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Cost-effectiveness of osteoporotic fracture risk assessment in people with intellectual disabilities: a UK NHS modelling study

Por: Png · M. E. · Frighi · V. · Holt · T. A. · Achana · F. · Smith · M. C. · Collins · G. S. · Roast · J. · Petrou · S.
Objectives

We compared the cost-effectiveness of alternative fracture risk assessment strategies for people with intellectual disabilities (ID) aged ≥40 years from a UK National Health Services perspective over a lifetime horizon.

Design

Cost-effectiveness analysis using a lifetime decision-analytical model.

Setting

UK primary care, with data from literature and national databases.

Participants

People with ID.

Interventions

Three strategies were assessed: (S1) Risk assessment using the UK QFracture score; (S2) use of IDFracture (a fracture risk prediction tool specifically developed for adults with ID); and (S3) conducting a one-time dual-energy X-ray absorptiometry (DXA) scan in all. S1 and S2 were followed by DXA scan for those at risk. At-risk individuals received treatment according to UK practice (bisphosphonates plus vitamin D and calcium for osteoporosis, and vitamin D and calcium alone for osteopenia).

Primary outcome measures

Direct healthcare costs and quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER).

Results

In the base case, S2 (ICER: –£2568/QALY) was dominant (ie, less costly and more effective) and S3 (ICER: £1678/QALY) was cost-effective relative to S1 for major osteoporotic fracture (MOF). For hip fracture, S2 (ICER: £32 116/QALY) and S3 (ICER: £49 536/QALY) were not cost-effective relative to S1 under the National Institute for Health and Care Excellence-recommended cost-effectiveness thresholds. Findings from the sensitivity analyses were predominantly consistent with the base-case results. Subgroup analyses showed that age-specific and gender-specific strategies could be used.

Conclusion

For people with ID aged ≥40 years, a proactive approach to risk assessment for MOF is not only clinically beneficial, but also cost-effective.

Association between older patients receiving geriatric co-management at the emergency department and acute hospital admissions compared to usual care: an observational, controlled study in the Netherlands

Por: Hogervorst · V. M. · Ribbink · M. · van Eekelen · R. · Buurman · B. M. · De Jonghe · A. · Macneil Vroomen · J. L.
Objectives

The aim of this study is to determine if a geriatric co-management model, referred to as ‘The Geriatric Emergency Medicine (GEM)-team’ is associated with less admissions to hospital in older patients compared with the usual care without increasing the risk of mortality or 30-day emergency department (ED) readmissions.

Design

This observational, controlled study used 18-month data prospectively collected from hospital records. Inverse probability weighting was used to account for baseline differences.

Setting

An ED at a suburban Dutch general hospital, receiving approximately 10 000 patients aged 70 or older per year.

Participants

All patients aged 70 or older were screened according to predefined criteria. When positively screened patients were presented at the ED on weekdays between 09:00–17:00, they received geriatric co-management. Outside these hours and when the capacity of the GEM team was reached, patients received care as usual.

Interventions

Geriatric co-management at the ED involves a geriatric multidisciplinary team in collaboration with the primary ED physician who share management and responsibility for the provided medical treatment and nursing care starting directly at the primary assessment.

Primary and secondary outcome measures

The primary outcome was hospital admission and secondary outcomes were the composite outcome of 30-day ED readmissions and mortality.

Results

Patients receiving geriatric co-management (n=972) had lower odds for hospitalisation (OR: 0.77, 95% CI 0.65 to 0.91) compared with the control group (n=1355) while 30-day ED readmissions and mortality did not differ between groups (OR: 1.11, 95% CI 0.91 to 1.36).

Conclusions

Geriatric co-management at the ED is associated with decreased hospital admissions while 30-day ED readmissions or mortality was not impacted. These preliminary results contribute to the evidence that geriatric co-management may be an effective intervention for older patients with frailty at the ED.

Indocyanine green fluorescence for intraoperative detection of liver tumours in minimally invasive surgery: protocol for the LIVERGREEN phase IV multicentre clinical trial

Por: Huerta · M. · Lopez-Ben · S. · Llado · L. · Sanchez-Cabus · S. · Mils · K. · Molina · V. · Dopazo · C. · Vidal · L. · Dalmau · M. · Caralt · M. · Roson · N. · Merino · X. · Armario · D. · Salcedo · M. T. · Pellino · G. · Sapisochin · G. · Gomez-Gavara · C. · LIVERGREEN Collaborative Grou
Introduction

Liver tumours are a leading cause of global morbidity and mortality. Current diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI) and intraoperative ultrasound (IOUS), have limitations in detecting liver neoplasms. Indocyanine green (ICG) has emerged as a promising tool for improving liver tumour detection. This study aims to assess the impact of preoperative ICG on intraoperative tumour detection in minimally invasive surgery and develop a machine-learning algorithm to enhance tumour detection using ICG fluorescence.

