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.

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

Background: Catatonia is a severe psychomotor syndrome predominantly associated with depressive, bipolar, and psychotic disorders. Untreated catatonia has a 10% mortality rate and may lead to complications such as renal failure, rhabdomyolysis, pneumonia, embolism, and contractures. High doses of the benzodiazepine lorazepam, a gamma-aminobutyric acid (GABA)-A receptor modulator, are the primary pharmacological treatment, enhancing GABA’s inhibitory effect, potentially reducing symptoms of catatonia. However, lorazepam is ineffective in about 25% of cases, leaving electroconvulsive therapy (ECT) as the only well-investigated alternative. Although often effective, ECT may have severe side effects and is not easily accepted among patients and caregivers. Therefore, there is an urgent need for novel therapies for catatonia. Sodium oxybate, a GABA precursor and GABA-B receptor agonist, is a promising alternative treatment based on observational data, but its efficacy has never been thoroughly investigated. Objective: This study aims to evaluate the efficacy and safety of sodium oxybate in treating catatonia unresponsive to lorazepam, while also capturing the natural course and determinants of catatonia through an observational cohort. Methods: The Laborit trial consists of a cohort study and an embedded single-blind randomized controlled trial (RCT). Patients with catatonia admitted to a psychiatric ward may join the study’s cohort, where their clinical characteristics are recorded. Standard care, including lorazepam up to 24 mg/day, will be administered. On day 4, the Bush Francis Catatonia Rating Scale (BFCRS) will be used to measure symptom response. Patients with ≤50% improvement on the BFCRS, compared to the score at start, will be eligible for the trial. A total of 42 patients will be randomly assigned to either the sodium oxybate group, after a 2-day lorazepam reduction period, or the continuation of lorazepam. The primary endpoint is response, measured by the BFCRS score change after 4 days of treatment. A ≥50% reduction in BFCRS will define a responder, who will continue allocated treatment for an additional 10 days, with a secondary endpoint at 14 days. Data will be analyzed using intention-to-treat and per-protocol methods, with chi-square and logistic regression tests to compare group response and remission rates. Results: This study was funded by the Dutch Brain Foundation (Hersenstichting) in December 2020. The study protocol was approved by the Amsterdam UMC Ethics Board on May 22, 2023. As of March 2025, the first 4 participants have been included in the cohort, with no trial participants enrolled yet. Conclusions: If positive, the results of this RCT may pave the way for international catatonia researchers and clinicians to introduce a new pharmacological treatment option for catatonia. Implementation could potentially benefit patients who endure this severe syndrome and present health care professionals with an additional treatment option. Trial Registration: ISRCTN ISRCTN11236443; https://tinyurl.com/4px5s4aa

Background: Diabetic retinopathy (DR) remains the primary vision complication of diabetes and the leading cause of blindness among adults, with up to 30% prevalence among low-income populations. Tele-retina is a cost-effective screening alternative to vision loss prevention, yet there is an adverse association between screening and income. Intersectionality theory notes that barriers to achieving health equity result from the intersection of personal and social characteristics. Experiences at this intersection are influenced by interpersonal and structural systems of oppression. Studies have found that tele-retina is the preferred strategy over standard of care screening for at-risk populations. No study has assessed the economic equity impact of DR screening using a theoretical foundation. Objective: This study aims to address shortcomings related to the utilization of intersectionality theory in the economic evaluation of DR screening. We propose conducting a distributional cost-effectiveness analysis (DCEA) of the tele-retina program. Methods: The study will be undertaken using a deductive theoretical drive sequential multimethod approach, consisting of two studies: (1) a modified Delphi study and (2) DCEA. The Delphi panel (patient partners, field experts, and decision makers; N=35-50) will select the social constructs (eg, age, gender) for at-risk populations and potential trade-offs between health maximization and equity. The research will be guided by a social theory framework (intersectionality theory) to understand the impact of social constructs on economic outcomes. Social constructs that are selected by the Delphi panel will be integrated into the validated tele-retina cost-effectiveness analysis model, which will serve as a case study for DCEA. Results: We have submitted the research ethics board application to the University Health Network Research Ethics Board and are expecting to begin recruitment for the Delphi study in Spring 2025. We anticipate beginning work on the model in the summer of 2025 and completing it by early 2026. Conclusions: The Delphi study will provide an understanding of which social factors are deemed necessary by the stakeholders for guiding the inequity in care access. Study results will offer information related to the net health benefit of the intervention and the health equity impact of the tele-retina program, hence providing a more comprehensive valuation of the tele-retina program, which is informative to policy makers and governments whose goal is to mitigate the drivers of health inequities. We anticipate that each of these drivers will raise important questions regarding the implications for decision-making that may have not yet been addressed by Canadian health technology assessment bodies, such as the Canada Drug Agency. This is the first Canadian study to (1) have social constructs for DCEA selected by the Delphi panel, (2) mainstream how health equity framework and social constructs are used in economic assessment, (3) improve DR screening programs by using health equity lens, and (4) scale and adopt “de-novo” integration of social constructs in economic models for program evaluation.

Background: Pain management in children with cancer may be inadequate due to poor pain assessment, and evaluation using suitable tools is necessary. Despite the availability of many pain assessment scales, few studies have summarized the existing assessment tools, making it challenging to select a suitable scale. Objective: This scoping review aims to map existing pain assessment tools for children with cancer and provide a comprehensive overview of pediatric cancer-related pain screening and assessment tools. Methods: The scoping review will be conducted according to the guidelines by the Joanna Briggs Institute and reported following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) framework. Electronic databases, including PubMed, CINAHL, CENTRAL, ICHUSHI (Japan Medical Abstracts Society), and Embase, will be searched to identify eligible studies, without date or language restrictions. We defined the eligibility criteria based on the PCC (Population, Concept, and Context) format. Studies that focused on assessment tools for evaluating pain in children (aged 0-18 years) with cancer in a hospital or at home will be included. Although there are no restrictions on study design, protocols and conference abstracts will be excluded. Two or more reviewers will select studies by reviewing the full text of relevant articles identified by titles and abstracts, and disagreements will be resolved through discussion. Two or more reviewers will extract predefined data items, including characteristics of included studies (eg, author name, title of publication, year of publication, purpose of study, study setting, study population, outline of the assessment tool, study design, and findings) and the characteristics of assessment tools (eg, types of tools, target population, assessor, validity, instructions, precautions, and advantages and disadvantages of the tools). Pain assessment tools will be summarized in tabular format and described in a narrative synthesis. Results: Through electronic database searches on November 20, 2023, we identified 3748 articles. This review will provide a comprehensive overview of pain assessment tools. The final report is planned for submission to a peer-reviewed journal in 2025. Conclusions: This scoping review is the first comprehensive effort to map existing tools on pediatric cancer-related pain assessment tools for infants, children, and adolescents aged <18 years, according to developmental stages. Based on the findings of this study, we will discuss future clinical and research implications for pain assessment and management in children with cancer. The findings are expected to enhance pain management practices in children with cancer and inform health care providers, policy makers, and other stakeholders.

