Obesity and related cardiometabolic comorbidities, including hypertension, dyslipidaemia, diabetes, metabolic dysfunction-associated steatotic liver disease and atherosclerotic cardiovascular disease, are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes and overall quality of life, yet evidence remains fragmented. The Modulate Obesity and relateD metabolic complIcations For Yielding improvements in IBD outcomes (MODIFY-IBD) initiative aims to synthesise evidence and generate consensus recommendations to guide practice and future research in this area. This study describes a protocol for a structured evidence synthesis and Research ANd Development/University of California, Los Angeles (RAND/UCLA) Appropriateness Method (RUAM) consensus process.

We will conduct three systematic reviews and a structured evidence synthesis organised into three domains: (1) the impact of obesity on IBD outcomes, (2) the burden of cardiometabolic complications in IBD and (3) the management of overweight, obesity and cardiometabolic comorbidities in IBD. A multidisciplinary international panel of gastroenterologists, surgeons, endocrinologists, hepatologists, cardiologists and dietitians will assess each statement using the RAND/UCLA appropriateness method. Panellists will rate the appropriateness of each statement (only those that fall within their area of expertise) on a 1–9 scale (1–3=inappropriate, 4–6=uncertain and 7–9=appropriate), with medians rounded up (eg, 6.5=appropriate). Agreement will be assessed using the RAND Disagreement Index (DI

This study will not involve direct patient participation, as it is based on evidence synthesis and expert consensus; therefore, formal research ethics committee approval will not be required. Patient representatives will contribute to the consensus process to provide contextual perspectives but no identifiable data will be collected.

Findings will be disseminated through publication in peer-reviewed journals, presentation at major gastroenterology and IBD conferences and communication with professional societies. A lay summary and patient-friendly infographic will also be developed to facilitate translation of recommendations into clinical practice.

CRD420251178843: a systematic review of the impact of obesity on inflammatory bowel disease outcomes.

CRD420251178799: a systematic review of cardiometabolic complications in inflammatory bowel disease.

CRD420251174653: management of overweight, obesity and cardiometabolic comorbidities in inflammatory bowel disease: a systematic review.

Prostate cancer diagnosis and treatment planning depend on accurate histopathological assessment of needle biopsies, particularly through the Gleason scoring system. The inherently subjective nature of the grading creates variability between pathologists, potentially resulting in suboptimal patient management decisions. These reproducibility challenges extend beyond Gleason scoring to encompass other critical diagnostic and prognostic markers, including cancer volume quantification and detection of cribriform morphology patterns and perineural invasion. Artificial intelligence (AI) applications in digital pathology have emerged as promising solutions for enhancing diagnostic consistency and accuracy, with recent research demonstrating that automated systems can match expert-level performance in prostate biopsy evaluation. Nevertheless, comprehensive validation studies have revealed concerning limitations in model generalisability when deployed across different clinical environments and patient populations. Recent systematic reviews revealed widespread risk-of-bias limitations and insufficient external validation in AI diagnostic studies, highlighting critical needs for accumulated evidence supporting generalisability before clinical implementation. Rigorous external validation with preregistered protocols using independent datasets from diverse clinical settings remains essential to establish the reliability and safety of AI-assisted prostate pathology systems.

This study protocol establishes a framework for the retrospective external validation of an AI system developed for prostate biopsy assessment, to be conducted on the case-control samples of the National Prostate Cancer Register of Sweden, ProMort study (1998-2015). The primary aim is to evaluate the AI model’s diagnostic accuracy and Gleason grading performance using completely independent datasets separate from any model development or previously used validation cohorts. The diversity of the validation samples, spanning multiple geographic regions, temporal collection periods and reference standards, allows evaluation of model robustness across varied clinical contexts. Secondary aims encompass evaluating AI performance in cancer length estimation and detection of cribriform patterns and perineural invasion. This protocol delineates procedures for data collection, reference standard clarification and prespecified statistical analyses, ensuring comprehensive validation and reliable performance assessment. The study design conforms to established reporting guidelines Checklist for Artificial Intelligence in Medical Imaging (CLAIM) and Standards for Reporting Diagnostic Accuracy Studies using Artificial Intelligence (STARD-AI), and recognised best practices for AI validation in medical imaging.

