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

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.

Background: Weight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need. Objective: Identification of predictive factors associated with successful weight loss after sequential exercise in women with obesity. Methods: The study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures. Results: Recruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026. Conclusions: This intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions. Trial Registration: ClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349

Background: Chronic low back pain (CLBP) is a common public health problem. Progressive loss of muscle strength leads to long-term chronic pain and disability. Yijinjing exercises, an ancient therapy dating back thousands of years, are widely used in China to treat low back pain. However, little is known about its benefits and scientific evidence for back extensor strength. This trial aimed to assess the efficacy of Yijinjing on disability and dorsal extensor strength in patients with CLBP. Objective: We present a randomized controlled study to evaluate the efficacy of the traditional Chinese exercise Yijinjing on disability and back extensor strength in patients with CLBP. Methods: This is a 2-arm, parallel-design, assessor-blinded, and analyst-blinded randomized controlled trial. The 106 participants with CLBP who were recruited will first receive basic traditional Chinese manual therapy to help relieve their physical discomfort. Second, they will be randomly divided into a Yijinjing group (n=53) and a control group with functional exercises (n=53) at a ratio of 1:1. The interventions for both groups will be carried out twice a week for 4 weeks. Patients in both groups will be followed up at 1 and 3 months after the intervention. The primary outcome is disability (measured by the Oswestry Disability Index). The secondary outcomes included pain intensity (assessed by the Numerical Rating Scale), data from isokinetic dynamometry, flexibility (assessed by the fingertip-to-floor test), mood (evaluated by the Pain Catastrophizing Scale and Fear Avoidance Beliefs Questionnaire), and quality of life (measured by the EQ-5D-5L). All adverse effects will be assessed using the Treatment Emerging Symptoms Scale, and data will be analyzed using an intention-to-treat analysis. Results: The trial was funded in December 2023. The Institutional Ethics Committee of Yueyang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, approved this study. The first patient was enrolled in February 2024, and as of August 2024, a total of 106 participants have been recruited. Data analysis has not yet begun and is expected to be published in January 2025. The protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR2400081105). Conclusions: If this trial proves effective, it will guide the setup of a randomized controlled trial to demonstrate whether traditional Chinese exercise Yijinjing improves disability in patients with CLBP and is more effective than usual stretching exercises. Clinical Trial: Chinese Clinical Trial Registry ChiCTR2400081105; https://www.chictr.org.cn/showprojEN.html?proj=214425

Background: Depression and anxiety are among the most common mental health concerns globally. Efficacious treatments such as cognitive behavioral therapy exist but remain difficult to access and scale. Cognitive behavioral immersion (CBI)—a cognitive behavioral skills training intervention delivered by peer coaches in the metaverse—has been developed to address these barriers. CBI can be used through a virtual reality headset or via flat-screen devices such as phones, tablets, or computers. Pilot data have established its usability among participants with clinical levels of depression and anxiety. However, more research is needed to determine whether CBI causes decreases in these symptoms and how delivery via virtual reality compares to flat-screen devices. Objective: This protocol aims to conduct a randomized controlled trial evaluating the efficacy of immersive CBI accessed via a virtual reality headset (CBI-VR) as compared to a less immersive (but more accessible) CBI condition accessed via a flat-screen device (CBI-FS) and each to a delayed access control (DAC). Methods: A total of 306 adults experiencing clinical levels of depressive symptoms are being recruited nationally to participate in this web-based trial. Participants will be randomized according to a 1:1:1 ratio to one of three conditions: (1) CBI-VR, (2) CBI-FS, and (3) DAC. The CBI program consists of eight weekly 60-minute group sessions led by trained peer coaches who teach cognitive behavioral skills. The acute period of each condition will last 8 weeks with a follow-up period of 6 months. The primary outcome is depressive symptoms; secondary outcomes are anxiety symptoms and quality of life. Outcomes will be assessed once at baseline, weekly during the course of the intervention, and monthly during follow-ups. We will use hierarchical linear models to assess differences in the rate of symptom change among conditions. We will also explore potential prognostic (demographics and immersion) and prescriptive (cognitive behavioral skills, group alliance, and program engagement) predictors, as well as potential mechanisms (cognitive change and social support) of response. Results: We hypothesize that participants randomized to either CBI group will experience greater symptom improvement than those in DAC and that CBI-VR participants will improve more than CBI-FS participants. This study was funded in September 2023. Data collection began in February 2024. As of January 2025, all 306 participants have been enrolled. Data collection should conclude by September 2025. Data have not yet been analyzed. Expected results to be submitted for publication in the winter of 2025. Conclusions: This trial will determine if CBI via either device is efficacious as compared to DAC and whether virtual reality enhances outcomes. Findings will contribute to the literature on using the metaverse and virtual reality to facilitate effective accessible mental health interventions, particularly for depression. Trial Registration: ClinicalTrials.gov NCT06418997; https://clinicaltrials.gov/study/NCT06418997

Background: Evidence suggests that the communication of type 2 diabetes (T2D) genetic risk alone has limited effectiveness on facilitating behavioral changes among individuals of European descent. Although the use of wearable devices has been associated with changes in behavior, the effects of combining personalized precision medicine with wearable devices on behaviors related to T2D prevention remain unclear. This study aims to assess the novel effects of T2D genetic risk communication and wearable device functions on objectively measured moderate to vigorous physical activity (MVPA) time among East Asian individuals with overweight or obesity.

