Contemporary Clinical Trials Communications

BackgroundHwa-byung (HB) is a Korean culture-bound syndrome characterised by prolonged suppression of anger and somatic complaints. No evidence-based digital therapeutic (DTx) has been developed for HB. We evaluated the feasibility, user experience (UX), and preliminary clinical effect of an acceptance and commitment therapy (ACT)-based DTx application, Hwa-free, for HB. MethodsAdults aged 19-80 years diagnosed with HB were enrolled in a four-week app-based intervention with assessment at baseline (Week 0), Week 2, Week 4, and Week 8 follow-up. The primary outcome was UX assessed via a 22-item survey at Week 4. Secondary outcomes included HB-related symptom and personality scales, depression, anxiety, anger expression, psychological flexibility, health-related quality of life, and heart rate variability. ResultsOf 45 screened, 30 were enrolled and 28 constituted the modified intention-to-treat population. Mean app use was 19.9 {+/-} 7.9 days (71.2% adherence over 28 days). Adverse events were infrequent and unrelated to the intervention. Positive response rates exceeded 80% for video content (items 2-4: 82.8-89.7%), HB self-assessment (86.2%), meditation therapy (86.2%), and in-app guidance (85.7%). Pre-post improvements from baseline to Week 4 were observed in 11 of 18 clinical scales, including HB Symptom Scale ({Delta} = -9.8, Cohens d = -0.92), Beck Depression Inventory-II ({Delta} = -13.3, d = -1.11), and state anger ({Delta} = -7.8, d = -0.96). The HB screening-positive rate declined from 100% at baseline to 55.6% at Week 8. ConclusionsHwa-free demonstrated adequate feasibility, acceptable UX, and preliminary evidence of clinically meaningful improvement in HB-related symptoms. Future randomised controlled trial is warranted. Trial registrationCRIS, KCT0011105

BackgroundScalable, low-burden behavioral interventions are needed to address rising subclinical mental health symptoms. However, few randomized controlled trials have evaluated ultra-brief, remotely delivered, meditation using multimodal outcome assessment under real-world conditions. MethodsWe conducted a fully remote randomized controlled trial (ClinicalTrials.gov: NCT06014281) evaluating a focused-attention meditation intervention delivered via brief instructor training and independent daily practice. A total of 299 meditation-naive adults were randomized to immediate intervention or waitlist control in a delayed-intervention design. Participants practiced [≥]10 minutes daily for 8 weeks within a 16-week study. Outcomes included validated self-report measures, web-based cognitive tasks, and wearable-derived physiological metrics. ResultsAcross randomized and within-participant replication phases, the intervention was associated with significant reductions in anxiety and mind wandering, with effects remaining stable during 8-week follow-up. Improvements were greatest among participants with higher baseline symptom burden. Sleep disturbance improved selectively among individuals with poorer baseline sleep. Secondary outcomes, including rumination, perceived stress, social connectedness, and quality of life, also improved. Cognitive performance showed modest improvements primarily among lower-performing participants. Resting heart rate exhibited nominal reductions. ConclusionsAn ultra-brief, fully remote meditation intervention requiring 10 minutes per day was associated with sustained improvements in psychological functioning and smaller, baseline-dependent effects on cognition in a non-clinical population. These findings support digital delivery of low-dose meditation as a scalable preventive mental health strategy.

We are pleased to submit our Original article entitled "Assessing medication-related burden and medication adherence among older patients from Central Nepal: A machine learning approach" for consideration in your esteemed journal. In this paper, we assessed medication burden using validated Living with medicines Questionnaire (LMQ-3) and medication adherence using Adherence to Medication refills (ARMS) Scale. In this paper we analysed our result through machine learning approach in spite of traditional statistical approach to identify the complex factors influencing both. Six ML architectures (Ordinary Least Square, LightGBM, Random Forest, XGBoost, SVM, and Penalized linear regression) were employed to predict ARMS and LMQ scores using various socio-demographic, clinical and medication-related predictive features. Model explainability was provided through SHAP (Shapley Additive exPlanations). Our study identified the moderate medication burden with moderate non-adherence among older adults. Requiring assistance for medication and polypharmacy were the strongest drivers for the medication burden and non-adherence. The high predictive accuracy by ML suggests the appropriate clinical intervention like deprescribing to cope with the high prevalent medication burden and non-adherence among older adults in Nepal.

