Contemporary Clinical Trials Communications

Background. Tandem colonoscopy meta-analyses estimate adenoma miss rates, which have been used as a proxy for colonoscopy sensitivity. Doing so overstates sensitivity because it ignores lesions missed by both exams. Methods. We introduce Bayesian and frequentist approaches to estimate white-light colonoscopy (WLC) sensitivity from tandem colonoscopy meta-analyses. Neither approach assumes that the second colonoscopy is perfect. We apply both approaches to reanalyze data from a recent tandem colonoscopy meta-analysis, overall and across ten subgroups. Sensitivity analyses assess how assumptions about the relative performance of enhanced colonoscopy versus WLC affect estimates. Results. Under our Baseline specification, overall WLC sensitivity estimated by the Bayesian model was 0.54 [0.41, 0.63] (posterior mean and 95% credible interval). Sensitivity rose with lesion size: 0.49 [0.35, 0.60] for 1-5 mm adenomas, 0.64 [0.43, 0.78] for 6-9 mm adenomas and 0.84 [0.70, 0.93] for lesions 10 mm or larger. The frequentist plausible range encompassed the Bayesian estimate. The model-implied miss rate (0.35 [0.30, 0.40]) matched the original meta-analysis estimate and was stable across prior specifications. Assuming enhanced colonoscopy was perfect overstated overall sensitivity by 0.12 [0.06, 0.20]. Limitations. Tandem colonoscopy data identify the miss rate but not WLC sensitivity, so estimates depend on an external assumption about the relative performance of enhanced colonoscopy versus WLC. As a result, WLC sensitivity estimates varied with the prior specification, especially for small and flat adenomas. Conclusions. WLC sensitivity may be meaningfully lower than previously assumed in CRC screening cost-effectiveness analyses. Modelers should use colonoscopy sensitivity estimates that do not assume a second colonoscopy exam is perfect.

Background: Real-world evidence on food-as-medicine programs for irritable bowel syndrome (IBS) is scarce, and single-arm evaluations overstate improvement because of regression to the mean (RTM). We estimated change in the IBS Symptom Severity Scale (IBS-SSS, 0-500) in a multi-omics personalized digital health food-as-medicine program, unadjusted and RTM-corrected. Methods: Retrospective single-arm cohort. Of 15,933 members with a valid baseline, 2,254 had a follow-up reading and 1,683 one at least 14 days after baseline. Change at 4, 12 (primary) and 26 weeks was estimated by baseline severity stratum, unadjusted and RTM-corrected by analysis of covariance. A responder fell by at least 50 points (the minimal clinically important difference benchmark). Sensitivity analyses covered equity, inverse-probability weighting and tipping-point analyses for members without a reading in each landmark window, a negative-control stratum and medication. The association of weight loss and dietary nutrient density with symptom change was evaluated within and between members. Results: At 12 weeks (n = 430) IBS-SSS fell by 43.88 points unadjusted (95% confidence interval [CI] -52.44 to -35.32; p < 0.001) and by 47.73 RTM-corrected (-55.48 to -39.98; p < 0.001); 720 of 1,339 symptomatic members (53.8%; 95% CI 51.1 to 56.4) fell by at least 50 points. Larger improvement in more severe members persisted after RTM correction (severe stratum, n = 37: unadjusted -127.43, RTM-corrected -60.71, 95% CI -97.75 to -23.68, p = 0.001). A higher meal nutrient density was associated with lower IBS-SSS within a member's own trajectory (p = 0.018) while weight change was not (p = 0.361). Improvement was similar across groups in spite of baseline differences by age and sex: RTM-corrected 12-week change did not differ by age (p = 0.458), body-mass index (p = 0.328), sex (p = 0.749), income (p = 0.486) or ethnicity (p = 0.170). Estimates were robust to weighting for members without a reading in the landmark window (RTM-corrected estimates moved by less than 2 points), and the change of those members would have had to be 39 to 73 points worse than observed before the mean change reached zero. Baseline medication use and starting a GLP-1 receptor agonist did not explain symptom changes. Conclusions: IBS-SSS fell significantly among program participants, with steeper improvement in the more severe group, even after RTM correction. The improvement was comparable across socioeconomic characteristics, age and sex and robust to the confounders and missing-data assumptions evaluated. These associations from a self-selected single-arm cohort warrant replication in independent studies.