Background: Despite documented effectiveness, the public health impact of vaccinations is severely limited by misperceptions, hesitancy, and poor acceptance. Messaging from health care providers has not yet been optimized to overcome these barriers and has not been tailored to groups that face health disparities, such as rural Americans. Because vaccines have become controversial, as illustrated by the public response to the SARS-CoV-2 vaccines, traditional approaches that use persuasive education or advice to change perspectives are unlikely to have long-term effects and may even be counterproductive. Alternatively, motivational interviewing (MI) is a conversational approach to address modifiable behavior and its empathic nature can be useful when navigating challenging topics. Although MI has been found to be efficacious in improving vaccination rates among children and adolescents, it is unknown whether MI can reduce vaccine hesitancy and health disparities among underserved rural adults. Further, the ideal mode of delivery for MI is unknown, especially “dose,” “intensity,” and integration with mobile health (mHealth). Therefore, it is essential to investigate the efficacy of MI in promoting vaccine uptake in rural populations to reduce health disparities. Objective: This study aims to develop and evaluate the feasibility, acceptability, and preliminary efficacy of our mHealth-based MI intervention to diminish SARS-CoV-2 vaccine hesitancy (MOTIVACC). Methods: This pilot study uses mixed methods. A 2-phase study will be conducted: convening a community advisory panel to understand barriers and facilitators to vaccination and mHealth uptake among adults (phase 1, n=16-20), and a pilot 3-group single-blind randomized controlled trial (RCT) for 8 weeks (phase 2, N=60). In the RCT, we recruit adults who have received no previous dose of the COVID-19 vaccine and randomize them into one of three arms: standard MI (SMI; n=20), intensive MI (IMI; n=20), or mHealth-based MOTIVACC (n=20). The primary RCT outcomes are positive change in vaccine hesitancy and intention to obtain the vaccines, measured on Likert scales. The secondary RCT outcome is the actual vaccine receipt. Results: Phase 1 of this study was approved by the ethics committees of both the University of Oklahoma and Oklahoma State University in July 2022, and was completed in June 2023. Phase 2 of this study was approved by the ethics committee at the University of Oklahoma in April 2024. Conclusions: This randomized trial will evaluate the preliminary efficacy of MI for targeting SARS-CoV-2 vaccine hesitancy, as well as compare traditional MI versus mHealth-based MI. This will provide pivotal data on scalable strategies to assist in navigating vaccine hesitancy, including in rural populations. Trial Registration: ClinicalTrials.gov NCT05977192; https://clinicaltrials.gov/study/NCT05977192

Background: Functional neurological disorder (FND), including functional movement disorders (FMDs), arises from disruptions in the perception-action cycle, where maladaptive cognitive learning processes reduce the sense of agency and motor control. FND significantly impacts quality of life, with patients often experiencing physical disability and psychological distress. Extended reality (XR) technologies present a novel therapeutic opportunity by leveraging biofeedback training to target sensory attenuation and amplification mechanisms, aiming to restore motor function and the sense of agency. Objective: This study aims to coproduce and evaluate the usability of an XR technology platform for FND rehabilitation, focusing on functional limb weakness. The platform integrates biofeedback training with haptic and visual feedback to support motor relearning and control. Methods: We propose to use an experience-based co-design framework to engage patients with FND, caregivers, and health care professionals in collaboratively designing the XR platform. Stakeholders can share their experiences through narrative interviews and co-design workshops, which can identify emotional touchpoints and prioritized patient-centered needs. Insights will be synthesized through qualitative analysis and used to guide the development of system requirements via quality function deployment, ensuring that the platform aligns with user needs. XR training tasks—virtual reality relaxation, XR position feedback, and XR force feedback—will be integrated as needed into a unified therapeutic game experience through 4-week Agile sprints. Usability will be assessed using the System Usability Scale and qualitative feedback, with themes analyzed in NVivo to identify key areas for subsequent improvement. Results: High usability scores (>85) were recorded for the XR position feedback tasks in the predesign study, reflecting excellent usability and participant satisfaction. However, the virtual reality relaxation and XR force feedback tasks exhibited interindividual variability, underscoring the need for personalization. Key themes included customization, comfort, accessibility, and XR technological quality, ensuring that the XR platform effectively addressed diverse patient needs. The predesign study highlighted the potential of XR technology for FMD rehabilitation by integrating biofeedback training into a patient-centered game design framework. Approaches such as experience-based co-design and quality function deployment can support coproduction by systematically addressing usability and accessibility challenges. Brain-based metrics may further strengthen this evaluation. Accordingly, this study will use portable brain imaging to capture dynamic functional connectivity in key brain regions, enabling personalized interventions. Conclusions: Through coproduction and iterative refinement, this study aims to demonstrate the promise of personalized XR gaming technology as a scalable, at-home solution for FMD rehabilitation. In this context, personalization and accessibility are critical for optimizing usability and long-term clinical outcomes, paving the way for at-home implementation within the FND stepped care model.

Background: Advancements in artificial intelligence (AI) have driven substantial breakthroughs in computer-aided detection (CAD) for chest x-ray (CXR) imaging. The National Taiwan University Hospital research team previously developed an AI-based emergency CXR system (Capstone project), which led to the creation of a CXR module. This CXR module has an established model supported by extensive research and is ready for application in clinical trials without requiring additional model training. This study will use 3 submodules of the system: detection of misplaced endotracheal tubes, detection of misplaced nasogastric tubes, and identification of pneumothorax. Objective: This study aims to apply a real-time CXR CAD system in emergency and critical care settings to evaluate its clinical and economic benefits without requiring additional CXR examinations or altering standard care and procedures. The study will evaluate the impact of CAD system on mortality reduction, postintubation complications, hospital stay duration, workload, and interpretation time, as wells as conduct a cost-effectiveness comparison with standard care. Methods: This study adopts a pilot trial and cluster randomized controlled trial design, with random assignment conducted at the ward level. In the intervention group, units are granted access to AI diagnostic results, while the control group continues standard care practices. Consent will be obtained from attending physicians, residents, and advanced practice nurses in each participating ward. Once consent is secured, these health care providers in the intervention group will be authorized to use the CAD system. Intervention units will have access to AI-generated interpretations, whereas control units will maintain routine medical procedures without access to the AI diagnostic outputs. Results: The study was funded in September 2024. Data collection is expected to last from January 2026 to December 2027. Conclusions: This study anticipates that the real-time CXR CAD system will automate the identification and detection of misplaced endotracheal and nasogastric tubes on CXRs, as well as assist clinicians in diagnosing pneumothorax. By reducing the workload of physicians, the system is expected to shorten the time required to detect tube misplacement and pneumothorax, decrease patient mortality and hospital stays, and ultimately lower health care costs.

Background: Rare diseases (RDs) have gained attention in public policy due to their complexity and low prevalence and the challenges they present in health care settings. Comprehensive care for people with RDs requires strengthening of services, programs, and care levels. It is imperative to make digital health tools available to support epidemiological surveillance, facilitate patient follow-up, and enhance the education and awareness of health care professionals (HCPs) regarding these conditions. Objective: This study aims to implement enhanced actions aligned with the Brazilian National Policy for Comprehensive Care for People with Rare Diseases to improve the attention and care provided to individuals. This will be achieved by developing a computational tool and establishing guidelines to optimize the regulation of the reference services for RDs, providing updated information to expedite diagnosis and promote collaboration. Methods: The methodology includes mapping the regulation processes in the Clinics Hospital of Ribeirão Preto Health Complex. Participants will include HCPs from the hospital complex and associated primary care centers and patients with a confirmed or suspected RD selected through medical records and patient associations. Data collection methods include questionnaires, semistructured interviews, and patient tracking using health information systems. The project will apply the 5W2H (what, who, where, when, why, how, and how much) framework to align tasks, responsibilities, and resources. Integrating digital tools adhering to the findability, accessibility, interoperability, and reusability principles will promote real-time monitoring, improved resource allocation, and enhanced workflow efficiency. Training initiatives will boost awareness and capacity among HCPs, while the computational tool seeks to streamline patient follow-up and tracking. Digital integration and interoperability will reduce referral process inefficiencies and support evidence-based decision-making. Education and awareness campaigns will fill knowledge gaps among HCPs and patients. Results: Ethics approval was granted on December 9, 2024. We conducted technical meetings with the IT team to align procedures for obtaining secondary data. Concurrently, we identified key guidelines and applied a knowledge management maturity questionnaire based on which we began mapping RD-related management processes. A computational ontology is currently under development to ensure semantic interoperability. This framework supported initiatives promoting education and awareness regarding RDs, targeting HCPs and patients. Conclusions: The study emphasizes the potential of digital health solutions to transform RD care by improving coordination, resource allocation, and stakeholder education. When effectively adopted, these solutions can enhance access to specialized care, reduce inefficiencies, and inform public health policies. Future efforts will focus on expanding the tool’s implementation, refining its functionalities, and evaluating its long-term impact on patient outcomes and system efficiency. This initiative highlights the crucial role of integrating digital technologies in managing RDs and underscores the need for ongoing collaboration among health care stakeholders to achieve sustainable improvements in patient care and policy development.

