Aspirin in primary prevention of cardiovascular disease and cancer : a systematic review of the balance of evidence from reviews of randomized trials

Background: Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses. Methods and Findings: Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82). Conclusions: Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed

Identifying and assessing the benefits of interventions for postnatal depression: a systematic review of economic evaluations

Abstract Background Economic evaluations of interventions for postnatal depression (PND) are essential to ensure optimal healthcare decision-making. Due to the wide-ranging effects of PND on the mother, baby and whole family, there is a need to include outcomes for all those affected and to include health and non-health outcomes for accurate estimates of cost-effectiveness. This study aimed to identify interventions to prevent or treat PND for which an economic evaluation had been conducted and to evaluate the health and non-health outcomes included. Methods A systematic review was conducted applying a comprehensive search strategy across eight electronic databases and other sources. Full or partial economic evaluations of interventions involving preventive strategies (including screening), and any treatments for women with or at-risk of PND, conducted in OECD countries were included. We excluded epidemiological studies and those focussing on costs only. The included studies underwent a quality appraisal to inform the analysis. Results Seventeen economic evaluations met the inclusion criteria, the majority focused on psychological /psychosocial interventions. The interventions ranged from additional support from health professionals, peer support, to combined screening and treatment strategies. Maternal health outcomes were measured in all studies; however child health outcomes were included in only four of them. Across studies, the maternal health outcomes included were quality-adjusted-life-years gained, improvement in depressive symptoms, PND cases detected or recovered, whereas the child health outcomes included were cognitive functioning, depression, sleep and temperament. Non-health outcomes such as couples’ relationships and parent-infant interaction were rarely included. Other methodological issues such as limitations in the time horizon and perspective(s) adopted were identified, that were likely to result in imprecise estimates of benefits. Conclusions The exclusion of relevant health and non-health outcomes may mean that only a partial assessment of cost-effectiveness is undertaken, leading to sub-optimal resource allocation decisions. Future research should seek ways to expand the evaluative space of economic evaluations and explore approaches to integrate health and non-health outcomes for all individuals affected by this condition. There is a need to ensure that the time horizon adopted in studies is appropriate to allow true estimation of the long-term benefits and costs of PND interventions

Additional file 2: of Identifying and assessing the benefits of interventions for postnatal depression: a systematic review of economic evaluations

Categorisation Criteria (details of the two-stage process used for study screening and selection). (DOCX 16 kb

Additional file 1: of Identifying and assessing the benefits of interventions for postnatal depression: a systematic review of economic evaluations

A search strategy carried out in Ovid MEDLINE (from 1946 to July Week 1 2015). (DOCX 18 kb

Additional file 4: of Identifying and assessing the benefits of interventions for postnatal depression: a systematic review of economic evaluations

Results of study assessment using Drummond’s checklist (adapted). (DOCX 21 kb

Additional file 3: of Identifying and assessing the benefits of interventions for postnatal depression: a systematic review of economic evaluations

Description of key methodological issues relating to outcomes (limitations as acknowledged by the authors of the included studies). (DOCX 20 kb

Participants' geographical location.

<p><i>Besides the lead contact or participating authors, other participants' locations were not stated/known (¹ – 15 studies, ² - 9 studies, ³ - 7 studies, ⁴ - 2 studies, ⁵ - 1 study).</i></p><p><i>* In 6 studies, OMERACT participants' information was extracted from the introductory paper.</i></p><p><i>** In 1 study, participants' location was based on where they had graduated from.</i></p

PRISMA flow diagram.

<div><p><i>Key</i>: CVD=Cardiovascular diseases; RCT=Randomised controlled trial; SR=Systematic Review.</p> <p>*Of the 27 included publications: a) CVD, SR=9, RCT=3; b) Cancer, SR=6; and c) Diabetes, SR=7, RCT=2. **One paper was identified from assessment of reference lists of excluded papers, this had been excluded at abstract sift but was not considered relevant until reading the paper in full. </p></div

Cumulative random effects meta-analysis of odds ratio for total CHD.

<p>Studies arranged according to recruitment year (data from Seshasai et al., 2012) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081970#B38" target="_blank">38</a>].</p

Identification of studies.

<p>Identification of studies.</p