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Going the distance: a cross-sectional geospatial analysis quantifying province-wide inequities in travel-based access, and fragility of access to French-language primary care provided by family physicians in Ontario, Canada

Por: Belanger · C. · Timony · P. E. · Belizaire · A. · Desilets · A. · Fitzsimon · J. P. · Gauthier · A. P. · Godfrey · L. · Karunananthan · S. · Kehoe MacLeod · K. · Muray · M.-N. · Peixoto · C. · Bjerre · L. M.
Objectives

Language-concordant care, or healthcare in one’s preferred language, is important both for health equity and for improving health outcomes. Linguistic minorities, like Francophones in Ontario, Canada, are at risk of poorer clinical outcomes if they receive non-language-concordant primary care. However, common ratio-based access measures can provide misleading views of minorities’ actual access levels. This cross-sectional geospatial study demonstrates a new way to measure primary care access using average travel time to the nearest five English- and French-speaking family physicians. We also introduce the concept of primary care access fragility, where a region’s primary care access may depend on one or a few local family physicians. Our research question is: are there differences in travel burden and access fragility for census subdivisions (CSDs) across language (English/French), rurality (urban/rural) and region (north/south) in the province of Ontario, Canada?

Design

We conducted a cross-sectional geospatial analysis to estimate English-language and French-language primary care travel burdens and access fragility in Ontario, Canada. We used population and boundary data from Statistics Canada’s 2021 census, road-network data from OpenStreetMaps, and family physician practice locations and language abilities from the College of Physicians and Surgeons of Ontario. We measured travel burden using Valhalla, an open-source road-network analysis platform.

Setting

We conducted our analysis for Ontario, Canada’s 577 CSDs, which correspond roughly to municipalities and with populations ranging from 5 inhabitants in Rainy Lake 17B to a high of 2 794 356 in Toronto.

Participants

Using public data from January 2026, we identified 15 762 family physicians practising in Ontario, of whom 11.0% reported speaking French. Patient data were obtained from the most recent 2021 census.

Primary and secondary outcome measures

Our first primary outcome measures were CSD-level mean travel time to the nearest five English-speaking family physicians, and CSD-level mean travel time to the nearest five French-speaking family physicians, which we compared to explore regional inequities in travel burden. Our secondary outcome measures were based on a novel notion of the travel burden component of ‘primary care access fragility’. This metric indicates how dependent a region’s access is on a small number of local physicians and is defined as the difference between the CSD-level mean travel time to the nearest one physician and to the nearest five physicians. As the difference in travel times grows, so too does access fragility.

Results

Median differences in French-language and English-language travel burdens were strongly significant across rurality, regions and overall (median difference 13.4 min, p

Conclusions

Compared with the general public, Ontario’s French-speakers face higher travel burdens to language-concordant family physicians and higher access fragility, especially in rural and northern regions. Our results are of interest to policymakers and health-system planners, and our methods are applicable to other populations and regions.

Adolescents perspectives on spectacle wear and adherence following a school-based outreach programme in Indonesia: a qualitative study

Por: Rahayu · T. · Barliana · J. D. · Lestari · Y. · Chandra · A. P. · Nadira · D.
Objective

The aim of this study is to explore in depth adolescents’ insights regarding experiences of spectacle lens wear and its correlation with self-perception, quality of life, social interactions, adherence and barriers.

Design

Qualitative design through individual interviews and thematic analysis.

Setting

Middle school students in five regions of Jakarta Province.

Participants

31 middle school adolescents who participated and received free spectacle wear by the Indonesian Ophthalmologist Association.

Methods

A set of semistructured questionnaires exploring adolescents’ perception regarding spectacle lens wear, adapted from the PedEyeQ. Interviews were conducted on site or through Zoom and were then transcribed.

Findings

Thematic analysis identified three themes, as follows: (1) experience with eyeglasses, (2) motivation and encouragement and (3) barriers to usage. This study found that more than half of adolescents received their first spectacles during the outreach programme, with most reporting improved vision and academic performance after spectacle wear. However, adherence varied, as some participants—particularly those with moderate to high myopia and astigmatism—did not use their new glasses due to discomfort, poor fit or dissatisfaction with visual clarity. While initial adaptation often involved dizziness or soreness, most adjusted within a week. The majority recognised the importance of spectacle wear, describing clearer vision, reduced eye strain and improved confidence, though a minority viewed it as unnecessary. Parents played a central role in influencing health-seeking behaviour, and limited prior access to eye examinations and geographic challenges restricted care for several adolescents. Financial concerns were reported by a small proportion, while psychological barriers such as fear of teasing or negative self-perception were the major barrier. Overall, adolescents highlighted both the benefits and challenges of spectacle wear, with motivation shaped by personal experience, parental influence and accessibility of eye care services.

Conclusions

Findings showed insight that adolescent understanding regarding eye health is imperative to support adherence. However, psychological barriers act as a major factor that impedes lens wear. Involving parents and teachers in understanding urgency and severity of eye health in adolescents, specifically refractive error and its long-term negative impact, as well as the prominent psychological barriers, may improve adolescent perception and adherence.

Navigating silence and voice: South Asian women healthcare professionals in the UK NHS during COVID-19 and beyond - a qualitative study

Por: Kauser · S. · Figueiredo · A. P. · Pandya · B. K.
Objective

To explore the experiences of South Asian female healthcare professionals in the UK National Health Service (NHS) during COVID-19, examining how the pandemic conditions exposed the ways in which race, gender and professional identity intersect to shape risk, silence and discrimination.

Study design

A qualitative study using semi-structured interviews.

Setting and participants

27 South Asian female doctors and nurses, employed across NHS trusts in London, Greater Manchester and Liverpool, were recruited through purposive snowball sampling between 2021 and 2022.

