Colorectal cancer patients with peritoneal metastases have a very poor prognosis. A minority of these patients is eligible for curative cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The peritoneal cancer index (PCI) is an important criterion to select patients for CRS-HIPEC. Due to challenges in peritoneal metastasis detection by imaging, the PCI is currently routinely assessed by invasive diagnostic laparoscopy in addition to CT and/or MRI. Yet, open-close procedures and early disease recurrence following CRS-HIPEC are common, indicating the need for better patient selection tools. Fibroblast activation protein (FAP)-targeted imaging has recently emerged as a promising strategy for visualising peritoneal disease. The aim of this study is to assess the potential value of FAP inhibitor positron emission tomography/CT (FAPI-PET/CT) as an alternative non-invasive tool for quantitative PCI assessment.

TROMPET is a prospective observational proof-of-concept study. A total of 25 colorectal cancer patients with suspected or verified peritoneal metastases who are eligible for CRS-HIPEC based on MRI will be included in this study. Patients younger than 18, pregnant and/or breastfeeding, with any contraindication(s) for MRI, PET, CT and/or CRS-HIPEC, and/or with a known additional malignancy within the past five years are excluded. Participants will receive [¹⁸F]AlF-FAPI-74 PET/CT prior to surgery. The primary objective is to determine the correlation between PCI scores determined by FAPI-PET/CT and ‘true’ PCI scores determined by histopathological analysis of all resected lesions. The secondary objectives include the correlations between PCI scores determined by FAPI-PET/CT, by MRI and during surgery, the potential of FAPI-PET/CT to detect extraperitoneal metastases, and molecular and immunohistochemical analysis of resected tissue to provide insight into the nature of FAPI-PET-positive lesions. The primary endpoint is all PCI scores determined by FAPI-PET and histopathology and their correlation on patient level. If this study shows that the PCI score can be accurately determined preoperatively by FAPI-PET/CT, it will form the basis for further developing FAPI-PET/CT as a quantitative, standardised, non-invasive diagnostic tool for selecting patients for CRS-HIPEC. Moreover, the ‘radiology-pathology’ setup of the study will allow us to characterise FAPI-PET-positive and PET-negative lesions in detail, providing further insight into the strengths and potential pitfalls of FAPI-PET/CT in the detection of peritoneal metastases from colorectal cancer.

This study is approved by the assigned Medical-Research-Ethics-Committee (METC NedMec) on 19-08-2024. All participants will provide written informed consent. Study results will be disseminated through (inter)national meetings and peer-reviewed publications.

2024-512301-16-01

To estimate uptake of obstructive sleep apnoea (OSA) screening and initiation and long-term use of positive airway pressure (PAP) treatment in a middle-aged and older general population cohort.

Prospective population-based cohort study.

Icelandic arm of the multinational Burden of Obstructive Lung Disease follow-up study II (2019–2021)

378 non-institutionalised adults aged 54–91 years were invited from a general population cohort. 26 with prior OSA diagnosis were excluded. Of the remaining participants, 334 (88.4%) completed a technically adequate home sleep apnoea test.

Those with an apnoea–hypopnoea index (AHI)≥15 events/hour were invited for clinical evaluation and when appropriate, referred for PAP treatment. Adherence was assessed 2 years after PAP initiation.

Primary outcomes were screening uptake and PAP initiation. Secondary outcomes included long-term PAP use and objective adherence 2 years after referral.

AHI≥15 was identified in 132/334 participants (39.5%). Of these, 123 (93.2%) attended clinical evaluation and 99 (75.0%) were referred for PAP treatment. Of those not referred, six declined PAP and the remainder were advised alternative management or reassessment. At 2-year follow-up, 53/99 (53.5%) were long-term PAP users, 43/99 (43.4%) had discontinued and 3/99 (3.0%) never initiated PAP. Objective adherence data were available for 47/53 long-term users; 21/47 (44.7%) met adherence criteria (≥4 hours/night on ≥70% of nights in the preceding 30 days).

Most adults accepted OSA screening when offered. Among those with moderate-to-severe OSA identified through population screening, most accepted evaluation and PAP treatment, with approximately half becoming long-term users. These findings suggest that population-based detection of OSA followed by routine clinical management is feasible. Future studies should identify subgroups most likely to benefit and evaluate alternative treatment strategies.

