Pilot and Feasibility Studies

Background Temperature instability during neonatal transport contributes to adverse outcomes in preterm and low birth weight infants. Hypothermia in this population is associated with increased risk of intraventricular haemorrhage (IVH), sepsis, and death. Current transport temperature management is reactive and manually controlled. The Heating On Transport WitH prEtErm and Low birth weight neonates using Servocontrol patient temperature management system (HOTWHEELS) trial aims to determine whether automated, servo-controlled thermoregulation provides superior thermal stability compared to standard care and reduces hypothermia-associated adverse outcomes. Methods This prospective, randomised, superiority trial is conducted by the Newborn Emergency Transport Service of Western Australia. Infants with a gestational age of less than or equal to 34 weeks and/or weight of 1500 g requiring transport are randomised to serve-controlled or standard thermal care. The primary outcome is the proportion of infants with a temperature between 36.5 and 37.5 degrees Celsius on arrival at the receiving neonatal unit. Secondary outcomes include the incidence of IVH in the first 7 days, mortality before discharge, the incidence of moderate (<36.0) and severe (<35.0) hypothermia for greater than 15 minutes and the temperature change during transport. Trial registration: ANZCTR12624000503527. Impact HOTWHEELS is the first randomised trial in neonatal transport to evaluate servo-controlled temperature control. We believe the findings will inform standards of temperature control during transport for preterm and low birth weight infants.

Background: Large language models (LLMs) configured as virtual patients may expand structured practice of clinical reasoning in health professions education. Before testing effectiveness, it must be established whether students engage with them and whether the resulting scores are complete, reliable, and related to performance with real patients. Our earlier pilot randomized trial found very low engagement with a less structured LLM-based approach. Objective: This study aimed to assess the feasibility (adherence, acceptability, and data completeness) of a revised, structured LLM-based clinical reasoning laboratory (Laboratorio de Inteligencia Artificial [LIA]) in undergraduate physical therapy education and to explore its measurement properties, including its association with clinical judgment with a real patient assessed with the Lasater Clinical Judgment Rubric (LCJR). Methods: In this single-arm pilot feasibility study, 27 third-year physical therapy students at a Spanish university completed, in 2024-2025, 3 virtual patient cases (lumbar, cervical, and thoracic spine pain) simulated by ChatGPT (GPT-4) over 4 weeks, each twice. ChatGPT scored each attempt from 0 to 4 on the same 10 dimensions of the Lasater Clinical Judgment Rubric (LCJR; 0-40 points) that human assessors applied (1-4 per dimension; 10-40 points) during a real patient encounter. Feasibility outcomes were case completion, data completeness, and satisfaction (0-10). Measurement outcomes were internal consistency and convergent validity (Spearman correlations between model-generated and human LCJR scores). Variability estimates informed the sample size of a future trial. Results: All 27 students were assessed with the LCJR; 22 (81%) completed at least 1 LIA case. Both attempts of the lumbar, cervical, and thoracic cases were completed by 78%, 63%, and 74% of students, respectively. Satisfaction data were available for 15 students (56%; mean 6.0, SD 1.3), and missing secondary data clustered in the third rotation. Internal consistency was excellent for the LCJR (alpha=.96) and ranged from .43 to .90 for model-generated ratings. Model-generated LIA scores clustered near the maximum (mean 36.0, SD 1.4). Among completers, LIA scores correlated weakly with the LCJR (rho=0.25, 95% CI -0.20 to 0.61; rho=0.44, 95% CI 0.05-0.71, when noncompleted attempts were scored as 0). Grade point average correlated almost perfectly with the LCJR (rho=0.96; n=22); after adjustment for it, the LIA-LCJR association disappeared (partial rho=-0.10). A future trial would require approximately 39 students per group (80% power, conservative variance). Conclusions: Delivering the LIA within the curriculum was feasible, but clinical judgment ratings generated by ChatGPT did not reflect those of human assessors with a real patient: they clustered near the maximum and showed no convergent validity once noncompletion was separated from performance. LLM-generated ratings should not be used as outcome or assessment measures without validation against human raters. Case calibration, completion tracking, and clarification of the GPA-LCJR relationship are also needed before a definitive trial. Trial Registration: ClinicalTrials.gov NCT06809634; https://clinicaltrials.gov/study/NCT06809634

