Background: The rising prevalence of mental health concerns among students is prompting universities to explore innovative solutions to support student well-being. This paper describes the protocol for the development, implementation, and evaluation of a mobile app designed to address the mental health and wellness needs of students. This project employs a student-centered approach, partnering with students from the initial needs analysis through to the final design and implementation stages. Objective: The app aims to increase the use of campus resources that address student mental health and wellness by improving the awareness of these resources through user-designated preferences that are established on the initial use of the app and then iteratively refined as it is used. The app is linked to the campus student’s electronic health record so that health and wellness services can be coordinated and enhanced and the student journey to and through care become more seamless. The long-term objective is to leverage data from both the app and electronic health record to improve individual and population health for the entire campus. Methods: At the beginning of the project, a comprehensive logic model was created to outline the core inputs, activities, outputs, outcomes, and long-term impacts that were desired for the app. The model emphasized the integration of the app within existing campus mental health and wellness services and its potential to foster a culture of well-being across the university community. An evaluation plan was developed that incorporates both quantitative and qualitative methods through biannual assessments to track trends and app impact across campus in addition to feasibility, acceptability, and usability as well as its reach, effectiveness, and sustainability. Validated measures such as the Patient Health Questionnaire and Generalized Anxiety Disorder scale were selected to track changes in mental health and wellness, while custom surveys and analytics will gauge user engagement and satisfaction. New students, including freshmen, transfers, and first-year medical students, are invited to participate after giving informed consent. They receive compensation for their involvement in both quantitative and qualitative assessments. Results: As of March 2025, we have collected over 600 survey responses from freshmen, transfer, and medical students. A second survey round and additional focus groups are planned for April to May 2025. No analyses have been conducted yet. The findings from this project have the potential to inform similar efforts at other institutions and contribute to the broader field of digital mental health innovation and the development of well-being interventions tailored for young people. Conclusions: By leveraging digital technology and actively engaging students in supporting their well-being, this initiative represents an innovative user-centered approach to improve mental health and wellness support on university campuses.

Background: There has been controversy over the extent to which technology use in general—and social media exposure specifically—may be associated with adverse youth mental health outcomes. To date, studies have generally been small and exploratory, relying on youth self-reports to characterize technology and social media use patterns. The goal of this study is to explore the associations between objectively collected data, gathered through a commercially available app, and youth mental health outcomes. Objective: The broad goal of this study is to characterize the association between objectively measured technology/social media use and a range of mental health–related outcomes. Three specific aims will be initially addressed. First, we aim to quantify the association between objectively measured smartphone use and measures of well-being. Second, we aim to differentiate types of engagement—specifically, the types of content consumed versus the overall time spent on the device—and examine their association with outcomes. Third, we aim to identify moderating factors, such as age, gender, and socioeconomic status, that might influence these relationships. A secondary broad objective of this research is to establish a freely available data resource that can be accessed by qualified investigators to address a much wider range of questions in the future. Methods: Up to 1000 male, female, and nonbinary youth aged 8-17 years (inclusive), along with their primary caregivers, will be enrolled in the study. Youth participants must have their own dedicated iOS- or Android-based smartphone or tablet, and both they and their parents must be willing and able to download and install the data collection app on their devices. The study is open to all US-based participants who meet these 2 criteria. Following electronic consent (eConsent), participants and their caregivers will complete a range of baseline measures electronically, including assessments of psychiatric and social functioning, as well as measures of loneliness, digital stress, and disordered eating. Caregivers will be asked to provide information on the participant’s health and mental health history. Youth and caregivers will then complete a similar battery of assessments 1, 2, and 3 months after baseline. Youth participants will also respond to daily questions about their mood, stress, physical activity, and sleep. Both youth and their caregivers will be compensated for completing measures at each time point. The data collection app gathers a wide range of daily data from the participant’s device, including temporal patterns of use, the number and frequency of various app usage, social interactions within apps, and keystroke data. A variety of analytic methods will be used to address key questions related to how technology and social media use are associated with mental health and wellness outcomes. Results: Enrollment for this study began on November 13, 2024. As of May 20, 2025, a total of 106 participants and their caregivers had consented to participate and provided baseline data. An additional 203 children and parents have consented and are currently undergoing eligibility verification and enrollment. Initial data analysis is anticipated to begin in late autumn 2025 or winter 2026, with the expected publication of initial findings in spring 2026. Conclusions: This study will be among the largest to date to collect both objective device usage data and validated, clinically relevant outcome measures. In accordance with our data-sharing policies, any qualified investigator will be able to access the study data, provided appropriate steps are followed. Trial Registration: ClinicalTrials.gov NCT06664944; https://clinicaltrials.gov/ct2/show/NCT06664944

Background: Physical activity (PA) has significant health benefits for older adults. However, many older adults in Hong Kong remain physically inactive. Interventions tailored to one’s current stage of change (SOC) are more effective than non-SOC-tailored ones in facilitating behavioral changes. Chatbots are potentially useful to deliver SOC-tailored interventions to promote PA among older adults. Objective: This randomized controlled trial (RCT) will compare the efficacy of an SOC- versus a non-SOC-tailored intervention in increasing the prevalence of meeting World Health Organization (WHO)-recommended PA levels 6 months after completion of the intervention among inactive community-dwelling individuals aged ≥65 years. Methods: This is a partially blinded (outcome assessors and data analysts) and parallel-group RCT. A total of 278 inactive community-dwelling people aged 65 years or more will be randomized evenly into either an intervention group or a control group. In the intervention group, a fully automated chatbot with natural language processing (NLP) functions will measure participants’ SOC related to PA and deliver web-based interventions tailored to their current SOC every week for 12 weeks. In the control group, the chatbot will not measure participants’ SOC but will deliver a non-SOC-tailored web-based intervention every week for 12 weeks. Participants will be interviewed at baseline (T0), after completion of the intervention (T1), and 6 months after T1 (T2). The primary outcome is the prevalence of meeting WHO-recommended PA levels (ie, at least 150 minutes of moderate-intensity aerobic PA, at least 75 minutes of vigorous-intensity aerobic PA, or an equivalent combination of moderate-to-vigorous physical activity [MVPA] every week). PA will be measured using the Chinese version of the International Physical Activity Questionnaire Short Form (IPAQ-SF) and accelerometers at T0, T1, and T2. Secondary outcomes include (1) minutes of MPVA, low-intensity PA, and sedentary time in the past week; (2) step counts in the past week; (3) SOC levels, perceived pros, perceived cons, and perceived self-efficacy related to PA; (4) compliance to the web-based interventions; and (5) cognitive status measured at T0, T1, and T2. Intention-to-treat analysis will be used for data analysis. Results: Recruitment started in November 2024. By February 2025, a total of 185 participants completed the baseline assessment and were randomly assigned to either the intervention group (n=93, 50.3%) or the control group (n=92, 49.7%). Recruitment will be completed by the end of June 2025. The follow-up assessment at T1 started in March 2025. Data collection is expected to be concluded in February 2026. Conclusions: The findings will extend the application of SOC and contribute to the evidence of the effectiveness of SOC-tailored and chatbot-delivered interventions. If the chatbot-delivered SOC-tailored intervention is proven effective to increase PA levels, it will require relative less resources to implement and maintain. It can be integrated into the existing WhatsApp groups operated by organizations providing services to older adults in Hong Kong and create public health impacts. Trial Registration: ClinicalTrial.gov: NCT06641492; https://clinicaltrials.gov/study/NCT06641492

Background: Given the high rates of HIV infection among young Black men who have sex with men in Jackson, Mississippi, and the underuse of pre-exposure prophylaxis (PrEP) in this population, there is a critical need for innovative interventions to promote PrEP use. Acceptance and commitment therapy (ACT) is a promising intervention for health behavior change. Objective: This study aims to develop and test an intervention, ACTPrEP, to increase PrEP use among young Black men who have sex with men. Methods: We conducted in-depth interviews with 20 young Black men who have sex with men and 10 PrEP staff to inform the development of ACTPrEP, an intervention that uses ACT to improve PrEP use. Specific ACTPrEP adaptations from the qualitative interviews included service settings (interventionists should be PrEP informed and well-integrated), target audiences (provide check-in calls, be caring, and authentically relate), modes of delivery (flexible delivery), and cultural adaptation (normalize PrEP use). A pilot randomized controlled trial will evaluate the feasibility and acceptability of ACTPrEP compared to that of Enhanced Standard of Care in promoting PrEP use among young Black men who have sex with men (N=66). We will specifically evaluate group differences in the proportion of participants who initiate PrEP, PrEP adherence, and PrEP persistence. Measures will be collected at baseline, 6 weeks, and 12 weeks. Results: Research activities began in September 2023 and will be ongoing through June 2026. Preliminary findings are anticipated to be available in late 2026. Conclusions: This study will inform the development of a larger randomized controlled trial to evaluate the efficacy of ACTPrEP for increasing PrEP use among young Black men who have sex with men. Trial Registration: ClinicalTrials.gov NCT05087680; https://clinicaltrials.gov/study/NCT05087680

Background: Preexposure prophylaxis (PrEP) remains one of the most efficacious interventions for preventing HIV, but its effectiveness is often limited by poor persistence. Although regional efforts have primarily focused on young women and men who have sex with men, heterosexual men in East and Southern Africa represent a crucial group to engage and retain in PrEP care—both to improve health outcomes for men and to interrupt HIV transmission chains. Men seeking sexually transmitted infection (STI) services are particularly vulnerable to HIV acquisition, yet only a few interventions have tested strategies for engaging and retaining these men in PrEP services. Systems navigation, which addresses barriers to health care access and enhances comfort in clinical settings, may offer a promising approach to improving persistent PrEP use among heterosexual men. Objective: This study will assess the effect of a peer-delivered systems navigator–facilitated HIV prevention package on PrEP persistence at 26 weeks among heterosexual men seeking STI clinical services in Lilongwe, Malawi. It will also evaluate the acceptability of the intervention and barriers to implementation among key stakeholders. Insights will inform the feasibility of a future randomized controlled trial. Methods: In this single-site pilot type I effectiveness-implementation hybrid randomized controlled trial, 200 heterosexual men seeking STI services and initiated on PrEP in Lilongwe, Malawi, will be randomized (1:2) to standard-of-care PrEP services or systems navigator–assisted PrEP care (intervention). Participants will be followed every 13 weeks for at least 26 and up to 52 weeks. PrEP use and engagement in care will be assessed through medical record review and intraerythrocytic tenofovir diphosphate measurement, using objective biomedical analyses via dried blood spot. Primary effectiveness and implementation outcomes include 26-week PrEP persistence (adapted to accommodate daily oral, event-driven oral, or injectable PrEP) and acceptability, respectively. Additional implementation outcomes include feasibility and cost. Exploratory objectives characterize preferences for PrEP modalities, perceived and experienced stigma, and the influence of gender norms on PrEP persistence. All clinical services, including the provision of PrEP and PrEP safety monitoring, are being conducted by the Malawi Ministry of Health. Results: HPTN (HIV Prevention Trials Network) 112 was funded in November 2023. Study recruitment began in April 2024 and closed in November 2024. As of February 3, 2025, the study has enrolled 199 participants, with follow-up expected through June 2025. No interim analyses were planned; data analysis for primary end points is expected in the summer of 2025. Conclusions: Improving PrEP use outcomes among heterosexual men in East and Southern Africa is critical to interrupting HIV transmission. This study offers unique insights into a low-resource, potentially scalable intervention, focusing on a group of men at particularly high risk of HIV acquisition—those with recent STIs. The hybrid RCT design addresses clinically relevant effectiveness questions and explores key determinants that will inform future multisite implementation trials. Trial Registration: ClinicalTrials.gov NCT06200545; https://clinicaltrials.gov/study/NCT06200545

