ORCID Profile
0000-0001-8496-6053
Current Organisations
University of Oxford
,
University of Bristol
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 07-2022
Publisher: National Institute for Health and Care Research
Date: 05-2023
DOI: 10.3310/MNJY9014
Abstract: Bleeding among populations undergoing percutaneous coronary intervention or coronary artery bypass grafting and among conservatively managed patients with acute coronary syndrome exposed to different dual antiplatelet therapy and triple therapy (i.e. dual antiplatelet therapy plus an anticoagulant) has not been previously quantified. The objectives were to estimate hazard ratios for bleeding for different antiplatelet and triple therapy regimens, estimate resources and the associated costs of treating bleeding events, and to extend existing economic models of the cost-effectiveness of dual antiplatelet therapy. The study was designed as three retrospective population-based cohort studies emulating target randomised controlled trials. The study was set in primary and secondary care in England from 2010 to 2017. Participants were patients aged ≥ 18 years undergoing coronary artery bypass grafting or emergency percutaneous coronary intervention (for acute coronary syndrome), or conservatively managed patients with acute coronary syndrome. Data were sourced from linked Clinical Practice Research Datalink and Hospital Episode Statistics. Coronary artery bypass grafting and conservatively managed acute coronary syndrome: aspirin (reference) compared with aspirin and clopidogrel. Percutaneous coronary intervention: aspirin and clopidogrel (reference) compared with aspirin and prasugrel (ST elevation myocardial infarction only) or aspirin and ticagrelor. Primary outcome: any bleeding events up to 12 months after the index event. Secondary outcomes: major or minor bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular events. The incidence of any bleeding was 5% among coronary artery bypass graft patients, 10% among conservatively managed acute coronary syndrome patients and 9% among emergency percutaneous coronary intervention patients, compared with 18% among patients prescribed triple therapy. Among coronary artery bypass grafting and conservatively managed acute coronary syndrome patients, dual antiplatelet therapy, compared with aspirin, increased the hazards of any bleeding (coronary artery bypass grafting: hazard ratio 1.43, 95% confidence interval 1.21 to 1.69 conservatively-managed acute coronary syndrome: hazard ratio 1.72, 95% confidence interval 1.15 to 2.57) and major adverse cardiovascular events (coronary artery bypass grafting: hazard ratio 2.06, 95% confidence interval 1.23 to 3.46 conservatively-managed acute coronary syndrome: hazard ratio 1.57, 95% confidence interval 1.38 to 1.78). Among emergency percutaneous coronary intervention patients, dual antiplatelet therapy with ticagrelor, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.06, 95% confidence interval 0.89 to 1.27). Among ST elevation myocardial infarction percutaneous coronary intervention patients, dual antiplatelet therapy with prasugrel, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.48, 95% confidence interval 1.02 to 2.12), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.10, 95% confidence interval 0.80 to 1.51). Health-care costs in the first year did not differ between dual antiplatelet therapy with clopidogrel and aspirin monotherapy among either coronary artery bypass grafting patients (mean difference £94, 95% confidence interval –£155 to £763) or conservatively managed acute coronary syndrome patients (mean difference £610, 95% confidence interval –£626 to £1516), but among emergency percutaneous coronary intervention patients were higher for those receiving dual antiplatelet therapy with ticagrelor than for those receiving dual antiplatelet therapy with clopidogrel, although for only patients on concurrent proton pump inhibitors (mean difference £1145, 95% confidence interval £269 to £2195). This study suggests that more potent dual antiplatelet therapy may increase the risk of bleeding without reducing the incidence of major adverse cardiovascular events. These results should be carefully considered by clinicians and decision-makers alongside randomised controlled trial evidence when making recommendations about dual antiplatelet therapy. The estimates for bleeding and major adverse cardiovascular events may be biased from unmeasured confounding and the exclusion of an eligible subgroup of patients who could not be assigned an intervention. Because of these limitations, a formal cost-effectiveness analysis could not be conducted. Future work should explore the feasibility of using other UK data sets of routinely collected data, less susceptible to bias, to estimate the benefit and harm of antiplatelet interventions. This trial is registered as ISRCTN76607611. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 27, No. 8. See the NIHR Journals Library website for further project information.