INTRODUCTION: Different biologically active products have been applied to manage pain and mandibular functional disability in intra-articular Temporomandibular Joint Disorders (TMD) but without effectively controlling the degenerative joint disease. Platelet concentrates aim to enhance tissue healing and facilitate its regeneration. Intra-articular injections of liquid Platelet-Rich Fibrin (PRF) in patients with TMD have demonstrated effectiveness in the management of pain and dysfunction, also having a stimulatory effect on cartilage and bone tissuOeBs.JECTIVE: This review aims to examine how research has been conducted regarding the use of PRF as a treatment tool for Temporomandibular Joint Disorders (TMD). INCLUSION CRITERIA: This review will focus on studies that address adults with TMD without restrictions on gender or ethnicity. TMD will be classified according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) physical axis (Axis I). Also, we will include publications in any language or date of publication. METHODS: This protocol will follow the JBI guidance for Scoping Reviews. We shall conduct a literature search to identify published research, with no limits on the year of publication/conception, format, or language. Two independent reviewers will screen and select publications based on inclusion criteria. The review decision process will be provided in a flowchart-based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations for Scoping Reviews. Finally, we shall present extracted data from each study in piloted forms in conceptual categories such as intervention type, population and sample size, duration of intervention, aims, the methodology adopted, key findings, and gaps in the research.

Background: From birth, many young Pacific people in Aotearoa New Zealand experience a disproportionately high burden of psychological distress, metabolic disease, and socioeconomic disparities within education and employment which contribute to significant health inequalities. Further research is needed to understand the drivers influencing these outcomes.

Background: The gut microbiota is attracting increasing interest as a factor possibly impacting colorectal cancer risk, therapy toxicity, and, as a consequence, patient’s quality of life. It has been observed that microbial imbalance in the gut and in cancer tissue is facilitated by a Western type of diet, rich in meat, sugars, and refined grains, while a Mediterranean diet, rich in low saturated fat and fibers, promotes gut eubiosis, and results in reduced risk of developing colorectal cancer. Specifically, a high fiber content diet has been associated with a reduced incidence of therapy related adverse events in patients with malignant melanoma.

Background: Human-machine interaction (HMI) has gained significant attention in the context of advanced production technologies, especially concerning trust and acceptance. However, the investigation of the subjective well-being of operators working with these technologies in manufacturing companies has been largely overlooked. Moreover, previous research mostly relied on a single data-collection method, either quantitative or qualitative, thereby failing to capture a rich picture of their cognitive and affective states. Objective: This cross-sectional study protocol aimed to fill that gap by examining operators’ subjective well-being and workplace dynamics, including fluency in HMI, negative attitudes toward technologies, and social relationships among coworkers in manufacturing companies. Methods: We adopt a mixed methods approach, incorporating both quantitative and qualitative data collection techniques. Quantitative data will be gathered via a digital survey containing self-report questionnaires. A path analysis will be performed to explore the multiple mediating roles of fluency in HMI and negative attitudes toward such technologies between cognitive and affective well-being. We further qualitatively investigate the operators’ lived experience in HMI using semistructured audio-recorded interviews. A thematic analysis relying on text-mining techniques will then be conducted to explore operators’ textual data. Results: We quantitatively expect that fluency in HMI may act as a protective factor for operators’ affective well-being, while negative attitudes toward advanced production technologies may contribute to the development or worsening of operators’ psychological distress. From a qualitative perspective, we intend to seamlessly merge quantitative insights to create a more comprehensive and well-grounded analysis. Moreover, the integrated interpretation of both the quantitative and qualitative data collected will generate a consensus report, which will aim to serve as a practical framework for guiding workplace policies and training programs meant to foster subjective well-being and effective HMI. At the time of publication, we have collected data from 12 participants and scheduled a further data collection session. Conclusions: Embracing one of the fundamental pillars of Industry 5.0, human-centricity, by detecting potential psychological issues early, organizations can create a workplace that prioritizes the well-being of operators. Early recognition and prevention are crucial to promoting operators’ mental well-being involved in HMI.

Background: Knowledge of the burden of disease at the national level is crucial for understanding regional health patterns and epidemiological trends. Regular updates and methodological enhancements are essential to produce accurate estimates that effectively represent the current health landscape, thereby assisting policymakers in resource allocation and strategic planning. Objective: The objective of this study protocol is to revise the list of diseases and injuries; estimate years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) in phase 1; and identify the list of risk factors and determine risk-attributable burdens in phase 2. Methods: The Malaysian Burden of Disease (MBOD) Study adopts the Global Burden of Disease Study approach, using various metrics to quantify health loss related to specific diseases, injuries, and risk factors. These metrics include deaths, YLLs, YLDs, and DALYs, which are calculated in terms of counts, age-specific rates, and all-age rates. In addition, this MBOD Study calculates risk-attributable deaths, YLLs, YLDs, and DALYs for all relevant risk factors. This study also conducts focus group discussions to develop the lists of diseases and injuries as well as risk factors. Results: By December 2024, we had successfully completed the focus group discussions, which led to the development of an updated and comprehensive list of diseases and injuries. Furthermore, mortality data collection is complete, and the calculation of YLLs is currently in progress. The YLD calculation is expected to conclude by the end of 2025. While phase 1 is underway, phase 2, which addresses risk factor estimation, is scheduled for completion in mid-2026. Conclusions: This MBOD Study offers a comprehensive and current framework for assessing the burden of disease in Malaysia, with continuous improvement initiatives to enhance the list of diseases and injuries and refine the methodology for more accurate estimation and risk factor analysis.

