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Introduction: The optimal duration of magnesium administration postpartum for prevention of eclampsia has not yet been established. Our objective was to investigate the effect of early discontinuation of postpartum magnesium on the rates of postpartum eclampsia compared to continuation for 24-hours postpartum., Material and Methods: Searches were performed using keywords related to "preeclampsia" and "magnesium sulfate" from inception of database until August 2023. Randomized controlled trials of women with preeclampsia were included if they received magnesium prior to delivery and were randomized to early discontinuation versus 24-hours of magnesium postpartum. The primary outcome was the rate of postpartum eclampsia., Results: Nine RCTs with 2183 women were included with five different magnesium administration time frames. In total, seven patients with postpartum eclampsia were reported in three studies. Eclampsia rates were not different between the two groups (5/1088 (0.5 %) after early discontinuation, versus 2/1095 (0.2 %) in the 24-hour group; RR 2.25, 95 % CI 0.5-9.9, I 2  = 0 %, 8 studies, 2183 participants). A number needed to treat was calculated; 374 women would need to receive 24-hours of magnesium postpartum to prevent one episode of postpartum eclampsia. The early discontinuation group had a significant decrease in time to ambulation (-9.1 h, 95 % CI -14.7 - (-3.6), I 2  = 98 %, 3 studies, 1509 participants) and breastfeeding (-8.4 h, 95 % CI -12.0 - (-4.8), I 2  = 98 %, 2 studies, 1397 participants)., Conclusions: Early magnesium discontinuation postpartum, usually ≤6 h or none at all, did not significantly increase the rate of postpartum eclampsia, however this study is likely underpowered to demonstrate a difference. The number needed to treat is similar to the number needed to treat for antepartum preeclampsia without severe features, for which magnesium is not recommended. The largest proportion of women did not receive magnesium postpartum after receiving at least 8 h of magnesium intrapartum (e.g., loading and maintenance dose). Thus, it is reasonable to consider not using magnesium postpartum, particularly if a woman has received similar adequate dose prior to delivery., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ben Willem Mol is supported by a NHMRC Practitioner Fellowship (GNT1082548). Dr. Ben Willem Mol reports consultancy for ObsEva, Merck Merck KGaA and Guerbet. Dr Jack Ludmir and Dr Paulino Vigil-de Gracia were both authors on included randomized trials. The other authors did not report any potential conflicts of interest., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AS owns 50% of the shares in Zuman International, which receives royalties for books AS has written and payments for presentations. AS additionally reports receiving presentation fees and travel reimbursements from Eli Lilly and Co, the Pharmacy Guild of Australia, Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres, the Pharmaceutical Society of Australia, and Metagenics, and serving on the Nestlé Health Science Optifast VLCD advisory board from 2016 to 2018. ALA is Principal Investigator on two publicly funded trials where the intervention is provided by WW (formerly Weight Watchers) at no cost. KS has received in kind support as meals from ‘Lite and Easy’ for a clinical trial of weight stigma in young women in the last 5 years. ER has previously received research funding from Unilever and the American Beverage Association for unrelated work. JAY reports unrelated grant funds to NICHD supporting his research from Soleno Therapeutics, Rhythm Pharmaceuticals, and Hikma Pharmaceuticals. HFS has previously received a salary from Novo Nordisk unrelated to the present work. YSD has previously received a salary from Novo Nordisk unrelated to the present work. HAR has received funding from the National Institutes of Health in the area of adult and pediatric weight management. HAR is a committee member for the evidence-based practice guidelines for pediatric weight management for the American Psychological Association and for the Evidence Analysis Library for the Academy of Nutrition and Dietetics for the topic of adult weight management and the prevention of type 2 diabetes. MIC is an employee and shareholder at WW International, Inc. TKK has received professional fees from Novo Nordisk, Nutrisystem, Gelesis and Johnson & Johnson. CKM has received research grants and research agreements from Commission on Dietetic Registration, Academy of Nutrition and Dietetics, Ohio State University (InFACT), Novartis, University of Michigan’s Michigan Institute for Clinical and Health Research, Elizabeth Blackwell Institute for Health Research, Egg Board, PCORI, Department of Defense, Access Business Group International LLC, IDEA Public Schools, Louisiana LIFT Fund, WW, Pack Health, American Society for Nutrition, RAND Corporation, Richard King Mellon Foundation (RKMF), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Evidation Health, Leona M. and Harry B. Helmsley Charitable Trust, State of Louisiana- Federal American Rescue Plan (ARP), United States Department of Agriculture (USDA), National Institute for Health Research (NIHR), National Science Foundation (NSF), Lilly, National Institutes of Health (NIH). CKM has served on advisory boards for EHE Health, Wondr Health, and the Nutrition Obesity Research Center at the University of Alabama Birmingham and consulted to Kitchry, Metagenics, WW, Florida Hospital, Gila Therapeutics, Zafgen, OpenFit/MXCXM Health Inc. CKM developed intellectual property (IP) to quantify dietary adherence and his institution has licensed this IP, resulting in receiving royalties via the institution from the licensing fees. CKM is part of US and European patent applications for a weight loss approach called the Body weight Management and activity tracking system and also occasionally gives lectures and talks where he is provided with an honorarium, including talks to the Obesity Action Coalition and Indiana University Bloomington. Finally, CKM serves as a developer and facilitator for continuing education events sponsored by the Commission on Dietetic Registration, and is a Planning Committee Member for the Bray Course. The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the Public Health Service, the Department of Health and Human Services, USUHS, or the U.S. Department of Defense., (Copyright: © 2023 Jebeile et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To compare severity and clinical outcomes from Omicron as compared with the Delta variant and to compare outcomes between Omicron sublineages., Methods: We searched the WHO COVID-19 Research database for studies that compared clinical outcomes for patients with Omicron variant and the Delta variant, and separately Omicron sublineages BA.1 and BA.2. A random-effects meta-analysis was used to pool estimates of relative risk (RR) between variants and sublineages. Heterogeneity between studies was assessed using the I 2 index. Risk of bias was assessed using the tool developed by the Clinical Advances through Research and Information Translation team., Results: Our search identified 1494 studies and 42 met the inclusion criteria. Eleven studies were published as preprints. Of the 42 studies, 29 adjusted for vaccination status; 12 had no adjustment; and for 1, the adjustment was unclear. Three of the included studies compared the sublineages of Omicron BA.1 versus BA.2. As compared with Delta, individuals infected with Omicron had 61% lower risk of death (RR 0.39, 95% CI 0.33 to 0.46) and 56% lower risk of hospitalisation (RR 0.44, 95% CI 0.34 to 0.56). Omicron was similarly associated with lower risk of intensive care unit (ICU) admission, oxygen therapy, and non-invasive and invasive ventilation. The pooled risk ratio for the outcome of hospitalisation when comparing sublineages BA.1 versus BA.2 was 0.55 (95% 0.23 to 1.30)., Discussion: Omicron variant was associated with lower risk of hospitalisation, ICU admission, oxygen therapy, ventilation and death as compared with Delta. There was no difference in the risk of hospitalisation between Omicron sublineages BA.1 and BA.2., Prospero Registration Number: CRD42022310880., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

