BackgroundFamily caregiving for individuals with Alzheimer disease and related dementias (ADRD) is characterized by increasing complexity, intensity, and demand across the disease trajectory. Formal home- and community-based services can provide knowledge, skills, and resources to enhance preparedness and self-efficacy, which may protect against adverse caregiving outcomes; however, awareness and uptake of these services remain low. As caregivers increasingly turn to the internet for information and support in their role, technology offers an opportunity to create a more seamless pipeline between assessment and service referral to match family caregivers with targeted services that meet their specific needs.ObjectiveThe primary objective of this study is to evaluate the feasibility and acceptability of CarePair—a mobile self-assessment and service referral platform—among ADRD family caregivers. Secondary objectives are to assess the preliminary efficacy of CarePair in reducing stress, depressive symptoms, and anxiety, and enhancing self-efficacy among caregivers randomized to the intervention versus an attention control condition. This study also aims to generate preliminary effect size estimates to inform sample size calculations for a future fully powered randomized controlled trial (RCT).MethodsThis pilot RCT will evaluate the feasibility, acceptability, and preliminary efficacy of CarePair. Eighty ADRD family caregivers will be enrolled and randomized in a 1:1 ratio to the intervention (n=40) or an attention control condition (n=40). Recruitment will be facilitated by the project study site located in an urban metropolitan area of the United States, targeting participants who report residing in and/or being in close proximity to any of the following locations: New York City, Long Island, and Westchester County, New York; Seattle, Washington; and Los Angeles, California. Primary feasibility outcomes include recruitment, retention, and completion rates; website usability; and intervention satisfaction. Exploratory analyses will assess preliminary efficacy on stress, depressive and anxiety symptoms, and self-efficacy.ResultsThis trial was funded by the National Institute on Aging in September 2023 and received approval from the institutional review board of the University of Southern California on September 10, 2025. Recruitment began in September 2025 and is scheduled to conclude in May 2026, with data collection scheduled to end in August 2026. As of February 2026, 44 participants have been enrolled and 22 have completed the study.ConclusionsThis pilot trial will offer foundational evidence regarding the feasibility and acceptability of the CarePair intervention. Study findings will determine if “go” criteria are met to warrant the advancement to a larger-scale efficacy trial. Participant insights will also be used to guide intervention refinements and digital platform optimization. By offering a low-burden, caregiver-centered mobile app, CarePair has the potential to facilitate and streamline the timely identification of needs and referral to relevant services for ADRD family caregivers.

Attention deficit/hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder worldwide, affecting approximately 5%-7% of school-aged children and 2%-5% of adults worldwide. However, there is still no reliable diagnostic tool for it. The lack of specific biomarkers further complicates the accurate diagnosis of ADHD. The SINCRONIA study seeks to develop and optimize an electroencephalogram (EEG)-based ADHD diagnostic classification algorithm by identifying biomarkers that provide optimal diagnostic performance. This protocol introduces a single-center, case-control study involving at least 165 participants, aged between 7 and 12 years, that is being conducted at the Puerta de Hierro University Hospital in Madrid, Spain. Participants will be allocated to 3 groups, including ADHD predominantly inattentive, ADHD predominantly combined or hyperactive/impulsive, and a control group, according to the best estimated diagnosis based on clinical interviews and a neuropsychological assessment that includes the Conners Continuous Performance Test. In addition, an EEG recording will be conducted separately, and functional connectivity metrics will be used to characterize brain networks associated with inhibitory control. The index test is expected to match or improve the clinical diagnosis of ADHD in children aged between 7 and 12 years and provide a set of eventual biomarkers that maximize diagnostic performance and provide pathophysiological clues. The SINCRONIA study began screening and recruitment in March 2023. Recruitment ended on December 11, 2024. A total of 165 eligible participants were enrolled. The SINCRONIA project is a high-quality, large-scale, unicenter study devoted to improving the objective diagnosis of ADHD by using EEG biomarkers. The EEG-based ADHD diagnosis is expected to have greater sensitivity and specificity than the Conners Continuous Performance Test.