Objective: To examine changes in function and pain interference among patients utilizing a digital exercise therapy application (DETA) for knee and shoulder pain. Methods: We conducted a retrospective analysis of data from patients utilizing a DETA for non-operative knee and shoulder pain. Primary outcomes for the study were 8-week changes in physical function, measured using the PROMIS-Physical Function (knee pain) and PROMIS-Upper Extremity Function (shoulder pain); and pain interference, measured using the PROMIS-Pain Interference. Data on patient characteristics was used to examine outcomes among specific patient subgroups. Results: We observed a 3.5 point (SD: 7.8) increase in function and a 3.9 point (SD: 7.5) decrease in pain interference overall (p<0.001), with changes in function and pain interference surpassing the minimal clinically important difference for patients with knee and shoulder pain. Patients with knee pain experienced greater improvements in function than those with shoulder pain (p=0.02), as did patients who report moderate-high levels of exertion during exercise compared to those reporting low levels of exertion (p=0.05). We saw greater reductions in pain interference among those with higher education (p=0.03), those with more acute symptoms (p=0.01) and those reporting moderate-high levels of exercise exertion (p=0.02). Conclusion: We observed a clinically meaningful improvement in pain interference and function among patients utilizing a DETA for knee and shoulder pain. Patients with knee pain, higher levels of education, more acute symptoms, and those who reported higher levels of exertion with exercise experienced the greatest changes in function and pain. Impact Statement: This study indicates that self-guided interventions, such as those delivered through a DETA, may be beneficial for patients with knee and shoulder pain. These results may also inform the development of patient profiles that can be used to identify patients most appropriate to receive care through a mobile application.

Children living with HIV face significant challenges with adherence to daily oral antiretroviral (ARV) treatment due to poor palatability, complicated dosing, and caregiver burden. Long-acting delivery systems designed specifically for children may help overcome these barriers. Microarray patches, also known as microneedle patches, are a needle-free drug delivery technology that could simplify treatment administration and improve adherence. This study explored the acceptability and usability of a pediatric ARV microarray patch prototype among stakeholders in South Africa and Uganda, two countries with a high burden of pediatric HIV. A formative study was conducted in 2024 with 48 participants, including caregivers, community health workers, health care providers, and decision-makers. Data were collected through qualitative methods: interviews, simulated use sessions, and observations. Participants demonstrated high usability of the prototype, with 97% completing all application steps and nearly all reporting the prototype as easy to use and expressing confidence in successful administration. Most participants found the prototypes size, wear time, and temporary skin changes acceptable, and all preferred a weekly patch over daily oral treatment. Applying multiple patches at once to achieve a therapeutic dose was considered feasible. Decision-makers foresaw strong programmatic fit of a pediatric ARV microarray patch if caregivers apply the patch at home following initial facility-based guidance. Overall, the pediatric ARV microarray patch prototype was perceived as highly acceptable and usable across diverse end users, findings that generally align with studies of microarray patches for other use cases (e.g., contraception, HIV pre-exposure prophylaxis, vaccine delivery). The simplicity, comfort, and convenience of a pediatric ARV microarray patch could substantially improve treatment adherence and quality of life for children living with HIV. Further development and clinical evaluation are warranted to advance this promising technology toward real-world use.

Background: School-based implementation of robot-assisted walking may support increased physical and social participation for children with physical disabilities, but evidence from an adequately powered trial is needed. This pilot study evaluated implementation strategies and study procedures to inform a future definitive trial. Methods: Participants were randomized to 12-weeks of robot-assisted walking or control, with subsequent crossover to the other condition. In the intervention arm, targeted dose was 75 minutes of robot-assisted walking, spread across three days/week. Implementation strategies for the child's classroom team included educational materials, centralized technical assistance, school champions, and on-going training. Implementation strategy evaluation focused on intervention protocol feasibility (i.e., weekly device use, troubleshooting) and fidelity (documentation of implementation strategy modifications). Preliminary estimates participation goal changes were obtained using the Canadian Occupational Performance Measure (COPM) 'Performance' scale (/10). Results: Eight children with neurodevelopmental physical disabilities participated (mean age 3.5, SD 0.5 years). Device use varied from 2.1 to 4.3 days/week (median 3.3) with a range of 48 to 96 minutes/week (median 80). Target use of >= 3 days/week was achieved for 66% of weeks and met the >=75-minute target for 33% of weeks. Troubleshooting occurred in 18.5% of sessions. Two implementation strategies were modified to improve feasibility. COPM mean change was 3.56 (SD 1.07) for robot-assisted walking and 2.11 (SD 2.41) for control (dz=0.74). Conclusions: This pilot study provided preliminary evidence regarding both the feasibility of robot-assisted walking implementation in schools and its potential effectiveness for children with physical disabilities. Findings support progression to a definitive trial.

