Trials

Background Randomized controlled trials (RCTs) often have incomplete methods reporting despite widespread adoption of the CONSORT guideline. The editorial process is supposed to detect these shortcomings and request clarifications from authors, which is time-consuming. We developed an LLM-based CONSORT Rohe Nordberg Report that highlights which CONSORT items appear fully or partially reported and checks page references claimed by authors, and then creates follow up questions for authors to more easily correct missing information. Methods This parallel-arm, superiority RCT will randomize eligible RCT submissions (after desk screening) 1:1 into intervention (editorial team and authors receive the Rohe Nordberg Report) or control (standard editorial review only). The primary outcome is whether manuscripts improve their reporting of CONSORT items in the Methods and Results sections between the original submission and first revision. This will be assessed by blinded human reviewers who evaluate the textual changes for improvements between the original and revised manuscripts for each relevant CONSORT item. Secondary outcomes include time to editorial decisions, rejection and non-resubmission rates, if authors can correctly identify where CONSORT items are reported, and extent of revisions. Human evaluators will be blinded to whether the manuscript was in the intervention or control group. Discussion By providing authors and the editorial team with specific follow up questions for each underreported CONSORT item, we hypothesize that basic underreporting will be more efficiently detected and corrected. Using blinded human reviewers as the primary outcome assessors ensures a rigorous, unbiased evaluation. If successful, this approach may help align manuscripts more closely with CONSORT standards, ultimately benefiting evidence synthesis.

BackgroundUnderrepresentation of minority groups in clinical trials worsens health disparities and reduces generalizability of results. Transthyretin-associated cardiac amyloidosis (ATTR), is a condition that disproportionately impacts some racial and ethnic groups yet the extent to which trial enrollment reflects disease burden remains unclear. Misalignment between disease prevalence and trial representation may delay treatment development and increase the economic burden of late diagnosis and mismanagement. MethodsThis was a systematic review of US-based ATTR clinical trials found on clinicaltrials.gov up to 2025 (search date February 12, 2025). Only completed trials with publicly available results were included. Demographic data were extracted at the trial level. An enrollment fraction (where EF = observed enrollment / expected enrollment based on Cardiac Amyloidosis Registry Study (CARS) prevalence; adequacy defined EF [&ge;] 0.75) was calculated for each group. ResultsOf the 264 clinical trials on ATTR identified, 16 met inclusion criteria. African Americans/Individuals of African descent had EFs below the adequate ratio of 0.75 in all phases of the trials reviewed compared to their Asian or White counterparts. Despite the FDA Final Rule in 2017, our study showed that there was increased study demographic reporting (60% to 85.7%), but a paradoxical decline for Black participants (EF 0.29 to 0.12, p < 0.001) and other minority participants. ConclusionsBlack individuals remain substantially underrepresented in U.S. ATTR-CM clinical trials despite improved demographic reporting after the 2017 Final Rule. Actionable strategies, community engagement, trial-site diversification, enrollment targets, and sponsor accountability are needed to improve representativeness and expand access.

Background: Clinical trials are essential for therapeutic development but increasingly face challenges due to imprecise inclusion criteria, leading to low event rates and the need for large sample sizes. This inefficiency makes modern trials costly and time-consuming. Despite the availability of extensive clinical, genomic, and biological data, current trial enrollment strategies do not fully leverage this information. Incorporating genomic information into trial design could enable risk-based participant enrichment by preferentially enrolling individuals with higher disease risk, thereby increasing event rates and improving trial efficiency. Methods: In this study, we developed an in silico framework for evaluating prognostic enrichment guided by polygenic risk scores (PRS) in clinical trial design using genomic and electronic health record data from large-scale biobanks. Naturally occurring protective genetic variants were used as analogs of therapeutic interventions, with variant carriers treated as 'treatment' arms and non-carriers as 'control' arms. We compared unenriched designs, in which carriers and non-carriers were drawn from the full population, against PRS-enriched designs in which both arms were restricted to participants in the upper 75%, 50%, or 25% of the PRS distribution, respectively. Across these four designs, we quantified disease prevalence, statistical power, sample size requirements, and time-to-event accrual. Results: We applied this approach to the UK Biobank using three model gene-disease pairs: the protective variant p.Arg46Leu in PCSK9 for coronary artery disease (CAD), p.Gln175His in ANGPTL7 for glaucoma, and p.Arg381Gln in IL23R for inflammatory bowel disease (IBD). Across all three disease contexts, PRS-enriched designs increased disease prevalence, improved empirical power, and accelerated event accrual relative to unenriched cohorts. At 80% power, restricting enrollment to the upper 25% of the PRS distribution reduced required per-arm sample sizes by approximately 60% for CAD-PCSK9 and 78% for IBD-IL23R. Consistent reductions in time-to-event were also observed across enriched strata, suggesting that PRS-enriched trials could achieve target event counts with both smaller sample sizes and shorter follow-up. However, for glaucoma-ANGPTL7, the most restrictive threshold did not yield additional gains over moderate enrichment, as reduced sample size attenuated the detectable difference between arms. These results highlight the need to balance enrichment for higher-risk participants against retaining a sufficient eligible population, and underscore that optimal PRS thresholds are disease-context dependent. Conclusions: These findings establish a generalizable, data-driven framework for prospectively evaluating PRS-guided prognostic enrichment prior to trial initiation. In general, PRS-guided study designs lead to improved empirical power, lower required sample sizes, and faster trials. As population-scale genomic data become increasingly available within healthcare systems and biobanks, this framework provides a scalable foundation for integrating genetic risk information into clinical trial design.