ObjectiveTo examine whether menopausal women who initiate systemic menopausal hormone therapy (MHT) around menopause (45-60 years old) have a different risk of developing dementia than those not taking MHT. DesignSystematic review and meta-analysis of randomised controlled trials and longitudinal observational studies. Risk of bias was assessed using ROB-2 and ROBINS I-V2. Data sourcesMEDLINE, Web of Science, EMBASE, and Cochrane Library to 27 March 2026. Eligibility criteria for selecting studiesStudies which measured dementia or cognitive decline in women who initiated systemic MHT between ages 45-60 or within 5 years of menopause, compared with placebo or no MHT. Authors contacted for additional details if needed. Main outcome measuresDementia, Alzheimers disease (AD), cognitive decline. Results10 studies totalling 213,678 participants (189,525 in studies with the primary population). There was no significant increased risk in women with a uterus for all cause dementia (pooled hazard ratio (HR): 1.12; 95% CI 0.91-1.31, N=78,613, I2 = 96.9%), but increased AD risk (HR: 1.14; 95% CI 1.02, 1.29, N=134,865, I2 = 35.6%). Results were similar in sensitivity analyses including women with or without a uterus. Results for cognitive decline were variable. ConclusionsMHT initiated around the age of menopause should not be prescribed for cognition or dementia prevention. It is not protective against dementia and may increase risk slightly. The magnitude of risk was similar in AD and dementia, but the latter with larger confidence intervals. Studies which followed up individuals rather than on health records lost people to follow up. This may account for difference in cognitive decline outcomes between studies, as people with cognitive impairment and dementia are more likely not to attend. MHT prescribing should balance benefits against risks, including evidence of a small increased dementia risk. There are few high-quality studies, so further research would inform recommendations. Systematic review registration Prospero CRD420251010663 What is already known on this topic?O_LIMenopausal hormone therapy (MHT) is effective for alleviating vasomotor symptoms. Contemporary guidelines recommend treatment should be initiated for such symptoms under age 60 and or within 10 years of menopause onset. C_LIO_LIA large randomised trial on the topic found increased risk of dementia in women initiating MHT after the age of 65. C_LIO_LIIt is unknown whether initiating MHT around the age of menopause impacts the risk of dementia or cognitive decline. C_LI What this study addsO_LIThere was no evidence that taking MHT around the time of menopause decreases the risk of dementia or cognitive impairment. C_LIO_LIThey should not be prescribed for these indications. C_LIO_LIWe were able to find more studies which examine this question by contacting authors for additional data. C_LIO_LIInitiating MHT in women with a uterus around the age of menopause increased the risk of Alzheimers disease slightly, by over 10%, and there is a similar but not significant effect in the fewer studies of all cause dementia. Women with or without a uterus show similar results. C_LIO_LIWe found no significant difference shown in cognitive decline, possibly due to loss to follow up. This may be because most studies of cognitive decline follow up C_LI

BackgroundCaring for people with dementia can impose a considerable psychological burden on caregivers, yet access to caregiver support in Malaysia remains limited. The World Health Organizations iSupport for Dementia program provides dementia education via textual, e-learning format. However, a culturally adapted Malaysian version has not been available. ObjectiveThis study aimed to develop and gather user feedback on a culturally adapted, multimedia version of iSupport tailored for Malaysia (iSupport-Malaysia). MethodsGuided by a four-phase cultural adaptation framework, the generic iSupport content was translated into Bahasa Malaysia, adapted to local customs, and transformed into multimedia lessons on an e-learning platform. A mixed-methods design was used to explore user perceptions and evaluate usability through four homogeneous focus group discussions and 15 individual usability test sessions with informal caregivers (FG: n=9; UT: n=9) and healthcare professionals (FG: n=11; UT: n=6). Focus groups examined aesthetics, ease of use, clarity, cultural relevance, comprehensiveness, and satisfaction. Usability testing involved Think Aloud tasks, post-test questionnaires, and brief interviews. Qualitative data was analysed thematically, and descriptive statistics summarised usability performance. ResultsiSupport-Malaysia demonstrated good usability (M=74.3{+/-}18.0), with most tasks completed without assistance. Strengths included interactive learning activities, peer discussion features, and flexible self-paced learning. Content was viewed as culturally appropriate, credible, and useful. Suggested improvements included enhancing visual aesthetics, shortening videos, refining quizzes, and increasing practical relevance. ConclusionUser insights indicate that iSupport-Malaysia is usable and culturally appropriate. These findings will inform refinement of the platform prior to the pilot feasibility study and provide recommendations for future multimedia-based caregiver interventions.