Background: In recent years, the rapid emergence and global spread of dengue has become a public health burden. Clinical surveillance alone has limited capacity, with delayed detection of upcoming outbreaks. Hence, the potential use of wastewaterbased surveillance (WBS) for early detection of incoming surges of dengue cases could complement proactive public health action. However, there are still substantial gaps in the standard approach for sampling and detection methods in dengue WBS. Objective: This review aims to determine the current methodological approach for the detection of dengue virus (DENV) in wastewater across geographical areas. Methods: The review will be conducted systematically following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In the initial stage, peer-reviewed publications from PubMed, Embase, Scopus, and Web of Science will be searched using predefined terms such as “Dengue” and “WBS.” Keywords will be adjusted to suit each database to identify studies related to DENV WBS from inception until June 2025. Subsequently, the references from relevant articles will be screened for eligibility. All data will be extracted from full-text articles highlighting the characteristics and methodological context of the investigated DENV WBS using a standardized form. The ROBINS-I (Risk of Bias in Non-randomized Studies - of Interventions) tool and the GRADE (Grading of Recommendations Assessment, Development, and Evaluations) system will be used to assess study bias and the quality of the evidence. Further descriptive analysis and meta-analysis will be applied to evaluate the methodologies for DENV WBS. Results: The data on DENV detection in wastewater will be synthesized by analyzing sampling techniques, viral detection method, study sites, geographic locations and dengue serotype. A meta-analysis will be conducted using a random-effects model if data are heterogeneous, with pooled estimates reported as 95% CIs. Heterogeneity will be assessed using I² and chi-square tests, with subgroup and sensitivity analyses conducted as needed. Findings will be reported in accordance with PRISMA 2020. As of October 2025, records have been identified from the databases and data analysis is expected to be completed by the first quarter of 2026. Conclusions: This protocol outlines a systematic approach to identifying and evaluating existing methods for detecting DENV in wastewater. This research aims to provide valuable insights into best practices for dengue surveillance and offer guidance for future research by highlighting current strengths and limitations in the field.

Background: Surgical resection is the primary curative treatment for early-stage lung cancer—the leading global cause of cancer mortality, responsible for nearly 1 in 5 cancer deaths in 2022. Obesity is a global health concern that may influence surgical outcomes; yet, its impact on perioperative outcomes following lung cancer surgery remains controversial. Objective: This protocol outlines a meta-analysis and systematic review to evaluate the association between obesity and perioperative outcomes in patients who underwent a lung cancer resection. Methods: Observational studies related to patients with lung cancer who underwent surgical resection were searched in 5 English and 3 Chinese literature databases: PubMed, Embase, Cochrane Library, Web of Science, MEDLINE, Chinese National Knowledge Infrastructure, Wanfang, and the Chinese Biomedical Database. The search period for these 8 electronic databases was from inception to 2025. The PROSPERO database and the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) database were also searched. Qualified studies were screened and selected by 2 authors independently. The literature obtained were imported into NoteExpress to screen the titles and abstracts. After reading the full text of the remaining studies, the final number of studies were determined. Two reviewers independently extracted data from the included studies by using a predesigned data extraction tool. The Newcastle-Ottawa Scale was used to evaluate the quality of the research. The primary outcome of this study was to evaluate the postoperative mortality in people living with obesity undergoing lung cancer surgical procedures. The secondary outcomes were the postoperative complications, average length of stay, blood loss during the operation, and operation time in people living with obesity undergoing lung cancer surgical procedures. For dichotomous data, we plan to present results as risk ratios with 95% CIs. For continuous data, we will use mean difference with 95% CIs. The Review Manager software (version 5.4) will be used for the meta-analysis and statistical analysis. Sensitivity analysis and Egger test will be performed with Stata software (version 16.0). Results: The results are not yet accessible because this is a protocol for a systematic review and meta-analysis. The protocol is registered in PROSPERO under the registration number CRD42025648330. By August 26, 2025, we completed the literature search of the 8 databases and completed the selection and extraction of data. Conclusions: This study will synthesize existing evidence to clarify whether obesity is a risk factor for adverse outcomes or if it confers a protective effect, as suggested by the obesity paradox. These findings will guide clinical decision-making and improve perioperative care for obese people with lung cancer. Trial Registration: PROSPERO CRD42025648330; https://www.crd.york.ac.uk/PROSPERO/view/CRD42025648330

Background: Urban Indigenous populations face disproportionate mental health challenges, including high rates of posttraumatic stress disorder, depression, and substance use disorders, yet they have limited access to health services, especially culturally relevant care. The mechanism for providing care to Indigenous people in the United States, the Indian Health Service, is significantly underfunded and only accessible to certain Indigenous people. With more than 70% of Indigenous individuals in the United States living in urban settings, there is a growing need for innovative health care solutions. A community-based, Indigenous-led health and mental health–focused nonprofit in the northeast United States developed ShockTalk, a tele–mental health linkage-to-care app tailored specifically for Indigenous communities, to fill this gap. Objective: This study aims to assess (1) the feasibility, including accessibility, experience, and value, of ShockTalk for practitioners and clients interested in providing or receiving culturally responsive mental health treatment, and (2) changes in client attitudes related to tele–mental health treatment value and trust in ShockTalk technology. Methods: This study outlines the development and pilot study of ShockTalk. The conceptual framework is based on the behavioral model of health care use. ShockTalk uses artificial intelligence to connect clients with Indigenous or culturally aligned therapists and facilitates access to care via Facebook Messenger. Using a prewaitlist or postwaitlist design, 5 client participants will be admitted to the study at first, and 5 additional participants at 3 months. Data collection includes presurveys and postsurveys on client attitudes toward mental health treatment and trust in the ShockTalk platform at baseline and a 3-month follow-up, followed by in-depth qualitative interviews at 3 months. A preliminary economic evaluation will track direct costs (ie, therapist time, platform fees, and administrative expenses) and compare relative costs across treatment doses. Analyses will assess the feasibility of data collection and inform a future full-scale trial. Results: This study was funded in April 2022. Data collection occurred between May 2022 and October 2024. In total, 4 client participants and 2 therapist participants were enrolled. Data analysis is complete and results are expected to be published in February 2026. Conclusions: This pilot study will offer insights into optimizing technology-based, culturally relevant mental health care. By examining varying levels of engagement and associated costs, this research seeks to identify the most effective and cost-efficient strategies for improving mental health outcomes in urban Indigenous populations in the United States. ShockTalk has the potential to shape future health care innovations in this field. Findings are expected to contribute significantly to Indigenous mental health care by offering insights into sustainable, accessible, and culturally appropriate telehealth interventions, guiding future policy and practice.