Data collection and usage were approved by the Swedish Regional Ethics Review Board and the Swedish Ethical Review Authority (permits 2012/1586-31/1, 2016/613-31/2, 2019-01395, 2019-05220). The study adheres to the Declaration of Helsinki principles, and findings will be made available in open access peer-reviewed publications.

Neurodevelopmental impairments in congenital heart disease (CHD) are the most frequent long-term morbidity. Adverse neurodevelopmental outcomes may start in the prenatal period. Maternal mental health may be a potentially modifiable risk factor for the optimisation of neurodevelopment in CHD. We propose to assess the impact of prenatal maternal mental health on 1-year neurodevelopmental outcomes in complex CHD.

Neuro-Moms CHD is a national multi-centre, prospective study of prenatal maternal mental health and neurodevelopmental outcomes in children with complex CHD who undergo neonatal open-heart surgery. Participants (n=87 mother-child dyads) will be recruited from five major French paediatric cardiology centres (Necker Children’s Hospital in Paris, Bordeaux Cardiology Hospital, Marseille Children’s Hospital, Montpellier University Hospital and Saint-Pierre Institute). Expecting women who receive a prenatal diagnosis of fetal complex cyanotic CHD that requires a neonatal open-heart surgery for the newborn are eligible to participate. They will complete self-reports on mental health, anxiety, depression and coping skills and will participate in a semi-structured psychological interview. Mothers will provide information on medical, sociodemographic and lifestyle factors. They will be enrolled during the third trimester of pregnancy and will participate at three time points: prenatal, T1; after the newborn’s cardiac surgery, T2; and between 12 and 18 months after birth of the child with CHD, T3. Children with CHD will undergo a standardised neurodevelopmental assessment when they turn 12–18 months old. The father or co-parent of the child with CHD will also participate in T1 and will complete mental health self-reports. We will use a structural equation model to estimate simultaneously the relationships among maternal mental health, prenatal factors and child neurodevelopment outcomes.

This study is sponsored by the French National Institute of Health and Medical Research. It was approved by the Ethics Committee on 5 November 2024 and is registered in a public trials registry (NCT06711666). Neuro-Moms CHD targets a public health question with important societal implications. Results are expected to be broadly communicated with the scientific community and the lay public. Dissemination of findings will be in the form of scientific articles in peer-reviewed journals and presentations at conferences. Any publication or communication will comply with the international recommendations: ‘Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly work in Medical Journals’ (http://www.icmje.org/recommendations). All participants will give written informed consent or assent to participate. The anonymised data to be collected in this study will be available within the manuscripts published.

NCT06711666; pre-results.

To identify the barriers and facilitators towards deceased organ donation among Pakistanis living globally.

Systematic review using narrative synthesis.

CINAHL, Medline with Full Text, Global Health and PsycINFO via EBSCO; Scopus via Elsevier; Web of Science via Clarivate; and PubMed through the US National Library of Medicine and the National Institutes of Health were searched between 1 January 1995 and 31 July 2024 and limited to English.

We included qualitative and cross-sectional studies involving Pakistani participants aged 18 years and above, conducted both within Pakistan and internationally across settings such as universities, religious venues, hospitals and workplaces.

Four independent reviewers were involved in screening, quality assessment and data extraction. A narrative synthesis method was employed to synthesise and integrate the data from qualitative and cross-sectional studies. The Joanna Briggs Institute tool was used to assess the quality of the included studies.

Out of 11 944 studies retrieved, 26 studies were included in the current review. Based on the narrative synthesis, the findings are presented under the following five themes: (1) knowledge of deceased organ donation, (2) willingness towards deceased organ donation, (3) collective decision-making overriding individual’s preferences, (4) religious uncertainty and its impact on deceased organ donation and (5) trust and the healthcare systems.

This review shows that decisions about deceased organ donation are shaped by family dynamics, religious beliefs and trust in healthcare. More diverse research is needed to uncover new gaps and improve donor registration and consent rates in Pakistan. A whole-systems approach, considering families, religion and trust, is essential for effective strategies.

CRD42022346343.

Glucosamine is a commonly used ‘over the counter’ dietary supplement. Previous research has identified an association between glucosamine use and several positive health outcomes. However, a plausible biological mechanism for these associations has not yet been identified, meaning the causality of these relationships remains unclear. A protective effect of glucosamine on the vascular endothelium has been suggested as one such possible mechanism. Albuminuria is an early marker of endothelial dysfunction within the kidney and is associated with progression of kidney disease and adverse cardiovascular outcomes. In order to provide insights into the potential biological mechanisms underlying a protective association of glucosamine use with health outcomes, we evaluated evidence for an association between glucosamine use and albuminuria in UK Biobank (N=436 200).

