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.

Background: Young adults from racial and ethnic minority (REM) groups are at greater risk of disengaging from vital mental health services than their majority group peers. Emerging research suggests developmentally tailored interventions that enable personalized exploration of cultural and structural contexts; encourage trust in relationships with service providers; enhance hope for recovery; and increase self-efficacy to adhere to treatment can improve engagement among underserved REM young adults with mental health disorders. Objective: Just Do You is a brief young adult treatment engagement intervention. Although Just Do You showed evidence of efficacy with medium effect sizes in a previous clinical trial, not all participants benefited, and some of the proposed mediators were not changed. Grounded in the multiphase optimization strategy (MOST), we propose to improve the provision and effects of Just Do You by testing a set of new candidate intervention components that complement the original Just Do You program. This can potentially enhance its effects on engagement and mental health service use for REM young adults. Methods: A total of 3 new candidate behavioral intervention components and their putative mediators were designed in collaboration with REM young adults and other key informants. The new candidate components and their mechanisms of action are (1) cultural identity (perceived cultural competency), (2) future self (hope), and (3) understanding environments (self-efficacy). A pilot optimization randomized controlled trial will be conducted in an outpatient mental health setting with REM participants aged 18-34 years (N=80). The candidate components will be tested in a 23-factorial design where all participants will receive Just Do You and be randomly assigned to one of 8 experimental conditions, each composed of a unique combination of candidate components. We will assess the new components’ acceptability and feasibility, and explore preliminary evidence of their effects on the primary outcome (engagement in mental health care) and mediators at a 3-month follow-up assessment. Results: The study began recruitment in December 2024 and is planned to continue through December 2026. Final study completion is planned for March 2027. The results will be disseminated via professional and scientific publications, presentations, and social media, as well as to members of the participant community. Conclusions: Findings from this study will supply critical deployment-focused evidence to inform a future randomized controlled trial as the next step in this program of research. We ultimately aim to create an effective, efficient, and scalable intervention to improve engagement and mental health outcomes among REM young adults. Trial Registration: ClinicalTrials.gov NCT06508450; https://clinicaltrials.gov/study/NCT06508450

Background: The 5-Cog paradigm is a 5-minute brief cognitive assessment coupled with a clinical decision support tool designed to improve clinicians’ early detection of cognitive impairment, including dementia, in their diverse older primary care patients. The 5-Cog battery uses picture- and symbol-based assessments and a questionnaire. It is low cost, simple, minimizes literacy bias, and is culturally fair. The decision support component of the paradigm helps nudge appropriate care provider response to an abnormal 5-Cog battery. Objective: The objective of our study is to evaluate the effectiveness, implementation, and cost of the 5-Cog paradigm. Methods: We will enroll 6600 older patients with cognitive concerns from 22 primary care clinics in the Bronx, New York, and in multiple locations in Indiana for this hybrid type 1 effectiveness-implementation trial. We will analyze the effectiveness of the 5-Cog paradigm to increase the rate of new diagnoses of mild cognitive impairment syndrome or dementia using a pragmatic, cluster randomized clinical trial design. The secondary outcome is the ordering of new tests, treatments, and referrals for cognitive indications within 90 days after the study visit. The 5-Cog’s decision support component will be deployed as an electronic medical record feature. We will analyze the 5-Cog’s implementation process, context, and outcomes through the Consolidated Framework for Implementation Research using a mixed methods design (surveys and interviews). The study will also examine cost-effectiveness from societal and payer (Medicare) perspectives by estimating the cost per additional dementia diagnosis. Results: The study is funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (2U01NS105565). The protocol was approved by the Albert Einstein College of Medicine Institutional Review Board in September 2022. A validation study was completed to select cut scores for the 5-Cog battery. Among the 76 patients enrolled, the resulting clinical diagnoses were as follows: dementia in 32 (42%); mild cognitive impairment in 28 (37%); subjective cognitive concerns without objective cognitive impairment in 12 (16%); no cognitive diagnosis assigned in 2 (3%). The mean scores were Picture-Based Memory Impairment Screen 5.8 (SD 2.7), Symbol Match 27.2 (SD 18.2), and Subjective Motoric Cognitive Risk 2.4 (SD 1.7). The cut scores for an abnormal or positive result on the 5-Cog components were as follows: Picture-Based Memory Impairment Screen ≤6 (range 0-8), Symbol Match ≤25 (range 0-65), and Subjective Motoric Cognitive Risk >5 (range 0-7). As of December 2024, a total of 12 clinics had completed the onboarding processes, and 2369 patients had been enrolled. Conclusions: The findings of this study will facilitate the rapid adaptation and dissemination of this effective and practical clinical tool across diverse primary care clinical settings. Trial Registration: ClinicalTrials.gov NCT05515224; https://www.clinicaltrials.gov/study/NCT05515224