Background: Alcohol use among young adults with HIV is disproportionately high compared to other age groups with HIV, despite its negative health-related consequences. However, alcohol use interventions tailored to the interests and needs of young adults with HIV are scarce. Self-management interventions that include self-monitoring components have the potential to improve chronic illness outcomes and mitigate alcohol misuse. Although wearable technologies promote self-monitoring behaviors and facilitate the delivery of personalized feedback, people rarely adhere to the long-term use of wearables. Objective: The primary aim of this pilot study is to test the feasibility and acceptability of translating theoretically grounded reciprocity and personalized feedback strategies. These strategies will be delivered through app-based messages to promote engagement in wearing a wrist-worn alcohol biosensor among young adults with HIV. Methods: A total of 40 young adults with HIV (aged 18-29 years) will be enrolled in a 30-day pilot microrandomized trial (MRT). The MRT is an experimental design that facilitates the development and optimization of mobile health just-in-time adaptive interventions. Participants will wear the BACtrack Skyn biosensor, a wrist-worn transdermal alcohol biosensor, and play a smartphone-based game geared toward earning points to care for virtual animals. Longer alcohol biosensor wear time will translate into earning more game points. Every morning and evening, participants will be randomized at equal probability to receive (1) a reciprocity message offering a no-strings-attached gift of either 100 game points or US $1, (2) a message with personalized feedback about their Skyn biosensor wear time, or (3) no message. Results: Data collected during this 30-day MRT will be used to examine the feasibility and acceptability of translating theoretically grounded strategies into messages suitable for a mobile health alcohol intervention tailored to young adults with HIV. Recruitment for this study began in spring 2024, with data collection wrapping up in spring 2025. Conclusions: This pilot MRT will provide valuable feasibility and acceptability data and set the stage for a full-scale MRT to optimize the integration of reciprocity and personalized feedback into a just-in-time adaptive intervention that increases engagement in biosensor-based alcohol self-management among young adults with HIV. Trial Registration: Clinicaltrials.gov NCT05431855; https://clinicaltrials.gov/study/NCT05431855

Background: Primary insomnia (PI), commonly identified by difficulties in initiating and/or maintaining sleep, negatively impacts both physical and mental health and increases the risk of occupational and vehicular accidents. Previous researches have indicated that shallow needling, a form of acupuncture, may ameliorate symptoms of primary insomnia. Nevertheless, the scientific evidence regarding its efficacy in enhancing sleep quality remains limited. Objective: This trial aims to assess the therapeutic efficacy of shallow needling in the treatment of chronic primary insomnia in adults. Methods: A single-center, prospective, assessor-blinded, and randomized controlled clinical trial with two parallel arms will be conducted in the Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine. A total of 124 participants with primary insomnia will be randomly divided into control group and treatment group in a ratio of 1:1 (n = 62 for each group). The control group will take eszopiclone orally at 1 mg once a day for 4 weeks. In addition to taking eszopiclone, the treatment group will receive shallow needling therapy once daily, five times a week, for 4 weeks. Data will be collected at three timeslots (pre, post, 4-weeks follow-up) and analyzed using SPSS 23.0. The primary outcome measure is Pittsburgh Sleep Quality Index (PSQI), Secondary outcome measures are Hamilton anxiety scale (HAMA), Insomnia Severity Index (ISI), Serum neurotransmitter detection (including the content of dopamine [DA], norepinephrine [NE], and melatonin [MT]), sleep parameters, and Magnetic Resonance Spectroscopy (MRS) of the thalamus. Results: This study has received formal ethical approval (Approval No: IRB 2023-014-02), the first participant was enrolled in August 2023, marking the official commencement of the trial. Participant recruitment for this study is currently in progress. Following the completion of recruitment, data processing and statistical analysis will be initiated. The final results of the study are expected to be prepared and submitted for publication in January 2026. Conclusions: This study will evaluate the therapeutic effectiveness and safety of shallow needling in the treatment of chronic insomnia, so as to provide the necessary scientific basis for the clinical application and promotion of shallow needling. The findings of this study may provide a scientific and standardized treatment protocol for shallow needling in adults with chronic insomnia. Clinical Trial: International Traditional Medicine Clinical Trial Registry ITMCTR2024000409; https://itmctr.ccebtcm.org.cn