The optimal cord management strategy at birth for each preterm baby is still unknown, despite more than 100 randomized controlled trials (RCTs) undertaken on this question. To address this, we brought together all RCTs examining cord management strategies at preterm birth in the iCOMP (individual participant data on COrd Management at Preterm birth) Collaboration, to perform an individual participant data network meta-analysis. In this paper, we describe the trials and tribulations around obtaining individual participant data to resolve controversies around cord clamping, and we derive key recommendations for future collaborative research in perinatology. To reliably answer outstanding questions, future cord management research needs to be collaborative and coordinated, by aligning core protocol elements, ensuring quality and reporting standards are met, and carefully considering and reporting on vulnerable sub-populations. The iCOMP Collaboration is an example of the power of collaboration to address priority research questions, and ultimately improve neonatal outcomes worldwide., Competing Interests: Disclosure All authors are secretariat members of the iCOMP Collaboration. There are no financial conflicts of interest to disclose. The iCOMP Collaboration is funded by a National Health and Medical Research Council (NHMRC) Project Grant (GNT1163585). ALS is funded by an NHMRC Investigator grant (GNT2009432)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Complete information in a trial protocol regarding study outcomes is crucial for obtaining regulatory approvals, ensuring standardized trial conduct, reducing research waste, and providing transparency of methods to facilitate trial replication, critical appraisal, accurate reporting and interpretation of trial results, and knowledge synthesis. However, recommendations on what outcome-specific information should be included are diverse and inconsistent. To improve reporting practices promoting transparent and reproducible outcome selection, assessment, and analysis, a need for specific and harmonized guidance as to what outcome-specific information should be addressed in clinical trial protocols exists., Objective: To develop harmonized, evidence- and consensus-based standards for describing outcomes in clinical trial protocols through integration with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement., Evidence Review: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for outcome-specific reporting to be addressed in clinical trial protocols., Findings: The scoping review and consultation with experts identified 108 recommendations relevant to outcome-specific reporting to be addressed in trial protocols, the majority (72%) of which were not included in the SPIRIT 2013 statement. All recommendations were consolidated into 56 items for Delphi voting; after the Delphi survey process, 19 items met criteria for further evaluation at the consensus meeting and possible inclusion in the SPIRIT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 9 items that elaborate on the SPIRIT 2013 statement checklist items and are related to completely defining and justifying the choice of primary, secondary, and other outcomes (SPIRIT 2013 statement checklist item 12) prospectively in the trial protocol, defining and justifying the target difference between treatment groups for the primary outcome used in the sample size calculations (SPIRIT 2013 statement checklist item 14), describing the responsiveness of the study instruments used to assess the outcome and providing details on the outcome assessors (SPIRIT 2013 statement checklist item 18a), and describing any planned methods to account for multiplicity relating to the analyses or interpretation of the results (SPIRIT 2013 statement checklist item 20a)., Conclusions and Relevance: This SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement provides 9 outcome-specific items that should be addressed in all trial protocols and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.

Importance: Clinicians, patients, and policy makers rely on published results from clinical trials to help make evidence-informed decisions. To critically evaluate and use trial results, readers require complete and transparent information regarding what was planned, done, and found. Specific and harmonized guidance as to what outcome-specific information should be reported in publications of clinical trials is needed to reduce deficient reporting practices that obscure issues with outcome selection, assessment, and analysis., Objective: To develop harmonized, evidence- and consensus-based standards for reporting outcomes in clinical trial reports through integration with the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement., Evidence Review: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for the reporting of outcomes in clinical trial reports., Findings: The scoping review and consultation with experts identified 128 recommendations relevant to reporting outcomes in trial reports, the majority (83%) of which were not included in the CONSORT 2010 statement. All recommendations were consolidated into 64 items for Delphi voting; after the Delphi survey process, 30 items met criteria for further evaluation at the consensus meeting and possible inclusion in the CONSORT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 17 items that elaborate on the CONSORT 2010 statement checklist items and are related to completely defining and justifying the trial outcomes, including how and when they were assessed (CONSORT 2010 statement checklist item 6a), defining and justifying the target difference between treatment groups during sample size calculations (CONSORT 2010 statement checklist item 7a), describing the statistical methods used to compare groups for the primary and secondary outcomes (CONSORT 2010 statement checklist item 12a), and describing the prespecified analyses and any outcome analyses not prespecified (CONSORT 2010 statement checklist item 18)., Conclusions and Relevance: This CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement provides 17 outcome-specific items that should be addressed in all published clinical trial reports and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.

Publishing systematic review protocols is a fundamental part of systematic reviews to ensure transparency and reproducibility. In this scoping review, we aimed to evaluate reporting of Cochrane systematic review protocols with network meta-analyses (NMA). We searched all Cochrane NMA protocols published in 2018 and 2019, and assessed the characteristics and reporting of methodologies relevant to NMA. We reported frequencies for each reporting item. Forty-five protocols were assessed, including two for overviews and 43 for intervention reviews. Thirty-three (73%) were labelled as NMA protocols in the title. Forty-two (95%) justified the need of an NMA and 40 (89%) used appropriate search strategies to identify potential eligible studies. About half (24, 53%) considered the transitivity assumption when reporting inclusion criteria and 35 (78%) specified potential effect modifiers. Forty-three (96%) reported statistical software for NMA, 25 (56%) reported NMA model choice, 32 (71%) reported framework choice and 32 (71%) reported assumption about heterogeneity variances. Protocols varied in whether they reported methods for relative ranking (35, 78%), statistical inconsistency (40, 89%), reporting bias (44, 98%) and sources of heterogeneity (39, 87%). In conclusion, Cochrane NMA protocols reported multiple NMA-specific items well, but could be further improved, especially regarding transitivity assumptions. Our recommendations for NMA protocol reporting based on this scoping review could assist authors, reviewers, and editors to improve NMA protocols., (© 2021 John Wiley & Sons, Ltd.)

