Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials.

BACKGROUND: Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and birth of a small-for-gestational-age (SGA) neonate. These complications are leading causes of maternal, fetal, and neonatal morbidity and mortality in high-income countries. Affected women are at high risk of recurrence in subsequent pregnancies; however, effective strategies to prevent recurrence are absent. Findings from our previous study-level meta-analysis suggested that low-molecular-weight heparin reduced the risk of recurrent placenta-mediated pregnancy complications. However, we identified significant heterogeneity in the results, possibly due to trial design or inclusion criteria. To identify which patients benefit from, and which outcomes are prevented by, low-molecular-weight heparin, we did an individual patient data meta-analysis. METHODS: We did a systematic review in May, 2013, which identified eight eligible randomised trials done between 2000 and 2013 of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. We excluded studies on the basis of the wrong population, the study being ongoing, inability to confirm eligibility of participants, intervention stopped too early, and no response from the principal investigator. We requested individual patient data from the study authors for eligible women (women pregnant at the time of the study with a history of previous pregnancy that had been complicated by one or more of the following: pre-eclampsia, placental abruption, birth of an SGA neonate [<10th percentile], pregnancy loss after 16 weeks' gestation, or two losses after 12 weeks' gestation) and recoded, combined, and analysed the data for our meta-analysis. The primary outcome was a composite of early-onset (<34 weeks) or severe pre-eclampsia, birth of an SGA neonate (<5th percentile), late pregnancy loss (≥20 weeks' gestation), or placental abruption leading to delivery, assessed on an intention-to-treat basis. We assessed risk of bias with the Cochrane Risk of Bias tool. This study is registered with PROSPERO, number CRD42013006249. FINDINGS: We analysed data from 963 eligible women in eight trials: 480 randomly assigned to low-molecular-weight heparin and 483 randomly assigned to no low-molecular-weight heparin. Overall, the risk of bias was not substantial enough to affect decisions regarding trial inclusion. Participants were mostly white (795/905; 88%) with a mean age of 30·9 years (SD 5·0) and 403/963 (42%) had thrombophilia. In the primary analysis, low-molecular-weight heparin did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (low-molecular-weight heparin 62/444 [14%] versus no low-molecular-weight heparin 95/443 (22%) absolute difference -8%, 95% CI -17·3 to 1·4, p=0·09; relative risk 0·64, 95% CI 0·36-1·11, p=0·11). We noted significant heterogeneity between single-centre and multicentre trials. In subgroup analyses, low-molecular-weight heparin in multicentre trials reduced the primary outcome in women with previous abruption (p=0·006) but not in any of the other subgroups of previous complications. INTERPRETATION: Low-molecular-weight heparin does not seem to reduce the risk of recurrent placenta-mediated pregnancy complications in at-risk women. However, some decreases in event rates might have been too small for the power of our study to explore. FUNDING: Canadian Institutes of Health Research.

Correction: Effectiveness of home-based records on maternal, newborn and child health outcomes: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0209278.].

Effectiveness of home-based records on maternal, newborn and child health outcomes: A systematic review and meta-analysis.

Home-based records (HBRs) may improve the health of pregnant women, new mothers and their children, and support health care systems. We assessed the effectiveness of HBRs on maternal, newborn and child health reporting, care seeking and self-care practice, mortality, morbidity and women's empowerment in low-, middle- and high-income countries. We conducted a systematic search in MEDLINE, EMBASE, CENTRAL, Health Systems Evidence, CINAHL, HTA database, NHS EED, and DARE from 1950 to 2017. We also searched the WHO, CDC, ECDC, JICA and UNAIDS. We included randomised controlled trials, prospective controlled trials, and cost-effectiveness studies. We used the Cochrane Risk of Bias tool to appraise studies. We extracted and analyzed data for outcomes including maternal, newborn and child health, and women's empowerment. We synthesized and presented data using GRADE Evidence Profiles. We included 14 studies out of 16,419 identified articles. HBRs improved antenatal care and reduced likelihood of pregnancy complications; improved patient-provider communication and enhanced women's feelings of control and empowerment; and improved rates of vaccination among children (OR: 2·39, 95% CI: 1.45-3·92) and mothers (OR 1·98 95% CI:1·29-3·04). A three-year follow-up shows that HBRs reduced risk of cognitive delay in children (p = 0.007). HBRs used during the life cycle of women and children in Indonesia showed benefits for continuity of care. There were no significant effects on healthy pregnancy behaviors such as smoking and consumption of alcohol during pregnancy. There were no statistically significant effects on newborn health outcomes. We did not identify any formal studies on cost or economic evaluation. HBRs show modest but important health effects for women and children. These effects with minimal-to-no harms, multiplied across a population, could play an important role in reducing health inequities in maternal, newborn, and child health.

Prevention and assessment of infectious diseases among children and adult migrants arriving to the European Union/European Economic Association: a protocol for a suite of systematic reviews for public health and health systems.

