Approximately 40% of women stop endocrine therapy for hormone-receptor-positive breast cancer within the first 5 years of prescribed treatment because of side effects. Musculoskeletal complaints are among the most frequently reported side effects. The Cancer Of the BReast Asanas (COBRA) study examines the effect of an 18-week yoga programme on endocrine therapy-associated musculoskeletal complaints in women with breast cancer.

In total, 140 women will be randomised in a 1:1 ratio to the intervention or waitlist control group. The intervention programme consists of two times a week 1-hour supervised Hatha or (easy) Vinyasa yoga classes at a yoga or sports centre for 18 weeks and once per week a half-hour at home using videos. The waitlist control group is asked to maintain their habitual lifestyle during the first 18 weeks and will participate in a similar yoga programme to the intervention group for the following 18 weeks. The control group yoga programme is offered live-remote. The primary outcome (musculoskeletal complaints) is assessed with the Brief Pain Inventory questionnaire at baseline and 18 weeks (primary comparison) and additionally at 36 weeks. Secondary outcomes include lower and upper extremity joint complaints, menopausal symptoms, fatigue, sleep, quality of life, anxiety and depression, cognitive complaints and habitual physical activity (all patient-reported), vital signs and anthropometrics, physical fitness, blood biomarkers, medication use, safety data and patient and teacher experiences. At baseline and 18 weeks, cognitive complaints are also assessed with an online neuropsychological test battery.

The COBRA study was approved by the Medical Ethical Committee of the University Medical Center Utrecht. The study started on 8 October 2024, and 65 participants have been included (20 January 2026). Results will be submitted to an international peer-reviewed journal.

NCT06480513.

To describe the prevalence and spatial distribution of anaemia among children aged 6–59 months in Madagascar and to explore individual-level and community-level correlates using data from the 2021 Madagascar Demographic and Health Survey.

A population-based cross-sectional study using secondary data from the 2021 Madagascar Demographic and Health Survey. Spatial statistical methods were used to assess geographic clustering and hotspot areas of anaemia.

The study was conducted across community and household levels throughout Madagascar, covering both rural and urban populations within the primary and secondary healthcare delivery contexts.

A weighted sample of 10 683 children aged 6–59 months was included. Sampling followed demographic health survey procedures, and only children with complete haemoglobin data were analysed.

No interventions were applied.

The primary outcome was anaemia, defined as haemoglobin

The overall point prevalence of anaemia was 47% (95% CI 45.60 to 48.36), showing significant spatial clustering (Global Moran’s I=0.136, p

Anaemia among Malagasy children remains a major public health concern and shows clear geographic variation. The findings describe important differences in prevalence across regions and population subgroups, providing useful evidence for public health planning and for generating hypotheses for future analytical research.

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.

RBR-6prps8g.

Postoperative neurocognitive disorders, including delirium and longer-term cognitive decline, are among the most common and costly complications of surgery in older adults, yet effective preventive strategies remain limited. Insomnia and sleep–circadian disruption are highly prevalent in this population, affecting up to one-third of older adults undergoing elective surgery and represent potentially modifiable risk factors that are rarely addressed in perioperative care. Cognitive Behavioural Therapy for Insomnia (CBT-I) is the first-line, evidence-based treatment for insomnia; however, its feasibility and efficacy have not been systematically evaluated for perioperative implementation. This protocol describes a pilot randomised controlled trial designed to evaluate the feasibility and acceptability of a condensed CBT-I intervention in the perioperative setting. The study will also explore its potential effects on insomnia and postoperative outcomes.