Introduction: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups., Methods and Analysis: Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events., Ethics and Dissemination: Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases., Prospero Registration Number: CRD42020177408., Competing Interests: Competing interests: AB, ALS, BJJ, KEH, MA, RKG, SL and LPS reports grants from NHMRC Ideas Grant TOPCHILD (Transforming Obesity Prevention for CHILDren) (GNT1186363); APE and CGA reports grants administered by the Inter-American Development Bank from The Government of Japan and The PepsiCo Foundation; ALT reports grants from National Institute of Health; BJT reports grants from NZ Health Research Council; EO reports grants from the US National Institutes of Health, and the Canadian Institutes for Health Research; IMP reports grants from NIH/NIDDK; JSS reports grants from PCORI, NIH NIDDK and NHLBI, and personal fees from Danone Organic, American Academy of Pediatrics, and Lets Move Maine; LTK and JKL reports grants from Fonds NutsOhra; MCR reports grants from National Institute on Minority Health and Health Disparities-National Institutes of Health/Center for Collaborative Research in Health Disparities, and personal fees from Rhythm Pharmaceuticals; RSG reports grants from US Department of Agriculture and NIH/NICHD., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity., Methods and Analysis: Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components., Ethics and Dissemination: The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders., Prospero Registration Number: CRD42020177408., Competing Interests: Competing interests: AB, ALS, BJJ, KEH, MA, RG, SL and LPS reports grants from NHMRC Ideas Grant TOPCHILD (Transforming Obesity Prevention for CHILDren) (GNT1186363); APE and CGA reports grants administered by the Inter-American Development Bank from The Government of Japan and The PepsiCo Foundation; AT reports grants from National Institute of Health; BJT reports grants from NZ Health Research Council; EO reports grants from the US National Institutes of Health, and the Canadian Institutes for Health Research; IMP reports grants from NIH/NIDDK; JS reports grants from PCORI, NIH NIDDK and NHLBI, and personal fees from Danone Organic, American Academy of Pediatrics and Lets Move Maine; LTK and JL reports grants from Fonds NutsOhra; MR reports grants from National Institute on Minority Health and Health Disparities-National Institutes of Health/Center for Collaborative Research in Health Disparities, and personal fees from Rhythm Pharmaceuticals; RSG reports grants from US Department of Agriculture and NIH/NICHD., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical Question: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19., Recommendation: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty)., How This Guideline Was Created: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Understanding the New Recommendation: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19., Updates: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline., Readers Note: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity., Competing Interests: Competing interests: All guideline panel members have completed the WHO interest disclosure form. All authors have completed the BMJ Rapid Recommendations interest of disclosure form. The WHO, MAGIC, and The BMJ judged that no panel member had any financial conflict of interest. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions. MAGIC and TheBMJ assessed declared interests from other co-authors of this publication and found no conflicts of interests., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Childhood obesity is a global problem. Early obesity prevention interventions are complex and differ in effectiveness. Novel frameworks, taxonomies and experience from the Early Prevention of Obesity in CHildren (EPOCH) trials were applied to unpack interventions., Objectives: Deconstruct interventions into their components (target behaviours, delivery features and behaviour change techniques [BCTs]). Identify lessons learned and future recommendations for intervention planning, delivery, evaluation and implementation., Methods: This multi-methods study deconstructed the four EPOCH interventions into target behaviours, delivery features and BCTs from unpublished and published materials using systematic frameworks. Additionally, semi-structured interviews were conducted with intervention facilitators and principal investigators., Results: Each trial targeted between 10 and 14 obesity-related behaviours. Key variations in delivery features related to intensity, delivery mode and tailoring. BCTs consistently used across trials included goal-setting, social support, shaping knowledge, role-modelling and credible source. Recommendations from interview analyses include the importance of stakeholder collaboration and consideration of implementation throughout the study process., Conclusions: The combination of frameworks, methodologies and interviews used in this study is a major step towards understanding complex early obesity prevention interventions. Future work will link systematic intervention deconstruction with quantitative models to identify which intervention components are most effective and for whom., (© 2020 World Obesity Federation.)

