Cancer is the leading cause of death and morbidity among children and adolescents worldwide. Functionality-based interventions are relevant among children and adolescents with an oncological diagnosis, whence studies summarising evidence on this topic are needed. This systematic review will summarise evidence on the effect of interventions to improve functionality indicators among paediatric patients diagnosed with cancer.

This protocol will follow Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)-Protocols reporting guidelines. The systematic review will be conducted according to the Cochrane Handbook and PRISMA 2020. Studies will be searched in MEDLINE (PubMed), Embase, Web of Science, CENTRAL, LILACS and PEDro. Additional searches will include Google Scholar, reference lists of included studies, relevant reviews and trial registries. Studies will be included if they implement a functionality-based intervention. They must evaluate effects among paediatric patients with an oncological diagnosis. Secondary outcomes will include health-related quality of life. There will be no limits to language or year of publication, and articles published in peer-reviewed journals will be accepted. Only randomised controlled trials will be included. Risk of bias will be assessed using the Cochrane Risk of Bias Tool 2. Two independent reviewers will select studies, extract data and assess risk of bias. A narrative synthesis and meta-analysis will be conducted if studies are clinically and methodologically homogeneous. Statistical heterogeneity will be assessed using Higgins’ inconsistency test (I^²). Meta-analysis may estimate combined effects using random-effects and the inverse variance method. The R statistical software will be used. The certainty of evidence will be evaluated for each outcome using the Grading of Recommendations Assessment, Development and Evaluation system.

This study used data from previously published studies, thus waiving submission to an Ethics Committee. Scientific dissemination strategies will include publication in peer-reviewed journals, conference presentations and workshops for the public.

CRD42024462833.

Despite global commitments to eliminate malnutrition, over half the world’s population remains affected. Multisectoral nutrition interventions targeting both proximate and distal causes of malnutrition are essential across the lifespan. Yet, current data collection lacks comprehensive nutrition intervention coverage measures, risking inaccuracies in tracking progress. The One Nutrition Coverage Survey (ONCS) aims to test new and refined coverage measurement methods, assess coverage equity and guide integration into large-scale household surveys.

The ONCS will be a cross-sectional, population-representative household survey conducted in four districts of Bangladesh (Rangpur, Sylhet, Dhaka and Khulna), selected for their geographic spread and urban–rural balance. A stratified multistage sampling approach will be used to select enumeration areas, and a total of approximately 3280 households randomly selected within each EA will be included in the survey. The survey will interview women of reproductive age (15–49 years), caregivers of children (0–9 years), adolescents (10–19 years) and pregnant women, collecting data on multisectoral nutrition interventions relevant to these groups. It will use both existing and new measures, while also capturing monetary and non-monetary costs for survey design to implementation. Data will be analysed to assess coverage, co-coverage and equity by sociodemographic characteristics, as well as the feasibility, accuracy and costs of the survey approach.

The study protocol and instruments were reviewed and approved by the International Centre for Diarrhoeal Disease Research, Bangladesh’s (icddr,b) Ethical Review Board in Bangladesh and the International Food Policy Research Institute’s Institutional Review Board in Washington, DC, USA. Adults provided signed informed consent and adolescents their assent. Findings will be shared through peer-reviewed publications, conferences and presentations in Bangladesh with key stakeholders. This study will yield new tools, methods and evidence for measuring multisectoral nutrition intervention coverage, applicable to other low-income and middle-income countries. Learnings from ONCS will enhance data collection aligned with national strategies, helping governments improve coverage assessments, inform decisions and strengthen programme monitoring.

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.

Rheumatoid arthritis (RA) is a heterogeneous disease, which current treatment guidelines insufficiently accommodate, as they predominantly emphasise the suppression of disease activity. However, a step towards personalised medicine is preferred to further optimise treatment and requires homogeneous subgroups with similarities in pathophysiological mechanisms and treatment responses. Prior research has already demonstrated notable differences in the pathophysiology of patients with autoantibody-positive and autoantibody-negative RA, as well as differences in treatment responses, which may serve as a strong basis for personalised medicine. Additionally, there is evidence suggesting that an early treatment response is indicative of future courses. Based on these findings, we designed a personalised medicine trial in RA that compares the effectiveness and cost-effectiveness of a tailor-made approach with routine care.

