ORCID Profile
0000-0001-6646-827X
Current Organisation
University of Oxford
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Publisher: BMJ
Date: 06-2021
DOI: 10.1136/BMJOPEN-2020-043906
Abstract: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful ex les and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility recruitment conduct/follow-up collecting benefits/harms and analysis/interpretation. Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.
Publisher: Elsevier BV
Date: 11-2010
Publisher: American Medical Association (AMA)
Date: 06-10-2020
Publisher: Elsevier BV
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 10-02-2021
DOI: 10.1038/S41467-021-21134-2
Abstract: Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for ex le in low- and middle-income countries.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 07-2014
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1038/KI.2010.550
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 2016
Publisher: Elsevier BV
Date: 02-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
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: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.AHJ.2010.08.012
Abstract: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Patients with advanced CKD (blood creatinine ≥ 1.7 mg/dL [≥ 150 μmol/L] in men or ≥ 1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-10-2020
Abstract: Conventional epidemiology associates increased body mass index (BMI) with higher risk of CKD. Diabetes and high BP explain half of the association. However, residual confounding factors preclude causal inferences and impede mediation assessments. A genetic approach (Mendelian randomization) may overcome these limitations. Analyses of 281,228 genotyped UK Biobank participants identified positive independent genetic associations between central and general adiposity with CKD, suggesting both are causal risk factors. Conventional approaches underestimate the role of known mediators. Diabetes and BP (and correlates) explain % of genetic associations between waist-to-hip ratio and CKD and two-thirds between BMI and CKD. In people without diabetes, obesity appeared to cause CKD. BP accounted for about half of the BMI-CKD associations. The size of any causal contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown. Data from 281,228 UK Biobank participants were used to estimate the relevance of waist-to-hip ratio and body mass index (BMI) to CKD prevalence. Conventional approaches used logistic regression. Genetic analyses used Mendelian randomization (MR) and data from 394 waist-to-hip ratio and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes mellitus and BP) by adjusting for measured values (conventional analyses) or genetic associations of the selected loci (multivariable MR). Evidence of CKD was found in 18,034 (6.4%) participants. Each 0.06 higher measured waist-to-hip ratio and each 5-kg/m 2 increase in BMI were associated with 69% (odds ratio, 1.69 95% CI, 1.64 to 1.74) and 58% (1.58 1.55 to 1.62) higher odds of CKD, respectively. In analogous MR analyses, each 0.06–genetically-predicted higher waist-to-hip ratio was associated with a 29% (1.29 1.20 to 1.38) increased odds of CKD, and each 5-kg/m 2 genetically-predicted higher BMI was associated with a 49% (1.49 1.39 to 1.59) increased odds. After adjusting for diabetes and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI fell by 56%. In contrast, mediator adjustment using multivariable MR found 83% and 69% reductions in chi-squared values for genetically-predicted waist-to-hip ratio and BMI models, respectively. Genetic analyses suggest that conventional associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate mediating roles of diabetes, BP, and their correlates. Genetic approaches suggest these mediators explain most of adiposity-CKD–associated risk.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 08-2012
Publisher: Massachusetts Medical Society
Date: 19-07-2100
Publisher: Oxford University Press (OUP)
Date: 26-02-2013
Publisher: Springer Science and Business Media LLC
Date: 05-2017
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 02-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
DOI: 10.2215/CJN.10371013
Publisher: Springer Science and Business Media LLC
Date: 16-07-2020
DOI: 10.1038/S41366-020-0642-3
Abstract: Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain. Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators. Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53–57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30–34%). Each 5 kg/m 2 higher BMI was associated with a 47% (46–49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33–37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure. Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity–albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2015
Publisher: Elsevier BV
Date: 04-2018
Publisher: Massachusetts Medical Society
Date: 28-09-2017
Publisher: Massachusetts Medical Society
Date: 25-02-2021
Publisher: Elsevier BV
Date: 09-2016
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 08-2017
Publisher: Springer Science and Business Media LLC
Date: 05-03-2021
DOI: 10.1038/S41467-021-22038-X
Abstract: A Correction to this paper has been published: 0.1038/s41467-021-22038-x.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Martin Landray.