Objectives: To assess the availability of key clinical trial registration data and compliance with legal reporting requirements for all Phase 2-4 drug trials registered on the new European Clinical Trial Information System (CTIS) registry. This study is the first ever assessment of data quality and legal compliance with reporting requirements on CTIS. Design: Cross-sectional observational study of CTIS registry data combined with manual review of results documents. Setting: Cohort of all 7,547 Phase II-IV clinical trials registered on CTIS as of November 2025. Main outcome measures: Number and proportion of missing data points in CTIS registration data. Proportion of completed clinical trials that are compliant with regulatory reporting requirements. Results: Trial registration data quality was high overall with more than 99% of expected data present. Of 234 clinical trials legally required to report results, fewer than half (49.6%) fully reported results within the required timeframe, 20 trials (8.5%) fully reported results late, and 98 trials (41.9%) failed to fully report results. Legal compliance was similar for adult trials (79/158) and paediatric trials (37/76). Conclusions: Sponsor compliance with legal reporting requirements is weak. Current efforts by European regulators to monitor and enforce compliance appear to be insufficient. New results reporting functions currently being set up by trial registries worldwide will require quality assurance processes. Trial registration: Study protocol prospectively registered on OSF: https://osf.io/sn4j2/overview

BackgroundSocial prescribing (SP) connects individuals with sources of support within their local communities and has been shown to improve loneliness. However, uptake from young people (YP) has been lower than for adults, in part due to them not accessing SP in primary care where it has been predominantly based. The INACT (INcreasing AdolesCent social and community support) programme is a novel, co-produced, SP pathway via schools for YP to access community assets and support. MethodsThis trial utilises a two-group (intervention vs. active control) parallel randomised design, with YP as the unit of randomisation. A minimum of 215 YP will be recruited across approximately 30 mainstream schools (primary and secondary) in England. YP reporting high levels of loneliness (7 or above on the Good Childhood index) will be randomly allocated to receive either SP or signposting. SP will consist of 6-12 sessions with a Link Worker who will work with individuals, on a one-to-one basis, to understand what matters to them and connect them with local sources of support, whilst pupils in the signposting arm will receive a leaflet from a school staff member detailing the same sources of support. YP will be followed up at 3, 6, and 12 months after treatment allocation. Secondary outcome measures include wellbeing, emotional difficulties, service use, health related quality of life, stress, emotional regulation, as well as intervention feasibility, acceptability and appropriateness. Data about health-related quality of life and service use will be used to investigate the cost-effectiveness of the INACT programme. DiscussionThis trial will provide robust evidence about the effectiveness and cost-effectiveness of the INACT programme and whether it can be recommended for use in practice. The trial is due to finish 30 June 2027.