Publisher: BMJ
Date: 20-07-2022
Abstract: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) covid-19 vaccines against infection and covid-19 disease in health and social care workers. Cohort study, emulating a comparative effectiveness trial, on behalf of NHS England. Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 Alpha variant was dominant. 317 341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a general practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable. Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national covid-19 vaccine roll-out. Recorded SARS-CoV-2 positive test, or covid-19 related attendance at an accident and emergency (A& E) department or hospital admission occurring within 20 weeks of receipt of the first vaccine dose. Over the duration of 118 771 person-years of follow-up there were 6962 positive SARS-CoV-2 tests, 282 covid-19 related A& E attendances, and 166 covid-19 related hospital admissions. The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks after vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 20 weeks after first-dose vaccination with BNT162b2 was 21.7 per 1000 people (95% confidence interval 20.9 to 22.4) and with ChAdOx1 was 23.7 (21.8 to 25.6), representing a difference of 2.04 per 1000 people (0.04 to 4.04). The difference in the cumulative incidence per 1000 people of covid-19 related A& E attendance at 20 weeks was 0.06 per 1000 people (95% CI −0.31 to 0.43). For covid-19 related hospital admission, this difference was 0.11 per 1000 people (−0.22 to 0.44). In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or covid-19 disease up to 20 weeks after vaccination. Incidence dropped sharply at 3-4 weeks after vaccination, and there were few covid-19 related hospital attendance and admission events after this period. This is in line with expected onset of vaccine induced immunity and suggests strong protection against Alpha variant covid-19 disease for both vaccines in this relatively young and healthy population of healthcare workers.
Publisher: Cold Spring Harbor Laboratory
Date: 05-01-2023
DOI: 10.1101/2023.01.04.22283762
Abstract: Quantifying the waning effectiveness of second COVID-19 vaccination beyond six months and against the omicron variant is important for scheduling subsequent doses. With the approval of NHS England, we estimated effectiveness up to one year after second dose, but found that bias in such estimates may be substantial.
Publisher: Oxford University Press (OUP)
Date: 08-07-2008
DOI: 10.1111/J.1467-985X.2008.00548.X
Abstract: We present models for the combined analysis of evidence from randomized controlled trials categorized as being at either low or high risk of bias due to a flaw in their conduct. We formulate a bias model that incorporates between-study and between-meta-analysis heterogeneity in bias, and uncertainty in overall mean bias. We obtain algebraic expressions for the posterior distribution of the bias-adjusted treatment effect, which provide limiting values for the information that can be obtained from studies at high risk of bias. The parameters of the bias model can be estimated from collections of previously published meta-analyses. We explore alternative models for such data, and alternative methods for introducing prior information on the bias parameters into a new meta-analysis. Results from an illustrative ex le show that the bias-adjusted treatment effect estimates are sensitive to the way in which the meta-epidemiological data are modelled, but that using point estimates for bias parameters provides an adequate approximation to using a full joint prior distribution. A sensitivity analysis shows that the gain in precision from including studies at high risk of bias is likely to be low, however numerous or large their size, and that little is gained by incorporating such studies, unless the information from studies at low risk of bias is limited. We discuss approaches that might increase the value of including studies at high risk of bias, and the acceptability of the methods in the evaluation of health care interventions.
Publisher: American Medical Association (AMA)
Date: 06-10-2020
Publisher: Wiley
Date: 06-04-2006
DOI: 10.1111/J.1541-0420.2006.00561.X
Abstract: In the regression analysis of clustered data it is important to allow for the possibility of distinct between- and within-cluster exposure effects on the outcome measure, represented, respectively, by regression coefficients for the cluster mean and the deviation of the in idual-level exposure value from this mean. In twin data, the within-pair regression effect represents association conditional on exposures shared within pairs, including any common genetic or environmental influences on the outcome measure. It has therefore been proposed that a comparison of the within-pair regression effects between monozygous (MZ) and dizygous (DZ) twins can be used to examine whether the association between exposure and outcome has a genetic origin. We address this issue by proposing a bivariate model for exposure and outcome measurements in twin-pair data. The between- and within-pair regression coefficients are shown to be weighted averages of ratios of the exposure and outcome variances and covariances, from which it is straightforward to determine the conditions under which the within-pair regression effect in MZ pairs will be different from that in DZ pairs. In particular, we show that a correlation structure in twin pairs for exposure and outcome that appears to be due to genetic factors will not necessarily be reflected in distinct MZ and DZ values for the within-pair regression coefficients. We illustrate these results in a study of female twin pairs from Australia and North America relating mammographic breast density to weight and body mass index.
