Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is a treatment for peritonitis carcinomatosa. These procedures often involve significant blood and fluid loss, leading to hyperdynamic circulation and vasodilation, necessitating intraoperative fluids and vasoconstrictors such as catecholamines. Excessive fluid administration to counteract vasodilation can cause intraoperative fluid overload, which is linked to increased postoperative complications. Vasopressin has emerged as a potential alternative to catecholamines, restoring vascular tone via non-adrenergic pathways and supporting perfusion pressure, potentially reducing the need for compensatory fluids solely administered to compensate for vasodilation. We hypothesise that compared with norepinephrine, vasopressin reduces cumulative intraoperative fluid administration during CRS-HIPEC within a goal-directed fluid therapy (GDFT) protocol, ultimately leading to a lowering of postoperative complications.

HiPress is a two-centre, two-arm randomised clinical trial with blinding of both patients and outcome assessors. A total of 70 adult patients undergoing CRS-HIPEC will be included. Patients will be randomised to receive either continuous low-dose argipressin or continuous low-dose norepinephrine. Both groups will receive standardised GDFT during the procedure. The primary endpoint is cumulative intraoperative fluid administration (mL). Secondary endpoints include direct fluid-related outcomes (eg, cumulative intraoperative fluid (ml/kg/hour), postoperative fluid balance until day five and ultrasound-assessed pulmonary oedema and venous congestion) and indirect fluid-associated outcomes (eg, quality of recovery, surgical and abdominal complications, acute kidney injury (AKI), pulmonary complications, length of ICU and hospital stay and 30-day mortality).

The study is enrolling patients since February 2025. The trial is approved by the Medical Research Ethics Committee (hereinafter: MREC) NedMec, The Netherlands (Ref: D-25-500202). Results of the trial will be published in an international peer-reviewed journal and announced at national and international scientific meetings.

Clinical Trials Information System (CTIS): European Union clinical trials register (EUCT) number: 2024–5 13 598-33-00

Chronic dyspnoea is a prevalent and clinically significant symptom, often indicative of underlying cardiorespiratory disease. It is frequently under-reported by patients and under-recognised in primary care, with these challenges exacerbated in rural and remote communities where disease burden is greater and patients experience barriers to timely diagnosis and management. The BREATHE SMART trial aims to implement and evaluate an innovative, fully digital self-screening system for chronic dyspnoea, integrated into general practice workflows and information technology infrastructure. This approach seeks to enhance early detection and management of chronic cardiorespiratory conditions across diverse practice settings.

This multisite proof-of-concept study will test a software platform delivering a preconsultation self-screening questionnaire across 40 general practices in urban, rural and remote Australia. The system identifies eligible patients (≥18 years, consenting to SMS communication with their practice), issues an automated SMS that administers a validated dyspnoea screening questionnaire, and summarises responses for integration into the electronic medical record. Process evaluation will assess acceptability and utility using deidentified audit data, software metrics and qualitative feedback from patients, staff and general practitioners (GPs) via surveys, interviews and focus groups. Approximately 12 000 patients will be screened over 12 months. Primary outcomes will include the proportion completing self-screening and prevalence of chronic dyspnoea and secondary outcomes will include the rate of newly diagnosed chronic dyspnoea-related conditions (ie, asthma, chronic obstructive pulmonary disease and heart failure) in the preceding 12 months and during the intervention period.

Ethics approval was granted by the University of New South Wales Human Research Ethics Committee (HREC) (iRECS6645) and the University of Notre Dame Australia HREC (2024-155). 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 practices.

ACTRN12624001451594.

In many countries, a high or increasing rate of sickness absence is challenging the sustainability of present sickness absence benefit schemes. Most sickness absence is certified on the grounds of common mental disorders or musculoskeletal disorders, and substantial effort has been invested in developing interventions promoting return to work for these patients. In Norway, the Health in Work ((HelseIArbeid), HIA) clinics were established as outpatients’ services within the specialised healthcare system, with the aim of improving health and supporting return to work. The HIA service admits patients with low-to-moderate anxiety/depression and/or musculoskeletal disorders. In this protocol, we describe the naturalistic multicentre randomised controlled trial Norwegian Sickness Absence Clinic Efficacy study, which aims to determine the effect of HIA on work participation and health.

The HIA outpatient service is staffed by clinical psychologists, physiotherapists, medical specialists in physical medicine and rehabilitation and employment support supervisors from the Norwegian Labour and Welfare Administration. Patients admitted to HIA have access to multidisciplinary assessment and treatment. The trial recruits’ patients from five HIA outpatient clinics in Northern Norway. Patients are randomised in equal proportions to either (1) rapid HIA (assessment within 4 weeks), (2) delayed HIA (assessment within 10–14 weeks) or (3) active control, which consists of a monodisciplinary examination at HIA close to diagnosis-specific deadline for examination as suggested by guidelines (8–26 weeks). The trial commenced recruitment on 16 January 2023 and will recruit 2500 patients. The aim is to assess the effect of the HIA service, with the hypothesis that the HIA concept is superior to what resembles treatment as usual, in improving employment and preventing long-term welfare dependency. Secondary outcomes include self-reported symptoms of health problems. We also examine the effect the service has on other healthcare utilisation. To date, no research has been conducted to assess the efficacy of the HIA service. If proven efficacious, and if there is an economic case for this investment in tailored healthcare delivery, the policy implication may be implementation of the service at scale. If not, adaptations or investments into other viable paths of treatment may be considered.