Results

This study was conducted during the COVID-19 pandemic, a period when existing workplace inequality became more visible and consequential. Although the research was initially motivated by evidence of disproportionate COVID-19 risk among ethnic minority healthcare staff, participants consistently foregrounded experiences of voice, silence and power within the NHS. It was through these accounts, situated in the heightened pressures and uncertainties of the pandemic, that four key themes emerged: (1) how discrimination and ethnic bias suppress voice; (2) fear of retaliation and the consequences of speaking out; (3) internalised cultural norms and the emotional labour of adaptation; and (4) finding voice through experience and action. Participants reported microaggressions, disproportionate disciplinary scrutiny and informal silencing tactics that left them feeling vulnerable and voiceless. For many, cultural expectations around hierarchy and respect inhibited confrontation, even in the face of unfair treatment. Some women engaged in self-reflexive strategies, learning to interpret institutional codes, recalibrating their behaviour or selectively speaking out. For many, this process of adaptation—learning, recalibrating and navigating institutional expectations—was less a path to upholding their agency and more a survival mechanism within a system they perceived as structurally biased. While a few participants described finding ways to speak out and support others through union membership and legal awareness, most described adaptation as emotionally taxing and ineffectual in the face of structural barriers. Silence (eg, withdrawing, transferring departments, leaving their roles altogether) remained the dominant strategy.

Conclusion

COVID-19 did not create these dynamics, but it did expose and intensify pre-existing constraints on voice in the NHS. Drawing on South Asian women’s accounts, this study provides insight into how institutional and cultural dynamics constrain voice and inclusion, particularly under conditions of heightened organisational pressure. We argue that voice is not just a personal capacity but a structural condition that can either reinforce silence or enable change. Our study highlights the need for structural reforms that strengthen psychological safety, ensure clarity around rights and protections and address the persistent gap between inclusion rhetoric and lived experience.

Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitor-induced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids: REACT trial protocol

Por: Fisher · B. A. · Rowe · A. · Hodson · C. · Wilkhu · M. · Williams · E. · Turner · E. · Allard · A. · Blake · T. · Bombardieri · M. · Cope · A. P. · Dubey · S. · Mankia · K. · Malley · T. · Moore · O. · Payne · M. · Plummer · R. · Tilby · M. · Tillett · T. · Wong · E. · Wu · Y. · Filer · A. · Pra
Introduction

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.

A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.

Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.

Methods and analysis

REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).

The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.

Ethics and dissemination

The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

ISRCTN18217497.

Delivering hospital care at home in a Dutch Tertiary University Hospital: protocol for a prospective feasibility cohort study evaluating a Virtual Ward for early discharge of inpatients

Por: van Herwerden · M. C. · Scholte · N. T. B. · Mkrtchjan · A. · Feyz · L. · Mol · A. P. · Aitken · J. · de Boer · R. A. · Chandoesing · P. P. · Gommers · D. A. M. P. J. · De Haan · B. · Den Hoed · C. M. · van den Hoogen · M. W. F. · Peeters · R. P. · Wlazlo · N. · Van Der Boon · R. M.
Introduction

Virtual Wards (VWs) facilitate hospital-level monitoring, diagnostics and treatment within patients’ homes, while the hospital team retains responsibility for care. International research indicates that VWs decrease hospital length of stay without increasing readmissions; however, the feasibility and key operational determinants within Dutch care remain uncertain. This protocol outlines the VW for Early Discharge in Patients Receiving Inpatient Care (VIP Care) study.

Methods and analysis

The VIP Care study is a single-centre prospective feasibility cohort study conducted at Erasmus University Medical Center (Erasmus MC), Rotterdam, the Netherlands. The study encompasses seven predefined subcohorts with n=51 eligible patients per subcohort: (1) bacterial, fungal or parasitic infections; (2) viral respiratory infections; (3) dehydration; (4) decompensated heart failure; (5) high-dose corticosteroid treatment; (6) post-transsphenoidal pituitary surgery follow-up and (7) severe inflammatory skin disease with or without bacterial or viral superinfection. Adults who require hospital-level monitoring and/or therapy may qualify for early discharge to the VW.

The VW integrates scheduled, patient-performed measurements using (European Conformity) CE-marked devices with structured symptom assessment submitted via a patient application, and data review in an electronic health record-integrated clinician cockpit. Submissions are evaluated by VW tele-nurses using prespecified Early Warning Score based thresholds and an escalation protocol. Patients receive a daily physician telephone review. Diagnostics and treatments are administered at home to hospital standards through established home-care services.

The primary outcome (feasibility) is adherence to transfer, defined as the proportion of eligible inpatients who provide written informed consent and are subsequently successfully transferred to the VW. The prespecified feasibility threshold is 30%. Secondary outcomes include reach (eligibility, invitation and consent rates among admitted patients), operational performance during the VW episode (alert frequency and handling, contact volumes and actions), length of stay on the ward and in the VW, emergency department reassessments and 30-day readmissions. Qualitative interviews will be conducted to identify implementation determinants.

Ethics and dissemination

The study received approval from the Erasmus MC Medical Ethics Committee (MEC-2024–0060; amendment MEC-2024–0060 A0001). Incremental risk is considered minimal. Written informed consent is obtained. Findings will be disseminated through peer-reviewed publications, conference presentations and an accessible lay summary.

Trial registration number

ClinicalTrials.gov NCT06936891; CCMO NL85516.078.24. Recruitment began in May 2025 and is ongoing.

Attributable societal cost of antimicrobial resistance in Ghana: a microsimulation study focusing on sociodemographic groups

Por: Fenny · A. P. · Otieku · E. · Amoah · R. O. · Jejeti · M. · Labi · A.-K. · Hedidor · G. K. · Enemark · U.
Objective

We performed a microsimulation analysis predicting the societal cost of antimicrobial resistance (AMR), which represents the potential cost savings if Ghana eliminates AMR.