Background:  The human papillomavirus (HPV) vaccine is an effective way to prevent HPV and its associated cancers. Provider recommendation has been shown to be one of the most successful strategies for increasing the uptake of the HPV vaccine; however, more training and resources are needed to help boost health care providers’ confidence and communication skills in recommending the HPV vaccine to their patients, particularly in underserved Hispanic communities where vaccination rates among all ages are lower. Objective:  This study aims to compare HPV educational and professional skills intervention effectiveness on improving provider recommendations and patient communication strategies with health care providers serving the El Paso United States–Mexico border region. Methods:  We will conduct a randomized, blinded, multiple posttest-only controlled behavioral trial using a parallel group design that will examine the effectiveness of a fully automated, web-based, culturally tailored HPV education and professional skills intervention containing unique reading material and video role-play, as compared to a standard Centers for Disease Control and Prevention fact sheet and video about general communication skills. Participants were recruited using a purposive sampling technique, both internet-based and in-person outreach events. Study data are being collected and managed using REDCap (Research Electronic Data Capture; Vanderbilt University) hosted at the University of Texas at El Paso. Chi-square analyses, ANOVA, and other statistical tests will be used with 2-tail α to reject null hypotheses at .05 to analyze the self-assessed outcome data. The Mauchly test of sphericity for each ANOVA and the Huynh-Feldt epsilon test or Greenhouse-Geisser correction to the degrees of freedom of the F-ratio will be reported for each significant effect. We may use multiple imputation procedures to handle the missing data (if applicable). This study is being conducted in the west Texas or southeast New Mexico region of the United States. Chi-square analyses will be used to assess associations between variables reported on the baseline provider knowledge, attitudes, and practice scales. We seek to examine self-assessed changes in provider attitudes and behaviors regarding HPV vaccine recommendation 1 month after receiving our unique multimedia and culturally tailored intervention. Results:  Research and data collection for this clinical trial began in December 2023. Participant recruitment was closed by May 2024 (N=128), with final data collection expected to be completed by December 2024. Conclusions:  This study team decided to report on the intervention protocol to help ensure transparency in the research process and facilitate the improvement of the research design. Tailored web-based educational programs for health care professionals, designed to address regional and patient population characteristics, may be a promising approach to enhancing the real-world implementation of clinical practice guidelines. Trial Registration: ClinicalTrials.gov NCT05120869; http://clinicaltrials.gov/ct2/show/NCT05120869

Background: Intestinal protozoal infections caused by Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum are prevalent in Malaysia. They cause severe diarrheal diseases with symptoms such as bloody stools, abdominal pain, stomach discomfort, and bloating. These infection outbreaks have been reported in diverse socioeconomic backgrounds and geographical regions usually during the rainy season or in areas with poor sanitation. Despite the importance of these infections, data on its overall prevalence, risk factors, and diagnostic methods remain limited. Objective: The aim of this study is to systematically review and synthesize evidence on the risk factors, prevalence, and detection methods for intestinal protozoal infections in Malaysia, offering insights that are applicable to other tropical and low-income regions. Methods: Studies on intestinal protozoal infections among Malaysian patients published after January 2010 up to November 2024 will be eligible for inclusion. The eligibility criteria include studies investigating infections caused by E. histolytica, G. lamblia, and C. parvum using validated diagnostic methods such as microscopy, molecular techniques, or immunoassays. Case reports, reviews, and studies without original data will be excluded. Comprehensive database searches will be conducted in PubMed/MEDLINE, Scopus, ProQuest, Web of Science, Google Scholar, and the Cochrane Library. The reference lists of selected papers are also checked. A standardized data extraction form will be used to record study characteristics, outcomes, and associated variables. Risk of bias will be assessed using the Joanna Briggs Institute tools and Newcastle-Ottawa Scale approach. Data synthesis will utilize a random effects model to estimate pooled prevalence and identify risk factors associated with these infections. Subgroup analyses will examine variations by geographic region and diagnostic method. Statistical heterogeneity will be assessed using I2 statistic and meta-regression. Publication bias will be assessed using Egger and Begg funnel plot test. The results are reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: This systematic review was funded in June 2024. Database searches were started in July 2024, and we identified 1652 papers as of December 2024 for screening. Completion of study screening is anticipated by May 2025, with data extraction and analysis expected to conclude by December 2025. Conclusions: Our study will address critical knowledge gaps in the epidemiology and risk factors of intestinal protozoal infections in Malaysia. Study limitations include potential bias in study selection, heterogeneity in diagnostic methods, and differences in the reporting quality of the included studies. Our findings will provide valuable insights into the prevalence of these infections, the associated risk factors, and the diagnostic techniques employed, which should strengthen public health measures, improve diagnostic procedures, and guide future research to reduce the prevalence of intestinal protozoal infections in Malaysia. Clinical Trial: PROSPERO (International Prospective Registry of Systematic Reviews) registration CRD42023456199; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023456199