Introduction: Rates of medical interventions in normal labour and birth are increasing. This prospective meta-analysis (PMA) proposes to assess whether the addition of a comprehensive multicomponent birth preparation programme reduces caesarean section (CS) in nulliparous women compared with standard hospital care. Additionally, do participant characteristics, intervention components or hospital characteristics modify the effectiveness of the programme? METHODS AND ANALYSIS: Population : women with singleton vertex pregnancies, no planned caesarean section (CS) or epidural. Intervention : in addition to hospital-based standard care, a comprehensive antenatal education programme that includes multiple components for birth preparation, addressing the three objectives: preparing women and their birth partner/support person for childbirth through education on physiological/hormonal birth (knowledge and understanding); building women's confidence through psychological preparation (positive mindset) and support their ability to birth without pain relief using evidence-based tools (tools and techniques). The intervention could occur in a hospital-based or community setting. Comparator : standard care alone in hospital-based maternity units., Outcomes: Primary : CS. Secondary : epidural analgesia, mode of birth, perineal trauma, postpartum haemorrhage, newborn resuscitation, psychosocial well-being. Subgroup analysis : parity, model of care, maternal risk status, maternal education, maternal socio-economic status, intervention components., Study Design: An individual participant data (IPD) prospective meta-analysis (PMA) of randomised controlled trials, including cluster design. Each trial is conducted independently but share core protocol elements to contribute data to the PMA. Participating trials are deemed eligible for the PMA if their results are not yet known outside their Data Monitoring Committees., Ethics and Dissemination: Participants in the individual trials will consent to participation, with respective trials receiving ethical approval by their local Human Research Ethics Committees. Individual datasets remain the property of trialists, and can be published prior to the publication of final PMA results. The overall data for meta-analysis will be held, analysed and published by the collaborative group, led by the Cochrane PMA group., Trial Registration Number: CRD42020103857., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Updates: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline., Clinical Question: What is the role of drugs in the treatment of patients with covid-19?, Context: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics., What Is New?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19., About This Guideline: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact., Future Recommendations: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations., Competing Interests: All GDG members have completed the WHO interest disclosure form. All authors have completed the BMJ Rapid Recommendations interest of disclosure form. The WHO, MAGIC and The BMJ judged that no GDG member or co-chair had any financial conflict of interest. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the GDG to make fully informed decisions. MAGIC and TheBMJ assessed declared interests from other co-authors of this publication and found no relevant conflicts of interests., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Network meta-analysis allows researchers to synthesise both direct and indirect evidence, thus enabling simultaneous comparisons of multiple treatments. A relatively recent addition to evidence synthesis in reproductive medicine, this approach has become increasingly popular. Yet, the underlying assumptions of network meta-analyses, which drive the validity of their findings, have been frequently ignored. In this article, we discuss the strengths and limitations of network meta-analyses. In addition, we present an overview of published network meta-analyses in reproductive medicine, summarize their challenges and provide insights into future research opportunities., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity., Methods: We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units. Infants born weighing less than 1500 g and aged less than 8 days, were eligible and randomly assigned (1:1) using minimising web-based randomisation to receive once daily 200 mg/kg pasteurised bovine lactoferrin supplements or no lactoferrin supplement added to breast or formula milk until 34 weeks' post-menstrual age (or for 2 weeks, if longer), or until discharge from the study hospital if that occurred first. Designated nurses preparing the daily feeds were not masked to group assignment, but other nurses, doctors, parents, caregivers, and investigators were unaware. The primary outcome was survival to hospital discharge or major morbidity (defined as brain injury, necrotising enterocolitis, late-onset sepsis at 36 weeks' post-menstrual age, or retinopathy treated before discharge) assessed in the intention-to-treat population. Safety analyses were by treatment received. We also did a prespecified, PRISMA-compliant meta-analysis, which included this study and other relevant randomised controlled trials, to estimate more precisely the effects of lactoferrin supplementation on late-onset sepsis, necrotising enterocolitis, and survival. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000247976., Findings: Between June 27, 2014, and Sept 1, 2017, we recruited 1542 infants; 771 were assigned to the intervention group and 771 to the control group. One infant who had consent withdrawn before beginning lactoferrin treatment was excluded from analysis. In-hospital death or major morbidity occurred in 162 (21%) of 770 infants in the intervention group and in 170 (22%) of 771 infants in the control group (relative risk [RR] 0·95, 95% CI 0·79-1·14; p=0·60). Three suspected unexpected serious adverse reactions occurred; two in the lactoferrin group, namely unexplained late jaundice and inspissated milk syndrome, but were not attributed to the intervention and one in the control group had fatal inspissated milk syndrome. Our meta-analysis identified 13 trials completed before Feb 18, 2020, including this Article, in 5609 preterm infants. Lactoferrin supplements significantly reduced late-onset sepsis (RR 0·79, 95% CI 0·71-0·88; p<0·0001; I 2 =58%), but not necrotising enterocolitis or all-cause mortality., Interpretation: Lactoferrin supplementation did not improve death or major morbidity in this trial, but might reduce late-onset sepsis, as found in our meta-analysis of over 5000 infants. Future collaborative studies should use products with demonstrated biological activity, be large enough to detect moderate and clinically important effects reliably, and assess greater doses of lactoferrin in infants at increased risk, such as those not exclusively receiving breastmilk or infants of extremely low birthweight., Funding: Australian National Health and Medical Research Council., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons., Objectives: (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA., Methods and Analysis: Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks' gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored., Ethics and Dissemination: Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases., Registration Number: Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12619001305112) and International Prospective Register of Systematic Reviews (PROSPERO, CRD42019136640)., Competing Interests: Competing interests: LD, ACK, CDPM, ED, HR, JK, JM, JJ, KF, OA, SH, VS, VD, WE-N and WT-M are Chief Investigators for potentially eligible trials., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Competing interests: We have read and understood the BMJ Group policy on declaration of interests and declare the following: all authors are convenors or members of the Cochrane PMA Methods Group and have been involved in numerous prospective meta-analyses. LA, DG, and JAB have published several methods articles on prospective meta-analyses and are authors of the prospective meta-analysis chapter in the Cochrane Handbook for Systematic Reviews of Interventions. LA manages the Australian New Zealand Clinical Trials Registry (ANZCTR). ALS and KEH work for the ANZCTR. JAB is a full time employee of Johnson & Johnson.

Objectives: The objective of this study was to determine the prevalence of trial registration in health research, whether trial registration status and timing vary depending on trial characteristics, and the relationship between trial registration status and risk of bias., Study Design and Setting: We systematically reviewed all clinical trials published from January to June 2017 in 28 high- and low-impact factor general and specialty medicine journals., Results: We identified 370 trials and assessed risk of bias in 183 trials. Trial registration rates were high; 95% of trials were registered prospectively or retrospectively before enrollment completion. Larger sample size, multiple recruitment countries, and primary industry funding were all predictors of earlier trial registration. Prospectively registered trials had a significantly lower risk of bias compared to unregistered trials across all domains. Prospectively registered trials had a similar risk of bias compared to retrospectively registered trials across four out of six domains, and a lower risk of bias across the remaining two domains., Conclusion: Trial registration is an imperfect proxy for risk of bias. Systematic reviewers should assess risk of bias on a case-by-case basis and conduct sensitivity analyses excluding high risk of bias studies. In the longer term, mechanisms should be implemented to facilitate prospective registration of all trials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors., Methods and Findings: Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference -0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes., Conclusions: In this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RJW provided expertise on a legal case for LabCorp for which he received compensation. The case was not related to the topic being presented. He is PI for several studies that CUMC receives grants for including support from commercial entities Natera, Inc.; Sequenom; Illumina, Inc. He does not receive compensation from any of these grants.

