefit compared with nonepidural injections on some measures, though few, low-quality studies directly compared controlled treatments, and only short-term outcomes (≤12 weeks) were examined.[

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Purpose There is a lack of consensus regarding need for Venous Thrombo Embolism (VTE) prophylaxis following arthroscopic knee surgery and open soft tissue knee reconstruction. Clear cut guidelines like ones for trauma surgery and arthroplasty do not exist and the published literature is limited to case reports with a few society guidelines. Given this lack of consensus, we conducted a modified Delphi questionnaire of international experts to provide recommendations on this topic. Methods The consensus statements were generated using an anonymised 3 round modified Delphi questionnaire, sent to an international panel of 38 knee surgeons, with an 80% agreement being set as the limit for consensus. The responses were analysed using descriptive statistics with measures like mode, median and box plots. Feedback was provided to all panelists based on responses from the previous rounds to help generate the consensus. Results Six consensus statements were generated after the three rounds of Delphi. Patient factors, prolonged surgery duration and family history of thrombogenic events emerged as the main points to be taken into consideration for prophylaxis. Conclusion It was established through this study, that there exists a select group of patients undergoing arthroscopic surgery that justify the usage of VTE prophylaxis. The expert responses to most of the questions in different scenarios favoured usage of VTE prophylaxis based on patient factors like advanced age, past history of VTE, smoking, oral contraceptive use etc. Level of evidence Level V. Supplementary Information The online version contains supplementary material available at 10.1007/s00167-022-06973-w.