Background: Access to methadone treatment can reduce opioid overdose death by up to 60%, but US patient outcomes are suboptimal. Federally allowed methadone treatment accommodations during the COVID-19 public health emergency were not widely adopted. It is likely that staff-level characteristics such as trauma symptoms influence the adoption of treatment innovation. Objective: Methadone Patient Access to Collaborative Treatment (MPACT) is a 2-phased project (pilot and field trial) to develop and test a staff-level, multimodal intervention to increase staff adoption of low-barrier, patient-centered methadone treatment practices and ultimately improve treatment retention and patient outcomes. Methods: A pilot and national trial will measure implementation feasibility, acceptability, and effects of the MPACT intervention on treatment practice change, clinic culture, patient retention, and patient posttraumatic stress symptoms (PTSS). The pilot will be a single-arm 5.5-month pilot study of MPACT conducted in 2 Arizona methadone treatment clinics (rural and urban) among 100 patients and 22 staff. The national trial will be a 20-month cluster randomized trial conducted among 30 clinics, 600 patients (20 per clinic), and 480 staff (18 per clinic). Data will be gathered by staff and patient surveys and patient chart review. The primary study outcome is increased patient methadone treatment retention measured as (1) time to first treatment interruption from study enrollment; (2) active in treatment at enrollment, day 30, 60, 90, and 120; and (3) continuous days in treatment during the study period. Secondary study outcomes include reductions in vicarious trauma and PTSS among enrolled opioid treatment program staff and PTSS among enrolled patients. Results: The pilot study was funded by the National Institute on Drug Abuse (award R61DA059889, funded September 2023), and the field trial will be funded under the associated R33 mechanism in September 2025. The pilot study was completed in March 2025. The randomized controlled trial will begin in December 2025. Both the pilot and trial have been approved by the University of Arizona Human Subjects Protection Program and have been registered with the clinical trials network. Conclusions: The MPACT study will provide a foundation for an evidence-based, staff-level intervention aimed at improving patient retention in methadone treatment. Future studies should examine the individual components of MPACT to determine their differential contributions to the primary outcome of patient methadone treatment retention and to secondary outcomes of staff and patient reduction in stress symptoms. Trial Registration: ClinicalTrials.gov NCT06513728; https://clinicaltrials.gov/study/NCT06513728 and ClinicalTrials.gov NCT06556602; https://clinicaltrials.gov/study/NCT06556602

Background: Metabolic disease is increasingly impacting women of reproductive age. In pregnancy, uncontrolled metabolic disease can result in offspring with major congenital anomalies, preterm birth, and abnormal fetal growth. Pregnancy also accelerates the complications of metabolic diseases in mothers resulting in an increased risk of premature cardiovascular events. Despite the convincing evidence that preconception care can largely mitigate the risks of metabolic disease in pregnancy, there are few data about how to identify the highest-risk women so that they can be connected with appropriate preconception care services. Objective: The aim of the study is to determine the maternal phenotype that represents the highest risk of having adverse neonatal and maternal pregnancy outcomes. Methods: This will be a prospective cohort study of 500 women recruited in early pregnancy. The primary outcome is a composite of offspring born small for gestational age (SGA) or large for gestational age (LGA) (customized birthweight ≤10th and ≥90th centile for gestational age). Secondary outcomes are (1) composite of adverse neonatal birth outcomes (SGA, LGA, major congenital abnormalities, preterm birth [<37 weeks’ gestation]) and (2) composite of new maternal metabolic outcomes (gestational diabetes, diabetes in pregnancy, type 2 diabetes [T2D] or prediabetes; gestational hypertension, preeclampsia, eclampsia or new essential hypertension after pregnancy; and gestational weight gain ≥20kg or new overweight/obesity at the 12-18 months postpartum visit). A multivariable logistic regression analysis will be conducted to identify candidate predictors of poor pregnancy outcomes due to metabolic disease. From this model, model coefficients and the associated 95% CIs will be extracted to derive the risk score for predicting the delivery of LGA/SGA offspring (primary outcome) and composites of adverse neonatal outcomes and maternal outcomes (secondary outcomes). Results: Seed funding for the project was acquired in November 2022 and subsequent funding was acquired in May 2024. The first participant was recruited on March 23, 2023. At the time of manuscript submission, 402 participants have been recruited. Data analysis has not yet been performed. Results are expected to be published in the first half of 2027. Conclusions: This is a prospective observational cohort study that intends to identify the metabolic disease risk factors, or combination of factors, that are most likely to cause adverse maternal and fetal health outcomes. These characteristics will be used to develop a risk calculator which will assist in identifying the highest risk women and in triaging them to appropriate services. The study has been approved by the institutional Human Research Ethics Committee (HREC/90080/MH-2022). Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12623000037606; https://tinyurl.com/yeytsxtp