Publisher: BMJ
Date: 06-2019
DOI: 10.1136/BMJOPEN-2019-029388
Abstract: ‘Real world’ bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified. We will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three ‘target trials’ in patient groups: percutaneous coronary intervention (PCI) coronary artery bypass grafting (CABG) conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event no prescription for DAPT or anticoagulants in the preceding 3 months a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study’s main limitation—that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD. This protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders. 76607611 Pre-results.
Publisher: Cold Spring Harbor Laboratory
Date: 06-06-2022
DOI: 10.1101/2022.06.06.22276026
Abstract: The UK COVID-19 vaccination programme delivered its first “booster” doses in September 2021, initially in groups at high risk of severe disease then across the adult population. The BNT162b2 Pfizer-BioNTech vaccine was used initially, with Moderna mRNA-1273 subsequently also used. We used the OpenSAFELY-TPP database, covering 40% of English primary care practices and linked to national coronavirus surveillance, hospital episodes, and death registry data, to estimate the effectiveness of boosting with BNT162b2 compared with no boosting in eligible adults who had received two primary course vaccine doses between 16 September and 16 December 2021 when the Delta variant of SARS-CoV-2 was dominant. Follow up was for up to 10 weeks. Each booster recipient was matched with an unboosted control on factors relating to booster priority status and prior immunisation. Additional factors were adjusted for in Cox models estimating hazard ratios (HRs). Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, COVID-19 death and non-COVID-9 death. Booster vaccine effectiveness was defined as 1−HR. Among 4,352,417 BNT162b2 booster recipients matched with unboosted controls, estimated effectiveness of a booster dose compared with two doses only was 50.7% (95% CI 50.1-51.3) for positive SARS-CoV-2 test, 80.1% (78.3-81.8) for COVID-19 hospitalisation, 88.5% (85.0-91.1) for COVID-19 death, and 80.3% (79.0-81.5) for non-COVID-19 death. Estimated effectiveness was similar among those who had received a BNT162b2 or ChAdOx1-S two-dose primary vaccination course, but effectiveness against severe COVID-19 was slightly lower in those classified as clinically extremely vulnerable (76.3% (73.1-79.1) for COVID-19 hospitalisation, and 85.1% (79.6-89.1) for COVID-19 death). Estimated effectiveness against each outcome was lower in those aged 18-65 years than in those aged 65 and over. Our findings are consistent with strong protection of BNT162b2 boosting against positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death.
Publisher: American College of Physicians
Date: 16-12-2008
Publisher: Cold Spring Harbor Laboratory
Date: 08-09-2023
Publisher: BMJ
Date: 15-12-2006
Publisher: National Institute for Health and Care Research
Date: 12-2009
DOI: 10.3310/HTA13600
Abstract: To determine the diagnostic performance and cost-effectiveness of colour vision testing (CVT) to identify and monitor the progression of diabetic retinopathy (DR). Major electronic databases including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Database of Systematic Reviews were searched from inception to September 2008. A systematic review of the evidence was carried out according to standard methods. An online survey of National Screening Programme for Diabetic Retinopathy (NSPDR) clinical leads and programme managers assessed the diagnostic tools used routinely by local centres and their views on future research priorities. A decision tree and Markov model was developed to estimate the incremental costs and effects of adding CVT to the current NSPDR. In total, 25 studies on CVT met the inclusion criteria for the review, including 18 presenting 2 x 2 diagnostic accuracy data. The quality of studies and reporting was generally poor. Automated or computerised CVTs reported variable sensitivities (63-97%) and specificities (71-95%). One study reported good diagnostic accuracy estimates for computerised CVT plus retinal photography for detection of sight-threatening DR, but it included few cases of retinopathy in total. Results for pseudoisochromatic plates, anomaloscopes and colour arrangement tests were largely inadequate for DR screening, with Youden indices (sensitivity + specificity - 100%) close to zero. No studies were located that addressed patient preferences relating to CVT for DR. Retinal photography is universally employed as the primary method for retinal screening by centres responding to the online survey none used CVT. The review of the economic evaluation literature found no previous studies describing the cost and effects of any type of CVT. Our economic evaluation suggested that adding CVT to the current national screening programme could be cost-effective if it adequately increases