Design

This study combined bacterial resistance epidemiology and cost data from Ghana to perform a microsimulation analysis focusing on sociodemographic groups, predicting the potential societal cost savings should Ghana eliminate AMR. The nationally representative data were collected from 12 reference laboratories across Ghana’s three geographical belts between June 2021 and December 2023. Case definition was enterobacterial third-generation cephalosporin (3GC) resistant infections, methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Mycobacterium tuberculosis. Using an adapted microsimulation framework, the simulation incorporated four integrated data modules: population demographics, infection epidemiology, healthcare resource use and expenditure and labour market characteristics. This approach allowed for the construction of synthetic individuals from national data sets and the projection of annual outcomes over a 7-year horizon. Costs were calculated from a societal perspective under a status quo scenario, assuming that admission rates, resistant infection probabilities and mortality rates remain the same. This analysis also considers a 2.1% annual population growth rate, a 5% discount rate for future costs and age-specific resistance risk profile. We stratified the outcome of interest by age groups, sex and wealth quintiles to account for distributional effects and reported the costs in purchasing power parity equivalent in international US dollars.

Setting

Ghana in West Africa.

Participants

A simulated population of AMR patients of all ages and sex.

Main outcome measures

Societal cost attributable to AMR in Ghana.

Results

Assuming probabilities of all-cause hospital admissions of 0.102 for females and 0.093 for males, along with probabilities of AMR infections of 0.239 and 0.193, we predicted nearly 78 000 (95% CI 72 000 to 83 520) annual AMR infections and approximately 6300 (95% CI 3900 to 8638) attributable deaths. MRSA and 3GC-resistant infections made up 20.2% and 79.2% of the predicted annual infections, corresponding to an estimated mean societal cost of about US$435 million. In decreasing order of magnitude, the estimated mean annual cost of productivity loss due to AMR attributable mortality accounted for 40.6% of the mean annual societal cost, followed by the cost to healthcare providers (24.1%), direct medical cost to patients and caregivers (22.4%), productivity loss for surviving patients and caregivers (10.4%) and direct non-medical costs to patients and caregivers (2.6%). Resistant infections in children under 5 and adults over 60 years contributed 48.2% and 26.9% of the estimated annual societal cost, respectively. Except for the number of resistant infections, the estimated mean annual costs between wealth quintile groups were significantly different (p=0.03) due to differences in productivity costs between wealth quintile groups.

Conclusion

The study shows that the societal cost implications attributable to AMR are enormous, requiring a concerted effort by society to mitigate the development and spread of AMR organisms.

Cost-effectiveness of cervical cancer screening among women living with HIV in India: study protocol

Por: Nirmalkar · A. P. · Mamulwar · M. · Godbole · S. · Shahabuddin · S. M. · Bembalkar · S. · Chauhan · A. S.
Introduction

Women living with HIV (WLHIV) face a higher risk of developing cervical cancer. India carries a significant burden of HIV, with an estimated 2.5 million people living with HIV in 2023. While the introduction of more effective antiretroviral therapy has improved the life expectancy of WLHIV, it has also extended the risk window for persistent human papillomavirus (HPV) infection and cervical disease progression. Cervical cancer prevention through HPV vaccination and regular screening remains the cornerstone of public health efforts. This study specifically aims to evaluate the cost-effectiveness of various cervical cancer screening strategies (at different intervals) among WLHIV in India.

Methods and analysis

The study will be conducted in three interlinked components. First, a meta-analysis will be undertaken to evaluate the diagnostic accuracy of different screening strategies in detecting cervical lesions in WLHIV. Second, primary data collection will be carried out to estimate the treatment costs of cervical cancer and HIV among WLHIV. This phase will also include the collection of health-related quality of life (HRQoL) data, to inform utility estimates for the modelling component. A total of 135 participants will be enrolled for cost data assessment. Of these, a subset of 71 participants will also be included for HRQoL assessment. This data collection will be undertaken in four tertiary public sector hospitals located across four Indian states, that is, Mizoram, Maharashtra, Tamil Nadu and Karnataka. Lastly, a decision analytical model will be developed to simulate the process of screening, diagnosis and treatment for cervical cancer in a hypothetical cohort of WLHIV. A structured comprehensive review of literature will be undertaken to inform model input parameters related to the natural history of cervical disease, progression and mortality among WLHIV. Model calibration will be performed using a likelihood-based approach to ensure consistency with empirical epidemiological data. Probabilistic sensitivity analysis will also be conducted to assess the impact of joint parameter uncertainty on model outcomes.

Ethics and dissemination

Ethical approval has been obtained from Ethics Committees of Indian Council of Medical Research–National AIDS Research Institute (NARI), Pune (Protocol No. NARI/EC/Approval/2024/716); B. J. Medical College and Sassoon General Hospitals, Pune (Ref. No. BJGMC/IEC/Pharmac/ND-0824297-297); Cancer Institute (WIA), Adyar, Chennai (Ref. No. IEC/2024/Nov-07); the Mizoram State Cancer Institute, Zemabawk, Aizawl (Ref. No. D.12016/2/2013-MSCI/IEC) and the KLE Academy of Higher Education and Research, Belagavi, Karnataka. The study findings will be disseminated through publications in peer-reviewed journals.

Interruptive versus Non-Interruptive Reminders for Statin tHerApy in Primary Care (INIRSHA-PC): protocol and statistical analysis plan for a randomised clinical trial

Por: Wright · A. P. · Choi · L. · Nairon · K. G. · Gatto · C. L. · Dear · M. L. · Van Winkle · G. · Lagalante · S. · Neal · E. B. · Wright · A. · Rice · T. W. · for the Vanderbilt Center for Learning Healthcare · Bernard · Dittus · Luther · Pulley · Self · Semler · Qian
Introduction

Statins are a cornerstone of cardiovascular disease prevention yet remain underused among eligible patients. Clinical decision support systems embedded in electronic health records (EHRs) are commonly used to encourage guideline-concordant prescribing. Interruptive reminders (eg, pop-ups) may be effective but interfere with clinical workflows and contribute to alert fatigue. Non-interruptive alerts are less intrusive, but their effectiveness remains unclear. The Interruptive versus Non-Interruptive Reminders for Statin tHerApy in Primary Care (INIRSHA-PC) trial is designed to evaluate the comparative effectiveness of interruptive and non-interruptive reminders on statin-prescribing rates.

