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As the burden of misconduct in medical research is increasingly recognised, questions have been raised about how best to address this problem. Whilst there are existing mechanisms for the investigation and management of misconduct in medical literature, they are inadequate to deal with the magnitude of the problem. Journal editors and publishers play an essential role in protecting the veracity of the medical literature. Whilst ethical guidance for journal editors and publishers is important, it is not as readily enforceable as legal obligations might be. This article questions the legal obligations that might exist for journal editors and publishing companies with respect to ensuring the veracity of the published literature. Ultimately, there is no enforceable legal obligation in Australia, the United Kingdom, or the United States. In light of this, more robust mechanisms are needed to deliver greater confidence and transparency in the investigative process, the management of concerns or findings of misconduct and the need to cleanse the literature. We show that the law disincentivises journals and publishers from ensuring truth in their publications. There are harmful consequences for medical care and public confidence in the medical profession and health care system when the foundations of medical science are questionable.

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.

Objective: To investigate pregnant women's preferences for risks of vaginal and caesarean birth, including possible impacts on future fertility. Methods: In this discrete choice experiment, low-risk nulliparous pregnant women recruited after 28 weeks of gestation evaluated eight choice sets, each between two different hypothetical births scenarios which intermixed the risks of planned caesarean or vaginal birth. Scenarios consisted of six attributes: pain, maternal health, neonatal health, risk of unplanned intervention, impact on fertility and risk of complications in the next pregnancy. All scenarios contained risks to neonatal health as neither vaginal nor caesarean birth guarantee an ideal outcome. Choice data were analysed using a conditional logistic regression model. Results: Between June and September 2023, 211 participants, including 34 from pilot interviews, completed the questionnaire. Influential attributes were maternal health (conditional odds ratio [COR] 1.29, 95% CI 1.17 to 1.42, p<0.001) and risk of unplanned intervention (COR 1.37, 95% CI 1.24 to 1.51, p<0.001), favouring caesarean birth. Conversely, impact on fertility (COR 0.75, 95% CI 0.68 to 0.83, p<0.001) and complications in the next pregnancy favoured vaginal birth (COR 0.90, 95% CI 0.82 to 1.00, p = 0.045). Conclusions: Participants weighed the included morbidity risks of planned caesarean and vaginal birth in a low-risk pregnancy approximately equally. To facilitate an informed birth decision, clinicians should, apart from neonatal outcomes, particularly consider discussing impacts on fertility, maternal health and the risks of unplanned intervention or future pregnancy complications. [ABSTRACT FROM AUTHOR]

Increasing integrity concerns in medical research have prompted the development of tools to detect untrustworthy studies. Existing tools primarily assess published aggregate data (AD), though scrutiny of individual participant data (IPD) is often required to detect trustworthiness issues. Thus, we developed the IPD Integrity Tool for detecting integrity issues in randomised trials with IPD available. This manuscript describes the development of this tool. We conducted a literature review to collate and map existing integrity items. These were discussed with an expert advisory group; agreed items were included in a standardised tool and automated where possible. We piloted this tool in two IPD meta‐analyses (including 116 trials) and conducted preliminary validation checks on 13 datasets with and without known integrity issues. We identified 120 integrity items: 54 could be conducted using AD, 48 required IPD, and 18 were possible with AD, but more comprehensive with IPD. An initial reduced tool was developed through consensus involving 13 advisors, featuring 11 AD items across four domains, and 12 IPD items across eight domains. The tool was iteratively refined throughout piloting and validation. All studies with known integrity issues were accurately identified during validation. The final tool includes seven AD domains with 13 items and eight IPD domains with 18 items. The quality of evidence informing healthcare relies on trustworthy data. We describe the development of a tool to enable researchers, editors, and others to detect integrity issues using IPD. Detailed instructions for its application are published as a complementary manuscript in this issue. [ABSTRACT FROM AUTHOR]