BackgroundType 2 diabetes is a growing challenge in low- and middle-income countries, where health systems face major capacity gaps. Participatory learning and action (PLA) has shown effectiveness in preventing type 2 diabetes in Bangladesh, but little is known about its use in other LMICs for diabetes. The EMPOWER-D (Engagement of community through Participatory learning and action for cOntrol and prevention of type 2 diabetes) trial is testing PLA for diabetes prevention in communities in Pakistan and Afghanistan. This protocol describes the plans for the embedded process evaluation (PE). MethodsThe PE will use a mixed-methods design across three sites, following the UK Medical Research Council framework for PE, examining implementation, mechanisms of impact and context. Implementation will be assessed using adaptation reports, fidelity checklists, attendance data, and supervisor reports. Mechanisms of impact will be explored through interviews, focus group discussions and photovoice. Contextual factors will be examined through interviews with participants, community mobilisers, supervisors, and key stakeholders. Quantitative data will be analysed descriptively, while qualitative data will undergo thematic analysis using a theory of change framework. Comparative analysis will identify common and context-specific influences. DiscussionThis is the first multi-country PE of a PLA intervention for diabetes prevention to our knowledge, and the first in Afghanistan and Pakistan. The study will provide insights into how the intervention was delivered, how and why it worked (or did not work), and the contextual factors shaping outcomes. Findings will inform the adaptation and scale-up of participatory approaches for non-communicable disease prevention in resource strained setting health systems. Trial registration: ClinicalTrials.gov: NCT06561126 (registered 23 August 2024); NCT06570057 (registered 26 August 2024).

Exercise training is a cornerstone of Cardiovascular Rehabilitation (CR) and, as of now, moderate-to-vigorous continuous exercise training (MICT) is the standard. New exercise modalities in the context of CR are constantly being explored to improve patient outcomes. These Canadian Association of Cardiovascular Prevention and Rehabilitation (CACPR) exercise training recommendations provide a synthesis of evidence-informed recommendations from existing documents, including recommendations around High-Intensity Interval training (HIIT). CACPR created a pan-Canadian Exercise Working Group with various knowledge users (e.g., kinesiologists/exercise physiologists, physiotherapists, cardiologists, and patients) with expertise in CR-based exercise, who developed knowledge gap questions related to exercise training based on a literature review and synthesis of all available recommendations. An independent evidence-synthesis team performed a rapid review and meta-analyses to address the questions. The working group used this data to develop relevant recommendations. The final guidelines include 12 recommendations for CR exercise, including nine from previous documents and three new recommendations based on HIIT. The previous recommendations address exercise assessments and prescriptions for CR for various patient profiles. The new recommendations suggest that HIIT can be used to improve exercise capacity in patients with coronary artery disease (CAD), heart failure (HF) or atrial fibrillation. They also state that HIIT is superior to MICT in patients with CAD, that patients with HF should be considered for either HIIT or MICT and that any HIIT interval duration can be used as part of CR. Overall, these recommendations provide guidance for exercise in Canadian CR programs.

BackgroundThe FACE-Q Skin Cancer Module is a validated patient-reported outcome measure for facial skin cancer surgery. However, the minimally important difference (MID)-- the smallest change in score perceived as meaningful by patients--has not been established. Without the MID, individual score changes cannot be interpreted clinically. This study aimed to determine the MID for all four FACE-Q Skin Cancer scales. MethodsProspective cohort study at a tertiary center (2017-2018). Patients completed the FACE-Q preoperatively and at 1 week, 3 months, and 1 year postoperatively. MID was estimated using distribution-based methods (0.5 standard deviation, standard error of measurement) and an anchor-based approach using the FACE-Q Adverse Effects scale as an implicit anchor. Internal consistency (Cronbachs ), effect sizes, and standardized response means were calculated. ResultsOf 287 enrolled patients, 111 had paired baseline-three-month data. All scales had strong internal consistency ( = 0.82-0.93). Cancer worry showed the largest improvement from baseline to three months (mean change -3.1 {+/-} 5.8; SRM = -0.54; p < 0.001). When we combined the estimates, the MID values (sum scores / 0-100 scale) were: Appearance Satisfaction 2.0 / 5.6, Psychosocial Distress 2.0 / 6.2, Cancer Worry 2.5 / 6.2, and Scar Satisfaction 2.0 / 6.2. Anchor-based estimates for the Scar scale (2.4 sum points) confirmed distribution-based findings. ConclusionsThis study establishes the first MID values for the FACE-Q Skin Cancer Module. A change of approximately 2-2.5 sum points (5-6 points on a 0-100 scale) represents a minimally important difference across all scales. These thresholds enable clinicians and researchers to interpret individual FACE-Q score changes and design adequately powered clinical trials.