Objectives: To evaluate change in physical function and probable sarcopenia following a 36-week community multicomponent exercise programme (Vivifrail model) across two consecutive cycles, and to assess the consistency of this change between cohorts. Study design: Quasi-experimental, single-arm, repeated-measures service evaluation. Ninety-two older adults (2025-2026 cohort; mean age 75.9 years, 88.0% women) completed baseline and post-intervention assessments; an independent 2024-2025 cohort (n = 86) was analysed jointly for replication (n = 178). Main outcome measures: Short Physical Performance Battery (SPPB) score (primary); Timed Up and Go (TUG), handgrip strength, 6-metre walk time and Mini-Mental State Examination (MMSE) (secondary); probable sarcopenia (EWGSOP2), SPPB-based frailty category, and a fall-risk indicator computed identically in both cohorts. Results: SPPB improved by a mean of 1.33 points (Cohen's d = 0.96; p < .001), with concordant improvement in all four secondary outcomes (all q < .005). 72.8% reached the substantial minimal clinically important difference. Probable sarcopenia fell from 17.4% to 5.4% (p = .006), and frailty category shifted toward higher functional levels (p < .001). Effect sizes were consistent between cohorts for SPPB, handgrip and 6-metre walk; the Time x Cohort interaction was significant for TUG only. In the pooled sample, elevated fall risk fell from 19.7% to 11.2% (p = .002). Conclusions: A 36-week multicomponent exercise programme was associated with clinically meaningful, reproducible improvement in physical function and a reduction in probable sarcopenia across two independent cohorts. The single-arm design precludes causal inference.

Background: Systematic reviews are critical for informing evidence-based medicine, policy, and future research. However, conducting a systematic review is labour- and cost-intensive and error-prone. Elicit is an AI tool that claims to replicate the systematic review process. Methods: Our study investigated Elicit's ability to replicate a systematic review by comparing its results with those of an existing systematic review recently published by our research group. We calculated accuracy, precision, sensitivity, error rate, and person-time savings at each stage of the systematic review. Results: At search, Elicit had poor overlap, finding 158 of the 5285 studies. For abstract and full-text screening, Elicit had moderate sensitivity and accuracy but poor precision, with a skew toward false positives. Elicit's data extraction tool was promising, with sentence-specific citations, and provided helpful information for 85% of values even when it did not find exact matches. Elicit offered person-time savings, taking 3.16 hours to complete the full systematic review process. Conclusions: Elicit shows promise as an adjunct screening and extraction AI tool, but in its current form, it is not ready as a standalone tool to replace the systematic review process.

Introduction: The TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) trial was a pan-European, multi-centre, phase II/III trial investigating the impact of prophylactic paracetamol (also known as acetaminophen) given during the first 5 days of life for children born before 29 weeks' gestational age (GA) on survival to 36 weeks' post-menstrual age without severe neonatal morbidities. However, due to time restrictions, long-term follow-up was not planned as part of the initial trial despite recommendations for neonatal trials to include endpoints measuring efficacy after discharge from the neonatal unit and on-going debate about the long-term effects of paracetamol in the neonatal period. This protocol describes a study to follow-up participants in the TREOCAPA trial at 2 years corrected age initiated after the trial's onset. Methods and analysis: The TREOCAPA Long Term (TREOCAPA-LT) study population consists of all children included in the TREOCAPA phase III trial in centres in countries participating in the follow-up study who are aged between 23.5 and 27.5 months corrected age during the study period. Families are contacted by the clinical teams and a parent or guardian is invited to complete an internet-based (online) questionnaire. The primary outcome is cognition, as measured by the non-verbal Cognitive Scale standard score from the Parent Report of Children's Abilities-Revised (PARCA-R) questionnaire. Secondary outcomes are moderate to severe neurodevelopment, health service use and costs. Data will be analysed according to the study groups to which children were randomised in the original TREOCAPA RCT. Ethics and Dissemination: The TREOCAPA-LT protocol was first approved by ethics' committees in France (the study's sponsor) and subsequently by all participating countries. Results from TREOCAPA-LT will be published in open access journals in accordance with the funder's regulations. Registration: https://clinicaltrials.gov/study/NCT06064825