Background: Average sugar consumption among young children in the United Kingdom exceeds the recommended intake. Many parents choose commercial baby foods believing these to be a healthy option. However, surveys show many products contain high levels of added or free sugars, despite labeling suggesting they are “natural” and “healthy.” Analysis of labels and studies with parents suggest changes such as removing misleading marketing or adding sugar warning labels may impact parents’ beliefs and food choices. However, the literature does not provide a comprehensive understanding of the range of changes to commercial baby food labels that might best support parents in choosing healthier foods for their children. Objective: This scoping review will explore the published and unpublished evidence base to better understand what is known about how labeling of baby foods impacts parents’ beliefs about a product’s sugar content and related purchasing and feeding decisions. Methods: The JBI guidelines for methodology of scoping reviews will be followed, and results will be reported using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. The population, concept, and context (PCC) framework will be used to determine eligibility criteria. The search will include various research methodologies, including both quantitative (observational and interventional) and qualitative studies. An initial search of MEDLINE (Ovid) and Embase (Ovid) was conducted to develop a full search strategy for MEDLINE, which is presented here. In addition to MEDLINE and Embase, we will search PsycINFO (Ovid), CINAHL (Ebsco), Web of Science (Core Collection) and the Cochrane Library. Reference lists of included studies will also be searched. Unpublished reports will be identified using Google, Google Scholar, relevant websites, policy statements, and government reports and by contacting relevant government and third-sector organizations. In a 2-stage process, 2 reviewers will independently screen titles and abstracts and then full texts. One reviewer will then extract data and a second will verify accuracy. Findings will be presented in tables and diagrams accompanied by a narrative summary. Results: The literature searches yielded 2071 records from 6 databases, with 1123 documents remaining after deduplication. The gray literature search used a customized Google search, a targeted search of 34 websites, and contact with 49 experts. Conclusions: We present a protocol for a scoping review to explore the evidence base to understand what is known about how the labeling of baby foods impacts parents’ beliefs about sugar content and related purchasing and feeding decisions. The results of the review will help policymakers better understand regulatory opportunities to improve the labeling of commercial infant foods to help families feed infants and young children lower-sugar diets.

Background: Patients and caregivers attending emergency units often experience elevated levels of stress and anxiety. Music has been used in waiting rooms to reduce stress and anxiety, but existing studies on music therapy in emergency unit waiting areas are scarce and have limitations such as low statistical power and limited music selection. Objective: The aim of this study is to determine the effect of live Environmental Music Therapy and prerecorded music on state anxiety, stress, pain, and well-being levels in patients and caregivers in the emergency unit waiting areas of 2 hospitals in Colombia. Methods: This study is a multicenter randomized clinical trial, with 3 arms: standard care + live Environmental Music Therapy, standard care + prerecorded music, and standard care only. The primary outcome measure is the 6-item State-Trait Anxiety Inventory (STAI-6). Secondary outcome measures are pain and stress levels, both measured with Visual Analogue Scales (VAS), and well-being, measured with the Well-Being Numerical Rating Scales (WB-NRSs). The scales will be applied before and after each intervention. A total of 246 patients (82 in each arm) and 147 caregivers (49 in each arm) will be randomized. Results: Data collection for this study started on September 3, 2024, and as of the submission of the study (November 2024), 216 patients and 134 caregivers have been enrolled. It is expected that the results will be available by May 2025. Conclusions: This study seeks to contribute to improving the mental health, well-being, and quality of care of patients and caregivers in the waiting area of the emergency units. This is the first study in Colombia investigating the effect of live music therapy and prerecorded music interventions in the emergency department. Trial Registration: ClinicalTrials.gov NCT06510153; https://clinicaltrials.gov/study/NCT06510153

Background: Current gold standard chronic pain management applies a biopsychosocial lens to clinical care, integrating medication, psychosocial support, and physical reconditioning to promote sustained treatment success, increase quality of life, and control symptoms. However, only 40% of patients with chronic pain report adequate pain management. Unfortunately, evidence describing implemented treatment pathways or models of care (MoCs) that consistently use this holistic approach is lacking. Objective: The aim of this study is to identify the barriers and facilitators to access and engagement in existing MoCs for chronic pain, explore aspects of the delivery of care that can be improved, and develop an improved MoC for pain clinics in New South Wales by directly liaising with people with chronic pain and their families. Methods: A 2-phase qualitative study will be conducted using semistructured focus groups. Both phases will follow the same structure, so patients, carers, and clinicians will independently provide input into the proposed MoC, which will then be summarized and integrated by the research team. Participants will be encouraged to interact and speak freely across three core domains: (1) experience of chronic pain management, (2) barriers and facilitators to delivering/accessing a gold standard MoC, and (3) key improvement points to existing models. Each focus group will last 90 minutes and be audio-recorded and transcribed verbatim for qualitative analysis. The focus groups in phase one will generate initial recommendations for primary changes to the existing MoC, and these will then be integrated and presented for evaluation, feasibility, and acceptability by stakeholder groups during phase two. Results: Data collection commenced in September 2023 and is expected to end by September 2025. As of February 2024, we have completed the focus group with clinicians (n=12) and patients (n=7) in phase one. Data have not been analyzed formally and will be reported in a future publication. Conclusions: Through the exploration of key stakeholders’ perspectives of the barriers preventing access and the delivery of care in the current MoC for chronic pain, we aim to co-design an appropriate, feasible, and acceptable pathway to be implemented in pain services in the future.

Background: With a predicted 2 million new cases identified globally in 2018, breast carcinomas are the most common cancer in women and the primary cause of cancer-associated mortality. In the management of breast cancer, neoadjuvant chemotherapy treatment (NACT) has become a mainstay, particularly for patients with inflammatory and locally advanced breast cancer. It increases the possibility of breast-conserving surgery, facilitates tumor downstaging, and gives early indications of the effectiveness of treatment. Evaluating the histopathological response after NACT is crucial for prognosis and guiding subsequent treatment decisions. This study explores the various histopathological assessment systems used in breast carcinoma patients after NACT, focusing on the residual cancer burden (RCB) score, Miller-Payne system, Chevallier classification, Sataloff classification, National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 system, and the American Joint Committee on Cancer residual tumor size (R) categories. We compare their methodologies, strengths, limitations, and clinical significance, providing a detailed analysis of their roles in improving patient outcomes. Objective: The aim of this study is to confirm the diagnosis of breast carcinoma based on histopathology, to evaluate various scoring systems through assessments of histomorphological features affecting post-NACT patients with breast carcinoma, to compare the various systems regarding the response to therapy and forming prognoses, and to develop an ideal histomorphological assessment system for breast carcinoma in post-NACT patients. The study also focused on how breast tumors respond to NACT and how this response can guide treatment decisions and improve the formulation of prognoses. Methods: This observational study will be retrospective and prospective; it will include 128 patients diagnosed with breast carcinomas who have undergone NACT and were referred to a tertiary care hospital between January 2019 and December 2024. Following chemotherapy, a thorough examination of the histopathological specimens will be conducted to assess any changes in histomorphology. Results: Data collection started in September 2021 and will be completed by December 2025. Data analysis began in January 2025, and the results are expected to be published in December 2025. Institutional ethics committee clearance was obtained prior to commencement of the study. This is a nonfunded academic study. Conclusions: This project aims to evaluate and compare histopathological assessment systems in patients with breast carcinoma after NACT. Various histopathological systems, such as the RCB score, the Miller-Payne grading system, and other systems, each provide valuable insights into how well tumors respond to chemotherapy. The aim is to reveal essential histopathological parameters, leading to the refinement and potential modification of grading systems to improve clinical decision-making, treatment outcomes, and personalized care; however, challenges persist in standardization and consensus.

Background: Occupational stress is associated with detrimental consequences that are addressed by mobile health (mHealth) solutions. Previous developments of apps for occupational stress have not yet fully exploited the potential of multilevel diagnostics through the integration of wearable sensors for interventions. Personalizing mHealth approaches in terms of intervention time and content, which requires the use of artificial intelligence, is the next logical developmental step. The "Relax" approach developed a corresponding prototype of an app-wearable system, which will be evaluated for effectiveness in terms of stress reduction and usability. Objective: This study protocol describes an evaluation study used to test the effectiveness and usability of the Relax approach. Methods: The evaluation study was designed as a 2-arm randomized trial with 2 phases, each with a 3-week intervention period. In both phases, employees were required to use the app to record daily stress and to wear a wearable sensor to measure heart rate variability. The app offered interventions based on algorithms, which altered the probability of their selection after learning from the data, thereby personalizing the user experience. In the second phase of the study, the sample was divided into 2 groups, varying the degree of personalization of the app. To analyze effectiveness, a 2-factorial mixed within-between design will be applied to compare the outcomes between both groups as well as in a pre-post comparison. In addition, exploratory analyses of the usability of the approach are planned. Results: The study was conducted during the spring and summer of 2024, with a total of 46 participants enrolled, and is ready for data analysis. Conclusions: The Relax approach, including a number of factors related to personalization that have not yet been incorporated into mHealth in current research, will provide new insights into the next steps of advanced mHealth solutions. Limitations of the study design, such as the lack of a control group and the sample representativity, have to be addressed. Clinical Trial: Open Science Foundation 10.17605/OSF.IO/MYRD9; https://osf.io/myrd9

Background: The aging of the population is a major issue in Canada, particularly in Quebec. For people older than the age of 65 years, aging is often associated with both mild and severe cognitive impairment. The management of these disorders increases the pressure on health care systems. Digital health technologies could be used to promote the cognitive health of older people living with cognitive disorders. However, to reap the full benefits of using digital health technologies, it is critical that older people with cognitive disorders engage with these technologies. A dose-response relationship has been demonstrated between the level of engagement with digital health technologies and the effectiveness of interventions in older people. It is thus important to understand how older people with cognitive impairment engage with digital health technologies and how this engagement can influence the success of digital health interventions. Objective: This study aims to describe how the engagement of older adults with cognitive impairment with digital health technologies is conceptualized and assessed, and how this engagement relates to the effectiveness of digital health interventions. Methods: We will use the scoping review method outlined by Arksey and O’Malley. We will apply a systematic approach following the Joanna Briggs Institute guidelines and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist to ensure reproducibility of the scoping review. A search strategy, created with a medical information specialist, will be applied to MEDLINE, Embase, CINAHL, Web of Science, and Google Scholar, without time restrictions. Two reviewers will independently select titles, abstracts, and full texts. Data extraction will be conducted by the research team and validated by a senior member, resolving disagreements by consensus or a third party if necessary. Descriptive analyses will be done using concept mapping for a narrative synthesis of the results by themes related to the research questions. Results: The development of the search strategy and the completion of the selection phases of the review were completed in July 2024. Data extraction and analysis began in August 2024, and results are expected to be available in November 2024. Conclusions: The results of this scoping review will provide a comprehensive overview of the different conceptualizations of engagement with digital health technologies in older people with cognitive impairment, as well as the tools to measure it. This will contribute to a better understanding of the relationships between levels of engagement and the effectiveness of digital health interventions in older people living with neurocognitive disorders.