BackgroundChronic stroke-related gait impairment remains a major source of disability. InTandem is an autonomous neurorehabilitation system delivering individualized, progressive rhythmic auditory stimulation for home-based gait rehabilitation. ObjectivesTo evaluate: (1) engagement during a 12-week autonomous, home-based intervention, (2) changes in walking endurance and functional mobility, and (3) outcome differences across pre-defined engagement and baseline speed subgroups. MethodsThis pragmatic, decentralized trial enrolled adults [&ge;]6 months post-stroke with residual gait deficits. Participants were asked to complete 30-minute sessions 3x/week for up to 12 weeks. Engagement was primarily assessed as the proportion achieving moderate-to-high weekly usage (> 4 weeks; benchmark p1 = 0.60). Changes in 6-Minute Walk Test (6MWT) distances and Timed Up and Go (TUG) times were analyzed using linear mixed-effects models. ResultsOf the 204 who initiated the intervention, 81.9% (95% CI [0.76-0.87]) engaged at least 4 weeks, meeting the primary endpoint (p < 0.001). Overall, 58.1% achieved high engagement (> 9 weeks), 23.9% moderate engagement (4-8 weeks), and 18.1% low engagement ([&le;]3 weeks). Significant improvements in 6MWT distance (+ 26.1 {+/-}5.6 m; 95% CI [14.99, 37.22]) and TUG times (-1.45{+/-}0.31 s; 95% CI [-2.06, -0.84]) (p < 0.001) were observed. Engagement influenced effectiveness: each additional week engaged predicted a 5.82 m greater gain in the 6MWT (SE = 2.05; 95% CI [1.77, 9.87], p < 0.005). ConclusionsAutonomous home-based delivery of music-based rhythmic auditory stimulation achieved moderate-to-high engagement and improved walking endurance and functional mobility, supporting InTandem as a scalable approach to chronic stroke gait rehabilitation. Trial registrationTrial registration: Clinicaltrials.gov NCT06051539. Registered on 20 September 2023. https://clinicaltrials.gov/study/NCT06051539

Background: Lumbar spinal stenosis (LSS) can cause pain and severe walking limitation. Although surgery aims to improve walking, many patients do not achieve clinically meaningful gains. Rehabilitation can improve outcomes, yet existing programmes lack robust evidence and theoretical underpinning. This study aimed to (1) co-design a theory-informed rehabilitation programme to improve walking after LSS surgery, and (2) evaluate feasibility of conducting a future trial and acceptability of the intervention. Methods: A multi-methods study included intervention co-design followed by a single-arm feasibility study. Co-design used an adapted Experience-Based Co-Design approach with patients, carers, and healthcare professionals (n=39), integrating the Behaviour Change Wheel. This resulted in STructured Rehabilitation and InDividualised Exercise and Education (STRIDE), delivered over 12-week pre- and 12-weeks post-surgery, targeting knowledge, expectations, perceived control, physical capability, and fears. Adults aged [&ge;]50 years awaiting LSS surgery were recruited to a before-after feasibility study. Feasibility outcomes included recruitment and retention. Acceptability was assessed using the Theoretical Framework of Acceptability questionnaire (0-5 (high acceptability)) and focus groups. Clinical outcomes measured at baseline, post-prehabilitation, and post-rehabilitation included 6-minute walk distance (6MWD) and mean daily step count over 7 days. Results: Fifteen of 31 eligible participants were recruited (48%; mean age 70 years), with 80% retained to study end (2 decided against surgery, 1 unable to complete final assessment). Acceptability was high (median 5/5, IQR 0). Participants valued the personalised, supportive approach and reported improved motivation and preparation for surgery, though travel was burdensome. Small pre-operative and moderate-to-large post-operative improvements were observed in 6MWD (+49.9 m and +81.6 m) and daily step count (+868 and +1405 steps/day). Conclusions: This co-designed, physiotherapy-led, behaviour-change rehabilitation programme was acceptable to participants, with encouraging recruitment, retention, and signals of improved walking following LSS surgery. The findings support progression to a future trial.