BACKGROUND: Federal policy now requires sponsors to submit diversity action plans for clinical trials, yet the modifiable features of trial design associated with enrolled composition remain poorly characterized. English-language proficiency requirements are written into eligibility criteria and recorded as free text in a public registry, making them visible and, in principle, amenable to revision, but their relationship to enrolled composition has been examined only within single disease areas and in small samples of trials. We examined whether these requirements and documented language accommodation were associated with the racial and ethnic composition of enrolled participants. METHODS AND FINDINGS: We conducted a cross-sectional study of interventional trials registered on ClinicalTrials.gov with at least one US site and posted results, using a registry snapshot retrieved in October 2026. The primary cohort comprised the 44,487 trials with exclusively US sites, of which 21,924 (49.3%) reported baseline race and 17,434 (39.2%) reported baseline ethnicity with counts that reconciled with the posted denominator. Both exposures were classified from free-text eligibility criteria using regular expressions validated against independent physician review of 150 trials. For the English-language requirement classifier, sensitivity was 88.2% and specificity was 99.2%. The outcome was the trial-level proportion of enrolled participants in each category, analyzed using generalized linear models adjusted for intervention class, therapeutic area, sponsor, phase, enrollment, sites, start year, US Census region, and the population composition of the trial's site states. An English-language proficiency requirement appeared in 5,736 trials (12.9%); its prevalence rose from 7.4% of trials starting in 2010 to 26.2% in 2023 (odds ratio [OR] per decade 2.91, P<0.001), whereas documented accommodation, an eligibility statement allowing participation in a language other than English (Spanish in 99.9% of flagged trials), remained rare (788 trials, 1.8%). The requirement was associated with lower enrolled proportions of Asian (OR=0.85, 95% CI 0.77-0.93, P=0.001) and Hispanic/Latinx participants (OR=0.85, 95% CI 0.79-0.91, P<0.001), with no evidence of an association for White participants (OR=0.99, 95% CI 0.95-1.04, P=0.75). Documented accommodation was associated with a higher proportion of Hispanic/Latinx participants (OR=3.23, 95% CI 2.82-3.71, P<0.001). Geographic adjustment did not change the statistical significance of the requirement associations and attenuated the accommodation association. The main limitations were the cross-sectional design, which precludes causal inference; the restriction of enrollment analyses to trials reporting baseline demographics, which were more recent than those without such reporting; and possible misclassification of automatically classified exposures. CONCLUSIONS: English-language proficiency requirements became more than three times as common between 2010 and 2023 and were associated with lower enrolled proportions of Asian and Hispanic/Latinx participants. Less common documented language accommodation was associated with a higher enrolled proportion of Hispanic/Latinx participants. Because these criteria are investigator-written and publicly recorded, they may be a tractable target for improving enrollment equity, although whether revising them changes who enrolls requires prospective evaluation

Epidemiological studies associate replacing animal-sourced with plant-sourced protein with lower colorectal cancer (CRC) risk, but controlled feeding studies have rarely tested how this substitution alters the gut microbiota and CRC-related biomarkers. In a 12-week randomized controlled feeding study, 136 healthy adults consumed diets providing 30 energy percent (E%), 50 E%, or 70 E% of protein from plant sources. Change in gut microbiota composition was the primary outcome; stool characteristics, fecal N-nitroso compounds (NOCs), and fecal and plasma bile acids (BAs) were secondary outcomes. The 70% plant-protein diet significantly restructured the gut microbiota, increasing fiber-associated Lachnospiraceae and Roseburia while reducing Methanobrevibacter and several asaccharolytic taxa. Microbial functional potential shifted toward plant-carbohydrate degradation, with lower amino acid degradation and methanogenesis. Fecal pH decreased, stool characteristics suggested faster colonic transit, and potentially carcinogenic total and haem-derived NOCs declined progressively with plant-protein replacement. The 70% plant-protein diet also reduced fecal secondary and taurine-conjugated BAs, including the CRC-associated BAs DCA and LCA. Plasma glucuronidated BAs increased, expanding the circulating pool of readily excreted BA conjugates. Higher insoluble fiber intake was associated with greater microbiota restructuring and lower fecal NOCs. Methanogen carriers had higher baseline fecal NOCs and features of slower colonic transit, and showed weaker microbiota and less favorable BA responses to the 70% plant-protein diet. Baseline methanogen carriage thus could be exploited for participant stratification in future dietary interventions.