To evaluate greenhouse gas (GHG) emissions from procedure room NanoNeedle arthroscopy (NA) and its associated clinical pathway, compared with conventional arthroscopy (CA) delivered in an operating room, focusing on non-complex knee arthroscopy procedures.

Hybrid carbon footprint analysis using process-based life-cycle methods combined with economy-wide input-output data that include environmental impact factors for medical devices and components of patient care pathways. Three care pathways were evaluated: (1) CA in an OR with preoperative MRI, (2) NA in a procedure room with MRI and (3) NA in a procedure room without MRI. Emissions were calculated for all pathway components, including patient and staff travel, diagnostic imaging, medical devices, the procedure itself and postoperative care.

UK National Health Service-based care pathway model for non-complex knee arthroscopy procedures.

The primary outcome was GHG emissions (kgCO₂e) per procedure pathway. Additional analyses assessed emissions by pathway component, adoption scenarios, conversion rates from NA to CA and sensitivity analyses for selected assumptions and input parameters.

The CA pathway generated 77.0 kgCO₂e per procedure, whereas the NA with MRI produced 45.0 kgCO₂e and NA without MRI 35.3 kgCO₂e, representing reductions of 42% and 54% of kgCO₂e, respectively. Major emission contributors for CA were patient travel, consumable items and general anaesthesia; for NA pathways, patient travel and the device itself were the leading contributors. Adoption modelling indicated that using NA without MRI for 5000–20 000 knee arthroscopy procedures could yield annual CO₂e savings ranging from 208 tons to 834 tons.

Knee arthroscopy delivered via the NA procedure room pathway has the potential to substantially reduce environmental impact compared with conventional OR-based care. As healthcare providers and policymakers increasingly consider environmental sustainability, technologies that enable alternative care models, such as NA in a procedure room setting, may represent a promising approach for reducing the carbon footprint of selected procedures.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhoea in adults, with recurrence rates of 15%–25% after a first episode and up to 65% after multiple recurrences. Recurrent CDI leads to significant morbidity, diminished quality of life, prolonged antimicrobial exposure and increased healthcare utilisation. Faecal microbiota transplantation (FMT) demonstrates high efficacy for multiple recurrent CDI, but its benefit when used earlier—after the first episode in high-risk patients or first recurrence—remains insufficiently studied. Emerging evidence suggests early FMT may improve sustained clinical cure rates and reduce recurrence. This trial evaluates whether early introduction of oral FMT following standard therapy improves outcomes compared with standard therapy alone.

This is a multicentre, randomised, open-label, pragmatic phase III superiority clinical trial conducted across eight Swiss clinical centres. A total of 100 adults will be enrolled. Patients with either (1) a first CDI episode and risk factors for recurrence or (2) a first CDI recurrence and who first receive the real-world standard of care anti-CDI antibiotics (10 days of vancomycin or fidaxomicin) are randomised 1:1 to oral FMT following standard antibiotic therapy or standard therapy alone. The intervention group receives within 12 hours to 4 days of the last antibiotics administration, 15 to 20 oral FMT capsules twice on two consecutive days if the CDI is non-severe; those with severe CDI receive an additional 2-day FMT course. The control group does not receive any additional treatment after completing the 10 days of standard therapy. The primary endpoint is the proportion of patients having experienced a CDI recurrence at 8 weeks post completion of treatment (assessed per-protocol and intention-to-treat). Secondary outcomes include early and late recurrence rates, sustained cure at 6 and 12 months, quality-adjusted life years, recurrence-free and overall survival at 12 months. Exploratory analyses include microbiota diversity, biomarker identification and assessment of immunologic and microbial predictors of recurrence. Safety/tolerability is also assessed.

The study will be conducted in accordance with International Council for Harmonisation Good Clinical Practice, the Declaration of Helsinki and Swiss regulatory standards. Results will be disseminated through peer-reviewed publications and conference presentations.

NCT05266807.

Sleep and circadian rhythm disturbances are proposed to be pathophysiological mechanisms underlying some cases of depressive and bipolar (mood) disorders. An unresolved clinical question is whether sleep and circadian-based therapies are effective antidepressants for young adults (18–30 years) with a mood disorder.