Abstract Background: Randomized trials show substantial weight loss with semaglutide and tirzepatide under structured care, but little is known about whether patients in routine practice continue therapy, reach a maintenance dose, and have their weight measured. Objectives: To describe the first year after initiation of semaglutide or tirzepatide for obesity, including care patterns, maintenance-dose attainment, weight documentation, and total body weight loss (TBWL). Methods: This retrospective cohort study used Epic Cosmos, an electronic health record network of >350 US health systems, to identify adults with obesity and without diabetes who initiated injectable semaglutide or tirzepatide in 2024. Outcomes over 12 months included prescribing persistence, discontinuation, switching, add-on therapy, and reinitiation; attainment of Food and Drug Administration (FDA)-labeled maintenance doses; availability of follow-up weight; and TBWL across progressively restricted populations. Results: Among 743,153 adults (60.1% semaglutide; mean age, 48.5 years; 72.5% female), 12-month prescribing persistence was 29.9% for semaglutide and 35.9% for tirzepatide. FDA-labeled maintenance-dose attainment was 28.3% and 55.0%, respectively, and only 8.8% and 16.4% remained prescribing persistent at a maintenance dose with a recorded weight at 12 months. About half of initiators lacked a 12-month weight. Among all initiators, [&ge;]5% TBWL was documented in 25.6% (semaglutide) and 30.4% (tirzepatide), rising to 51.9% and 61.9% among those with recorded weight, 66.1% and 79.5% among those also prescribing persistent, and 82.9% and 87.3% among those further at a maintenance dose. Conclusions: In routine practice, most patients initiating semaglutide or tirzepatide did not remain on therapy, reach a maintenance dose, and have weight documented through the first year. Documented weight loss was greatest among those completing each step of care, suggesting continuation, dose escalation, and monitoring as targets for improvement.

Background: Clinical decision support (CDS) systems may improve chronic pain management by providing guideline-based recommendations within clinical workflows. However, low clinician use can limit their effectiveness. Understanding the association between CDS use and guideline-recommended care may help distinguish implementation challenges from limitations in CDS functionality. Objective: To estimate the association of OneSheet, a CDS system for chronic pain management, and guideline-recommended care when the system was used during patient encounters. Methods: We conducted a per-protocol secondary data analysis of data from a pragmatic randomized clinical trial conducted from October 2020 to May 2022 across 25 primary care clinics at 2 academic health systems in Indiana and North Carolina. The parent trial enrolled 137 primary care clinicians. This analysis included 145511 eligible chronic pain encounters and 15480 long term opioid therapy (LTOT) encounters that occurred after OneSheet implementation. OneSheet use at a patient encounter was the exposure of interest. Propensity score matching was used to create comparable groups of encounters with and without OneSheet use. Outcomes included documentation of pain-related goals, documentation of pain and function using the Pain, Enjoyment of Life and General Activity (PEG) scale, prescription drug monitoring (PDMP) review, urine drug screening (UDS) orders, and naloxone orders. Results: OneSheet was used in 959 of 145511 chronic pain encounters (0.7%) and 582 of 15480 LTOT encounters (4.0%). In matched analyses, OneSheet use was associated with increased documentation of pain-related goals (relative risk (RR)=11.70 (95% CI 4.25-32.50) and PEG score documentation (RR=9.70 (95% CI 4.14-22.31). Among LTOT encounters, OneSheet use was associated with increased UDS ordering (RR=1.52 (95% CI 1.40-1.65) and PDMP review (RR=1.06 (95% CI 1.03-1.09), but decreased naloxone ordering (RR=0.13 (95% CI, 0.02-0.90). Conclusions: OneSheet use was associated with several guideline-recommended chronic pain management actions, suggesting that they system may support care quality when clinicians use it. However, use was rare, indicating that increasing routine use through better workflow integration may be necessary to achieve population-level improvements in chronic pain care.

