JMIR Research Protocols

Objective: To identify patient- and clinician-reported barriers, facilitators, and design requirements for a centralized cascade-screening program for familial hypercholesterolemia (FH) in the United States. Methods: From June through November 2023, we conducted individual telephone interviews with 20 patients with FH and 10 clinicians recruited from UT Southwestern Medical Center, Parkland Health, the North Texas Veterans Affairs, and other clinical settings. Interview guides were informed by the Consolidated Framework for Implementation Research. Transcripts were coded in Dedoose using a piloted codebook, with discrepancies and emergent themes resolved through consensus. An advisory panel then helped translate interview findings into program design requirements and implementation strategies. Results: Five themes characterized barriers and facilitators to centralized cascade screening: (1) health-system access and fragmentation, including screening and treatment costs, transportation, and cross-system coordination; (2) privacy and trust, including concerns about genetic information and unsolicited outreach; (3) family relationships and practical burden, including competing demands, language barriers, limited contact, fear, and denial; (4) clinician capacity and workflow, including limited time, knowledge, and genetic-counseling capacity; and (5) communication and care continuity. Participants recommended proband pre-notification of relatives, culturally and linguistically responsive materials, secure data exchange, standardized scripts, flexible testing pathways, and centralized coordination. These findings informed a program model incorporating a secure pedigree platform, educational and communication resources, testing coordination, and linkage to follow-up care. Conclusions: Patients and clinicians identified multilevel determinants that a centralized FH cascade-screening program must address. The findings support specific design requirements but do not establish program feasibility or effectiveness, which require prospective evaluation.

Background Stroke remains one of the leading causes of mortality and long-term disability worldwide, with low- and middle-income countries bearing a disproportionate share of the global disease burden. In India, delays in risk identification, fragmented referral pathways, and limited continuity of preventive care present significant challenges, particularly in rural communities. As a frontline health worker Accredited Social Health Activists (ASHAs) are strategically positioned to support community-based stroke prevention; however, existing workflows are frequently constrained by multi-tasking, predominantly paper-based documentation and fragmented digital systems. Advances in mobile health, artificial intelligence along with digital health ecosystem provided by Ayushman Bharat Digital Mission (ABDM) provide an opportunity to strengthen community healthcare through integrated digital platforms. Objective This protocol describes the design, system architecture, and prospective evaluation framework of ASHA Assist India, an integrated AI-assisted mobile health platform intended to support community-based stroke prevention by connecting citizens, ASHA workers, Primary Health Centres (PHCs), and higher levels of healthcare facilities within a unified digital ecosystem. Methods ASHA Assist India has been designed as a modular, cloud-based digital health platform supporting standardized data collection, longitudinal health monitoring, referral management, and AI-assisted clinical decision support. The proposed system comprises four user-facing applications corresponding to citizens, ASHA workers, PHCs, and referral hospitals, integrated through a centralized backend providing authentication, secure data management, interoperability, analytics, and notification services. The AI framework includes three planned analytical modules: (i) population-level stroke risk stratification, (ii) longitudinal stroke risk prediction, and (iii) acute stroke symptom recognition. A prospective implementation study is planned to evaluate platform usability, feasibility, workflow integration, implementation outcomes, and operational performance within routine community healthcare settings. Future validation of the AI modules will be conducted using prospectively collected longitudinal datasets. Expected Impact The proposed platform aims to strengthen community-based stroke prevention by improving digital workflow integration, facilitating coordinated referral pathways, and supporting longitudinal monitoring through the existing healthcare providers at health and wellness centres like ASHA, Community Health Officers (CHOs), ANM, etc. Beyond stroke prevention, the modular architecture is intended to provide a scalable framework for future digital health programmes addressing multiple non-communicable diseases within primary healthcare systems. Publication of this protocol establishes a transparent implementation and evaluation framework that may guide future research, digital health innovation, and implementation science in resource-constrained settings.