MELODY (Melatonin for Depression in Youth) is an investigator-initiated, single-centre, phase 3, randomised controlled trial with two blinded pharmacological arms (melatonin vs placebo) and one open-label digital intervention arm (digital cognitive behavioural therapy for insomnia (dCBT-I)). The trial is testing whether 12 weeks of adjunctive melatonin or dCBT-I are more effective than pill placebo at reducing depressive symptoms in 660 young people aged 18–30 years with a Structured Clinical Interview for (Diagnostic and Statistical Manual of Mental Disorders, fifth edition; SCID-5) diagnosis of Major Depressive Disorder or Bipolar Disorder type II, moderate to severe depressive symptoms and significant sleep or sleep-wake complaints. The week 12 primary outcome is depressive symptoms (Quick Inventory of Depressive Symptomatology, Adolescent version). Secondary outcomes include partial remission of the Major Depressive Episode (SCID-5) and change in other mental health symptoms, sleep, functioning or quality of life. A subset of participants will undergo in-home assessment of sleep physiology (Sleep Profiler) and in-lab assessment of circadian rhythms (dim-light melatonin onset) to examine biological changes. A 6-month follow-up will explore durability of treatment effects. Mediation analyses will test whether sleep or circadian rhythm changes play a causal role in antidepressant effects.

MELODY has been reviewed and approved by the Human Research Ethics Committee (HREC) of the Sydney Local Health District (HREC Approval Number: X23-0450, Protocol version: 1.4, 7/7/25). The findings of the MELODY trial will be disseminated into the scientific and clinical communities via refereed publications, talks and other professional and media outlets. The Brain and Mind Centre’s Lived Experience Working Group will contribute to dissemination of MELODY’s findings via youth-friendly methods (eg, social media videos, explainers).

ACTRN12624000017527.

Depression is a prevalent mental health condition often occurring after traumatic brain injury (TBI) in both children and adults. Sex, gender and other social determinants of health (SDoH) (e.g., race/ethnicity or socio-economic status) play an important role in depression-related and TBI-related healthcare utilisation (e.g., diagnosis, treatment and management of the conditions). Despite this, no reviews have examined how sex and gender, along with other SDoH, influence depression-related healthcare utilisation among individuals who sustained a TBI ≤19 years of age. The review’s objective will be to synthesise evidence on sex-based and/or gender-based findings, along with other SDoH, in depression-related healthcare utilisation among individuals who sustained a TBI ≤19 years of age.

Searches will be conducted on Ovid Medline, Embase, American Psychological Association PsycINFO and Cumulative Index of Nursing and Allied Health Literature from database inception to the search date. The review will follow the Joanna Briggs Institute evidence synthesis framework for knowledge synthesis and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)-P, PRISMA-Equity guidelines and PROGRESS-Plus for reporting results. Included studies will be peer-reviewed articles published in any language that examined individuals who sustained a TBI at ≤19 years of age, reported depression-related healthcare services and provided sex-stratified and/or gender-stratified results. Studies will be excluded if they were grey literature, included individuals who sustained a TBI at >19 years without age-stratified results, reported healthcare services for conditions other than depression without depression-specific stratification or did not provide sex-stratified or gender-stratified results. A narrative synthesis will be conducted to identify themes and attributes describing how sex, gender and other SDoH influence depression-related healthcare utilisation. Methodological quality will be assessed using the National Heart, Lung and Blood Institute Quality Assessment Tool.

No institutional ethics approval will be required as this study will not conduct primary data collection. The review will be disseminated as a peer-reviewed publication.

CRD420261301669.

To examine COVID-19 vaccine uptake among people diagnosed with sexually transmitted and bloodborne infections (STBBIs), people with healthcare-documented methamphetamine use and those experiencing both exposures in Manitoba, Canada.

Population-based retrospective matched cohort study using linked administrative healthcare, laboratory and vaccination data.

Manitoba, Canada, from 1 March 2020 to 31 March 2022.