Background: Suicidal ideation is increasing among university students. Despite growing demand for services, university counseling centers (UCCs) face limited resources to meet the complex needs of students who are suicidal. Objective: The Comprehensive Adaptive Multisite Prevention of University Student Suicide (CAMPUS) Trial evaluates 4 treatment sequences within UCCs to develop evidence-based treatment guidelines. Methods: The CAMPUS Trial consists of a feasibility study followed by a sequential multiple-assignment randomized trial (SMART). The original CAMPUS protocol was modified during the COVID-19 pandemic to accommodate new UCC tele–mental health services, including remote treatment, assessments, and monitoring. A smaller-scale feasibility study was conducted to (1) evaluate implementation of hybrid telehealth and in-person interventions and (2) fine-tune online procedures. Following the feasibility study, university students (aged 18-25 years) seeking UCC services with moderate to severe suicidal ideation will enroll in the CAMPUS Trial. Student participants are randomly assigned to 1 of 4 treatment sequences with 2 stages of intervention. In stage 1, students receive 4 to 6 weeks of either (1) a suicide-focused treatment—Collaborative Assessment and Management of Suicidality—or (2) enhanced treatment as usual. Treatment responders enter the maintenance phase. In stage 2, nonresponders are rerandomized for an additional 1 to 8 weeks of (1) Collaborative Assessment and Management of Suicidality or (2) an intensive skills-based treatment—dialectical behavior therapy for UCC settings. UCC counselors will enroll in the CAMPUS Trial to complete measures about their experience working with students who are suicidal. CAMPUS Trial administration includes representation from all sites to facilitate cross-site coordination and an advisory board of stakeholders from all UCCs to facilitate treatment implementation. Results: Student participant recruitment began on October 25, 2022, and ended on May 16, 2024. As of November 2024, data collection for the SMART was ongoing with active study participants. Data collection was completed in November 2024, and as of April 2025, data analysis is underway. Full results will be available in 2025. Conclusions: The CAMPUS Trial offers a model for future SMARTs for the treatment of suicidal thoughts or behaviors (or both) across various settings. The results will inform treatment guidelines for students presenting with suicidality at UCCs. Trial Registration: ClinicalTrials.gov NCT04707066; http://clinicaltrials.gov/ct2/show/NCT04707066

Background: Firefighters are at an increased risk of cancer and other health conditions compared with the general population. However, the specific exposures and mechanisms contributing to these risks are not fully understood. This information is critical to formulate and test protective interventions. Objective: The purpose of the Fire Fighter Cancer Cohort Study (FFCCS) is to conduct community-engaged research with the fire service to advance the evaluation and reduction of firefighter exposures, along with understanding and mitigating effects leading to an increased risk of cancer and other health conditions. This involves establishing a long-term (>30 years) firefighter multicenter prospective cohort study. Methods: The structure of the FFCCS includes a fire service oversight and planning board to provide guidance and foster communication between researchers and fire organizations; a data coordinating center overseeing survey data collection and data management; an exposure assessment center working with quantitative exposure data to construct a firefighter job exposure matrix; and a biomarker analysis center, including a biorepository. Together, the centers evaluate the association between firefighter exposures and toxic health effects. Firefighter research liaisons are involved in all phases of the research. The FFCCS research design primarily uses a set of core and project-specific survey questions accompanied by a collection of biological samples (blood and urine) for the analysis of biomarkers of exposure and effect. Data and samples are collected upon entry into the study, with subsequent collection after eligible exposures, and at intervals (eg, 1-2 years) after enrollment. FFCCS data collection and analysis have been developed to evaluate unique exposures for specific firefighter groups; cancer risks; and end points in addition to cancer, such as reproductive outcomes. Recruitment is carried out with coordination from partnering fire departments and eligible participants, including active career and volunteer firefighters in the United States. Results: The FFCCS protocol development was first funded by the US Federal Emergency Management Agency in 2016, with enrollment beginning in February 2018. As of September 2024, >6200 participants from >275 departments across 31 states have enrolled, including recruit and incumbent firefighters. Biological samples have been analyzed for measures of exposure and effect. Specific groups enrolled in the FFCCS include career and volunteer structural firefighters, women firefighters, trainers, fire investigators, wildland firefighters, firefighters responding to wildland-urban interface fires, and airport firefighters. Peer-reviewed published results include measurement of exposures and the toxic effects of firefighting exposure. Whenever possible, research results are provided back to individual participants. Conclusions: The FFCCS is a unique, community-engaged, multicenter prospective cohort study focused on the fire service. Study results contribute to the evaluation of exposures, effects, and preventive interventions across multiple sectors of the US fire service, with broad implications nationally.

Background: Head impacts are common in contact sports such as boxing and occur at times of elevated core body and brain temperatures induced by the exercise. Following impact, elevated brain temperature may lead to the development of exacerbated brain injury that can be monitored by blood biomarkers. Blood-brain biomarkers S100B and glial fibrillary acidic protein (GFAP) reflect glial injury; neurofilament light (NFL), axonal injury; and Neuron-Specific Enolase (NSE) and Tubulin-associated unit (tau), neuronal injury. Time to peak levels post injury for these biomarkers varies. Levels of S100B l peak early post injury, while NSE, GFAP, and tau are regarded as subacute markers, and NFL shows prolonged increases. We attempt to cover a large spectrum of first week postfight alterations in blood-brain biomarkers and their response to head-neck cooling. Objective: We hypothesized that acute head-and-neck cooling, recently shown to shorten return-to-play in concussed ice hockey players, applied acutely following a boxing bout, is associated with an attenuated concentration of blood biomarkers and improved symptom rating. Methods: The trial is academically driven and funded by external and hospital research funds. Young, healthy elite boxers aged ≥18 years are recruited. Before, and immediately after a competitive boxing bout consisting of 2 or 3 rounds of 2 minutes each, blood samples are drawn. Boxers are randomized to intervention or control management by 1:1 allocation before baseline testing. After the initial postfight blood sample is drawn and symptom rating using the Sports Concussion Assessment Tool-5 (SCAT-5) has been collected, the boxers receive either acute selective head-and-neck cooling for 45 minutes or routine postfight management. The number of head impacts is counted in all boxers on match video recordings. In both groups, blood samples are drawn 45 minutes after the initial postbout blood sample, as well as 3 and 6 days post fight. At all blood sampling time points, the number of symptoms (NOS) and symptom severity score (SSS) are assessed using the symptom rating part of the SCAT-5. The primary endpoint is the difference in biomarker levels (GFAP, NFL, tau, UCH-L1, neuronal-specific enolase) immediately post fight and preintervention, to those obtained at 6 days post fight. The postfight SCAT-5 NOS and SSS are secondary endpoints. Results: Recruitment started in November 2021 and is ongoing. So far, 41 boxers have been included: 20 controls and 21 cooled. Data collection started in October 2024 following the completion of blood sample analysis. We expect to recruit more boxers before the middle of 2025, but challenges with recruitment may limit this. Conclusions: There is no treatment available for boxing-induced brain injury. Biomarkers are surrogate yet objective markers of brain injury, and the head-and-neck cooling treatment may attenuate the concentration of brain injury–related biomarkers as well as reduce symptoms induced by head impacts attained during a boxing fight. Trial Registration: ClinicalTrials.gov NCT06386484; https://clinicaltrials.gov/study/NCT06386484