The SLEEP-BOOST study is a single-site, randomised controlled pilot trial conducted at Massachusetts General Hospital. The study will enrol 50 older adults (≥65 years) undergoing elective orthopaedic surgery with insomnia symptoms (Insomnia Severity Index≥10). Participants will be randomised 1:1 to either a condensed CBT-I intervention or a patient contact-matched Sleep Hygiene Education control group. All participants will complete 3 weeks of preoperative actigraphy and daily sleep diaries, with follow-up assessments at 2 weeks, 1 month and 3 months after surgery. The primary outcome is feasibility, assessed through adherence metrics, protocol engagement and acceptability. Secondary outcomes will be treated as exploratory including insomnia severity, sleep quality, actigraphy-derived sleep and circadian metrics, cognitive trajectories, postoperative pain, mood, functional status and incidence of postoperative neurocognitive disorders.

This protocol has received ethics approval from Massachusetts General Hospital Institutional Review Board (Protocol #2024P000780). Dissemination is expected to include peer-reviewed journal articles, reports, conference presentations as well as websites or social media platforms of relevant sleep treatment organisations. Participants will receive a summary of the study results.

NCT06375265.

Obesity and related cardiometabolic comorbidities, including hypertension, dyslipidaemia, diabetes, metabolic dysfunction-associated steatotic liver disease and atherosclerotic cardiovascular disease, are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes and overall quality of life, yet evidence remains fragmented. The Modulate Obesity and relateD metabolic complIcations For Yielding improvements in IBD outcomes (MODIFY-IBD) initiative aims to synthesise evidence and generate consensus recommendations to guide practice and future research in this area. This study describes a protocol for a structured evidence synthesis and Research ANd Development/University of California, Los Angeles (RAND/UCLA) Appropriateness Method (RUAM) consensus process.

We will conduct three systematic reviews and a structured evidence synthesis organised into three domains: (1) the impact of obesity on IBD outcomes, (2) the burden of cardiometabolic complications in IBD and (3) the management of overweight, obesity and cardiometabolic comorbidities in IBD. A multidisciplinary international panel of gastroenterologists, surgeons, endocrinologists, hepatologists, cardiologists and dietitians will assess each statement using the RAND/UCLA appropriateness method. Panellists will rate the appropriateness of each statement (only those that fall within their area of expertise) on a 1–9 scale (1–3=inappropriate, 4–6=uncertain and 7–9=appropriate), with medians rounded up (eg, 6.5=appropriate). Agreement will be assessed using the RAND Disagreement Index (DI

This study will not involve direct patient participation, as it is based on evidence synthesis and expert consensus; therefore, formal research ethics committee approval will not be required. Patient representatives will contribute to the consensus process to provide contextual perspectives but no identifiable data will be collected.

Findings will be disseminated through publication in peer-reviewed journals, presentation at major gastroenterology and IBD conferences and communication with professional societies. A lay summary and patient-friendly infographic will also be developed to facilitate translation of recommendations into clinical practice.

CRD420251178843: a systematic review of the impact of obesity on inflammatory bowel disease outcomes.

CRD420251178799: a systematic review of cardiometabolic complications in inflammatory bowel disease.

CRD420251174653: management of overweight, obesity and cardiometabolic comorbidities in inflammatory bowel disease: a systematic review.

Accurately capturing social contact data is essential for developing effective mathematical models to forecast disease trends and evaluate interventions. There are limited population-based data of social contacts in the USA which limits our ability to accurately model infectious disease transmission.

To fill in this gap, we conducted a staggered longitudinal cohort study in metropolitan Atlanta, Georgia, USA. We aimed to characterise contact patterns and examine how they varied by (1) participant demographics, (2) seasonality and (3) self-managed and medically-attended symptoms. Once per month for 6 months, participants reported individual contacts they can name, individual contacts they cannot name and contacts that occurred in group settings. We defined individual contacts as a two-way conversation with five or more words in the physical presence of another person or physical skin-to-skin contact and group contacts as contacts with a group of people with whom participants talked, interacted or shared space. Participants were enrolled on a rolling basis, and data is collected from November 2024 through April 2026. Data analysis will generate age-specific contact matrices using individual contacts and compare contact rates by symptoms. We will also analyse the number and characteristics (eg, indoor/outdoor) of each type of contact. The contact matrices and results will be publicly available for the wider modelling community.