Manitoba residents aged ≥16 years with laboratory-confirmed chlamydia or gonorrhoea, syphilis or HIV and/or healthcare-documented methamphetamine use during the 4 years before 1 March 2020 were classified into eight mutually exclusive exposure cohorts. Individuals were matched with comparators without the corresponding exposure based on age, sex, geographical region and area-level income quintile.

Receipt of ≥2 COVID-19 vaccine doses. Poisson regression models incorporating person-time were used to estimate adjusted rate ratios (aRRs) and 95% CIs.

Compared with matched comparators, vaccine uptake was lower in the Syphilis Only (aRR 0.83, 95% CI 0.80 to 0.86), Syphilis Plus (aRR 0.77, 95% CI 0.74 to 0.79), Chlamydia/Gonorrhoea Only (aRR 0.91, 95% CI 0.90 to 0.92), Chlamydia/Gonorrhoea Plus (aRR 0.74, 95% CI 0.72 to 0.77), Methamphetamine Only (aRR 0.71, 95% CI 0.68 to 0.73) and Methamphetamine plus STBBI cohorts (aRR 0.64, 95% CI 0.62 to 0.67). Uptake in the HIV Only cohort was similar to that among matched comparators (aRR 0.97, 95% CI 0.93 to 1.00). Lower uptake was concentrated among individuals living in lower-income areas.

COVID-19 vaccine uptake was lower among several populations affected by STBBIs, methamphetamine use or both, with the greatest disparity among people experiencing intersecting STBBI and methamphetamine-related exposures. Integrating vaccination with HIV, STBBI, harm-reduction and addiction services may improve vaccine equity during future public health emergencies.

Fatty infiltration (FI) of the rotator cuff (RC) muscles reflects chronic deterioration in muscle quality associated with tendon injury, disuse, ageing and nerve injury. Accurate and reliable assessment of FI based on imaging interpretation is essential for evaluating muscle degeneration, guiding rehabilitation planning and enabling meaningful comparisons across clinical and research settings. Several semi-qualitative grading systems and quantitative measurement approaches across imaging modalities, including CT, MRI, ultrasound and advanced techniques such as Dixon MRI have been used to assess FI; however, the reproducibility of FI grading or quantification at the level of image interpretation varies widely. This protocol outlines a systematic review and meta-analysis designed to evaluate the inter-rater and intra-rater reliability of imaging-based FI assessment at the level of image interpretation in RC disorders.

The review will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) guidelines and is preregistered in PROSPERO (CRD420251242564). Searches will be conducted in MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Library from inception to the search date. Two reviewers will independently screen, extract data and assess study quality using the Quality Appraisal of Reliability Studies (QAREL) checklist. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework will be used to guide interpretation of reliability-related measurement properties. The primary outcomes will be inter-rater and intra-rater reliability reflecting the consistency of image-based FI grading or quantification. Where appropriate, pooled reliability estimates will be calculated separately by imaging modality (eg, MRI, CT and US) and by type of reliability (inter-rater and intra-rater). When quantitative pooling is not feasible because of limited studies or substantial heterogeneity, findings will be synthesised narratively and presented in summary tables. These will be synthesised using a restricted maximum likelihood random-effects model in R software, version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria) with the metafor package.

Ethical approval is not required as the review will use only published data. The results will be disseminated through a peer-reviewed publication and conference presentations to inform research and clinical practice in musculoskeletal imaging.

CRD420251242564.

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are leading benchmarks for reliance approval pathways, while many regulatory authorities streamline their review processes by referencing these authorities’ evaluations and decisions. Major postmarketing (MPM) modifications, reflecting benefit–risk updates, are often added to approved labels. This study aimed to identify variables associated with significant MPM safety modifications by FDA and EMA to understand their potential impact on regulatory decision-making in the reliance process.

Retrospective cohort study of new drug applications and supplemental indications approved by the Israeli Ministry of Health (MOH) between 2014 and 2019. The primary outcome was time to first MPM safety modification by the FDA/EMA. Associated factors, including clinical and regulatory variables, were examined using both univariate and multivariable Cox regression analyses.

Applications with FDA and/or EMA approval at the time of assessment in Israel were included.