Cardiovascular disease (CVD) remains the leading cause of mortality in the United States, despite being largely preventable through effective management of risk factors. This study evaluates the impact of Phase II cardiac rehabilitation (CR) on functional capacity and quality of life, using data from the Montana Outcomes Project Cardiac Rehabilitation Registry. Functional capacity improvements were assessed via the six-minute walk test (6MWT) and Dartmouth COOP questionnaire, with statistical analyses exploring the influence of CR session attendance, demographic factors, and referring diagnoses. Results demonstrated significant gains in 6MWT, with a mean improvement of 330.73 feet (p < .0001), and quality of life scores across all subgroups. A dose-response relationship was observed, indicating greater improvements with increased CR sessions (p < .0001), though diminishing returns were observed beyond 24-35 visits. Demographic factors and complex conditions influenced outcomes, underscoring the need for tailored strategies to enhance CR access and effectiveness. These findings highlight the critical role of CR in improving patient outcomes and emphasize the importance of addressing barriers to participation in underserved populations.

IntroductionFamily Constellation Therapy (FCT) has been widely disseminated in clinical, public health, and judicial settings despite persistent concerns regarding its theoretical basis, safety, and the limited availability of rigorous randomised evidence supporting its clinical use. ObjectiveThe aim of this systematic review is to assess the effects of FCT across all clinical conditions, explicitly considering both benefits and harms; and summarise the characteristics of studies and intervention settings used in randomised controlled trials of FCT. MethodsFollowing a prospectively registered protocol (CRD420251136190), we conducted a systematic search of seven databases (PubMed, EMBASE, APA PsycInfo, CENTRAL, BVS, Web of Science, and CINAHL) and grey literature (ICTRP and ProQuest database) without language or date restrictions to identify published and unpublished randomised controlled trials of FCT. Study selection, data extraction, risk of bias (RoB 2), and certainty of evidence (GRADE) were performed in duplicate. Statistical analyses followed a prospectively registered analysis plan with prespecified criteria for data pooling and for handling analytical limitations. ResultsNo reliable evidence was found to support the use of FCT for any condition across both clinical and non-clinical samples. All trials included were judged to be at high risk of bias and all comparisons were rated as very low-certainty evidence. Concerns regarding potential adverse effects were identified, and the available data was insufficient to establish the effectiveness of the intervention, precluding any clinical recommendation. ConclusionClinicians, policymakers, and consumers should reconsider adopting FCT while reliable evidence is not available.

Background: Progression of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) can lead to worsening congestion requiring diuretic intensification (DI), heart failure (HF)-related hospitalizations (HFH), and death. Tafamidis was the only approved ATTR-CM therapy in the US from 2019 until the 2024 approval of acoramidis, which achieves near-complete ([&ge;]90%) TTR stabilization. As head-to-head trials are lacking, real-world comparative effectiveness (CE) data are needed to guide treatment selection. Objective: To evaluate real-world CE of acoramidis versus tafamidis in newly treated patients with ATTR-CM. Methods: Retrospective study using Komodo Healthcare Map (R) US claims data tokenized to Claritas. Patients newly initiating acoramidis or tafamidis between 12/11/2024 and 04/30/2025 with [&ge;]1 prescription claim (first defined as index date) and [&ge;]6 months of continuous enrollment preindex date were included and followed until disenrollment, death, treatment switch, or study end date (07/31/2025). Outcomes included DI (initiation or dose-equivalent escalation of oral loop diuretics, parenteral loop diuretic use, or addition of thiazide-like diuretic) and a composite of DI, HFH (inpatient admission with a HF-related ICD-10-CM diagnosis code in any position), and mortality. Propensity score weighting balanced baseline characteristics, disease severity, comorbidity burden, and baseline medication use. Time-to-event outcomes were assessed using weighted Cox proportional hazards models. Results: After weighting, acoramidis (n=170) and tafamidis (weighted sample size=448) patients were comparable at baseline (mean age, 78.6 vs 78.7 years; male, 80.0% vs 80.2%) with mean follow-up of 139 and 143 days, respectively. DI cumulative incidence curves separated early and remained divergent, with acoramidis significantly reducing the hazard of DI events by 43% compared with tafamidis (11.8% vs 20.5%; HR, 0.57; 95% CI, 0.35-0.92; P=0.021). Acoramidis also had a significantly lower risk of composite events, with a 34% reduction in hazard compared with tafamidis (17.6% vs 26.4%; HR, 0.66; 95% CI, 0.44-0.99; P=0.046). Conclusions: In this first real-world CE study of newly treated patients, acoramidis had significantly lower risk of DI events and composite events of DI, HFH, and mortality than tafamidis, potentially supporting improved clinical stability with acoramidis initiation. Additional evaluation with longer follow-up, larger cohorts, and/or prospective clinical outcomes is warranted.

IntroductionColorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, despite advances in conventional oncological therapies. In recent years, various studies have made advances in integrative oncology, such as investigating the use of Chinese Herbal Medicine (CHM) as a complementary therapy alongside conventional oncological therapies to alleviate treatment-related adverse effects, improve quality of life, and potentially enhance therapeutic outcomes. Despite this, clinical practice in this area remains highly heterogeneous, with limited standardized guidelines on key areas of concern such as (1) optimal intervention, (2) recommended stage and duration of intervention, (3) safety considerations, and (4) possible herb-drug interactions. Hence, this study aims to establish expert consensus on the usage of CHM as a complementary therapy in the management of CRC, to support safe, consistent, and evidence-informed clinical practice. Methods and AnalysisWe will employ a modified Delphi technique to achieve consensus amongst a panel of international experts in various fields related to integrative oncology. Prior to the study, a list of questionnaire items was developed based on a systematic review of existing clinical practice guidelines on CRC. An international panel will be invited based on established international profile in integrative oncology research and clinical practice, and by peer referral. Two rounds of Delphi will be conducted using anonymous online questionnaires. Consensus will be considered reached if at least 50% of the panel strongly agree/disagree that an item should be included or excluded while strong consensus will be set at 76%. Items which achieve strong consensus after Round 1 will be removed, before being sent out for Round 2 with a summary of Round 1 responses for a final consensus. Ethics and DisseminationEthics approval has been obtained from the Institutional Review Board of Nanyang Technological University (IRB-2025-1222). Our findings will be disseminated through peer-reviewed publications and conference presentations. Strengths and limitations of this studyO_LIThis study will develop an expert consensus which aims to guide future integration of Chinese Herbal Medicine (CHM) as a complementary therapy into colorectal cancer (CRC) management. C_LIO_LIKey concerns in areas such as determining the (1) optimal intervention, (2) recommended stage and duration of intervention, (3) safety considerations, and (4) possible herb-drug interactions, thereby laying the groundwork for potential future incorporation of CHM into CRC treatment protocols alongside conventional oncology approaches has been identified, thus limiting implementation in clinical practice. C_LIO_LIDesigning a study e-guide, followed by the consensus rounds study online will facilitate participants responses and the dissemination of information from previous rounds. C_LI

Abstract Background: Acute ischemic stroke (AIS) remains a significant cause of disability worldwide. Current treatments, primarily intravenous thrombolysis (IVT), are limited by narrow time windows and reperfusion injury, leading to suboptimal outcomes for many patients. Chuanzhi Tongluo (CZTL), a traditional Chinese medicine, has been preliminarily recognized as a novel cerebral protection agent in animal models. Objectives: This trial investigates the efficacy and safety of CZTL capsule in patients with AIS who are not eligible for IVT or who experience early neurological deterioration after IVT. Methods and design: The CONCERN trial is an investigator-initiated, prospective, multicenter, double-blind, parallel-control, randomized clinical study in China. An estimated 1,208 eligible participants will be consecutively randomized to receive CZTL capsule therapy or placebo in 1:1 ratio across approximately 70 stroke centers in China. All enrolled patients are orally administered 2 capsules of CZTL or placebo 3 times a day together with antiplatelet agents for 3 months. Outcomes: The primary endpoint is an excellent functional outcome, defined as a score of 0 or 1 on the mRS at 90 days. Lead safety endpoints included 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. Conclusions: Results of CONCERN trial will determine the clinical efficacy and safety of the traditional Chinese medicine CZTL capsule in the treatment of AIS patients. Trial registry number: ChiCTR2300074147 (www.chictr.org.cn).