Methods and analysis

INIRSHA-PC is a single-centre, pragmatic, three-arm, parallel-group randomised controlled trial embedded in the EHR at Vanderbilt University Medical Center. The trial will enrol adults aged 18–74 seen in primary care who are eligible for, but not currently prescribed, statin therapy. The planned sample size is 3000 patients (1000 per arm). Enrolled patients will be randomised 1:1:1 to (1) interruptive reminder, (2) non-interruptive reminder or (3) no reminder (usual care). The primary outcome is statin prescription within 24 hours of enrolment. Secondary outcomes are statin prescribing within 12 months and low-density lipoprotein cholesterol levels measured between 30 days and 12 months after enrolment. Enrolment began on 14 August 2024. The study is expected to be completed on 19 November 2025.

Ethics and dissemination

The trial has been approved by the Vanderbilt University Medical Center Institutional Review Board with waiver of patient informed consent (IRB number: 240419). Results will be disseminated through peer-reviewed publication and presentation at scientific conferences.

Trial registration number

NCT06456658.

The PROTECT trial: Effect of titrated versus conventional induction of general anaesthesia using a target-controlled infusion system on haemodynamics in patients undergoing non-cardiac surgery - protocol for a multicentre, expertise-based randomised contr

Por: Funk · S. · Lohri · M. D. · Kopp Lugli · A. · Schindler · C. · Wiencierz · A. · Mnich · K. · Schläpfer · M. · Gaberdiel · A. P. · Puhan · M. A. · Steiner · L. A. · Gomes · N. V. · Dell-Kuster · S.
Introduction

Hypotension is a frequent complication after induction of general anaesthesia leading to end-organ injury, for which elderly and multimorbid patients are particularly susceptible. The extent of hypotension depends, among other factors, on the dose and rate of propofol administration. Target-controlled infusion systems are widely used to administer short-acting anaesthetics such as propofol and remifentanil. Commonly, induction is started with a fixed effect-site concentration. Titration, an alternative method of induction using an incremental augmentation of propofol, leads to a reduced induction dose and rate of propofol. We hypothesise that the titration method improves haemodynamic stability compared with conventional induction.

Methods and analysis

This multicentre, expertise-based randomised controlled trial takes place at four Swiss hospitals. Patients ≥55 years of age undergoing non-cardiac surgery under general anaesthesia using propofol target-controlled infusion are randomised to either a conventional or a titrated anaesthesia induction method. Patients, statisticians and, if resources allow, outcome assessors will be blinded. The primary endpoint is the mean arterial pressure under the individual baseline mean arterial pressure (area under threshold) during the first 30 min after start of induction. Secondary endpoints include the maximum deviation from baseline mean arterial pressure, haemodynamic rescue methods, propofol consumption and neurocognitive recovery after regaining consciousness.

A total of 320 patients are required to have an 80% chance of observing superiority of titration for the area under the threshold as significant at the 5% level, assuming a true difference of 100 mm Hg*min. The area under threshold and the maximum deviation will be compared between arms using mixed linear regression models.

Ethics and dissemination

Ethical approval has been obtained from all responsible ethics committees (BASEC2025-01007). The results will be presented at international meetings and published in peer-reviewed journals and may contribute to a change in clinical practice for anaesthesia induction using target-controlled infusion systems with propofol.

Trial registration number

clinicaltrials.gov (NCT06980688) and www.humanforschung-schweiz.ch (HumRes67022).

Association of influenza viral genetic information with severity markers in patients hospitalised with influenza: multicentre retrospective cohort study

Por: Myint · A. P. · Shirreff · G. · Baillie · V. · Bal · A. · Boutros · C. F. · Burtseva · E. · Coulibaly · D. · Danilenko · D. · Dbaibo · G. · Destras · G. · Dia · N. · Draganescu · A. C. · Giamberardino · H. I. G. · Komissarov · A. B. · Koul · P. A. · Laguna-Torres · V. A. · LeBlanc · J.
Objective

The objective of this study was to determine the association between viral subtype/clade and disease severity.

Design

Multicentre retrospective cohort study.

Setting

This study used data from the Global Influenza Hospital Surveillance Network (GIHSN). The dataset comprised hospitalised influenza patients with viral sequencing data across 14 countries, collected from August 2022 through October 2023.

Participants

A total of 761 hospitalised patients were enrolled during the study period, and 745 patients were included in the analysis. We excluded patients with missing data on explanatory or outcome variables, those infected with viral clades represented by fewer than 11 sequences, and those enrolled at study sites contributing fewer than 5 patients.

Outcome measures

Disease severity was defined by admission to intensive care unit (ICU), receipt of non-invasive oxygen supplementation, 3-variable definition (ICU, mechanical ventilation or death) or 4-variable definition (3-variable plus oxygen supplementation).

Outcomes were analysed in association with subtype or clade using the mixed-effects logistic regression models, adjusting for age group, sex, underlying medical conditions, influenza vaccination status, antiviral use, country income level and epidemic period, while study site was included as a random effect.

Results

745 patients were included: 263 A(H1N1)pdm09, 380 A(H3N2), 102 B/Victoria. A(H1N1)pdm09 infection was associated with increased odds of ICU admission (adjusted ORs (aORs) 2.5, 95% CI 1.1 to 5.8) compared with A(H3N2). 6B.1A.5a.2a.1 clade of A(H1N1)pdm09 was associated with increased severity compared with 6B.1A.5a.2a clade (aOR 3.0, 95% CI 1.0 to 9.5) and (aOR 5.4, 95% CI 1.6 to 18.3) for the 3-variable and 4-variable definitions respectively. Among A(H3N2), the (3C.2a1b.2a.)2b clade showed a trend toward increased severity using the 4-variable definition compared with the 2a.1b clade (aOR 2.9, 95% CI 0.8 to 10.0).