The PeRsonalIsed Medicine in RA (PRIMERA) trial is a multicentre, open-label, randomised controlled trial that includes 300 adult patients with newly diagnosed, DMARD-naïve RA, according to 2010 American College of Rheumatology/EULAR criteria. Patients are randomised into either routine care or a tailor-made approach. Both management approaches use a treat-to-target strategy, aiming for low disease activity (LDA, Disease Activity Score using 44 joints (DAS) ≤2.4). In routine care, initial treatment consists of methotrexate along with a single intramuscular dose of glucocorticoids (GCs) and treatment can be intensified after 3, 7 and 10 months if LDA is not reached. Conversely, initial treatment in the tailor-made approach depends on the presence of autoantibodies, with patients with autoantibody-positive and autoantibody-negative RA starting with hydroxychloroquine or methotrexate together with a single intramuscular dose of GCs, respectively. Medication intensifications will be allowed at months 1, 3, 4, 7 and 10. Intensifications at months 1 and 4 depend on whether patients have an early sufficient response to GCs and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively. The tailor-made approach is superior to routine care if no more biological DMARDs (bDMARDs) or tsDMARDs are used after 10 months of treatment, while the mean DAS over time is lower. Our primary outcome is the proportional difference in bDMARD or tsDMARD usage after 10 months of treatment between routine care and the tailor-made approach. Secondary outcomes are DAS over time, time to achieve LDA, cost-effectiveness and patient-reported outcome measurements over time.

Ethical approval has been granted by Erasmus MC Medical Ethics Review Committee (MEC-2020-0825). The results will be disseminated through peer-review journals and medical congresses.

ISRCTN16170070.

An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.

This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.

No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.

CRD42025644244.

Cardiovascular diseases, overweight, type 2 diabetes and chronic kidney disease increase the risk of cardiovascular events.

Glucagon-like peptide-1 analogues are recommended by the European Society of Cardiology and the American College of Cardiology to lower the risk of death and progression of cardiovascular disease in patients with cardiovascular disease and type 2 diabetes. Semaglutide, tirzepatide and liraglutide are approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of type 2 diabetes mellitus and overweight. CagriSema is currently not approved, but several phase III trials are ongoing.

No previous systematic review has investigated the effects of semaglutide, tirzepatide, CagriSema and liraglutide, which may not be disease-specific, on hard binary outcomes for all trial populations at increased risk of cardiovascular events.

We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index—Science) and clinical trial registries from their inception and onwards to identify relevant randomised trials. We expect to perform the literature search in December 2025. Two review authors will independently extract data and assess the risk of bias. We will include randomised trials assessing the effects of semaglutide, tirzepatide, CagriSema and/or liraglutide in participants with an increased risk of cardiovascular events. The primary outcome will be all-cause mortality. Secondary outcomes will be myocardial infarction, stroke and all-cause hospitalisation. Data will be synthesised by aggregate data meta-analyses, Trial Sequential Analyses and network meta-analysis, risk of bias will be assessed with Cochrane Risk of Bias tool V. 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations and the Confidence in Network Meta-Analysis approach.

This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.

CRD42024623312.

Systematic literature reviews (SLRs) are essential for synthesising research evidence and guiding informed decision-making. However, SLRs require significant resources and substantial efforts in terms of workload. The introduction of artificial intelligence (AI) tools can reduce this workload. This study aims to investigate the preferences in SLR screening, focusing on trade-offs related to tool attributes.

A discrete choice experiment (DCE) was performed in which participants completed 13 or 14 choice tasks featuring AI tools with varying attributes.

Data were collected via an online survey, where participants provided background on their education and experience.

Professionals who have published SLRs registered on Pubmed, or who were affiliated with a recent Health Economics and Outcomes Research conference were included as participants.

The use of a hypothetical AI tool in SLRs with different attributes was considered by the participants. Key attributes for AI tools were identified through a literature review and expert consultations. These attributes included the AI tool’s role in screening, required user proficiency, sensitivity, workload reduction and the investment needed for training. Primary outcome measures: The participants’ adoption of the AI tool, that is, the likelihood of preferring the AI tool in the choice experiment, considering different configurations of attribute levels, as captured through the DCE choice tasks. Statistical analysis was performed using conditional multinomial logit. An additional analysis was performed by including the demographic characteristics (such as education, experience with SLR publication and familiarity with AI) as interaction variables.