sensitivity and is relatively inexpensive. The deterministic base-case analysis indicated that the cost per quality-adjusted life-year gained may be 6364 pounds and 12,432 pounds for type 1 and type 2 diabetes respectively. However, probabilistic sensitivity analysis highlighted the substantial probability that CVT is not diagnostically accurate enough to be either an effective or a cost-effective addition to current screening methods. The results of the economic model should be treated with caution as the model is based on only one small study. There is insufficient evidence to support the use of CVT alone, or in combination with retinal photography, as a method for screening for retinopathy in patients with diabetes. Better quality diagnostic accuracy studies directly comparing the incremental value of CVT in addition to retinal photography are needed before drawing conclusions on cost-effectiveness. The most frequently cited preference for future research was the use of optical coherence tomography for the detection of clinically significant macular oedema.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2011
Publisher: Elsevier BV
Date: 08-2017
Publisher: Elsevier BV
Date: 08-2012
Publisher: Public Library of Science (PLoS)
Date: 09-09-2014
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2023
DOI: 10.1101/2023.05.12.23289914
Abstract: The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment. With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk in iduals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models. Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81 .22) [BA.1] and 1.22 (0.96 .56) [BA.2] corresponding HRs for sotrovimab versus untreated were 0.76 (0.66 .89) [BA.1] and 0.92 (0.79 .06) [BA.2]. Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period. UKRI, Wellcome Trust, MRC, NIHR and HDRUK.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2020
DOI: 10.1186/S13063-020-04641-3
Abstract: Primary objective: To estimate the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization. Secondary objectives: To examine whether the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization varies between subgroups related to treatment characteristics, disease severity at the time of randomization, patient characteristics, or risk of bias. To examine the effect of corticosteroids compared with usual care or placebo on serious adverse events. Prospective meta-analysis of randomized controlled trials. Both placebo-controlled and open-label trials are eligible. Hospitalised, critically ill patients with suspected or confirmed COVID-19. Intervention groups will have received therapeutic doses of a steroid (dexamethasone, hydrocortisone or methylprednisolone) with IV or oral administration immediately after randomization. The comparator groups will have received standard of care or usual care or placebo. All-cause mortality up to 28 days after randomization. Systematic searching of clinicaltrials.gov , EudraCT, the WHO ISRCTN registry, and the Chinese clinical trials registry. Additionally, research and WHO networks will be asked for relevant trials. These will be based on the Cochrane RoB 2 tool, and will use structured information provided by the trial investigators on a form designed for this prospective meta-analysis. We will use GRADE to assess the certainty of the evidence. Trial investigators will provide data on the numbers of participants who did and did not experience each outcome according to intervention group, overall and in specified subgroups. We will conduct fixed-effect (primary analysis) and random-effects (Paule-Mandel estimate of heterogeneity and Hartung-Knapp adjustment) meta-analyses. We will quantify inconsistency in effects between trials using I 2 statistics. Evidence for subgroup effects will be quantified by ratios of odds ratios comparing effects in the subgroups, and corresponding interaction p-values. Comparisons between subgroups defined by trial characteristics will be made using random-effects meta-regression. Comparisons between subgroups defined by patient characteristics will be made by estimating trial-specific ratios of odds ratios comparing intervention effects between subgroups then combining these using random-effects meta-analysis. Steroid interventions will be classified as high or low dose according to whether the dose is greater or less than or equal to 400 mg hydrocortisone per day or equivalent. We will use network meta-analysis methods to make comparisons between the effects of high and low dose steroid interventions (because one trial randomized participants to both low and high dose steroid arms). CRD42020197242 The full protocol for this prospective meta-analysis is attached as an additional file, accessible from the Trials website (Additional file 1). To expedite dissemination of this material, the familiar formatting has been eliminated this Letter serves as a summary of the key elements of the full protocol for the systematic review.