Background Scientific mistrust contributes to lower participation and underrepresentation of Black Americans in genomics studies limiting understanding of how genomic variation and environmental exposures influence health disparities. Community-engaged research requires rebuilding scientific trust; however, there is a need for practical models that operationalize guidance for researchers without community-engaged research training. Therefore, we developed an educational intervention for genomics researchers initiating partnerships with Black American communities. Our intervention creates a bidirectional teaching environment that allows potential community and academic partners to discuss areas of expertise for each stakeholder, partnership perspectives and needs, while exploring modules related to genomics research and community-academic partnership. We report a novel and structured approach for prospective academic and community partners to mutually orient one another and assess partnership practicability. Methods Ten participants, recruited through established community channels, attended a four-hour workshop containing nine interactive modules about scientific mistrust, research safeguards, community-engaged research, genomics, and research for community-defined goals. We also experimented with humor to enhance engagement and trust. We used mixed-methods, single-arm research design and assessed feasibility through recruitment success and retention. Using inductive rapid thematic analyses, we assessed participant responses to eight workshop prompts. Preliminary quantitative data, used for descriptive purposes due to low sample size, were analyzed from pre- and post-Likert scale surveys assessing associations between the intervention and four domains, including scientific trust. Results All 10 enrolled participants completed the study, meeting a priori criteria of 100% for recruitment and show rate. Engagement was strongest during early workshop modules and declined in later modules. Survey data completeness was limited by missing responses. Survey instrument design limitations were identified for modification in future studies. Participants articulated expectations for partnership that aligned with community-based participatory research principles. Conclusions The intervention is feasible to deliver as a bidirectional educational experience in partnership with a community organization. The strongest implementation refinements needed were workshop duration, module prioritization, and survey instrument design, particularly the trust domain. A community advisory board is co-developing modules and refining the intervention to evaluate in a pilot version of the study with a larger sample.

Background: Maternal obesity is associated with lower breastfeeding initiation, shorter breastfeeding duration and lower rates of exclusive breastfeeding. Although breastfeeding intention predicts initiation, little is known about how first-time mothers living with obesity experience the transition from antenatal intention to postpartum reality. Aim: This qualitative study explored breastfeeding expectations, intentions, attitudes and early breastfeeding challenges among first-time mothers living with obesity in Switzerland. Methods: Seven semi-structured interviews were conducted with first-time mothers living with obesity in German-speaking Switzerland. Interviews were audio-recorded, transcribed verbatim and analysed using reflexive thematic analysis according to Braun and Clarke. Results: All participants intended to breastfeed and described breastfeeding as part of motherhood. However, most experienced a postpartum reality that differed from their expectations. Three themes were developed: antenatal engagement with and expectations of breastfeeding, postpartum breastfeeding reality, and everyday breastfeeding life. Women received little antenatal breastfeeding counselling and faced challenges related to medicalised birth, delayed lactogenesis II, breast anatomy, pain, insufficient milk supply, pumping and inconsistent professional support. Several women described feelings of failure when breastfeeding did not work as hoped. Conclusion: First-time mothers living with obesity may have strong breastfeeding intentions but still experience major challenges after birth. Breastfeeding support should start during pregnancy and be realistic, respectful and weight-inclusive.

Introduction Research demonstrates neurodevelopmental differences in children who are HIV-exposed, but uninfected (CHEU) compared to their peers born unexposed. CHEUs are at higher risk for prematurity and low birth weight, both known risk factors for developmental delays. Despite increasing evidence, HIV exposure remains underrecognised as a risk factor for poor development by policy-makers and early childhood development (ECD) programs. We trialed an ECD intervention for CHEUs based on the Nurturing Care Framework developed by WHO, UNICEF, and the World Bank to improve neurodevelopmental outcomes in this vulnerable population. Design We conducted a randomized controlled trial of an ECD intervention for mothers living with HIV and their children born HIV-exposed, aged six to 24 months, living in peri-urban Lusaka. The intervention was delivered through bi-weekly home visits over 18 months using the curriculum adapted from the Nurturing Care Framework. The curriculum addressed nutrition, maternal wellness, child health, developmental milestones, and interactive caregiving. Method The primary outcome was measured by the Malawi Developmental Assessment Tool (MDAT) at six and 18 months post enrollment, which assesses developmental scores via a context-validated, direct observation tool across four domains: gross motor, fine motor, language, and social development. Participants were also assessed at six, 12 and 18 months post enrollment using the Caregiver Reported Early Development Instrument (CREDI). MDAT assessors were blinded to the intervention and control arm. Results We enrolled 308 mother-infant pairs, randomized 1:1 into an ECD intervention (CHEU control, n = 155; CHEU intervention, n = 153). At six months post enrollment, the intervention was associated with modest improvements in two developmental domains, particularly cognitive (Adjusted 0.28, 95% CI: 0.09 to 0.46; p= 0.004) and social-emotional development (Adjusted 0.29, 95% CI: 0.08 to 0.49; p= 0.07). At 18 month post enrollment, adjusted models demonstrated a moderate positive effect with gross motor development, with participants showing a 0.24 standard deviation higher score compared with the control group (95% CI: 0.02-0.46; p=0.034). Conclusion The findings indicate that the intervention may have a moderate impact on cognitive and social-emotional outcomes after six months, as well as on gross motor functions after eighteen months of intervention.