Background: Maternal mental health disorders are associated with adverse maternal and infant health outcomes. Despite advances in screening and treatment, disparities in maternal mental health disorders continue to disproportionately affect Black mothers and birthing persons. While there are studies that have examined maternal mental health, a gap in research remains in understanding the protective and risk factors of Black maternal mental health in Canada. Identifying the risks and protective factors is critical for advancing equitable and inclusive policies and practices that promote maternal well-being and optimal outcomes for Black perinatal populations. Objective: This paper presents an outline of a study protocol that seeks to identify the protective and risk factors of Black maternal mental health and to engage Black mothers and birthing persons from the Greater Toronto Area in codesigning a culturally safe and inclusive best practices model to inform policy and interventions. Methods: The proposed study will use an exploratory 3-phase sequential mixed methods approach underpinned by the principles of health equity and community-based participatory research. Phase 1 will involve engaging Black mothers and birth persons (n=300) in a survey to examine the psychosocial determinants of Black maternal mental health, including depression, anxiety, discrimination, strong Black women trope, attitude toward seeking mental health, support, and stigma. In phase 2, we will conduct 6 focus groups and individual interviews (n=60) to explore the stressors in the context of Black mothers and birth persons’ everyday lives, psychosocial and support needs, and conditions that promote their resilience. Finally, phase 3 will engage Black women and birthing persons (n=30) in a codesign session using the concept mapping method to identify priority areas for action to inform policy and programming. We will use SPSS version 26 (IBM Corp) to analyze the survey data, drawing on both descriptive and inferential statistics. NVivo (Lumivero), a qualitative data analysis software, will be used to organize the data from phase 2 into meaningful themes informed by Braun and Clarke’s thematic analysis approach. Results: Ethics approval was granted in July 2024. Data collection for phase 1 started in December 2024 and will be completed in April 2025. Findings from phase 1 will inform phases 2 and 3 of this study, which will be conducted in the third quarter of 2025. We will disseminate the results of this study in the second and third quarters of 2025. Conclusions: The findings will generate the much-needed knowledge to shift policy, practice, and research and support capacity building among Black mothers and birthing persons. In addition, the proposed study will contribute to informing policy initiatives and interventions at the health system and community level to advance mental health equity and build capacity among service providers to provide culturally safe and equitable mental health care.

Background: The COVID-19 pandemic and the protracted lockdowns have heavily impacted university students’ mental health. Digital Escape Games represent a good means to reach students and propose them solutions for their psychological well-being. Objective: This study aimed to evaluate a cocreated digital Escape Game on students’ mental health in the aftermath of the COVID-19 pandemic, called EscapeCovid Game. The evaluation of the effectiveness of this stand-alone intervention concerns mental health outcomes (mental health literacy, appraisal and change of beliefs about mental health, management of emotions, and development of coping strategies) and the appreciation and relevance of the game. Methods: A randomized controlled trial with pre- and posttest data collection (online questionnaires with validated scales) is conducted among 500 students in Bordeaux, France, to evaluate the EscapeCovid Game cocreated with students, researchers, health professionals, and web developers. A subsample of students is randomly selected for responding to a semistructured interview following a mixed methods design. Recruitment is done through mail invitations from student associations and presentations in university classes. Half of the sample of the trial plays the Escape Game, while the other half receives an email with mental health–related information. Within the game, students discuss their personal experiences. The text is further used for the qualitative analyses. The whole study is carried out online. Results: The EscapeCovid Game has been developed, tested, and finalized by the end of March 2023. As of November 4, 2024, a total of 191 students have answered the baseline questionnaire (90 intervention vs 101 control). A total of 23 students have played the game and 53 are in the control arm. Among participants, by the end of September 20, 2023, twenty were interviewed (10 intervention and 10 control) reaching sample saturation. According to preliminary results, the EscapeCovid Game has had a positive impact on all defined outcomes, while the email has been effective in increasing knowledge on resources available and on coping strategies and meditation techniques. We expect the trial to be completed by the end of June 2025. Conclusions: The mixed methods findings of this study are due to demonstrate the effectiveness of the EscapeCovid Game in improving students’ mental health outcomes. Preliminary results from the qualitative substudy are promising: in the aftermath of the COVID-19 crisis, this intervention is intended to promote players’ mental health through gamification, knowledge transfer, and a learning-by-doing approach. Trial Registration: ClinicalTrials.gov NCT06720792; https://clinicaltrials.gov/study/NCT06720792

