Proactive deprescribing is the process of stopping a medicine and comprises four steps: (1) identify a patient for potential stop of a medicine, (2) evaluate a patient for potential stop of a medicine, (3) stop a medicine and (4) monitor after stopping.

The CHARMER (CompreHensive geriAtRician-led MEdication Review) trial is a stepped-wedge design to evaluate the effectiveness and cost-effectiveness of a behaviour change intervention to increase proactive deprescribing in hospitals. The CHARMER intervention comprises a deprescribing action plan, deprescribing briefings, videos of successful deprescribing consultations, deprescribing case studies workshop and a deprescribing performance dashboard. The process evaluation will explore trial processes, CHARMER intervention implementation, CHARMER behavioural mechanisms of action and contextual factors influencing these aspects.

The convergent parallel design process evaluation will follow the UK Medical Research Council guidance. We will interview: staff involved in CHARMER implementation, geriatricians and pharmacists who receive the intervention and research delivery staff involved in patient/carer recruitment and data collection. We will also interview patients/carers and primary care practitioners. Interviews will be supplemented with recordings of implementation activities and completed implementation manuals. Questionnaires will capture the extent to which the four proactive deprescribing steps are enacted by intervention recipients, measure the behavioural mechanisms by which the CHARMER intervention operates and capture the patient experience of proactive deprescribing. Qualitative data will be analysed thematically and then mapped to Normalisation Process Theory to explore implementation and the Theoretical Domains Framework to explore behaviour change. Most quantitative data will be analysed descriptively; however, changes in staff questionnaire responses preintervention and postintervention will be analysed using a Mann-Whitney test. We will triangulate qualitative and quantitative findings to explain intervention effects.

Ethical and governance approvals have been obtained by the Wales 2 Research Ethics Committee and the Health Research Authority, respectively. The dissemination strategy will be underpinned by the evidence-based Guide to Disseminating Research (GuiDiR) targeting healthcare practitioners, policy makers and patient-facing organisations.

ISRCTN13248281.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a significant procedural adverse event (AE), occurring in 5–15% of cases and leading to substantial morbidity and mortality. Aggressive prolonged intravenous (IV) fluid regimens have demonstrated efficacy in reducing PEP in clinical trials. However, these regimens typically involve continuous infusion of IV fluids over 8–24 hours following ERCP, making them impractical for outpatient settings. Data on shorter hydration protocols are lacking. The STRIPE study aims to address this gap by evaluating short-term peri-procedural IV fluid regimens as a practical alternative for mitigating PEP.

This proof-of-concept, parallel-arm, randomised controlled trial will evaluate the impact of various short-term IV fluid regimens on post-ERCP serum amylase levels, a surrogate marker for PEP. Participants undergoing ERCP will be randomised into five groups, receiving 500 mL, 1000 mL, 1500 mL, 2000 mL or 2500 mL of IV Ringer’s lactate during the peri-procedural period. Patients, endoscopists and outcome assessors will be blinded to treatment allocation during the peri-procedural period. The primary outcome is the serum amylase level 24 hours post-ERCP. Secondary outcomes include PEP, 30-day AEs and unplanned healthcare encounters including those related to volume overload or cardiovascular AEs, duration of hospitalisation (for inpatients), death within 30 days and other relevant laboratory markers at 24 hours. A total of 505 participants (101 in each arm) will be enrolled to ensure adequate power after accounting for attrition and/or sample loss.

This trial was registered on clinicaltrials.gov on 7 February 2024. The study was approved by the University of Calgary Conjoint Health Research Ethics Board (REB23-0625). On study completion, data will be made available on reasonable request to the corresponding author after completion of the study. Study dissemination and knowledge translation is planned via presentations at scholarly meetings, publications in peer-reviewed journals and, ideally, via adoption of results into clinical practice guidelines.

NCT06260878.

Type 2 diabetes (T2D) is a growing global public health challenge, with a rapidly increasing burden in sub-Saharan Africa. Medical nutrition therapy (MNT) is a cornerstone of T2D management; however, its design, delivery and implementation vary across health systems, cultural contexts and resource environments. Most synthesised evidence and guideline development originate from Western settings, while MNT approaches in African contexts remain heterogeneous and less systematically characterised. This scoping review aims to map and compare MNT strategies for T2D across Western and African contexts.

This scoping review will follow the Arksey and O’Malley framework and its enhancements, aligned with Joanna Briggs Institute guidance. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Searches will be conducted in PubMed, Embase, CINAHL, Scopus, CABI Global Health and African Journals Online, supplemented by grey literature and citation searching. Eligible sources will include studies and programme reports describing MNT interventions for adults with T2D published between 2000 and 2025 in Western or African settings. Eligibility will be defined using the Population–Concept–Context framework. Two reviewers will independently screen studies and extract data using a standardised, framework-informed charting form based on the Consolidated Framework for Implementation Research (CFIR) and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. Data will be synthesised using descriptive numerical summaries, framework-informed thematic synthesis (deductive coding with inductive refinement), and comparative evidence matrices.