Methods and analysis

This prospective, multicentre, phase IV clinical trial adheres to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Patients with liver tumours eligible for minimally invasive surgery and a preoperative imaging test will be included. ICG will be administered intravenously 24 hours before surgery. Intraoperative procedures will include IOUS, ICG mapping and photographic documentation. Patients will be followed for 90 days to assess tumour progression, morbidity and mortality. The photographic analysis will enable the development of an artificial intelligence algorithm using machine learning and neural networks to identify lesions based on ICG fluorescence. The estimated sample size is 173 patients and the trial is predicted to accrue in 3 years.

Ethics and dissemination

The trial will be conducted in accordance with the Declaration of Helsinki and the Spanish Agency of Medicines and Medical Devices (AEMPS) guidelines. Approved by the local institutional Ethics Committee and the AEMPS, the results will be shared with the scientific community through publications and conferences.

EudraCT number

2023–5 08 316-27-00.

Trial registration number

NCT06398028.

Protocol version

V.12, 18 March 2025

Changes in the epidemiology of heart failure in the decade 2014-2023: insights from the AQUORE retrospective cohort study

Por: Lancia · L. · Dante · A. · Caponnetto · V. · Petrucci · C. · Masotta · V. · Mammarella · L. · Romano · S.
Objective

Heart failure (HF) is a major public health issue due to its high morbidity, mortality and healthcare burden. This study aimed to provide estimates of HF incidence, survival rates, outcome changes and their predictive factors in a central Italian population over the decade 2014–2023.

Design

Population-based retrospective cohort study.

Setting

Hospital discharge records from all hospitals in L'Aquila Province of Italy were analysed.

Participants

All residents who experienced a HF index hospitalisation between 2014 and 2023 were included. HF index hospitalisation was defined as the first hospitalisation for HF in patients with no prior hospitalisation from the same diagnosis for at least 4 years.

Primary outcome measures

The primary outcomes were age-standardised and sex-standardised incidence rates of HF index hospitalisations and all-cause mortality following index hospitalisation. Incidence rate ratios (IRRs), survival and their associated factors were analysed with negative binomial regression models, Kaplan-Meier analysis and Cox proportional hazards models, respectively.

Results

A total of 6965 incident cases from 17 588 HF hospitalisations in the decade under study were analysed. The overall standardised incidence rate was 1.73 per 1000 person-years, with significant differences by age and sex. Incidence rates decreased by 17% from 2014–2018 to 2019–2023 (IRR: 0.834; 95% CI 0.743 to 0.936). Cumulative 1-year and 5-year survival were 70.05% and 36.38%, respectively, with a progressively higher mortality risk in older people. Compared with the 2014–2018 cohort, the 2019–2022 cohort showed improved survival at 30 and 90 days and at 1 year overall and by age groups, with

Conclusions

HF incidence declined, particularly in older populations, and remained higher in men, while survival rates improved. Despite these trends, HF continues to represent a substantial clinical and public health burden.

Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) used in ambulatory palliative care for adult patients with cancer in low-income and middle-income countries: a systematic review protocol

Por: Mathew · M. · Ghoshal · A. · Kabukye · J. K. · Shetty · N. · Dhyani · V. S. · Chakraborty · S. · Shetty · D. K. · B · B. · Salins · N.
Introduction

The global burden of cancer is increasingly concentrated in low-income and middle-income countries (LMICs), where health systems face significant challenges such as late-stage diagnosis, limited resources and restricted access to specialised care. Palliative care plays a vital role in improving symptom control and quality of life for patients with cancer, particularly as care delivery shifts toward ambulatory and community-based settings. In this context, patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are crucial for capturing patients’ perspectives on the quality of care. However, the use and characteristics of these instruments in ambulatory palliative care settings within LMICs remain poorly understood. This systematic review aims to identify and map PROMs and PREMs used among adult patients with cancer receiving ambulatory palliative care in LMICs, and to examine their content, psychometric properties and alignment with key domains of quality palliative care.