Background: Recruitment of diverse participants remains a challenge in cardiovascular clinical trials. Little is known about how recruitment efficiency and advertising costs with web-based tools vary across US communities. We evaluated an online recruitment platform and examined the cost of acquiring both all-comers and diverse participants in relation to community-level income. Methods: The Heartbeat Study evaluated a digital recruitment strategy to identify US participants for the ongoing Phase 3 LIBREXIA-AF trial. Online advertisements directed individuals with atrial fibrillation to a pre-screening website, where demographic and health data were collected. Advertising impressions, clicks, and costs were recorded. Participant ZIP codes were linked to Core Based Statistical Areas (CBSAs) and CBSA-level income. We measured recruits from underrepresented groups (women, African Americans, Latinos) completing online registration per $100,000 in advertising expenses. Click-weighted linear regression evaluated associations between CBSA income and advertising efficiency. Results: A total of 1,406 recruits completed online registration, with 1,319 participants from 260 CBSAs included in the geographic analysis. Participants were 73 years old on average; 547 (41.5%) were women, 59 (4.5%) African American, and 44 (3.3%) Latino. A total of $163,949.13 was spent on 82,681,711 impressions and 454,750 clicks. Recruits per $100,000 in advertising spend were 334 for women, 36 for African Americans, and 27 for Latinos. CBSA-level income was modestly inversely associated with cost per impression (R2=0.058; p<0.001) and cost per click (R2=0.038; p=0.005), but not recruitment yield for African Americans (p=0.99), Latinos (p=0.37), or women (p=0.21) (R2 range, 0.000-0.13). Conclusions: In this national analysis, online advertising enabled broad engagement across diverse US communities, but income was not associated with recruitment yield among women, African American, or Latino participants. Minority representation remained limited, suggesting digital recruitment alone may be insufficient to improve trial diversity. Targeted, culturally and linguistically tailored strategies may be needed to enhance diverse recruitment.

Background People with lower levels of literacy or health literacy may struggle to understand conventional health information. Video animations show promise as information tools, yet it is unclear whether video animations help reduce these inequalities in understanding. This study examined whether the effectiveness of video animations in health settings differs according to level of literacy or health literacy. Methods We drew on trials from a recent systematic review of video animations about healthcare or public health topics for patients or the public. We extracted available data on literacy, health literacy, or proxy indicators. One reviewer extracted data and a second checked all entries. Where possible, we conducted subgroup analyses of low and high literacy levels or interaction meta-analyses comparing low versus high literacy groups; otherwise, results were summarised narratively. Results From 88 eligible trials, we extracted health literacy data for 12. Across nine trials reporting knowledge, animations mostly improved knowledge compared with controls in both lower and higher health literacy groups. Effects on attitudes and behaviours were mixed and often small, with few studies reporting results by health literacy level. Across the subgroup analyses available, there was no consistent evidence of a pooled interaction effect of animations according to low and high literacy groups, but both statistical heterogeneity and small subgroup sizes limited precision of estimates. Across 88 trials, 54 (61%) reported education level, 22 (25%) did not, and 12 (14%) involved children or adolescents likely to have similar education levels. Conclusions Overall, the available data suggest that video animations can improve knowledge outcomes in both lower and higher health literacy groups, but their impact on attitudes and behaviour is less clear. Because literacy was rarely reported or analysed in the trials, it remains uncertain whether animations help to reduce literacy-related inequalities in access to, and use of health information.

