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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.

Background Tubal ectopic pregnancies can cause significant morbidity or even death. Current treatment is with methotrexate or surgery. However, methotrexate treatment can fail in approximately 30% of women. Gefitinib, an epidermal growth factor receptor inhibitor, may improve the effects of methotrexate. We assessed the efficacy of administering oral gefitinib with methotrexate, versus methotrexate alone, to treat a tubal ectopic pregnancy. Objectives To test the hypothesis a combination of gefitinib with methotrexate can increase resolution of stable tubal ectopic pregnancy without the need for surgery, compared with methotrexate alone. Design A randomised, double-blind, placebo-controlled, multicentre, superiority trial. Setting Fifty UK hospitals. Participants A target of 328 women with a stable, tubal ectopic pregnancy. Intervention Women were randomised to combination of methotrexate and gefitinib or methotrexate and placebo. All participants received a single intramuscular dose of methotrexate 50 mg/m2 and were randomised in a 1:1 ratio of oral gefitinib (250 mg daily for 7 days) or placebo. Main outcome measures The primary outcome was surgical intervention for resolution of ectopic pregnancy. Secondary outcomes were the need for an additional dose of methotrexate, time to resolution of the ectopic pregnancy, number of treatment-associated hospital visits, safety and tolerability, acceptability of treatment and return to menses. Results Between 2 November 2016 and 6 October 2021, 328 women were randomly allocated to methotrexate and gefitinib (n = 165) or methotrexate and placebo (n = 163). Three women in the placebo group withdrew. Surgical intervention occurred in 30% (50/165) of the gefitinib group and in 29% (47/160) of the placebo group (adjusted risk ratio 1.15, 95% confidence interval 0.85 to 1.58; adjusted risk difference −0.01, 95% confidence interval −0.10 to 0.09; p = 0.37). Without surgical intervention, median time to resolution was 28.0 days in the gefitinib group and 28.0 days in the placebo group (subdistribution hazard ratio 1.03, 95% confidence interval 0.75 to 1.40). The need for additional methotrexate doses, number of additional hospital visits, participant acceptability, time to return of menses and serious adverse events were similar in both groups. Diarrhoea and rash were more common in the gefitinib group. Conclusions The addition of gefitinib to standard medical management with methotrexate to treat tubal ectopic pregnancy is not clinically effective as it does not reduce subsequent surgical intervention and is associated with higher rates of reported symptoms than placebo. Limitations We were unable to investigate how different gefitinib doses or modes of delivery would impact on the results. Future work Questions that remain unaddressed relate to the use of methotrexate and gefitinib combination treatment for other extrauterine and uterine ectopic pregnancy, such as caesarean scar pregnancies, or in the management of choriocarcinoma. Trial registration This trial is registered as ISRCTN 67795930 and EudraCT 2015-005013-76. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme and will be published in full in Efficacy and Mechanistic Evaluation; Vol. 10, No. 1. The gefitinib and placebo were supplied by Astra Zeneca. See the NIHR Journals Library website for further project information. Plain language summary What was the question? A tubal ectopic pregnancy is where a fertilised egg is not growing in the womb. The pregnancy cannot be saved and the woman is at risk of losing her fallopian tube and if this pregnancy is left to grow can even die. Current treatment is with methotrexate or surgery. An operation can happen because either the ectopic pregnancy has ruptured and caused internal bleeding, the medical treatment has not worked and the ectopic pregnancy needs to be removed or the patient can chose to have an operation. However, methotrexate treatment can fail in approximately 30% of women. We carried out research to see if the addition of a new drug (gefitinib, a drug used for lung cancer) to methotrexate could lower the number of women needing an operation to remove their ectopic pregnancy. What did we do? We involved 328 women with a stable tubal ectopic pregnancy, who were being treated medically with methotrexate, and randomly assigned them to have methotrexate alone or a combination of methotrexate and gefitinib. The gefitinib was taken in tablet form for 7 days, and the methotrexate was given as an injection. We followed the women up in line with their clinical care until their ectopic pregnancy resolved or they had surgery to remove the ectopic pregnancy. What did we find? The addition of gefitinib to methotrexate did not reduce the number of women who required surgery to remove their ectopic pregnancy. More women taking gefitinib experienced side effects, such as a facial rash or diarrhoea. What does this mean? Treatment with methotrexate remains the only drug treatment option for ectopic pregnancy. More research is needed. Scientific summary Background Tubal ectopic pregnancy (EP) can cause significant morbidity or even death. Current treatment is with methotrexate (MTX) or surgery. However, MTX treatment can fail in approximately 30% of women. Preclinical studies have shown that tubal implantation sites express high levels of epidermal growth factor receptor (EGFR) and that gefitinib (an EGFR antagonist) augments MTX-induced regression of pregnancy-like tissue. Clinical evidence from uncontrolled phase I and II trials has raised the possibility that a combination of MTX and gefitinib could be a more effective medical treatment than MTX alone to treat stable tubal EP. Objectives To test the hypothesis, a combination of gefitinib with MTX can increase resolution of stable tubal EP without the need for surgery, compared with MTX alone. Design A randomised, double-blind, placebo-controlled, multicentre, superiority trial. Setting This trial took place in 50 hospitals in the UK. Participants A target of 328 women with a stable, tubal EP. Intervention Participants were randomly assigned in a 1:1 ratio to receive either gefitinib and MTX or matched placebo and MTX with the use of minimisation to balance trial-group assignments according to baseline human chorionic gonadotropin levels (