Background: Lower limb amputation rates are increasing owing to aging and vascular diseases. However, no standardized rehabilitation protocol has been established for regaining walking ability. Conventional rehabilitation delays prosthetic gait training until 6-8 weeks post amputation, prolonging recovery and increasing medical expenses. Objective: This study aims to evaluate the impact of neurorehabilitation using the Hybrid Assistive Limb (HAL) for Medical Use Lower Limb Type, developed by Japan's Tsukuba University and the robotics company Cyberdyne, on gait acquisition, improvement in activities of daily living (ADL), and enhancement of quality of life (QOL) in patients with lower limb amputation, and assess the effectiveness of early HAL-assisted gait training before and after amputation. Methods: This single-arm trial will include 20 patients undergoing unilateral transfemoral or transtibial amputations. HAL-assisted gait training will be performed 5 days per week (30 minutes per session) until postoperative week 8. The primary outcome is a 2-minute walking distance, while secondary outcomes include muscle strength, balance, gait parameters, and ADL/QOL measures. Statistical analyses will be conducted using SPSS (IBM Corp), and results obtained at the following time points will be compared: preoperative, postintervention, and 6-month follow-up. Results: The planned sample size is 20 patients, calculated using JMP version 12 (SAS Institute) based on an expected 1.5-fold improvement in 6-minute walk distance (effect size 0.8, α=.05, power=0.8). Analyses will be performed using SPSS version 15.0 (IBM Corp). The 2-minute walk test (primary outcome) and secondary outcomes will be compared at baseline, post intervention, and 6-month follow-up using 1-way analysis of variance or Kruskal-Wallis test, and P values <.05 and 95% CIs will be reported. Conclusions: This is the first study to apply HAL-assisted neurorehabilitation to patients with lower limb amputations. Early gait training may increase prosthetic gait acquisition rates, shorten rehabilitation and hospitalization periods, and reduce medical costs. If effective, this study may contribute to the development of a Japan-originated rehabilitation program and provide clinical evidence supporting broader HAL implementation for patients with lower limb amputations. Clinical Trial: Japan Registry of Clinical Trials jRCTs062200031; https://jrct.mhlw.go.jp/latest-detail/jRCTs062200031

Background: Self-reported dietary intake data are crucial in nutrition and health research; however, their accuracy is compromised by challenges such as portion size estimations, food identification, memory-related bias, social desirability bias, and reactivity bias. Dietary assessment in adolescents is particularly challenging due to irregular eating habits, meal skipping, and parent or peer influences, potentially resulting in misreporting. Leveraging adolescents’ receptiveness to technology, we investigated the use of an innovative smartphone app (Traqq) that facilitates dietary assessment using repeated short recalls instead of traditional 24-hour recalls. Evaluation studies of the Traqq app in Dutch adults have shown successful results, but its suitability for other target populations, such as adolescents, requires further investigation. Objective: We designed a comprehensive, 3-phase study to evaluate the Traqq app’s accuracy using repeated short recalls, usability, and user perspectives among Dutch adolescents aged 12 to 18 years. This manuscript details the study setup, research methods, and basic characteristics in phases 1 and 2. Methods: In phase 1, adolescents (aged 12-18 years) downloaded the Traqq app and completed a demographic questionnaire. It was used on 4 random school days over 4 weeks, using 2-hour recalls on 2 days and 4-hour recalls on 2 days. A food frequency questionnaire and 2 interviewer-administered 24-hour recalls served as dietary reference methods to assess the Traqq app’s accuracy. In addition, usability was evaluated using the System Usability Scale and an experience questionnaire. In phase 2, user experiences were further explored through semistructured interviews within a subsample of 24 adolescents. These first 2 phases of this mixed methods study are now finalized for data collection. Phase 3 will focus on collecting user insights to inform app customization through cocreation sessions. Results: Recruitment concluded in September 2022 with 102 adolescents; 98 (96%) provided dietary data via the Traqq app, and 79 (78%) completed the evaluation questionnaire. Adolescents had a mean age of 15 (SD 2) years. The mean BMI was 19.9 (SD 3) kg/m2. A total of 64 (63%) participants were girls, 81 (84%) attended high school, and 88 (92%) were born in the Netherlands. Interviews were held with 6 (25%) boys and 18 (75%) girls. Cocreation sessions will be planned after all data have been analyzed. Conclusions: In this holistic study, we combine quantitative and qualitative methods to evaluate the dietary assessment performance among adolescents of the Traqq app, which was initially designed for adults. Specifically, next to quantitative comparisons of the Traqq app’s dietary assessment methods, we conducted semistructured interviews, and we will carry out cocreation sessions. With this user-centered, synergistic approach, we aim to establish a list of requirements for a dietary assessment app for adolescents, resulting in more efficient assessments, improved compliance, and enhanced overall accuracy in this population. Clinical Trial: ISRCTN Registry ISRCTN46230386; https://www.isrctn.com/ISRCTN46230386

Background: Transgender, nonbinary, and gender diverse (TGD) young adults face a disproportionately high mental health burden, including 2- to 4-fold increased risk of suicidality and depressive distress compared to their cisgender peers. Family and community support are protective factors that may mitigate these adverse outcomes, representing key targets for mental health interventions. Objective: This randomized controlled trial (RCT) evaluates the effectiveness of TransHealthGUIDE, a novel digital, app-based education and support intervention aimed at reducing past 3-month suicidal ideation and past 2-week depressive distress among TGD young adults. Participants are randomized 1:1 to an immediate intervention arm or a 6-month deferred intervention arm (waitlist control). Methods: From 2021 to 2024, a multidisciplinary team of academic and community partners conducted formative research and codeveloped a digital app containing 33 self-paced modules, communication, and interactive resources. The content is grounded in the Social Ecological Suicide Prevention Model and the Gender Minority Stress and Resilience Framework, designed to enhance family support and community connection for TGD young adults and their families. TGD young adults (ages 18-24 years) and their caregivers are prospectively enrolled and randomized in 10 US states (California, Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New York, Oregon, Vermont, and Washington, DC). Participants complete self-reported surveys at baseline, 6 months, and 12 months, assessing sociodemographics, family support, community connection, suicidal ideation, depressive distress, and intervention acceptability. App usage and engagement are tracked via metadata. The target sample size is 500 TGD young adults, with 50% (n=250) identifying as people of color and 125 TGD young adult-caregiver dyads. Results: TGD young adult and caregiver communities, including our community advisory board (CAB), have guided all aspects of the project: study design (eg, waitlist control), survey development (eg, self-reported rather than clinician-administered suicidality measures and inclusion of social justice activism as a form of support), intervention content (eg, text, infographics, interviews with TGD people and caregivers, and simulations), and digital app safety features (eg, a quick-exit button for privacy). Recruitment and study screening began on January 21, 2025. As of May 2, 2025, a total of 149 individuals completed a study screener, with 132 (88.6%) of 149 found eligible. Enrollment visits began on April 23, 2025. As of May 2, 2025, five TGD young adults have been enrolled. Ongoing engagement with the CAB will inform iterative improvements throughout the trial. Conclusions: Scalable, app-based interventions tailored to meet the needs of TGD young people hold promise for population-level mental health impact. This RCT—targeting suicidality and depressive distress via education and support for both TGD young adults and their caregivers—addresses a critical gap in mental health interventions for this underserved population. Trial Registration: ClinicalTrials.gov NCT06177600; https://clinicaltrials.gov/study/NCT06177600