467 applications met the inclusion criteria. Oncology therapeutics (HR 2.19 (95% CI 1.71 to 2.80)), approval based on early phase clinical trials data—phase 1 (HR 3.14 (95% CI 1.29 to 7.63)) and phase 2 (HR 1.97 (95% CI 1.47 to 2.64)), facilitated approval pathways (HR 1.68 (95% CI 1.31 to 2.17)) and approval based on a surrogate endpoint (HR 1.92 (95% CI 1.31 to 2.46)), were associated with higher rates of MPM modifications. MPM modifications were documented in 53.1% of applications that underwent a single Advisory Committee on Drug Registration (ACDR) review cycle, compared with 68.67% of applications that required multiple review cycles (HR 1.6, (95% CI 1.19 to 2.16), p=0.001). In multivariable analysis, oncology indications (HR 1.71 (95% CI 1.31 to 2.25)), facilitated approval pathways (HR 1.46 (95% CI 1.13 to 1.92)) and applications approved following multiple review cycles (HR 1.42 (95% CI 1.14 to 2.58)) were found to be predictive factors correlated with MPM modifications.

By considering these associated factors, regulators can strengthen the reliance pathway assessment process, supporting a balance between streamlined evaluation procedures and maintaining rigorous safety and efficacy standards.

With improvements in in vitro culture techniques, there has been a steady shift in practice to transfer in vitro fertilisation (IVF) embryos at the blastocyst-stage to increase pregnancy rates per embryo transfer (ET) and reduce the risk of multiple pregnancy. In patients with fewer embryos (≤5 zygotes), fresh cleavage-stage ET is still commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst-stage in vitro. However, evidence for improved outcomes with cleavage-stage embryo transfer in this subgroup of patients is lacking. We will compare blastocyst-stage to cleavage-stage ET with regard to cumulative live birth rates (CLBR) per oocyte retrieval and other patient-centred cycle outcomes in patients with ≤5 zygotes.

Multicentre, randomised pragmatic comparative effectiveness trial with superiority design comparing blastocyst-stage to cleavage-stage ET in patients with ≤5 zygotes. This trial will enrol and randomise 1126 women aged 18–44 undergoing IVF to either fresh cleavage-stage or blastocyst-stage ET at eleven IVF centres. Surplus embryos will be vitrified at the blastocyst-stage. The primary outcome is the CLBR per oocyte retrieval. Secondary outcomes include: multiple pregnancy, pregnancy loss

The Institutional Review Board at Beth Israel Deaconess Medical Center (BIDMC) provides central regulatory oversight. Results will inform timing of embryo transfer in patients with ≤5 zygotes and will be disseminated through academic publications, meeting presentations and communications to advocacy groups and patient participants.

NCT06746129.

Anxiety disorders are the most common youth mental health problems in the USA. Most children do not receive treatment and among the few who do, many do not experience significant improvement. Thus, there is an urgent need to identify novel intervention targets to improve treatments for childhood anxiety. Past research demonstrates that parent anxiety plays a role in the development and maintenance of child anxiety, but empirical evidence for the mechanisms that drive this transmission is lacking. Interpretation bias, or the tendency to perceive threat in ambiguous situations, may lead parents to engage in anxiety-promoting parenting behaviours, which may transfer this cognitive bias to their children, resulting in youth anxiety. Given the current lack of empirical evidence supporting this theorised mechanism, the present study will test effects of parent interpretation bias on parent behaviour and child interpretation bias. Our central hypothesis is that parent interpretation bias influences child interpretation bias through its effects on anxiety-promoting parenting behaviours. The study will also evaluate potential moderators of these theorised relationships, such as parent sex, race and ethnicity, parent anxiety, child age and child sex.

We will randomise 300 parents of children aged 7–12 to a smartphone app-delivered interpretation bias manipulation condition or a self-assessment control condition. Through a series of study assessments over the course of 3 months, parents and children will complete self-report, interview, behavioural and daily diary measures to assess the primary proximal outcome (anxiety-promoting parenting behaviours), the secondary distal outcome (child interpretation bias) and moderators. To test our central hypothesis, we will first use hierarchical linear modelling to assess whether parents in the interpretation bias manipulation condition show fewer anxiety-promoting parenting behaviours compared with control, and whether children of those parents show improved interpretation bias compared with control. We will then implement mediation models to evaluate whether a reduction in anxiety-promoting parenting behaviours mediates the association between parent and child interpretation bias.