IntroductionCurrent evidence suggests that patient health passports may improve care for patients with chronic illnesses. This systematic review aimed to evaluate the impact of patient health passports on health outcomes in adults with diabetes. MethodsA systematic review was conducted in February 2025 following PRISMA 2020 guidelines, using Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, Web of Science, and Scopus. The review included studies of adult diabetic patients using paper or digital patient health passport as part of their care in comparison with the standard of care. Data were analysed using meta-analysis and a thematic analysis where appropriate; otherwise, the data are presented narratively. Quality appraisal was undertaken using the Cochrane Collaboration tool for assessing risk of bias and Evidence-based librarianship checklist. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. ResultsEleven studies (n=14,350) were included. Seven studies were randomised controlled trials, two were retrospective in nature, one was a qualitative and one was a pre-post study. Overall, the studies are limited in design, resulting in high or unclear risk of bias across multiple domains. Results of the meta-analysis of five studies showed a statistically significant mean difference reduction in HbA1c and total cholesterol in favour of the intervention group; however, the certainty of the evidence is low or very low. The narrative analysis of the data revealed little to no improvement in body mass index, blood pressure, blood glucose, and cholesterol levels. Patients opinions and perceptions revealed some benefits in usability, perceived value, and in enhancing collaboration. ConclusionThis review provides evidence suggesting that patient health passports may improve patient care and can inform the design of future high-quality studies. However, the low certainty of the evidence highlights the need for high-quality studies with larger sample sizes. Key PointsO_LIPatient health passports show promise in enhancing diabetes management, however current evidence is limited by high risk of bias; future high-quality studies are required to confirm efficacy. C_LIO_LINurses are pivotal in this process as they play a central role in diabetes education, self-management support and continuity of care. C_LIO_LIPatient health passports could be considered as a structured tool to facilitate ongoing monitoring, reinforce adherence, enhance communication between patient and nurses/multidisciplinary team. C_LI

Aims: To understand how users believe continuous glucose monitoring (CGM) changes their behaviour, which app features they credit, and whether endorsing more mechanisms of action (MoAs) is linked to reported diet and physical activity change. Methods: We surveyed 112 U.S. adults with type 1 or type 2 diabetes who had used a Dexcom or Abbott Libre CGM within 12 months. Participants rated 26 MoA statements mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model, identified contributing app features, and reported CGM-attributed diet and physical activity change. Logistic regression examined MoA count and COM-B domains as predictors of behaviour change. Results: Participants (mean age 54.5 years; 60.7% female) reported dietary (82.1%) and physical activity (46.4%) change and endorsed a median of 18 MoAs, most often relating to knowledge, skills and behavioural consequences. Real-time glucose and graphs were attributed to many MoAs. Each additional MoA was associated with higher odds of dietary (OR 1.27, 95% CI 1.15-1.44) and physical activity change (OR 1.27, 95% CI 1.16-1.43). Motivation made the strongest distinct contribution among COM-B domains. Conclusions: Users perceive CGM as engaging many behavioural mechanisms; endorsing more was linked to behaviour change. Motivation may be a key target for CGM-based behavioural support.

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

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.