Objectives: To identify and review evaluations of strategies to recruit men aged 50 years and over to randomised controlled trials (RCTs)., Design: Systematic review and narrative synthesis., Data Sources: MEDLINE, EMBASE, CINAHL and ORRCA databases were searched to 1 December 2017., Eligibility Criteria: Studies using quantitative methods to evaluate recruitment strategies to RCTs of men aged 50 years and older., Data Extraction and Synthesis: A single reviewer extracted data (for each strategy, number of participants approached, screened and randomised, and cost). Study quality was assessed using National Heart, Lung and Blood Institute Quality Assessment Tools and considered study design, description of interventions, description and measurement of outcomes, completeness of outcome reporting, performance of statistical testing and consideration of confounders. Recruitment strategies were categorised by the recruitment stage they addressed., Results: Sixteen studies (n >14 000) were included: one good quality, ten fair quality and five poor quality. Studies evaluated strategies to identify prospective participants, and to improve the processes for assessing participant eligibility, providing participant information and seeking consent. In good and fair quality studies, the most effective strategies for identifying participants were referral from an affiliated health service provider (two studies), mass mailing (five studies) and media coverage (two studies). Community outreach activities such as displaying posters and attending local community events were not effective (two studies). Trial-specific training of site recruitment staff, developed using qualitative analysis of recruitment visits (two studies), and provision of study information to prospective participants at a multidisciplinary, group information session (one study) both improved recruitment., Conclusion: Improved engagement of men aged 50 years and older in RCTs is needed. A gender-sensitised approach to RCT recruitment may help to address this need. We have identified several promising recruitment strategies that merit further evaluation., Prospero Registration Number: CRD42017060301., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Introduction: Accumulating evidence has shown an association between maternal supine going-to-sleep position and stillbirth in late pregnancy. Advising women not to go-to-sleep on their back can potentially reduce late stillbirth rate by 9%. However, the association between maternal right-sided going-to-sleep position and stillbirth is inconsistent across studies. Furthermore, individual studies are underpowered to investigate interactions between maternal going-to-sleep position and fetal vulnerability, which is potentially important for producing clear and tailored public health messages on safe going-to-sleep position. We will use individual participant data (IPD) from existing studies to assess whether right-side and supine going-to-sleep positions are independent risk factors for late stillbirth and to test the interaction between going-to-sleep position and fetal vulnerability., Methods and Analysis: An IPD meta-analysis approach will be used using the Cochrane Collaboration-endorsed methodology. We will identify case-control and prospective cohort studies and randomised trials which collected maternal going-to-sleep position data and pregnancy outcome data that included stillbirth. The primary outcome is stillbirth. A one stage procedure meta-analysis, stratified by study with adjustment of a priori confounders will be carried out., Ethics and Dissemination: The IPD meta-analysis has obtained central ethics approval from the New Zealand Health and Disability Ethics Committee, ref: NTX/06/05/054/AM06. Individual studies should also have ethical approval from relevant local ethics committees. Interpretation of the results will be discussed with consumer representatives. Results of the study will be published in peer-reviewed journals and presented at international conferences., Prospero Registration Number: CRD42017047703., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Specialised surveillance using total body photography and digital dermoscopy to monitor people at very high risk of developing a second or subsequent melanoma has been reported as cost effective., Objectives: We aimed to estimate the 5-year healthcare budget impact of providing specialised surveillance for people at very high risk of subsequent melanoma from the perspective of the Australian healthcare system., Methods: A budget impact model was constructed to assess the costs of monitoring and potential savings compared with current routine care based on identification of patients at the time of a melanoma diagnosis. We used data from a published cost-effectiveness analysis of specialised surveillance, and Cancer Registry data, to estimate the patient population and healthcare costs for 2017-2021., Results: When all eligible patients, estimated at 18% of patients with melanoma diagnosed annually in Australia, received specialised surveillance rather than routine care, the cumulative 5-year cost was estimated at $93.5 million Australian dollars ($AU) ($US 64 million) for specialised surveillance compared with $AU 120.7 million ($US 82.7 million) for routine care, delivering savings of $AU 27.2 million ($US 18.6 million). With a staggered introduction of 60% of eligible patients accessing surveillance in year 1, increasing to 90% in years 4 and 5, the cumulative cost over 5 years was estimated at $AU 98.1 million ($US 67.2 million), amounting to savings of $AU 22.6 million ($US 15.5 million) compared with routine care., Conclusions: Specialised melanoma surveillance is likely to provide substantial cost savings for the Australian healthcare system.

Objective: To compare the effects of immediate delivery an expectant management among women whose pregnancies were complicated by preterm prelabor rupture of membranes (PROM) in the late preterm period (from 34 0/7 weeks until 36 6/7 weeks of gestation)., Data Sources: PubMed, Scopus, ClinicalTrials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception until December 2016., Methods of Study Selection: We included all randomized controlled trials with individual participant data reporting on late preterm PROM with randomization to immediate delivery or expectant management. The primary outcome was a composite of adverse neonatal outcomes: probable or definitive neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, stillbirth, or neonatal death., Tabulation, Integration and Results: Of eight eligible trials (total n=3,203 mothers), three (2,563 mothers, 2,572 neonates) had individual participant data available. The composite adverse neonatal outcome occurred in 9.6% of neonates in the immediate delivery group and 8.3% in the expectant management group (relative risk [RR] 1.20, 95% CI 0.94-1.55). Neonatal sepsis rates were 2.6% and 3.5%, respectively (RR 0.74, 95% CI 0.47-1.15). Neonates in the immediate delivery group were more likely to be diagnosed with respiratory distress syndrome (RR 1.47, 95% CI 1.10-1.97), and to be admitted to the neonatal intensive care unit or special care nursery (RR 1.17, 95% CI 1.11-1.23) and had longer admissions. Mothers randomized to immediate delivery were less likely to have an antepartum hemorrhage (RR 0.57, 95% CI 0.34-0.95) or chorioamnionitis (RR 0.21, 95% CI 0.13-0.35), but more likely to undergo cesarean delivery (RR 1.26, 95% CI 1.08-1.47)., Conclusion: In women with late preterm PROM, immediate delivery and expectant management resulted in comparable rates of the composite of adverse neonatal outcomes. Effects on individual secondary maternal and neonatal outcomes were mixed., Systematic Review Registration: PROSPERO, 42016032972.

Background: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former., Methods: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials., Results: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74)., Conclusions: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

Background: The effects of delayed cord clamping of the umbilical cord in preterm infants are unclear., Objective: We sought to compare the effects of delayed vs early cord clamping on hospital mortality (primary outcome) and morbidity in preterm infants using Cochrane Collaboration neonatal review group methodology., Study Design: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese articles, cross-referencing citations, expert informants, and trial registries to July 31, 2017, for randomized controlled trials of delayed (≥30 seconds) vs early (<30 seconds) clamping in infants born <37 weeks' gestation. Before searching the literature, we specified that trials estimated to have cord milking in >20% of infants in any arm would be ineligible. Two reviewers independently selected studies, assessed bias, and extracted data. Relative risk (ie, risk ratio), risk difference, and mean difference with 95% confidence intervals were assessed by fixed effects models, heterogeneity by I 2 statistics, and the quality of evidence by Grading of Recommendations, Assessment, Development, and Evaluations., Results: Eighteen randomized controlled trials compared delayed vs early clamping in 2834 infants. Most infants allocated to have delayed clamping were assigned a delay of ≥60 seconds. Delayed clamping reduced hospital mortality (risk ratio, 0.68; 95% confidence interval, 0.52-0.90; risk difference, -0.03; 95% confidence interval, -0.05 to -0.01; P = .005; number needed to benefit, 33; 95% confidence interval, 20-100; Grading of Recommendations, Assessment, Development, and Evaluations = high, with I 2  = 0 indicating no heterogeneity). In 3 trials in 996 infants ≤28 weeks' gestation, delayed clamping reduced hospital mortality (risk ratio, 0.70; 95% confidence interval, 0.51-0.95; risk difference, -0.05; 95% confidence interval, -0.09 to -0.01; P = .02, number needed to benefit, 20; 95% confidence interval, 11-100; I 2  = 0). In subgroup analyses, delayed clamping reduced the incidence of low Apgar score at 1 minute, but not at 5 minutes, and did not reduce the incidence of intubation for resuscitation, admission temperature, mechanical ventilation, intraventricular hemorrhage, brain injury, chronic lung disease, patent ductus arteriosus, necrotizing enterocolitis, late onset sepsis or retinopathy of prematurity. Delayed clamping increased peak hematocrit by 2.73 percentage points (95% confidence interval, 1.94-3.52; P < .00001) and reduced the proportion of infants having blood transfusion by 10% (95% confidence interval, 6-13%; P < .00001). Potential harms of delayed clamping included polycythemia and hyperbilirubinemia., Conclusion: This systematic review provides high-quality evidence that delayed clamping reduced hospital mortality, which supports current guidelines recommending delayed clamping in preterm infants. This review does not evaluate cord milking, which may also be of benefit. Analyses of individual patient data in these and other randomized controlled trials will be critically important in reliably evaluating important secondary outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate., Methods and Findings: Trials in which women considered at risk of preterm birth (<37 weeks' gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited., Conclusions: Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