Background: Prenatal anxiety affects between 20% and 30% of pregnant people and is associated with adverse prenatal health conditions, birth outcomes, and postpartum mental health challenges. Individuals from racial and ethnic minority groups, sexual and gender minority groups, and those with low income are all at heightened risk for prenatal anxiety due to disproportionate exposure to adverse social determinants of health. Digital cognitive behavioral therapy (dCBT) has been shown to reliably reduce anxiety in mostly White and middle- to higher-income samples, but its efficacy in low-income and marginalized pregnant people is understudied. Objective: We propose a randomized controlled trial of a dCBT (Daylight app, Big Health, Ltd) in a sample of low-income pregnant people oversampled for racial, ethnic, sexual, and gender minority identity. Methods: Participants (N=132) will be randomized to the intervention or waitlist control group using a 1:1 allocation ratio. The intervention will be a self-guided application that uses an online therapist to teach and encourage the practice of 4 key cognitive behavioral therapy skills (eg, identifying catastrophic thinking and increasing physical relaxation) that can reduce anxiety. The primary outcome will be generalized anxiety symptoms; secondary outcomes will include depressive symptoms, stress, pregnancy-specific anxiety, and insomnia symptoms. Focus groups with a subset of participants will provide qualitative data about the acceptability of dCBT. Results: Recruitment began in June 2024. Data will be analyzed using linear mixed models, which will be fit with treatment condition (dCBT and waitlist control group) as the between-group factor, time (baseline, 3, 6, and 10 weeks post randomization) as a within-group factor, and a group-by-time interaction. Linear mixed models produce unbiased parameter estimates in situations where there are different numbers of observations per record and will accommodate intent-to-treat and sensitivity analyses. Conclusions: This clinical trial will evaluate the efficacy and acceptability of a self-guided dCBT for prenatal anxiety among low-income and marginalized pregnant people, a group that continues to experience substantial barriers to accessing in-person evidence-based psychotherapy. Clinical Trial: ClinicalTrials.gov NCT06404450; https://clinicaltrials.gov/study/NCT06404450

Background: Asthma affects 1 in every 12 persons in the United States, resulting in 1.9 million emergency department (ED) visits annually. However, the lack of patient-reported outcome measures (PROMs) validated for use in the ED limits the evaluation of interventions to improve ED asthma care. Objective: To address this knowledge gap, this study protocol will (1) develop and test the validity and reliability of the Patient Reported Outcomes for Acute Asthma Care and Treatment instrument (PROAACT), (2) test whether receiving more guideline-concordant ED care is associated with improved PROAACT responses, and (3) evaluate the association between PROAACT score and subsequent ED revisits and hospitalizations. Methods: This is a prospective cohort study of adult patients visiting the ED for acute asthma exacerbation across 3 EDs at an urban, tertiary care health system. Eligible patients are 18 years or older, have a prior diagnosis of asthma (self-reported or documented in the electronic health record), are English-speaking, and experiencing an ED visit for asthma exacerbation as determined by the treating clinician. Enrolled participants complete an initial PROM survey during their ED visit assessing their symptoms in the preceding 7 days, then complete a follow-up survey 7 days after ED discharge assessing changes in the symptoms in the subsequent 7 days. To test whether guideline-concordant care is associated with improved PROAACT scores, we will conduct a retrospective chart review of medications ordered during the ED visit, and then compare guideline adherence to changes in PROAACT scores. To test whether improved PROAACT scores are associated with fewer return ED visits and hospitalizations, we will extract all-cause ED visits and hospitalizations within 30 days from a regional health information exchange, and then compare usage to changes in PROAACT scores. We will use item response theory to develop scale responses based on summed item responses, which will allow us to test associations with clinical outcomes, including adherence to guideline-recommended care and return ED visits and hospitalizations. Results: Recruitment is ongoing and has experienced numerous challenges related to the COVID-19 pandemic. To date, we have enrolled over 250 participants and have completed over 200 follow-ups. Recruitment is expected to conclude in spring 2025. Conclusions: Our study is intended to validate the use of PROMs during ED visits for acute asthma exacerbation among adult patients. Completion of the proposed aims will result in one of the first PROMs intended for use among adult ED patients and support the feasibility of collecting PROMs in the ED setting. Trial Registration: Clinical Trials.gov NCT04349020; https://clinicaltrials.gov/study/NCT04349020

Background: Rumination is a transdiagnostic process present in several psychological disorders, involving repetitive negative thinking that individuals may perceive as difficult to control. While the roles of numerous mechanisms underlying rumination have been supported, experiential avoidance (EA) still lacks empirical backing, despite a strong theoretical foundation, partly due to difficulties in examining EA in an ecologically valid context. One promising approach to addressing this challenge is through reducing EA using mobile health (mHealth) and ecological momentary intervention (EMI), and assessing any subsequent decrease in rumination’s deleterious outcomes. Objective: This paper outlines the protocol for a randomized controlled trial using a novel mHealth EMI to address EA in the context of rumination. The app was developed by a multidisciplinary team, incorporating feedback from potential end users. Methods: Consenting individuals (target N=60) who meet the inclusion criteria (self-reporting problems with repetitive negative thinking) will be randomly assigned to 1 of 4 conditions: (1) intervention with therapist support and daily sampling, (2) intervention without support and with daily sampling, (3) partial intervention (emotion validation EMI only) with daily sampling, or (4) control (daily sampling only). The intervention consists of a series of modules delivered over 4 weeks, with assessments conducted before and after intervention, and again at 1-month follow-up (plus an additional 3-month follow-up for intervention participants). Data will be collected both through online self-report assessments and via the app itself. The potential of the EMI to modify the maladaptive feature of repetitive negative thinking will be assessed using mixed-design ANOVA, while the links between avoidance-mood and rumination-mood, in terms of the moderating effect of trial condition, will be evaluated using multilevel models. These will be assessed as primary outcomes. Secondary outcomes are the effects of a supporting therapist on postintervention outcomes in the intervention groups, and time spent using the app as a measure of engagement (analyzed using the mixed-design analysis of covariance). Compliance will be defined as completing both of the first 2 weeks of intervention content in full, and 5 out of the 6 exercises from weeks 3 and 4. Additionally, the study will control for both the amount of time spent in the app and the length of responses to open-ended questions. Results: Recruitment and enrollment for the trial are expected to begin in May 2025 and be completed by July 2025. Data collection will conclude once the target sample size for each of the 4 conditions has been reached. The main results of the trial are expected to be submitted for publication in October 2025. Conclusions: The outcomes of this research trial will not only provide insights into the clinical capabilities of the app, including its usability and acceptability in real-world contexts (and its potential future viability as a scalable product), but will also offer valuable theoretical insights into the role of EA in maladaptive rumination. Trial Registration: ClinicalTrials.gov NCT06570694; https://clinicaltrials.gov/ct2/show/NCT06570694

Background: Pain experienced during childbirth can significantly impact the progress of labor and the well-being of both the mother and the fetus. Effective management of labor pain is a crucial component of childbirth care. Nonpharmacological methods of pain relief offer notable advantages over pharmacological approaches, including enhanced maternal and fetal safety, equitable access to health care, and greater availability. Among the nonpharmacological options, transcutaneous electrical nerve stimulation (TENS) and acupoint stimulation are two commonly used methods for alleviating pain during labor. However, the clinical efficacy of these methods remains inconsistent, which hinders the generation of high-quality evidence for clinical practice. Objective: This study aims to assess the effects of acupoint stimulation combined with TENS on labor pain, delivery outcomes, and childbirth experience for women undergoing a trial of labor. Methods: This is a 12-month stepped wedge cluster randomized trial to be conducted in 4 labor and delivery units (LDUs) at the Obstetrics and Gynecology Hospital of Fudan University. Each unit will implement 4 types of interventions: TENS, acupoint stimulation, TENS combined with acupoint stimulation, and a control group. We aim to recruit approximately 588 pregnant women. The project will be evaluated using both quantitative and qualitative data. Quantitative data will include visual analog scale (VAS) scores, the nonpharmacological to pharmacological pain management interval (NPI), the rate of epidural analgesia, and childbirth outcomes. Qualitative data will include interviews with the women and midwives. Results: The study commenced on April 1, 2023, and as of March 29, 2024, a total of 600 eligible participants have been enrolled, surpassing the initial target of 588. Data collection has been completed, including quantitative assessments of labor pain intensity, analgesic use, and childbirth outcomes, alongside qualitative interviews with participating women. Currently, data analysis is in progress, with preliminary findings anticipated to be available by March 2025. We hypothesize that TENS combined with acupoint stimulation will demonstrate greater efficacy in managing labor pain compared with standard care. This effect may be observed in key outcome measures, including the VAS score and enhanced maternal childbirth experience. Conclusions: This study protocol details the interventions of acupoint stimulation and TENS for women undergoing a trial of labor. We introduce a novel outcome indicator termed NPI, which monitors whether the application of nonpharmacological pain relief measures can delay or prevent the use of epidural analgesia. The integration of qualitative and quantitative methods will enrich the research on TENS and acupoint stimulation technology within the realm of nonpharmacological labor pain relief, providing high-quality evidence for the future establishment of industry standards and guidelines. Trial Registration: Chinese Clinical Trial Registry ChiCTR2300069705; https://tinyurl.com/2s3mkhr7

Background: Young people living with HIV face challenges in consistently adhering to antiretroviral therapy (ART). Although mobile health interventions, particularly those using SMS text messaging, have been implemented to improve ART adherence, many lack a focus on specific behavioral mechanisms. Interventions incorporating behavioral change techniques (BCTs), especially those emphasizing customization, may enhance effectiveness. WhatsApp offers potential for delivering tailored, behaviorally grounded interventions with diverse communication features. We hypothesize that WhatsApp messages self-designed by participants, with spontaneous targeting of BCTs, could be more effective than standard WhatsApp messages designed by the researchers to improve ART adherence. Objective: The objective of this study is to evaluate the effectiveness of WhatsApp messages created by participants (self-designed) compared to WhatsApp messages designed by the researchers (standardized) over adherence to ART at 16 weeks of intervention in young people living with HIV who receive HIV care under routine conditions at a public hospital in Lima, Peru. Methods: A 2-arm randomized controlled trial with a parallel assignment of 1:1, with no blinding of study intervention, was performed. Eligible participants are consenting people living with HIV aged 18-29 years who receive HIV care at the study center and whose mobile phones support WhatsApp. Following informed consent and a baseline survey on clinical and personal preferences (eg, timing and frequency of messages), participants are randomized to the control group (messages designed by the research team) or to the experimental group (messages designed by participants), stratified by sex, educational level, current ART intake, and history of ART abandonment. Participants in both groups receive up to 3 WhatsApp messages per week for 16 weeks. ART adherence, the primary outcome, is measured using the Simplified Medication Adherence Questionnaire (SMAQ) at 4, 8, 12, and 16 weeks. Monthly feedback questionnaires on user experience are also administered. The WhatsApp chat format allows two-way communication between participants and the research team throughout the study. We will compare ART adherence between 2 groups at 16 weeks under the intention-to-treat principle, with no interim analysis planned. Based on an estimated 10% difference in adherence, 78.9% power, and a 2-sided α of .05, the target sample size was set at 120, later increased to 131 to include a 2-week pilot phase. Results: In March 2024, we started enrolling and randomizing participants. The study follow-up will continue until the last participant completes 16 weeks of intervention (November 2024). As of February 2025, we are in the process of data curation. Conclusions: This trial will compare the effectiveness of standardized vs self-designed WhatsApp messages on ART adherence measured at 16 weeks among young people living with HIV receiving routine care in a low-resource setting in Lima. Trial Registration: ClinicalTrials.gov NCT06500013; https://clinicaltrials.gov/ct2/show/NCT06500013