Conclusions

This analysis highlights the differential impact of influenza subtypes and clades on disease severity in hospitalised patients. Future research should investigate the role of specific viral mutations of these clades in modulating immune evasion or disease severity. These findings reinforce the GIHSN’s critical role in global surveillance. Ongoing genomic surveillance is crucial for understanding the clinical impact of emerging influenza variants and informing public health responses.

Digital support for chronic dyspnoea management in primary care: protocol for the BREATHE (Breathlessness Rapid Evaluation and Therapy) cluster randomised controlled trial

Por: Martin · A. · Sunjaya · A. P. · Giskes · K. · McKeough · Z. · Hespe · C. M. · Arnott · C. · Billot · L. · Campain · A. · Scowcroft · C. P. · Atkins · E. R. · Jan · S. · Scott · H. A. · Chua · A.-V. · Jenkins · C. R. · on behalf of the BREATHE Investigators · Peiris · Marks · Praveen
Introduction

Chronic dyspnoea is a prevalent symptom, and primary care is ideally placed to identify and manage it. However, chronic dyspnoea is under-reported by patients and can be a diagnostic dilemma for practitioners. A fully automated system of patient screening, coupled with a clinical decision support system (CDSS) that uses a validated and evidence-based dyspnoea algorithm, may improve detection, diagnosis and management of the condition. There is currently no CDSS validated for chronic dyspnoea diagnosis and management in primary care in Australia. The objectives of this study are to assess the clinical impact of a CDSS for chronic dyspnoea in primary care. We hypothesise that the use of the CDSS will lead to a clinically significant improvement in patient-reported dyspnoea scores, reduced time to diagnosis and healthcare costs at 12 months compared with standard care.

Methods and analysis

The BREATHE study is an open-label, cluster-randomised controlled trial of standard of care compared with a CDSS. General practices (n=40) in metropolitan, regional/rural and rural/remote settings will be recruited and randomised equally to pre-screening for chronic dyspnoea and usual standard-of-care management or pre-screening and CDSS-guided management. The CDSS includes an algorithm derived from a robust data and clinical knowledge model and incorporates evidence-based recommendations for the assessment and management of chronic dyspnoea. It is integrated into general practice medical software systems, fitting in the workflow of general practitioners (GPs). Eligible patients will be ≥18 years old and will have previously consented to receive SMS communication from their practice. In-scope patients will receive an automated text message prior to their GP appointment and will be screened for chronic dyspnoea (≥4 weeks). Patients identified with chronic dyspnoea will be invited to participate in the BREATHE study and followed up for 12 months. The primary outcome is improvement in the Dyspnoea-12 (D-12) score from baseline to 12 months, measured by the Dyspnoea-12 (D-12) questionnaire. Secondary outcomes include disease-specific questionnaires to assess changes in clinical outcomes, time to final diagnosis, quality of life, healthcare utilisation and costs incurred to patients.

Trial registration number

The trial is registered at ANZCTR (ACTRN12624001451594). ANZCTR is a primary registry that meets the requirements of the ICMJE and is listed on the ICTRP Registry Network.

Ethics and dissemination

The study protocol has been approved by the University of New South Wales Human Research Ethics Committee (HREC) (iRECS6645) and complies with the National Health and Medical Research Council ethical guidelines. Participating practices and each GP will provide written, informed consent. All patients being screened will provide electronic informed consent. Results of the study will be disseminated through various forums, including peer-reviewed publications and presentation at national and international conferences. Following the study, participating practices will be provided with a summary of the findings of the study, together with a full copy of any publications and a plain language statement for participants, which will be made available in the practice reception area.

Potential benefits of group cognitive-behavioural therapy for insomnia in outpatients with coronary heart disease versus usual care: an early economic evaluation

Por: Pacheco · A. P. · Dammen · T. · Munkhaugen · J. · Papageorgiou · C. · Kvaerner · K. J. · Stome · L. N.
Objective

Insomnia afflicts about half of outpatients with coronary heart disease (CHD) and worsens prognosis. We aimed to simulate the potential socioeconomic savings of integrating group cognitive–behavioural therapy for insomnia (gCBT-I) into cardiac outpatient care for patients with CHD compared with usual care.

Design

Early health technology assessment using prospective and cross-sectional cohort data.

Setting

Secondary care for outpatients with CHD in Norway in a non-university hospital setting.

Participants

A hypothetical cohort of 100 outpatients with CHD and insomnia.

Interventions

Weekly sessions of gCBT-I over 5 weeks versus usual care.

Primary and secondary outcome measures

Potential savings related to possible effects on revascularisations and hospitalisations due to a recurrent CHD event, and reduced sick leave. Representative data on healthcare consumption and sick leave rates were collected from the NORwegian CORonary cohort study (n=528). Costs of productivity loss were drawn from public sources and calculated using a conservative human capital approach. Estimates of therapeutic effectiveness in conveying insomnia remission by gCBT-I were informed by results from randomised trials and meta-analyses.

Results

Rates of healthcare consumption and sick leave were higher in outpatients with CHD and insomnia compared with those without insomnia. Our model indicated that treating 100 patients with gCBT-I would cost 2406. If patients treated with gCBT-I show similar rates of revascularisations and hospitalisations as those without insomnia, there is a maximum potential saving of 117,221 per 100 patients tied to healthcare consumption. Similarly, the maximum potential savings related to reduced productivity loss from sick leave range from 53,244 to 692,172.

Conclusion

Treating insomnia among outpatients with CHD has the potential for substantial reduction of socioeconomic costs related to healthcare consumption and sick leave. Implementation into routine outpatient care seems relevant, but randomised controlled trials investigating the effects of gCBT-I in this population are warranted.