Publisher: Wiley
Date: 07-08-2011
Publisher: Wiley
Date: 19-07-2004
DOI: 10.1002/SIM.1825
Abstract: The process of developing and validating a prognostic model for survival time data has been much discussed in the literature. Assessment of the performance of candidate prognostic models on data other than that used to fit the models is essential for choosing a model that will generalize well to independent data. However, there remain difficulties in current methods of measuring the accuracy of predictions of prognostic models for censored survival time data. In this paper, flexible parametric models based on the Weibull, loglogistic and lognormal distributions with spline smoothing of the baseline log cumulative hazard function are used to fit a set of candidate prognostic models across k data sets. The model that generalizes best to new data is chosen using a cross-validation scheme which fits the model on k-1 data sets and tests the predictive accuracy on the omitted data set. The procedure is repeated, omitting each data set in turn. The quality of the predictions is measured using three different methods: two commonly proposed validation methods, Harrell's concordance statistic and the Brier statistic, and a novel method using deviance differences. The results show that the deviance statistic is able to discriminate between quite similar models and can be used to choose a prognostic model that generalizes well to new data. The methods are illustrated by using a model developed to predict progression to a new AIDS event or death in HIV-1 positive patients starting antiretroviral therapy.
Publisher: American Medical Association (AMA)
Date: 27-09-2023
Publisher: BMJ
Date: 29-06-2009
DOI: 10.1136/BMJ.B2393
Publisher: Oxford University Press (OUP)
Date: 18-04-2013
DOI: 10.1093/IJE/DYT010
Publisher: Oxford University Press (OUP)
Date: 08-07-2010
DOI: 10.1093/AJE/KWQ137
Abstract: Multiple imputation is increasingly recommended in epidemiology to adjust for the bias and loss of information that may occur in analyses restricted to study participants with complete data ("complete-case analyses"). However, little guidance is available on applying the method, including which variables to include in the imputation model and the number of imputations needed. Here, the authors used multiple imputation to analyze the prevalence of wheeze among 81-month-old children in the Avon Longitudinal Study of Parents and Children (Avon, United Kingdom 1991-1999) and the association of wheeze with gender, maternal asthma, and maternal smoking. The authors examined how inclusion of different types of variables in the imputation model affected point estimates and precision, and assessed the impact of number of imputations on Monte Carlo variability. Inclusion of variables associated with the outcome in the imputation model increased odds ratios and reduced standard errors. When only 5 or 10 imputations were used, variability due to the imputation procedure was substantial enough to affect conclusions. Careful preliminary analysis identified the scope for multiple imputation to reduce bias and improve efficiency and provided guidance for building the imputation model. When data are missing, such preliminary analyses should be routinely undertaken and reported, regardless of whether multiple imputation is used in the final analysis.
Publisher: BMJ
Date: 22-07-2011
DOI: 10.1136/BMJ.D4002
Publisher: BMJ
Date: 20-07-2022
Abstract: To estimate waning of covid-19 vaccine effectiveness over six months after second dose. Cohort study, approved by NHS England. Linked primary care, hospital, and covid-19 records within the OpenSAFELY-TPP database. Adults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals. People who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks. Adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged ≥65 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years. 1 951 866 and 3 219 349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2 422 980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the ≥65 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24) to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness ≥80% for BNT162b2, and ≥75% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1). The rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-05-2007
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2022
DOI: 10.1101/2022.07.29.22278186
Abstract: The COVID-19 booster vaccination programme in England used both BNT162b2 and mRNA-1273 vaccines. Direct comparisons of the effectiveness against severe COVID-19 of these two vaccines for boosting have not been made in trials or observational data. On behalf of NHS England, we used the OpenSAFELY-TPP database to match adult recipients of each vaccine type on date of vaccination, primary vaccine course, age, and other characteristics. Recipients were eligible if boosted between 29 October 2021 and 31 January 2022, and followed up for 12 weeks. Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death. We estimated the cumulative incidence of each outcome, and quantified comparative effectiveness using risk differences (RD) and hazard ratios (HRs). 1,528,431 people were matched in each group, contributing a total 23,150,504 person-weeks of follow-up. The 12-week risks per 1,000 people of positive SARS-CoV-2 test were 103.2 (95%CI 102.4 to 104.0) for BNT162b2 and 96.0 (95.2 to 96.8) for mRNA-1273: the HR comparing mRNA-1273 with BNT162b2 was 0.92 (95%CI 0.91 to 0.92). For COVID-19 hospitalisations the 12-week risks per 1,000 were 0.65 (95%CI 0.56 to 0.75) and 0.44 (0.36 to 0.54): HR 0.67 (95%CI 0.58 to 0.78). COVID-19 deaths were rare: the 12-week risks per 1,000 were 0.03 (95%CI 0.02 to 0.06) and 0.01 (0.01 to 0.02): HR 1.23 (95%CI 0.59 to 2.56). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, prior SARS-CoV-2 infection and clinical vulnerability. Booster vaccination with mRNA-1273 COVID-19 vaccine was more effective than BNT162b2 in preventing SARS-CoV-2 infection and COVID-19 hospitalisation during the first 12 weeks after vaccination, during a period of Delta followed by Omicron variant dominance.