BackgroundAdjuvant endocrine therapy is a cornerstone in managing estrogen receptor–positive early breast cancer but may adversely affect metabolic health, including weight gain, insulin resistance, and dyslipidemia. These changes increase the risk of cardiovascular disease and may influence breast cancer outcomes. However, the timing and magnitude of early metabolic changes following endocrine therapy initiation remain poorly characterized. Conventional definitions such as metabolic syndrome rely on dichotomous thresholds and may lack sensitivity to detect early treatment-related metabolic changes, highlighting the need for refined assessment approaches.ObjectiveThis prospective follow-up study aims to investigate early metabolic effects of initiating adjuvant endocrine therapy in women with estrogen receptor–positive early breast cancer and to compare conventional and expanded approaches to metabolic health classification.MethodsThis single-center, prospective observational study was conducted at Aarhus University Hospital, Denmark. Women aged≥18 years with early-stage estrogen receptor–positive breast cancer initiating adjuvant endocrine therapy and without pre-existing diabetes were eligible. Metabolic health was assessed at baseline and after 3 months using biometric measurements (weight, waist and hip circumference, waist-to-hip ratio, and blood pressure) and non-fasting blood samples (plasma glucose; hemoglobin A1c, (HbA1c); lipid profile; and estradiol). The 3-month follow-up was selected to capture early metabolic changes while aligning with routine clinical care to minimize additional visits and reduce selection bias. Metabolic health will be evaluated using two conventional measures and two extended, exploratory measures. Conventional measures are metabolic syndrome (MetS), defined as meeting ≥3 of 5 established criteria (blood pressure ≥130/85 mmHg, triglycerides >2 mmol/l, high-density lipoprotein cholesterol <1.295 mmol/l, waist circumference >88 cm, and plasma glucose >7.8 mmol/l), and the Metabolic Syndrome z score (MetS-Z), a continuous standardized composite of the MetS components. Additional extended measures are exploratory: the extended MetS, which expands the standard MetS definition by incorporating low-density lipoprotein cholesterol (>3 mmol/l), body mass index (≥30 kg/m²), waist-to-hip ratio (>0.85), and HbA1c (≥42 mmol/mol), and the EMETA score, a standardized composite of the extended MetS components calculated using the same approach as the MetS-z score.ResultsThe study was funded in July 2024. Recruitment occurred between November 2024 and April 2025, and follow-up was completed in September 2025. Statistical analyses are planned for February 2026, with results expected to be published in summer 2026.ConclusionsThis study is expected to provide insights into early metabolic changes following initiation of adjuvant endocrine therapy and evaluate different approaches to classifying metabolic health. The aim to inform future research by helping to identify patients at increased risk of cardiometabolic complications and adverse breast cancer outcomes, warranting confirmation and validation of expanded metabolic measures in longer-term, larger cohorts.

Frailty is a progressive, dynamic clinical syndrome characterized by reduced physiological reserves and increased vulnerability to stressors, leading to adverse outcomes in older adults. Despite its clinical significance, routine detection of frailty remains challenging owing to subtle presentations and time constraints during assessments. Longitudinal studies are essential for capturing its biological trajectory and identifying early biomarkers. This scoping review aims to systematically identify and map biomarkers-including inflammatory, hormonal, metabolic, genetic, and imaging-based markers-investigated for their longitudinal associations with frailty in older adults. Studies involving older adults with comorbid conditions (eg, cancer, infectious diseases, cardiovascular diseases) will also be included when frailty is assessed as an outcome. We will conduct a comprehensive literature search in 6 databases (PubMed, CINAHL, Cochrane Library, Scopus, Web of Science, and Embase). We will include longitudinal studies that examine the association between objectively measured biomarkers and frailty, as assessed with validated tools, in older adults. Studies published in English, Korean, or Chinese will be considered, with no restriction on publication date. We identified 3315 records after duplicate removal in an exploratory search conducted in July 2024, indicating a substantial body of literature for review. We plan to complete this review by December 2026. This review will identify and describe longitudinal biomarkers that precede frailty in older adults, highlighting their potential for personalized clinical application. Anticipated limitations include reliance on observational study designs, methodological heterogeneity, and limited causal inference. PRR1-10.2196/83312.