BackgroundPractical alcohol risk-reduction strategies are widely recommended in public-facing alcohol guidance, but randomized evidence from socially interactive drinking episodes remains limited. We conducted a pilot cluster randomized trial to evaluate the feasibility and preliminary effects of a package intervention comprising practical drinking-strategy information, participant self-selection of same-day strategies, and a brief commitment declaration in a social drinking laboratory. MethodsThis single-center, parallel-group pilot trial was conducted in Japan. Pre-existing social groups participated. One or two groups scheduled in the same session slot were combined into a time-slot allocation unit, which was randomized 1:1 either to the package intervention or to alcohol-related knowledge only. The primary outcome was total pure alcohol intake during the first 120 min. Session satisfaction on a Visual Analog Scale (VAS) was a prespecified secondary participant-experience outcome. ResultsOf 83 interested individuals, 63 were randomized and 59 participants in 17 social groups and 12 allocation units were included in the modified intention-to-treat analysis. The mean paired intervention-control difference for 120-min alcohol intake was-8.84 g (95% confidence interval [CI]-27.92 to 10.23; exact sign-flip p = 0.281). The corresponding exploratory 0-30 min difference was-4.90 g (95% CI-10.48 to 0.68; exact sign-flip p = 0.094). In a genotype-adjusted participant-level sensitivity analysis, the intervention coefficient for 120-min intake was-16.0 g (95% CI-30.9 to-1.1; p = 0.036). Session satisfaction was high in both arms with no clear between-arm difference. Next-day follow-up was 100%, and no adverse-event-related discontinuations occurred. ConclusionsThe intervention was feasible to deliver in a socially interactive drinking setting, and session satisfaction was high in both arms. Primary allocation-unit estimates favored lower alcohol intake but were imprecise. Larger trials are needed to estimate effects more precisely, while considering the potential influence of genotype imbalance on effect estimation in East Asian samples. Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000060685. Registered 17 February 2026.

Objectives: To examine the pattern, magnitude, and demographic distribution of measurable improvements across five outcome parameters following three monthly pharmacist-led nutritional counselling sessions delivered to community-dwelling participants in semi-urban India. Design: Secondary analysis of interventional follow-up data from a prospective community-based study. Setting: Schools and colleges in Narasaraopeta, Andhra Pradesh, India, from September 2021 to March 2022. Participants: Of 1,200 participants assessed at baseline, 1,135 (94.6%) completed at least one counselling session and formed the analysis cohort. The age range was 10 to 60 years. The majority of participants, 92.4%, were aged between 11 and 20 years. All 1,135 were anaemic at baseline. Interventions: Three structured monthly counselling sessions were delivered by pharmacy students under qualified faculty pharmacist supervision. Each session included individualised dietary guidance, lifestyle modification advice, and culturally adapted written health education materials. Primary and secondary outcome measures: Cumulative proportion of participants achieving measurable improvement in body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHR), and haemoglobin (Hb) concentration at each session, stratified by age group and sex. Results: All five parameters showed progressive cumulative improvement across sessions. By session three, 44 participants (3.6%) showed improved BMI, 39 (3.25%) achieved reduced WC, 34 (2.8%) reduced HC, 33 (2.75%) improved WHR, and 115 (9.5%) demonstrated improved Hb. Adolescents aged 11 to 20 years were consistently the most responsive subgroup. Haemoglobin showed the steepest improvement trajectory, rising from 1.75% at session one to 9.5% at session three, representing a 5.4 fold increase achieved through dietary counselling alone without pharmacological supplementation. Conclusions: Three monthly pharmacist led nutritional counselling sessions produce measurable and progressive improvements in both anthropometric and haematological outcomes in community settings. Adolescents are the most responsive population. These findings support the integration of pharmacists into community non communicable disease prevention programmes in India and provide a replicable low resource model applicable to comparable global settings.

Background: Cognitive impairment poses a significant challenge to healthcare systems worldwide, impacting patient autonomy, social participation, and quality of life, while placing a considerable burden on caregivers. Non pharmacological interventions, particularly cognitive training and non invasive brain stimulation, have emerged as promising therapeutic strategies. Objective: This study aims to quantify the synergistic effects of transcranial direct current stimulation (tDCS) with cognitive training on cognitive function across a spectrum of pathologies that induce cognitive impairment. Methods: We conducted a systematic review and metaanalysis following PRISMA guidelines. We searched PubMed for randomized controlled trials that investigated the effect of combined tDCS and cognitive training compared with cognitive training alone. The analysis was based on the GRADE framework for systematic reviews and metaanalyses. Results: Across 27 studies including 1,012 participants, tDCS combined with cognitive training showed a small effect compared with cognitive training alone (SMD = 0.36, 95% CI: 0.15 0.56). The effect was found only immediately after the intervention and declined during follow-up. Conclusion: tDCS combined with cognitive training may provide a small, short term benefit for cognitive function, but high heterogeneity across studies and loss of effect at follow up underscore the need for larger, better standardized trials to clarify its clinical value.