Background: Erythritol and xylitol, naturally present in fruits and vegetables, are widely used as alternative sweeteners with minimal glycemic and insulinemic effects. Both are also produced endogenously, with elevated plasma concentrations reported in metabolic disorders and cardiovascular disease. Recently, two interventional studies reported enhanced platelet aggregation after acute oral intake of erythritol or xylitol, raising concerns about potential prothrombotic effects. We investigated whether acute exposure to erythritol or xylitol increases platelet reactivity in healthy individuals. Methods: We conducted a randomized, single-blind, crossover study in 14 healthy participants who received erythritol (50 g), xylitol (33.5 g), or water. Platelet aggregation was assessed ex vivo, together with circulating markers of platelet activation (P-selectin), endothelial activation (sVCAM-1), and coagulation (D-dimer), as well as plasma erythritol and xylitol concentrations. Complementary in vitro experiments were performed using platelet-rich plasma from 11 healthy participants exposed to increasing concentrations of erythritol or xylitol, followed by assessment of platelet aggregation. Results: Despite substantial increases in circulating erythritol and xylitol concentrations following oral intake, neither erythritol nor xylitol increased ex vivo platelet aggregation compared with water. Consistently, no relevant changes were observed in P-selectin, sVCAM-1, or D-dimer concentrations. Direct in vitro exposure of platelet-rich plasma to increasing concentrations of erythritol or xylitol likewise did not enhance platelet aggregation. Conclusions: In healthy individuals, acute oral intake of erythritol or xylitol did not increase platelet aggregation or circulating markers of platelet activation, endothelial activation, or coagulation. These findings were supported by in vitro experiments showing no direct effect of erythritol or xylitol on platelet aggregation. Our results do not support an acute platelet-activating effect of erythritol or xylitol under the conditions studied. Registration: URL: https://clinicaltrials.gov/study/NCT04966299; Unique identifier: NCT04966299.

Looping is a major cause of difficult and painful insertion during unsedated colonoscopy, yet strategies are largely guided by trial and error; prolonged insertion may jeopardise completion, discourage future surveillance and is associated with lower adenoma detection. In this randomised trial of 141 patients, protocolised review of pre-existing abdominal-pelvic computed tomography (CT) anticipated colonic anatomy and shortened caecal intubation time by 136 s, while reducing pain, discomfort and operator workload and increasing willingness to repeat colonoscopy. Effects were largest in N-loop and alpha-loop configurations, which accounted for 83% of patients. Routinely acquired CT could support anatomy-informed colonoscope insertion especially when anesthesia services are limited or sedation poses an elevated risk.

BackgroundSevere community-acquired pneumonia (CAP) remains a leading cause of mortality in children under five. The PediCAP trial evaluated oral step-down therapy using dispersible amoxicillin or amoxicillin/clavulanate tablets in African children hospitalised with severe CAP. Dispersible tablet formulations are preferred in children; however, pharmacokinetic data for oral amoxicillin/clavulanate in paediatric populations remain limited. We characterised the pharmacokinetics of 4:1, 7:1, and 14:1 dispersible amoxicillin/clavulanate tablets in children enrolled in the PediCAP trial and predicted target attainment under different dosing schemes. MethodsChildren were randomised within 24 hours of starting intravenous antibiotics to oral step-down therapy with weight-banded dosing of twice-daily amoxicillin/clavulanate (4:1, 7:1, or 14:1). Plasma concentrations were quantified following intensive sampling and analysed using nonlinear mixed-effects modelling with allometric scaling and postmenstrual age-dependent clearance maturation. Pharmacodynamic indices included %fT>MIC for amoxicillin and %fT>Ct for clavulanate. ResultsA total of 157 children (median [range] age, 12 [2-70] months; weight, 8.4 [4.0-22.0] kg) contributed 707 paired concentrations. Amoxicillin was described by a two-compartment model and clavulanate by a one-compartment model, both with sequential zero-and first-order absorption. Typical clearance for an 8-kg individual at full maturation was 11.8L/h for amoxicillin and 6.1L/h for clavulanate. Pharmacokinetics were similar between the formulation ratios. Weight-banded dosing achieved balanced exposures across weight groups. Amoxicillin achieved 40%fT>MIC for MICs[&le;]2mg/L. A proposed clavulanate target of 20%fT>0.5mg/L was achieved in most children even at the lowest amoxicillin/clavulanate ratio. ConclusionWeight-banded dosing using dispersible amoxicillin/clavulanate tablets provide consistent exposure profiles in African children with severe CAP. SUMMARYPopulation pharmacokinetic modelling of dispersible amoxicillin/clavulanate tablets (4:1, 7:1, 14:1) in 157 African children with severe pneumonia showed weight-banded dosing achieved consistent and adequate amoxicillin and clavulanate exposures across formulations.