Background: Chronic pain is a debilitating condition that disproportionately impacts US veterans who manage numerous negative pain-related outcomes. There is an urgent need for accessible, engaging, and innovative treatments that can help veterans with chronic pain better self-manage their pain at home and improve their daily functioning. Technology-delivered acceptance- and mindfulness-based interventions for pain have shown strong efficacy, particularly when they are engaging and tailored to specific client needs. However, more research is needed to assess the impact of such interventions, particularly in terms of pain-related functioning and quality of life. Objective: The primary aim of this study is to test the efficacy of Veteran Acceptance and Commitment Therapy for Chronic Pain (VACT-CP), an online self-management pain program, compared to an active online control (Online Pain School) for improving pain-related functioning in a 3-site randomized controlled trial. The secondary aim is to explore psychological flexibility as a potential mediator between pain severity and pain-related functioning. Methods: This study will use a mixed methods approach to examine the efficacy of VACT-CP in a 2-arm, multisite, randomized controlled superiority trial including 200 participants with chronic musculoskeletal pain compared to Online Pain School. Participants will be assigned to 1 of these 2 online interventions. Both interventions will include 7 modules delivered over 7 weeks, with each module lasting approximately 15 minutes. Mixed effects models will be used to analyze the primary hypothesis that participants in the VACT-CP group will have greater improvement in pain-related functioning (Brief Pain Inventory–Interference subscale) than those in the active control group (Online Pain School). The main acceptance and commitment therapy process mediator (ie, Multidimensional Psychological Flexibility Inventory), pain-related functioning outcomes (Brief Pain Inventory–Interference subscale), and quality of life (Veterans RAND 36-Item Health Survey) will be measured at baseline, end of treatment, and 3 and 6 months after treatment. In addition, qualitative exit interviews will be conducted with a random set of 30 VACT-CP users (n=10, 33% per site) to obtain intervention usability, feasibility, and acceptability information. Results: The recruitment for this study began in January 2025. It is expected to continue through January 2027. Data collection is expected to be completed by June 2027, and primary data analyses are expected to be completed by early 2028. Conclusions: Online interventions such as VACT-CP and Online Pain School have the potential to expand access to behavioral interventions that improve quality of life and provide nonpharmacological pain treatment options for veterans experiencing chronic pain. However, research on their impact and underlying mechanisms of change is required to support this area of potential at-home programming. Trial Registration: ClinicalTrials.gov NCT06058624; https://clinicaltrials.gov/study/NCT06058624

Background: Probation officers and other professionals who work with youth in the legal system often experience high chronic workplace stress, which can contribute over time to elevations in anxiety, depression, and workplace burnout. Emotion dysregulation appears to function as a common mechanism underlying these elevations, and growing evidence suggests it can be improved with mindfulness meditation. Implemented successfully, app-based meditation programs could provide professionals with real-time tools for mitigating the effects of chronic workplace stress. Objective: This paper describes the protocol for a hybrid type 2 effectiveness-implementation pilot randomized controlled trial (RCT) of Bodhi AIM+, a meditation app adapted with and for professionals who work with youth in the legal system. The adaptation process and implementation plan, as well as the pilot RCT design, were guided by theoretically driven implementation science frameworks. The primary outcome of the pilot RCT is app adherence (ie, ongoing app usage per objective analytics data). Methods: The RCT will be fully remote. Officers and other professionals who work with youth in the legal system (N=50) will be individually randomized to use the meditation app or an active control app matched for time and structure. All participants will be asked to follow a 30-day path of brief audio- or video-guided content and invited to use additional app features as desired. In-app analytics will capture the objective usage of each feature. An adaptive engagement design will be employed to engage nonusers of both apps, whereby analytics data indicating nonuse will trigger additional support (eg, text messages promoting engagement). Mental health outcomes and potential moderators and covariates will be self-reported at baseline, posttest, and 6 months. Participants will also complete 1-week bursts of ecological momentary assessment (EMA) at baseline and over the last week of the intervention to capture the mechanistic target (ie, emotion regulation) in real time. All participants will be invited to complete qualitative posttest interviews. Descriptive statistics will be calculated for quantitative data. Qualitative data will be analyzed using a combined deductive-inductive approach. The quantitative and qualitative data will be incorporated into a mixed methods triangulation design, allowing for the evaluation of app adherence and other implementation outcomes as well as related barriers and facilitators to implementation. Results: Enrollment into the trial started in December 2024 and is currently underway. Study results are anticipated to be available in 2026. Conclusions: Completion of this pilot trial will inform a future, fully powered RCT to formally evaluate the effectiveness and implementation of Bodhi AIM+. Its use of implementation science methods, coupled with digital technology, positions the present study not only to help make meditation tools available to an important workforce at scale but also to inform broader efforts at implementing and evaluating health apps within workplace settings. Trial Registration: ClincialTrials.gov NCT06555172; https://clinicaltrials.gov/study/NCT06555172

Background: For young people who have experienced homelessness, relative housing stability alone is insufficient to achieve socioeconomic inclusion. There is little peer-reviewed research investigating interventions targeting socioeconomic inclusion outcomes for youth who have experienced homelessness. Our previous community-engaged work signaled that identity capital (purpose, control, self-efficacy, and self-esteem) may mediate socioeconomic inclusion outcomes for youth exiting homelessness. This 12-month pilot randomized controlled trial (RCT) explores whether portable rent subsidies and an intervention targeting identity capital hold promise as a way to facilitate socioeconomic inclusion for youth exiting homelessness and living in market rent housing in Ontario, Canada. Objective: The objectives of this study were (1) to examine the feasibility and acceptability of an RCT of targeted economic and identity-based supports to foster socioeconomic inclusion (primary objective), (2) to estimate the effect of adding identity-based supports to economic supports (intervention group) compared with economic supports alone (control group) at the 12-month end point with respect to self-reported proxy indicators of socioeconomic inclusion (secondary objective), and (3) to explore, among the intervention group, whether the estimated effect of the intervention differs by baseline variables or level of engagement with the intervention (exploratory objective). Methods: This study is a convergent mixed methods, 2-arm parallel RCT, open-label design with 1:1 allocation. All youth participants (n=40) received rent subsidies; half were randomly assigned an identity capital intervention (co-designed leadership guide+coach). The overall study was guided by community-based participatory action research axiology. The qualitative component used a qualitative descriptive design underpinned by critical social theory. The measures used were (1) recruitment, enrolment, and dropout metrics; self-report composite checklists regarding intervention engagement; coaching session attendance; and qualitative focus groups (primary measures); (2) education, employment, and training; housing security; and identity capital (secondary measures); and (3) impact of baseline variables (eg, participant demographics such as gender or mental health symptoms as measured by the Global Appraisal of Individual Needs–Short Screener) or level of engagement with intervention (coaching session attendance) on secondary measures (exploratory measures). Results: Recruitment and enrolment began March 1, 2023, and ended June 19, 2023. Data collection began March 7, 2023, and ended June 17, 2024. Qualitative and quantitative data analyses concluded on August 20, 2024. Conclusions: Findings from this RCT will help inform the way we conceptualize the types of supports that are necessary to sustain successful exits from homelessness. The intervention was co-designed with youth who have experienced homelessness, and their voices will continue to inform the next iteration of this work. Clinical Trial: ClinicalTrials.gov NCT05781503; https://clinicaltrials.gov/study/NCT05781503