Univariable and multivariable ordinal logistic regression were performed to evaluate evidence for an association between self-reported glucosamine use and albuminuria (measured as urine albumin creatinine ratio (uACR) categories). As a secondary analysis, we performed Mendelian randomisation (MR) to demonstrate the difficulties in inferring causality in this relationship using currently available data, using summary genetic data from UK Biobank and CDKGen (N=67 452).

We found that people who used glucosamine were more likely to be in a lower uACR group (OR 0.81, 95% CI 0.80 to 0.83, px10^–16). This association was robust to sensitivity analyses and was maintained after adjustment for age, sex and measures of obesity. In our MR analysis, we found little evidence for an association of genetically proxied glucosamine use on albuminuria (change in log uACR (mg/g) per SD change in genetic liability=1.11, 95% CI –3.01 to 5.23, p=0.60).

We found that detectable albuminuria was common in UK Biobank participants and we are the first to show that use of glucosamine supplements was associated with lower levels. Though this fits with a plausible biological role of the vascular endothelium in a potential protective effect of glucosamine use on many health outcomes, whether this relationship is causal or confounded remains unclear. We further discuss the inherent difficulties in using genetic instruments to proxy supplement use in MR analyses and highlight the need for a genome-wide association study of measured circulating glucosamine levels.

To identify the barriers and facilitators to accessing services for neurodevelopmental disorders (NDDs) among the carers of individuals from Black, Asian and minority ethnic groups in the UK.

A scoping review.

Seven databases: PubMed, Cochrane, MEDLINE Full Text, APA PsycINFO, Scopus, CINAHL and Web of Science were searched for relevant studies up to the end of March 2025. Titles and abstracts and, where appropriate, full-text articles were screened based on predefined inclusion and exclusion criteria. Two reviewers independently screened the 6454 studies, with data extraction carried out by two reviewers. A narrative synthesis of the findings was undertaken.

A total of 15 studies were included in the review, the majority of which were qualitative (n=9; 60%). Among the Black, Asian and minority ethnic populations represented, South Asians comprised the predominant group. The review underscores that the barriers faced by Black, Asian and minority ethnic communities are multifactorial, which includes: (1) language and communication barriers, (2) cultural and religious influences, (3) stigma, (4) formal and informal support systems and (5) experience with healthcare services.

Access to neurodevelopmental care for carers from Black, Asian and minority ethnic groups in the UK is shaped by complex, multifactorial barriers. These communities are not homogeneous, and evidence gaps make it unclear whether challenges are shared or distinct. Greater understanding is needed to inform culturally appropriate, evidence-based policy and practice. Further research is essential to address disparities and improve equitable access across all groups.

Exposure to prescription opioids following traumatic injury can increase the risk of developing tolerance, persistent opioid use and opioid use disorder. The mechanisms underlying opioid tolerance or dependence are not well understood, and no biomarkers predict risk. Opioid exposure causes epigenetic modifications, including alterations in microRNA (miRNA) expression. Several miRNAs, which regulate synaptic plasticity, are hypothesised to underlie substance use disorders and influence µ-opioid receptor levels, modulating opioid tolerance. This project aims to develop a bio-behavioural signature to predict persistent opioid use and chronic pain up to 6 months post-discharge.

The study will use a prospective cohort design, enrolling 180 adult patients at a Level I Trauma Center who are prescribed opioids at discharge. Prospective data will be collected in the hospital and at 7 days and 1, 3 and 6 months post-discharge. Biological data (genotyping and miRNA levels) and clinical measures of opioid use, pain, pain sensitivity (EEG) and psychosocial functioning will be collected at each time point. Bayesian regression methods will be used to identify baseline clinical, genetic, epigenetic and psychosocial predictors of opioid use and pain outcomes at 6 months post-discharge. Growth mixture modelling will identify distinct subgroups with varying trajectories, followed by Bayesian hierarchical modelling to predict trajectory classification based on predictor variables.

Ethics approval for this study was obtained from the University of Texas Health Science Center at Houston Committee for the Protection of Human Subjects (HSC-MS-24–0314). Findings will be disseminated in peer-reviewed scientific journals and at national and international conferences.