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1093/BJA/AEL256
Abstract: Postoperative vomiting (POV) remains one of the commonest causes of significant morbidity after tonsillectomy in children. A variety of prophylactic anti-emetic interventions have been reported, but there has only been a limited systematic review in this patient group. A systematic search was performed by using Cochrane Controlled Trials Register, MEDLINE and EMBASE to identify double-blind, randomized, placebo-controlled trials of prophylactic anti-emetic interventions in children undergoing tonsillectomy, with or without adenoidectomy. The outcome of interest was POV in the first 24 h. Summary estimates of the effect of each prophylactic anti-emetic strategy were derived using fixed effect meta-analysis. Where appropriate, dose-response effects were estimated using logistic regression and 22 articles were identified. Good evidence was found for the prophylactic anti-emetic effect of dexamethasone [odds ratio (OR) 0.23, 95% CI 0.16-0.33], and the serotinergic antagonists ondansetron (OR 0.36, 95% CI 0.29-0.46), granisetron (OR 0.11, 95% CI 0.06-0.19), tropisetron (OR 0.15, 95% CI 0.06-0.35) and dolasetron (OR 0.25, 95% CI 0.1-0.59). Metoclopramide was also found to be efficacious (OR 0.51, 95% CI 0.34-0.77). There is not sufficient evidence to suggest that dimenhydrinate, perphenazine or droperidol, in the doses studied, are efficacious, nor were gastric aspiration or acupuncture. In conclusion, dexamethasone and the anti-serotinergic agents appear to be the most effective agents for the prophylaxis for POV in children undergoing tonsillectomy.
Publisher: Mary Ann Liebert Inc
Date: 2008
Abstract: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection to describe the clinical characteristics of women and men receiving HAART. The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. Twenty-nine centers in 13 countries participated. Among 33,164 in iduals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.
Publisher: Springer Science and Business Media LLC
Date: 12-11-2020
DOI: 10.1038/S41467-020-19478-2
Abstract: Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets s led from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, we highlight the challenge of interpreting observational evidence from such non-representative s les. Collider bias can induce associations between two or more variables which affect the likelihood of an in idual being s led, distorting associations between these variables in the s le. Analysing UK Biobank data, compared to the wider cohort the participants tested for COVID-19 were highly selected for a range of genetic, behavioural, cardiovascular, demographic, and anthropometric traits. We discuss the mechanisms inducing these problems, and approaches that could help mitigate them. While collider bias should be explored in existing studies, the optimal way to mitigate the problem is to use appropriate s ling strategies at the study design stage.
Publisher: American College of Physicians
Date: 05-2023
DOI: 10.7326/M21-4269
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-10-2004
DOI: 10.1161/01.CIR.0000145165.80130.B5
Abstract: Background— We examined the associations of a range of parental and early life characteristics with systolic blood pressure at 5 years of age. Methods and Results— Information from 3864 children who were followed up prospectively from their mother’s first antenatal clinic assessment was used. Maternal age, body mass index, and smoking during pregnancy were all positively associated with offspring systolic blood pressure at 5 years of age. The systolic blood pressure of children whose mothers had smoked throughout pregnancy was on average 0.92 mm Hg (95% CI 0.17 to 1.68) greater than that of children whose mothers had never smoked, after full adjustment. Children who had been breast fed until at least 6 months had lower systolic blood pressure than those who were breast fed for a shorter duration. Paternal body mass index and child’s weight, height, and body mass index were all positively associated with blood pressure at age 5. Conclusions— Because childhood blood pressure tracks into adulthood, interventions aimed at early life risk factors, such as quitting smoking during pregnancy, breast feeding, and prevention of obesity in all family members, may be important for reducing the population distribution of blood pressure and thus cardiovascular disease risk.