Background. Recent meta-analyses of randomized controlled trials (RCTs) claimed efficacy of higher-dose fluvoxamine (2 x 100 mg/day, as opposed to 2 x 50 mg/day) in prevention of disease deterioration in adults with mild - moderate COVID-19 disease. Objectives. Investigate whether such claims are supported by the data. Methods. Systematic review and meta-analysis of RCTs evaluating higher-dose fluvoxamine in this indication. Results. Seven studies declared as RCTs were identified, one of which was severely biased (open-label, non-standardized and unreported standard of care as a control), and eventually ended as non-randomized (huge attrition). Composite endpoints of deterioration in the 6 included placebo-controlled trials contained elements susceptible to error and bias. Three trials were small (<100 patients/arm), three were larger (270 - 750 patients/arm). Deaths and need for mechanical ventilation were sporadic and observed in only one trial. Hospitalizations were also sporadic in 5/6 trials. Frequentist methods generally appropriate for random-effects analysis of low number of trials with rare outcomes (generalized linear mixed models, beta-binomial or binomial-normal) greatly underestimated heterogeneity, but still did not document benefits regarding the composite endpoints or hospitalizations. Bayesian hierarchical models revealed huge heterogeneity and indicated no benefit regarding: (i) composites of deterioration, large trials OR = 0.78 (95% CrI 0.55 - 1.21); multiplicity corrected OR = 0.87 (0.64 - 1.21); (ii) hospitalizations, small trials OR = 0.88 (0.45 - 1.72); large trials OR = 0.94 (0.52 - 1.75); all trials OR = 0.81 (0.47 - 1.43). Heterogeneity was unlikely due to clinical particulars (vaccination status, treatment duration, time horizon), and more likely due to unidentified bias. Conclusions. RCTs do not support efficacy of higher-dose fluvoxamine in prevention of disease deterioration in adults with mild - moderate COVID-19 disease.

BackgroundSymptom diaries are widely used in acute respiratory infection trials to capture patient-reported symptom severity and recovery. Longer questionnaires may provide a more complete clinical picture but can increase participant burden and reduce adherence. Evidence directly comparing long and short formats within the same trial is limited. ObjectiveTo compare adherence, symptom trajectories, agreement between recovery measures, and predictive performance for recovery-related outcomes between a short and long symptom diary in an outpatient SARS-CoV-2 trial MethodsThis secondary analysis of the CanTreatCOVID trial compared a 9-item Abbreviated Diary and a 34-item FLU-PRO Plus Diary over 14 days in non-hospitalized participants with confirmed SARS-CoV-2 infection. Outcomes included diary initiation, completion, completion rate, compliance, symptom trajectories, agreement between recovery outcomes, and predictive performance. Analyses used logistic regression, generalized estimating equations, survival models, and predictive modelling. ResultsOf 712 participants, 638 used the Abbreviated Diary and 74 the FLU-PRO Plus Diary. Baseline characteristics were similar between groups. Diary type was not significantly associated with diary initiation or full 14-day compliance, whereas treatment assignment was associated with higher adherence (p < 0.0001). Completion rates were slightly higher in the Abbreviated group (68.1% vs. 64.4%), but differences were not statistically significant. Agreement between "feeling recovered" and "return to usual health" was strong to excellent ({kappa} = 0.8371-0.8859), while agreement with "return to usual activities" was moderate ({kappa} = 0.5273-0.6583). Predictive models performed well for both diaries (AUCs 0.87-0.94), with only marginal gains from including the extended FLU-PRO Plus items. ConclusionIn this outpatient SARS-CoV-2 trial, abbreviated and extended symptom diaries produced comparable adherence, symptom trajectories, and predictive performance. Future research should extend follow-up beyond 14 days to capture longer-term patterns and test diary performance in more diverse and digitally underserved populations.