Background: The World Health Organization reports that HIV and AIDS remain a significant public health concern in sub-Saharan Africa, which hosts over 60% of the global population of people living with HIV. Among these, there were 1.2 million pregnant women with HIV in 2023 who likely experienced challenges related to the pregnancy itself, the fear of infecting their newborn babies, and issues related to HIV stigma and disclosure. However, their experiences have not been summarized to inform tailored interventions to assist them in their journey to delivery. Objective: This scoping review aims to synthesize the existing evidence related to the experiences of pregnant women with an HIV-positive status in sub-Saharan African countries. Methods: A review of the relevant literature will be guided using the Joanna Briggs Institute methodological framework for scoping reviews. Studies will be eligible for inclusion if they report on reactions to a new HIV diagnosis and the management of these reactions. All eligible studies from 2014 to 2025 in English and French will be included. The following databases will be used for the search: PubMed, MEDLINE, EBSCOhost (CINAHL with Full Text), Scopus, and Web of Science. All identified records will be collated and uploaded into EndNote X21 for management. Eligible studies will be screened by 2 independent reviewers, and disagreements will be solved through discussion. Data extracted via a validated data extraction form developed for this review will be analyzed using content analysis and presented in a narrative format. NVivo (version 12) will be used to facilitate the data analysis process. This protocol is aligned with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Results: We will include studies on timely intervention with antiretroviral therapy, close medical monitoring, careful planning around delivery, and comprehensive support for both mother and child. The findings will be disseminated through medical education conferences and publications. The database search was completed in March 2025, and the results are expected to be published in December 2025. Conclusions: This review will provide a comprehensive narrative of the experiences of pregnant women with a positive HIV status in sub-Saharan Africa and how they react when they are first diagnosed with HIV, as well as how they manage the news. It is anticipated that there will be evidence of mixed reactions to and balanced management of a new HIV diagnosis among pregnant women.

Background: Older adults represent the majority of individuals diagnosed with cancer in the United States and often face complex treatment decisions that require balancing survival benefits with quality-of-life considerations. Despite the emphasis on shared decision-making (SDM), many patients report that clinical guidance does not reflect their personal values. Values-clarification tools have shown slight improvements in aligning care with patient values; however, the factors by which these tools influence decision-making are less studied. Objective: This pilot study aims to estimate the quality of values-clarification and SDM processes that occur during simulated diagnosis encounters for advanced cancer among participants who do and do not receive a values-clarification tool. Methods: Pilot randomized study using simulated patient-clinician encounters to assess how values are elicited, processed, and integrated into treatment decisions. Participants aged 60 years and older with an advanced cancer diagnosis will be randomized to receive either a digital values-clarification instrument codeveloped through stakeholder engagement, referred to as Values and Outcomes to Improve Cancer Experiences (VOICE), or a general communication guide from the American Cancer Society (ACS). Each participant will engage in 2 simulated encounters (values-based and nonvalues-based), conducted by trained medical students portraying oncologists. The simulations are structured using a situational awareness framework. A novel rating scale, referred to as VECTORS (Values Elicitation and Clarification of Treatment Options Rating Scale), will measure the quality of rapport building, clinician engagement, and patient engagement through observation. Additional validated instruments will be used to quantify observed (OPTION-5) and patient-reported (CollaboRATE) SDM behaviors and patients’ perceived usefulness of either VOICE or the ACS guide (PrepDM [Preparation for Decision-Making]). Qualitative interviews will be used to better understand participants’ experiences during encounters and perceptions of VOICE or the ACS guide. Results: The study was conducted between September 2024 and December 2024, with a total of 44 participants, and is ready for data analysis. Conclusions: This pilot study will provide preliminary evidence into the quality of values-clarification processes occurring during patient-clinician encounters among older adults making treatment decisions for advanced cancer.