Kaiser Permanente Interregional Institutional Review Board (IRB) reviewed and approved all submitted study documents. An IRB Authorization Agreement was established with the Emory University IRB documenting the roles and responsibilities of each study site. On study completion, de-identified individual level contact data as well as contact matrices and analytical code will be made publicly available on GitHub/Zenodo platform. Study findings will be published in scientific journals and presented at conferences.

Potentially inappropriate prescriptions (PIPs) in older adults, such as long-term use of benzodiazepines, proton pump inhibitors without indication or antipsychotics in dementia, are associated with adverse events and increased healthcare utilisation. Despite clinical guidelines discouraging their use, PIPs remain frequent in primary care. An audit and feedback (A&F) intervention of PIPs to general practitioners (GPs), led by pharmacists, may reduce the prescription of PIPs in primary care.

A two-arm, pragmatic, controlled trial will be conducted to evaluate the effectiveness of an A&F-based intervention and a pharmacist-led intervention to reduce the proportion of patients aged ≥65 years receiving inappropriate prescriptions. A total of 170 participating GPs, 85 per group, are required. GPs will be randomised into intervention or control groups (1:1). The intervention includes feedback reports, pharmacist-led academic detailing and access to online training modules. The primary outcome is the proportion of older adults receiving at least one PIP at 12 months as well as the total number of PIPs. A random effects Tobit regression model, censored at 0 and 100, will be used to estimate between-group differences adjusted for baseline prescribing. Subgroup analyses will explore heterogeneity of effect by baseline prescribing level and healthcare region. Implementation outcomes, including reach, fidelity, engagement and maintenance, will be evaluated using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, combining quantitative and qualitative data.

Ethical approval was obtained by the Balearic Island Committee Ethics (IB5219/23PI). Study findings, including primary and secondary outcomes and qualitative implementation results, will be disseminated through peer-reviewed publications and stakeholder reports.

ISRCTN14449434.

This study aimed to assess the prevalence and independent predictors of refractive error among adults with diabetes in Addis Ababa, Central Ethiopia.

A multicentre hospital-based cross-sectional study was conducted using a systematic random sampling method.

This study was conducted at public referral hospitals’ diabetic care clinics of Addis Ababa, Central Ethiopia from 13 May to 17 August 2025.

The study included 391 adult patients with diabetes who met the inclusion criteria.

Data were collected using face-to-face interviews completed by an interviewer, ophthalmic examinations and reviewed medical records.

In this study, 391 participants (a response rate of 92.4%) participated. The median age of the participants was 54 years IQR (46–62). The prevalence of refractive error was 55.7% (95% CI 50.7 to 60.7). Older age, female sex, longer diabetes duration, poor glycaemic control, hypertension, diabetic retinopathy and cataract were positively associated with refractive error.

This study found a high prevalence of refractive error among patients with diabetes in Central Ethiopia. Older age, female sex, longer diabetes duration, poor glycaemic control (assessed by both fasting blood glucose and haemoglobin A1c), hypertension, diabetic retinopathy and cataract were significantly associated with refractive error.

Hepatocellular carcinoma (HCC) recurs in most patients after curative treatment. Late recurrence (>2 years after curative treatment) typically indicates de novo tumours in the residual liver. Although contrast-enhanced computed tomography (CECT) and MRI are widely used for post-treatment follow-up, they each have limitations including radiation exposure, high cost and limited access. The abbreviated MRI using gadoxetic acid versus multiphasic CECT for detection of late recurrent HCC after curative treatment (AMRICT) trial aims to compare gadoxetic acid-enhanced abbreviated MRI using hepatobiliary phase imaging (HBP-AMRI) and multiphasic CECT for detecting late recurrent HCC after curative treatment.