Background: The health sector collects a plethora of electronic health data via digital technologies, such as electronic health records (EHRs) and electronic medical records (EMRs). The primary use of EHRs includes supporting service delivery, providing data on patient information, and health care operations. Secondary uses of these systems can include quality improvement activities and research, and possibly inform policy. One underexplored secondary use of data from these systems is to enable health care professionals to understand their performance, reflect on their practice, and potentially support enhanced professional and workplace learning. There is growing interest and an increase in policies to focus on motivating the use of this type of data as part of mandatory Continuing Professional Development. Despite this, the design of EHRs is not conducive to the use of these systems for reflective practice, and there are few best practice guides for how to scaffold the use of these data for secondary use. Objective: The aim of this project is to determine how EHRs and EMRs can be leveraged to enable formative performance feedback for health care professionals. The primary objective is to explore the use of these systems by health care professionals to further understand the current and possible future use of these records for reflective practice, performance feedback, and workplace learning. Methods: The project will use a mixed methods design to enable a holistic picture of participant behaviors. Study data are being collected over 3 phases. Phase 1 consists of interviewing health care professionals and clinicians about their experiences with EHRs and EMRs. Phase 2 will involve surveying health care professionals about specific EHR features, and phase 3 will encompass workshopping discussions around EMR functionality and design with key informants. Participants for phases 1 and 2 will be a convenience sample of health care professionals who self-select and volunteer to participate in the study. Participants for phase 3 will consist of policy makers, representatives from peak bodies, technology vendors, health care professionals, and others. Data from phase 1 will be thematically analyzed to identify key features of EMR and EHR design for prioritization in phase 2. Phase 2 survey responses will be descriptively analyzed to understand the most important features in record design to support reflective practice. Phase 3 workshop data will be thematically analyzed to identify design insights for EHRs and EMRs that support professional learning. Results: The project is currently in its interview phase and is expected to publish results in mid-2025. Conclusions: The project will generate new knowledge on the extent to which data collected by workplace technologies provide health care professionals with formative performance feedback. It will also develop a conceptual design for EHRs that supports health care professional learning, which could be leveraged by developers of these technologies in future implementations.

Background: Invasive coronary angiography (ICA) is the gold standard in the diagnosis of coronary artery disease (CAD). Being invasive, it carries rare but serious risks including myocardial infarction, stroke, major bleeding, and death. A large proportion of elective outpatients undergoing ICA have nonobstructive CAD, highlighting the suboptimal use of this test. Coronary computed tomographic angiography (CCTA) is a noninvasive option that provides similar information with less risk and is recommended as a first-line test for patients with low-to-intermediate risk of CAD. Leveraging artificial intelligence (AI) to appropriately direct patients to ICA or CCTA based on the predicted probability of disease may improve the efficiency and safety of diagnostic pathways. Objective: he CarDIA-AI (Coronary computed tomographic angiography to optimize the Diagnostic yield of Invasive Angiography for low-risk patients screened with Artificial Intelligence) study aims to evaluate whether AI-based risk assessment for obstructive CAD implemented within a centralized triage process can optimize the use of ICA in outpatients referred for nonurgent ICA. Methods: CarDIA-AI is a pragmatic, open-label, superior randomized controlled trial involving 2 Canadian cardiac centers. A total of 252 adults referred for elective outpatient ICA will be randomized 1:1 to usual care (directly proceeding to ICA) or to triage using an AI-based decision support tool. The AI-based decision support tool was developed using referral information from over 37,000 patients and uses a light gradient boosting machine model to predict the probability of obstructive CAD based on 42 clinically relevant predictors, including patient referral information, demographic characteristics, risk factors, and medical history. Participants in the intervention arm will have their ICA referral forms and medical charts reviewed, and select details entered into the decision support tool, which recommends CCTA or ICA based on the patient’s predicted probability of obstructive CAD. All patients will receive the selected imaging modality within 6 weeks of referral and will be subsequently followed for 90 days. The primary outcome is the proportion of normal or nonobstructive CAD diagnosed via ICA and will be assessed using a 2-sided z test to compare the patients referred for cardiac investigation with normal or nonobstructive CAD diagnosed through ICA between the intervention and control groups. Secondary outcomes include the number of angiograms avoided and the diagnostic yield of ICA. Results: Recruitment began on January 9, 2025, and is expected to conclude in mid to late 2025. As of April 14, 2025, we have enrolled 81 participants. Data analysis will begin once data collection is completed. We expect to submit the results for publication in 2026. Conclusions: CarDIA-AI will be the first randomized controlled trial using AI to optimize patient selection for CCTA versus ICA, potentially improving diagnostic efficiency, avoiding unnecessary complications of ICA, and improving health care resource usage. Clinical Trial: ClinicalTrials.gov NCT06648239; https://clinicaltrials.gov/study/NCT06648239/

Background: Walking difficulties are a common and costly problem. However, disability associated with the decline in walking ability is not an inevitable consequence. With an aging population, it is increasingly important to establish strategies to help older adults preserve the capacity to live independently and function well in late life. Preclinical mobility limitation (PCML), which is characterized by subtle changes or limitations in mobility that precede disability, manifests as changes in how daily tasks such as walking are performed. Persons with PCML are at increased risk for the onset of disability and chronic disease. For that reason, PCML is a critical stage in the natural history of functional change when there is the opportunity for primary prevention interventions. Objective: To evaluate the effect of a 12-week online mobility self-management program (Stepping Up) on mobility outcomes, including walking speed, aerobic exercise capacity, dual-task cost, physical functioning (balance and strength), balance confidence, extent of community mobility, self-management of mobility, and quality of life in older adults with PCML. Methods: This randomized controlled trial (RCT) will recruit 249 older adults (aged 55-75 years) screened for PCML. Participants will be assigned to the Stepping Up program, a telephone-based coaching walking program or an online chair-based yoga program. Programs will be delivered over 12 weeks and participants will undergo virtual assessments with a blinded physiotherapist at baseline, 12, 24, and 36 weeks. An economic evaluation will be conducted alongside this RCT. Results: A total of 253 participants were enrolled in the trial. Data collection commenced in August 2021 and will be completed in October 2025. Data analysis will begin in November 2025 and results will be published in the Summer of 2026. Conclusions: To our knowledge, PCML has not been addressed by primary prevention interventions that incorporate both task-oriented motor learning exercise and mobility self-management sessions. Results will establish if the Stepping-Up program has the potential to serve as a model for sustainable, accessible, and cost-effective programming for individuals with early mobility limitations. Trial Registration: ClinicalTrials.gov NCT04368949; https://clinicaltrials.gov/study/NCT04368949

Background: Impaired gait adaptability is one of the major causes of falls among older adults owing to inappropriate gait adjustments in cluttered environments. Training programs designed to improve gait adaptability behavior in a systemic approach may prevent falls in older adults. Recently, virtual reality (VR) technology has been prominent as a relevant gait training tool because of its training implementation potential. Objective: This study was designed to compare the effectiveness of a VR-based gait training program (VR group) for improving gait adaptability behavior and, thus, reducing the risk of falls relative to a conventional training program such as Nordic walking (NW; NW group). We hypothesized that the VR-based gait training program will lead to greater gait adaptability improvements. Methods: We will be conducting a randomized controlled trial with pretests, posttests, retention tests, and follow-up. In total, 40 healthy independent-living community dwellers (aged between 65 and 80 years) will be allocated, after a general medical examination, to the VR or the NW group for a training program of 6 weeks. Primary outcomes related to gait adaptability capacities (ie, analysis of adjustments made in different locomotor tasks) and acceptance of the VR device (ie, analysis of acceptance) will be assessed before and after the intervention and 1 month after the completion of the training program (retention). A follow-up will be done during the 12 months after the completion of the gait training program. Results: Data collection will begin in September 2025, and the first results are expected in December 2025. Conclusions: The findings of this study may demonstrate the relative relevance of a gait training program in VR versus a conventional one for improving gait adaptability behavior in healthy older adults and, thus, prevent the chances of a fall.

Background: Individuals with autism spectrum disorder (ASD) often exhibit low dietary diversity due to food selectivity, leading to various forms of malnutrition, such as obesity or micronutrient deficiencies. Objective: The main objective of the AUT-MENU project is to improve meal acceptance among individuals with ASD. A secondary goal is to evaluate the effectiveness of a nutrition education course for parents of enrolled participants to reduce food selectivity. Methods: The study is a bicentric intervention conducted in 3 care centers (Pavia and Milan) and 1 secondary school (Rome), involving approximately 200 participants with ASD aged 3 to 35 years. The study consists of an observational phase (T0) and an intervention phase (T1). At T0, biographical data, clinical characteristics, and dietary patterns of participants are collected. Based on T0 findings and existing nutritional recommendations for individuals with ASD, targeted menus are developed and tested. At T1, the same assessment tools used at T0 will be applied to evaluate intervention effects. Additionally, a nutrition education course for caregivers will be implemented between T0 and T1, with a pre- and postcourse knowledge questionnaire to assess its effectiveness. Results: Due to different timelines depending on the centers and schools involved, participant enrollment and data collection will take place at different times between Pavia, Milan, and Rome. In September 2024, enrollment was held in the Pavia and Milan care centers for a total of 74 participants enrolled. In Rome, the enrollment phase has not yet started; activities are expected to be carried out similar to those in Pavia and Milan. Conclusions: The AUT-MENU study is expected to yield significant insights and improvements in meal acceptance among individuals with ASD, particularly through the introduction of targeted menus in collective catering settings both in care centers and schools. Trial Registration: ClinicalTrials.gov NCT06266377; https://clinicaltrials.gov/study/NCT06266377

Background: Severe weather events, exacerbated by climate change, can lead to hardships such as displacement, resource scarcity, and social network disruptions. Such disasters impact mental health, triggering conditions such as anxiety, depression, and posttraumatic stress disorder. For communities in the Gulf South, the increasing frequency of disasters often further exacerbates already disastrous levels of inequality. In this context, there is an urgent need for evidence-based, multilevel, community-based interventions to support individual and community mental health and resilience. Objective: This protocol describes the design of a community-based participatory research (CBPR) study to improve individual and community mental health in Gulf South communities by examining the implementation and effects of the multilevel, community-based intervention, Communities Organizing for Power through Empathy (COPE). Specifically, this study aims to (1) examine factors affecting the implementation, effectiveness, and adoption of the COPE intervention and (2) test its effects on mental health and community resilience. We hypothesize that participants in the COPE intervention will experience greater reductions in psychological distress (eg, perceived stress, anxiety, and depression); improvements in protective factors (eg, social support and coping self-efficacy); and community participation as compared with an attention control group. Methods: The Consolidated Framework for Implementation Research guides our analysis of data collected from surveys, fidelity and field notes, interviews, and focus groups to examine aim 1. We examine aim 2 primarily via a 2-arm pragmatic stepped-wedge cluster randomized trial (SW-CRT) with individuals (approximately n=300) in clusters (faith-based and secular community-based organizations; approximately n=15) in a disaster-prone community in the US Gulf Coast. The cluster-based design implemented in steps supports the community-based nature of the study where timelines differ by organization. A total of 5 self-assessments will be conducted both in person and via email at later time points. We will integrate mixed methods in our analyses for aim 1 by combining themes from interviews and focus groups with implementation measures, and for aim 2 by constructing a data matrix to combine findings from the SW-CRT with thematic analyses of field notes and interviews. Results: The SW-CRT is being conducted from June 2022 to June 2025. Recruitment began in April 2023, to conclude in spring 2025, to assess mental health, social support, and community resilience at 5 time points. Data analysis and dissemination of results are expected by spring of 2026. Conclusions: This protocol is among the first to use a CBPR approach to examine the implementation and effectiveness of a multilevel intervention on psychological distress and resilience. This study provides new insights into how CBPR can enhance intervention implementation research and expand the evidence on community-based mental health interventions during disasters. Policy makers should consider integrating CBPR approaches into disaster response frameworks to ensure culturally relevant and sustainable outcomes. Trial Registration: ClinicalTrials.gov NCT06093737; https://clinicaltrials.gov/study/NCT06093737