The study received responses from 187 participants with diverse experience in performing SLRs and AI use. The familiarity with AI was generally low, with 55.6% of participants being (very) unfamiliar with AI. In contrast, intermediate proficiency in AI tools is positively associated with adoption (p=0.030). Similarly, workload reduction is also strongly linked to adoption (p

The findings suggest that workload reduction is not the only consideration for SLR reviewers when using AI tools. The key to AI adoption in SLRs is creating reliable, workload-reducing tools that assist rather than replace human reviewers, with moderate proficiency requirements and high sensitivity.

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.

Sleep is a biological necessity with vital effects on all tissues and organs of the body. Preoperative sleep disturbance is associated with increased postoperative pain intensity and opioid consumption. Given that insomnia is a potentially modifiable risk factor, interventions targeting sleep prior to surgery may improve postoperative pain control and enhance key outcomes of recovery.

Promoting Sleep to Alleviate Pain-Arthroplasty (PROSAP-A) is a randomised, parallel group, two arm, controlled trial evaluating the effects of preoperative sleep-promotion on postoperative pain control, brain health and physical recovery. The main objective is to investigate whether preoperative insomnia treatment in patients scheduled to undergo total knee arthroplasty (TKA) or total hip arthroplasty (THA) may improve acute postoperative pain control. 100 adults with insomnia disorder (Insomnia Severity Index score >10 and confirmed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for persistent insomnia disorder), scheduled to undergo primary TKA or THA, will be randomised to preoperative cognitive behavioural therapy for insomnia (CBT-I) or an active comparator control intervention, sleep education therapy (SET). Both interventions will be delivered over 4 weeks in hybrid format through a digital self-guided platform in combination with weekly telehealth video sessions with a psychologist (CBT-I) or research nurse (SET). A video-assisted booster session will be provided 1–2 weeks postoperatively. The primary outcome measure is acute postoperative pain intensity, averaged over the first 7 postoperative days (POD). Secondary outcome measures include long-term postoperative pain control, changes in quantitative sensory testing variables (eg, temporal summation, conditioned pain modulation), sleep, cognition (eg, attention, memory, processing speed, executive function), mental health, health-related function, physical activity, quality of life and blood biomarkers. Participants will undergo on-site evaluation preoperative (preintervention and postintervention) and 6 months postoperative. Additional remote assessments will take place during POD1–7, 3 and 12 months postoperative.

The Swedish Ethical Review Authority has approved the PROSAP-A trial protocol. Results will be published in international peer-reviewed journals and summaries will be provided to funders and participants of the trial.

NCT06145516.

Distal radius fractures account for one-fifth of all fractures in the active elderly population and may cause chronic pain, loss of hand function and reduced work productivity, imposing a significant socioeconomic burden. Most are initially treated with closed reduction and casting, but 30% subsequently require surgery due to insufficient realignment. The current approaches for analgesia for closed reduction are suboptimal. A brachial plexus nerve block provides complete pain relief and muscle relaxation distal to the elbow, potentially creating better conditions for realignment of the fractured bone ends. This may ultimately translate into reduced need for surgery and result in better functional outcomes and fewer complications compared to a haematoma block, which is the current standard care in Denmark.

The BLOCK Trial is an investigator-initiated, parallel-group, allocation-concealed, outcome assessor and analyst-blinded, superiority, randomised, controlled, clinical multicentre trial performed at 11 Danish emergency departments. Eligible adult patients with a distal radius fracture who need closed reduction will be included and allocated 1:1 to either an ultrasound-guided brachial plexus nerve block or a haematoma block. The primary outcome is the proportion of patients with distal radius fracture surgery 90 days after closed reduction. We will include 1716 participants to detect or discard a relative risk reduction of surgery of 20%. Secondary outcomes include treatment-related complications, patient-reported wrist function, pain during closed reduction and proportion of patients with unacceptable radiographic fracture position immediately after closed reduction.

The trial is approved by the Danish Medicines Agency and the Danish Research Ethics Committees (EU CT number: 2024-512191-35-00). All results will be summarised on www.theblocktrial.com, clinicaltrials.gov and euclinicaltrials.eu after publication. Primary and secondary outcome results from 0 to 90 days will be presented in the main article and submitted to a peer-reviewed journal. Results from outcomes on the 12-month follow-up will be presented separately.

NCT06678438.