Background: As musculoskeletal physiotherapy evolves toward advanced practice and direct access, evaluating high levels of clinical competence has become pressing. Quality indicators underpin large-scale audit systems, but indicators discriminating advanced competence remain insufficiently defined. Objective: To identify and characterize indicators capable of discriminating high levels of clinical competence in musculoskeletal physiotherapy. Methods: A modified Delphi comprised an exploratory pre-round and two consensus rounds. Experienced French-speaking musculoskeletal physiotherapists were recruited using an expertise scoring grid. Candidate indicators, generated from open-ended responses and existing quality indicators, were rated on 6-point Likert scales for relevance, formulation, and tool adequacy. Consensus was predefined as [&ge;]75% of ratings [&ge;]5. Results: Thirty-two experts completed the pre-round, 29 the first round, and 27 the second (84% retention), generating 49 candidate indicators. Thirteen reached consensus for relevance, and 10 also for formulation. Retained indicators primarily reflected advanced clinical reasoning: real-time adaptation, hypothesis prioritization, decision-making under uncertainty, and error management. Only one outcome indicator reached consensus: clinical performance weighted by case complexity. Conclusion: High levels of clinical competence in musculoskeletal physiotherapy appear characterized less by standardized outcome attainment than by managing complexity, uncertainty, and error through advanced clinical reasoning. These findings may inform competence-oriented audit and feedback systems. Trials registration: Not applicable.

Background: Gender-affirming medical care (GAMC) for children and adolescents in Australia has become increasingly politicized, despite care being provided in accordance with latest evidence-based international guidelines. Critics of GAMC claim that current assessment and deliberation processes are insufficient, and that too many young people are accessing medical interventions, no longer identifying as trans, and expressing treatment regret. These claims have led to widespread bans on the provision of paediatric GAMC, despite growing evidence regarding harms caused by such bans. Aim: This study sought to describe the care journeys of the young people attending Australia's largest paediatric gender service, with a focus on reporting the rates at which young people commenced medical interventions, re-identified with their birth-assigned sex, and expressed regret about their treatment. Methods: The Royal Children's Hospital Gender Service (RCHGS) is a statewide service that provides individualised multidisciplinary care to trans and gender diverse young people in Victoria, Australia. An initial extended triage appointment explores the needs and goals of the young person and their family. Some proceed to receive individualised multidisciplinary care (MDC) at RCHGS which can include psychosocial assessment and management, family support, and medical interventions including pubertal suppression (PS) and gender-affirming hormonal therapy (GAHT). We undertook a retrospective file audit of all patients who had attended at least one RCHGS appointment and been discharged between 1/1/2017-31/12/2024. For each person, key data were extracted from their electronic medical record and recorded in REDCap. Results: 1,391 patients were discharged over the 8-year study period and many different care trajectories were observed. 814 (58.5%) did not access ongoing MDC. Of the remaining 577, 353 (25.4% of total cohort) started a medical intervention ((PS: n=64/1391 (4.6%); estradiol: n=97/1391 (7.0%); testosterone: n=244/1391 (17.5%)). For those who started these medical interventions, the median duration and number of sessions from first appointment until commencement of medications was 530 (IQR: 371-693) days and 9 (IQR: 7-13) sessions. 346 of these patients (98.0%) had data on gender identity at discharge and subsequent care pathways. 7 (2.0%) re-identified with their birth-registered sex and stopped treatment: 4 did so after commencing PS (4/61=6.6% of those starting PS), 2 did so after commencing testosterone, and 1 did so after commencing estradiol (3/341=0.9% of those starting GAHT). Just one of these patients, who had been on estradiol for 1 month, expressed treatment regret given concerns about initial breast budding and future fertility. Conclusion: This study highlights varied trajectories of those referred to paediatric gender services, directly challenges claims used to justify restrictions on paediatric GAMC and underscores the importance of a person-centred approach to care.

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.

Aims: Our primary aim was to determine the immediate effects of using a supported stepping device on the real-time locomotor behavior of pre-walking infants with Down syndrome (DS). Our secondary aim was to characterize the role of the caregiver in facilitating infant locomotor behavior by quantifying infant-initiated and caregiver-initiated walker movement, and to test whether walker movement encourages stepping behavior. Methods: Pre-walking infants with DS played with their caregiver in two conditions--with and without assistance from a wheeled suspension walker. To examine changes across development, we recorded infants across one to four sessions from 10 to 19 months of age. Results: Across developmental stages, we found that suspension walkers robustly increased infants' locomotor behavior: The walker increased upright time, percent time stepping, stepping rate, upright bout rate, percent time locomoting, and total bout rate. Most walker movement was initiated by caregivers, and infants stepped more while the walker was moving compared to stationary. Conclusions: Even without practice, pre-walking infants with DS were able to take advantage of the suspension walker to increase their locomotor behavior. Caregivers facilitated infants' activity by moving the walker. Future work will examine the potential of overground suspension walkers for home-based intervention.