Methods and analysis

This systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) guidelines. The search will be conducted across seven databases from the database inception to December 2025. Two independent reviewers will screen titles, abstracts and full-text articles using Rayyan software to identify studies involving adults (≥18 years) with cancer in ambulatory palliative care settings. Data extraction will capture study characteristics, instrument content and psychometric properties. The final review will be reported in accordance with the PRISMA-COSMIN for Outcome Measurement Instruments. A narrative synthesis will be conducted, mapping the identified instruments against the eight domains of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care to identify measurement gaps and inform future instrument development. A meta-analysis will be conducted if sufficient homogeneity exists.

Ethics and dissemination

This review will include only published data; therefore, no approval is required. The findings of this review will be presented at conferences and published in an open-access peer-reviewed journal.

PROSPERO registration number

CRD420251273579.

LIFE-UP Day audit to monitor implementation of post-intensive care syndrome prevention practices: a multicentre cross-sectional study in Belgian intensive care units

Por: Rousseau · A.-F. · Khai · N. · DOrio · V. · Fraipont · V. · Gurdebeke · C. · Minguet · G. · Pinck · E. · Verscheure · S. · Wertz · D. · Lambermont · B. · Berger-Estilita · J.
Objective

To evaluate the feasibility and relevance of the LIFE-UP Day audit, a simple, 1-day benchmarking tool based on the multidisciplinary LIFE-UP bundle (Limit sedation, optimise nutritional Intakes, engage Families, promote Exercise and follow-UP the patients after discharge) and assessing the implementation of postintensive care syndrome (PICS) prevention strategies in daily practice.

Design

Exploratory multicentre cross-sectional audit study.

Setting

Eight Belgian adult intensive care units (ICUs), between April and July 2024.

Participants

All patients present at 08:00 on the audit day and hospitalised for ≥24 hours.

Main outcome measures

An independent nurse collected data on sedation, analgesia, nutrition, family empowerment, physical exercise and post-ICU follow-up. A multidimensional LIFE-UP composite score (raw 0–10 points), normalised to a 5-point scale, was created to quantify adherence to PICS prevention practices based on current recommendations. Feasibility was evaluated through data accessibility, resource needs, cooperation of ICU teams and the ability to complete the audit within 1 day. Relevance was evaluated through adherence to the bundle, assessed by comparing LIFE-UP scores between ICUs. Quantitative results were expressed as median and IQR.

Results

The audit was tested in 87 patients aged 68 (59–74) years, 9 (5–15.5) days after their admission. The audit was feasible across all ICUs: necessary data were available, resources required were minimal and cooperation was excellent. The LIFE-UP score highlighted significant variability between ICUs (2.5 (1.75–2.75), p

Conclusions

The LIFE-UP Day audit proved feasible and provides a first structured framework for benchmarking. Broader implementation will be essential to validate the LIFE-UP score, refine the model and ultimately determine whether it can translate into improved patient and family outcomes.

Can a fluorescent imaging device (MolecuLight) function as an adjunct to surgical debridement during revision knee arthroplasty for periprosthetic infection in a tertiary centre: a feasibility study

Por: Archer · J. E. · Adlan · A. · Sumathi · V. · Stevenson · J.
Objectives

Radical surgical debridement is central to the eradication of prosthetic joint infection. Surgeons are taught that the adequacy of debridement is critical to the success of revision procedures. We aimed to assess the feasibility of using a handheld fluorescent imaging device as an adjunct to tissue debridement in the management of periprosthetic joint infection (PJI) after standard radical debridement.

Design

Prospective feasibility trial.

Setting

This was performed at a tertiary prosthetic joint infection unit (The Royal Orthopaedic Hospital, Birmingham, UK), multidisciplinary team (MDT).

Participants

10 patients with established PJI managed through a tertiary prosthetic joint infection MDT were recruited between January 2023 and December 2023. All patients underwent standard management, including radical debridement.

Intervention

After completion of standard radical debridement, the device was used to identify any remaining areas of fluorescence. These areas underwent excision for further intraoperative microbiological and histological sampling to analyse if the represented areas had residual bacterial load.

Primary outcome

To assess whether the fluorescence imaging device is able to detect additional areas of fluorescence which led to positive tissue sampling.

Results

In all cases, the device was able to identify areas of fluorescence, indicating further debridement. In eight cases, an organism was isolated after additional microbiological sampling and culture. In all eight cases, the same isolate was identified with the standard sampling. Additional histological sampling was performed in eight cases and confirmed acute infection in three cases. The remaining five cases demonstrated histologically inflammatory tissue consistent with chronic infection.