This prospective multicentre intra-individual comparison trial will enrol 455 participants who have undergone surgical resection or local ablation for HCC and remained recurrence-free for over 2 years. Each participant will undergo two imaging sessions at 6±2 month intervals, using both HBP-AMRI and multiphasic CECT. The primary endpoint is the detection rate of all-stage HCC. The secondary endpoints include the false referral rate of all-stage HCC and detection and false referral rates of Barcelona Clinic Liver Cancer stage 0–A HCC and of stage 0 HCC. Structured imaging protocols and quality assessments will be implemented for both modalities.

This study was approved by the Institutional Review Boards of the three participating institutions (approval number: 2023–1630 (Asan Medical Center), H-2407-146-1556 (Seoul National University Hospital) and B-2410-929-401 (Seoul National University Bundang Hospital)) and registered at ClinicalTrials.gov (NCT06537193). Findings will be disseminated through peer-reviewed journals, scientific meetings, public forums and guideline updates.

ClinicalTrials.gov: NCT06537193. Participant enrolment began on 12 December 2024, and is ongoing.

Despite the high rates of early enrolment in preschool and of poor mental health in adolescence in Sweden, knowledge regarding their association in Sweden is lacking. We investigated whether age at starting preschool and weekly hours spent at preschool in different ages are associated with mental ill-health in Swedish adolescents.

A cohort study based on data from KUPOL (Swedish acronym for ‘Knowledge about Adolescents Mental Health and Learning’).

We used data from KUPOL, a longitudinal study conducted during 2013–2018, involving Swedish adolescents born 2000–2001. We included in the current analyses adolescents with available information on the exposures and the outcomes of interest (n=2261).

Study participants and their parents completed questionnaires concerning the child’s age (in months) at start of preschool, the average weekly hours in preschool in different ages, the adolescent’s mental health, lifestyle, school-related, psychosocial and parental sociodemographic factors. We analysed the association between preschool-related factors and mental health using logistic regression.

Children enrolled in preschool at the age of 12–15 months had increased odds of high overall and externalising problems score on the Strengths and Difficulties Questionnaire relative to those enrolled at 20 months or later. The corresponding ORs (95% CIs) were 1.39 (95% CI 1.02 to 1.90) and 1.52 (95% CI 1.08 to 2.16), while the corresponding population attributable fractions were 8% and 9%, respectively. There were no associations between age at start of preschool and internalising problems, nor between the average weekly hours at preschool and mental health.

We found weak and inconsistent evidence for a link between early preschool attendance and mental health in adolescence; population attributable fractions suggest limited public health implications for the studied associations. The results should be interpreted in light of the methodological constraints of observational studies, the multitude of our comparisons and the sample selection.

In the context of declining total fertility rates, many governments are seeking the optimal blend of policy interventions to encourage childbirth. Scholars have mapped how pronatal policy agendas are shaping social policies, yet there has been less attention on how such agendas shape health policies. This review will map and synthesize the evidence on how pronatal policies affect sexual and reproductive healthcare.

A scoping review will be conducted using two searches. One search will identify relevant peer-reviewed papers in Medline, EMBASE, social policy and practice, global health and Web of Science databases. A second search will identify relevant grey literature from Overton and Policy Commons databases. Sources will be managed using Rayaan software and studies selected based on specified inclusion criteria. Data will be extracted using a customised extraction form, mapped and subsequently synthesised using narrative approach.

This review will be disseminated through a peer-reviewed manuscript and conference presentations. Ethics and patient engagement are not required for a scoping review.

CRD420251156155.

Induction of labour (IOL) is a commonly performed obstetric intervention, particularly when delivery is deemed more beneficial than continuing the pregnancy due to maternal or fetal indications. When the cervix is unfavourable for delivery, cervical ripening is performed prior to IOL. A wide variety of mechanical, pharmacological and combination methods are used, but the optimal approach balancing efficacy, safety and patient experience remains uncertain. Conventional aggregate data (AD) meta-analyses lack individual-level data, limiting exploration of patient-level factors for personalised medicine and do not address concerns about the trustworthiness of data presented in peer-reviewed randomised controlled trials (RCTs). This protocol describes an individual participant data (IPD) network meta-analysis (NMA) designed to evaluate and rank cervical ripening methods for IOL using only high quality, trustworthy data.