Background: Substance use is a high-impact biopsychosocial problem in Chile, where 21% of adults have experienced a severe alcohol use episode. In the past year, the prevalence rates were 12.5% for marijuana, 0.8% for cocaine, and 0.4% for cocaine base paste. Cannabis prevalence in Chile is higher than the global (4.2%) and South American (3.58%) averages. Cocaine prevalence in Chile is lower than in South America (1.62%) but higher than the global average (0.42%). No international reports are available for cocaine base paste. Mental health and substance use programs in Chilean primary care involve psychologists and social workers. Solution-focused brief interventions (SFBIs) are based on solution-focused brief therapy, a strengths-based and person-centered approach in which practitioners adopt a stance of “not being the expert,” respecting clients’ needs and perspectives. Objective: This study aims to determine whether the SFBI implemented by psychosocial teams (psychologists and social workers) for individuals with alcohol and other drug use in primary health care centers leads to better outcomes than usual care. Methods: We will conduct a randomized controlled clinical trial (ClinicalTrials.gov registration pending) comparing a 3-session SFBI (experimental group) with a single session of brief counselling as usual care (control group) in primary care. Interventions will be delivered in person by a psychologist or social worker. A total of 320 participants are expected to be recruited during preventive routine checkups using the Alcohol, Smoking, and Substance Involvement Screening Test. Participants reporting intermediate- to high-risk substance use on this screening tool will be randomly assigned to each group. Research assistants will administer instruments at baseline and at 3-, 6-, and 9-month follow-ups and will be blinded to the assigned treatments. The primary outcome assessed will be substance use patterns, while secondary outcomes include background information, depressive symptoms, anxiety symptoms, and motivation for treatment. Statistical analyses, including t tests, ANOVA, and Fisher exact tests will be conducted depending on variable type and normality. A qualitative component to assess acceptability and pertinence will include focus groups with participants and practitioners, followed by a content analysis. Results: Funding for this study started in April 2024. As of the submission date of this protocol, 55 practitioners from 9 primary health care centers have been trained in SFBIs. Recruitment began in February 2025, with 73 participants enrolled and 23 who dropped out. Recruitment will continue until December 2026. No analyses have been conducted to date. Findings are expected to be published during the second half of 2028. Conclusions: This study strengthens primary care by integrating targeted psychosocial interventions for substance use into existing programs, thereby enhancing real-world applicability. If effective, the intervention could be adopted into routine care and inform public policy on mental health and substance use. Trial Registration:

Background: Negative symptoms of schizophrenia, such as lack of motivation, pleasure, social interest, and expression, are key contributors to functional impairments in people with schizophrenia. While psychosocial interventions have demonstrated efficacy, no Food and Drug Administration–approved pharmacotherapies exist specifically to target these symptoms. Evidence-based digital therapeutics (DTx) may offer novel, scalable treatment options to augment existing treatments. Objective: This article describes the study design and methods of a phase 3, multicenter, double-blind, randomized controlled study (CONVOKE). It aims to evaluate the effectiveness and safety of CT-155/BI 3972080 (CT-155), a smartphone-based DTx, as an adjunct to standard-of-care antipsychotic medication in adults with experiential negative symptoms of schizophrenia. Methods: Eligible participants were 18 years or older with a primary diagnosis of schizophrenia receiving stable antipsychotic medication for ≥12 weeks, scored ≥2 on average in at least 2 Clinical Assessment Interview for Negative Symptoms Motivation and Pleasure subscale (CAINS-MAP) domains, and were smartphone owners. Participants were randomized 1:1 to CT-155 (intervention arm) or a digital control app (control arm). CT-155 integrates aspects of multiple evidence-based psychosocial therapeutic techniques, incorporating principles of in-person psychotherapy aimed at targeting negative symptoms. Development of CT-155 was informed by patients during early clinical learning studies using earlier versions of the app. The digital control included elements of the disease educational components of CT-155 and daily digital check-ins. Participants were blinded to their assigned intervention. A blind-to-hypothesis was used so participants appropriately engaged with both apps. Accordingly, participants were informed that they would receive one of 2 interventions under investigation. Investigators, designated site personnel, and central raters were blinded throughout the study. The study comprised a 2-week screening period, 16-week active period, and a 4-week follow-up period. Change in experiential negative symptoms from baseline to Week 16 (primary end point) was assessed using CAINS-MAP (centrally rated). Other study end points included Clinical Assessment Interview for Negative Symptoms Expressivity, Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Dysfunctional Attitudes Scale, Clinical Global Impressions-Severity, and Patient Global Impression of Improvement Scale. Frequency and severity of adverse events were also assessed, as well as engagement and adherence to either app. Results: Study enrollment began in March 2023 and was completed in January 2025. Overall, 457 participants were enrolled across 66 clinical study sites in the United States. Conclusions: We summarize an innovative trial design for CONVOKE, a phase 3 randomized controlled study aimed at assessing the effectiveness, engagement, and safety of CT-155 as an adjunct to standard-of-care for people with negative symptoms of schizophrenia. CONVOKE is the largest-to-date and most robust clinical trial evaluating the effectiveness and safety of a DTx in schizophrenia. The study protocol included a centrally rated primary end point (CAINS-MAP), blind-to-hypothesis, with an appropriately designed digital control. Clinical Trial: ClinicalTrials.gov NCT05838625; https://www.clinicaltrials.gov/study/NCT05838625