Conclusion

This study is encouraging for the feasibility of using this device as an adjunct for debridement in the surgical management of PJIs; further evaluation is underway.

Effects of pronatal policies on sexual and reproductive health services: a protocol for a scoping review

Por: Mburu · G. · Galati · A. · Chou · D. · Genatra · B. · Kiarie · J. · Boydell · V.
Introduction

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

Methods and analysis

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

Ethics and dissemination

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

PROSPERO registration number

CRD420251156155.

Effectiveness of anaemia interventions in indigenous populations across the globe: a systematic review protocol

Por: Thatoju · P. K. · Mallya · S. D. · Dhyani · V. S. · Shetty · R. S. · Kotebagilu · N. P. · Pattanshetty · S. M. · Bhat · R. G. · Kunder · M. A. · Kumar · A. · Kaur · H. · Poobalan · A.
Introduction

Anaemia is highly prevalent among the indigenous population globally. Several interventions have been used to prevent and manage nutritional anaemia, including dietary measures, health education, oral iron supplements, food fortification and intravenous iron therapy. This protocol describes a systematic review and meta-analysis to assess the effectiveness of interventions for the prevention and treatment of nutritional anaemia in indigenous populations worldwide.

Methods and analysis

The review will include randomised controlled trials, quasi-experimental studies and observational studies evaluating interventions, including but not limited to iron and folic acid supplementation, dietary modifications, food fortification, deworming and health education. A robust search strategy will be developed, and six electronic bibliographic databases and Google Scholar will be searched from 2000 to 2025. Two reviewers will independently screen the identified studies, extract data, conduct a critical appraisal and evaluate quality using the Joanna Briggs Institute tool. Based on the level of heterogeneity, a meta-analysis will be conducted using either a fixed-effect or random-effects model, with pooled estimates, and 95% CIs. The I2 statistic will be used to evaluate heterogeneity. When meta-analysis is not feasible, narrative synthesis will be conducted. The impact of the intervention type and delivery model will be investigated using subgroup analysis.

Ethics and dissemination

This systematic review has been registered with PROSPERO. Ethical approval is not required as the study does not collect primary data from participants. The findings will be communicated via peer-reviewed journal articles and presentations at national and international conferences.

PROSPERO registration number

CRD420251120554.

Connection, confluence and convergence: a protocol for reviewing policies on antimicrobial resistance and plastic pollution

Por: Shah-Rohlfs · R. · Landicho · J. · Endoma · V. · Sornillo · B. J. · Treskova · M. · Rocklöv · J. · McMahon · S. A. · Renosa · M. D. C.
Introduction

Antimicrobial resistance (AMR) and plastic pollution are converging global crises that threaten both human health and environmental sustainability. Despite the growing recognition of these challenges, few legislative and policy frameworks acknowledge the complex interplay between antibiotic misuse and environmental plastic contamination. This protocol seeks to bridge that gap by critically examining policies in Europe and the Philippines, focusing on those that target antibiotic misuse and plastic pollution in human and animal health.

Methods and analysis

Document analysis will be employed to systematically review relevant legislative and policy frameworks. We will retrieve laws, regulations and policy documents from official databases, government websites and other sources using broad inclusion criteria. The extraction process and analysis will be guided by the READ (Ready, Extract, Analyse, Distill) approach which will ensure a thorough examination of how these documents address the dual challenges of AMR and plastic pollution. Particular attention will be paid to identifying policy gaps, overlaps and synergies that may affect the overall effectiveness and coherence of current governmental responses.

Ethics and dissemination

This policy review has been granted exemption from ethical review by the Research Institute for Tropical Medicine (RITM-IRB No. 2024-35), Philippines. The results are expected to provide a robust evidence base to inform the development of integrated policies at the nexus of global public health and environmental sustainability. Findings will be disseminated at academic conferences and peer-reviewed publications and to key stakeholders within European, Philippine, and international organisations.

Trial registration number

The detailed protocol is pre-registered and openly available on the Open Science Framework (https://osf.io/3tkn2/overview).