Background: A healthful diet in early childhood is essential for healthy growth and disease prevention. Parents influence children’s diets through supportive (eg, structure and autonomy support) and unsupportive (eg, coercive control and indulgence) food parenting practices. Historically, much of this work has focused on parents’ “usual” feeding behaviors using survey methods. However, recent studies using ecological momentary assessment methods have allowed assessment of food parenting behaviors in “real time.” This work has revealed that the practices used by parents to feed children vary across contexts and are influenced by factors such as stress or time constraints. Research is needed to understand the dynamic nature of food parenting and its impact on children’s diets. Objective: This study aimed to describe the methods and procedures used in the Preschool Plates cohort study, which aimed to (1) describe within- and between-day fluctuations in food parenting practices across time and context, (2) examine the longitudinal impact of within- and between-day fluctuations in food parenting practices on child dietary intake, and (3) identify momentary predictors of within- and between-day fluctuations in food parenting practices across time and context. Methods: Preschool Plates is a longitudinal cohort study examining the impact of food parenting practices on the dietary intake of 3- to 5-year-old children. A total of 273 parent-preschooler dyads consented and enrolled, and 254 (93%) dyads completed baseline data collection. Dyads will be followed for 2 years using state-of-the-art measures, including an 8-day ecological momentary assessment protocol to assess food parenting, contemporary measures of food parenting, and 3 interview-led 24-hour dietary recalls, collected at baseline, 6 months, 12 months, and 24 months. Child height and weight will be measured at 3 time points. Results: Recruitment for our baseline sample (N=254) occurred between October 2023 and September 2024. Participants will complete follow-up data collection after 6 months, 12 months, and 24 months. A racially and ethnically diverse cohort was enrolled, with 28.3% (72/254) of enrolled participants identifying as White and 71.7% (182/254) identifying as non-White. Conclusions: Findings from the proposed study will inform the development of anticipatory guidance for feeding young children and randomized controlled trials designed to intervene on parents’ responses to momentary factors to encourage interactions with children around feeding that promote optimal diet quality. For example, findings could inform the development of an ecological momentary (ie, real time) intervention that delivers content to participants’ mobile devices in response to real-time assessments of context and circumstance.

Background: Patients with ischemic stroke are at high risk of recurrence, making preventive care an important factor. Current antiplatelet therapy for recurrence prevention treatment has several limitations. Recent retrospective observational studies suggested that HH333, an herbal prescription, has an inhibitory effect on stroke recurrence in small-vessel diseases. Objective: This study aims to propose a protocol for evaluating the efficacy and safety of HH333 in patients with ischemic stroke induced by small-vessel disease. Methods: In this multicenter, double-blind, randomized, prospective, pilot clinical trial, 236 patients from 3 university Korean medicine hospitals in South Korea with ischemic stroke caused by small-vessel disease will be recruited and randomly assigned to either the HH333 or the placebo group. Both patients and investigators will be blinded to prevent access to the allocation results. The HH333 group will take 2 capsules of HH333 once daily for 720 days, whereas the placebo group will take HH333 placebo capsules in the same manner. Efficacy will be assessed using the recurrence rate of ischemic stroke, which will be assessed on days 30, 90, 180, 270, 360, 450, 540, 630, 720, and 750 after starting the medication. The effects on quality of life and fatigue with the Fatigue Severity Scale (FSS), Fatigue Assessment Scale (FAS), and Korean Patient Health Questionnaire (K-PHQ-9), functional improvement with Korean National Institutes of Health Stroke Scale (K-NIHSS), modified Rankin Scale (mRS), Korean modified Barthel Index (K-mBI), and Korean Montreal Cognitive Assessment (K-MoCA) and Pattern Identification also will be evaluated on days 0, 90, 180, 270, 360, 450, 540, 630, and 720 after starting the medication. Safety will be evaluated by performing blood and urine tests and electrocardiography on days 30, 90, 180, 270, 360, 450, 540, 630, and 720 after starting the medication. Results: Recruitment for the study started on May 22, 2024, and is scheduled to end on November 30, 2026. As of November 13, 2024, a total of 12 participants have been randomized. Conclusions: The protocol will provide a detailed process for a clinical trial evaluating the efficacy of preventing recurrent ischemic stroke caused by small-vessel disease and improving neurologic symptoms and the safety of HH333 in ischemic stroke. The results of this study provide a basis for alternative treatments to prevent and treat ischemic stroke. Trial Registration: Clinical Research Information Service KCT0009431; https://tinyurl.com/y2ctvje8

Background: Over the past 2 decades, the gut microbiota has emerged as a key player in human health, being involved in many different clinical contexts. Yet, many aspects of the relationship with its host are poorly documented. One obstacle is the substantial variability in wet-laboratory procedures and data processing implemented during gut microbiota studies, which poses a challenge of comparability and potential meta-analysis. Objective: The study protocol described here aimed to better understand the relationship between health, dietary habits, and the observed heterogeneity of gut microbiota composition in the general population. “Le French Gut – Le microbiote français” aimed to collect, sequence, and analyze 100,000 fecal samples from French residents using a high-quality shotgun metagenomic pipeline, complemented with comprehensive health, lifestyle, and dietary metadata. Methods: “Le French Gut – Le microbiote français” is a prospective, noninterventional French national study involving individuals, the creation of a biological collection (feces), and the exploitation of data from questionnaires and the National Health Data System (Système National des Données de Santé). This national study is open to all metropolitan French adult residents, excluding those who have undergone a colectomy or digestive stoma, or who have had a colonoscopy or taken antibiotics in the last 3 months. This is a home-based trial in which volunteers complete a questionnaire with insights about their health and habits, and in which stool samples are self-collected. Data analysis is structured into 6 work packages, each focusing on a specific aspect of the gut microbiome, including its composition and associations with lifestyle, quality of life, and health. Results: This paper outlines the study protocol, with recruitment having started in September 2022 and expected to continue until the end of December 2025. As of January 2025, a total of 20,000 participants have been enrolled. The first scientific publications based on the data analysis are expected by mid-2025. Conclusions: “Le French Gut” aims to provide a reference database and new ecosystem tools for understanding the relationship between the gut microbiota, its host, and diet. We expect to be able to find new signatures or targets and promote the design of innovative preventive strategies, personalized nutrition, and precision medicine. Trial Registration: ClinicalTrials.gov NCT05758961; https://clinicaltrials.gov/study/NCT05758961

Background: Dry eye disease (DED) is a common ocular condition with diverse and heterogeneous symptoms. Current treatment standards of DED include the post facto management of associated symptoms through topical eye drops. However, there is a need for predictive, preventive, personalized, and participatory medicine. The DryEyeRhythm mobile health app enables real-time data collection on environmental, lifestyle, host, and digital factors in a patient’s daily environment. Combining these data with genetic information from biobanks could enhance our understanding of individual variations and facilitate the development of personalized treatment strategies for DED. Objective: This study aims to integrate digital data from the DryEyeRhythm smartphone app with the Tohoku Medical Megabank database to create a comprehensive database that elucidates the interplay between multifactorial factors and the onset and progression of DED. Methods: This prospective observational cohort study will include 1200 participants for the discovery stage and 1000 participants for the replication stage, all of whom have data available in the Tohoku Medical Megabank database. Participants will be recruited from the Community Support Center of Sendai, Miyagi Prefecture, Japan. Participant enrollment for the discovery stage was conducted from August 1, 2021, to June 30, 2022, and the replication stage will be conducted from August 31, 2024, to March 31, 2026. Participants will provide demographic data, medical history, lifestyle information, DED symptoms, and maximum blink interval measurements at baseline and after 30 days using the DryEyeRhythm smartphone app. Upon scanning a registration code, each participant’s cohort ID from the Tohoku Medical Megabank database will be linked to their smartphone app, enabling data integration between the Tohoku Medical Megabank and DryEyeRhythm database. The primary outcome will assess the association between genetic polymorphisms and DED using a genome-wide association study. Secondary outcomes will explore associations between DED and various factors, including sociodemographic characteristics, lifestyle habits, medical history, biospecimen analyses (eg, blood and urine), and physiological measurements (eg, height, weight, and eye examination results). Associations will be evaluated using logistic regression analysis, adjusting for potential confounding factors. Results: The discovery stage of participant enrollment was conducted from August 1, 2021, to June 30, 2022. The replication stage will take place from August 31, 2024, to March 31, 2026. Data analysis is expected to be completed by September 2026, with results reported by March 2027. Conclusions: This study highlights the potential of smartphone apps in advancing biobank research and deepening the understanding of multifactorial DED, paving the way for personalized treatment strategies in the future.

Background: Early-onset hypertension (HT) presents compounded risks for cardiovascular, renal, and other systemic complications. Childhood HT is associated with HT during adulthood and detrimental lifelong cardiovascular disease events. However, most of the cases are not detectable as HT measurement in children is complicated and unstable. The global prevalence of HT among children is rapidly increasing. A previous study (2019) reported that the pooled global HT prevalence is 4.0% and the number is believed to be elevated. However, prevalence estimates of childhood HT have rarely been synthesized globally. Objective: This study aims to systematically pool all evidence from published articles and synthesize the evidence on the global prevalence of childhood HT and antihypertensive (anti-HT) use among children and its effects. Methods: This systematic review of observational and experimental studies will investigate the overall prevalence of HT and anti-HT use among children. We will search articles from 4 web-based databases: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Scopus using the specific keywords across the databases. During the article search conducted until October 2024, we retrieved 14,575 articles. Articles published in the English language with full text and are peer-reviewed journals included children aged between 0 and 18 years, confirmed with HT or high blood pressure (BP) on at least 3 separate occasions, and stated the definition of HT will be included in this protocol. Study selection and reporting will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and the Meta-Analysis of Observational Studies in Epidemiology guidelines and Cochrane Risk of bias tool (ACROBAT) for experimental studies. Data will be extracted using a standardized data extraction form using Microsoft Excel software and the studies’ quality will be assessed using the Joanna Briggs Institute’s guideline according to the study design. We will use STATA software (version 17.0; StataCorp LLC) to calculate the global pooled prevalence and RevMan software (version 5.4; StataCorp LLC) to observe the effect of anti-HT use and BP among children. The risk of bias will be assessed using a funnel plot. Results: We retrieved 14,575 articles from 4 databases in October 2024. We will report the current global overall or pooled prevalence of HT as well as by region, risk factors, anti-HT use, and the anti-HT BP-lowering effect among the general children population. The findings will be presented in summary table findings and forest plot. This review is expected to be completed in the middle of 2025. Conclusions: This review will provide a comprehensive synthesis of the overall prevalence of HT among children—a public health issue of growing concern with long-term impact. This review will also provide important information to inform practice in developing effective strategies for preventing and managing childhood HT. Clinical Trial: PROSPERO CRD42024500248; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024500248