Background: The estimated number of people living with HIV (PLHIV) in India in 2023 is 2.54 million (range 2.16-3.03 million). With the initiation of antiretroviral therapy (ART) and the “Test and Treat” policy, the life expectancy of PLHIV on ART has substantially increased, consequently leading to a higher rate of comorbidities among PLHIV. The Joint United Nations Programme on HIV/AIDS (UNAIDS) 2025 targets aim for about 90% of PLHIV to have access to integrated and comprehensive health care services, with a concerted effort to reach the End of AIDS by 2030. Hence, the National Integrated Bio-Behavioral Surveillance (IBBS) among PLHIV (IBBS-PLHIV) has been implemented for the first time in India to establish a baseline understanding of the prevalence of sexually transmitted infections (STIs), noncommunicable diseases (NCDs), and related risk behaviors among PLHIV. Objective: The primary aim of IBBS-PLHIV is to estimate the levels of HIV-related risk behaviors and the prevalence of other STIs and NCDs among PLHIV. The specific objectives are identifying the levels of HIV-related sexual and injecting risk behaviors; estimating the prevalence of STIs such as syphilis, hepatitis B virus, and hepatitis C virus; estimating the prevalence of NCDs such as diabetes and hypertension; understanding the lifestyle and behavioral risks associated with NCDs; and assessing the levels of violence, stigma, and discrimination experienced by PLHIV. Methods: IBBS-PLHIV will be a cross-sectional, biennial surveillance among PLHIV aged 15 years or older. The first round will be implemented at 120 ART centers across 28 states, accounting for approximately 95% of the total estimated PLHIV. Consenting, eligible PLHIV will be recruited through consecutive sampling. The overall sample size at each ART center is approximately 225, and the surveillance period is 3 months. Behavioral data on demographics, reproductive and sexual health, lifestyle and sexual behaviors, stigma, and discrimination will be collected. Blood samples will also be collected to test for STIs and NCDs. Results: IBBS-PLHIV was initiated on January 1, 2024, in a phased manner. Data collection was carried out over 3 months and completed by June 2024 across all 120 sites. A total of 25,257 PLHIV were recruited for the surveillance, including 11,921 males, 11,855 females, and 1481 hijra/transgender individuals. Data entry, followed by data matching and validation of all records, was completed in December 2024. The data are currently being analyzed, and the final findings are expected to be disseminated by December 2025. Conclusions: Data collected through IBBS-PLHIV will help monitor the levels of HIV-related sexual and injecting risk behaviors among PLHIV. Additionally, it will provide estimates of the prevalence of NCD comorbidities and STI coinfections such as diabetes, hypertension, syphilis, and viral hepatitis. These findings will serve as a baseline and are expected to offer valuable insights for facilitating comprehensive HIV care and management through the effective integration of HIV and broader health service delivery.

Background: Given the high prevalence of coronary heart disease among older adults and aging populations, there is a need for secondary prevention interventions to help older adults become more physically active. Web-based interventions could be considered for this purpose, knowing that internet use is growing rapidly among older adults. In addition, since older adults would appreciate developing a trusting relationship with a nurse, web-based interventions should include this support, which is not widely observed in the literature. Objective: This study aims to evaluate a web-based nursing intervention aimed at promoting physical activity in people 65 years and older with coronary heart disease. Methods: A web-based nursing intervention was developed according to the Intervention Mapping framework in collaboration with a team of health care professionals (n=5) and based on the needs of older adults (n=10). The 7-week intervention (1 session per week) aims to support older adults living with coronary artery disease in resuming, maintaining, or increasing their level of physical activity after coronary bypass surgery or percutaneous coronary intervention. The intervention offers educational content on coronary heart disease and physical activity, suggestions for physical activity, reflective activities, case histories of older adults who have experienced different journeys, an electronic physical activity diary to track progress, and support from a nurse through feedback to increase knowledge, motivation, and sense of self-efficacy. The preliminary effects and impacts of the intervention will be assessed through a mixed method pilot study with a sequential explanatory design. First, a single-group pre-post test will be used to assess the intervention’s preliminary effects on physical activity (electronic journal), quality of life (36-Item Short Form Health Survey version 2), knowledge (quiz), motivation, and self-efficacy (visual analog scale) of 30 older adults living with coronary heart disease, as well as the feasibility of the intervention. Second, a descriptive qualitative design will use semistructured interviews to assess the intervention’s impacts as perceived by 8-12 older adults and its acceptability. Quantitative data on the effects of the intervention will be integrated with the collection and analysis of qualitative data to assess the impact perceived by older adults, using matrices. Nonparametric statistics and a thematic analysis will be produced. A joint display will be used to integrate mixed data. Results: The results of this study will provide insight into the preliminary evaluation of a web-based nursing intervention to support older adults living with coronary heart disease as they increase their physical activity levels. The recruitment commenced in June 2024, and data collection should be completed by June 2025. Conclusions: With the potential to promote older adults’ health, this study could guide the development of new interventions to meet the needs of an aging population. Clinical Trial: ClinicalTrials.gov NCT06197347; https://clinicaltrials.gov/study/NCT06197347

Background: Respiratory impairment is a major concern in amyotrophic lateral sclerosis (ALS), shortening survival and lowering quality of life. One therapy with promise to delay respiratory decline in ALS is acute intermittent hypoxia (AIH), consisting of alternating periods of breathing mildly hypoxic (9%-12% O2) and normoxic (21% O2) gas. AIH stimulates spinal, serotonin-dependent neuroplasticity in rodent models, conferring functional benefits in diverse physiological systems without detectable pathology. However, in rodent models, AIH-induced neuroplasticity is constrained by distinct signaling cascades initiated by spinal adenosine.