Development and cross-site validation of machine-learning models for diagnosis and prognosis of stable angina with and without obstructive coronary artery disease: a study protocol

Por: Deng · J. · Patel · S. K. · Fung · M. · Heybati · K. · Layard · B. · Wang · B. · Rubin · B. · Simard · T. · Hibbert · B. · Anderson · T. · Subasri · V.
Introduction

Angina with no obstructive coronary artery disease (ANOCA) affects millions and is frequently under-recognised because diagnostic pathways and risk tools predominantly target obstructive coronary artery disease (CAD). This protocol describes shared methods for two machine-learning (ML) studies: (1) differentiating ANOCA from stable angina with obstructive CAD and (2) predicting long-term mortality among patients with ANOCA and obstructive CAD.

Methods and analysis

We will develop and cross-site validate ML classification models using a multicentre retrospective cohort drawn from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry and institutional datasets from the University of Ottawa Heart Institute and the University Health Network. Eligible participants are adults (≥18 years) undergoing initial cardiac catheterisation for chest pain/anginal equivalents since 1995, excluding prior revascularisation, major structural heart disease and predefined non-anginal indications. Outcomes are (1) ANOCA (0% to

Model development will use nested cross-validation with stratified k-fold inner-loop tuning and leave-one-site-out cross-validation for repeated external validation. Candidate predictors will be harmonised across sites, filtered for missingness and refined using expert/directed acyclic graph-guided selection plus Boruta and Least Absolute Shrinkage and Selection Operator. Preprocessing includes appropriate encoding, missing-data imputation (multivariate imputation by chained equations) and feature scaling. Algorithms will include elastic-net logistic regression, random forest, LightGBM and multilayer perceptron models; hyperparameters will be optimised via Bayesian optimisation. Performance and threshold tuning will be reported. Explainability and subgroup fairness will be assessed using SHapley Additive exPlanations. Final models will be deployed as a web-based clinical risk calculator.

Ethics and dissemination

Ethics approval has been obtained from the University of Calgary and the University Health Network (#24-5916). Analyses will use deidentified data in secure environments; only aggregate results will be reported. Findings will be disseminated via peer-reviewed publications, conferences and a web-based calculator.

Why do older people not adhere to a healthy lifestyle: a qualitative exploration of perceived barriers among older people living in a low-income and middle-income country setting

Por: Jayasinghe · V. · Ferdinando · R. · Abeysena · C.
Objective

To explore perceived barriers to adhering to a healthy lifestyle among older people living in a Sri Lankan setting.

Design

Qualitative thematic analysis of in-depth interviews among older people.

Setting

The study was conducted in Kalutara district, Sri Lanka.

Participants

In total, 28 older people aged between 60 years and 74 years were interviewed.

Results

Six major themes were identified following the analysis. They were named as lack of knowledge, financial difficulties, poor health status, domestic constraints, cultural norms and changing the living environment. Lack of knowledge emerged through two subthemes, namely lack of information and lack of services. Domestic constraints were derived from family commitments and domestic conflicts, while cultural norms came via beliefs and customs. Poor health status emerged through three subthemes, namely disabilities, diseases and polypharmacy, while changing the living environment emerged via adaptation and urbanisation.

Conclusion

This study provides evidence of real-life perceptions on why older people do not adhere to a healthy lifestyle. Barriers are multifaceted and complex, yet those dimensions need to be considered heavily while developing lifestyle programmes to get maximum benefit for the older people.

[89Zr]bevacizumab PET/CT imaging of vestibular schwannomas for the prediction of bevacizumab treatment effect in patients with symptomatic NF2-related schwannomatosis: a study protocol for a phase II single centre, prospective, feasibility trial

Por: Douwes · J. P. J. · Tops · A. L. · Dibbets-Schneider · P. · Verbist · B. M. · Fuentealba Bassaletti · C. A. · Jansen · J. C. · Koetsier · K. S. · van Dam · V. S. · Koot · R. W. · van Velden · F. H. P. · Pool · M. · Vugts · D. · Schopman · J. E. · Goeman · J. J. · De Geus-Oei · L.-F.
Introduction

Treatment with bevacizumab achieves both tumour stabilisation or regression and preservation or improvement of hearing. However, the efficacy of bevacizumab varies between patients and within patients. Side effects due to bevacizumab treatment are also common. It would be of value to predict therapeutic response prior to initiating therapy to prevent unnecessary exposure in patients unlikely to benefit.

