Background: The findings of individual epidemiological studies that suggest an association between some Persistent Organic Pollutants (POPs) and Gestational Diabetes Mellitus (GDM) are inconclusive. Objectives: To estimate the strength of the association between POPs exposure and GDM in a systematic review with meta-analysis. Search strategy: MEDLINE, Scopus, and Web of Science were searched until 2022. Selection criteria: Cohort and case-control studies analyzing the association between POPs and GDM in healthy pregnant women. Data collection and analysis: Quality was assessed using QUIPS scale and standardized mean differences (SMD) and 95% confidence intervals (CI) was pooled using random-effect model. Main results: Fourteen articles including 11,422 participants were selected. The risk of bias of included studies was high in 4 (28.6%), moderate in 9 (64.3%) and low in 1 (7.14%). Only six POPs showed a significative SMD between GDM cases and controls: Perfluorobutanesulfonic acid (PFBS) 0.33 (95% CI 0.23, 0.43; I2=0%); Perfluorodecanoic acid (PFDA) -0.11 (95% CI -0.20, -0.01, I2 = 0.0%); 2,2’,3,4,4’,5,5’-Heptachlorobiphenyl (PCB 180) 0.37 (95% CI 0.19, 0.56; I2=25.3%); 2,2’,4,4’,5-Decabromodiphenyl ether (BDE 99) 0.36 (95% CI 0.14, 0.59; I2=0%); 2,2’,4,4’,6-Decabromodiphenyl ether (BDE 100) 0.42 (95% CI 0.19, 0.38; I2=0%); and, Hexachlorobenzene (HCB) 0.22 (95% CI 0.01, 0.42, I2=39.6%). For other POPs, no statistically significant association was observed. Conclusion: The available evidence is variable on quality and results were heterogeneous making impossible to establish a clear association between POPs exposure and risk of GDM. Improve the methodology of epidemiological studies assessing the association of POPs and risk of adverse clinical outcomes are needed.

Background: Science integrity initiatives require specific recommendations for randomised clinical trials (RCT). Objective: To prepare a set of statements for RCT integrity through an international multi-stakeholder consensus. Methods: Following prospective registration (https://osf.io/bhncy, https://osf.io/3ursn), the consensus was developed via: multi-country multidisciplinary stakeholder group composition and engagement; evidence synthesis of 55 systematic reviews concerning RCT integrity; anonymised two-round modified Delphi survey with consensus threshold based on the average percent of majority opinions; and, a final consensus development meeting. Results: There were 30 stakeholders representing 14 countries from 5 continents including trialists, ethicists, methodologists, statisticians, consumer representative, industry representative, systematic reviewers, funding body panel members, regulatory experts, authors, journal editors, peer-reviewers and advisors for resolving integrity concerns. Delphi survey response rate was 86.7% (26/30 stakeholders). There were 111 statements (73 stakeholder-provided, 46 systematic review-generated, 8 supported by both) in the initial long list, with 8 additional statements provided during the consensus rounds. Through consensus the final set consolidated 81 statements (49 stakeholder-provided, 41 systematic review-generated, 9 supported by both). The entire RCT life cycle was covered by the set of statements including general aspects (n=6), design and approval (n=11), conduct and monitoring (n=19), reporting of protocols and findings (n=20), post-publication concerns (n=12), and future research and development (n=13). Conclusion: Implementation of this multi-stakeholder consensus statement is expected to enhance RCT integrity.

Background: The trustworthiness of randomised clinical trials (RCTs) is suffering a crisis of confidence. Objectives: We undertook an umbrella review of the research integrity literature concerning RCTs. Search strategy and selection criteria: Following prospective registration (https://osf.io/3ursn), two reviewers independently searched PubMed, Scopus, Cochrane Library and Google Scholar, without language or time restrictions until November 2021. We included systematic reviews covering any aspect of research integrity throughout the RCT lifecycle. Data collection and analysis: We assessed methodological quality using a modified AMSTAR-2 tool and collated the main findings. Main results: There were 55 relevant reviews summarising a total of 6001 studies (median per review 63; range 8-1106 studies). The overall quality of 53 (96.4%) reviews was critically low. Eight (14.6%) reviews focused on the general aspects of a RCT, 12 (21.8%) on the design and approval, 6 (10.9%) on the conduct and monitoring, 21 (38.2%) on the reporting of protocols and findings, one (1.8%) on post-publication concerns and 7 (12.7%) on future research and development. The integrity issues covered were varied, the most common being the importance of ethics (10/55, 18.2%) and transparency (10/55, 18.2%). Conclusions: Various research integrity issues covering RCT lifecycle, captured from mostly low-quality reviews, provided a broad overview emphasising the need for high level of ethical standards and professionalism. Many gaps in the RCT integrity landscape were also identified. There is a need to generate multistakeholder consensus to create specific RCT integrity standards.