BackgroundLasers have wide applications in medicine and dermatology, but are associated with pain and anxiety, particularly in younger patients. Pain mitigation is often limited to topical anesthetics in the outpatient setting. Distraction techniques are limited by the need for ocular protection, which can include adhesive eye patches that can completely occlude vision. Virtual reality is effective at managing procedural pain and anxiety under other short medical procedures and is a promising tool for this population. ObjectiveThis trial aims to assess the safety, feasibility, and efficacy of Virtual Reality Pain Alleviation Therapeutic (VR-PAT) for pain management during outpatient laser procedures. Methods40 patients requiring outpatient laser therapy for at least two sessions will be recruited from a pediatric hospital in the midwestern United States for this crossover randomized, two-arm clinical trial with a 1:1 allocation ratio. During the first laser visit, the participant will be randomly assigned to either play the VR-PAT game during their procedure or wear the headset with a dark screen. Participants will answer questions about their pain (Numeric Rating Scale (NRS) 0-10), anxiety (State Trait Anxiety Inventory for Children, NRS 0-10, Modified Yale Preoperative Anxiety Scale (mYPAS)), and pain medication usage. Those playing the VR-PAT will additionally report simulator sickness symptoms and their experience playing the game. At their second laser visit, participants will crossover to the opposite intervention from their first visit. The primary outcomes are the difference in self-reported pain and anxiety between the two interventions. Feasibility outcomes include the proportion of screened patients who are eligible, consent, and complete both visits and adverse events reported. To evaluate the efficacy of pain reduction, composite scores of pain score, pain medication will be calculated for each laser visit. To evaluate the efficacy of anxiety reduction, the change of mYPAS scores will be compared between control and VR groups at each visit using Wilcoxon rank sum tests. All statistical analyses will follow the intention-to-treat principle in regard to intervention assignment at each visit. ResultsThe study was funded in January 2023 and began enrollment at that time. A total of n=44 participants were recruited and data collection was completed in November 2025, with n=40 subjects completing both visits. The sample was balanced with n=40 subjects using the intervention and participating in the control condition. The age range of the complete sample was 6 to 21 years at recruitment and was 55% female sex. Data analysis is in progress with final results planned for June 2026. ConclusionsFindings from this innovative randomized clinical trial will provide early evidence on the efficacy of the VR-PAT for reducing self-reported pain and anxiety during outpatient laser procedures. The results from this trial will inform a large-scale, multisite study. Trial RegistrationClinicalTrials.gov: NCT05645224 [https://clinicaltrials.gov/study/NCT05645224]

IntroductionOver one billion people worldwide have hypertension. In Zimbabwe, prevalence is an estimated 38%, surpassing the global average of 34%, and >50% of hypertensives are undiagnosed. The Community BP groups (Com-BP) study examined whether community groups of people living with hypertension, provided with BP machines and led by trained Facilitators could improve awareness, screening and support for those diagnosed with hypertension, to help blood pressure (BP) control. We present findings from the quantitative evaluation of the Com-BP pilot intervention. MethodsThe acceptability of the Com-BP intervention, its potential effectiveness in improving knowledge, attitudes and practices (KAP) and in reducing BP among hypertensive adults in Zimbabwe, was evaluated. Cross-sectional surveys using standardised questionnaires, and BP and Body Mass Index (BMI) assessments, were done at the start and end of the pilot intervention. Statistical evidence of difference between baseline and follow-up was examined using Wilcoxon signed-rank test for continuous data and McNemars test for categorical data. ResultsFourteen groups (seven urban and seven rural) were formed and 151 participants joined over a median of 5months. Retention in the groups was 97.9% (137/140 recruited at baseline), with approximately equal numbers from the urban and rural sites. Median age at baseline was 54 years (IQR 45-66y; min-max 30-92y) and the majority (79%, n=108) were female. Most participants (82.5%, n=113) rated their experience of the group sessions as excellent. The proportions of participants with changes in KAP from baseline to endline were as follows: 45.3% (n=62) to 81.0% (n=111) (p=0.004) able to identify at least two pre-disposing factors for hypertension; 65.0% (n=89) to 77.4% (n=106) (p=0.02) reporting [&ge;]1day of vigorous physical activity/week; 28.5% (n=39) to 13.9% (n=19) (p=0.001) reporting salt added to meals at the table. There was no statistical evidence of any difference in medication adherence, p=0.06. The proportion of participants with uncontrolled hypertension was 58.1% (n=79) at baseline and reduced to 31.8% (n=43) at follow-up (p<0.001). DiscussionCommunity groups for improving awareness, detection and support are acceptable and led to improvements in self-reported KAP and prevalence of uncontrolled BP. Further research on the sustainability and impact of the intervention is required.

