An affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria.

The DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026.

This study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public.

NCT06331195.

To examine whether Indigenous Peoples’ and Local Communities’ (IPLC) ontologies are associated with knowledge, attitudes and practices (KAP) related to wildlife cohabitation and zoonotic disease transmission in biodiversity-rich areas of Latin America.

Cross-sectional household survey using a standardised KAP questionnaire. Ontologies were classified using latent class analysis. Associations between ontology classes and outcomes were assessed using multivariable logistic regression models.

Urban, rural and protected areas in biodiversity-rich regions of Bolivia, Brazil, Chile and Guatemala.

A total of 2903 individuals aged ≥10 years were recruited through random household sampling (response rate 85%).

Primary outcomes were defined according to the KAP framework. Knowledge outcomes comprised combined knowledge of zoonotic disease transmission from wildlife to humans and knowledge of zoonotic risks associated with wildlife trade. Perceived training needs related to zoonotic disease prevention were analysed as a secondary knowledge outcome measure. Attitudes were measured through risk perception, operationalised as concern about zoonotic disease transmission. Practices included self-reported hunting and slaughtering of wildlife.

The analysis identified three distinct ontology classes: Relational environmentalism (52% of the population), characterised by strong spiritual connections to animals and a tendency to protect wildlife; Dualistic environmentalism (28%), with a weaker spiritual connection to animals but a commitment to wildlife conservation; and Neutral (20%), demonstrating little spiritual connection to animals and a neutral attitude towards wildlife conservation. In the logistic regression analyses, both environmentalism groups exhibited greater knowledge of zoonotic transmission and concern about outbreaks, with members of the Relational class demonstrating higher levels of these attributes. Furthermore, members of the Dualistic environmentalism class were less likely to have close contact with animals.

In Latin America’s biodiversity-rich regions, individuals whose ontology aligns with environmentalism appear to demonstrate a heightened awareness of zoonoses, particularly those who adhere to a Relational environmentalism perspective. Consequently, the integration of IPLC cultural knowledge holds potential to enhance wildlife conservation measures and contribute to the mitigation of disease transmission. Further research is needed to explore causal pathways and the integration of culturally grounded approaches into public health interventions.

To quantify sex- and age-related differences in hypercholesterolaemia diagnosis and associated comorbidities around the menopausal transition, using a population-based real-world dataset.

Retrospective, multicentre, non-interventional observational cohort study.

Region-wide public healthcare system data (primary and secondary care) from Andalusia (Spain), 2016–2022.

All adult patients meeting inclusion criteria with a recorded diagnosis of hypercholesterolaemia between 1 January 2016 and 31 December 2022 (n=557 034; 227 834 men and 329 200 women).

None.

Primary outcomes were age- and sex-stratified patterns of hypercholesterolaemia diagnosis and comorbidity burden before and after age 50 years (proxy for post-menopausal age). Secondary outcomes included comorbidity-specific comparisons between sexes across age strata and trajectory-based analyses (OR trajectories and incidence-ratio summaries).

Women were diagnosed later than men (mean age 59.1 vs 56.0 years; mean difference 3.1 years, 95% CI 3.03 to 3.17). Hypercholesterolaemia diagnoses in women rose sharply around ages 50–55 and remained higher than in men at older ages. Comorbidity patterns differed by sex across age strata: compared with men, women aged ≥50 years had higher frequencies of osteoporosis (42 255 vs 2623), anxiety disorder (94 916 vs 31 374) and hypertension (147 538 vs 91 532), with statistically significant differences for these comparisons (p

Menopause age is a pivotal period associated with a shift towards higher hypercholesterolaemia diagnosis rates and a greater burden of specific comorbidities in women. These findings support sex-specific prevention and management strategies, particularly targeting the menopausal transition and early post-menopause.