Ethical approval for this study was granted by the Mass General Brigham Institutional Review Board (2022P003245). We will disseminate the results of this study to the scientific community, clinical community and the public through several channels such as peer-reviewed publications in scientific journals, national conferences, hospital lectures, press releases and Psychology Today blog posts.

NCT05665491.

Diagnostic and therapeutic management of patients with periprosthetic joint infections (PJIs) remains challenging. This national cohort aims to describe the epidemiology, clinical phenotypes, management strategies and outcomes of patients with PJI.

This is a national, multicentre, prospective, longitudinal, observational cohort study of patients who underwent revision for PJI of the hip, knee, shoulder, elbow or ankle. Participating centres are university or non-university tertiary healthcare facilities located in Switzerland. Episodes include likely and confirmed PJI, as defined by the European Bone and Joint Infection Society criteria. During routine clinical visits around revision surgery, data are collected and patients are followed-up thereafter for a minimum of 2 years. The primary objective is infection outcome and secondary objectives include functional outcome and patient satisfaction and evaluation of host, infection, microbiological and treatment factors associated with treatment failure and poor functional outcomes, both in the overall population and across subgroups. A minimum of 329 patients would be needed to have sufficient statistical power to carry out these analyses.

Ethical approval has been granted by the Research Ethics Committee under protocol number 2021-01791. All patients provide written informed consent for inclusion in the study. Study findings will be disseminated through publications in peer-reviewed journals and presented at national and international conferences in the fields of orthopaedics, infectious diseases and microbiology. We plan to leverage the platform within the cohort to conduct future studies and interventional trials.

NCT07473089.

Shared decision making (SDM) in healthcare is an ethical imperative and essential to patient-centred care. SDM is particularly useful when several preference-sensitive treatment options exist and in the setting of chronic conditions or longitudinal management. Chronic pain management embodies these characteristics, yet SDM often remains insufficient in this population. Decision aids are designed to facilitate SDM by helping patients and clinicians understand treatment options, clarify patient values, and guide collaborative decision processes. Despite their importance, the use of decision aids in pain management is inconsistent and their reported effectiveness has been variable. However, the current landscape of decision aids for pain management has not been described. This lack of understanding of what tools exist, how they are structured, what decisions they address and how they were developed makes it difficult to advance implementation efforts or identify meaningful gaps in available resources. As such, the purpose of this systematic review is to identify and characterise decision aids for pain management across the lifespan. Specifically, this review will describe the clinical decisions addressed, decision aid structures and delivery formats, development processes and outcomes used to evaluate the impact of existing decision aids.

Electronic searches were performed in PubMed, CINAHL and Ovid Embase from inception through January 2026. Studies will be assessed for quality using the Mixed Methods Appraisal Tool. Data will be extracted and presented with the aim of describing the: (a) content and structures of pain-related decision aids, (b) development processes used to create existing pain-related decision aids and (c) outcome measures used to evaluate the impact of decision aids in clinical care.

This review does not require ethics approval. Findings will be disseminated to clinicians, researchers and patients through journal publications, conference presentations and in collaboration with patient partners.

CRD420251085288

To investigate the association between attention-deficit/hyperactivity disorder (ADHD) and cardiometabolic risk profile at the time of type 2 diabetes (T2D) diagnosis and examine longitudinal changes in cardiometabolic measures following T2D diagnosis.

A nationwide cohort study using linked Swedish health registers.

Adults aged 18–65 years with a first recorded diagnosis of T2D between 1996 and 2020. ADHD, treated as a lifetime condition, was identified through diagnostic and prescription records.

The cardiometabolic risk profile, comprising nine clinical parameters and two behavioural factors, was assessed at T2D diagnosis and was tracked for up to 5 years post-diagnosis. Linear regression (β_ADHD) and Poisson regression models with robust variance (risk ratios (RRs)) compared cardiometabolic risk factors at diagnosis between individuals with and without ADHD. Generalised estimating equations (β_ADHD*t) assessed longitudinal changes in clinical parameters following the diagnosis.