Background: Systematic reviews are key tools to enable decision making by healthcare providers and policymakers. Despite the availability of the evidence based Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA-2009 and PRISMA-P 2015) statements that were developed to improve the transparency and quality of reporting of systematic reviews, uncertainty on how to deal with pediatric-specific methodological challenges of systematic reviews impairs decision-making in child health. In this paper, we identify methodological challenges specific to the design, conduct and reporting of pediatric systematic reviews, and propose a process to address these challenges., Discussion: One fundamental decision at the outset of a systematic review is whether to focus on a pediatric population only, or to include both adult and pediatric populations. Both from the policy and patient care point of view, the appropriateness of interventions and comparators administered to pre-defined pediatric age subgroup is critical. Decisions need to be based on the biological plausibility of differences in treatment effects across the developmental trajectory in children. Synthesis of evidence from different trials is often impaired by the use of outcomes and measurement instruments that differ between trials and are neither relevant nor validated in the pediatric population. Other issues specific to pediatric systematic reviews include lack of pediatric-sensitive search strategies and inconsistent choices of pediatric age subgroups in meta-analyses. In addition to these methodological issues generic to all pediatric systematic reviews, special considerations are required for reviews of health care interventions' safety and efficacy in neonatology, global health, comparative effectiveness interventions and individual participant data meta-analyses. To date, there is no standard approach available to overcome this problem. We propose to develop a consensus-based checklist of essential items which researchers should consider when they are planning (PRISMA-PC-Protocol for Children) or reporting (PRISMA-C-reporting for Children) a pediatric systematic review. Available guidelines including PRISMA do not cover the complexity associated with the conduct and reporting of systematic reviews in the pediatric population; they require additional and modified standards for reporting items. Such guidance will facilitate the translation of knowledge from the literature to bedside care and policy, thereby enhancing delivery of care and improving child health outcomes.

Background: The optimum time for commencing antiplatelet therapy for the prevention of preeclampsia and its complications is unclear. Aggregate data meta-analyses suggest that aspirin is more effective if given prior to 16 weeks' gestation, but data are limited because of an inability to place women in the correct gestational age subgroup from relevant trials., Objective: The objective of the study was to use the large existing individual participant data set from the Perinatal Antiplatelet Review of International Studies Collaboration to assess whether the treatment effects of antiplatelet agents on preeclampsia and its complications vary based on whether treatment is started before or after 16 weeks' gestation., Study Design: A meta-analysis of individual participant data including 32,217 women and 32,819 babies recruited to 31 randomized trials comparing low-dose aspirin or other antiplatelet agents with placebo or no treatment for the prevention of preeclampsia has been published previously. Using this existing data set, we performed a prespecified subgroup analysis based on gestation at randomization to antiplatelet agents before 16 weeks, compared with at or after 16 weeks, for 4 of the main outcomes prespecified in the Perinatal Antiplatelet Review of International Studies protocol: preeclampsia, death of baby, preterm birth before 34 weeks, and small-for-gestational-age baby. Individual participant data for the subgroups were combined in a meta-analysis using RevMan software. Heterogeneity was assessed with the I 2 statistic. The χ 2 test for interaction was used to assess statistically significant (P < .05) differences in treatment effect between subgroups., Results: There was no significant difference in the effects of antiplatelet therapy for women randomized before 16 weeks' gestation compared with those randomized at or after 16 weeks for any of the 4 prespecified outcomes: preeclampsia, relative risk, 0.90, (95% confidence interval, 0.79-1.03; 17 trials, 9241 women) for <16 weeks and relative risk, 0.90 (95% confidence interval, 0.83-0.98; 22 trials, 21,429 women) for ≥16 weeks (interaction test, P = .98); death of baby, relative risk, 0.89 (95% confidence interval, 0.73-1.09; 15 trials, 8626 women) for <16 weeks and relative risk, 0.92 (95% confidence interval, 0.79-1.07; 21 trials, 22,336 women) for ≥16 weeks (interaction test, P = .80); preterm birth prior to 34 weeks, relative risk, 0.90 (95% confidence interval, 0.77-1.04; 19 trials, 9155 women) for <16 weeks and relative risk, 0.91 (95% confidence interval, 0.82-1.00; 25 trials, 22,117 women) for ≥16 weeks (interaction test, P = .91); and small-for-gestational-age baby, relative risk, 0.76 (95% confidence interval, 0.61-0.94; 13 trials, 6393 women) for <16 weeks and relative risk, 0.95 (95% confidence interval, 0.84-1.08; 18 trials, 14,996 women) for ≥16 weeks (interaction test, P = .08)., Conclusion: The effect of low-dose aspirin and other antiplatelet agents on preeclampsia and its complications is consistent, regardless of whether treatment is started before or after 16 weeks' gestation. Women at an increased risk of preeclampsia should be offered antiplatelet therapy, regardless of whether they are first seen before or after 16 weeks' gestation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting in an increased incidence of adverse neonatal outcomes and health system costs. Evidence regarding the effectiveness of NAS prevention and management strategies is very weak and further research initiatives are critically needed to support meta-analysis and clinical practice guidelines. In NAS research, the choice of outcomes and the use of valid, responsive and feasible measurement instruments are crucial. There is currently no consensus and evidence-based core outcome set (COS) for NAS., Methods/design: The development of the NAS-COS will include five stages led by an international Multidisciplinary Steering Committee: (1) qualitative interviews with parents/families and a systematic review (SR) to identify items for inclusion in a COS. The SR will also identify participants for the Delphi survey, (2) a three-round Delphi survey to gain expert opinion on the importance of health outcomes influencing NAS management decisions, (3), a consensus meeting to finalize the items and definitions with experts and COS users, (4) feasibility and pilot testing, development of the COS and explanatory document and (5) implementation planning., Discussion: Since standardized outcome measurement and reporting will improve NAS clinical research consistency, efficacy and impact, this COS will reflect the minimum set of health outcomes which should be measured in trials evaluating interventions for preventing or treating NAS.