Background: Abortion is safe when carried out using a method recommended by the World Health Organization (WHO), appropriate to the pregnancy duration, and by someone with the necessary skills. lobally, around 73 million induced abortions take place each year. Around 95% of maternal deaths occur in developing countries due to childbirth and pregnancy-related complications. Methodology: A descriptive cross-sectional study was used for the study among the married reproductive (20-45 years) age women using a non-probability purposive sampling technique. A self-developed semi-structured questionnaire was used via face-to-face interview for data collection. The collected data were analyzed using SPSS 16.0 version descriptive and inferential statistics were used to find the association between variables. Results: The findings of the study show that among 118 respondents, nearly two-thirds (57.6%) of the respondents had adequate knowledge and less than half (42.4%) of the respondents had inadequate knowledge regarding safe abortion. The study further shows that there was a significant association between the level of knowledge regarding safe abortion and education status and education level with p-value <0.05. Conclusion: The study concludes that nearly two third of the respondents have adequate knowledge regarding safe abortion. Educational status significantly influenced their level of knowledge. Thus, we could provide correct knowledge, education, and enhance awareness to married women in the reproductive age group.

Importance Non-inferiority trials are becoming increasingly popular in abdominal surgery. The non- inferiority margin is critical in the interpretation and conclusion of these trials. Objective This systematic review aims to assess the methodological and reporting quality of non- inferiority randomized controlled trials in abdominal surgery. Evidence Review Non-inferiority trials were systematically identified by searching Ovid Medline, Embase and the CENTRAL databases from 2006 until December 2025. Randomized controlled trials in adult patients with any type of abdominal surgical intervention in at least one trial arm and a sample size greater than or equal to 100 were eligible for inclusion. The primary outcome was the definition of the non- inferiority margin. Secondary outcomes were the reporting of the non-inferiority margin, the robustness of its estimation, the uncertainty of the point estimate and the adequacy of conclusions. Findings A total of 11 045 trials were identified, of which 101 were eligible, enrolling 44 370 patients. Most trials provided a rationale for the non-inferiority design, while six (5.9%) trials did not. Previous literature was commonly used (n=56; 55.4%), but the non-inferiority margin was most often based on a clinical fixed margin or on historical comparison of the treatment and the active comparator. Based on the margin, investigators tolerated substantially worse outcomes of the treatment compared to the comparator. Conclusions were appropriate based on the confidence interval and the predefined non- inferiority margin in 88 (87.1%) of trials. The clinical judgement of the conclusion was overall adequate. Confidence interval estimations were reported in 16 (15.8%) of trials. Simulation studies were limited by the reporting quality. Conclusions and Relevance Clinical fixed margins are commonly used in abdominal surgery non-inferiority randomized controlled trials, however, substantial shortcomings in reporting limit the interpretability and reproduction of study findings. Based on the findings of this study, guidance on surgical- specific non-inferiority margin definitions is needed.

Background: Cardiovascular health is affected by health behaviors, but postpartum behavioral influences are not well understood. We examined whether intrinsic motivation (IM) is longitudinally associated with long-term postpartum health behaviors (healthy eating, physical activity, self-weighing) and cardiovascular health (Life's Essential 8 [LE8] scores). Methods: The prospective Pregnancy, Lifestyle and Environment Study-2 (PETALS-2) followed women enrolled in the PETALS study at Kaiser Permanente Northern California during pregnancy (N=311). Data were collected via validated self-report surveys and objective measurements during pregnancy and 6-24 months postpartum (2017-2021). Health behaviors were dichotomized by sample-specific 75th percentiles (P75) or pre-specified thresholds (attaining guideline-recommended moderate-to-vigorous physical activity [MVPA, {greater than or equal to}150 minutes/week]; self-weighing regularly [{greater than or equal to}once/week]). Separate analyses lagged IM by timepoint to assess longitudinal associations between behavior-specific IM and immediate subsequent health behaviors; and between an IM composite and immediate subsequent LE8 scores. Results: Each one-unit higher IM score was associated with greater likelihood of Healthy Eating Index-2015 scores {greater than or equal to}P75 at 24 months postpartum (RR=1.42; 95% CI=1.07, 1.88); attaining MVPA guidelines at 6 (1.48; 1.03, 2.12), 12 (1.85; 1.26, 2.71), and 24 months postpartum (1.66; 1.22, 2.27); and regular self-weighing at 6 (1.53; 1.03, 2.27) and 12 months postpartum (1.65; 1.15, 2.36). Each one-unit higher composite IM score was associated with higher LE8 scores at 6, 18, and 24 months postpartum (18-month mean estimate=2.34; 95% CI=0.67, 4.02). Conclusions: Greater IM was associated with healthier behaviors and cardiovascular health through 24 months postpartum. Future research should test whether interventions targeting IM improve health behaviors and long-term maternal cardiovascular health.