Although physical activity is associated with better physical functioning, the effects of initiating regular physical activity among older adults with persistent inactivity remain unclear. We conducted a sequential target trial emulation using Health and Retirement Study (HRS) data to estimate the effect of physical activity initiation versus noninitiation on incident mobility difficulty. Participants were included in the analysis if they were aged [&ge;]65 years at the previous wave, reported no regular physical activity at the previous two waves, and had no mobility, activities of daily living (ADL), or instrumental activities of daily living (IADL) difficulties at baseline. Stabilized inverse probability of treatment weighting was applied to adjust for measured confounding. Weighted cumulative incidence was then estimated with death treated as a competing event, and risk differences were calculated at approximately 2, 4, and 6 years. At 2 years, the cumulative incidence of mobility difficulty was 32.75% among initiators and 39.73% among noninitiators, with a risk difference of -6.98 percentage points (95% CI, -13.11 to -0.88). At 4 and 6 years, risk differences were -2.90 percentage points (95% CI, -9.77 to 4.29) and -5.44 percentage points (95% CI, -12.27 to 1.99), respectively. Initiating regular moderate or vigorous physical activity was associated with a lower risk of incident mobility difficulty at approximately 2 years among older adults with persistent inactivity. This difference was less evident at later follow-up, and no clear differences were observed for incident ADL or IADL difficulty.

Despite the numerous benefits associated with higher dietary quality, many older Veterans do not meet national dietary recommendations. Existing programs are not typically tailored for older Veterans who may experience physical and environmental limitations that hinder their ability to access and prepare healthy foods. This project piloted the incorporation of age-friendly, tailored, virtual nutrition education into an existing health promotion program for older Veterans. Programming followed an iterative design process over two years. Year 1 included 14 weeks of virtual nutrition education on healthy aging paired with weekly produce bags and recipe suggestions. In Year 2, virtual nutrition education shifted to more hands-on learning emphasizing basic meal preparation and adaptive cooking strategies for mobility limitations. Produce distribution in Year 2 shifted to a farmer's market model, based on feedback from year 1, allowing participants to self-select items. Primary outcomes included program satisfaction, dietary intake assessed via 24-hour recall to calculate the Healthy Eating Index (HEI-2015), and health-related quality of life (PROMIS Global Health). Findings demonstrate the feasibility and acceptability of a virtual nutrition program incorporating age-friendly cooking instruction and adaptive strategies to improve dietary quality among older Veterans.

TrialCalibre1 is an agentic system that connects clinical evidence, study design, and executable analyses. It supports reference-trial replication, direct target-trial emulation, and BenchExCal, which combines benchmarking, extension, and cal ibration sensitivity analysis. We evaluated an ASCET-based benchmark and an extension comparing clopidogrel with aspirin among adults aged 81-90 years us ing synthetic PCORnet-style claims. Two reviewers assessed benchmark extrac tion, protocol decisions, and implementation. After discussion, 53/62 and 50/62 assessable SQL checks were rated met; both reviewers rated 12/13 assessable R checks met. Protocol and proxy disagreements remained. A separate ten-question routing development set yielded 10/10 route matches and 7/7 applicable reference trial matches. The agent benchmark and extension included 6,069 and 1,602 pa tients. The extension risk ratio was 0.848 (95% CI 0.569-1.184), with a calibrated sensitivity estimate of 1.274 (0.439-3.700). The human implementation provided descriptive comparisons, not same-data validation. Dose proxies, unpopulated co variates, residual imbalance, implementation deviations, and ignored cross-cohort covariance limited interpretation. This case demonstrates a connected workflow whose protocols, code, and results can be reviewed.