Publisher: Cold Spring Harbor Laboratory
Date: 18-10-2021
DOI: 10.1101/2021.10.13.21264937
Abstract: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines against infection and COVID-19 disease in health and social care workers. Cohort study, emulating a comparative effectiveness trial. Linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform. 317,341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a GP practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable. Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national COVID-19 vaccine roll-out. Recorded SARS-CoV-2 positive test, or COVID-19 related Accident and Emergency attendance or hospital admission occurring within 20 weeks of vaccination. The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks post-vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 6 weeks after vaccination with BNT162b2 was 19.2 per 1000 people (95%CI 18.6 to 19.7) and with ChAdOx1 was 18.9 (95%CI 17.6 to 20.3), representing a difference of -0.24 per 1000 people (95%CI -1.71 to 1.22). The difference in the cumulative incidence per 1000 people of COVID-19 accident and emergency attendance at 6 weeks was 0.01 per 1000 people (95%CI -0.27 to 0.28). For COVID-19 hospital admission, this difference was 0.03 per 1000 people (95%CI -0.22 to 0.27). In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.
Publisher: BMJ
Date: 09-2023
Publisher: Public Library of Science (PLoS)
Date: 07-2014
Publisher: American Medical Association (AMA)
Date: 10-08-2021
Publisher: Oxford University Press (OUP)
Date: 15-05-2010
DOI: 10.1086/652283
Publisher: BMJ
Date: 12-10-2016
DOI: 10.1136/BMJ.I4919
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2011
Publisher: Cold Spring Harbor Laboratory
Date: 23-03-2022
DOI: 10.1101/2022.03.23.22272804
Abstract: The rate at which COVID-19 vaccine effectiveness wanes over time is crucial for vaccination policies, but is incompletely understood with conflicting results from different studies. This cohort study, using the OpenSAFELY-TPP database and approved by NHS England, included in iduals without prior SARS-CoV-2 infection assigned to vaccines priority groups 2-12 defined by the UK Joint Committee on Vaccination and Immunisation. We compared in iduals who had received two doses of BNT162b2 or ChAdOx1 with unvaccinated in iduals during six 4-week comparison periods, separately for subgroups aged 65+ years 16-64 years and clinically vulnerable 40-64 years and 18-39 years. We used Cox regression, stratified by first dose eligibility and geographical region and controlled for calendar time, to estimate adjusted hazard ratios (aHRs) comparing vaccinated with unvaccinated in iduals, and quantified waning vaccine effectiveness as ratios of aHRs per-4-week period. The outcomes were COVID-19 hospitalisation, COVID-19 death, positive SARS-CoV-2 test, and non-COVID-19 death. The BNT162b2, ChAdOx1 and unvaccinated groups comprised 1,773,970, 2,961,011 and 2,433,988 in iduals, respectively. Waning of vaccine effectiveness was similar across outcomes and vaccine brands: e.g. in the 65+ years subgroup ratios of aHRs versus unvaccinated for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test ranged from 1.23 (95% CI 1.15-1.32) to 1.27 (1.20-1.34) for BNT162b2 and 1.16 (0.98-1.37) to 1.20 (1.14-1.27) for ChAdOx1. Despite waning, rates of COVID-19 hospitalisation and COVID-19 death were substantially lower among vaccinated in iduals compared to unvaccinated in iduals up to 26 weeks after second dose, with estimated aHRs .20 ( % vaccine effectiveness) for BNT162b2, and .26 ( %) for ChAdOx1. By weeks 23-26, rates of SARS-CoV-2 infection in fully vaccinated in iduals were similar to or higher than those in unvaccinated in iduals: aHRs ranged from 0.85 (0.78-0.92) to 1.53 (1.07-2.18) for BNT162b2, and 1.21 (1.13-1.30) to 1.99 (1.94-2.05) for ChAdOx1. The rate at which estimated vaccine effectiveness waned was strikingly consistent for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test, and similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the Omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination doses.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2011
End Date: 2019
Funder: Medical Research Council
View Funded Activity