Mobile clinical-support applications can facilitate access to evidence-based information at the point of care, but evidence on their usability and perceived usefulness among newly graduated physicians working in health facilities with limited capacity is scarce. We assessed physicians experiences with BMJ Best Practice using a convergent mixed-methods study. All 81 eligible physicians assigned to rural facilities were invited; 32 enrolled and received application access and training. After three months, participants completed an online survey, and 23 reported using the application. Ten physicians reporting the highest consultation frequency were purposively selected for semi-structured interviews. Survey findings showed a predominantly favorable perception of usability: for most items, 70%-90% of participants agreed or strongly agreed with the statements assessed. Among users, 14 of 23 (60.9%) used the mobile application and 9 (39.1%) used the web version. Interviews indicated that participants valued rapid searches, organized and evidence-based information, and support for diagnostic reasoning, referral decisions, learning, and clinical confidence. Barriers included limited connectivity, difficulties searching in Spanish, automatic updates, challenges locating or using some calculators, and treatment information that was sometimes insufficiently specific. Most importantly, participants could not always implement recommendations because suggested medicines, diagnostic tests, or other resources were unavailable in their facilities. Mobile clinical-support applications may complement decision-making and learning among early-career physicians in rural primary care. However, their practical value depends not only on usability and evidence quality, but also on adaptation to users language, workflow, connectivity, and local service capacity.

Problematic Internet Use (PIU)--marked by compulsive or maladaptive online behavior--is an emerging public health issue among adolescents and is associated with psychological distress, social difficulties, and academic problems. In Finnmark County, Norways northernmost and ethnically diverse region, limited research has examined the underlying mechanisms of PIU among Sami and non-Sami youth, despite increasing levels of digital engagement. This study protocol outlines a population-based cross-sectional survey investigating the associations between social norms (descriptive and injunctive), ethnic identity, and ethnicity-based discrimination in relation to PIU among Sami and non-Sami adolescents in Finnmark. Guided by Social Norm Theory and Ethnic Identity Theory, the study aims to examine risk and resilience factors associated with adolescents digital behavior in a geographically sparsely populated, multiethnic region. A population-based, cross-sectional school survey will include all upper secondary school students in Finnmark County (N {approx} 2,230). A culturally adapted, bilingual questionnaire (Northern Sami - Norwegian) will measure problematic internet use, perceived social norms in family, peer, and school contexts, ethnic identity, ethnicity-based discrimination, positive internet use, and key covariates. Ethnicity will be classified based on indicators of Sami language use and self-identification. Data will be prepared using prespecified quality procedures and analyzed with partial least squares structural equation modeling (PLS-SEM) to examine associations between social norms, ethnic identity, ethnicity-based discrimination, and internet use outcomes, including mediation and moderation. Group differences between Sami and non-Sami adolescents will be assessed using PLS Multi-Group Analysis. The findings may inform the development of culturally appropriate approaches to screening, prevention, and early intervention, and are relevant for mental health services, school-based programs, and public health strategies targeting Indigenous youth in rural and semi-rural regions.

Background Mirror therapy (MT)-specifically paradigms using mirror visual feedback (MVF)-is widely used in neurorehabilitation; however, mechanistic implementations vary substantially in movement content, rhythmicity and attentional demands. This protocol describes an acute mechanistic, within-participant fNIRS screening study designed to compare three prespecified upper-limb mirror-therapy task paradigms and to quantify associated subjective experience after each condition in healthy adults during a single visit. Methods and analysis This is a single-centre, within-participant, randomised crossover study conducted at Wuhan Wuchang Hospital (Wuhan, China). Healthy adults aged 18-35 years will complete three task conditions once each in a counterbalanced order using a 3*3 Latin-square scheme: UMT1 (task-oriented rhythmic functional movement), UMT2 (open-ended free movement with auditory control), and UMT3 (non-functional rhythmic movement). fNIRS will be acquired using the NirSmart-6000A system during a standardised block design. The primary outcome is ROI-level HbO activation quantified as GLM-derived {beta} estimates within the prespecified primary ROIs (bilateral SM1/M1 and bilateral PMC). Secondary outcomes include ROI-level windowed {Delta}HbO (5-20 s post-onset relative to the immediately preceding rest; descriptive only), ROI-level {Delta}HbR, and post-condition subjective ratings (illusion, immersion, confusion and fatigue; 1-7 Likert). Condition effects will be analysed using linear mixed-effects models with fixed effects for condition and period and prespecified multiplicity-adjusted pairwise contrasts. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Wuchang Hospital Affiliated to Wuhan University of Science and Technology (Approval No.: 2025-112-01; approved on 2025-08-21). The study is expected to be minimal risk. Findings will be disseminated through publication of this protocol manuscript and subsequent results manuscripts and conference presentations. Trial registration number Chinese Clinical Trial Registry (ChiCTR2600116634). This study is conducted as a prespecified mechanistic sub-study under the overarching registered project.