Background: Cardiometabolic disease is a leading cause of death, and most therapies suppress established pathology rather than restore functional capacity. Pulsed electromagnetic field (PEMF) therapy is a non-invasive stimulus touted as a potential complementary approach that may engage adaptive responses, with practical potential for home-based use. We systematically reviewed and meta-analysed PEMF effects on cardiometabolic outcomes. Methods: We searched seven electronic databases and Google Scholar from inception to 31 August 2026 for studies of PEMF in adults, healthy or with cardiometabolic conditions. Between-group differences were rescaled into minimal clinically important difference (MCID) units to facilitate comparison across diverse outcomes. Established anchor-based MCIDs were used where available; otherwise, 0.5 pooled within-arm SD was used. Effects were pooled using multilevel random-effects models with study-clustered robust variance, with subgroup, sensitivity, and exploratory dose-response analyses. The review was registered with PROSPERO (CRD420261404575). Results: Ten studies (353 participants) were included. PEMF was associated with an overall benefit of 0.54 MCID units (95% CI 0.08-1.00). Effects were largest in hypertension (1.24 MCID units, 0.52-1.96), with no observed heterogeneity across two double-blind trials (I2=0%). Exploratory multivariable meta-regression associated greater cumulative exposure and lower frequency with larger effects. Conclusions: PEMF therapy may offer a non-invasive, non-pharmacological adjunct for improving cardiometabolic outcomes, with potential for home-based use. The most compelling signal was observed in hypertension, where the pooled effect exceeded one clinically important difference, although confirmation in larger trials is required.

Introduction: Adolescents experience high rates of depression and anxiety, yet globally 80% of adolescents and almost all in low-and middle-income countries (LMICs) lack access to adolescent-friendly treatments. The African Youth in Mind (Y-MIND) set out to adapt the youth version of the Friendship Bench and assess its feasibility for delivery in Ghana. Methods: In this feasibility cluster randomised controlled trial, we recruited participants aged 15 to18 years with probable diagnosis of moderate to severe depression ascertained with the Patient Health Questionnaire (PHQ-9) total score > 9 from six Senior High Schools in Navrongo, Ghana. Schools were randomly allocated (1 to 2) to enhanced usual care (EUC) alone or EUC combined with Y-MIND, prior to recruitment of participants. Primary outcomes were feasibility (intervention delivery; conducting a fully powered trial). Secondary outcomes were intervention appropriateness, acceptability, and probable depression symptom severity and remission on the PHQ-9. Results: Between July and August 2024, we enrolled and allocated 67 participants (43 [64%] to the EUC plus Y-MIND group and 24 [36%] to the EUC alone group), of whom 64 (95.5%) completed the 5-month primary outcome assessment (41 [95.3%] in the EUC plus Y-MIND group and 23 [95.8%] in the EUC alone group). The feasibility of delivering the Y-MIND intervention from the perspective of adolescents had a mean score of 4.3 (0.5). Therapy quality score was 94.8% (95% CI: 93.0, 96.6), while therapy competence was 86.6% (95% CI: 81.2, 92.2). We observed initial clinical benefits, including lower severity of depressive symptoms among adolescents in the Y-MIND group as compared to those in the EUC group, with most participants achieving symptomatic remission at the month 5 follow-up. Conclusion: The Y-MIND school-based psychological treatment model demonstrated good acceptability and feasibility, with high recruitment, retention, treatment adherence, and provider competence. While preliminary findings indicate potential improvements in depressive symptoms, the study was not designed to establish effectiveness. These findings justify progression to a fully powered trial to determine clinical effectiveness, cost-effectiveness, and the scalability of the intervention within routine school settings in LMICs. Trial registration: Clinicaltrials.gov (NCT06740084).