Background: Inherited bleeding disorders involve prolonged bleeding due to clotting protein deficiencies, with hemophilia A and B being the most common types. The severity of bleeding in people with hemophilia depends on the deficient factor level. Treatment includes coagulation factor concentrates, nonreplacement preparations, gene therapies, and physiotherapy, whereby bleeding is prevented, symptoms are reduced, and the quality of life is improved. Closed kinetic chain exercises improve joint stability and neuromuscular control by stabilizing the proximal base, making them favored in musculoskeletal rehabilitation. Proprioceptive exercise training improves the sensorimotor system’s adaptability and injury prevention through tailored programs involving progressively complex movements and surfaces. Objective: The aim of this study is to investigate the effects of closed kinetic chain exercises and proprioceptive exercise training on improving balance and walking in people with hemophilia. Methods: This study is a 3-arm, parallel-group randomized controlled trial with 63 people with hemophilia aged 13-25 years who meet the inclusion criteria. The primary outcome measures are medio-lateral swing, anterior-posterior swing, walking speed, and Hemophilia Joint Health Score. Secondary outcome measures are kinematic assessment of gait, one-leg stand test, 6-minute walk distance (6MWD) test, proprioception assessment, and the Functional Independence Score in Hemophilia. Participants will be evaluated with the Biodex balance system for postural sway, 10-meters walking test for gait speed, Hemophilia Joint Health Score for joint health, Kinovea 2D motion analysis for kinematic evaluation of gait, one-leg stand test for balance measurement, 6MWD for functional capacity, digital goniometer for proprioception, and Functional Independence Score in Hemophilia for functional independence. Participants will be randomly assigned to a closed kinetic chain exercise group, a proprioceptive exercise group, or a control group. All participants in exercise training groups will receive a 30-minute education session on joint protection techniques and energy conservation prior to the first exercise session. Closed kinetic chain exercises will include progressive lower limb exercises of approximately 45 minutes each session. Proprioceptive exercise training will focus on vibration training; reposition exercises and proprioception exercises will be administered to increase proprioceptive input for the same duration as the other group. The control group will receive no intervention. All participants will undergo 24 exercise sessions (2 days a week for 12 weeks). After the treatment, the initial measurements will be repeated. Results: This study began in September 2023 and is scheduled to be completed in May 2025. A total of 34 participants have completed the study to date. Conclusions: This study will investigate the effects of 2 different exercises on functional parameters in people with hemophilia. The effects of different exercise protocols on parameters such as postural sway, walking speed, and joint health will be evaluated. It is predicted that both exercise methods may have positive effects on balance and gait. Trial Registration: Clinical Trials.gov NCT05879549; https://clinicaltrials.gov/study/NCT05879549

Background: Applied behavior analysis (ABA) is a scientific approach that applies principles of learning and motivation to assess, design, implement, and evaluate social and environmental modifications to produce meaningful changes in human behavior. It has been widely used in various settings, particularly in the treatment of individuals with autism spectrum disorders and other developmental disabilities. Recently, compassion has emerged as a topic of growing scientific interest within ABA. To improve socially relevant behaviors, it is essential to explore how behavior analysts can provide maximum support to clients and promote significant changes through compassionate care. Although compassion skills have been studied by ABA researchers, the literature still presents gaps in understanding how these skills can be effectively integrated into ABA practice. Objective: This study aimed to map, identify, and provide data available in the existing literature on compassion skills and applied behavior analysis. Methods: This scoping review will follow the methodological framework of Arksey and O’Malley with previously proposed refinements. The search strategy will use combinations of descriptors and their synonyms according to the Health Sciences Descriptors and MeSH (Medical Subject Headings) terms, using the PCC (population, concept, and context) mnemonic, combined with the Boolean operators AND Mesh OR. The electronic databases to be searched include Embase, Index Psicologia, Lilacs, PubMed, Scopus, and Web of Science. Studies published between 2020 and 2024 in English, Portuguese, and Spanish will be included. Two independent reviewers will screen titles, abstracts, and full texts, with a third reviewer resolving any disagreements. Results: As this is a protocol, results are pending. The review will synthesize definitions of compassion in ABA, map compassionate skills, analyze existing interventions, and identify outcomes associated with compassionate ABA practice. Conclusions: This scoping review is expected to contribute to the evolution of ABA toward a more compassionate and holistic approach, potentially leading to improved outcomes for clients and practitioners. The findings may inform the development of compassion training programs and influence care policies in ABA. Trial Registration: OSF Registries 10.17605/OSF.IO/F3A6H; https://osf.io/f3a6h

Background: In Sub-Saharan Africa (SSA), clinical and research investments for oncology screening, diagnosis, and therapy are exceedingly modest, compared to those in higher-income regions. Diseases that are difficult to prevent or treat, such as primary brain and central nervous system (CNS) tumors, are especially challenging in low-resource settings. Objective: In order to review and synthesize existing evidence to identify research and service gaps, we will conduct a scoping review to assess epidemiological data, clinical series, and health outcomes associated with brain and CNS tumors in SSA. Methods: This scoping review is guided by the Scoping Review Chapter of the JBI (Joanna Briggs Institute) Manual for Evidence Synthesis. We will search the following databases: Ovid MEDLINE, Embase, Cochrane Library, Scopus, references from salient publications, and the gray literature, the latter focused on the International Agency for Research on Cancer (IARC) and other major global health organizations. We will review titles and abstracts of potentially eligible studies and then full texts by 2 independent reviewers. We will include data from both primary and CNS cancers in persons of all ages. Data will be abstracted independently using piloted data extraction forms, and we will present results according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) and PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols) guidelines. Results: A total of 2857 articles were identified through our search strategy. After title and abstract screening, which was completed on February 23, 2025, by 2 independent reviewers, 222 studies met the eligibility criteria, while 2203 were excluded. Full-text screening began on March 3, 2025, and will be followed by data abstraction and analysis from April 15, 2025, until the end of May 2025. The study is expected to be completed by July 2025. Conclusions: SSA faces substantial challenges in the diagnosis and treatment of CNS tumors due to health care infrastructure limitations, insufficient reporting, and diagnostic supply shortages. The high fatality rates are attributed to underdiagnosis and misdiagnosis as infectious diseases, despite low incidence rates (IRs). The inadequate neurosurgery facilities and pathology resources further complicate the treatment and prognosis. A scoping review will investigate the true burden of underdiagnosis and gaps in outcomes in children and adults in SSA. Trial Registration: OSF Registries osf.io/57zvc; https://osf.io/57zvc

Background: Nonmedical use of prescription opioids remains a critical public health issue; 8.5 million people in the United States misused opioids in 2022. Most people obtain prescription opioids for misuse from family or friends. Thus, facilitating secure storage and disposal of opioid medications during and after treatment is needed to prevent medication diversion and subsequent misuse. Objective: The primary objective of this study is to test the feasibility and efficacy of a novel intervention that uses a persuasive, informational SMS text message reminder system to enhance the impact of secure storage and disposal of unused opioid medications. We hypothesize that the SMS text message intervention will increase secure storage during treatment and disposal of prescription opioids after treatment. Methods: We will use a 2-arm randomized controlled trial to test the intervention for feasibility and efficacy. Participants (aged 18+ years who have received an opioid prescription in the past 2 weeks) will be randomly assigned to either receive the SMS text message intervention or standard-of-care educational materials. Participants in the intervention will receive 4 SMS text messages related to secure storage and 3 messages related to disposal. All participants will complete baseline, midpoint (day 25), and postintervention (day 45) evaluation surveys. We will test whether receipt of the intervention is associated with two primary outcomes, which are (1) secure storage of prescription opioid medication (locked vs unlocked) and (2) disposal of unused prescription opioid medication (disposed vs not disposed). We will use multiple logistic regression to test the main hypotheses that the intervention will be positively associated with secure storage (locked vs unlocked) and disposal (yes vs no) behaviors, which will allow us to control for demographic variables known to influence the outcomes. This protocol represents the entire structure of the randomized controlled trial. Results: Recruitment for the randomized controlled trial was launched in April 2024, and data collection was completed in December 2024. The final sample size is 484. Data analyses for the main hypothesis will be completed by May 2025, and the main hypothesis manuscript will be submitted for publication by May 2025. Conclusions: Results from this study will indicate whether a text message reminder system can increase secure storage and disposal behaviors for individuals who receive opioid medication. This type of intervention has the potential to be integrated into currently used health care delivery systems, such as prescription pickup reminders at pharmacies. Thus, the intervention is scalable across systems of care, thus expanding the reach of secure storage and disposal programs to prevent prescription opioid misuse. Trial Registration: ClinicalTrials.gov NCT05503186; https://clinicaltrials.gov/study/NCT05503186