BackgroundMultimorbidity is common among U.S. skilled nursing facilities (SNFs) residents and complicates pharmacologic management, yet real-world evidence on treatment patterns in this population remains limited. This study evaluated medication order rates and identified resident- and facility-level factors among SNF residents with multimorbidity. MethodsRetrospective, observational study using electronic health record (EHR) data from PointClickCares Life Sciences database. Participants were 728,222 residents active in a U.S. SNF on April 30, 2025 with at least one documented diagnosis of hypertension, hyperlipidaemia, type 2 diabetes (T2D), depression, or Alzheimers disease and related dementias (ADRD). The outcome was presence of guideline-recommended medication order for each condition, modelled with modified Poisson regression to estimate adjusted prevalence risk ratios (RRs) and 95% confidence intervals. ResultsMedication order rates were 79% for ADRD, 79.1% for T2D, 87.7% for hypertension, 83.3% for hyperlipidaemia, and 90.8% for depression. Rates varied across comorbidity combinations: ADRD was associated with lower medication order prevalence, while cardiometabolic multimorbidity profiles associated with higher prevalence. Black/African American identity had the lowest likelihoods of a medication order for 3 of 5 conditions (RRs of 0.93 to 0.92), while having hypertension or hyperlipidaemia medication order was associated with higher likelihood of having orders for 3 of remaining 4 conditions (RRs of 1.02 to 1.19). ConclusionsMost SNF residents with multimorbidity had a medication order for common chronic conditions, although important variability and disparities remain. Differences by comorbidity profile and social context underscore the need for targeted strategies supporting equitable, integrated prescribing and person-centred care in SNFs.

Background: Ambient artificial-intelligence (AI) scribes are being deployed beyond medicine into allied-health practice, but comparative evidence mainly concerns physician documentation. Objective: To compare quality and transcript-grounded clinical-risk error burden of AI-generated and allied health professional notes from identical simulated consultations. Methods: Paired simulation across dietetics, physiotherapy, occupational therapy and speech and language therapy (five consultations each; 20 pairs; 40 notes). Heidi generated an unedited first-draft note and a professional documented each encounter. Professionals rated PDQI-9 quality. Professional and automated review identified unsupported statements and omissions; two language models graded clinical risk. Co-primary outcomes were PDQI-9 score and Critical+High error density. Results: Mean PDQI-9 scores were 38.45 and 35.05 for AI and professional notes (paired difference +3.40, 95% CI +0.01 to +6.79; Wilcoxon p=0.042; dz=0.47). The Bayesian estimate was +3.47 (94% equal-tailed credible interval +0.66 to +6.30; P[AI>professional]=0.989). Automated-reviewer all-error density was 3.35 vs 8.55 per note (professional-minus-AI difference 5.20, 95% CI 3.85 to 6.55); omission density was 1.45 vs 5.20 (difference 3.75, 2.80 to 4.65). Critical+High density was 0.35 vs 0.75 (difference 0.40, -0.10 to 1.00). The pooled quality result was driven principally by dietetics. Conclusions: AI-generated notes achieved modestly higher pooled quality and fewer transcript-grounded errors, chiefly omissions; serious-error evidence was inconclusive. Small discipline samples and incomplete ground truth preclude safety or discipline-wide superiority claims.

The efficacy of current antiretroviral interventions for prevention of vertical HIV transmission is both a triumph and a challenge for future efficacy studies of novel agents, including long-acting antiretroviral agents. Given the effectiveness of current antiretroviral interventions, standard randomized controlled trials to assess novel interventions targeted towards further reducing vertical HIV transmission may be infeasible due to required sample sizes. To address this study design challenge, we propose a novel augmented clinical trial design, where a randomized trial with an active comparator is augmented with a concurrent observational cohort to supplement the standard-of-care arm. The proposed design and analysis can overcome sampling biases, and an associated diagnostic can evaluate potential biases from unmeasured covariates. The proposed trial design is illustrated with an example and studied further using a simulation study. In the illustrative example, an augmented trial with a 3:1 allocation ratio in the trial component yielded an unbiased treatment effect estimate, as compared to the trial component alone, and the standard error was reduced substantially. Although the total sample size of the augmented trial was larger than a similarly powered 1:1 standard trial, the sample size of the augmented trial's trial component was half the size of the standard trial and within the range of historically similar trials, thereby providing both feasibility and potential cost advantages. Although limitations with this design remain, many of these limitations can be mitigated by careful study planning and coordination. Augmented trials provide a potentially applicable solution to studying the efficacy of long-acting antiretrovirals for infant postnatal prophylaxis against HIV.