Chronic musculoskeletal pain (CMP) is a leading cause of incurred personal healthcare costs and disability in the USA. It disproportionately affects rural populations, who are more likely to be uninsured, lack access to a regular healthcare provider and experience a higher prevalence of CMP. As a result of reduced access to non-pharmacological care, there is greater reliance on opioids. The Auricular Point Acupressure – Self-Management (APA-SM) program is a simple, needleless, evidence-based therapy that empowers individuals to self-manage their pain. Preliminary studies, including a recent UG3 pilot testing, demonstrated feasibility, safety and significant improvements in pain and function. Guided by Bandura’s self-efficacy model and informed by stakeholder input, APA-SM integrates a smartphone application, ecological momentary assessment and personalized motivational messaging to enhance adherence and behavior change. This study protocol describes the design of a real-world, hybrid effectiveness-implementation, randomized controlled trial to evaluate the clinical impact and sustainability of APA-SM in rural settings.

We will conduct a pragmatic, three-arm randomized controlled trial in Texas and South Carolina, enrolling 693 adults with CMP (231 per group). Participants will be randomized to: (1) APA-SM with remote training, (2) APA-SM with in-person training or (3) education control. The primary outcome is pain impact measured by the PEG (composite score of pain intensity, interference on enjoyment of life, and general activity) scale at immediate post-intervention (4 weeks), with follow-up at 1, 3 and 6 months. Secondary outcomes include National Institutes of Health Helping to End Addiction Long-Term Clinical Pain Core common data elements (eg, psychological functioning, disability, sleep, quality of life), opioid use and patient-reported adherence and satisfaction. Implementation outcomes will be assessed at both the patient and provider levels, guided by the RE-AIM framework. Cost-effectiveness will be estimated using implementation costs and incremental cost-effectiveness ratios, and predictive factors for APA-SM treatment response will be identified using statistical machine learning approaches and historical electronic health record data. The target sample size (231 per group) provides 90% power to detect a moderate effect size (Cohen’s d=0.35), accounting for 25% attrition. Randomization occurs at the participant level to reflect real-world delivery and minimize contamination.

This study, sponsored under grant number 4UH3AT012728, has single Institutional Review Board (IRB) approval at UTHealth Houston, Texas, USA (HSC-SN-25-0443). A Data Safety Monitoring Board will oversee adverse event reporting and trial conduct. Dissemination will occur through peer-reviewed publications, conference presentations, stakeholder workshops and community-based reports tailored for rural health systems and policymakers.

This trial will provide the first large-scale evaluation of APA-SM in rural U.S. populations, integrating digital health tools and implementation science methods to help address disparities in pain management. By assessing clinical effectiveness, implementation outcomes, cost-effectiveness and predictive response factors, study results will inform scalable strategies for integrating APA-SM further into rural communities and healthcare systems. If successful, APA-SM has the potential to improve pain care access, reduce opioid reliance and provide a sustainable, patient-centered model for chronic pain management.

NCT07179016.

Approximately one-third of people with epilepsy (PWE) experience resistance to treatment, including pharmacological therapies, epilepsy surgery, vagus nerve stimulation (VNS) and dietary interventions such as the ketogenic diet (KD). Emerging evidence suggests that the gut microbiota may influence seizure susceptibility and treatment response through the microbiota-gut-brain axis, potentially contributing to treatment resistance. The MiCrobiota-gut-brain Axis in Resistant Epilepsy project investigates how gut microbial features and associated host epigenetic signatures affect clinical outcomes in PWE undergoing diverse treatment strategies.

This is a multicentre, prospective, longitudinal study involving four clinical centres in Italy and one self-financing partner. Participants aged 3–50 years will be enrolled and stratified into four intervention cohorts: newly diagnosed drug-naïve epilepsy scheduled to start anti-seizure medications, focal drug-resistant epilepsy (DRE) undergoing epilepsy surgery, DRE receiving VNS, and DRE initiating KD. Clinical assessments (including body mass index calculation, self-reported monthly seizure count, dietary evaluation, quality of life scale and gastrointestinal symptoms scale), electroencephalography, MRI and biological sample collection (stool and blood) will be obtained at baseline and longitudinally at two or three timepoints over a 12-month observation period. Gut microbiota changes over time will be assessed via metagenomics (using 16S ribosomal RNA sequencing) and metaproteomics; the associated host DNA methylation profiles will be obtained from blood using Illumina EPIC arrays. Primary endpoints include identification of microbial or host methylation changes predictive of therapeutic response (ie, reduction from baseline in monthly seizure count) to the intervention. Data will be analysed using multivariate models and mixed-effect regression. Further, omics data and corresponding metadata will be integrated using multi-omics approaches to identify molecular signatures biomarkers predictive of treatment response and prognosis in PWE.