ABSTRACT Background Medical students face demanding academic schedules and elevated stress levels, predisposing them to poor sleep quality. Sleep hygiene, a set of behavioural and environmental practices aimed at optimising sleep, has been identified as a modifiable determinant of sleep quality, yet its role among medical students in Sudan remains unstudied. Objectives To assess current sleep hygiene practices among medical students at UMST and determine their association with sleep quality outcomes. Methods A facility based cross-sectional study was conducted at UMST among 240 medical students from three academic batches (3rd, 4th, and 5th year), selected via stratified random sampling. Data were collected using two validated self administered instruments: the Pittsburgh Sleep Quality Index (PSQI) and the Sleep Hygiene Index (SHI). Descriptive statistics, independent sample t tests, one way ANOVA, chi-square tests, Pearson correlation, and binary logistic regression were performed using SPSS version 23. Results Poor sleep quality (PSQI >5) was prevalent in 72.1% of participants (mean PSQI 7.25 +/- 2.66), and poor sleep hygiene (SHI >16) in 92.5% (mean SHI 27.1 +/- 7.9). SHI score (continuous) was the only significant independent predictor of sleep quality on logistic regression (OR = 1.13 per unit increase; 95% CI: 1.08-1.19; p < 0.001), equivalent to a 3.4-fold increase in odds per 10-unit rise in SHI score. Female sex was additionally identified as a significant predictor (OR = 1.88; 95% CI: 1.00-3.53; p = 0.049). A significant positive correlation was observed between PSQI and SHI scores (r = 0.359, p < 0.001). Conclusion Poor sleep hygiene is highly prevalent among UMST medical students and is the most significant modifiable predictor of poor sleep quality, with each unit increase in SHI score increasing the odds of poor sleep quality by 13%. These findings highlight a gap in sleep health education within Sudanese medical institutions and support the integration of targeted sleep hygiene interventions into the medical curriculum. Keywords: sleep hygiene; sleep quality; medical students; Sudan; PSQI; SHI; cross-sectional study

Importance: Adverse neighborhood conditions can lead to poorer health outcomes, potentially through accelerated biological aging. However, whether these relationships are explained by individual- or neighborhood-level factors remains unclear. Objective: To examine the association between neighborhood deprivation, measured by the Area Deprivation Index (ADI), and epigenetic age acceleration and assess whether individual- and neighborhood-level characteristics mediate or modify these associations. Design: Cross-sectional study using data from a Yale Stress Center study between 2008 and 2012. Data analysis was conducted from July 2025 to January 2026. Setting: Community-based sample from the greater New Haven, CT area. Participants: A total of 370 healthy adults aged 18 to 50 years without major psychiatric, medical, or cognitive disorders who provided blood samples for DNA methylation analysis. Main Outcomes and Measures: Epigenetic age acceleration measured from DNA methylation using four second-generation epigenetic clocks, with associations assessed among aging, neighborhood deprivation, and individual- and neighborhood-level factors. Results: Data were analyzed from 370 participants (212 women [57.3%], 158 men [42.7%]; mean [SEM] age, 29.3 [0.46] years). Greater neighborhood deprivation was associated with greater lifetime adversity ({beta}=0.112, p<.001) and lower educational attainment ({beta}=-0.019, p=.012), and accelerated epigenetic aging as measured by GrimAge ({beta}=0.037, p<.001), PCGrimAge ({beta}=0.019, p<.001), and PCPhenoAge ({beta}=0.041, p<.001), but not PhenoAge (p=.23). In multivariable models accounting for individual factors, neighborhood deprivation remained associated with these three clocks. Lifetime adversity partially mediated the association between ADI and accelerated GrimAge (20.3% of total effect) and PCGrimAge (23.3%). Race moderated the direct association between ADI and epigenetic aging, with stronger associations between neighborhood deprivation and accelerated GrimAge ({beta}=0.061, p=.004) and PCPhenoAge ({beta}=0.057, p=.02) observed among Black participants compared to White. Conclusions: Greater neighborhood deprivation was associated with accelerated epigenetic aging across multiple second-generation clocks, with lifetime adversity partially mediating these associations. Stronger effects were observed among Black participants. These findings suggest that neighborhood environments and cumulative stress may contribute to biological aging and racial disparities in aging trajectories.