Pittsburgh Brain Health Initiative (BHI): protocol and methods for an observational study of cognitive function in former professional football players and controls

Por: Okonkwo · D. O. · Collins · M. W. · Kontos · A. P. · Lopez · O. · Mountz · J. M. · Wisniewski · S. R. · Edelman · K. L. · Benso · S. · Holland · C. · Beers · S. R. · Soose · R. J. · Harrison · T. · Mucha · A. · Puccio · A. · Mancinelli · M. · Borrasso · A. · Rosario · B. L. · Laymon · C.
Introduction

Long-term brain health profiles following exposure to repetitive head impacts and/or concussions in contact sports are a public health focus and the subject of a national debate. The true prevalence rates of mild cognitive impairment (MCI) or neurobehavioural dysregulation are unknown in the nearly 20 000 current/living former professional football players. Here, we describe the procedures and methodology of the prevalence study of cognitive function in former professional football players from the Brain Health Initiative at the University of Pittsburgh. The objective is to define the prevalence of normal cognitive function versus neurodegeneration in former professional football players through clinical, neuroimaging and biomarker assessments.

Methods and analysis

Participants include former professional football players aged 29–59 years at study onset who played a minimum of three professional football games in three professional seasons and non-exposed controls. Participants are recruited by two mechanisms, a random and non-random sample. The full study protocol includes a 3–4-day, multidomain assessment (eg, neurological, neurocognitive, psychiatric, sleep, vestibular, orthopaedic and cardiovascular) for neurodegenerative disease and overall health and function, including MRI, positron emission tomography scans, analysis of blood plasma and cerebrospinal fluid, neurocognitive assessments, applanation tonometry, overnight sleep study and informant interview. A multidisciplinary clinical panel conducts a blinded diagnostic consensus conference to adjudicate the presence of MCI and/or traumatic encephalopathy syndrome, which serve as the study’s primary and secondary outcomes, respectively. Point prevalence of these for both the exposed and unexposed cohorts will be calculated as the primary statistical analysis.

Ethics and dissemination

The University of Pittsburgh Institutional Review Board approved the study prior to recruiting human subjects (protocol numbers STUDY19010008: sIRB - Brain Health Initiative (Part 1) and STUDY19030211: sIRB - Brain Health Initiative (Part 2)). The results will be disseminated in peer-reviewed journals and as presentations at national and international scientific conferences.

Incidence of all-cause mortality in prisons: research protocol for a global registry study and systematic literature review with meta-regression analyses

Por: Mundt · A. P. · Rozas-Serri · E. · Asencio Rojas · B. I. · Morales-Rojas · A. · Cifuentes-Gramajo · P. A. · Alvarado · S. · Baranyi · G. · Borschmann · R. · Fazel · S. · Kinner · S. A.
Introduction

People in prison experience disproportionate health burdens compared with community-based populations, including elevated rates of infectious and non-communicable diseases, mental illness and substance use disorders. Previous studies have consistently shown increased rates of mortality following release from incarceration, particularly from external (unnatural) causes such as suicide and violence. However, evidence on mortality incidence during imprisonment is scarce, and many deaths may be preventable through targeted health and prevention interventions. This study aims to synthesise worldwide evidence on all-cause mortality incidence in prisons.

Methods and analysis

We will conduct a worldwide registry study combined with a systematic literature review and meta-regression analysis. Eligible sources will report deaths among incarcerated people between 2005 and 2025 at the national or, where more appropriate, the subnational jurisdictional level. Mortality data will be retrieved from official reports of prison administrations and direct contact with prison authorities. Also, data from international databases and the scientific literature will be reviewed. Incidence rates of all-cause mortality per 100 000 person-years will be calculated and reported for each jurisdiction, alongside standardised mortality ratios comparing imprisoned populations with general population estimates.

Ethics and dissemination

Since the study relies on anonymised routine data registries available from different sources, an exemption certificate was granted by the Ethics Committee of Diego Portales University (UDP) in Santiago, Chile. Findings will be submitted for publication in a peer-reviewed academic journal.

Trial registration number

https://osf.io/vkzae.

Psychometric Evaluations of the Hospital Survey on Patient Safety Culture Version 2.0 in Ethiopia (E-HSoPSC 2.0): A Cross-Sectional Study

Por: Fekadu · G. · Marshall · A. P. · Muir · R. · Tobiano · G. · Ireland · M. J.
Objectives

To evaluate the psychometric properties of the Hospital Survey on Patient Safety Culture (HSoPSC) version 2.0 in Ethiopian public hospitals.

Design

A cross-sectional study.

Settings

Five public hospitals in Eastern Ethiopia.

Participants

Healthcare professionals (N=582).

Main outcome measure

An adapted and contextualised version of HSoPSC 2.0 was used to conduct structural validity using exploratory and confirmatory factor analyses (EFA and CFA). Convergent and discriminant validity were evaluated through item loadings and interfactor correlations, respectively. Reliability was measured using McDonald’s omega and Cronbach’s alpha.

Results

CFA indicated a poor model fit for the original 10-factor, 32-item HSoPSC 2.0 across all statistical indices: relative chi-square (²/df=7.71), root mean square error of approximation (RMSEA=0.108), standardised root mean square residual (SRMR=0.088), comparative fit index (CFI=0.814) and Tucker-Lewis’s index (TLI=0.780). Consequently, a comprehensive EFA was conducted, which identified a revised model comprising 5-factor, 21-item. This model accounted for 62.8% of the total variance and demonstrated strong construct validity, with excellent fit indices (²/df=3.67, RMSEA=0.068, SRMR=0.034, CFI=0.969, TLI=0.945). Internal consistency, assessed via McDonald’s omega and Cronbach’s alpha, exceeded the acceptable threshold of 0.70 across all dimensions, except for Response to Error (0.66). The convergent and discriminant validity of the new model was confirmed, ensuring an accurate representation of the underlying constructs.

Conclusions

The original HSoPSC 2.0 with 10-factor, 32-item failed to demonstrate structural validity in the Ethiopian healthcare context. In contrast, a revised 5-factor, 21-item model showed strong validity and acceptable reliability. This adapted version provides a culturally and contextually relevant tool for assessing patient safety culture in Ethiopian healthcare settings.