Background: Successful recovery from alcohol use disorder requires long-term lapse risk monitoring. Self-monitoring is difficult, given the dynamic, complex interplay of the many risk factors over time. An automated recovery monitoring support system embedded with a machine learning lapse prediction model could improve sustained, adaptive, and personalized self-monitoring by delivering daily support messages. Objective: We propose to optimize the components included in daily support messages to increase engagement with a recovery monitoring support system. Methods: The participants will include 304 US adults with moderate to severe alcohol use disorder. Participants will complete daily surveys and provide geolocation data for 17 weeks. Participants will receive daily support messages, starting in week 2, that convey a combination of individualized information from a lapse prediction model. Manipulated message components include (1) lapse probability and lapse probability change, (2) an important model feature, (3) a risk-relevant recommendation, and (4) message personalization on tone preference. Results: The National Institute on Alcohol Abuse and Alcoholism funded this project (R01AA031762) on August 9, 2024, with a funding period from August 20, 2024, to July 31, 2029. The institutional research board of the University of Wisconsin-Madison Health Sciences approved this project (IRB #2024-0869). Enrollment will begin in December 2025. Conclusions: Message components that either increase engagement or improve clinical outcomes will be recommended for use in future recovery monitoring support systems and digital therapeutics. International Registered Report Identifier (IRRID): PRR1-10.2196/81697

Background: One of the main recognizable challenges in the digital mental health interventions field is that users adhere to these interventions in their unguided forms poorly. Studies have shown that a persuasive system design focused on encouraging users to make positive behavior changes in their lives can increase user engagement and a program’s efficacy. This design approach can be referred to as therapeutic persuasiveness (TP) and includes a call to action, monitoring, ongoing feedback, and program adaptation based on user state. The goal of this study is to examine the causal impact of TP on program completion and outcomes in unguided digital mental interventions. We aim to examine these questions in digital parent training programs (DPTs) aimed at treating children’s behavior problems. Objective: This study aims to (1) examine the impact of TP quality on usage, reduction in child behavior problems, and improvement in parenting variables; (2) examine the maintenance of treatment gains over a follow-up period; and (3) examine mediational pathways, including whether adherence to the program (measured by module completion rates) mediates reported changes. Methods: A randomized controlled trial will be conducted to compare 2 interventions that use the same evidence-based components of established DPTs, but that differ in terms of the quality of TP (standard: DPT-STD; enhanced TP: DPT-TP). We will recruit parents from 160 families with children aged 3-7 years with behavior problems who will be randomized into one of the 2 intervention arms. We will measure child behavior problems and related parenting variables at 5 time points: before (T1), during (T2 and T3), and after the intervention (T4 and T5). Program usage will be passively collected. Results: The study was funded in October 2023, and enrollment began in September 2024. As of the end of December 2024, 100 participants were enrolled in the study. Analyses are expected to be completed by September 2027. Conclusions: Identifying conceptual scientific theories that draw a link between active ingredients embedded within a digital intervention function and their outcomes is crucial in advancing our understanding of what influences usage and outcomes. Trial Registration: ClinicalTrials.gov NCT06514326; https://clinicaltrials.gov/study/NCT06514326

When retrieving information, people often shift over time from “Remembering” high levels of detail about a study episode to simply “Knowing” the information absent such detail. This “Remember-Know” shift is well-documented for true information, and recent work suggests that this effect exists, but is attenuated, for false information. One explanation for this difference is that true information is better represented in people’s prior knowledge, supporting retention of this content as “Known” over time. In this registered report we tested this hypothesis by measuring people’s reported retrieval experiences (e.g., “Remembering” or “Knowing”) for true and false information at two levels of anticipated prior knowledge. While we replicate the “Remember-Know” shift, we do not find that it differs by anticipated prior knowledge. We also examine the relation between retrieval experiences and the production of encountered information, as well as the impact of repeated testing on retrieval experiences.

Background: With current data supporting an increasing population of older people experiencing homelessness (OPEH) requiring unique spatial and placemaking considerations in end-of-life care, understanding the environmental factors that influence their well-being is crucial. Objective: This protocol paper provides a comprehensive overview for evaluating hospice environments tailored to the needs of OPEH. Methods: The Aging in the Right Place study aims to address this gap by developing and implementing the Aging in the Right Place-Hospice Environmental Assessment Protocol (AIRP-HEAP) and AIRP-HEAP secondary observation tools. The AIRP-HEAP tool evaluates the built and natural environment within hospice settings. Adaptations were made to ensure alignment with the unique needs of OPEH, such as reconceptualizing spiritual care and expanding the definition of family accommodation. Additionally, the AIRP-HEAP secondary observation tool supplements this by capturing contextual data on the surrounding neighborhood of the hospice site, providing a holistic understanding. Results: Data were collected at Maggie’s Lodge hospice between November and December 2024 using the AIRP-HEAP and AIRP-HEAP secondary observation tools. The dataset is currently being cleaned, with analysis planned between May and December 2025. The anticipated results will highlight the importance of considering environmental factors in hospice environments and inform recommendations to improve end-of-life care for OPEH. Conclusions: Data collected using these audit tools can guide environmental modifications in hospice settings to facilitate aging and end-of-life care in the right place. Thus, this protocol paper aims to promote the adoption of best practices in hospice design to better support this marginalized population.