The study received ethical approval from the Research Ethic Board (Comitato Etico Territoriale Lombardia 3, ID 4896 – parere numero 4896_17.07.2024_N_bis). All participants or their legal guardians will provide written informed consent. Results will be disseminated through peer-reviewed publications, conference presentations or lay summaries targeting patient organisations.

ClinicalTrials.gov Identifier NCT07010445, registered on 2 May 2025.

The increasing global burden of long-term illnesses necessitates high-quality data to inform effective interventions, particularly in low-resource settings. Despite the critical role of data collectors in health research, their lived experiences and challenges remain understudied, especially in low- and middle-income countries (LMICs) like Nigeria. This study explored the experiences, barriers and facilitators encountered by field researchers working with individuals living with long-term illnesses.

A qualitative, descriptive phenomenological design was employed, involving in-depth interviews with 12 research coordinators across 12 healthcare facilities in Nigeria. Participants were purposively selected from the Nigeria Implementation Science Alliance–Model Innovation and Research Centres. Data were analysed using Colaizzi’s phenomenological method, with thematic analysis to identify key patterns.

Field researchers described both rewarding experiences and significant obstacles. While they found value in contributing to impactful research, they faced emotional strain from engaging with sensitive narratives. Key barriers included low health literacy, cultural and religious constraints, hesitation to engage in the study and logistical constraints such as unreliable infrastructure. Facilitators included prefield training, trust-building and support systems. Recommendations emphasised ethical adherence, continuous skill development, context-appropriate incentives and streamlined data collection tools.

The study underscores the need for systemic support for data collectors, including mental health resources, adaptive methodologies and institutional policies that address logistical and emotional issues. These findings advocate for participant-centred, ethically sound research practices to enhance data quality and collector well-being in long-term illness studies.

Future research needs to evaluate interventions to optimise data collection processes in LMICs.

Upper aerodigestive tract endoscopy is routinely performed for the diagnosis and staging of head and neck cancers. These procedures are commonly conducted under general anaesthesia with spontaneous ventilation to optimise surgical exposure and avoid tracheal intubation. However, maintaining adequate oxygenation remains challenging, particularly in patients with altered airway anatomy due to prior surgery or radiotherapy.

Standard practice often involves a preliminary laryngoscopy to insert a nasopharyngeal oxygen catheter, which may increase procedural complexity and interfere with surgical conditions. High-flow nasal oxygen (HFNO) has emerged as a promising alternative for maintaining oxygenation in various perioperative settings.

The OPTIGO trial aims to determine whether HFNO is non-inferior to nasopharyngeal oxygen insufflation in preventing intraoperative oxygen desaturation during upper aerodigestive tract endoscopy.

The OPTIGO study is a multicentre, prospective, randomised, open-label, non-inferiority trial conducted in three French centres. A total of 610 adult patients scheduled for endoscopic procedures of the pharynx, larynx and oesophagus will be randomised in a 1:1 ratio to receive either HFNO or standard oxygenation via a nasopharyngeal oxygen catheter.

The primary outcome is the occurrence of intraoperative oxygen desaturation, defined as a peripheral oxygen saturation ≤85% at any time from induction to the end of the procedure.

Secondary outcomes include intraoperative complications, postoperative laryngeal pain, surgeon comfort, duration of the procedure, anaesthetic drug consumption, and perioperative gas exchange.

This study has been approved by the independent ethics committee CPP Est 1 (10 April 2025; EudraCT 2025-A00278-41). The trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines.

Results will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals.

CPP Est 1 EudraCT 2025-A00278-41 (Clinical trial NCT07004699).

Care provided in people’s own homes (domiciliary care) is an increasingly important part of long-term care. There are various services, including home visits, live-in care and housing with care. Some people directly employ care staff, called personal assistants. Services vary in quality, price and availability, and there is currently little evidence of the value these services provide to the public purse and individuals. This study protocol presents planned research to fill this important gap.