Background: Moderate- to high-intensity walking training (M-HIT) is an established intervention for improving walking capacity in chronic stroke. Musculoskeletal (MSK) adverse events commonly occur during M-HIT, yet tools to identify individuals at higher risk are limited. Baseline clinical characteristics may provide insight into susceptibility to training-related MSK adverse events during M-HIT. Thus, this study aimed to develop and internally validate a model for predicting MSK adverse events during a 12-week M-HIT program in chronic stroke using baseline clinical characteristics. Methods: Participants (n=100) from HIT-Stroke Trials 1 and 2 were included. Baseline clinical characteristics included measures of orthopedic history, pre-existing pain, motor function, recent exercise history, demographics and health characteristics, stroke chronicity, and psychological health. Logistic regression models evaluated all possible combinations of baseline characteristics with up to three predictors. Leave-one-out cross-validation was used for internal validation to mitigate overfitting. Predictive performance was quantified using the C-statistic, and the candidate model with the highest cross-validated C-statistic was selected as the final model. Results: MSK adverse events occurred in 32.0% of participants. The optimal three-variable model included prior orthopedic condition (Odds ratio [OR] 3.02 [95% CI 1.14-8.64]), Fugl-Meyer lower extremity motor score (OR 1.14 [95% CI 1.02-1.28]), and self-reported participation in regular walking exercise (OR 0.17 [95% CI 0.05-0.49]) at baseline. This model demonstrated moderate discrimination (cross-validated C-statistic = 0.74; apparent C-statistic = 0.78). Conclusions: Participants reporting at least one pre-existing lower extremity or lumbar spine orthopedic condition and those with better lower-extremity motor function exhibited greater odds of experiencing MSK adverse events during M-HIT, while participants reporting participation in regular walking exercise had lower odds. These findings suggest that baseline clinical characteristics may help identify individuals at elevated risk for MSK adverse events during M-HIT who may warrant closer monitoring or risk-reduction strategies. Future studies are needed for external validation. Clinical Trial Registration: https://ClinicalTrials.gov; Unique identifiers: NCT03760016, NCT06268041

1.This paper reports the statistical analysis plan for the AVERT-DOS trial: A Phase 3, Multi Arm, Multi Stage, Covariate Adjusted, Response Adaptive, Randomised Trial to Determine Optimal Early Mobility Training after Stroke. It contains a trial overview, regulatory information and details of the planned main analyses for the study protocol version Version 5; 15 June 2025.

IntroductionAdverse event (AE) reporting transparency is essential for evidence-based surgical practice, yet substantial reporting gaps persist despite Consolidated Standards for Reporting Trials (CONSORT) Harms guidance. The Medical Dictionary for Regulatory Activities (MedDRA) provides standardized terminology for AE classification, but its association with AE reporting quality remains unexplored. ObjectivesThe purpose of this study was to establish the frequency of Medical Dictionary for Regulatory Activities (MedDRA) utilization in gastrointestinal and abdominal surgical trials, identify predictors of its adoption, and quantify the association between MedDRA use and adverse event reporting quality as measured by Completeness scores, registry-publication Concordance, and overall Transparency indices. DesignCross sectional analysis of matched randomized controlled trial registry-publication pairs. Participants116 gastrointestinal and abdominal surgery randomized controlled trials registered on ClinicalTrials.gov with results posted between September 2009 and December 2024 and an associated peer-reviewed publication. Primary and Secondary Outcome MeasuresPrimary outcomes were differences in AE reporting quality between MedDRA-documenting and non-documenting trials, measured using Harms Reporting Completeness score (0-8), Concordance score (0-7), and Harms Transparency Index (0-15). Secondary outcomes included prevalence of MedDRA adoption and predictors of MedDRA documentation via univariable logistic regression. ResultsAmong 116 included trials, only 22 (18.8%) explicitly documented MedDRA use. Industry-funded trials (OR=29.32, 95% CI=8.94-118.50, p<0.001) and those with at least one U.S. site (OR=4.59, 95% CI=1.22-30.02, p=0.050) demonstrated significantly higher rates of MedDRA adoption. Trials documenting MedDRA use demonstrated significantly improved reporting across all three score parameters: Completeness score (p<0.001), Concordance score (p=0.002), and Transparency Index (p<0.001). MedDRA use was also associated with lower rates of registry-publication discordance across key safety metrics: serious adverse event (SAE) participant count registry-publication discordance was 59.1% in MedDRA documenting trials and 85.1% in non-MedDRA trials; mortality reporting discordance was 60.0% in MedDRA trials and 82.1% in non-MedDRA trials. ConclusionDespite strong association with improved AE reporting completeness and registry-publication concordance, MedDRA adoption in gastrointestinal and abdominal surgical trials remains below 20%, concentrated among industry-funded studies. The predominance of unstandardized terminology and free-text strategies promotes reporting inadequacies that complicate evidence synthesis and undermine evidence-based surgical practice. Journals, funding agencies, academic institutions, and researchers should prioritize the adoption of standardized AE terminology to enhance transparency and improve surgical research. Trial RegistrationPROSPERO CRD420251081191. Strengths and Limitations of this StudyO_LIThis is the first study to quantify the association between MedDRA use and adverse event reporting quality in surgical trials C_LIO_LIDual independent screening and extraction with pre-registered protocol minimizes bias and enhances reproducibility C_LIO_LIAnalysis limited to gastrointestinal and abdominal surgery; generalizability to other surgical subspecialties remains uncertain C_LIO_LIRequired explicit MedDRA documentation; trials using MedDRA without disclosure would be misclassified as non-users C_LIO_LIConcordance assessment examined numerical agreement without evaluating clinical significance of discrepancies C_LI