Music is a central component of psychedelic settings, yet little experimental work has examined how psilocybin and musical composition influence music-evoked emotional responses in healthy volunteers. This exploratory, double-blind, placebo-controlled study assessed these effects during the plateau phase of psilocybin and the corresponding time window in placebo sessions following oral administration of psilocybin (0.26 mg/kg) or placebo. The study consisted of two parts. In Part 1 (n = 19), a pilot stage, the first half of participants rated music-induced affective valence for eight compositions representing different genres/subgenres (Rock/Punk, Metal/Industrial Metal, Metal/Industrial Metal, Classical/Baroque, Electronic/Dub, Folk/Nordic Folk, Electronic/Techno, Electronic/Trance, Electronic/Psytrance) using a visual analogue scale (VAS). Based on Part 1, the classical composition with the highest overall affective valence and the psytrance composition with the largest psilocybin-placebo contrast (i.e., the composition most responsive to psilocybin) were selected for Part 2 (n = 17), in which the second half of participants assessed emotional responses to music using the Geneva Emotional Music Scale (GEMS-9). Psilocybin increased wonder, transcendence, and joyful activation across both contrasting compositions. Relative to each other, the classical composition elicited greater peacefulness, tenderness, and nostalgia, whereas the psytrance composition elicited greater tension across both psilocybin and placebo conditions. A composition x condition interaction was observed for sadness: under psilocybin, sadness increased during the classical composition and decreased during the psytrance composition. These findings suggest that psilocybin and contrasting musical compositions independently influence different aspects of music-evoked emotional responses, with limited interaction effects, and point to potential implications for protocol design and music selection in psychedelic settings.

Background: The practice of hospitalizing emergency department (ED) patients with chest pain after ruling out acute myocardial infarction (AMI) varies widely. The long-term outcome and cost implications of this variation are uncertain. Methods: Analyzing 2007-2021 claims from a national commercial insurer, we identified 223,569 adults (18 years or older) ED visits with a principal diagnosis of chest pain without major secondary cardiopulmonary diagnoses, seen by 19,001 clinicians in 2,273 EDs. Within each ED, clinicians with the highest and lowest terciles of risk-adjusted hospitalization rates were classified as high- versus low-admitting. Primary outcomes were 30- and 180-day subsequent AMI hospitalizations. Secondary outcomes included 7-day cardiac testing, 30-day coronary intervention, and 30-day total and out-of-pocket costs. We estimated adjusted rate ratios (aRRs) and relative cost differences using generalized estimating equations, adjusting for patient and visit characteristics. Results: Patients had a mean age of 48.6 years, and 53.9% were female; measured characteristics were similar between groups. Compared with low-admitting clinicians, visits to high-admitting clinicians had higher 7-day cardiac testing (13.1% vs 10.8%; aRR 1.22, 95% CI 1.17-1.27) and 30-day coronary interventions (4.3% vs 3.8%; aRR 1.16, 95% CI 1.09-1.23). AMI hospitalization did not differ at 30 days (0.60% vs 0.60%; aRR 1.00, 95% CI 0.84-1.15) or 180 days (0.85% vs 0.87%; aRR 0.97, 95% CI 0.85-1.10). Thirty-day total costs were higher after visits to high-admitting clinicians (relative change 11.3%, 95% CI 8.8-13.8), and out-of-pocket costs $1,000 or more were more common (32.0% vs 29.6%; relative change 8.2%, 95% CI 6.1-10.3). Conclusions: Higher clinician hospitalizing tendency for ED chest pain is associated with greater downstream testing, more coronary interventions, and higher costs without lower short- or intermediate-term AMI risk. Reducing marginal admissions among high-admitting clinicians may decrease spending and practice variation with minimal impact on AMI outcomes.

Background: People with severe mental illness (SMI) report poorer oral health outcomes than the general population, are less likely to attend regular dental check-ups, and may require additional support to visit a dentist. Our previous research showed that interventions tailored to their needs and support from the mental health care system are needed to improve oral health outcomes in people with SMI. Although there is some provision of urgent dental care for people with SMI, there are currently limited available interventions that integrate dental and mental health care and provide dental support in a mental healthcare setting. To address this gap, the aims of the SMILE project are to 1) co-develop and 2) test the feasibility and acceptability of an oral health intervention for people with SMI, delivered by mental health professionals in secondary community mental health care settings. This paper describes the protocol for the feasibility and acceptability testing of the SMILE intervention. Methods: This is a single-arm, non-randomised feasibility trial assessing the feasibility and acceptability of an intervention to support the oral health of mental healthcare service users with SMI. The intervention was co-produced with service users, carers, mental health and dental health professionals, and includes advice on maintaining good oral hygiene and lifestyle habits to maintain good oral health. The main aim of the study is to assess the feasibility and acceptability of delivering the intervention, using quantitative data collected at baseline, three and six-month follow-up, and qualitative interviews with participants and mental health staff involved in delivering the intervention. Results: The study results will determine whether the intervention can be successfully delivered in secondary community mental health care settings and inform the most appropriate primary and secondary outcomes for a future trial. Conclusion: The findings of this study will inform the feasibility of progression to the pilot stage of a randomised controlled trial to assess the clinical and cost effectiveness of delivering an oral health intervention in a mental healthcare setting.

