Trial of healthy relationship initiatives for the very early years (THRIVE), evaluating Enhanced Triple P for Baby and Mellow Bumps additional social and care needs during pregnancy and their infants who are at higher risk of maltreatment : study protocol for a randomised controlled trial

THRIVE was funded by the National Institute for Health Research Public Health Research Programme (PHR Project: 11/3002/01). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Intervention Subvention Funding was provided by the CSO and Scottish Government (GN12KH589 THRIVE). Neither the trial funders nor Sponsor (NHS Greater Glasgow & Clyde Health Board (Reference GN12KH589)) will have any involvement in the implementation of the study design or the analysis of the data. The Sponsor will, however, play an active role in the delivery of the interventions, through employing and managing group facilitators. The Sponsor will also be the grant holder of the subvention funding, granted by the CSO and the Scottish Government to deliver the groups. Approval for all documentation to be used with the trial must be granted by the Sponsor as it will be delivered to NHS patients. Likewise, permission must be sought from the trial funders prior to any public engagement regarding the trial including conference presentations or academic articles.Peer reviewedPublisher PD

Optimal strategies for monitoring lipid levels in patients at risk or with cardiovascular disease: a systematic review with statistical and cost-effectiveness modelling

Background: 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. Objective: To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD. Data sources: We searched databases and clinical trials registers from 2007 [including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials (CCT) register, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL)] to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink (CPRD) and St Luke’s Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature. Methods: 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. Results: 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 (HR) 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. Limitation: Heterogeneity in meta-analyses. Conclusions: 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