ORCID Profile
0000-0002-8416-2159
Current Organisation
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 15-03-2013
Publisher: Springer Science and Business Media LLC
Date: 18-10-2012
Publisher: National Institute for Health and Care Research
Date: 02-2014
DOI: 10.3310/HTA18140
Publisher: Springer Science and Business Media LLC
Date: 10-08-2012
DOI: 10.1007/S00125-012-2653-7
Abstract: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.
Publisher: National Institute for Health and Care Research
Date: 12-2015
DOI: 10.3310/HTA191000
Abstract: Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation. To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD. We searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke’s Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature. In two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year. A total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high ( I 2 = 98%) similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention. Heterogeneity in meta-analyses. While acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence. This study is registered as PROSPERO CRD42013003727. The National Institute for Health Research Health Technology Assessment programme.
Publisher: Oxford University Press (OUP)
Date: 04-2011
DOI: 10.1373/CLINCHEM.2010.157586
Abstract: The measurement of hemoglobin A1c (Hb A1c) is employed in monitoring of patients with diabetes. Use of point-of-care testing (POCT) for Hb A1c results at the time of the patient consultation potentially provides an opportunity for greater interaction between patient and caregiver, and more effective care. To perform a systematic review of current trials to determine whether POCT for Hb A1c, compared with conventional laboratory testing, improves outcomes for patients with diabetes. Searches were undertaken on 4 electronic databases and bibliographies from, and hand searches of, relevant journal papers. Only randomized controlled trials were included. The primary outcome measures were change in Hb A1c and treatment intensification. Metaanalyses were performed on the data obtained. Seven trials were found. There was a nonsignificant reduction of 0.09% (95% CI −0.21 to 0.02) in the Hb A1c in the POCT compared to the standard group. Although data were collected on the change in proportion of patients reaching a target Hb A1c of & .0%, treatment intensification and heterogeneity in the populations studied and how measures were reported precluded pooling of data and metaanalysis. Positive patient satisfaction was also reported in the studies, as well as limited assessments of costs. There is an absence of evidence in clinical trial data to date for the effectiveness of POCT for Hb A1c in the management of diabetes. In future studies attention to trial design is needed to ensure appropriate selection and stratification of patients, collection of outcome measures, and action taken upon Hb A1c results when produced.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jennifer Hirst.