Background: Rising health care costs are a major concern in most Western countries. The substitution of healthcare stands as a strategic approach aimed at mitigating costs while offering medical services in proximity to patients' residences. An illustrative instance involves the migration of outpatient hospital care to primary care settings. Notably, the insertion of intrauterine devices (IUDs) can be safely executed within primary care contexts. In order to establish a pragmatic objective for the rate of IUD substitution, we conducted an evaluation of regional disparities in healthcare substitution pertaining to the insertion of intrauterine devices. Furthermore, we investigated disparities in the follow-up ultrasound and reinsertion of IUDs between primary and secondary healthcare environments. Methods: All women who underwent IUD insertion in Dutch primary care (by general practitioners and midwives) and secondary care (by hospital physicians) between January 1, 2016, and December 31, 2020 were included. The main outcome measures were the case-mix adjusted IUD insertion rates at the regional level by care setting and the proportions requiring follow-up ultrasound and IUD reinsertion within three months. Results: Of the 840,766 IUD placements, 74% were inserted in primary care and 26% in secondary care. The proportion inserted in primary care increased from 70% in 2016 to 77% in 2020. The observed substitution rate ranged from 58 to 82% between regions. Compared with health care professionals in primary care, those in secondary care performed more ultrasounds to verify IUD placement (23% vs. 3%; p-value < 0.01) and more IUD reinsertions within three months (6% vs. 2%; p-value < 0.01). Conclusions: IUDs are increasingly being inserted in Dutch primary care, with peak regional IUD insertion care substitution rates at ≥ 80%. IUD insertion care substitution to primary care appears to be associated with significantly fewer women having follow-up ultrasound or IUD reinsertion within three months. [ABSTRACT FROM AUTHOR]

Background: Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. Objectives: To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. Search strategy: The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Selection criteria: Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. Data collection and analysis: An individual participant data meta‐analysis was carried out. Main results: Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low‐dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low‐dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low‐dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low‐dose vaginal misoprostol (aOR 0.80, 95% CI 0.65–0.98, P = 0.03, I2 = 0%). Conclusions: Low‐dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low‐dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone. This article includes Author Insights, a video abstract available at: https://vimeo.com/915799731. [ABSTRACT FROM AUTHOR]

Objective: To describe clinicians' attitudes, knowledge and practice relating to the anti‐müllerian hormone (AMH) test. Design: Cross‐sectional nationwide survey. Setting: Australia. Population or Sample: A total of 362 general practitioners (GPs), gynaecologists and reproductive specialists. Methods: Clinicians were recruited through relevant professional organisations, with data collected from May 2021 to April 2022. Main outcome measures: Clinicians' attitudes, knowledge and practice relating to the AMH test, measured using multiple choice, Likert scales and open‐ended items. Results: Fifteen percent of GPs (n = 27) and 40% of gynaecologists and other specialists (n = 73) order at least one AMH test per month. Specialists reported raising the idea of testing most of the time, whereas GPs reported that patient request was more common. Half of clinicians lacked confidence interpreting (n = 182, 51%) and explaining (n = 173, 48%) an AMH result to their patients. Five percent (n = 19) believed the test was moderately/very useful in predicting natural conception/birth and 22% (n = 82) believed the same for predicting premature menopause, despite evidence that the test cannot reliably predict either. Forty percent (n = 144) had previously ordered the test to help with reproductive planning and 21% (n = 75) to provide reassurance about fertility. Conclusions: Clinicians reported use of AMH testing in clinical circumstances not supported by the evidence. With the proliferation of direct‐to‐consumer testing, efforts to support clinicians in the judicious use of testing and effectively navigating patient requests are needed. [ABSTRACT FROM AUTHOR]

Aim: This study aims to examine the association between body mass index (BMI) and mode of delivery, progression of labour, and intrapartum interventions. Methods: This was a retrospective matched cohort study including Class III obese (BMI ≥40 kg/m2) and normal BMI (BMI <25 kg/m2) women planning a vaginal birth who had a live, singleton delivery from January 2015 to December 2018. Patients were matched (1:1) based on age, gestational age, parity, onset of labour and birth weight. The primary outcome was caesarean delivery (CD). Secondary outcomes were delivery outcomes, intrapartum management and interventions. Rates of each outcome were compared with matched analysis, and duration of labour with time‐to‐event analysis. Results: We studied two groups of 300 pregnant women. The CD rate was significantly higher for obese women than the normal BMI cohort (19.3% vs 13.3%; risk ratio (RR) 1.43, 95% CI 1.02–1.98, P = 0.035). Cervical dilation prior to CD for failure to progress was slower in obese than normal BMI (0.04 vs 0.16 cm/h). The obese cohort had a longer duration of labour in those who underwent induction (13.70 vs 11.48 h, P = 0.024). Intrapartum intervention rates were higher for obese women, with significant differences in rates of fetal scalp electrodes (72.7% vs 22.7%, RR 3.20, 95% CI 2.58–3.99, P < 0.001), intrauterine pressure catheters (18.3% vs 0%, P < 0.001), epidural analgesia (44.0% vs 37.0%, RR 1.20, 95% CI 1.01–1.44, P = 0.040) and fetal scalp lactate sampling (8.0% vs 3.0%, RR = 2.67, 95% CI 1.33–5.33, P = 0.004). Conclusion: Class III obesity is associated with an increased risk of CD and intrapartum interventions. [ABSTRACT FROM AUTHOR]