We will identify eligible parallel-group RCTs enrolling pregnant women with a singleton, cephalic fetus at ≥34 weeks’ gestation requiring cervical ripening, through comprehensive searches of Ovid MEDLINE, Embase, Emcare, Scopus, Cochrane Pregnancy and Childbirth Register, WHO International Clinical Trials Registry Platform, clinicaltrials.gov and reference lists of prior reviews. The interventions we consider will be selected via Delphi consensus with international clinical experts. Eligible trial investigators will be invited to contribute de-identified IPD; AD will be used if IPD is unavailable. Trials will be assessed for trustworthiness using the Trustworthiness in RAndomised Clinical Trials checklist and the IPD Integrity Tool, with only eligible studies included in the primary analysis. All statistical analyses will follow a pre-specified statistical analysis plan (SAP) finalised before any analyses are conducted. A two-stage, contrast-based, frequentist IPD-NMA will compare cervical ripening methods for three co-primary outcomes: vaginal birth, composite adverse perinatal outcomes and composite adverse maternal outcomes. Subgroup analyses will assess effect modifiers (eg, parity, age and previous caesarean), with treatment rankings presented using the surface under the cumulative ranking curve and rank-heat plots. Sensitivity analyses will examine the impact of bias, missing data and population criteria.

This study has been approved by the Monash University Human Research Ethics Committee (No. 48189). IPD will be de-identified and securely transferred for storage on a Monash University-hosted shared network drive. Findings will be disseminated via peer-reviewed publications, conference abstracts and the Cervical Ripening for Induction of Labour Collaborative Evidence Network Meta-Analysis (CIRCLE-NMA) website (https://circlenma.com). Patient and public involvement will guide the communication and interpretation of results.

CRD420251077464.

Growing evidence exists about the pivotal role of immune mechanisms in the physiopathology of atrial fibrillation (AF). Drugs that modulate the immune system (immunomodulators) may contribute to the development of AF. We aimed to identify immunomodulators that are associated with AF to better define their safety profile, and elucidating their mechanisms of action could yield novel insights into AF’s immune physiopathology.

A descriptive and disproportionality analysis of claims data.

World pharmacovigilance database VigiBase until 1 March 2025.

First, we ascertained the association of immunomodulators with AF over-reporting with a disproportionality analysis evaluating the multivariable-adjusted reporting odds ratio (aROR) for AF reporting performed for 141 immunomodulators in VigiBase. Then, a literature review was done to explore the underlying mechanisms of AF through immunomodulator mechanisms.

A total of 6 148 556 reports encompassing at least one of the 141 immunomodulators were identified in Vigibase. Our primary analysis revealed 20 immunomodulators associated with AF over-reporting. The three immunomodulators with the greatest signal were: recombinant interleukin-11 with an aROR=20.91 (99.96% CI 12.08 to 36.17), efgartigimod alfa with an aROR=6.75 (99.96% CI 3.96 to 11.52) and recombinant interleukin-2 with an aROR=6.15 (99.96% CI 3.62 to 10.45). A derivative literature review posited a hypothetical immune ‘vicious circle’ promoting AF, involving T helper cells, macrophages and natural killer cells which could lead to electrophysiologic and histologic atrial remodelling.

Twenty Food and Drug Administration (FDA)-labelled immunomodulators are associated with AF overreporting in Vigibase with a substantial signal on recombinant IL-11. These data contribute substantively to the prevailing understanding of the safety profile of these immunomodulators. Moreover, these findings support a multidirectional interaction between the immune system and AF development and might lead to considering future therapeutic targets.

NCT06095791.