Background: Individuals with poststroke hemiplegia often develop spasticity, which increases disability. Antispastic treatments such as baclofen and botulinum toxin are commonly prescribed in poststroke recovery. However, their impact on motor recovery, especially when administered within the first 2 months after stroke, remains unclear. Objective: This study aims to compare the motor recovery effects of botulinum toxin versus oral baclofen. The hypothesis is that botulinum toxin is more supportive of motor recovery than baclofen and enhances functional recovery. Methods: The study is a multicenter, controlled phase IV, comparative, prospective, randomized, double-blind, double-dummy, superiority trial to compare the toxin and baclofen, and a noninferiority trial to compare the toxin and the placebo. It focuses on the time course of the Fugl-Meyer Motor Assessment (FMA) as the primary outcome. The main inclusion criterion is patients with a single stroke in the past 2 months. Treatment comprises 1 intramuscular injection at treatment initiation and oral tablets for 4 months. Randomized patients are allocated to 3 arms: botulinum toxin with placebo baclofen, baclofen with placebo botulinum toxin, and placebo baclofen with placebo botulinum toxin. FMA scores are assessed at pretreatment, 1 month, and 3 months later. Spasticity, functional abilities, activities of daily living, pain, and quality of life are also evaluated. Adverse effects are monitored. A positive difference of 13 points in the FMA time course between the botulinum toxin and baclofen groups is considered a relevant effect. The data analysis plan involves linear regression models to compare primary and secondary outcomes, with adjustments for covariates such as age, center, and associated treatments. Subgroup analyses will examine proportional recovery profiles, and missing data in Fugl-Meyer scores will be addressed using imputation methods. Results: A total of 179 participants were randomized across 18 centers, with inclusions delayed due to the COVID-19 pandemic. As of December 2024, the data manager currently has all the data, and a review of data quality is in progress. No statistical analysis has been conducted so far, and the blind will be lifted after the analysis. Conclusions: This study identifies the most suitable spasticity treatment, considering the specificities of the stroke and constraints during the recovery phase. It will provide recommendations for the primary treatment of early spasticity post stroke. Trial Registration: ClinicalTrials.gov NCT02462317; https://clinicaltrials.gov/study/NCT02462317; European clinical trials (EudraCT) 2010-022881-28; https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-022881-28/FR

Background: The global burden of chronic diseases is increasing and becoming a public health issue throughout the world. The use of telenursing is increasing significantly during and after the COVID-19 pandemic to treat and prevent chronic diseases. Telenursing is growing in many countries to reduce health care costs, increase the number of aging and chronically ill populations, and increase health care coverage to distant, rural, small, or sporadically populated regions. Among its many benefits, telenursing may help to solve increasing shortages of nurses, reduce distances, save travel time, and keep patients out of the hospital. Objective: The objective of this study is to apply the self-management telenursing program and telenursing system developed by the researchers to Bangladesh and to evaluate its feasibility and efficacy (improved diabetes control in participants). Methods: This is a pilot, quasi-experimental pre- and post-intervention study. Diabetes patients who will attend the Grameen Primary Health Centers (PHCs) in Bangladesh will be enrolled between September 2024 and August 2025. We include patients who have been diagnosed with type 2 diabetes, both sexes, ages 18-75 years old, all types of treatment, willing to participate and give us consent. We exclude patients who have been diagnosed with gestational diabetes, diabetes as a secondary cause, complication of chronic kidney disease (CKD) stage 5, Hemoglobin A1c (HbA1c) is less than 7% for the past 1 year with CKD stage 1 or 2, no complications or complications with good control, having enough knowledge (had education before) and implemented good practice regarding diabetes management assessed by the research nurses, and disabled persons who need other person’s support for daily living. The sample size was calculated and found 70. Written informed consent will be obtained from all the participants. The study protocol got approval from the National Research Ethics Committee of the Bangladesh Medical Research Council (BMRC/NREC/2022-2025/336) on September 08, 2024. The outcome of this study is to evaluate the effects of telenursing intervention by controlling HbA1c. Results: The project was funded in 2024. The enrollment of the participants started on October 26, 2024, and the required sample (n=70) enrollment was completed in February 2025. Data analysis will be started after completion of data collection and results will be expected to be submitted for publication in 2026. Conclusions: Diabetic patients will acquire disease-specific management skills. Setting and monitoring goals ensures the continuation of the desired behavior and gives the patients control over their lifestyle. After developing self-management skills, patients assess their lab data and lifestyles including diet, and understand their condition so that they can work with their physiological data by acquiring knowledge of both the disease and self-care. By making self-supported decisions, the patients will be able to manage their diet, exercise, and medication. Trial Registration: ClinicalTrials.gov NCT06632652; https://clinicaltrials.gov/study/NCT06632652

Background: Yearly screening for microvascular complications of diabetes mellitus (DM), namely diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic foot complications (DFC), is recommended to reduce their incidence, and delay or prevent their progression. Poor adherence to screening is common, but prospective data on the magnitude and predictors of nonadherence to DR, DN, and DFC screening in Singapore are unavailable. Objective: The Understanding Non-Adherence to Diabetes Complications Screening study aims to determine the rates, predictors, and clinical and economic impact of nonadherence to diabetic complications screening in patients with type 2 diabetes in Singapore. The study describes the methodology and participants’ baseline characteristics that may be associated with nonadherence to DM complications screening. Methods: In this prospective, mixed methods, clinic-based study, patients who underwent DR, DN, or DFC screening and were offered an annual rescreening appointment, were recruited from 6 primary care centers. Patients’ sociodemographic, medical, clinical, and patient-reported characteristics were recorded at baseline. Nonadherence to DR, DN, or DFC screening is defined as not attending the annual rescreening appointment within 4 months of the scheduled rescreening date. Adherence and clinical data will be recorded at 16 months post enrollment. Additionally, selected participants and health care professionals will undergo qualitative interviews to elicit barriers or facilitators of adherence to rescreening. Results: Ethical approval was obtained in November 2016. Study enrollment commenced across the 6 sites between June 2018 and February 2019, and baseline data collection ended at all sites in January 2020. 974 eligible patients (2123 screenings; median age of 61.0, IQR 55.0-67.0 years; male: 515, 52.9%; Chinese: 624, 64.1%) consented and completed the baseline assessment. Of these, 734 (75.4%), 603 (61.9%), and 786 (80.7%) attended DR, DN, and DFC screening, respectively. Most (n=793, 81.4%) attended more than 1 complication screening on the same day; had received secondary or lower education (n=701, 71.9%); had hypertension (n=711, 73.4%) and dyslipidemia (n=828, 85.1%); and 43.1% (n=419) were obese (BMI>27.5 kg/m2). Median DM duration and hemoglobin A1c levels were 6.3 (IQR 3.0-12.0) years and 6.9% (6.4%-7.6%), respectively. Over half (n=532, 55.1%) had not received prior DM education. Furthermore, participants reported low levels of diabetes-related self-efficacy (median 1.4, IQR 1.0-3.9 out of 5). Conclusions: At baseline, we have successfully enrolled almost 1000 patients with type 2 diabetes scheduled for annual DR, DN, or DFC rescreening, and potential predictors of nonadherence to rescreening were systematically collected. Follow-up phases will focus on establishing the rates and associated modifiable predictors of nonadherence to DR, DN, or DFC rescreening, which may inform program initiatives.

Background: Patients with spinal cord injury (SCI) who develop urinary tract infection (UTI) present differently than the non-SCI population. UTIs can cause loss of quality of life and even lead to life-threatening complications including urosepsis. Challenges in SCI management include distinguishing symptomatic UTI from asymptomatic bacteriuria (ASB), which occurs often in patients with SCI, and the lack of standardization in UTI diagnosis in SCI. Objective: This study aims to set the foundation for the development of a risk score to improve diagnostic accuracy of UTI after SCI. Methods: This study will use data from the Veterans Health Administration Corporate Data Warehouse from national outpatient clinics. It will use 2 approaches: (1) a case-control study comparing frequency-matched healthy SCI cases (n=2000) with healthy non-SCI controls (n=2000) to establish a physiologic baseline for vital sign and lab measurements after SCI and (2) a retrospective cohort study of patients with SCI (n=400) to determine the positive predictive value of the baseline vital signs and lab measurements found in step 1, from which a threshold for clinically meaningful UTI after SCI will be established. Results: The study was funded in May 2023, and initial data extraction started in early 2024 and is expected to be completed in 2026. Data extraction, analysis, and results for aim 1 were completed as of manuscript submission. For aim 1, we hypothesize that SCI will be associated with lower temperature, heart rate, and systolic blood pressure when compared with non-SCI controls. SCI will also be associated with higher baseline levels of pyuria and peripheral white blood cells when compared with non-SCI controls. Data extraction for aim 2 will begin in year 1, and analysis and results will be completed in year 2. For aim 2, we hypothesize that pyuria, heart rate, and temperature measurements will have a high positive predictive value for clinically meaningful UTI. Conclusions: Once complete, this study will be the basis for our future work developing a risk score to aid with the diagnosis of UTI after SCI and prevent antibiotic overuse in patients with SCI.

Background: Continuous positive airway pressure (CPAP) therapy is the gold standard treatment for treating obstructive sleep apnea (OSA). However, patient adherence to CPAP therapy remains a critical challenge, with many individuals finding it difficult to maintain consistent use due to discomfort, lack of understanding, or perceived inconvenience. Augmented reality (AR) offers a novel approach to overcoming these barriers by providing interactive real-time guidance to users, potentially enhancing adherence rates. Objective: This clinical trial aims to examine the feasibility of AR implementation and the effect of AR on improving CPAP adherence in patients with OSA. Methods: A randomized controlled trial with a parallel assignment will be conducted. Participants will be randomly assigned to either an experimental group receiving AR-guided CPAP therapy or a control group receiving standard care. The study will span 6 months, with assessments at baseline (T0), and with follow-ups at 1 month (T1), 3 months (T2), and 6 months (T3) post intervention. The primary outcome measure is CPAP adherence, defined as using the CPAP device for more than 70% of sleep time, with a minimum of 4 hours per night. Secondary outcomes will evaluate the common adverse effects associated with CPAP therapy, device usability, and time required for CPAP machine use education. Results: This study is funded by the Ministry of Science and Technology, Taiwan (August 2023 to July 2026) and was registered in August 2024 (ClinicalTrials.gov NCT06520592). Participant recruitment is scheduled to begin in April 2025, and by September 2025, we expect to have enrolled 40 participants (50% of the target sample of 80). Preliminary analyses of CPAP adherence at 1 month and usability data are currently underway. Final data collection is anticipated to be completed by December 2025, with results expected to be published by Fall 2026. Conclusions: Anticipated findings suggest that AR-guided CPAP therapy may significantly enhance patient adherence by improving mask fitting and providing effective, interactive education. If validated, this innovative approach could pave the way for more personalized technology-driven interventions in OSA management and other chronic conditions requiring long-term therapy adherence. Trial Registration: ClinicalTrials.gov NCT06520592; https://clinicaltrials.gov/study/NCT06520592