Background: An individual education plan (IEP) is a key element in the support of the schooling of children with special educational needs or disabilities. The IEP process requires effective communication and strong partnership between families, school staff, and health care practitioners. However, these stakeholders often report their collaboration as limited and difficult to maintain, leading to difficulties in implementing and monitoring the child’s IEP. Objective: This paper aims to describe the study protocol used to evaluate a technological tool (CoEd application) aiming at fostering communication and collaboration between family, school, and health care in the context of inclusive education. Methods: This protocol describes a longitudinal, nonrandomized controlled trial, with baseline, 3 month, and 6-month follow-up assessments. The intervention consisted of using the web-based CoEd application for 3 months to 6 months. This application is composed of a child’s file in which stakeholders of the support team can share information about the child’s profile, skills, aids and adaptations, and daily events. The control group is asked to function as usual to support the child in inclusive settings. To be eligible, a support team must be composed of at least two stakeholders, including at least one of the parents. Additionally, the pupil had to be aged between 10 years and 16 years, enrolled in secondary school, be taught in mainstream settings, and have an established or ongoing diagnosis of autism spectrum disorder, attention-deficit/hyperactivity disorder, or intellectual disability (IQ<70). Primary outcome measures cover stakeholders’ relationships, self-efficacy, and attitudes toward inclusive education, while secondary outcome measures are related to stakeholders’ burden and quality of life, as well as children’s school well-being and quality of life. We plan to analyze data using ANCOVA to investigate pre-post and group effects, with a technological skills questionnaire as the covariate. Results: After screening for eligibility, 157 participants were recruited in 37 support teams, composed of at least one parent and one professional (school, health care). In September 2023, after the baseline assessment, the remaining 127 participants were allocated to the CoEd intervention (13 teams; n=82) or control condition (11 teams; n=45). Conclusions: We expect that the CoEd application will improve the quality of interpersonal relationships in children’s IEP teams (research question [RQ]1), will show benefits for the child (RQ2), and improve the well-being of the child and the stakeholders (RQ3). Thanks to the participatory design, we also expect that the CoEd application will elicit a good user experience (RQ4). The results from this study could have several implications for educational technology research, as it is the first to investigate the impacts of a technological tool on co-educational processes.

Background: Seasonal influenza has an estimated global reach of 3-5 million infections, with 290,000-650,000 influenza-related deaths yearly. Despite its efficacy in reducing morbidity and mortality, influenza vaccination rates remain low globally and in South Africa. Youth between the ages of 18 and 34 years are not prioritized for influenza vaccines although influenza surveillance in South Africa shows that individuals aged 19-44 years present the highest asymptomatic episodes and the lowest medically attended illness. This creates an opportunity to investigate if and how vaccine demand can be created in the absence of clear imperatives to vaccinate. The study tests the effectiveness of tailored, context-specific education, and community engagement, including community and social media to increase influenza vaccination uptake. Tailored, context-specific education, community engagement, reliable vaccine supply, and free, localized access are all critical for improving perceptions of, increasing confidence in, and motivating the uptake of vaccination. Objective: This study will explore strategies to increase influenza vaccine uptake amongst economically marginalized youth aged 18-34 years in Soweto (South-Western Townships), South Africa, where influenza vaccines are not universally accessible through the public health system for this age group. Methods: The Bambisana Study uses an innovative approach, including community influencers and social media to increase the uptake of influenza vaccines through designing and testing an integrated communications strategy targeted at economically marginalized youth in Soweto, South Africa. The study uses a mixed methods pretest-posttest intervention design to test the effects of the interventions. The intervention will consist of the following components: (1) social media campaign, (2) microinfluencers on and offline, and (3) nonsocial media focused, offline microinfluencer-led engagement within communities. Quantitative data will be collected using a randomized household sample pre- and posttests, and clinic surveys with vaccinees and clinic attendees who declined vaccination. Focus group discussions (FGDs) will be conducted pre- and post intervention with participants aged ≥18 years, and 20 key informant interviews (KIIs) will be conducted with key influencers including religious leaders, traditional healers, and youth leaders. FGDs and KIIs will be audio-recorded and transcribed into English for analysis using framework thematic analysis, and quantitative data analyses will be conducted using SAS Enterprise (Guide 7.15; SAS Institute). Results: This study was funded in December 2022, with recruitment having started in May 2023. As of May 2024, all data collection is complete, with data analyses and preparation of peer-reviewed publications in progress. The first results are expected to be submitted for publication in November 2024. Conclusions: Enhancing perceptions of, bolstering confidence in, and fostering uptake of vaccination relies heavily on the efficacy of yearly influenza vaccination initiatives, personalized education tailored to specific contexts, active community involvement, consistent vaccine availability, and easily accessible, cost-free distribution channels at the local level.

Background: Long-chain omega-3 polyunsaturated fatty acids (LCPUFAs) are essential fatty acids that protect cellular structures and provide energy, particularly for fetal growth and development. The maternal supplementations of omega-3 LCPUFA may affect the rate of intelligence in early childhood development. Objective: This systematic review aims to synthesize available evidence on the impact of omega-3 LCPUFA supplementation during pregnancy toward intelligence in early childhood development by analyzing the outcomes specifying the aspects of intelligence such as neurodevelopment, social-emotional, language, attention, behavior, cognition, vision, hearing, and motor skills. Methods: We will only include randomized controlled trials on pregnant women supplemented with omega-3 LCPUFA interventions and the outcome measured is the children’s intelligence. Based on the World Health Organization's definition of early childhood, we will include children aged 8 years or younger. Children’s intelligence can be indicated using several tools measuring their intelligence index, such as neurodevelopment, social-emotional, language, attention, behavior, cognition, vision, hearing, and motor skills. Irrelevant and unavailable studies will be excluded. A systematic search will be conducted in 3 electronic databases, namely PubMed, Scopus, and Cochrane using relevant and synonymous terms. Study screening and selection will be conducted by the authors based on eligibility criteria. Upon encountering conflicting decisions, a discussion will be held to reach a consensus. The screening and selection process will be recorded using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The included studies will be subjected to bias and quality assessment in accordance with the Critical Appraisal Skills Programme (CASP) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment tool for randomized controlled trials. Results: An initial search was conducted on November 1, 2023, which returned 1998 studies for screening. The extracted data will be classified into groups and subgroups according to the indicator of intelligence measured in the study. Next, the extracted data will be summarized using tables of evidence. Whenever possible, a meta-analysis of homogeneous groups of studies will be conducted using statistical software such as RevMan (version 5.4; Cochrane Collaboration). Studies with significant heterogeneity will be discussed narratively. The systematic review is estimated to be published in November 2025. Conclusions: This systematic review will systematically pool the evidence on the potential use of omega-3 LCPUFA supplementation to improve children’s intelligence status. This review is also important in addressing any existing knowledge gaps on this topic. Finally, a deeper understanding of the association between the consumption of omega-3 LCPUFA supplementation during pregnancy and children’s intelligence will aid policy makers, health care practitioners, and mothers with more informed evidence-based decisions. Trial Registration: PROSPERO CRD42023463910; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023463910

Background: Mental health needs in the community surged during the pandemic, with concerning reports of increased negative mood symptoms among youth. At the same time, preventive psychoeducational interventions were insufficient within frontline youth mental health services in Hong Kong, and research specifically addressing youth loneliness remained limited on an international scale. Given the association between loneliness and other mental health symptoms, psychoeducational programs that empower adolescents to cope with emotions may help address both the research gap and local demand. As such, Tuned In, a previously validated intervention program originally developed in Australia, was introduced to the local context. Cultural adaptations and an added focus on loneliness were incorporated into the project to enhance its acceptability and test its effectiveness. Objective: This study aims to evaluate an adapted version of the Tuned In music-based psychoeducation program, designed to reduce loneliness, depression, and anxiety symptoms among young people in Hong Kong by enhancing their emotion regulation skills. Methods: Participants aged 16-19 years will be randomly assigned to either the experimental or control group. The experimental group will receive an online, group-based psychoeducation program focused on emotion recognition and management, delivered weekly over 4 consecutive weeks. The intervention is grounded in Russell’s emotion circumplex model and music psychology, and program content included: The 2D model and characteristics of emotions from different quadrants (session 1); happiness and loneliness (session 2); high-arousal and negative-valence emotions, for example, stress and anxiety (sessions 3); and anxiety, perfectionism, and a celebration of achievement (session 4). Both therapist- and participant-selected music will be used in the intervention to provide a rich repertoire for group discussion, psychoeducation, reflection, and the practice of social skills. The main outcome measures will be assessed using the Emotion Regulation Questionnaire, the Difficulties in Emotion Regulation Scale, the Depression Anxiety Stress Scale, and the De Jong Gierveld Loneliness Scale. Feedback on the project arrangement will be gathered through qualitative input. A mixed methods analysis will be conducted following data collection. Results: The project was successfully funded in February 2023 by the Health and Medical Research Fund in Hong Kong and commenced in August 2023. As of September 16, 2024, a total of 316 completed questionnaires had been received through Qualtrics for screening purposes, with 89 participants deemed eligible for the program. The project is scheduled to conclude in August 2025, with results to be published thereafter. Conclusions: Participants are expected to show improvements in emotion regulation, along with reductions in mood symptoms and loneliness, following the intervention. Trial Registration: ClinicalTrials.gov NCT06147297; https://clinicaltrials.gov/study/NCT06147297