Elevated systolic blood pressure (SBP) is a major modifiable driver of cardiovascular morbidity. Digital food-as-medicine and home-blood-pressure-monitoring programs increasingly support its management outside the clinic, but most published evaluations are single-arm, pre/post designs; because enrolment is conditioned on an elevated baseline reading, regression to the mean (RTM) is expected to inflate any observed improvement, and this is rarely checked against an internal comparator. We conducted a retrospective, single-arm cohort study of home blood-pressure monitoring within a commercial digital food-as-medicine program serving a US employer-sponsored population with obesity. Of 329 members included, 136 were at-goal (<130/80 mmHg), 74 at Stage 1 (130-134/80-84 mmHg) and 119 at Stage 2 ([&ge;]135/85 mmHg) at baseline; follow-up SBP was evaluable for 128, 68 and 112 members in these strata at 3 months and for 62, 34 and 53 at 6 months, respectively. The primary estimand was the unadjusted within-member change in home SBP at 6 months among members with Stage-1 and Stage-2 blood pressure at baseline; a secondary estimand corrected for RTM using an ANCOVA linear mixed model with the at-goal stratum as an internal negative-control population. Among Stage-1 members (n = 34), unadjusted SBP change was -4.36 mmHg (95% CI -7.43 to -1.28; p = 0.0069), paired with an RTM-corrected secondary change of -3.33 mmHg (-6.40 to -0.26; p = 0.033). Among Stage-2 members (n = 53), unadjusted change was -10.17 mmHg (-12.94 to -7.40; p < 0.001), paired with an RTM-corrected secondary change of -5.50 mmHg (95% CI -8.50 to -2.50; p = 0.00037); RTM accounted for ~24% and ~46% of the unadjusted decline in Stage-1 and Stage-2, respectively. RTM-corrected estimates were robust to sensitivity analyses on measurement modality, seasonality, covariates and model specification, with no evidence of attrition bias. Program participation was associated with a decline in home SBP among Stage-1 and Stage-2 members that remained significant, though smaller, after RTM correction, supporting RTM-adjusted SBP change as the appropriate metric for evaluating food-as-medicine interventions.

Abstract Background: Despite the high stroke burden in the elderly, their thrombolysis utilization is suboptimal partly due to heightened hemorrhagic risk. Observational data suggest that low-dose thrombolysis may offer comparable efficacy to standard-dose with a trend toward reduced symptomatic intracranial hemorrhage (sICH), yet high-level evidence for low-dose thrombolysis in this broad population remains absent. Objective: To evaluate the safety and efficacy of low-dose intravenous tenecteplase thrombolysis in elderly stroke patients within 4.5 hours of ischaemic stroke onset. Methods and design: The DATE-AGING trial is a multicenter, prospective, randomized, open-label, blinded-end point (PROBE) non-inferiority study. Eligible participants are elderly patients (aged [&ge;]70 years)with acute ischemic stroke who meet current guideline recommendations for intravenous thrombolysis within 4.5 hours of symptom onset will be randomly assigned to Low-dose Tenecteplase group (0.175 mg/kg, max 17.5 mg) or Standard-dose Tenecteplase group (0.25 mg/kg, max 25 mg). The primary outcome was excellent functional outcome, defined as a mRS 0-1 assessed at 90-day post-randomization. Safety outcomes included sICH within 36 hours and mortality at 90 days. Discussions: The DATE-AGING trial is intended to provide high-quality evidence for low-dose tenecteplase intravenous thrombolysis in elderly patients with acute ischemic stroke. Trial registry number: NCT07294209(https://clinicaltrials.gov/study/07294209). Keywords: elderly patients, acute ischemic stroke, intravenous thrombolysis, low-dose tenecteplase