Background and Objectives: Robotic-assisted natural orifice specimen extraction surgery (NOSES) is a minimally invasive approach for mid-rectal cancer, but it is technically complex and lacks a standardized operational framework. This study aimed to propose and preliminarily validate a structured modular robotic NOSES II surgical procedure for mid-rectal cancer. Methods: This was a retrospective observational study that consecutively enrolled 11 patients with mid-rectal cancer who underwent modular robotic NOSES-II surgery at our center between December 2024 and August 2025. All procedures were performed by the same surgical team strictly following the predefined six-module structured surgical protocol. Perioperative indicators, pathological outcomes, and patient-reported outcomes (PROs) at 4 to 8 months postoperatively were collected. Key techniques were analyzed via high-definition surgical videos. Results: All 11 procedures were completed successfully without conversion to open surgery. The mean operative time was 299.6 plus or minus 54.2 minutes, and the mean intraoperative blood loss was 94.1 plus or minus50.6 mL. The mean number of harvested lymph nodes was 17.4 plus or minus 8.4, with a 100% R0 resection rate. No severe complications (Clavien-Dindo grade [&ge;] III) occurred. The mean postoperative hospital stay was 8.2 plus or minus 1.5 days. Postoperative PROs indicated good defecatory function, urinary function, and overall quality of life. Conclusions: Preliminary findings demonstrate that the structured modular robotic NOSES-II procedure is safe and feasible for the treatment of mid-rectal cancer. This modular protocol provides a clear and reproducible technical framework for this complex procedure, and it is expected to achieve favorable functional preservation while ensuring oncological radicality.

Background: Although the acute phase of the COVID-19 pandemic has passed, SARS-CoV-2 continues to cause outpatient morbidity. Antioxidant micronutrients support immune regulation and may offer a low-cost, scalable adjunctive treatment in early infection. Objective: To evaluate a pilot combination antioxidant therapy within CanTreatCOVID. Methods: This pilot sub-protocol enrolled non-hospitalized adults across five Canadian provinces (September 5th, 2024-March 31st, 2025) with mild-to-moderate SARS-CoV-2 infection within five days of symptom onset. Participants were randomized to usual care plus a 10-day antioxidant regimen (selenium 300 g, zinc 40 mg, lycopene 45 mg, vitamin C 1.5 g) or usual care alone. Pilot objectives assessed feasibility, retention, adherence, and safety. The primary outcome was hospitalization or death within 28 days; exploratory outcomes included recovery and symptom measures by day 14. Results: Eighty-one participants were randomized (41 antioxidant; 40 usual care). Retention was high 85.4% antioxidant; 82.5% usual care), and 90.2% of antioxidant participants completed the intervention course. Adverse events were infrequent (9.8% vs 2.5%), with no serious adverse events reported. No deaths occurred in either group; no hospitalizations occurred in the antioxidant arm versus 2/40 (5%) in usual care. By day 14, recovery was reported in 32/40 (80.0%) participants receiving antioxidants versus 23/36 (63.9%) in usual care (OR 2.128; 95% CI 0.7474.871). Sustained alleviation of all symptoms occurred in 38/40 (95.0%) versus 29/36 (80.6%), respectively (OR 3.498; 95% CI 0.872 --10.017). Return to usual activity by day 14 occurred in 38/40 (95.0%) versus 30/36 (83.3%) (OR 3.113; 95% CI 0.762--9.022). Adjusted between-group differences in dietary intake were not statistically significant. Conclusions: Combination antioxidant therapy was feasible to deliver in a decentralized outpatient setting, with high adherence and tolerability. While the trial was not powered for definitive efficacy conclusions, consistent directional improvements across symptom outcomes support evaluation of this host-directed antioxidant strategy in larger trials. Keywords: Adaptive Platform Trial; Antioxidant Therapy; SARS-CoV-2 ; Outpatient Therapeutics; Micronutrient Supplementation Trial registration number: https://clinicaltrials.gov/study/NCT05614349