This will be a cross-sectional study based on surveys of care recipients, their unpaid carers as well as formal care providers. In the first half of 2026, we will survey 1850 people accessing domiciliary care either through a homecare agency, a housing with care scheme or by directly employing personal assistants and 400 unpaid carers, all based in England. We will conduct a cost-effectiveness analysis taking a ‘production function’ approach and use quality of life as measured by the Adult Social Care Outcomes Toolkit as the main outcome of interest.

The study received ethical approval from the School of Social Sciences Staff Review Committee at the University of Kent on 20 May 2025 (reference 1195) and the Health Research Authority, London—Camberwell St Giles Research Ethics Committee on 28 October 2025 (reference 25/LO/0652). Implications around consent, data protection and confidentiality, risk and participant payment are discussed. In addition to academic outputs (eg, academic articles, conference presentations), we aim to coproduce news items and blogs with people with lived experience of accessing long-term care and jointly present findings at events aimed at the care sector. Moreover, we will offer participating care providers benchmarking briefs based on our findings.

Fibromyalgia is a polysymptomatic central sensitisation disorder characterised by widespread pain, fatigue, sleep disturbances and neuropsychiatric features. Hyperbaric oxygen therapy modulates neuroinflammation, mitochondrial function and neuroplasticity, thereby yielding analgesic and functional benefits.

Evaluate the efficacy and optimal timing of hyperbaric oxygen therapy as an adjunct to standard care for fibromyalgia.

This single-centre, randomised, cross-over group, assessor-blinded clinical trial was conducted in the Department of Rheumatology at the University Hospital of the Federal University of Juiz de Fora, Juiz de Fora, Brazil, and adhered to Consolidated Standards of Reporting Trials (CONSORT) guidelines. Women (18–70 years) with a diagnosis of fibromyalgia for ≥2 years were randomised 1:1 to early hyperbaric oxygen therapy plus standard care or standard care alone (delayed group). Intention-to-treat (ITT) analysis was conducted with all 56 participants (mean age: 51.0±9.8 years; mean body mass index: 30.5±5.1 kg/m²).

Standardised care (education, exercise and pharmacotherapy) plus hyperbaric oxygen therapy was delivered at 2.3 atmospheres absolute for 90 min, five times per week, over 8 weeks (total 32–40 sessions). The early group received hyperbaric oxygen therapy during weeks 0–8, while the delayed group received it during weeks 8–16, following the same protocol.

Primary endpoints included the Fibromyalgia Impact Questionnaire-Brazilian Portuguese (FIQR-Br), the pain visual analogue scale (VAS) and the Symptoms Assessment Scale-40 (EAS-40) for psychopathology. Secondary endpoints included the 12-Item Short-Form Health Survey (SF-12) physical and mental components and adverse effects. Assessments were conducted at baseline, 8 weeks and 16 weeks, and analysed using a mixed-design 2x3 analysis of variance (group: early vs delayed; time: baseline, 8 weeks and 16 weeks) with Greenhouse-Geisser corrections as needed, followed by Bonferroni post hoc tests. Missing data were assessed using Little’s missing completely at random (MCAR), and considering the ITT analysis, the means imputed for missing data were estimated through expectation maximisation. Effect sizes were reported as partial ² and Cohen’s d with α=0.05.

44 participants completed the study, and the overall withdrawal rate was 21.4% with no baseline between-group differences. Significant time effects were observed for all primary outcomes and the SF-12 outcome (pxtime interactions were significant for FIQR-Br, VAS, EAS-40 and SF-12 physical and mental (p≤0.02; interaction ² up to 0.23), indicating improvements during active hyperbaric oxygen therapy exposure. Compared with standard care alone over 8 weeks, combined treatment achieved greater gains: FIQR-Br, –31.1% vs –14.4%; VAS, –54.0% vs –33.5%; EAS-40, –28.4% vs –3.7%; SF-12 physical, +39.1% vs +14.8%; SF-12 mental, +57.4% vs +31.9%. Large within-group effect sizes were observed (eg, VAS d=2.5–2.7; FIQR-Br d=1.4–1.7). Efficacy was equivalent regardless of time started, and the benefits converged by the end of each hyperbaric oxygen therapy phase. After stopping hyperbaric oxygen therapy, the FIQR-Br and SF-12 mental component scores regressed towards standard care levels, whereas residual improvements persisted for up to 8 weeks in VAS, EAS-40 and SF-12 physical component scores. Adverse events were infrequent; one case of otalgia required extended management. Withdrawals were primarily due to non-compliance or intolerance to chamber confinement. No serious or unexpected safety concerns were reported.