Background: Veterans are more likely to experience chronic pain than civilians, with significant negative impacts on long-term health outcomes. Evidence for the effectiveness of prescription opioids for chronic pain management is limited, and chronic use of opioids is associated with an increased risk of sleep-disordered breathing, cardiovascular complications, and bowel dysfunction, as well as opioid misuse and overdose. Veterans Affairs (VA) and Department of Defense guidelines are prioritizing low-risk, evidence-based interdisciplinary pain management strategies while optimizing pain-related outcomes (PRO) for veterans. Commission on Accreditation of Rehabilitation Facilities (CARF)–Accredited VA Interdisciplinary Pain Rehabilitation Programs (IPRPs) have shared characteristics, while maintaining their unique characteristics as individual pain management programs. Though little is known about the characteristics of VA’s IPRPs (eg, staffing, services, and patients served), implementation, and sustainability of these mandated programs. Objective: The goals of our operational partner-driven evaluation are to (1) characterize IPRPs across multiple program factors, including but not limited to, service delivery methods, team composition, program characteristics, services and modalities offered, and patients served; (2) triangulate data to inform data visualization that characterizes and illustrates the IPRPs individually and collectively as a system of care; and (3) identify patient-reported outcomes (PROs) and metrics to measure program effectiveness and determine overlap across IPRPs. Methods: This partnered-driven program evaluation will use a sequential mixed methods prospective design, including interviews and surveys. The Consolidated Framework for Implementation Research (CFIR), Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, and Expert Recommendations for Implementing Change (ERIC) strategies will be used to contextualize qualitative data. Rapid content analysis will be used to iteratively analyze qualitative data, while descriptive statistics will be used to analyze quantitative data. Datasets will be triangulated to support data visualization for partners to inform clinical and operational decision support. Results: As of April 2025, All IPRP sites are engaged, and survey and interview data have been collected and prepared for analysis. The results and deliverables will inform VA CARF-accredited IPRP characterization, evaluation, and implementation as a learning health system. Conclusions: The results of this evaluation will characterize CARF-accredited IPRPs and identify determinants affecting the implementation of this complex intervention, made up of multiple evidence-based practices. Partner-driven data will inform the state of implementation at each site, and quantitative measures will provide options for collecting standardized outcome measures for continued program evaluation. This operational partner-driven evaluation will inform future efforts for quality improvement to improve veterans’ pain management outcomes. This protocol informs the use of a mixed methods approach to evaluate a multimodal intervention (ie, IPRP), made up of multiple evidence-based practices to treat a complex comorbid condition. Future work may include data management infrastructure development and cost evaluations to inform clinical and operational decision-making.

Background: Stigma toward people with addiction is a well-documented phenomenon that dramatically impacts help-seeking, treatment, and recovery. Interventions aimed at reducing stigma toward those with addiction must overcome the frequent mischaracterization of addiction as a failure of judgment rather than a chronic, treatable illness. Previous research has demonstrated that social contact with people recovering from addiction can promote empathy and reduce stigma, but social contact is difficult to scale. Short, animated storytelling (SAS) is a novel health communication approach that scales easily because it can leapfrog barriers associated with language, culture, literacy, and education levels. Objective: This study will investigate the effect of a cross-culturally accessible SAS video intervention aimed at reducing stigma and increasing empathy toward people with addiction. We also seek to gain insight into the mechanisms of action of this SAS intervention by measuring the contribution of sound design to their effect. Methods: We will conduct a randomized controlled trial with 13,500 adult participants from the United States, the United Kingdom, and South Africa, recruited online via Prolific Academic and randomized into 3 arms, per country. The 2 intervention arms will receive a wordless, social contact–based SAS video, one arm with a soundtrack and one without. The third arm will receive an educational video about addiction. Validated questionnaires will be used to assess our primary outcome, addiction stigma, and secondary outcomes, optimism, warmth toward the subject, and hopefulness, at baseline, immediately post exposure, and 2 weeks later. Ethics clearance was obtained on August 15, 2024, from the Stanford University institutional review board (protocol 76457). Results: This trial was funded in January 2025 by the Heidelberg Institute of Global Health, the Faculty of Medicine at Heidelberg University, in Germany. As of March 2025, no data have been collected. The estimated start date for this trial is May 15, 2025. We expect to complete data collection by July 1, 2025, and expect results to be published in the spring of 2026. Conclusions: Here, we present the protocol for an online, multicountry, randomized controlled trial. This trial is designed to measure the effect of an innovative approach to global health communication (wordless, short, and animated storytelling) on addiction stigma in 3 global regions. These findings will inform the design of future scalable, digital health storytelling interventions for global audiences while exploring the capacity of SAS to shift public health attitudes and perceptions. Furthermore, if effective, the intervention described here could be disseminated broadly via social media and other online platforms. Clinical Trial: ClinicalTrials.gov NCT06705205; https://clinicaltrials.gov/study/NCT06705205

Background: Childhood trauma is pervasive, with approximately 50% of adolescents experiencing at least one potentially traumatic event before adulthood. Eight percent to 33% of potentially traumatic event–exposed adolescents develop posttraumatic stress disorder (PTSD), which can cause extreme suffering and coincides with numerous comorbid illnesses and high-risk behaviors. PTSD can be effectively treated in adolescents through weekly sessions of eye movement desensitization and reprocessing or trauma-focused cognitive behavioral therapy. Despite the availability of these treatments, numerous severely traumatized adolescents do not receive available treatment options due to high treatment avoidance. In adolescents who receive care, a large group of youth does not experience a sufficient symptom decrease after regular treatment. In addition, dropout rates during prolonged treatment are substantial, varying between 10% and 30%. This underscores the need for innovative and brief trauma treatment. Pilot studies indicate that Brief Intensive Trauma Treatment (BITT) can be a safe and effective treatment for adolescents with PTSD. However, randomized controlled trials on its effectiveness are crucial and urgently needed. Objective: This is the first study to test the effectiveness of a 1-week BITT in adolescents with PTSD and comorbid symptoms and their caregivers. Methods: This multicenter, single-blinded randomized controlled trial will be conducted in 4 youth care centers in the European and Caribbean Netherlands: Levvel, Karakter, Fornhese-GGz Centraal, and Mental Health Caribbean (Bonaire). We will randomize adolescents (12-18 years old) with PTSD to a BITT (n=50) or waitlist control group (WLCG; n=50). BITT comprises 1-week (ie, 5 consecutive workdays) intensive trauma treatment, encompassing daily 90-minute manualized sessions of trauma-focused cognitive behavioral therapy and eye movement desensitization and reprocessing. The day begins and ends with psychomotor therapy. Caregivers receive daily parental counseling sessions consisting of psychoeducation and social support skill training. We will conduct measurements at similar intervals for both groups: at baseline; directly after BITT or WLCG; and at 3, 6, and 9 months’ follow-up. The WLCG will receive BITT after the 3-month follow-up assessment. We will assess all study parameters using digital or face-to-face questionnaires and semistructured interviews. We will assess the primary outcome PTSD symptoms using the Child and Adolescent Trauma Screen 2 (CATS-2) and the Clinician-Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition])-Child/Adolescent Version (CAPS-CA-5). Results: As of September 2022, we enrolled 104 participants. Data will be collected until December 2025. Results are expected to be published in the summer of 2026. Conclusions: This first, innovative study on BITT’s effectiveness may enhance treatment outcomes for PTSD by preventing dropout, reducing avoidance, shortening therapy duration, and empowering therapists by working together intensively. This research will provide valuable insights across cultures for treating severely traumatized adolescents who do not benefit sufficiently from regular treatment. Trial Registration: ClinicalTrials.gov NCT06143982, http://clinicaltrials.gov/ct2/show/NCT06143982

Background: The identification of moderators of exposure-based cognitive behavior therapy (EXCBT) outcome has the potential to: (1) guide the judicious application of the limited resource of EXCBT, and/or (2) identify additional treatment targets for ameliorating the deleterious effects of an identified moderator, thereby enhancing clinical response. Experimental and clinical studies have provided intriguing findings for the moderating influence of positive affect on EXCBT outcomes. Mixed findings for state positive affect (at the time of extinction/exposure trials) as a predictor of EXCBT outcomes stand in contrast to evidence that baseline levels of trait positive affect may be a more effective predictor. As such, questions remain about the best way to assess positive affect as a potential treatment moderator. Objective: This study was designed to investigate: (1) the relative value of state and trait positive affect for predicting the outcome of a single-session virtual-reality exposure intervention for public speaking anxiety in adults attending college, and (2) the role of three related constructs—optimism, hopefulness, and mental health self-efficacy—that may explain the predictive significance of trait positive affect. Methods: State affect is manipulated at an experimental level with affect induction procedures; trait positive affect is measured at baseline. Three dependent measures–a primary outcome of public speaking anxiety and secondary outcomes of social phobia and self-reported valence--are examined. This study relies on a team science approach and is conducted across 12 collaborating sites through the Exposure Therapy Consortium, allowing for replication of all findings across diverse study sites across the world. Results: Data collection for the current study began in October 2024 and is projected to end by August 2025. We expect to complete data analysis and submit results for publication in approximately October 2025. Conclusions: The current study will help to clarify the relationship between positive affect (state and trait), exposure learning, and three related constructs (optimism, hopefulness, mental health self-efficacy). These findings will illuminate strategies for future treatment improvement and enhanced efficacy. Clinical Trial: ClinicalTrials.gov Identifier NCT06593847; https://clinicaltrials.gov/study/NCT06593847

Background: Measles and polio pose significant public health challenges globally, particularly in low-resource settings such as the Philippines, where vaccine coverage falls short of the World Health Organization’s (WHO’s) targets, with hard-to-reach populations contributing to the “last mile.” This research addresses the “last mile” challenge in routine immunization efforts by bridging the vaccination gap in marginalized populations. Objective: We describe the implementation of a cluster randomized controlled trial to evaluate the impact of an education toolkit aimed at improving confidence in measles and polio vaccines among communities living in extreme poverty in the Philippines. Methods: Developed with local stakeholders, our intervention consists of a 10-minute video and vaccination reminders delivered by health trainers. It is embedded within the Soap Opera Trial, a large cluster randomized controlled trial conducted by the International Care Ministries that evaluates a 15-episode soap opera series combining drama with aspirational messages on hope, self-worth, and education, aimed at improving participants’ knowledge and practices in health, hygiene, nutrition, and livelihood. A total of 180 communities with 5400 participants will be randomly assigned to the intervention and control arms. By leveraging an existing community-based education program on health and livelihood run by our local partner, the proposed intervention will be delivered to participants in the intervention arm of the existing program, while those in the control arm will receive standard participatory adult learning sessions on health education. The primary outcome is the first-dose measles-containing vaccine coverage among participants’ children aged 1 year. Secondary outcomes include the 2-dose measles-containing vaccine coverage among children aged 2 to 6 years, polio vaccination coverage among children aged 1 year, and participants’ knowledge of measles and polio vaccines. The absolute differences in these outcomes between the intervention and control arms will be estimated using generalized estimating equations while adjusting for baseline levels and covariates. In addition, we will conduct a process evaluation. Results: Between January 31 and February 29, 2024, we recruited 66.9% (3613/5400) of the participants for the trial. Data collection is ongoing at the time of manuscript submission. Conclusions: Findings from this trial will provide critical insights into effective strategies for enhancing vaccine confidence and uptake in marginalized populations. By leveraging community-based approaches and local partnerships, this study aims to improve public health responses to vaccine-preventable diseases and contribute to global efforts to eradicate measles and polio. Furthermore, the findings will inform scalable interventions that can be adapted to similar contexts, potentially reducing health disparities and advancing global health equity. Trial Registration: ClinicalTrials.gov NCT06218368; https://clinicaltrials.gov/study/NCT06218368