Aim: This study determined current international clinical practice and opinions regarding initial fractional inspired oxygen (FiO2 ) and pulse oximetry (SpO2 ) targets for delivery room resuscitation of preterm infants of less than 29 weeks of gestation., Methods: An online survey was disseminated to neonatal clinicians via established professional clinical networks using a web-based survey programme between March 9 and June 30, 2015., Results: Of the 630 responses from 25 countries, 60% were from neonatologists. The majority (77%) would target SpO2 between the 10th to 50th percentiles values for full-term infants. The median starting FiO2 was 0.3, with Japan using the highest (0.4) and the UK using the lowest (0.21). New Zealand targeted the highest SpO2 percentiles (median 50%). Most respondents agreed or did not disagree that a trial was required that compared the higher FiO2 of 0.6 (83%), targeting the 50th SpO2 percentile (60%), and the lower FiO2 of 0.21 (80%), targeting the 10th SpO2 percentile (78%). Most (65%) would join this trial. Many considered that evidence was lacking and further research was needed., Conclusion: Clinicians currently favour lower SpO2 targets for preterm resuscitation, despite acknowledging the lack of evidence for benefit or harm, and 65% would join a clinical trial., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Paediatric systematic reviews differ from adult systematic reviews in several key aspects such as considerations of child tailored interventions, justifiable comparators, valid outcomes and child sensitive search strategies. Available guidelines, including PRISMA-P (2015) and PRISMA (2009), do not cover all the complexities associated with reporting systematic reviews in the paediatric population. Using a collaborative, multidisciplinary structure, we aim to develop evidence-based and consensus-based PRISMA-P-C (Protocol for Children) and PRISMA-C (Children) Extensions to guide paediatric systematic review protocol and completed review reporting., Methods and Analysis: This project's methodology follows published recommendations for developing reporting guidelines and involves the following six phases; (1) establishment of a steering committee representing key stakeholder groups; (2) a scoping review to identify potential Extension items; (3) three types of consensus activities including meetings of the steering committee to achieve high-level decisions on the content and methodology of the Extensions, a survey of key stakeholders to generate a list of possible items to include in the Extensions and a formal consensus meeting to select the reporting items to add to, or modify for, the Extension; (4) the preliminary checklist items generated in phase III will be evaluated against the existing evidence and reporting practices in paediatric systematic reviews; (5) extension statements and explanation and elaboration documents will provide detailed advice for each item and examples of good reporting; (6) development and implementation of effective knowledge translation of the extension checklist, and an evaluation of the Extensions by key stakeholders., Ethics and Dissemination: This protocol was considered a quality improvement project by the Hospital for Sick Children's Ethics Committee and did not require ethical review. The resultant checklists, jointly developed with all relevant stakeholders, will be disseminated through peer-reviewed journals as well as national and international conference presentations. Endorsement of the checklist will be sought simultaneously in multiple journals., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Systematic reviews and meta-analyses are at the top of the 'evidence hierarchy' when assessing the effectiveness of health interventions. As such, they are important sources of synthesized information for decision-makers including consumers, clinicians, funders, payers, regulators, and researchers. The main reasons for undertaking systematic reviews and meta-analyses are to minimize bias and to maximize data by collating all the relevant, available evidence on a particular topic. In order to correctly inform decision-makers, but not mislead them, a number of key methodological conditions need to be met when undertaking these types of analysis. In this article we first review the history of systematic reviews and meta-analyses and then outline those conditions that may lead to the correct, or incorrect, use of these types of study. Also, new variations on standard systematic review methods are explored, with the pros and cons of each outlined., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: This study will assess measures of vascular health and inflammation in Aboriginal Australian adults with chronic kidney disease (CKD), and determine if intensive periodontal intervention improves cardiovascular health, progression of renal disease and periodontal health over a 24-month follow-up., Methods: The study will be a randomised controlled trial. All participants will receive the periodontal intervention benefits, with the delayed intervention group receiving periodontal treatment 24 months following baseline. Inclusion criteria include being an Aboriginal Australian, having CKD (a. on dialysis; b. eGFR levels of < 60 mls/min/1.73 m(2) (CKD Stages 3 to 5); c. ACR ≥ 30 mg/mmol irrespective of eGFR (CKD Stages 1 and 2); d. diabetes plus albuminuria (ACR ≥ 3 mg/mmol) irrespective of eGFR), having moderate or severe periodontal disease, having at least 12 teeth, and living in Central Australia for the 2-year study duration. The intervention involves intensive removal of dental plaque biofilms by scaling, root-planing and removal of teeth that cannot be saved. The intervention will occur in three visits; baseline, 3-month and 6-month follow-up. The primary outcome will be changes in carotid intima-media thickness (cIMT). Secondary outcomes will include progression of CKD or death as a consequence of CKD/cardiovascular disease. Progression of CKD will be defined by time to the development of the first of: (1) new development of macroalbuminuria; (2) 30 % loss of baseline eGFR; (3) progression to end stage kidney disease defined by eGFR < 15 mLs/min/1.73 m(2); (4) progression to end stage kidney disease defined by commencement of renal replacement therapy. A sample size of 472 is necessary to detect a difference in cIMT of 0.026 mm (SD 0.09) at the significance criterion of 0.05 and a power of 0.80. Allowing for 20 % attrition, 592 participants are necessary at baseline, rounded to 600 for convenience., Discussion: This will be the first RCT evaluating the effect of periodontal therapy on progression of CKD and cardiovascular disease among Aboriginal patients with CKD. Demonstration of a significant attenuation of CKD progression and cardiovascular disease has the potential to inform clinicians of an important, new and widely available strategy for reducing CKD progression and cardiovascular disease for Australia's most disadvantaged population., Trial Registration: This trial is registered with the Australian New Zealand Clinical Trial Registry ANZCTR12614001183673.

Background: Sharing data from clinical trials could assist with the advancement of science and medicine, potentially providing a better understanding of both the benefits and risks of medicines and other treatments. Sharing data also allows for questions to be addressed at the meta-analysis level that cannot be addressed within individual studies., Purpose: In this article, we offer some practical recommendations that will allow researchers to readily combine datasets from different studies and sources, thereby enabling meta-analyses that could have significant impact on advancing medicine., Methods: The authors relied on their collective experience in the conduct and reporting of clinical trials to define the areas of potential concern related to responsible sharing of clinical trial data. We conducted a review of the literature and engaged in an iterative consensus-building process., Results: To further the goal of responsible sharing of clinical trial data, collaboration on a consistent set of data standards and methods across both industry and academia is sorely needed. Protection of participant privacy is a paramount principle. The additional questions of who maintains, funds, and oversees databases of participant-level data will be important to resolve. Requiring researchers to register their requests for participant-level data and to provide details of their intended research would allow others to evaluate the proposed research plan, consistent with the principles of science and transparency., Limitations: The recommendations represent the views of the individual authors. We recognize that other approaches to data sharing that have been advocated are also based on sound ethical and scientific principles.