Methods and analysis

We aim to recruit 25 patients with NF2-related schwannomatosis (NF2) with bilateral vestibular schwannomas. Patients will receive an intravenous injection of 37 MBq [89Zr]bevacizumab followed by positron emission tomography (PET)/CT imaging 4 days later. After clinical evaluation at baseline, patients undergo bevacizumab treatment and are followed up at 3 and 6 months. The primary objective is to examine associations between pretreatment [89Zr]bevacizumab uptake on PET/CT and changes in multiple hearing outcomes and radiological characteristics of the target tumour following treatment. Secondary outcome measures include vestibular functioning, patient reported outcome measures, cranial nerve functionality, peripheral neurology, non-target schwannoma response and renal function. Given the explorative nature of the study, associations between PET-derived metrics and clinical and radiological outcomes will be examined without formal hypothesis testing, using generalised estimating equations to account for within-patient correlation. Pairwise associations will be summarised in an association matrix with multiplicity addressed using an all-resolutions inference approach, and findings will be considered hypothesis generating.

Ethics and dissemination

This study was submitted via the Clinical Trials Information System reviewed and approved by the Medical Research Ethics Committee Leiden–The Hague–Delft Delft. The study findings will be disseminated through publication in peer-reviewed scientific journals and by presentation at national and international conferences.

Trial registration number

The trial is registered at ClinicalTrials.gov Protocol Registration and Results System under the registration ID: NCT05685836.

Identification of immunomodulators associated with atrial fibrillation reporting to better understand AF immunologic mechanisms: a Vigibase retrospective disproportionality analysis and a literature review

Por: Font · J. · Dolladille · C. · Divoux · J. · Chretien · B. · de Boysson · H. · Legallois · D. · Ollitrault · P. · Champ-Rigot · L. · Ferchaud · V. · Pellissier · A. · Milliez · P. · Alexandre · J.
Objectives

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

Design

A descriptive and disproportionality analysis of claims data.

Settings

World pharmacovigilance database VigiBase until 1 March 2025.

Primary and secondary ouctomes

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

Results

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

Conclusions

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

Trial registration number

NCT06095791.

Prevalence of presbyopia among social safety net beneficiaries with the cognitive, numeracy and dexterity skills required for smartphone use: a cross-sectional analysis of THRIFT RCT screening data from Kurigram, Bangladesh

Por: Aftab · I. B. · Chakma · T. · Pant · S. · Sigwadhi · L. N. · Shitol · S. A. · Rahman · H. M. M. · Alam · J. · Haque · E. · Chadalavada · H. P. · Murtaza · F. · Chan · V. F. · Little · J.-A. · Khanna · R. C. · MacKenzie · G. · Gudwin · E. · Lohfeld · L. · Clarke · M. · Shonchoy · A. · Congd
Objectives

To determine the prevalence of presbyopia and associated risk factors among Bangladeshi recipients of elderly social safety net payments who were not currently using mobile financial services (MFS) and demonstrated numeracy, dexterity and cognitive prerequisites for smartphone use during eligibility screening for the Transforming Households with Refraction and Innovative Financial Technology (THRIFT) trial. Accessing these payments requires use of online banking, as with a smartphone.

Design

Cross-sectional analysis of trial eligibility screening data.

Setting

Community-based screening conducted in two rural subdistricts in Kurigram District, Bangladesh.

Participants

Among 13 944 Old Age Allowance and Widows’ Allowance (WA) beneficiaries screened, 953 met trial eligibility criteria, including passing a smartphone readiness assessment and completing near vision examinations.

Primary and secondary outcome measures

Presbyopia, defined as binocular presenting near visual acuity of N6.3 or worse, correctable to at least N5 with near vision glasses and with distance vision of ≥6/12 in both eyes.

Results

Among 953 participants (mean age 61.4±7.2 years, 62.6% women), presbyopia prevalence was 62.6% (95% CI 59.5 to 65.7). Presbyopia was significantly positively associated with female gender (adjusted prevalence ratio (APR)=1.19, 95% CI 1.02 to 1.41) and receiving WA (APR=1.20, 95% CI 1.04 to 1.38) in multivariable analyses.

Conclusions

This study highlights a substantial burden of uncorrected presbyopia among a prescreened, randomised control trial-eligible subgroup of social safety net beneficiaries in rural Bangladesh, who were not currently using MFS but demonstrated cognitive and functional capacity to use mobile phones, potentially hampering their ability to carry out online banking. Delivery of reading glasses may improve digital financial access and facilitate broader financial inclusion, a hypothesis currently being tested in the parent THRIFT trial.

Trial registration number

NCT05510687.