BackgroundEffective collaborative practice among health care professionals is crucial for addressing intimate partner violence (IPV) during pregnancy. Therefore, the development and evaluation of an evidence-based intervention for health care professionals is required to work toward meeting the key priorities of the National Plan to End Violence Against Women and Children 2022‐2032. The consistency, modality, and effectiveness of IPV-focused education vary, and some midwives lack the confidence to respond effectively to disclosures, often due to limited knowledge, education, and skills. This issue is further amplified in interdisciplinary settings, where a lack of cohesiveness and collaboration can negatively impact the experience for pregnant women seeking or needing support.ObjectiveThe objective of this study is to design, implement, and evaluate an evidence-informed, simulation-based, interprofessional education intervention to improve health care professionals’ collaborative response to IPV disclosures during the perinatal period in the South Australian maternity health care sector.MethodsThis study adopts an exploratory mixed methods research design with 3 key phases. Phase 1 explores the experiences of women with lived experience of IPV in pregnancy (a minimum of 9 participants), and health care professionals providing perinatal care (4‐8 participants in approximately 4‐8 focus group offerings). The data will inform the development of the educational program. Phase 3 focuses on the evaluation of the intervention to determine the perceived impact. There will be several offerings of the workshops to capture a minimum of 42 health professional participants.ResultsQualitative data will be collected first from interviews with women with lived experience of IPV in the perinatal period and focus groups with health professionals who have provided care across that context. Phase 3 comprises quantitative survey data through a single-group quasi-experimental pretest-posttest design to determine the perceived impact of the workshop.ConclusionsThis study aims to provide insights into the effectiveness of educational interventions designed to enhance collaboration within interdisciplinary teams in the context of IPV.

BackgroundDespite a global decreasing trend in neglected tropical diseases (NTDs), progress is not on track to meet the Sustainable Development Goals by 2030. Evidence suggests a positive effect of conditional cash transfer programs on controlling NTDs. However, it remains to be evaluated whether other financial incentive programs exert similar effects on NTD-related service utilization and treatment outcomes in low- and middle-income countries (LMICs).ObjectiveThis systematic review aims to evaluate the effects of cash transfer and incentive programs on NTD-related service utilization and treatment outcomes in LMICs; to examine how covariates, program design, and implementation plan influence these outcomes; and to examine how NTD-related service utilization and treatment outcomes influence nutritional status and health in LMICs.MethodsThis review will follow the PICOS (Population, Interventions, Comparators, Outcomes, Study Design) framework. The population of this review will be restricted to adults and children of all ages in LMICs. For intervention selection, we will include any program or policies addressing socioeconomic disadvantage through the provision of cash transfers or incentive programs, including but not limited to in-kind transfers, food vouchers, free medicine vouchers, discount coupons, and microcredit to households or individuals. Eligible comparators will be the population who did not receive any intervention, recipients of interventions from before the intervention, and populations or areas exposed to different levels of intervention coverage. The primary outcomes will be service utilization and treatment outcomes related to any of the 21 NTDs prioritized by the World Health Organization. Studies without any financial incentive intervention will be excluded. Studies available in English between 2000 and 2024 will be searched in databases, including PubMed, Google Scholar, Scopus, Cochrane, Embase, and CINAHL. Screening, data extraction, and risk of bias assessment will be conducted independently by two reviewers, and discrepancies, if any, would be resolved by a third reviewer. Quality assessment will use the Revised Cochrane Risk of Bias for randomized trials (RoB 2), Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I), the Joanna Briggs Institute (JBI) checklist for cross-sectional studies, and the Critical Appraisal Skills Programme (CASP) tool for qualitative studies. Data synthesis will involve narrative summaries by tables and figures, a meta-analysis will be undertaken, and subgroup analyses will be performed where feasible.ResultsThis project is supported by the Children’s Investment Fund Foundation and was funded in March 2024. As of January 15, 2026, article search and title-abstract screening have been completed, and full-text screening is expected to be completed by February 2026. Findings will then be synthesized and reported by the end of April 2026.ConclusionsThe limitations of the study may include potential language bias and methodological heterogeneity, which may limit the feasibility of meta-analysis. The findings of this review will inform policymakers in developing more effective strategic plans for controlling NTDs in LMICs.