BackgroundPatient education is critical to safe and effective postoperative bariatric surgery care. Large language models (LLMs) may improve access to personalized patient education but evidence regarding direct patient use in clinical settings remains limited. We evaluated BariBot, an LLM-powered educational application for patients undergoing bariatric surgery. MethodsWe conducted a prospective, single-arm mixed-methods feasibility study at a tertiary academic medical center from May 2024 to May 2025. Adult patients undergoing bariatric surgery used BariBot independently on postoperative day 1. The application provided conversational postoperative education and adapted language complexity to participants educational attainment. Outcomes included feasibility, usability, acceptability, perceived trustworthiness, and anticipated future use. Usability was assessed using the System Usability Scale (SUS). Immediately after BariBot use, participants completed a semi-structured qualitative interview assessing acceptability, perceived trustworthiness, and anticipated future use. Interview transcripts underwent thematic analysis. ResultsSixteen participants completed the BariBot use session, SUS assessment, and post-intervention interview. No technical failures prevented application use, and no participant requested early discontinuation. The median SUS score was 91.3 (IQR, 81.3-98.1), consistent with excellent perceived usability. Qualitative analysis showed that participants valued the applications immediacy, structured responses, conversational context, ability to address follow-up questions, judgement-free nature, and future availability between clinical encounters. Trust was strengthened by alignment with prior clinical guidance and perceived institutional association, although participants emphasized the need for transparency, clinician oversight, and use as an adjunct rather than a replacement of clinician guidance. ConclusionsBariBot was feasible to implement and was associated with high perceived usability and acceptability postoperatively after bariatric surgery. Larger, longitudinal, and comparative studies are needed to evaluate safety during unsupervised use and determine whether LLM-based educational applications improve patient understanding, engagement, and clinical outcomes.

Abstract Background Community-based exercise may support physical and cognitive recovery after stroke, but the preferences of stakeholders involved in receiving, supporting and delivering these programmes are poorly understood. This study piloted a discrete choice experiment (DCE) that aimed to evaluate stroke survivors, carers, clinicians, and fitness instructors preferences for community-based exercise programmes for stroke survivors. The pilot aimed to assess the feasibility of conducting and analysing data for a larger-scale study and inform the sample size for a definitive DCE. Methods A DCE design was developed using literature reviews, stakeholder consultations, and evaluations of current services. Six attributes were included in the design: location, price, session frequency, individualisation, carer involvement, and recovery. Sixteen Bayesian D-optimal choice sets were developed, then blocked into two sets of eight to reduce cognitive burden. Main-effects were analysed using a mixed logit model, and stakeholder differences were explored using a conditional logit interaction model. Willingness to pay was also calculated. Results Overall, 161 respondents started the survey and 106 (66%) fully completed it. Stakeholders significantly preferred programmes that were delivered at a leisure centre, lower priced, individualised, had carer-specific sessions and offered greater chances of recovery. The largest willingness-to-pay estimates were {pound}49.41/ month for 80% chance of meaningful recovery vs 20%, and {pound}18.61/ month for leisure centre delivery vs online. Significant preference heterogeneity was identified in the main-effects model. Exploratory stakeholder interactions suggested clinicians were more price sensitive and placed greater importance on recovery and carer-specific sessions than stroke survivors, while fitness instructors placed greater importance on programme location and recovery. Carer interaction estimates were unstable due to the small subgroup sample. Conclusions The pilot supported the feasibility of the DCE design and analytical approach but identified limitations in the recruitment methods and survey completion. Addition of face-to-face recruitment methods are recommended for a larger-scale study. A larger sample size is required to investigate differences in preferences between stakeholder groups.