This review will use publicly available data and does not require ethical approval. Findings will be disseminated through peer-reviewed publication, conference presentations and stakeholder-oriented knowledge translation activities to inform culturally relevant, context-appropriate and implementation-ready MNT strategies across diverse health system settings.

Large-for-gestational-age (LGA) and macrosomic births pose significant maternal and neonatal health risks, particularly in low- and middle-income countries (LMICs), where access to care are often limited. Despite well-established associations between LGA, macrosomia, and various risk factors, the relative contributions of these factors remain underexplored in LMICs. This study aims to identify risks factors for LGA and macrosomia in LMICs, with an emphasis on modifiable ones, and quantify their population attributable fractions (PAFs).

A systematic review will be conducted across the following databases: MEDLINE, Scopus and ProQuest Central and regional databases (Africa Index Medicus, Index Medicus for South Asia and Latin America and Caribbean literature of health sciences). Eligible studies will include observational studies, reviews and interventional research conducted between 2000 and 2025 that report on prevalence or association of risk factors for large-for-gestational-age (LGA) and/or macrosomia births in low- and middle-income countries (LMICs). Data extraction will encompass study characteristics, prevalence/incidence estimates, risk factor distributions and measures of association. Quality assessment will be performed by two independent reviewers using the Newcastle-Ottawa Scale for observational cohort, case–control and cross-sectional studies. While Cochrane Risk of Bias Tool will be used for randomised controlled trials and a Measurement Tool to Assess Quality of Systematic Reviews 2 (AMSTAR-2) for systematic reviews and meta-analyses. Meta-analyses using a random-effects model, which accounts for population heterogeneity, will synthesise risk estimates for factors examined in three or more studies from LMICs, up-to-date meta-analysis including all relevant studies identified through our search. Population attributable fractions for individual and combined risk factors will be calculated.

This systematic review will use only previously published information. Ethical approval is therefore not required. The results will be submitted for publication in a peer-reviewed journal and the findings will be presented at international conferences to engage relevant stakeholders including policymakers and public health organisations in LMICs with the aim of informing the development of targeted interventions to reduce the burden of LGA and macrosomia births in the region.

Data on long-term outcomes after surgical repair of pulmonary valve stenosis are limited. This study evaluated survival, clinical outcomes and quality of life (QoL) after surgery during childhood.

Single centre, longitudinal cohort study evaluating consecutive patients with pulmonary valve stenosis who underwent surgical repair between 1968–1980 and were evaluated every decade since 1990.

Of the original cohort of 89 operated patients, 11 died (12%), including 2 who died within 30 days postsurgery (2%), and 7 (8%) were lost to follow-up. Survival at 50 years follow-up was 87%, which was not significantly different from the GDP. Of the remaining 71 survivors, 32 refrained earlier from participating in this cohort study, leaving 39 eligible, of whom 34 (87%) participated again (50% male, median age 48 years) with a median follow-up of 45 (range 40–52) years. Event-free survival was 50%, with supraventricular tachycardia (14%) and reintervention (13%) being the most frequent events, although less frequently in the last 10 years. At last follow-up, biventricular function was preserved in most patients. Reduced right and left ventricular ejection fraction (EF) was found in 33% and 13%, respectively. Exercise capacity and maximum rate of oxygen consumption were mildly impaired in 14% and 32% of patients. Patients who underwent an infundibulectomy during initial surgery were significantly more likely to undergo reintervention (HR=8.32, p=0.003). Patient-reported QoL scores remained stable over time and consistently exceeded those of the age-matched GDP.

Fifty-year survival after surgery for pulmonary valve stenosis was excellent and comparable to the GDP. Most patients maintained preserved ventricular function, functional capacity and excellent QoL. Routine lifelong follow-up may not be necessary for all patients, but should be considered for those who underwent an infundibulectomy or have residual lesions.

Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy.

This single-centre, 6-month, randomised controlled trial at Dasman Diabetes Institute will enrol 232 adults with obesity, randomised (1:1:1:1) to control, resistance exercise, protein supplementation or combined resistance exercise and protein in conjunction with semaglutide or tirzepatide therapy. Resistance exercise will be home-based and involve three sessions per week, progressing from one to three sets targeting major muscle groups. Protein supplementation will target 1.6 g/kg/day via dietary adjustment and protein products. Assessments at baseline and 6 months will include MRI measured quadriceps cross-sectional area (primary outcome), plus measures of secondary outcomes of MRI measured liver fat content and stiffness and intramuscular fat, body composition (dual energy X-ray absorptiometry), strength, physical function, dietary assessment, physical activity levels, sleep patterns, quality of life, glycaemic control and metabolic biomarkers.