BackgroundDespite the availability of effective vaccines, flu and COVID-19 uptake remains suboptimal, including among Indigenous communities in California who face unique barriers to accessing public health information. While previous research has evaluated health communication message content and design, fewer studies have systematically compared different dissemination strategies for the same intervention, leaving gaps in understanding optimal approaches for reaching marginalized populations.ObjectiveThis protocol describes a three-arm dissemination study designed to compare the effectiveness of different strategies for distributing COVID-19 and flu vaccine promotion videos among Indigenous Peoples residing in California, including American Indian and Alaska Natives, and migrant Indigenous Peoples from Latin America.MethodsFollowing extensive formative work, including cross-sectional surveys, social network analyses, a discrete choice experiment, and qualitative focus groups conducted with guidance from an Indigenous Community Advisory Board, we developed four 30-second vaccine promotion videos available in English and Spanish, two targeting American Indian and Alaska Native communities and 2 targeting Latin American communities. Videos will be translated to four Indigenous languages (Purépecha, Mam, Zapoteco, and Mixteco). The study compared three dissemination strategies implemented over a two-month period: (1) targeted social media advertisements on Facebook and Instagram, (2) distribution through community-based organizations using their established communication channels, and (3) peer-to-peer sharing through Indigenous community members (“seeds”) recruited from previous research. Primary outcomes focus on dissemination effectiveness, defined by measures of reach (eg, link shares, clicks and video views), engagement (eg, watch time and survey completion), and message impact (eg, trust in the message and vaccination intent), assessed using Bitly link tracking, YouTube analytics, and follow-up surveys. Descriptive and comparative analyses will be conducted to assess differences across dissemination strategies.ResultsThe study was funded in January 2023. Intervention development was completed in July 2025. Dissemination activities and data collection across all three study arms were conducted between October 6, 2025, to November 28, 2025, aligned with the COVID-19 and influenza vaccination season in the United States. Data consolidation, cleaning, and analyses began January 2026 and primary results are expected to be submitted for publication in Spring 2026.ConclusionsThis study addresses a critical gap in health communication research by providing a systematic methodology for comparing digital dissemination strategies within Indigenous communities. The combination of community-informed recruitment, multilingual accessibility, and comprehensive digital tracking tools offers a replicable model for evaluating how public health messages spread through different channels, particularly for populations historically excluded from traditional outreach efforts.

BackgroundHypertension is a chronic condition and a leading risk factor for cardiovascular disease, stroke, and premature mortality worldwide. While blood pressure (BP) monitoring—via clinical, home, or ambulatory measurements—remains the primary diagnostic tool, each method is limited by variability, device inaccuracy, and difficulties in detecting atypical BP patterns such as masked or white-coat hypertension. These challenges underscore the need for innovative, complementary diagnostic approaches.ObjectiveThis systematic review and meta-analysis aims to synthesize current evidence on the role of metabolomic profiling in the detection and understanding of hypertension. Specifically, it seeks to evaluate whether metabolomics can identify preclinical metabolic signatures, improve diagnostic accuracy, and elucidate pathophysiological mechanisms underlying hypertension, thereby complementing traditional BP monitoring.MethodsA systematic search will be conducted in PubMed, Embase, Web of Science, Scopus, and CENTRAL from inception to the present supplemented with manual screening of metabolomics repositories (MetaboLights and Metabolomics Workbench) to ensure comprehensive coverage. This systematic review will include studies involving adults (aged ≥18 years) that investigate metabolomic biomarkers in hypertension using validated analytical platforms such as nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry, or liquid chromatography–mass spectrometry. Eligible studies must stratify participants into hypertensive, prehypertensive, or normotensive groups and report associations between metabolites and BP measurements. Two independent reviewers will conduct study selection, data extraction, and risk-of-bias assessment using version 2 of the Cochrane risk-of-bias tool for randomized trials and the Risk of Bias in Nonrandomized Studies of Interventions and Risk of Bias in Nonrandomized Studies of Exposures tools, with evidence certainty evaluated via the Grading of Recommendations Assessment, Development, and Evaluation framework. A meta-analysis will be performed where possible using random-effects models and subgroup analyses to address heterogeneity.ResultsDatabase search, screening, and data extraction are ongoing as of January 2026. The results will summarize metabolomic profiles (such as stearidonate and hexadecadienoate), diagnostic accuracy metrics (eg, area under the curve and sensitivity), and metabolic pathways associated with hypertension once data synthesis is completed. The systematic review and meta-analysis is expected to be published in August 2026.ConclusionsThis review will identify metabolites showing consistent hypertension associations and document methodological requirements for clinical translation, including standardization of sample collection, analytical platforms, and data processing. The findings will inform longitudinal validation studies and establish evidence-based pathways for potential applications in hypertension risk assessment and clinical trial design. Validation of consistently identified metabolite-hypertension associations in independent, prospective cohorts will be critical for establishing causality and assessing the temporal stability of metabolomic signatures. The review will also identify methodological gaps requiring standardization, such as sample collection protocols, analytical platform harmonization, and data processing procedures, which must be addressed before metabolomic findings can be translated into clinical applications.