ObjectiveThis study evaluates the impact of systemic GLP-1 receptor agonist (GLP-1RA) use on surgical wound healing in high-risk surgical populations, including patients with diabetes, and implications for perioperative planning and healing outcomes. ApproachThis pilot retrospective cohort study compared adult surgery patients with non-healing postoperative wounds by their GLP-1RA use. Outcomes included healing status, time to wound closure, and number of surgical interventions. ResultsThe cohort included 35 non-GLP-1RA users and 16 GLP-1RA users with comparable baseline characteristics, except for significant higher prevalence of venous insufficiency among users. Though median time to closure was similar for all patients, users required fewer surgical interventions and their wounds reached closure in significant difference from non-users. Among patients with diabetes, all GLP-1RA users healed significantly compared to non-users. InnovationThe impact of GLP-1RA therapy on wound healing in high-risk reconstructive and soft-tissue surgery remains poorly defined. This pilot cohort addresses that gap, offering an early signal that GLP-1RA use is associated with improved wound healing and fewer postoperative interventions. These findings may inform perioperative practice by identifying a systemic pharmacologic factor that optimizes surgical outcomes in high-risk populations. ConclusionGLP-1RA use was associated with higher healing rates and fewer interventions, particularly among patients with diabetes. These findings support a beneficial role in surgical wound healing and warrant larger multi-site studies.

Background: Mainstreaming genetic testing has emerged as a strategy to improve access and reduce wait times for patients who may benefit from genetic testing. Ensuring patients fully grasp the implications of testing when formal genetic counselling is not provided, remains a focus for ongoing research. Methods: Patients diagnosed with hypertrophic or dilated cardiomyopathy were offered genetic testing between September 2024 and September 2025 through either the mainstreaming model conducted in cardiology clinics or a referral to Medical Genetics where patients attended an online webinar or a one-on-one genetic counselling appointment. Uptake of testing, time to testing, informed choice and patient satisfaction were evaluated. Results: Among patients offered genetic testing, uptake was higher in the mainstreaming pathway (82%) compared with a referral to Medical Genetics (69%). The difference in access was predominately due to patients not following through with their Genetics referral. Mainstreaming reduced wait times where patients referred to Genetics waited a median of 94-185 additional days to be offered genetic testing. Despite improved access, only 62% of mainstreamed patients were considered informed, compared to 91% of patients that attended a patient webinar through Medical Genetics (p < 0.01). Satisfaction with decision-making was high across both pathways. Conclusion: Integrating genetic testing into cardiology practices increased access and reduced wait times; however, patients demonstrated significantly lower rates of informed decision making compared to those who attended a patient webinar offered through Medical Genetics. These findings highlight the importance of structured education to support informed decision making within mainstreaming pathways.

Objective To map the presence, public availability, and content of clinical trial data sharing policies (DSP), data management and sharing plans (DMSP), and data use agreements (DUA) among the most prolific public and private clinical trial sponsors operating in the European Union, and to identify key areas of convergence, divergence, and constraint in the context of General Data Protection Regulation (GDPR). Eligibility criteria We included organisation-level documents describing approaches to clinical trial data sharing or data management from the top 20 public and top 20 private sponsors ranked by the number of trials registered in the EU Clinical Trials Information System (CTIS). Eligible materials comprised publicly available or sponsor-shared policies, guidelines, statements, templates, and agreements relevant to clinical trial data sharing or management. Sources of evidence Evidence was identified through systematic searches of sponsors' public websites, structured Google searches, and major data management plan platforms (DMPTool, DMPonline, DMP Assistant), complemented by direct contact with sponsors to verify findings and request missing documentation. All sources were archived and catalogued. Charting methods Two reviewers independently extracted data using a structured form, capturing the existence, accessibility, and content of data sharing policies, data management and sharing plans, and data use agreements. Quantitative data were summarised descriptively, and a non-interpretive descriptive content analysis was conducted to characterise recurring policy elements and areas of heterogeneity. Results Among 40 sponsors, private sponsors were substantially more likely than public sponsors to make trial-specific data sharing policies and data use agreements publicly accessible, often via established data sharing platforms. Public sponsors more frequently referenced data management and sharing plans, but these were heterogeneous in scope and often embedded within broader institutional governance documents rather than tailored to clinical trials. Across sectors, GDPR compliance, data protection, and legal safeguards were emphasised, while operational aspects such as dataset readiness, review criteria, and downstream responsibilities varied widely. Overall response rate to sponsor verification was 37.5%. Conclusion Clinical trial data sharing governance in the EU shows a marked sectoral imbalance among the top sponsors. Private sponsors tend to provide more detailed and operationally explicit documentation, whereas public sponsors often articulate high-level commitments without trial-specific guidance. Greater clarity and standardisation, particularly among public sponsors, could improve transparency and facilitate responsible data reuse, while remaining compatible with GDPR requirements.