Background: Individuals who are socioeconomically disadvantaged have high smoking rates and face barriers to participating in smoking cessation interventions. Computer-tailored health communication, which is focused on finding the most relevant messages for an individual, has been shown to promote behavior change. We developed a machine learning approach (the Adapt2Quit recommender system), and our pilot work demonstrated the potential to increase message relevance and smoking cessation effectiveness among individuals who are socioeconomically disadvantaged. Objective: This study protocol describes our randomized controlled trial to test whether the Adapt2Quit recommender system will increase smoking cessation among individuals from socioeconomically disadvantaged backgrounds who smoke. Methods: Individuals from socioeconomically disadvantaged backgrounds who smoke were identified based on insurance tied to low income or from clinical settings (eg, community health centers) that provide care for low-income patients. They received text messages from the Adapt2Quit recommender system for 6 months. Participants received daily text messages for the first 30 days and every 14 days until the end of the study. Intervention participants also received biweekly texting facilitation messages, that is, text messages asking participants to respond (yes or no) if they were interested in being referred to the quitline. Interested participants were then actively referred to the quitline by study staff. Intervention participants also received biweekly text messages assessing their current smoking status. Control participants did not receive the recommender messages but received the biweekly texting facilitation and smoking status assessment messages. Our primary outcome is the 7-day point-prevalence smoking cessation at 6 months, verified by carbon monoxide testing. We will use an inverse probability weighting approach to test our primary outcome. This involves using a logistic regression model to predict nonmissingness, calculating the inverse probability of nonmissingness, and using it as a weight in a logistic regression model to compare cessation rates between the two groups. Results: The Adapt2Quit study was funded in April 2020 and is still ongoing. We have completed the recruitment of individuals (N=757 participants). The 6-month follow-up of all participants was completed in November 2024. The sample consists of 64% (486/757) female participants, 35% (265/757) Black or African American individuals, 51.1% (387/757) White individuals, and 16% (121/757) Hispanic or Latino individuals. In total, 52.6% (398/757) of participants reported having a high school education or being a high school graduate; 70% (529/757) smoked their first cigarette within 30 minutes of waking, and half (379/757, 50%) had stopped smoking for at least one day in the past year. Moreover, 16.6% (126/757) had called the quitline before study participation. Conclusions: We have recruited a diverse sample of individuals who are socioeconomically disadvantaged and designed a rigorous protocol to evaluate the Adapt2Quit recommender system. Future papers will present our main analysis of the trial. Trial Registration: ClinicalTrials.gov NCT04720625; https://clinicaltrials.gov/study/NCT04720625

Background: Occupational cancer and acute cardiac events are the leading causes of death among firefighters. Increased exposure to toxicants on the fire ground, such as polycyclic aromatic hydrocarbons, benzene, and per- and poly-fluoroalkyl substances (PFAS), has been linked to certain cancers, cardiovascular disease, accelerated epigenetic aging, and other adverse health effects. PFAS are a major concern because they are persistent, can bioaccumulate, and are present in several firefighting tools. Compared to the general population, firefighters have elevated serum levels of some types of PFAS. A randomized clinical trial in Australian firefighters found that routine blood and plasma donation for 1 year led to decreased serum PFAS levels, although health outcomes were not directly measured in that study. Objective: In collaboration with fire service leadership in Arizona, the Firefighter Collaborative Research Project (FCRP) was established to evaluate the effectiveness of 3 interventions in a randomized controlled trial design to reduce serum PFAS levels, reduce cancer and cardiovascular risk, and improve overall health and wellness in US firefighters. Methods: This study aimed to recruit and enroll up to 1500 active firefighters between August 2023 and October 2024. Between August 2023 and October 2024, active firefighters were recruited and randomized into a study arm based on their eligibility, including serum PFOS levels, for the specific arms. The trial arms include (1) blood and plasma donation, (2) zone 2 physical activity, and (3) intermittent fasting. FCRP outcomes include serum PFAS reduction (arm 1), epigenetic age acceleration (all arms), cardiovascular conditioning (arm 2) and cognitive outcomes (all arms), mental health (all arms), and overall disease risk (all arms). Each study arm includes an intervention and a control group. At enrollment and end of the study, participants provide blood and urine samples and complete a comprehensive questionnaire on their occupational and health history, exposures, and lifestyle behaviors. At the end of the study, participants also participated in a cognitive evaluation. Depending on the study arm, participants may additionally complete a cardiopulmonary exercise test at baseline and follow-up, a mid-study survey, and a mid-study blood and urine collection. Results: Participant activities and data collection will conclude by December 2025. Conclusions: The FCRP is a randomized controlled trial that aims to test the effectiveness of fire service–selected interventions in reducing serum PFAS levels. Study results will contribute to potential interventions that could be used to reduce serum PFAS levels in firefighters. Trial Registration: ClinicalTrials.gov NCT05869747; https://clinicaltrials.gov/study/NCT05869747

Background: Stroke is a leading cause of serious, long-term disability and has a sudden onset. Upon discharge to the home setting, families are thrust into providing care, often without sufficient training from health care providers. Aligned with current patient and caregiver guidelines, the Telehealth Assessment and Skill-Building Kit (TASK III) is a nurse-led intervention designed to empower caregivers to address their own needs and those of the survivor using innovative skill-building strategies. Objective: This study aims to test the short-term (immediately after the intervention at 8 wk) and long-term (12, 24, and 52 wk) efficacy of the TASK III intervention, compared with an information, support, and referral (ISR) group, to improve caregiver life changes (ie, changes in physical health, physical functioning, emotional well-being, and general health) as a result of providing care. Methods: A randomized controlled clinical trial design will be used with baseline data collection from 296 family caregivers by telephone after the stroke survivor is discharged home. Caregivers randomly assigned to the ISR group (n=148, 50%) will receive information from the American Heart Association about stroke family caregiving. Caregivers randomly assigned to the TASK III group (n=148, 50%) will receive a TASK III resource guide and information from the American Heart Association. Both groups will receive 8 weekly calls from a nurse, with a booster call a month later. Outcomes will be assessed by blinded data collectors at 8, 12, 24, and 52 weeks. The primary outcome (at 8 wk) is caregiver life changes measured by the Bakas Caregiving Outcomes Scale. Secondary outcomes are depressive symptoms; other symptoms (eg, stress, fatigue, sleep, pain, and shortness of breath); unhealthy days; diet; exercise; and self-reported health care use. Mediators are task difficulty, threat appraisal, and self-efficacy. Program evaluation outcomes (satisfaction and technology ratings) will also be analyzed. Results: The trial was registered on March 10, 2022. Enrollment and random assignment of the first participant was on November 30, 2022, with an anticipated completion of recruitment by November 30, 2025. Completion of the primary end point data analysis is anticipated by August 31, 2026, with results expected to be reported on ClinicalTrials.gov by April 1, 2027. As of October 9, 2024, a total of 198 (66.9% of the proposed total sample of 296) family caregivers have been enrolled and randomly assigned to the TASK III group (n=98, 49.5%) or the ISR group (n=100, 50.5%). The last update was performed on January 25, 2024. Conclusions: If the TASK III intervention is shown to be efficacious in the proposed randomized controlled clinical trial, our next goal will be to translate TASK III into ongoing stroke systems of care, providing a tremendous public health impact. Trial Registration: ClinicalTrials.gov NCT05304078; https://clinicaltrials.gov/study/NCT05304078