Increasing concerns about the trustworthiness of research have prompted calls to scrutinise studies' Individual Participant Data (IPD), but guidance on how to do this was lacking. To address this, we developed the IPD Integrity Tool to screen randomised controlled trials (RCTs) for integrity issues. Development of the tool involved a literature review, consultation with an expert advisory group, piloting on two IPD meta‐analyses (including 73 trials with IPD), preliminary validation on 13 datasets with and without known integrity issues, and evaluation to inform iterative refinements. The IPD Integrity Tool comprises 31 items (13 study‐level, 18 IPD‐specific). IPD‐specific items are automated where possible, and are grouped into eight domains, including unusual data patterns, baseline characteristics, correlations, date violations, patterns of allocation, internal and external inconsistencies, and plausibility of data. Users rate each item as having either no issues, some/minor issue(s), or many/major issue(s) according to decision rules, and justification for each rating is recorded. Overall, the tool guides decision‐making by determining whether a trial has no concerns, some concerns requiring further information, or major concerns warranting exclusion from evidence synthesis or publication. In our preliminary validation checks, the tool accurately identified all five studies with known integrity issues. The IPD Integrity Tool enables users to assess the integrity of RCTs via examination of IPD. The tool may be applied by evidence synthesists, editors and others to determine whether an RCT should be considered sufficiently trustworthy to contribute to the evidence base that informs policy and practice. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Melatonin has been suggested to have a biological role in the onset and progress of labor. We tested the hypothesis that the addition of melatonin during an induction of labor will reduce the need for a cesarean birth.This trial underwent protocol amendments that are detailed in the main text of the article. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12616000311459). At a multi‐center health service including secondary and tertiary obstetric hospitals, we performed a randomized, double‐blind, placebo‐controlled trial in women with a singleton cephalic pregnancy, free of significant maternal or perinatal complications who were undergoing induction of labor (with or without cervical ripening). Women were randomized to 10 mg melatonin vs placebo, with cervical ripening as required, and then 6‐h during their induction of labor to a maximum of four doses or until birth. The primary outcome was cesarean birth. Secondary outcomes included labor, maternal, and neonatal outcomes. Data were analyzed using intention to treat. Sub‐group analyses based on mode of ripening and parity were also performed.Between 2019 and 2021 we randomized 189 women (103 to melatonin and 86 to placebo). The study was prematurely terminated due to logistical complications resulting from the COVID‐19 pandemic. Cesarean rates were 28/103 (27.2%) in the melatonin group versus 20/84 (23.3%) in the placebo group (RR 1.17 95% CI 0.71–1.92). There were no significant differences in rate of cesarean birth between the melatonin and placebo groups for failure to progress (13.4% and 9.3%, respectively, RR 1.46; 95% CI 0.64–3.32) or suspected fetal distress (10.7% and 10.5%, respectively, RR 1.02; 95% CI 0.44–2.34). The melatonin group had significantly lower rates of spontaneous vaginal birth within 24 h (35.0% vs. 50.0%; RR 0.70 95% CI 0.50–0.98). The rates of secondary outcomes such as total length of labor, rate of postpartum hemorrhage, and instrumental birth were comparable. Babies born in the melatonin group were more likely to need admission to the special care nursery, namely for hypoglycemic monitoring (18.5% vs. 8.1% RR 2.26; 95% CI 1.00–5.10).In women undergoing induction of labor, melatonin does not reduce the cesarean section rate. Melatonin use intrapartum may also be associated with neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

Introduction: The 2024 Australian evidence‐based guideline for unexplained infertility provides clinicians with evidence‐based recommendations for the optimal diagnostic workup for infertile couples to establish the diagnosis of unexplained infertility and optimal therapeutic approach to treat couples diagnosed with unexplained infertility in the Australian health care setting. The guideline recommendations were adapted for the Australian context from the rigorous, comprehensive European Society of Human Reproduction and Embryology (ESHRE) 2023 Evidence‐based guideline: unexplained infertility, using the ADAPTE process and have been approved by the Australian National Health and Medical Research Council. Main recommendations: The guideline includes 40 evidence‐based recommendations, 21 practice points and three research recommendations addressing: definition — defining infertility and frequency of intercourse, infertility and age, female and male factor infertility;diagnosis — ovulation, ovarian reserve, tubal factor, uterine factor, laparoscopy, cervical/vaginal factor, male factor, additional testing for systemic conditions; andtreatment — expectant management, active treatment, mechanical‐surgical procedures, alternative therapeutic approaches, quality of life. Changes in assessment and management resulting from the guideline: This guideline refines the definition of unexplained infertility and addresses basic diagnostic procedures for infertility assessment not considered in previous guidelines on unexplained infertility. For therapeutic approaches, consideration of evidence quality, efficacy, safety and, in the Australian setting, feasibility, acceptability, cost, implementation and ultimately recommendation strength were integrated across multidisciplinary expertise and consumer perspectives in adapting recommendations to the Australian context by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, which had not been used in past guidelines on unexplained infertility to formulate recommendations. The Australian process also included an established data integrity check to ensure evidence could be trusted to guide practice. Practice points were added and expanded to consider the Australian setting. No evidence‐based recommendations were underpinned by high quality evidence, with most having low or very low quality evidence. In this context, research recommendations were made including those for the Australian context. The full guideline and technical report are publicly available online and can be accessed at https://www.monash.edu/medicine/mchri/infertility and are supported by extensive translation resources, including the free patient ASKFertility mobile application (https://www.askfertility.org/). [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. WHAT IS KNOWN ALREADY HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. STUDY DESIGN, SIZE, DURATION This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012–2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). PARTICIPANTS/MATERIALS, SETTINGS, METHODS The study included 69 children aged 6–9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. MAIN RESULTS AND THE ROLE OF CHANCE School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. LIMITATIONS, REASONS FOR CAUTION The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. WIDER IMPLICATIONS OF THE FINDINGS This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. STUDY FUNDING/COMPETING INTEREST(S) The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER NCT05168228 [ABSTRACT FROM AUTHOR]