Objective: This analysis assessed the acceptability and recruitment implications of a high-throughput, community-based biomechanics protocol among individuals with knee osteoarthritis (OA). Design: During the Shared Strides Study, high-throughput markerless biomechanics assessment was conducted at community sites to help facilitate research engagement in the OA population. In this cross-sectional study, biomechanics data during a set of activities of daily living (ADLs) and questionnaire data were collected. Adults aged 40 years or older with knee OA participated at one of four sites across Gainesville, FL--two on-campus and two community-based. Eligible individuals were either screened over the phone and scheduled for a specific date and time or screened on site for potential same-day participation. Participant acceptability of the community-based biomechanics data collection approach was assessed using a 15-item custom questionnaire. Recruitment characteristics and participant preferences were compared across sites. Results: The high-throughput community-based data collection approach was well received. Compared with on-campus sites, community-based sites had higher engagement from walk-in participants and new research participants (40% of the sample). Familiarity with, and distance to, a data collection site were important factors in research engagement in this population. No differences in demographic characteristics existed between sites (p > 0.05), but recruitment resulted in a large sample size (n = 85) likely representative of the communities surrounding the selected sites. Conclusions: Integrating markerless motion capture with a community-based research approach may enhance the participant experience and facilitate larger, more heterogeneous sample sizes, ultimately reducing bias and homogeneity in current OA biomechanics research.

Background: Patient-reported outcome measures provide essential data on treatment quality across diverse populations. The FACE-Q Skin Cancer Module was developed to assess outcomes specific to facial skin cancer patients. Longitudinal data characterizing outcome trajectories from surgery through early recovery remain limited. Objective: We tracked how patient outcomes change from preoperatively through three months after surgery using the FACE-Q Skin Cancer Module in a prospective cohort of 288 patients undergoing facial skin cancer surgery. Methods: Participants completed the module preoperatively and at 1 week and 3 months postoperatively. Five scales were evaluated: Appearance, Psychosocial Distress, Cancer Worry, Scars, and Adverse Effects. Friedman tests assessed overall change across timepoints; paired t-tests and Wilcoxon signed-rank tests evaluated pairwise comparisons. Results: Of 288 enrolled patients (mean age 68.6+/-11.9 years, 46.5% female), 252 (87.5%) and 220 (76.4%) completed 1-week and 3-month follow-up, respectively. Facial appearance declined at 1 week (55.6 to 52.0, p=0.005) and returned to baseline by 3 months (57.0, p=0.274). Psychosocial distress increased acutely (14.5 to 19.0, p<0.001) with partial recovery at 3 months (17.1, p=0.012). Cancer worry decreased substantially (delta=-7.8, SRM=-0.54, p<0.001), and scar satisfaction improved from 1 week to 3 months (delta=+9.4, SRM=0.54, p<0.001). Adverse effects showed the largest improvement (delta=-12.8, SRM=-0.88, p<0.001). Women showed less improvement in facial appearance than men (delta=-2.2 vs +4.9, p=0.022). Clinical meaningfulness was assessed using minimally important difference thresholds: 36.9% of patients achieved meaningful improvement in appearance, 39.6% remained stable, and 23.4% experienced meaningful deterioration. Conclusions: Short-term outcomes follow a predictable pattern, with acute perioperative worsening followed by recovery by 3 months for most patients.