Daridorexant in children and adolescents with insomnia disorder: study protocol for a multicentre randomised controlled trial

Por: Coloma · P. · Coury · D. · Wernette · S. · Beevers · V. · Dubois · C. · Di Marco · T. · Dursun · O. T. · Bruni · O.
Introduction

Insomnia disorder imposes a significant burden on children and adolescents; however, treatment options are limited. This paper describes the first controlled study to investigate the efficacy and safety of daridorexant, a dual orexin receptor antagonist, in children and adolescents with or without comorbid neurodevelopmental disorders, allowing its evaluation in a broad paediatric population.

Methods and analysis

This multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding Phase 2 trial includes male and female participants aged ≥10 to

Ethics and dissemination

This study has been approved by the respective health authorities and institutional review boards/independent ethics committees for each participating site and country and is conducted in accordance with the Declaration of Helsinki. Ethics approval has been obtained for each participating country/site. Regardless of the outcomes, the results will be published in an international peer-reviewed scientific journal.

Trial registration number

NCT05423717.

Development and acceptability of a patient decision aid for people with degenerative cervical myelopathy: an international mixed-methods study

Por: Gamble · A. R. · Anderson · D. B. · McKay · M. J. · Davies · B. · Macpherson · S. · Van Gelder · J. · Hoffmann · T. · McCaffery · K. · Stevens · S. X. · Ammendolia · C. · Chauhan · R. V. · Zipser · C. M. · Boerger · T. F. · Tetreault · L. A. · Fehlings · M. G. · Dustan · E. · Nugent · C
Objectives

To develop and user-test a patient decision aid for people diagnosed with degenerative cervical myelopathy and who are considering surgery.

Design

Mixed-methods study describing the development of a patient decision aid.

Setting

A draft decision aid was developed by a multidisciplinary steering group (including study authors with degenerative cervical myelopathy, health professionals and researchers) informed by the best available evidence, authorship consensus and existing patient decision aids.

Participants

Patient-participants and health professional-participants who manage people with degenerative cervical myelopathy were recruited through social media and the steering group’s research and practice network. Quantitative questionnaires were used to gather baseline data, descriptive feedback, refine the decision aid and assess its acceptability. Qualitative semi-structured interviews were conducted online to gather feedback on the decision aid and were analysed using reflexive thematic analysis.

Results

We conducted 32 interviews: 19 patient-participants and 13 health professional-participants who manage people with degenerative cervical myelopathy (neurosurgeons, neurologists, physiotherapists, orthopaedic surgeons, general practitioners, rehabilitation and pain specialists and consultant occupational physicians and chiropractors). Participants were from 10 countries (Australia, Canada, Cyprus, Germany, Ireland, New Zealand, Sweden, Switzerland, United Kingdom and USA). Most participants rated the decision aid’s acceptability as good-to-excellent and agreed with most aspects of the decision aid (eg, defining degenerative cervical myelopathy, management recommendations, potential benefits and harms, questions to consider asking a health professional).

Conclusion

Our patient decision aid was rated as an acceptable tool by both health professional-participants who treat degenerative cervical myelopathy and patient-participants with lived experience of degenerative cervical myelopathy. This decision aid can be used by clinicians and people with degenerative cervical myelopathy to help with shared decision making following a diagnosis of degenerative cervical myelopathy. A study testing the potential benefits of this decision aid in a clinical setting is recommended.

A genomic locus uniquely encoded by blueberry-infecting <i>Xylella fastidiosa</i> strains affects motility and biofilm formation in vitro, and virulence in planta

by Navdeep Kaur, Marcus V. Merfa, Alexandra K. Kahn, Rodrigo P. P. Almeida, Leonardo De La Fuente