Background: Endometriosis is a chronic, often debilitating condition with a current significant delay from symptom onset to diagnosis. Objectives: To investigate the accuracy of symptoms, clinical history and non-invasive tests to predict pelvic endometriosis. Data sources: Medline, Embase, Web of Science and Scopus from conception to September 2022. Selection criteria: Primary test accuracy studies assessing selected non-invasive tests against a reference standard diagnosis for endometriosis. Data extraction and synthesis: Two authors independently conducted data extraction and study quality assessment. Grading of evidence was performed using a novel visual pentagon model. Meta-analyses of test accuracy was estimated using bivariate random effects models. Results: The 125 included studies (250,574 participants) showed mixed quality. Studies applying non-surgical (database/self-reporting) reference standard had a greater risk of bias. In 98 studies applying surgical reference standard, summary diagnostic odds ratios were: dysmenorrhoea 2.56 (95% confidence interval 1.99-3.29); pelvic pain 2.56 (1.73-3.74); dyschezia 2.05 (1.36-3.10); dyspareunia 2.45 (1.71-3.52); family history of endometriosis 6.79 (4.08-11.3); nulligravidity of 2.01 (1.62-2.50); BMI ≥30kg/m2 0.37 (0.19-0.68); TVUSS endometrioma 91.2 (44.0-189); TVUSS invasive endometriosis 26.1 (9.28-73.5); and CA-125 >35U/mL 16.0 (8.09-31.7). Sensitivity analysis excluding all high-risk studies found concordant results. Conclusions: This meta-analysis collated the performance of non-invasive tests for endometriosis across a comprehensive and geographically varied population. Study quality was mixed, however results were consistent with high-risk studies excluded. These findings will inform future prediction models for triage in primary care. Funding: This research received no specific funding. Keywords: Endometriosis; diagnosis; laparoscopy; pelvic pain; sub-fertility

Background: Cervical cancer affects 3,197 women in the UK, and 604000 women worldwide annually, with peak incidence seen between 30-34 years of age. For many, fertility-sparing surgery is an appealing option where possible. However, absence of large-scale data, along with a notable variation in reported outcomes in relevant studies may undermine future efforts for consistent evidence synthesis. Objectives: To systematically review the reported outcomes measured in studies that include women who underwent fertility-sparing surgery for cervical cancer and identify whether variation exists. Search Strategy: We searched MEDLINE, EMBASE, and CENTRAL from inception to February 2019. Selection Criteria: Randomised controlled trials, cohort and observational studies, and case studies of more than 10 participants from January 1990 to date. Data Collection and Analysis: Study characteristics and all reported treatment outcomes. Main results: 104 studies with a sum of 9535 participants were identified. Most studies reported on oncological outcomes (97/104), followed by fertility and pregnancy (86/104), post-operative complications (74/104), intra-operative complications (72/104), and quality of life (5). There were huge variation and heterogeneity in reported outcomes, with only 12% being good quality and 87% being of poor quality. Conclusions: There is significant heterogeneity in the reported outcomes. An agreed Core Outcome Set (COS) is necessary for future studies to effectively harmonise reported outcomes that are measurable and relevant to patients, clinicians, and researchers. This systematic review sets the groundwork for the development of a COS for fertility sparing surgery in cervical cancer. Funding: British Medical Association’s Strutt and Harper Grant.

Objective: To evaluate the effectiveness of virtual reality as a distraction technique in the management of acute pain and anxiety during outpatient hysteroscopy. Methods: A parallel group, prospective randomised controlled trial was conducted at a UK University Hospital (August to October 2018) (ClinicalTrials.gov Id: NCT03699280). Forty consenting, eligible women were randomised to virtual reality intervention (immersive video content as a distraction method) or standard care during outpatient hysteroscopy. Pain and anxiety outcomes were measured as a numeric rating score (scale of 0-10). Results: Compared to standard care, women with virtual reality intervention experienced less average pain (score 6.0 vs 3.7, mean difference 2.3, 95% CI 0.61-3.99, p=0.009) and anxiety (score 5.45 vs 3.3, mean difference 2.15, 95% CI 0.38-3.92, p=0.02). Conclusion: Virtual Reality was effective in reducing pain and anxiety during outpatient hysteroscopy in a pilot trial. Its wide potential role in ambulatory gynaecologic procedures needs further evaluation.