Language discordance can impede community-based research and health communication where trained interpreters are limited. Although multimodal artificial intelligence systems can provide real-time spoken translation, performance with under-resourced languages during spontaneous field interactions remains poorly characterized. We evaluated ChatGPT-4o during bidirectional English-Nepali voice translation in a community setting near Dhulikhel Hospital, Nepal. In this cross-sectional field study, 30 primarily Nepali-speaking adults were recruited by convenience sampling. ChatGPT-4o mediated conversations using standardized English questions and spontaneous Nepali responses. A bilingual Nepali-English reviewer assessed 485 translated utterances using a 3-point accuracy scale and an inductively developed framework for translation and conversational deviations. Of 485 translations, 282 (58.1%) received the highest accuracy rating, 134 (27.6%) a moderate rating, and 69 (14.2%) the lowest. Mean accuracy was higher for English-to-Nepali than Nepali-to-English translation (2.63 {+/-} 0.53 vs 2.23 {+/-} 0.86); 63 of 69 low-accuracy translations (91.3%) occurred in the Nepali-to-English direction. Among 329 deviation tags, the most frequent were distortion of intended meaning (17.1%), overly formal or unnatural phrasing (14.7%), omission (14.2%), and addition of content (11.5%). Some fluent outputs substantially altered meaning or introduced information not expressed by the speaker. ChatGPT-4o demonstrated potential for real-time English-Nepali communication but also produced errors that could alter interpretation of participant responses. Accuracy was lower and more variable for Nepali-to-English translation; however, translation direction was confounded with input type because Nepali inputs were spontaneous and English inputs standardized, limiting conclusions about directional performance. These findings support cautious use for low-stakes conversational exchange and human verification when errors could affect research validity, clinical decisions, or participant understanding. As multimodal AI evolves, performance should be reevaluated across languages, real-world conditions, and model versions, with bilingual oversight and community partnership remaining central to responsible use.

Introduction: Continuous glucose monitoring (CGM) offers an advancement over traditional self-monitoring of blood glucose (SMBG) for people living with type 1 diabetes (T1D). However, evidence on the acceptability and feasibility of different CGM use cases in African populations remains limited. Methods: This was a pragmatic three-arm, randomised controlled trial on CGM conducted among people living with T1D in three public healthcare clinics in South Africa. Participants were assigned to Arm 1 (continuous CGM), Arm 2 (periodic CGM), or Arm 3 (SMBG). Diabetes education was provided at all study visits. Feasibility was assessed by adherence to CGM use and through the Glucose Monitoring Satisfaction Survey (GMSS). Diabetes distress was measured by the Diabetes Distress Scale (DDS), health-related quality of life (HRQoL) by the EQ-5D scales, and acceptability using the Theoretical Framework of Acceptability (TFA). Surveys were collected on paper and transferred to OpenClinica. Analyses were performed in R. The trial was registered in the Clinical Trials Registry (NCT05944718) on July 13, 2023. Results: A total of 83 participants were included in Arm 1, 85 in Arm 2, and 80 in Arm 3. CGM mean active time was 55% in Arm 1 versus 69% in Arm 2. The proportion of participants meeting the [&ge;]70% active time threshold was higher in Arm 2 (52%) than in Arm 1 (34%). Diabetes' distress declined across arms during the intervention period, with no significant difference between arms; distress increased slightly six months post-intervention but remained below baseline. At 6 months, glucose monitoring satisfaction was significantly higher in both CGM arms than in the SMBG arm, and satisfaction increased over time in CGM arms. Health-related quality of life remained stable across arms during the intervention period with no significant difference between arms. High acceptability was observed in both CGM arms, with higher ratings in the periodic arm. Conclusions: CGM was acceptable to people living with type 1 diabetes and feasible to use in public-sector clinics in South Africa, with high acceptability under continuous and periodic use. Health-related quality of life remained stable across arms, and diabetes-related distress declined, during the intervention period, across arms. Glucose monitoring satisfaction rose significantly in both CGM arms compared to SMBG. Periodic CGM might be a promising and potentially more scalable option than continuous use for public-sector care.