Impact of drug-resistance diagnosis based on whole-genome sequencing on the treatment adequacy of patients with drug-resistant pulmonary tuberculosis in the state of Sao Paulo, Brazil: a protocol for a non-randomised controlled trial (Gen-TB ProCura)

Por: Rosa · C. D. · Ferrazoli · L. · dos Santos · D. P. · Pedace · C. · Soler-Camargo · N. C. · Silva-Pereira · T. T. · Brandao · A. P. · Bollela · V. R. · Cruz · A. L. G. · Feliciano · C. S. · Ferreira · P. R. A. · Jorge · E. P. · de Miranda · S. S. · de Oliveira · R. S. · Oliveira · M.
Introduction

Since 2018, WHO has endorsed the use of whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex isolates to detect drug-resistant tuberculosis (DR-TB). This endorsement was based on the assumption that a faster and more detailed description of the resistance profile would improve treatment prescription for DR-TB by healthcare providers, and hence the treatment outcomes of patients. Nonetheless, this assumption has not been tested in routine clinical practice and different scenarios. In Brazil, WGS is not routinely used for the diagnosis of DR-TB, having been carried out in only a few centres for research purposes. With this trial, we will evaluate whether a WGS-based drug-resistance report improves treatment adequacy in patients with pulmonary DR-TB, compared with the current standard-of-care diagnostic methods used in the state of São Paulo, Brazil.

Methods and analysis

We will conduct a non-randomised controlled clinical trial with two arms to compare the intervention group (ie, individuals receiving a WGS-based report) with a historical control group (i.e., individuals who received resistance diagnostics based on the standard of care of conventional genotyping and phenotyping techniques). The primary outcome will be the proportion of patients whose treatment scheme was adequate based on complete resistance profile determined by WGS and/or phenotypic drug-susceptibility testing (pDST). Other secondary outcomes will also be considered. The target sample size is 88 eligible patients per group. The intervention group will be prospectively recruited over 18 months and the control group will be composed of patients diagnosed with pulmonary DR-TB up to 2 years before the start of the trial. To ensure comparability, isolates from the control group will undergo WGS retrospectively, and pDST will be performed retrospectively in both groups. This clinical trial will take place in six medical centres for the treatment of DR-TB in the state of São Paulo. This study is intended to support the implementation of the WGS in the routine diagnosis of DR-TB in the state of São Paulo.

Ethics and dissemination

Ethical approval was obtained from the Human Research Committee of the Institute of Biomedical Sciences, University of São Paulo, Brazil (CAAE: 79497924.1.1001.5467). Study results will be published in peer-reviewed journals and disseminated to policymakers and stakeholders.

Trial registration number

U1111-1308-4669.

Weighing the impact of evidence in orthopaedic trauma registries: a systematic review of national and international registry data

Por: George · A. J. · Ashwood · N. · Dekker · A. P. · Wilson · P. · Crawford · A. · Mukherjee · A.
Objectives

Worldwide, there are 15 established trauma databases collecting data to better understand the patterns of injury and effectiveness of interventions, but interpreting the information is hampered by the varied approaches. The aim of this study was to determine the impact, practices, evolution in design and methods of analysis that are standardised and comparable within registries.

Design

A thematic analysis using a narrative synthesis was used to develop threads for future study and identify the limitations in current practice.

Data sources

PubMed, Ovid, Scopus and EMBASE were searched on the 2 October 2025. At the same time, ChatGPT (Open artificial intelligence) identified the most cited articles in orthopaedic trauma registries, cross-referencing lists as a form of triangulation to aid in snowballing references.

Eligibility criteria

The review included 174 papers from trials and observational studies that analyse data from established trauma orthopaedic registries published in English.

Data extraction and synthesis

Two independent reviewers used standardised methods to search, screen and code included studies assessing the papers using the Strengthening the Reporting of Observational Studies in Epidemiology checklist to assess the observational and cohort studies and the Downs and Black Quality Criteria for the remaining papers.

Results

Outcome measures other than mortality are poorly collected, undermining the value of registries. Trauma patients reported considerable impairment 6 and 12 months after injury. Association between level of trauma care and mortality is evident for major trauma populations, but does not hold for general trauma populations. Level I trauma centres produce improved survival in severely injured, but this association could not be proven for non-fatal outcomes in general populations. There is a disparity between resources allocated to save and salvage cases within major trauma units, and hence, routine cases often have lower priority and delayed care.

Conclusions

There is a need to develop a standardised and reproducible method to evaluate data quality in trauma registries. National performance guidelines and trauma centre audits are integral steps towards optimum results. Routine collection of postinjury outcome measures beyond mortality will enable the development of quality improvement metrics that better reflect patient outcomes.

State of Ohio Adversity and Resilience (SOAR) study protocol: a comprehensive, multimodal, family-based, longitudinal observational investigation of risk and resilience in mental health and substance use disorders

Por: King · A. P. · Langenecker · S. · Gorka · S. M. · Turner · J. · Wang · L. · Wastler · H. · Gonzalez · M. · Christian · L. M. · Keck · C. · Olsen · R. · Kim · H. · Klamer · B. · Fernandez · S. · Adler · C. · Andari · E. · Barrenger · S. L. · Bonfine · N. · Bozzay · M. · Brown · S. L. · Browni
Introduction

Deaths related to drug overdose and suicide in the USA have increased 500% and 35%, respectively, over the last two decades. The human and economic costs to society associated with these ‘deaths of despair’ are immense. Great efforts and substantial investments have been made in treatment and prevention, yet these efforts have not abated these increasing trajectories of deaths over time. The COVID-19 pandemic has exacerbated and highlighted these problems. Notably, some geographical areas (eg, Appalachia, farmland) and some communities (eg, low-income persons, ‘essential workers’, minoritised populations) have been disproportionately affected. Risk factors have been identified for substance use and suicide deaths: forms of adversity, neglect, opportunity indexes and trauma. Yet, the biological, psychological and social mechanisms driving risk are not uniform. Notably, most people exposed to risk factors do not become symptomatic and could broadly be considered resilient. Achieving a better understanding of biological, psychological and social mechanisms underlying both pathology and resilience will be crucial for improving approaches for prevention and treatment and creating precision medicine approaches for more efficient and effective treatment.