Background: Hypercholesterolemia is a significant risk factor for cardiovascular diseases, necessitating effective management strategies. Herbal interventions have gained attention as potential alternative or complementary therapies to conventional lipid-lowering medications. Objective: This systematic review aims to evaluate the effectiveness of various herbal interventions in managing hypercholesterolemia. Methods: A comprehensive literature search will be conducted across multiple databases, including PubMed, MEDLINE, EMBASE, EBSCO, Cochrane Library, DHARA, AYUSH research portal, WHO portal, Shodhganga, and Google scholar as well as dissertations and thesis work available in the public domain and unpublished works from university websites for studies published from January 2020 onward. Randomized controlled trials investigating the impact of herbal interventions on cholesterol levels will be included. The primary outcome is the change in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels. Data extraction and quality assessment will be performed independently by 3 reviewers, and discrepancies will be resolved by a fourth reviewer. All statistical analyses will be conducted using the Cochrane Collaboration software program, RevMan Web. Results: Following an initial screening, 96 studies were identified. After removing duplicates, 7 studies were excluded, leaving 89 studies ready for data extraction. The results of these studies will be synthesized and analyzed upon completion. Conclusions: This review aims to synthesize evidence on the potential benefits of herbal interventions in managing hypercholesterolemia. Preliminary findings suggest that specific herbal interventions may contribute to lower cholesterol levels, potentially complementing standard hypercholesterolemia management strategies. The findings will be systematically analyzed and presented upon completion of the review, providing insights into the effectiveness of integrating these interventions into current treatment protocols.

Background: The benefits of physical activity are well established in people with multiple sclerosis (MS); yet, most people with MS are insufficiently active. Although many apps and devices are available to promote physical activity, these are not connected to electronic health records (EHRs), making it difficult for health care providers to prescribe and monitor their patients’ physical activity. The ExerciseRx platform is an innovative cloud-based, Health Insurance Portability and Accountability Act–compliant software platform (app+provider dashboard) that was developed to bridge the gap between consumer activity tracking devices, such as personal smartphones, and the EHR. The ExerciseRx app tracks a patient’s physical activity using their existing personal smartphone and provides a personalized graded progression in step count goals to increase step count gradually and safely over time. The ExerciseRx app also translates the activity data into actionable metrics on a provider dashboard within the EHR that the provider can use to make activity recommendations and monitor patients’ progress; they can also support patients by providing semiautomated weekly feedback and encouragement in meeting physical activity goals.

Background: Abnormal cell growth that can multiply and transfer to other bodily parts is referred to as cancer. Chemotherapy is a standard treatment for cancer patients. During or after treatment, patients may have varying degrees of cognitive impairment caused by the drug, which can negatively impact their quality of life. Cognitive impairment brought on by chemotherapy is one of the most frequent side effects that occur both during and after chemotherapy. Cognitive effects after and during chemotherapy have not been addressed in patients. Objective: To evaluate the effectiveness of cognitive rehabilitation on cognition and quality of life in chemotherapy-induced cognitive impairment. Methods: In this Randomized Control Trial (RCT), 60 subjects with chemotherapy-induced cognitive impairments secondary to any cancer will be randomised into 2 groups by the sequentially numbered opaque sealed envelope approach. The cognitive functions will be measured as the outcome measures, which include all the recall strategies, executive function tasks, information processing speed, and attention. Both groups will receive intervention every day for 4 weeks. Wilcoxon signed the rank test for data analysis, and students paired the “t” test, which will be used to study within-group effects. Mann-Whitney U Test and students Unpaired “t” Test will be used to compare groups at pre-treatment and post-treatment. Results: As of November 2024, we will enrol 60 participants, and the data collection process will start from November 2024November 2025. The expected results of the effect of cognitive rehabilitation on cognition and quality of life in chemotherapy-induced cognitive impairment in cancer patients will be significant, and the expected results will be published at the end week of November 2025. Conclusions: The study design is a framework to plan and test the feasibility of the intervention. The cognitive therapy will improve the cognition in chemotherapy-induced cognitive impairment patients. Trial Registration: Clinical Trials Registry India CTRI/2024/04/065805; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTAyNTE1&Enc=&userName= International Registered Report Identifier (IRRID): DERR1-10.2196/66011

Background: Chronic pain is one of the most common and debilitating health conditions. Treatments for chronic low back pain typically focus on biomedical treatment approaches. While psychosocial treatments exist, multiple barriers prevent broad access. There is a significant unmet need for integrative, easily accessible, non-opioid solutions for chronic pain. Virtual reality (VR) is an immersive technology allowing innovation in the delivery of behavioral pain treatments. Behavioral skills-based VR is effective at facilitating pain management and reducing pain-related concerns. Continued research on these emerging approaches is needed. Objective: In this randomized controlled trial, we seek to test the efficacy of a self-administered behavioral skills-based VR program as a nonpharmacological home-based pain management treatment for people with chronic low back pain (cLBP). Methods: We will randomize 180 individuals with cLBP to 1 of 2 VR programs: (1) EaseVRx (8-week skills-based VR program); or (2) Sham VR (control condition). All participants will receive a VR headset to minimize any biases related to the technology’s novelty. The Sham VR group had 2D neutral content in a 3D theater-like environment. Our primary outcome is average pain intensity and pain-related interference with activity, stress, mood, and sleep. Our secondary outcomes include patient-reported physical function, sleep disturbance, pain self-efficacy, pain catastrophizing, pain acceptance, health utilization, medication use, and user satisfaction. We hypothesize superiority for the skills-based VR program in all of these measures compared to the control condition. Team statisticians blinded to treatment assignment will assess outcomes up to 6 months posttreatment using an approach suitable for the longitudinal nature of the data. Results: The study was approved by the Western Institutional Review Board on July 2, 2020. The protocol (NCT04415177) was registered on May 27, 2020. Recruitment for this study was completed in July 2020, and data collection will remain active until March 2021. In total, 186 participants were recruited. Multiple manuscripts will be generated from this study. The primary manuscript will be submitted for publication in the winter of 2020. Conclusions: Effectively delivering behavioral treatments in VR could overcome barriers to care and provide scalable solutions to chronic pain’s societal burden. Our study could help shape future research and development of these innovative approaches.