Background: Low-dose computed tomography (LDCT) screening is promising for the early detection of lung cancer (LC) and the reduction of LC-related mortality. Despite the implementation of LC screening programs worldwide, recruitment is challenging. While recruitment for LC screening is based on physician referrals and mass advertising, novel recruitment strategies are needed to improve the enrollment of high-risk individuals into LC screening. Objective: We aim to identify whether patients with LC can act as advocates to enroll their family members and close contacts into LC screening and whether this strategy increases screening uptake at the population level. Methods: We designed a prospective cohort study comprising 2 cohorts constituted between June 2023 and January 2024 with a prospective follow-up of 18 months. Patients with LC (cohort 1) are approached at clinics of the McGill University Health Centre, educated on tools for communicating with family members and close contacts about the benefits of LC screening, and invited to refer their close ones. Referred individuals (cohort 2) are directed to this study’s web-based questionnaire to assess their LC risk score with the PLCOm2012 (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) prediction model. Individuals meeting the eligibility criteria for LC screening (PLCOm2012 score ≥2% and aged 55-74 years) are directed toward the Quebec LC screening program. Data collected include sociodemographic characteristics, health literacy and smoking status (all participants), patient activation (cohort 1), perceived risk of LC, and generalized anxiety at baseline and at 28 days (cohort 2). LDCT completion within 18 months from referral is assessed from health records. Focus groups will identify the barriers and facilitators in the uptake of LC screening and preventative behaviors based on perceived genetic and clinical LC risks. The primary outcomes are the number of referred participants per survivor of LC and the mean risk of LC of the referred population based on PLCOm2012 scores. The secondary outcomes are the proportion of (1) participants eligible for LC screening; (2) participants eligible for screening who complete LDCT screening within 18 months of referral from a survivor of LC; (3) participants showing interest in genetic testing to inform LC risk; and (4) participants showing interest in a smoking cessation program. Multivariable logistic regression will identify the predictive factors of being referred for LC screening. PLCOm2012 scores will be compared for referred participants and controls from the provincial LC screening program. Results: Overall, 25 survivors of LC and 84 close contacts were enrolled from June 2023 to January 2024, with followed up through July 2025. The results are expected by the end of 2025. Conclusions: We describe an approach to LC screening referral, leveraging patients with LC as advocates to increase screening awareness and uptake among their family and peers. Trial Registration: ClinicalTrials.gov NCT05645731; https://clinicaltrials.gov/ct2/show/NCT05645731

Background: To improve the performance of health care institutions, reduce overmedication, and minimize the waste of medical resources, China is committed to implementing a clinical pathway management model. This study aims to standardize nursing practices, foster clinical thinking in nurses, and promote patient recovery. Objective: The purpose of this study is to evaluate the clinical effects of a traditional Chinese medicine (TCM) nursing program based on nursing pathways for patients with type 2 diabetes mellitus (T2DM). Methods: This study uses a prospective, randomized, single-blind, parallel-controlled design. Based on sample size calculations, the study will include 594 patients with diabetes, with 2 groups of 297 patients: an observation group will receive a TCM nursing program based on clinical pathways, while a control group will receive routine care. Both groups will be evaluated before and after the intervention using assessment indicators. The primary outcome is the quality of life score, measured by a diabetes-specific quality of life questionnaire. Secondary outcomes include hospital stay duration, medical expenses, health knowledge, blood glucose control, symptom scores, and patient satisfaction. Results: This study was funded in August 2021 and has received approval from the Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences (2022-022-KY-01). The trial is ongoing, with the first patient enrolled in September 2022. The study is expected to conclude in April 2025. To date, 380 patients have been recruited, with 202 randomized into the study, though no statistical analysis of the data has yet been conducted. A single-blind method is used; nurses are aware of group assignments and intervention plans, while patients remain blinded. Final results are planned for release in the first quarter of 2025. Conclusions: This study seeks to integrate existing national standardized nursing protocols with clinical pathways to implement more efficient and higher-quality nursing practices. The goal is to standardize nursing procedures, enhance patients’ quality of life, and improve self-care and medication adherence after discharge. Trial Registration: International Traditional Medicine Clinical Trial Registry ITMCTR2022000048; https://tinyurl.com/y4jd68h4

Background: The Canadian long-term care (LTC) workforce cares for increasingly complex residents. With greater care needs come greater demands. Despite this, LTC staffing and resources are largely unchanged and underresearched over the last decade. The Atlantic provinces are home to the oldest population in Canada, indicating a high need for LTC. The health and well-being of the LTC workforce are critical components of care quality, yet only in Western Canada are such data routinely and systematically collected. Translating Research in Elder Care is a 2-decade research program studying the LTC work environment and has found strong links between the working conditions of LTC staff and resident outcomes. We draw upon their success to generate the evidence needed to understand, support, and manage the LTC workforce in Canada’s four Atlantic provinces. Objective: This study aims (1) to assess the quality of work life among staff in LTC homes in Atlantic Canada; (2) to examine the effects of the work environment on the quality of work life; and (3) to build capacity for research in the LTC sector in Atlantic Canada among knowledge users, researchers, and trainees. The objective of this paper is to describe the approach needed to examine the quality of work life and health of care staff in LTC homes. Methods: Stratified random sampling will be used to recruit homes in Atlantic Canada. The sampling frame was designed to recruit 25% of the LTC homes in each of the 4 provinces with proportional representation by size; ownership model; and, if applicable, region or language. Key outcome variables include measures of mental health and well-being, quality of work life, intention to leave, workplace context, and missed or rushed care. Primary data will be obtained through structured interviews with care aides and web-based surveys from registered nurses, licensed practical nurses, managers, and allied health providers. Eligible participants were from an LTC home with at least 25 residents, 90% of whom were aged 65 years or older, and had worked in the home for at least 3 months. Multivariate analyses include regression analysis for explaining predictors of quality of work-life outcomes and multilevel modeling for more complex relationships of staff outcomes by provinces and LTC home characteristics. Results: Data collection and cleaning are complete as of October 2024 (N=2305). Care aides (n=1338), nurses (n=724), allied health providers (n=154), and managers (n=89) from 53 homes make up the sample. Data analysis is ongoing. Initially, individual reports will present descriptive data for each participating LTC home. Concurrent analysis is planned for publication in peer-reviewed journals. Conclusions: This peer-reviewed research protocol lays the foundation for a comprehensive analysis of the effects of the work environment on the quality of work life of LTC staff in Atlantic Canada.

Background: In India, heavy menstrual bleeding or menorrhagia (Raktapradara) constitutes about 15% to 20% of all gynecological admissions in an institution. Of these, 43% of patients are aged 20-40 years. This condition is worsening because of the high prevalence of anemia among Indian women. Menorrhagia can have a significant impact on women’s lives. Medical treatment is usually the first choice in excessive bleeding, but it reduces menstrual blood loss by only 50%, and up to 50% of women undergo surgical treatment within 5 years. However, none of these treatments proved their definite efficacy in spite of the high price and side effects. This condition presents a major financial burden on health care services. In Ayurveda, encouraging work has been done on the compound drug Ashokarishta, and the drug Trinakantamani pishti is indicated in Ayurvedic classics and the Ayurvedic Formulary of India. Also, these medicines have been used in Ayurvedic practice for a long time. However, no clinical trial has been carried out on these formulations. Objective: The primary objective is to evaluate the efficacy of Ayurvedic intervention in the management of menorrhagia, and the secondary objective is to assess the efficacy of Ayurvedic intervention on the quality of life of the women with menorrhagia. Methods: This ongoing study is an open-label, interventional, randomized controlled trial, with a sample size of 140 in the treatment and control groups combined (including 20% dropouts), and will be carried out within the duration of 36 months. Participants in the treatment group will receive Ayurvedic treatment, that is, 20 mL of Ashokarishta, 250 mg of Trinakantamani pishti, and 1 iron and folic acid tablet (100 mg of elemental iron and 1.5 mg of folic acid) twice a day orally for 3 months. Participants in the control group will receive a 500-mg tranexamic acid tablet thrice a day for 7 days from the first day of menses for 3 cycles and 1 iron and folic acid tablet twice a day orally for 3 months. The primary outcomes are changes in the amount of uterine bleeding evaluated by the Pictorial Blood Loss Assessment Chart, changes in the duration of bleeding, and attainment of a normal quantity of blood loss during the interval of cycles. The secondary outcome is changes in the Menorrhagia Impact Questionnaire. Results: As of December 2024, a total of 79 patients have been enrolled. Data analysis should be completed by February 2026. The study will be reported following standard guidelines for reporting randomized controlled trials. Clinical results will be disseminated through conferences and peer-reviewed publications in a relevant journal. Conclusions: The Ayurvedic approach may provide an evidence-based therapeutic tactic for the management of menorrhagia. Trial Registration: Clinical Trial Registry India CTRI/2023/05/052929; https://tinyurl.com/3cd6mxrn