INTRODUCTION: The European Centre for Disease Prevention and Control is developing evidence-based guidance for voluntary screening, treatment and vaccine prevention of infectious diseases for newly arriving migrants to the European Union/European Economic Area. The objective of this systematic review protocol is to guide the identification, appraisal and synthesis of the best available evidence on prevention and assessment of the following priority infectious diseases: tuberculosis, HIV, hepatitis B, hepatitis C, measles, mumps, rubella, diphtheria, tetanus, pertussis, poliomyelitis (polio), Haemophilus influenza disease, strongyloidiasis and schistosomiasis. METHODS AND ANALYSIS: The search strategy will identify evidence from existing systematic reviews and then update the effectiveness and cost-effectiveness evidence using prospective trials, economic evaluations and/or recently published systematic reviews. Interdisciplinary teams have designed logic models to help define study inclusion and exclusion criteria, guiding the search strategy and identifying relevant outcomes. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: There are no ethical or safety issues. We anticipate disseminating the findings through open-access publications, conference abstracts and presentations. We plan to publish technical syntheses as GRADEpro evidence summaries and the systematic reviews as part of a special edition open-access publication on refugee health. We are following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols reporting guideline. This protocol is registered in PROSPERO: CRD42016045798.

Considerations from the risk of bias perspective for updating Cochrane reviews.

Authors of Cochrane reviews are expected to update their reviews every 2 years. The updating process helps to ensure that reviews are current and include recent evidence. However, the updating process is time-consuming for authors, particularly when Cochrane methods evolve and authors are required to revisit some of the originally included studies.The Cochrane Collaboration's 'Risk of bias' tool is a mandatory component of Cochrane reviews, providing an assessment of the potential biases of included studies. The tool has been modified most recently in 2011, and the expectation is that new versions will continue to be produced and utilised in all Cochrane reviews. In this commentary we discuss, in the context of updating scenarios that are likely to be encountered, the potential options systematic review authors may have recourse to when the Cochrane Collaboration's 'Risk of bias' tool has been modified between the original review and its update. We recommend that authors who are updating reviews should revise their original assessments of included studies using the most recent version of the risk of bias tool. Despite the increased workload, use of the most recent version of the tool facilitates consistency of methods and reporting both across and within reviews, and ensures currency to the methodological rigour.

Managing the incidence of selective reporting bias: a survey of Cochrane review groups.

BACKGROUND: Selective reporting bias (SRB), the incomplete publication of outcomes measured or of analyses performed in a study, may lead to the over- or underestimation of treatment effects or harms. Cochrane systematic reviews of interventions are required to assess the risk of SRB, achieved in part by applying the Cochrane risk of bias tool to each included randomised trial. The Cochrane Handbook outlines strategies for a comprehensive risk of bias assessment, but the extent to which these are followed by Cochrane review groups (CRGs) has not been assessed to date. The objective of this study was to determine the methods which CRGs require of their authors to address SRB within systematic reviews, and how SRB risk assessments are verified. METHODS: A cross-sectional survey was developed and distributed electronically to the 52 CRGs involved in intervention reviews. RESULTS: Responses from 42 CRGs show that the majority refer their authors to the Cochrane Handbook for specific instruction regarding assessments of SRB. The handbook strategies remain variably enforced, with 57 % (24/42) of CRGs not requiring review authors to search for included trial protocols and 31 % (13/42) not requiring that contact with individual study authors be attempted. Only half (48 %, 20/42) of the groups consistently verify review authors' assessments of the risk of SRB to ensure completeness. CONCLUSIONS: A range of practices are used by CRGs for addressing SRB, with many steps outlined in the Cochrane Handbook being encouraged but not required. The majority of CRGs do not consider their review authors to be sufficiently competent to assess for SRB, yet risk of bias assessments are not always verified by editors before publication. The implications of SRB may not be fully appreciated by all CRGs, and resolving the identified issues may require an approach targeting several steps in the systematic review process.

The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: protocol for a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of children and adolescents, with a significant impact on health services and the community in terms of economic and social burdens. The objective of this systematic review will be to evaluate the comparative efficacy and safety of pharmacological and non-pharmacological treatments in children and adolescents with ADHD. METHODS: Searches involving PubMed/MEDLINE and the Cochrane Database of Systematic Reviews will be used to identify related systematic reviews and relevant randomized trials. Search results will be supplemented by reports from the regulatory and health technology agencies, clinical trials registers and by data requested from trialists and/or pharmaceutical companies. We will consider studies evaluating pharmacological interventions (e.g. stimulants, non-stimulants, antidepressants), psychological interventions (e.g. behavioural interventions, cognitive training and neurofeedback) and complementary and alternative medicine interventions (e.g. dietary interventions, supplement with fatty acids, vitamins, minerals, aminoacids, herbal treatment, homeopathy, and mind-body interventions including massage, chiropractic, acupuncture, yoga, meditation, Tai chi). Eligible control conditions will be placebo, waitlist, no treatment and usual care. Randomized controlled trials of a minimum of 3 weeks duration will be included. The primary outcomes of interest will be the proportion of patients who responded to treatment and who dropped out of the allocated treatment, respectively. Secondary outcomes will include treatment discontinuation due to adverse events, as well as the occurrences of serious adverse events and specific adverse events (decreased weight, anorexia, insomnia and sleep disturbances, anxiety, syncope and cardiovascular events). Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles in duplicate. Data will be abstracted and risk of bias will be appraised by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects pairwise meta-analyses and Bayesian network meta-analyses will be conducted where appropriate. DISCUSSION: This systematic review and network meta-analysis will compare the efficacy and safety of treatments used for ADHD in children and adolescents. The findings will assist patients, clinicians and healthcare providers to make evidence-based decisions regarding treatment selection. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014015008 .