Background: The clinically appropriate range for oxygen saturation in preterm infants is unknown. Previous studies have shown that infants had reduced rates of retinopathy of prematurity when lower targets of oxygen saturation were used., Methods: In three international randomized, controlled trials, we evaluated the effects of targeting an oxygen saturation of 85 to 89%, as compared with a range of 91 to 95%, on disability-free survival at 2 years in infants born before 28 weeks' gestation. Halfway through the trials, the oximeter-calibration algorithm was revised. Recruitment was stopped early when an interim analysis showed an increased rate of death at 36 weeks in the group with a lower oxygen saturation. We analyzed pooled data from patients and now report hospital-discharge outcomes., Results: A total of 2448 infants were recruited. Among the 1187 infants whose treatment used the revised oximeter-calibration algorithm, the rate of death was significantly higher in the lower-target group than in the higher-target group (23.1% vs. 15.9%; relative risk in the lower-target group, 1.45; 95% confidence interval [CI], 1.15 to 1.84; P=0.002). There was heterogeneity for mortality between the original algorithm and the revised algorithm (P=0.006) but not for other outcomes. In all 2448 infants, those in the lower-target group for oxygen saturation had a reduced rate of retinopathy of prematurity (10.6% vs. 13.5%; relative risk, 0.79; 95% CI, 0.63 to 1.00; P=0.045) and an increased rate of necrotizing enterocolitis (10.4% vs. 8.0%; relative risk, 1.31; 95% CI, 1.02 to 1.68; P=0.04). There were no significant between-group differences in rates of other outcomes or adverse events., Conclusions: Targeting an oxygen saturation below 90% with the use of current oximeters in extremely preterm infants was associated with an increased risk of death. (Funded by the Australian National Health and Medical Research Council and others; BOOST II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry numbers, ACTRN12605000055606 and ACTRN12605000253606.).

Objective: To quantify and describe current cancer clinical trial activity in Australia and help guide future trials research using trial registries., Design and Setting: Data from cancer trials recruiting in Australia at 31 March 2009 were extracted from the Australian New Zealand Clinical Trials Registry and ClinicalTrials.gov. A regression model was used to identify factors associated with industry sponsorship., Main Outcome Measures: The proportion of cancer trials compared with estimated burden of disease for each cancer., Results: There were 368 interventional cancer trials open to recruitment. The most-researched cancer was breast cancer, accounting for 17% of trials. Only 7% of trials were in lung cancer, yet lung cancer is responsible for the greatest burden of disease. Industry was the primary sponsor in 43% of trials. Drug treatments were tested in most trials (69%). Trials were more likely to be industry sponsored if they tested systemic rather than local treatments (OR, 16.71; 95% CI, 4.70-59.43), included patients with advanced rather than early disease (OR, 3.76; 95% CI, 1.78-7.94) and used random rather than non-random allocation (OR, 1.78; 95% CI, 1.06-3.00)., Conclusion: There is variation in the number of trials according to cancer site, with some cancers being underrepresented relative to their burden of disease. Industry sponsorship is more likely for trials that investigate systemic therapy, recruit patients with advanced disease and are randomised.

Background: Clinical trials registries are now operating in the USA, Europe, Australia, China, and India and more are planned. Trial registries could be an excellent source of information about clinical trials for patients and others affected by cancer as well as health care professionals, but may be difficult for patients to navigate and use., Purpose: An opportunity arose in Australia to develop a consumer friendly cancer clinical trials website (Australian Cancer Trials Online (ACTO), www.australiancancertrials.gov.au) using an automated data feed from two large clinical trial registries. In this article, we describe aspects of this new website, and explore ways in which such a website may add value to clinical trial data which are already collected and held by trial registries., Methods: The development of ACTO was completed by a Web company working in close association with staff at the Australian New Zealand Clinical Trials Registry (ANZCTR), and with consumer representatives. Data for the website were sourced directly and only from clinical trial registries, thus avoiding the creation of an additional trials database. It receives an automated, daily data feed of newly registered cancer clinical trials from both the ANZCTR and Clinical Trials.gov., Results: The development of ACTO exemplifies the advantage of a local clinical trial registry working with consumers to provide accessible information about cancer clinical trials to meet consumers' information needs. We found that the inclusion of a lay summary added substantial value for consumers, and recommend that consideration be given to adding a lay summary to the mandatory data items collected by all trial registries. Furthermore, improved navigation, decision support tools, and consistency in data collection between clinical trial registries will also enable consumer websites to provide additional value for users., Limitations: Clinical trial registration is not compulsory in Australia. If the additional cancer items (including a lay summary) are not provided by registrants of cancer trials on ANZCTR, this can compromise the quality and usefulness of the data for the end-user, in this case consumers, as they may encounter gaps in the data., Conclusion: Expanding the World Health Organization Trial Registration Data Set to include this additional information, particularly the lay summary, would be valuable. A well-coordinated system of clinical trial registration is critical to the success of efforts to provide better access for all to inform about clinical trials.

Objectives: To assess how trial information reported in conference abstracts differs to their subsequent full publication., Methods: Randomized trials reported at the American Society of Clinical Oncology conference (1992) were identified. CENTRAL and PubMed (December 2002) were searched to identify corresponding full publications. A checklist (based on CONSORT) was used to compare abstracts for 37 trials with their full publication., Results: Some aspects were well reported. Ninety-five percent of study objectives, 92% of participant eligibility, 100% of trial interventions, and 84% of primary outcomes were the same in both abstract and full publication. Other areas were more discrepant. Forty-six percent reported the same number of participants randomized in the abstract and full publication; only 22% reported the same number analyzed (median number analyzed per trial was 96 for abstracts and 117 for full publications). Eighty-two percent of trials were closed to follow-up in the full publication compared to 19% of abstracts. Lack of information was a major problem in assessing trial quality: no abstracts reported on allocation concealment, 16% reported on blinding and 14% reported intention to treat analysis. These figures were 49, 19, and 46%, respectively, for full publications., Conclusion: The information given for trials in conference proceedings can be unstable, especially for trials presenting early or preliminary results, and needs to be improved.