Patients with a brain tumour receive evidence-based clinical care in Australia but a focus on supportive care, including social connection, is often deficient. Digital health platforms hold promise to support these patients and their carers. Existing platforms often lack end-user co-design, evidence-based development and rigorous evaluation. Recognising this unmet need, we co-designed Brain Tumours Online, a digital supportive care platform to streamline access to educational resources, symptom management tools, and peer support for patients, carers, and healthcare professionals. In this article, we present our evaluation approach for Brain Tumours Online to advance methodological thinking in the evaluation of multi-faceted, co-designed digital health platforms. In contrast to standardised procedures in clinical trials, digital health interventions such as supportive care platforms are more complex due to their interactive nature, no prescriptive protocols for usage and the dynamic content of web-based information. Thus, traditional evaluation approaches often fall short in evaluating such multi-faceted digital health supportive care platforms. To address these challenges, we developed a bespoke, logic-modelling based evaluation approach to assess the usability, engagement, impact, and economic value of our platform. Our pragmatic but rigourous evaluation approach required the adaptation of existing evaluation frameworks, subject-matter, and lived experience expert knowledge. Our implementation science and co-design approach are shared in different papers. Our study outcomes will also be shared in a separate paper. In the current paper, we share our approach to the evaluation of Brain Tumours Online and provide insights that may be of value for other researchers interested in the nuances of trialing multi-faceted digital health supportive care platforms.

Despite known carcinogenic properties, indoor tanning remains popular among young adults and may contribute to early-onset melanoma. Our study aims to compare early-onset melanoma incidence by state availability of tanning beds. We analyzed population-based melanoma incidence data (2019-2023) from the National Program of Cancer Registries and calculated Incidence Rate Ratios (IRR) using verified state-level quintiles of tanning bed availability. Overall, in the Midwest/South regions, melanoma incidence increased with greater tanning-bed availability, from 8.7 cases per 100,000 population in Quintile 1 to 14.8 cases per 100,000 population in Quintile 5 (IRR = 1.69; CI = 1.65-1.74). No such relationship was found in the Northeast/West regions. In conclusion, we found that in Southern and Midwest states, increased availability of tanning beds was associated with higher early-onset melanoma in non-Hispanic White males and females, in both metro and non-metro counties. Policies which reduce tanning bed availability in high utilization regions may have potential to reduce early-onset melanoma.

Introduction Anatomical endoscopic enucleation of the prostate (AEEP) techniques, including bipolar enucleation (B-TUEP), holmium laser enucleation (HoLEP), thulium laser enucleation (ThuLEP), and thulium fibre laser enucleation (ThuFLEP), demonstrate comparable clinical outcomes for benign prostatic hyperplasia. As clinical equivalence is increasingly established, cost becomes a key determinant of modality selection. We performed a cost minimisation analysis comparing index procedural costs across AEEP modalities from an institutional perspective. Methods A cost minimisation model was developed from the institutional perspective, incorporating amortised capital costs, maintenance, and consumables. In addition to the base-case scenario of 180 cases per year, we modelled two additional case volume scenarios: low (50 cases/year) and high (500 cases/year) volume. Thu:YAG laser fibres were modelled on two scenarios: disposable single-use, and reusable fibres (up to 10 cases per fibre). Breakeven analysis determined the threshold volume at which each laser modality achieves cost parity with B-TUEP, and one-way sensitivity analysis was performed on key cost parameters. Analysis was limited to index procedural costs calculated in Singapore dollars. Results At the base case of 180 cases per year, B-TUEP had the lowest index procedure cost (SGD 1,018), followed by ThuFLEP (SGD 1,584), ThuLEP (1,599), and HoLEP (SGD 1,655). Breakeven analysis demonstrated that HoLEP, ThuLEP, and ThuFLEP can never achieve cost parity with B-TUEP when laser fibres are single-use, as laser modalities carry higher costs on both capital and per-case dimensions. ThuLEP with reusable fibres (10 uses per fibre) was the only modality to cross below B-TUEP, at a breakeven volume of 198 cases per year. At 500 cases per year with reusable fibres, ThuLEP achieved the lowest cost (SGD 847), representing a 15.4% saving over B-TUEP. Sensitivity analysis identified annual case volume and B-TUEP loop cost as the most influential parameters. Conclusion Index procedural costs in AEEP are strongly influenced by case volume and consumable strategy. While B-TUEP remains cost-efficient at low volume, high-volume practice combined with reusable Thu:YAG fibre technology enables cost parity and potential cost advantage for laser enucleation. These findings highlight the importance of economies of scale and device utilisation in technology adoption.