The study is approved by the Regional Committee for Medical Research Ethics (REC North, #122770). Results from the study will be disseminated at national and international scientific conferences, to funders and participating outpatient clinics in seminars and in peer-reviewed scientific journals.

NCT05310695.

In the first 2 years of the COVID-19 pandemic, Hong Kong adopted strict public health and social measures to stop community transmission of SARS-CoV-2. These include border screening and control, isolation of cases and quarantine of their contacts and universal masking. During this period, attack rates in Hong Kong were among the lowest globally.

To estimate the seroprevalence of COVID-19 among healthcare workers (HCWs) in Hong Kong in 2020 and 2021.

We reviewed contact tracing data from the Hong Kong Department of Health to identify COVID-19 cases reported among HCWs. Between June 2020 and December 2021, we conducted a longitudinal cohort study to estimate the seroprevalence of COVID-19 among HCWs working in hospitals and clinics in Hong Kong during the first 2 years of the COVID-19 pandemic.

Overall seropositivity of COVID-19 by plaque reduction neutralisation test during the first (May–October 2020) and second round (November 2020–April 2021) of the study was 0% (95% CI 0.00% to 0.49%) and 0.52% (95% CI 0.14% to 1.33%). After COVID-19 vaccines were offered to HCWs in February 2021, seroprevalence by surrogate virus neutralisation assay among cohort participants who provided biannual blood samples rose to 68.7% (95% CI 65.9%, 71.3%) and 80.2% (95% CI 76.8%, 83.2%) in round 3 (May–October 2021) and the first 2 months of round 4 (November–December 2021).

Seroprevalence in Hong Kong HCWs in our study was low despite considerable exposure to confirmed COVID-19 cases in some study participants. However, the low rate of community transmission may have also contributed to the observed low seroprevalence among HCWs in our cohort.

To explore women’s expectations and experiences of care and support from pregnancy to childbirth in Burkina Faso, with a focus on the role and impact of companions and providers.

An exploratory qualitative study based on in-depth interviews with purposively sampled participants and employing reflexive thematic analysis.

Two public hospitals in urban Burkina Faso having implemented the ‘QUALIty DECision-making by women and providers for appropriate use of caesarean section’ intervention.

24 purposively selected postpartum women with variation in terms of parity, mode of birth, labour companionship experiences, education level and occupation were interviewed before discharge from the hospital.

The two themes generated from the analysis elucidate how women rely on providers and companions to navigate uncertainty and vulnerability experienced during pregnancy and childbirth. Women viewed providers as essential for managing the biomedical risks of childbirth and voiced their need for care at critical moments. They expected companions to enhance the non-clinical aspects of their experiences by providing spiritual support and alleviating feelings of loneliness. However, participants also expressed ambivalence about companions witnessing intimate aspects of their birth experience and valued the ability to choose a companion as means to preserve personal integrity.

Both providers and labour companions play an essential role in enhancing women’s experiences of pregnancy and childbirth in Burkina Faso. Additional research and programmatic efforts are needed to support women’s equitable participation in patient–provider interactions and operationalise the notion of choice of a labour companion in a contextually appropriate manner.

Leprosy is a chronic disease caused by the bacillus Mycobacterium leprae and remains a public health concern in endemic countries. Early diagnosis is fundamental to prevent transmission and irreversible disabilities. Histopathological identification of acid-fast bacilli in tissue specimens is traditionally considered the laboratory reference standard; however, its sensitivity is limited, particularly in paucibacillary forms. Immunohistochemistry (IHC) has been proposed as an adjunctive diagnostic tool for detecting M. leprae antigens in tissue samples, but its diagnostic accuracy has not been systematically synthesised. This protocol outlines a systematic review aimed at evaluating the sensitivity and specificity of IHC in the laboratory diagnosis of leprosy.

This systematic review of diagnostic test accuracy studies will include analytical observational studies and clinical trials evaluating IHC in human subjects with suspected leprosy. The reference standard will be defined as the identification of acid-fast bacilli in skin biopsy specimens from patients with compatible clinical presentation using conventional staining methods (eg, Fite-Faraco), with the exclusion of alternative mycobacterial infections when applicable. Searches will be conducted in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Scopus, Web of Science and BVS/LILACS (Biblioteca Virtual em Saúde/Latin American and Caribbean Health Sciences Literature), as well as grey literature sources, at 31 May 2026. Two independent reviewers will perform study selection, data extraction using a standardised Microsoft Excel form and risk of bias assessment using the Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity estimates will be calculated. If appropriate, a bivariate random-effects meta-analysis will be conducted using RevMan (Review Manager) and Stata.

Ethical approval is not required because this study will use publicly available data. The results will be submitted to a peer-reviewed journal and presented at scientific conferences.

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?

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.

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.

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.

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.

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

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.

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.

Qualitative design through individual interviews and thematic analysis.

Middle school students in five regions of Jakarta Province.

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

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.

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.

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.

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.

A qualitative study using semi-structured interviews.

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.

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.

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.

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.

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.

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.

ISRCTN18217497.

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.

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.

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.

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

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

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.

Ghana in West Africa.

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

Societal cost attributable to AMR in Ghana.

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.

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.

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.

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.

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.

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.

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.

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.

NCT06456658.

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.

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.

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.

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

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

Multicentre retrospective cohort study.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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

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

A hypothetical cohort of 100 outpatients with CHD and insomnia.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

https://osf.io/vkzae.