Background: Adolescent girls and young women constitute a priority population disproportionately affected by HIV, accounting for 25% of annual HIV incidence among people older than 15 years in Kenya. Although oral preexposure prophylaxis (PrEP) is effective in reducing HIV acquisition, its protective benefit has been limited among adolescent girls and young women in sub-Saharan Africa because of low uptake, adherence, and persistence. Intimate partner violence (IPV) and relationship power inequities are widespread among adolescent girls and young women and contribute to higher HIV incidence and lower PrEP use. Interventions are needed to support sustained PrEP use among adolescent girls and young women by addressing IPV and relationship dynamics. Objective: This study aims to test the effectiveness of Tu’Washindi na PrEP (“We are Winners with PrEP”), a multilevel community-based intervention, to increase uptake and adherence to PrEP and reduce IPV among adolescent girls and young women in Siaya County, Kenya. Methods: The Tu’Washindi na PrEP intervention was co-designed by our team and adolescent girls and young women using participatory methods and includes 3 components delivered over 6 months: an 8-session, empowerment-based support club for adolescent girls and young women, community sensitization targeted toward male partners, and PrEP education events for couples. The intervention will be evaluated using a cluster randomized controlled trial across 22 administrative wards in Siaya County, Kenya, enrolling 72 adolescent girls and young women per ward (total N=1584). The primary objectives are to test the effectiveness of the intervention on PrEP uptake and adherence immediately after delivery (month 6 after enrollment) and 6 months later (month 12). As secondary objectives, we will test the intervention effect on IPV. A rigorous process evaluation will explore mechanisms of change, contextual factors, and implementation considerations to inform future refinement and scale-up, using programmatic data, participant questionnaires, and qualitative interviews with participants and intervention providers. Results: Data collection started in September 2022. As of December 2024, enrollment has been completed in 16 of the 22 study wards, with 72.6% (1150/1584) of participants enrolled. We anticipate that data collection will be completed in May 2026 and results will be available by mid-2027. Conclusions: The study builds directly on our promising formative and pilot research to develop the evidence base for this youth-designed, multilevel HIV prevention intervention. If effective, Tu’Washindi will be ideally positioned for sustainable integration into existing youth-focused programming to expand and support PrEP use in this priority population. Trial Registration: ClinicalTrials.gov NCT05599581; https://www.clinicaltrials.gov/study/NCT05599581

Background: Current treatments for schizophrenia and other psychotic disorders have limited efficacy, with high rates of nonresponse to “gold standard” treatments. New approaches are therefore urgently required. Objective: The aims of this pilot study are to investigate the feasibility, acceptability, safety, and usability of Hybrid treatment (primary aim); and to explore Hybrid’s treatment efficacy and engagement of treatment targets (secondary aim). The primary aim will be assessed via face-to-face user experience surveys on a (self-assessed) 5-point Likert scale (and qualitative open-ended questions) examining: (1) acceptability, (2) helpfulness, (3) engagement, and (4) perceived safety. We will also examine consent and completion rates, and the number of sessions attended. Our threshold for moving on to efficacy trials will be at least 70% of our participants to rate 3 and above (which corresponds to agree or strongly agree) that the intervention package was acceptable, feasible, and safe. The secondary aims will be assessed by observing whether individuals achieve self-directed modulation of high-β neurophysiological activity (neural target) and progression upwards through the VR-based exposure hierarchy (psychological target), and by assessing symptom change scores. This study developed a new treatment approach for auditory verbal hallucinations, a major symptom of psychotic disorders, that integrates advances in psychological therapy (cognitive behavioral therapy for psychosis), technology (virtual reality, VR), and neuroscience (electroencephalography-based neurofeedback). Methods: Hybrid takes a “symptom capture” approach using individually tailored VR-based exposure exercises. Participants (N=10) will receive the intervention package weekly over 12 face-to-face sessions. Here, participants will be progressively exposed to symptom triggers and develop methods of downregulating neural activity associated with these symptoms (neurofeedback component) while concurrently receiving clinician-delivered cognitive behavioral therapy for psychosis. Results: As of February 2025, Hybrid has commenced (unblinded) recruitment activities from Orygen clinical services in Northwestern Melbourne, Australia. A total of 75 individuals have been approached and 64 individuals have been prescreened (41 individuals were deemed eligible, 15 individuals were ineligible, and 8 individuals declined or did not respond to contact attempts) and 5 individuals have been included in the study. Of the 5 individuals who have commenced the Hybrid treatment, 4 are actively engaged in the program and 1 individual has withdrawn. We expect recruitment to conclude in July 2025 and for the results to be published in 2026. Conclusions: The Hybrid study is piloting a novel approach that has the potential to address the shortcomings of current treatments for psychotic symptoms. If there is favorable evidence for the acceptability, feasibility, safety and usability of Hybrid, the study team will move on to efficacy trials. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12624000357550; https://tinyurl.com/24ey8hpy

Background: Diabetes distress (DD) is a common emotional response to living with diabetes. If not addressed, DD can have negative impacts on diabetes management, including the progression to mental health conditions such as depression and anxiety. Routine screening and treatment for DD is recommended, with primary care being an ideal setting given that the majority of people with diabetes receive their diabetes care from primary care providers. However, consistent screening of DD does not routinely occur in primary care settings. Research is needed to understand how to effectively and feasibly integrate DD screening and treatment into routine diabetes care. Objective: This study aims to (1) design and implement individualized technology-supported DD workflows, (2) evaluate the primary outcome of determining the acceptability and feasibility of integrating technology-based workflows to provide treatment for DD, and (3) evaluate the secondary outcomes of changes in DD, depression, and anxiety (baseline, 3 months, and 6 months) in patients receiving screening and personalized treatment. Methods: In total, 30 English and Spanish-speaking primary care patients with either type 1 or type 2 diabetes will receive screening for DD during clinical visits and subsequent support from an artificial intelligence (AI)–based health care chatbot with interactive tailored messaging. In addition, the use of electronic consultation with a specialist or referral to a behavioral health provider could occur depending on the severity and source of DD. The use of electronic consultations allows providers convenient and timely asynchronous access to a range of specialty care providers. Health outcomes will be measured through changes in validated screening measures for DD, depression, and anxiety. Digital outcomes will be measured through surveys assessing user experience with technology and system usability, and by system performance data. Qualitative data on acceptability and satisfaction with the clinical workflows and technological interventions will be collected through interviews with patients and clinical providers. Descriptive statistics will summarize quantitative outcome measures and responses to closed-ended survey items, and rapid thematic and content analysis will be conducted on open-ended survey and interview data. Results: Workflows for screening and treating DD have been approved and clinical staff have received training on the process. Electronic surveys for screening measure collection have been created. Data from visit screeners will be entered into the electronic medical record during the medical appointment. Recruitment will begin late June-July 2024. Conclusions: This study is expected to demonstrate the feasibility and acceptability of integrating individualized workflows for DD into primary care. Improving clinical and digital interventions for addressing DD in primary care can provide alternative care options for busy clinical providers. This study is intended to deliver whole-person diabetes care to people with diabetes within a primary care setting.