Among 80 607 individuals with T2D, 1204 (1.5%) had an ADHD diagnosis. At T2D diagnosis, individuals with ADHD were younger and had statistically significantly higher body mass index (BMI) (β_ADHD: 1.93 (95% CI 1.54 to 2.32)), triglycerides (β_ADHD: 0.31 (95% CI 0.17 to 0.45)) and smoking prevalence (RR: 1.58 (95% CI 1.44 to 1.74)) compared with those without ADHD. Other cardiometabolic risk factors did not differ significantly. Over the subsequent 5 years, trajectories in cardiometabolic risk factors were broadly similar, except for a greater reduction in BMI in individuals with ADHD (β_ADHD*t: –0.26 (95% CI –0.34 to –0.17)), independent of baseline BMI and glucose-lowering medications. After inverse probability of treatment weighting, the BMI reduction was substantially reduced and not significant (β_ADHD*t: –0.05 (95% CI –0.17 to 0.07)).

Among adults with newly diagnosed T2D, those with co-occurring ADHD had broadly similar cardiometabolic profiles to those without ADHD but presented at a younger age with a modestly higher BMI, triglycerides and smoking prevalence. Individuals with ADHD also showed a slightly greater reduction in BMI over time following T2D diagnosis. Despite modest overall cardiometabolic differences, incorporating ADHD status into preventive diabetes care may help identify a younger, more vulnerable subgroup who could benefit from targeted risk factor management.

Osteopenia, defined as a bone mineral density (BMD) T-score between –1.0 and –2.5, is a precursor to osteoporosis and fragility fracture which results in substantial morbidity. Patients with gastrointestinal (GI) cancer are particularly vulnerable due to disease-specific mechanisms of bone loss and treatment-related toxicities, which compound the risk of osteoporotic fractures and adverse oncological outcomes. Despite this, the global prevalence of osteopenia and incidence of osteoporotic fracture in GI cancer populations remains poorly quantified, limiting opportunities for targeted surveillance, preventive strategies and policy development.

This systematic review and meta-analysis will estimate the global prevalence of osteopenia and global incidence of osteoporotic fracture in cohorts of adults with non-metastatic GI cancer and explore variation across treatment type, cancer site, geographical region and diagnostic modality.

This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidance. We will conduct a comprehensive search of MEDLINE, Embase, CINAHL, PubMed, Web of Science, Cochrane Central and ClinicalTrials.gov from 1994 to 2026. Eligible studies will include observational or interventional cohorts reporting prevalence of osteopenia, assessed using dual-energy X-ray absorptiometry (DXA) or CT scan, or incidence of fragility fracture, as determined by imaging findings, administrative codes or clinical history in cohorts of adult non-metastatic cancer populations. Five reviewers will independently and in pairs screen citations and full-text articles, extract data, and assess study quality using the Joanna Briggs Institute checklist for prevalence studies for each outcome. The primary outcome is the global pooled prevalence of osteopenia (diagnosed using DXA), calculated using a random-effect generalised linear mixed model. Secondary outcomes are the global pooled incidence rate of fragility fracture, and the pooled fragility fracture incidence rate ratio (IRR) comparing patients with GI cancer with the general population. All estimates will be presented with 95% confidence intervals. Heterogeneity will be assessed with I², ² and prediction intervals for each outcome. Sources of heterogeneity in osteopenia prevalence will be explored through subgroup analyses by primary cancer location, treatment exposure, and geographical region. Sensitivity analyses, including an analysis of the pooled prevalence of osteopenia diagnosed using CT, and limited to studies deemed low risk of bias, will be performed. Publication bias will be evaluated using Doi plots supplemented with Luis Furuya-Kanamori indices. We will assess certainty in the evidence-base in duplicate by using the Grading of Recommendations Assessment, Development and Evaluation methodology for systematic reviews involving prognosis.

This study is a secondary analysis of aggregate, de-identified data extracted from previously published studies. As such, no new data were collected from human participants, and formal ethics board approval is not required. All aggregated data and analytical code used to complete this study will be made available on request to the corresponding author. The findings from this study will be disseminated through publication in a peer-reviewed scientific journal and presentation at national and international conferences.

CRD420261286673.