Objectives: The primary aim of this study was to assess the feasibility of delivering an adapted problem-solving skills (PSS) intervention by quantifying the recruitment, follow-up and completion rates using a brief problem-solving intervention for people with a mental health diagnosis in two Polish prisons. Design: IAPPS is an open, multi-centred, parallel group feasibility randomised controlled trial (RCT). Setting: Two prisons in Poland. Participants: Men in custody aged 18 years and older, having a mental illness and living within the prison therapeutic unit. Interventions: The intervention consisted of an adapted PSS skills intervention plus care as usual (CAU) or care as usual only. Delivered in groups of up to five people in 1.5-hour sessions over the course of two weeks. Main outcome measures: Primary outcomes - rate of recruitment, follow-up, and feasibility to deliver the intervention. Secondary outcomes included measures of depression, general mental health, and coping strategies. Results: 129 male prisoners were screened, 64 were randomly allocated, with a mean age of 53.5 years (SD 14, range 23-84). 59 (95%) prisoners were of Polish origin. Our recruitment rate was 48%. There was differential follow up with those in the intervention group less likely to complete the post-test battery versus those who received care as usual. Outcome measures were successfully collected at both time points. Conclusions We were able to recruit, retain and deliver the intervention within the prison setting; some logistical challenges limited our assessment of intervention engagement. Our data helps to demonstrate how use of the RCT study design can be implemented and delivered within the complex prison environment. Trial registration number ISRCTN 70138247, protocol registration date May 2021

Background: Few studies have examined racioethnic disparities in cardiovascular disease (CVD) in women after breast cancer treatment, who are at higher risk due to cardiotoxic cancer treatment. Methods: Based on the Pathways Heart Study of women with a history of breast cancer, this analysis examines the association between cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) and CVD events with self-reported race and ethnicity, as well as genetic similarity. Multivariable logistic and Cox proportional hazards regression models were used to test race and ethnicity and genetic similarity with prevalent and incident cardiometabolic risk factors and CVD events. Results: Of the 4,071 patients in this analysis, non-Hispanic Black (NHB), Asian, and Hispanic women were more likely to have prevalent and incident diabetes than non-Hispanic White (NHW) women. Analysis of genetic similarity revealed results consistent with self-reported race and ethnicity. For CVD risk, NHB women were more likely to develop heart failure and cardiomyopathy than NHW women. In contrast, Hispanic women were at lower risk of any incident CVD, serious CVD, arrhythmia, heart failure or cardiomyopathy, and ischemic heart disease, which was consistent with the associations found with Native American ancestry. Conclusions: This is the largest multi-ethnic study of disparities in CVD health in breast cancer survivors, demonstrating corroborating findings between self-reported race and ethnicity and genetic similarity. The results highlight disparities in cardiometabolic risk factors and CVD among breast cancer survivors that warrant more research and clinical attention in these distinct, high-risk populations.

Progress in pharmacological treatment development for neurodevelopmental disorders is hindered by a misalignment between targeted mechanisms, outcome measures, and trial designs. This study was initiated as a post-trial access pathway for bumetanide and later expanded with treatment-naive participants. Within this framework, we implemented a parent-cocreated sensory outcome measure set (PROMset) in an unmasked, multiple-baseline single-case experimental design with randomized baseline periods of 2-12 weeks, followed by 6 months of bumetanide treatment (up to 1.5 mg twice daily). Participants (7-19 years) had atypical sensory reactivity and a diagnosis of ASD, ADHD, epilepsy, or TSC. The primary outcome was a PROMset comprising seven PROMIS item banks assessing anxiety, depressive symptoms, sleep disturbance, fatigue, sleep-related impairment, cognitive function, and peer relationships. Secondary outcomes included SSP, SRS-2, RBS-R, and ABC. Of 113 enrolled participants (mean age 13.2 [SD 2.7], 64% male), 102 completed the trial and 95 had analyzable PROMsets. At baseline, PROMset scores showed substantial impairment across domains (mean deviation =9.0 T-score points, p<.001) and correlated with sensory reactivity (SSP; r=-0.40, p<.001). Individual-level analyses showed improvement in 24-41% of participants per PROM domain, most frequently in anxiety and depressive symptoms (41% and 38%; mean across-case Cohen's d=-1). Overall, 83% improved on at least one domain. Group-level analyses showed improvement across all secondary outcomes (p<.001), with superiority over historic placebo for RBS-R and SSP. Integrating PROMsets with individualized trial designs can reveal clinically meaningful changes, supporting a more sensitive and patient-centered framework for treatment evaluation in heterogeneous populations.