Traditional Chinese medicine (TCM) functions according to the concepts of "holism" and treatment based on syndrome differentiation, and it has achieved good clinical results in treating patients with dysmenorrhea, which is a common gynecological disorder. However, there are currently no international clinical practice guidelines involving TCM therapies for dysmenorrhea. This study aims to establish a protocol for the development of such guidelines. This protocol will provide a road map for the development of the first international clinical practice guidelines on TCM therapy for dysmenorrhea. The guidelines will be developed with reference to the General Rules of Preparation of Diagnosis and Treatment Guideline in Traditional Chinese Medicine and the Western Medicine Guideline and Traditional Chinese Medicine Guideline: Improving Together in Mutual Learning. They will be developed in accordance with the Appraisal of Guidelines for Research and Evaluation II and the World Health Organization guideline handbook and will make recommendations based on systematic reviews. We have established a guideline working group and will formulate clinical questions using the participants, interventions, comparisons, outcomes, and study design framework. The recommendations will be developed through evidence retrieval, synthesis, and the Delphi method. We will consider the preferences and values of patients, as well as the costs and the pros and cons of interventions. This work was supported by the National Key R&D Program of China (grant 2019YFC1712000) in 2019. The writing group for guidelines was formed in January 2021. The literature search and screening process began in May 2022. So far, the literature search and 2 rounds of the Delphi method have been completed. The protocol will provide a road map for the development of the first international clinical practice guidelines on TCM therapy for dysmenorrhea. The guideline will be developed in accordance with this protocol, which may provide support and evidence for TCM treatment in patients with dysmenorrhea. There is currently a need for clinical practice guidelines in TCM for the treatment of dysmenorrhea.

Oral disease remains a global public health concern, disproportionately affecting socioeconomically disadvantaged populations. Adults with disabilities or health conditions face additional barriers to dental care, including physical accessibility, communication challenges, and heightened anxiety. These factors contribute to care avoidance and poorer oral health outcomes. While virtual reality (VR) has shown promise in reducing procedural anxiety in pediatric and private dental settings, its application in adult public dentistry, particularly for people with disabilities, remains underexplored. This study aims to evaluate the feasibility, usability, and acceptability of Smileyscope, a Therapeutic Goods Administration-approved head-mounted VR headset, in reducing dental anxiety and enhancing care experiences for adults with disabilities in public dental clinics. A mixed methods convergent design will be implemented across community dental sites in Victoria, Australia. In total, 50 adult patients and up to 10 dental staff members will be recruited. Primary feasibility indicators include recruitment rate (≥60% consent), completion rate (≥80% System Usability Scale [SUS] completion), and usability threshold (mean SUS ≥68). The primary analysis will be descriptive, with 95% CIs reported. Quantitative data will be collected using the visual analog scale for willingness, the SUS, and the technology acceptance model questionnaire. Qualitative data from semistructured interviews will be thematically analyzed. The study is co-designed with a disability advocate and integrates lived experience throughout all phases, including recruitment, evaluation, and dissemination. The project was funded in 2025, and ethics approval was granted by Peninsula Health Human Research Ethics Committee (project ID 117565). Data collection is scheduled for October 2025 to March 2026 at the participating community dental sites. Primary feasibility estimates and qualitative themes are expected to be submitted for publication in mid‑2026. This protocol outlines a feasibility study that will inform scalable models for VR integration into public dental services. The findings will contribute to improved oral health equity and patient-centered care, advancing the evidence base for inclusive digital health innovation in dentistry. PRR1-10.2196/85916.