Hyperbaric oxygen therapy, delivered under a standardised protocol, is an effective and well-tolerated adjunct to multimodal fibromyalgia care. Timing can be individualised: early initiation for rapid relief or stepped introduction after optimised usual care, with comparable overall efficacy. The durability of the benefit appears to be exposure dependent, and maintenance or booster schedules merit further evaluation.

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Mental health problems among undergraduate medical students are a major global public health concern that emerge early during training and are shaped by demanding educational environments, emotional stressors and organisational pressures. Although research has expanded rapidly, the literature remains fragmented across themes, regions and methods. This scoping review aims to map the global quantitative literature on medical students’ mental health and identify gaps in scope, geography, methodology and equity.

This scoping review will be conducted in accordance with the Joanna Briggs Institute methodological guidance and reported in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. We will include quantitative studies assessing mental health among undergraduate medical students. MEDLINE (Ovid), Web of Science (Clarivate), the Cochrane Library (Wiley) and PsycINFO (Ovid) will be searched without date or language restrictions using a keyword-based search strategy. Two reviewers will independently screen titles, abstracts and full texts and extract data using a standardised form. Data will include publication year, country, study design, sample size, mental health measures, thematic domains and patterns of collaboration. Mental health domains will be classified using an a priori thematic framework encompassing psychological symptoms and distress, psychological resources, academic environment, social support and physical health and lifestyle factors. Equity-related variables (sex, gender identity, sexual orientation, race/ethnicity, socioeconomic status) will be operationalised based on analytical use. Results will be synthesised descriptively using tables and visualisations.

Ethical approval is not required. Findings will be disseminated through publication and presentations. The dataset and code will be openly available on publication.

Protocol registration will be made available online via the Open Science Framework (doi:10.17605/OSF.IO/2EHNU).

Iron-folic acid (IFA) supplementation in pregnancy is recommended by the WHO, with a dose of 60 mg of iron in contexts where anaemia remains a severe public health problem. Iron-containing supplements may cause side effects that affect acceptability and adherence in a dose-response manner. Maternal multiple micronutrient supplements (MMS), which include iron and folic acid plus additional micronutrients, are also recommended in the context of rigorous research, and programmes are considering transitioning from IFA to MMS containing 30 mg of iron. We will evaluate the effect of iron dose in MMS on maternal acceptability, side effects, adherence and preferences.

The Multiple Micronutrient Supplementation (MMS) Iron Dose Acceptability Crossover Trial is an individually randomised, quadruple-blind, non-inferiority crossover trial of daily antenatal MMS supplementation formulations that contain 60 mg, 45 mg and 30 mg elemental iron among pregnant women in Dar es Salaam, Tanzania. A total of 156 pregnant participants will be randomised to a sequence in which they receive each of the three MMS formulations for 1 month. Participants, investigators, outcome assessors and data analysts will be blinded to the treatment sequence. The primary trial outcome is participant-reported acceptability of each MMS formulation, measured on a Likert scale. Secondary and tertiary outcomes include preferred and least preferred formulation, identification of MMS formulation, reported side effects and adherence assessed by pill count. Regression analyses will be used to assess differences between formulations and will account for sequence and period effects of the crossover trial design. Qualitative in-depth interviews from a subsample of participants will be conducted to understand women’s perceptions and experiences taking the different MMS formulations.

The trial protocol was approved by Harvard T. H. Chan School of Public Health Institutional Review Board (IRB), the Ifakara Health Institute IRB, the Muhimbili University of Health and Allied Sciences IRB, the National Health Research Ethics Sub-Committee and the Tanzania Medicine and Medical Device Authority. Results will be shared through publications and presentations at the local, regional and international levels.

ClinicalTrials.gov Identifier: NCT06069869.