Background: Sub-Saharan Africa (SSA) bears the highest global burden of under-5 mortality, with congenital heart disease (CHD) as a major contributor. Despite advancements in high-income countries, CHD-related mortality in SSA remains largely unchanged due to limited diagnostic capacity and centralized health care. While pulse oximetry aids early detection, confirmation typically relies on echocardiography, a procedure constrained by a shortage of specialized personnel. Artificial intelligence (AI) offers a promising solution to bridge this diagnostic gap. Objective: This study aims to develop an AI-assisted echocardiography system that enables nonexpert operators, such as nurses, midwives, and medical doctors, to perform basic cardiac ultrasound sweeps on neonates suspected of CHD and extract accurate cardiac images for remote interpretation by a pediatric cardiologist. Methods: The study will use a 2-phase approach to develop a deep learning model for real-time cardiac view detection in neonatal echocardiography, utilizing data from St. Padre Pio Hospital in Cameroon and the Red Cross War Memorial Children’s Hospital in South Africa to ensure demographic diversity. In phase 1, the model will be pretrained on retrospective data from nearly 500 neonates (0-28 days old). Phase 2 will fine-tune the model using prospective data from 1000 neonates, which include background elements absent in the retrospective dataset, enabling adaptation to local clinical environments. The datasets will consist of short and continuous echocardiographic video clips covering 10 standard cardiac views, as defined by the American Society of Echocardiography. The model architecture will leverage convolutional neural networks and convolutional long short-term memory layers, inspired by the interleaved visual memory framework, which integrates fast and slow feature extractors via a shared temporal memory mechanism. Video preprocessing, annotation with predefined cardiac view codes using Labelbox, and training with TensorFlow and PyTorch will be performed. Reinforcement learning will guide the dynamic use of feature extractors during training. Iterative refinement, informed by clinical input, will ensure that the model effectively distinguishes correct from incorrect views in real time, enhancing its usability in resource-limited settings. Results: Retrospective data collection for the project began in September 2024, and to date, data from 308 babies have been collected and labeled. In parallel, the initial model framework has been developed and training initiated using a subset of the labeled data. The project is currently in the intensive execution phase, with all objectives progressing in parallel and final results expected within 10 months. Conclusions: The AI-assisted echocardiography model developed in this project holds promise for improving early CHD diagnosis and care in SSA and other low-resource settings.

Background: Patient satisfaction with total knee arthroplasty (TKA) is strongly influenced by alignment between expectations and outcomes. Despite a satisfaction rate of 80-90%, dissatisfaction affects 10-20% of patients and is expected grow with the increasing volume of TKA procedures globally. Misaligned expectations, often driven by unrealistic or overly optimistic recovery views, can lead to unmet goals, dissatisfaction and unnecessary healthcare utilisation. Addressing these gaps through improved pre-surgical education has the potential for enhancing patient satisfaction, optimising outcomes and reducing burden on the healthcare system. Objective: The main objectives of this study are to develop and evaluate a pre-surgical educational program, which focusses on patient expectations of surgical outcomes, and facilitates patients setting realistic post-surgical goals. We will also assess ability of the program to modify patient expectations, impact expectation fulfillment, improve satisfaction with post-surgical outcomes and impact patient health literacy. Methods: A targeted education program will be developed in consultation with key stakeholder groups including consumer advocates, orthopaedic surgeons, healthcare providers, physiotherapy and rehabilitation specialists to address realistic patient expectations of TKA outcomes. Alpha testing with consumers will provide insights of the appropriateness of the program being developed. The ability of the program to modify patient expectation will be assessed in a longitudinal, parallel group, two-armed randomized controlled trial, involving 150 patients identified by their orthopaedic surgeon as requiring TKA. Randomly allocated participants will take part in the education program within 5 weeks prior to their scheduled TKA (intervention group) or will be allocated to standard preoperative education (control group). The primary outcome will be a change in the Hospital for Special Surgery Total Knee Replacement Expectations Survey (HSS-TKR) transformed score measured prior to and following the intervention. At 6 months following TKA, expectation fulfillment and overall satisfaction will be measured. Inferential statistics will be used to test for differences in, or associations between, outcome measures within and between study arms. Methods appropriate to both dependent and independent samples will be utilised, including non-parametric methods for data in violation of normality and variance assumptions. Results: The education program will be developed from January to September 2025. The randomized trial will run from October 2025 to March 2027, with data analysis completed by April 2027 and results published in peer-reviewed journals by September 2027. Conclusions: This study will provide evidence on the effectiveness of a novel pre-surgical educational program in shaping patient expectations, promoting realistic goal setting, and improving TKA satisfaction. Findings will inform strategies to improve TKA patient care, health literacy and satisfaction, potentially reducing dissatisfaction and associated burden on healthcare. Clinical Trial: Australian New Zealand Clinical Trials Registry ACTRN12624001465549p; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388664

Background: Parkinson disease (PD), a prevalent neurodegenerative disorder characterized by motor and nonmotor symptoms, is becoming increasingly prevalent worldwide. Conventional treatment for PD involves dopamine therapy, including levodopa; however, this treatment is ineffective for nonmotor symptoms and may cause adverse effects. The gut-brain axis has been hypothesized to promote PD, and regulation of gut microbiome, which modulates the gut-brain axis, is emerging as a treatment target. Acupuncture and moxibustion exert therapeutic effects on PD and modulate the gut microbial composition. Objective: We present a protocol for analyzing the effects of acupuncture and moxibustion on gut microbiome and exploring its association with symptoms in patients with PD. Methods: This single-group, prospective, observational study will recruit 60 patients with idiopathic PD and 20 healthy participants. Baseline gut microbiome patterns and motor and nonmotor symptoms of both groups will be compared. Patients with PD will be treated with acupuncture, moxibustion, and intradermal acupuncture twice a week for 12 weeks (24 sessions total). Motor and nonmotor symptoms and gut microbiome changes in patients with PD will be compared before starting treatment (day 0), during treatment (6 weeks), at the end of treatment (12 weeks), and 2 months after the end of treatment (20 weeks). The correlation between motor and nonmotor symptoms of PD changed by acupuncture and moxibustion treatment and changes in gut microbiome will be analyzed. Healthy participants will be assessed for motor and nonmotor symptoms of PD and gut microbiome after screening. Results: This study was supported by the National Research Foundation of Korea, funded by the Ministry of Science and ICT (Information and Communication Technology), Republic of Korea, and recruitment for the study started on October 21, 2021. As of February 19, 2025, recruitment and observation ended, and data analysis is being conducted. Conclusions: This is the first clinical study to assess the effects of acupuncture and moxibustion on gut microbiome and explore its association with symptoms in patients with PD. The results will provide clinical evidence to explain the microbiome-gut-brain axis mechanism of acupuncture and moxibustion for PD and suggest the possibility of acupuncture as an alternative therapy for PD. Trial Registration: Clinical Research Information Service KCT0006669; https://tinyurl.com/42jsxs5a

Background: Iron deficiency is the most widespread nutritional deficiency worldwide, and it is the primary cause of anemia, particularly in low- and middle-income countries such as Indonesia. Iron deficiency has a multifactorial etiology involving complex interactions between genetic factors, especially the transmembrane protease serine 6 (TMPRSS6) rs855791 variant, which encodes matriptase-2, a protein involved in regulating hepcidin expression, and nongenetic factors, including sociodemographics, nutritional status, iron intake, and menstrual patterns. Women of reproductive age, including medical students, are susceptible to iron deficiency owing to unhealthy dietary habits, growth requirements, and menstruation. Iron deficiency among medical students may lead to decreased academic performance and productivity. Additionally, as future mothers, women may experience a heightened risk of delivering children with intellectual disabilities and various psychosocial impairments. Owing to the significant consequences of this condition, identifying the underlying causes of iron deficiency is crucial. The high prevalence of iron deficiency in Indonesia poses a challenge in addressing these contributing factors to effectively reduce its occurrence. Objective: This study aims to investigate the association of the TMPRSS6 rs855791 variant and nongenetic factors with iron deficiency among female medical students in Yogyakarta, Indonesia. Methods: This is a case-control study. We will recruit female medical students from the Faculty of Medicine, Public Health, and Nursing of Universitas Gadjah Mada in Yogyakarta, Indonesia. The inclusion criteria are being a final-year female undergraduate medical student who has not entered the clinical clerkship phase, aged 18 to 24 years, not pregnant, providing written consent, and having no history of chronic and inflammatory diseases, congenital diseases, hematological disorders, or blood transfusions during the last 3 months. Participants will be excluded if the C-reactive protein level is higher than 5 mg/L. Participants will be further grouped according to iron status criteria. Profiles of hemogram and iron markers will be compared between the case and control groups using the independent samples 2-tailed t test or the Mann-Whitney U test, while genotype and allele frequencies will be analyzed using the chi-square test. One-way ANOVA or the Kruskal-Wallis test will be used to assess the impact of different genotypes on iron marker levels. Multivariate analysis will be performed with logistic regression to determine factors independently associated with iron deficiency risk. P≤.05 will be considered statistically significant. Results: The study received funding in January 2025. Data collection began in February 2025 and is anticipated to conclude by October 2025. At the time of manuscript submission, 115 participants had been enrolled. The study findings are expected to be published in 2026. Conclusions: This study will determine the interaction between the TMPRSS6 rs855791 variant and nongenetic factors that contribute to the risk of iron deficiency among female medical students in Yogyakarta, Indonesia.

According to the action-specific account of perception, perception is scaled by one’s ability to act in interaction with environmental objects. Witt et al. (2005) were the first to report the tool-use effect that supports this notion. In their study, participants either used a reach-extending tool to touch the targets or reached out to the targets with their finger. Their results indicated that targets appeared closer when participants reached with the tool. The present study aims to directly replicate their study as a registered report to confirm the previous findings. Additionally, we will further investigate whether the inherent functionality of a tool influences perceived distance. To explore this, the tool’s inherent functionality will be manipulated while maintaining the tool’s physical length unchanged. In the same reaching task, we predict that alterations in a tool’s functionality are likely to influence perceived distance, even if the tool’s physical length remains constant.

Background: Heterogeneity in outcome selection and measurement methods has been noted in studies examining the minimization of physical restraint use in adult intensive care units (ICUs). This variability undermines evidence synthesis, limiting the development of evidence-based approaches to minimize restraint use and improve patient outcomes. Objective: This protocol outlines the methods for developing international consensus on core outcomes and standardized measurement approaches for studies focused on physical restraint minimization in adult ICUs. Methods: We will follow the Core Outcome Measures in Effectiveness Trials Handbook. Drawing on our previous work, including a scoping review of studies on physical restraint minimization and interviews with family members, we will compile a list of potential outcomes for a 2-round Delphi survey. In round 1, stakeholders will rank outcomes using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) scale. In round 2, they will review the aggregated results for rescoring and refinement. A consensus meeting using the modified nominal group technique will finalize the core outcome set, followed by another meeting to agree on standardized measurement methods. Results: Research ethics board approval is in progress. Recruitment has not yet begun. Project initiation is anticipated in January 2026, with completion planned for April 2027 and publication of findings is expected by June 2027. Conclusions: This study will be the first to establish a core outcome set and a core outcome measurement set for minimizing restraint use in adult ICUs. Standardization will enhance comparability across future studies and support evidence synthesis. The resulting outcome and measurement sets will provide a foundation for high-quality research and guide evidence-based strategies to improve patient safety and care in ICU settings. Trial Registration: COMET Initiative 3368; https://tinyurl.com/yubfzre9