Background: Chronic neuropathic pain affects 69% of adults with spinal cord injury (SCI). Medication, as a primary treatment, has insufficient benefits and significant risks for addiction and adverse effects. Of the available mind and body approaches, Qigong is the most accessible for adults with SCI, with evidence for effectiveness in reducing pain. Still, there is insufficient evidence to make recommendations for adults with SCI. Thus, the feasibility of Qigong in SCI needs to be established. We previously demonstrated feasibility in a pilot study, in which 18 non-Hispanic White adults with SCI completed a 12-week remote Qigong program. However, three additional key elements need to be addressed before performing a larger effectiveness study: (1) feasibility and acceptability of Qigong in adults with SCI with health disparities, (2) feasibility of a study design with a control group, and (3) objective outcome measures.

Background: Sexuality is multidimensional and complex, and involves identity development, attraction, and behavior. Heterosexual-identified men who have sex with men (H-MSM) experience sexual identity and behavior discordance, yet it is unknown how H-MSM compare to concordant heterosexual men and gay, bisexual, and queer (GBQ+) men in terms of sexuality constructs. Objective: This study aims to survey adult cisgender men in Canada, the United States, and the United Kingdom to gain greater insights into how demographics, identity development, attraction, behavior, technology use, relationship negotiation and communication skills, and pre-exposure prophylaxis and life satisfaction relate to each other, and then to interview H-MSM for an in-depth follow-up on survey concepts. Methods: Purposive sampling will be used to recruit men via online and offline venues. Data collection will be multifaceted and include an online questionnaire for adult cisgender men and a subsequent interview for H-MSM. The survey will be available in English, French, and Spanish. Structural equation modeling, underpinned by hegemonic masculinity and sexual script theories, will be performed to test the relationships among survey variables. Interpretive phenomenology will be employed on the qualitative data to consider how unique sociocultural factors influence the sexuality and experiences of H-MSM, allowing for similarities and differences across participants to be identified and explored. Results: Data collection began on November 26, 2024, and as of February 2025, data collection remains ongoing. We expect to conclude data collection and data cleaning by mid-summer 2025. Data analysis will begin in fall 2025. Our findings will provide a more nuanced understanding of the identity development, attraction, behavior, relationship negotiation, and technology use of H-MSM in comparison with GBQ+ men and concordant heterosexual men. Conclusions: This research aims to broaden the scope of existing literature and support advancements in interventions and knowledge to support the overall health and well-being of H-MSM. An examination of potential differences among H-MSM, concordant heterosexual men, and GBQ+ men aims to improve the understanding of H-MSM as a distinct population, without dismissing them as closeted GBQ+ men. This study aims to provide key insights into avenues for research and practice with men whose sexuality and sexual behaviors may be outside of commonly accepted norms.

Background: The incidence of chronic diseases associated with physical inactivity is on the rise, being one of the leading risk-increasing factors for early death rates throughout the world. Often, physical activity interventions fail to deliver sustained adherence over time due to limiting tailoring to individual baseline characteristics, leaving out contextual changes over time. One solution for this issue may be the use of adaptive interventions relying on contextual multiarmed bandits, a type of reinforcement learning algorithm, that can use baseline and contextual individual data to personalize aspects of the intervention, such as developing personalized workout plans. Objective: The main objectives of this study are (1) to determine the effectiveness of contextual bandits for automated goal setting in the context of a web-based physical activity intervention, (2) to understand the role of user characteristics impacting ideal workout schedules based on adherence to predetermined goals, and (3) to explore the influence of user autonomy on recommendation effectiveness. Methods: We developed a protocol for a web-based adaptive intervention trial to investigate the effectiveness of goal recommendation (task difficulty) based on reinforcement learning. The web application (named Apptivate) creates workout routines with 3 different difficulty levels, changing the total workout duration as well as rest times between exercises. Physical activity professionals validated the routine design, ensuring that workouts match recommended guidelines for healthy adults. An initial pilot was conducted, aiming for 800 university students to test the web application for 1 week, to provide initial data to calibrate the algorithm as well as overall feedback for the web application. For the main study, a total of 500 university students will be recruited to participate for 40 days during early 2026. Participants will be divided into 3 groups: user choice (no recommendation), user choice with automated recommendations (contextual bandits), and automated plans without choice. Results: The pilot was conducted in September 2025. Data analysis for the pilot is undergoing, and the main study is planned for early 2026. Our main statistical analysis includes a direct comparison (paired tests) between success rates across intervention arms, as well as by difficulty level and individual characteristics. Conclusions: Physical activity maintenance is key to achieving long term health goals. Tailored digital interventions are promising strategies for physical activity adherence, but personalization often fails to consider dynamic contextual changes. The proposed protocol for a physical activity intervention using adaptive experimentation can provide robust causal inference on the role of choice versus autonomy when goal difficulty is tailored under an adaptive data-driven approach.