Xylella fastidiosa (Xf) is an insect-transmitted, xylem-limited bacterial plant pathogen that infects hundreds of plant species. This pathogen causes bacterial leaf scorch in southern highbush blueberry (Vaccinium corymbosum interspecific hybrids) in the southeastern United States, a disease that has not yet been reported elsewhere. Previously, a comparative genomic analysis of Xf and ancestral host species identified evolutionary events of gene gain and loss related to host range specificity. Here, by using a similar workflow, we identified two loci that are significantly found in blueberry-infecting strains. Locus_1088 included a hypothetical protein and a small part of the N-terminus of an orphan RelE toxin, while Locus_2741 was annotated as a hypothetical protein. Using a protocol based on natural competence, mutants were generated in three Xf subsp. multiplex strains from blueberry. Less biofilm, more planktonic growth, and increased twitching motility as compared to its wild-type (WT) were observed for the strain LA-Y3C_1088 mutant. In blueberry virulence assays, the LA-Y3C_1088 mutant caused significantly more severe symptoms than LA-Y3C_WT, whereas no significant differences were observed for other mutated strains. Interestingly the mutation of Locus_1088 additionally disrupted a toxin (part of a toxin-antitoxin system) that is likely responsible for the phenotypic changes observed. However, because the two independent mutants were not generated, we could not determine whether the phenotype resulted from disruption of hypothetical protein or the toxin. Additionally, since the coffee-isolated but never tested in blueberry Xf subsp. fastidiosa strain CFBP8073 was found to encode the two blueberry-associated loci studied here, its virulence was assessed in blueberry. This strain caused severe symptoms comparable to the control strain AlmaEm3 from blueberry. Due to the complexity of understanding host specificity in Xf, any advance in identifying genetic markers for host specificity in this devastating pathogen could greatly improve management of Xf worldwide.

Use of ambient AI scribe in physicians clinical documentation: a protocol for a systematic review on effectiveness, efficiency, and satisfaction

Por: Garcia Sanchez · C. · Goer · V. · Kharko · A. · Hägglund · M. · Hagström · J. · Schwarz · J. · Blease · C. R.
Introduction

Clinical documentation is a significant driver of burnout among physicians. Ambient artificial intelligence (AI) scribes, which leverage generative large language models to automate the creation of clinical notes from patient–physician conversations, are rapidly emerging as a potential solution. While these tools promise to enhance efficiency and reduce administrative tasks, concerns about the quality, accuracy and potential biases persist. There is now a need for a systematic synthesis of evidence to evaluate the impact of these technologies in clinical practice. To assess the effects of ambient AI scribes on physicians’ clinical documentation, the specific objectives are to: (1) evaluate the effectiveness of these tools on documentation, including accuracy and completeness; (2) synthesise evidence on the impact on physician efficiency after adoption, including time spent on documentation and (3) examine physicians’ satisfaction with these tools, including physicians’ perceived burden.

Methods and analysis

A systematic review of quantitative or mixed-method studies as well as preprints will be conducted. We will perform a comprehensive search of four electronic databases (PubMed, IEEE Xplore, APA PsycInfo and Web of Science, along with medRix and ClinicalTrials.gov for preprints) for empirical studies published between January 2023 and March 2026. The review will synthesise studies comparing physicians’ use of ambient AI scribes with traditional documentation approaches. Given the anticipated heterogeneity of the studies, a narrative synthesis will be employed to summarise the findings. Where common quantitative outcomes exist, effect sizes will be calculated using Hedges’ g, mean differences or risk ratios/odds ratios as appropriate. The overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.

Ethics and dissemination

As no patient data are involved in the data collection, no ethical approval is acquired. Results will be disseminated in a peer-reviewed, open-access journal, and presented at relevant academic conferences.

PROSPERO registration number

CRD420251149086.

Sleep inadequacy and the relationship with mucosal immunity and upper respiratory symptoms in elite swimmers: A longitudinal study leading into the Commonwealth Games

by Lauren H. Baker, Terun Desai, Jonathan Sinclair, Amy V. Wells

Objectives

To monitor sleep patterns of elite swimmers and explore sleep as a potential risk factor for upper respiratory symptoms (URS) alongside salivary Immunoglobulin A (IgA) in elite swimmers, over an 8-month competitive season.

Design

Secondary analysis of an 8-month longitudinal study in elite international swimmers leading into either the Commonwealth Games 2018 or Swim Cup Eindhoven.

Methods

Fourteen elite swimmers (age ± SD = 19.9 ± 0.8 years, height = 178.9 ± 6.3 cm, and mass = 75.0 ± 7.7 kg) were recruited. Self-reported sleep quality, URS data and salivary IgA was obtained weekly on a standardised day. Quantitative sleep parameters were measured using wrist-worn actigraphy four times for two-week bouts; during low, moderate, high training loads and once leading into competition.

Results

Swimmers waking fatigued was positively associated with frequency (p  Conclusions

Perceived fatigue on waking was significantly associated with both frequency and severity of URS, and inversely associated with mucosal immunity (salivary IgA), providing novel insight into the relationship between sleep, fatigue and illness in this cohort. Although causality cannot be established, the high prevalence of inadequate sleep shown in elite swimmers highlights the importance of individual sleep monitoring to support recovery and inform strategies aimed at illness prevention.

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