Methods and analysis

The State of Ohio Adversity and Resilience (SOAR) study is a prospective, longitudinal, multimodal, integrated familial study designed to identify biological, psychological and social risk and resilience factors and processes leading to mental health disorders, substance use disorders, substance overdose, suicide and associated psychological/medical comorbidities which reduce life expectancy and quality of life. It includes two nested longitudinal samples: (1) WD Survey: an address-based random population epidemiological sample of 15 000 individuals (unique households) representative of the state of Ohio assessed for psychosocial, psychiatric, behavioural health and substance use factors and (2) Brain Health Study: a family-based, multimodal, deep-phenotyping study conducted in 1200 families (up to 3600 persons aged 12–72 years) including MRI, electroencephalography, blood biomarkers and psychiatric diagnostic interviews, as well as neuropsychological, psychosocial functioning and family/community history, dynamics and support assessments. SOAR is designed to discover, develop and deploy advanced predictive analytics and interventions to transform mental health prevention, diagnosis, treatment and recovery.

Ethics and dissemination

All participants will provide written informed consent (or parental permission and assent for minors). The study was approved by The Ohio State University Institutional Review Board (study numbers 2023H0316 (Brain Health) and 2023H0350 (Wellness Survey). The Brain Health study was also approved by institutional review boards at each partnering institution involved in conducting participant assessments. Findings will be disseminated to academic peers, clinicians and healthcare consumers, policymakers and the general public, using local and international academic channels (academic journals, evidence briefs and conferences) and outreach (workshops and seminars).

Photobiomodulation for postoperative pain relief following conventional periapical surgery: a randomised controlled study protocol

Por: Cirisola · R. W. C. · Moya · L. E. P. · Olazabal · M. V. G. · Wagmann · D. A. A. · Suarez · G. P. · Wince · C. · Bruno · M. L. H. · Salaberry · D. R. · Sobral · A. P. T. · Longo · P. L. · Motta · L. J. · Bussadori · S. K. · Duran · C. C. G. · Fernandes · K. P. S. · Mesquita-Ferrari
Introduction

Photobiomodulation (PBM) has shown promising effects in managing postoperative pain following conventional periapical surgery, although current evidence remains limited. This study aims to assess the effect of PBM on postoperative pain 24 hours after periapical surgery.

Methods and analysis

A randomised, controlled, double-blind trial will include 34 patients undergoing periapical surgery in the maxillary region, randomly assigned to an experimental group (n=17) or control group (n=17). The experimental group will receive PBM (GaAlAs diode laser, 808 nm, 100 mW, 4 J/cm², applied at five vestibular points) and placebo ibuprofen immediately and 24 hours postoperatively. The control group will receive simulated PBM and active ibuprofen. The primary outcome is postoperative pain assessed by the visual analogue scale at 24 hours. Secondary outcomes include pain at the seventh day, paracetamol intake, oedema, ecchymosis, soft tissue status and temperature at 24 hours and 7 days. Radiographic evaluation of healing will be performed at 1 and 3 months. Statistical analysis will be conducted based on data distribution, using repeated measures ANOVA (Analysis of Variance) or non-parametric equivalents for longitudinal outcomes, and appropriate tests for categorical variables. Significance will be set at p

Ethics and dissemination

The study was approved by the Human Research Ethics Committee of Universidad Católica del Uruguay (process no. 220914). Results will be disseminated to participants, healthcare professionals, the public and scientific communities.

Trial registration number

NCT05935306.

Economic evaluation of a hybrid type 1 effectiveness-implementation trial comparing a community health worker palliative care intervention to enhanced standard of care in African American patients across four cancer centres in the USA: a study protocol

Por: Monton · O. · Drabo · E. F. · Masroor · T. · Fuller · S. · Woods · A. P. · Siddiqi · A. · Malone · T. B. · Johnston · F. M.
Introduction

Despite increasing palliative care capabilities in the USA, utilisation rates remain low for patients with advanced cancer, particularly among African American patients. To address this gap, a theory-driven, stakeholder-informed community health worker (CHW) palliative care intervention for African American patients with advanced cancer and their informal caregivers is currently being assessed through a hybrid type 1 effectiveness-implementation trial at four cancer centres across the USA. To improve the quality and efficiency of palliative care delivery, inform resource allocation and guide broad-scale implementation, it is essential to generate evidence on the economic value of palliative care programmes. The objectives of this study are to evaluate the cost-effectiveness and estimate the social value of a CHW palliative care intervention for African American patients with advanced cancer and their caregivers.

Methods and analysis

We will conduct cost-effectiveness analyses (CEAs) and a social return-on-investment (SROI) analysis to assess the value of the CHW palliative care intervention compared with enhanced standard of care. Standard, extended and distributional CEAs will be performed from the perspectives of an adopting organisation or payer (eg, Medicaid), the US healthcare sector and society. An SROI analysis will also be conducted to assess the social value of the intervention. These analyses will focus on estimating the costs, health and distributional impacts of the intervention.

Ethics and dissemination

This study protocol was approved by the Johns Hopkins Medicine Institutional Review Board (IRB00372476). All methods will be carried out in accordance with relevant guidelines and regulations. Written informed consent will be obtained from all subjects prior to study participation. This manuscript does not contain participant-level data. The full protocol will be available from the corresponding author on reasonable request. The dissemination of findings from the clinical trial and accompanying economic evaluation outlined in this manuscript will be multifaceted to maximise reach and impact. Research findings will be presented at relevant scientific conferences, submitted for publication in peer-reviewed journals and shared with community stakeholders, including hospital leaders and administrators, providers, CHWs and patient advocacy groups.

Trial registration number

NCT05407844.

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