The study has received ethical approval from the Dasman Diabetes Institute Ethical Review Committee (HR-RA-2025-01, 19 February 2025) and is registered at ClinicalTrials.gov (NCT06885736, 26 June 2025). Written informed consent will be obtained from all participants, with no financial compensation provided. Data will be reported in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines, ensuring participant anonymity. Findings will be disseminated through peer-reviewed publications and presentations at national and international conferences.

NCT06885736.

Healthcare services are mainly organised around single health conditions and need reconfiguration to meet the needs of people with multiple long-term conditions (multimorbidity). Typically, people are offered annual reviews for each of their long-term conditions separately. In a randomised controlled trial, a comprehensive computerised template based on a personalised care model increased the person-centredness of multimorbidity reviews in primary care, but there were implementation challenges. We sought to understand and address the challenges of implementing a template to support personalised primary care for people with multimorbidity (PP4M).

To explore the extent of implementation and factors influencing uptake of the PP4M intervention. To understand factors influencing implementation and normalisation of the template.

Convergent parallel mixed methods within a non-randomised hybrid implementation-effectiveness study. Normalisation Process Theory (NPT) informed design, data collection and analysis.

Primary care (general practices) in three English regions.

Quantitative: Patients aged 18 years or over and had at least three types of long-term conditions (routine data collection); staff involved in using the template in implementation practices (Normalisation MeAsure Development (NoMAD) questionnaire).

Qualitative: Staff at implementation practices.

A multimorbidity computerised template to support personalised annual reviews. NPT-informed implementation package delivered to implementation practices included: process mapping, software support and training.

Routine medical record data; NoMAD questionnaires and qualitative interviews in implementation practices.

Measures of reach, fidelity, acceptability and sustainability.

Quantitative data: descriptive statistics, logistic regression and difference-in-difference models. Qualitative data analysis conducted using NPT coding manual.

In practices that received an NPT-informed implementation package, use of the template increased more, across patients with a range of demographics and health conditions, than in those that did not receive the implementation package (OR 2.86 (95% CI 2.34 to 3.49)). The implementation package successfully triggered NPT processes of coherence and cognitive participation, and, to a lesser extent, collective action and reflexive monitoring. Contextual factors, including a lack of staff generalist skills and disease-specific incentives, impeded engagement and sustained implementation.

Focusing on the processes of normalisation as mechanisms of implementation facilitated development of an implementation strategy with potential to trigger those mechanisms, but did not sufficiently address contextual factors. Implementation strategies to support personalised care must consider wider system and practice level contextual factors, such as incentives and staff training.

https://doi.org/10.1186/ISRCTN40295449 (2022–08-03, retrospectively registered.)

While almost half of older adults admitted to hospital are prescribed potentially inappropriate medicines, less than 1% have a medicine proactively deprescribed during admission in the UK. The CompreHensive geriAtRician-led MEdication Review (CHARMER) intervention is designed to address geriatricians’ and pharmacists’ barriers and enablers to deprescribing. The CHARMER definitive trial will evaluate effectiveness, cost-effectiveness and safety.

A stepped-wedge cluster randomised controlled trial will be conducted in 20 hospitals in England, with four hospitals in reserve. All hospitals will collect baseline data. Every 3 months, five hospitals will be randomised to receive the intervention. The intervention, implemented by a local project manager, comprises a hospital action plan to set deprescribing as an organisational goal; workshops for pharmacists and geriatricians to change beliefs about deprescribing; weekly briefings between geriatricians and pharmacists to discuss opportunities for deprescribing; benchmarking reports to compare deprescribing performance across participating hospitals. With an average of 200 patients admitted and discharged during each step, the study will have 89.5% power at 5% significance level and intra-class correlation coefficient of 0.05 to detect a 3% difference in 90-day re-admission rate from 16.7% versus 13.7%. Anonymised routinely collected data, including readmissions, will be obtained for all patients admitted during the study period. Enhanced data collection periods of 1 month during control and intervention periods will be used to recruit patients and data for secondary outcomes and process evaluation.

A stepped-wedge design enabled a smaller number of hospitals and patients to be included than a traditional cluster-randomised design. The complexity of intervention implementation necessitated a project manager in addition to the principal investigator responsible for trial conduct. Using routinely collected data for the primary outcome measure should ensure that the trial has sufficient power on completion. Planned enhanced data collection for short periods of time improves trial efficiency.

ISRCTN13248281.

To describe prescription patterns, dosing and persistence of guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction in Singapore, and to identify factors associated with the use of quadruple therapy (ACE inhibitor (ACEi)/angiotensin II receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter-2 (SGLT2) inhibitor).

Retrospective, observational cohort study.

Secondary and tertiary care settings across seven public hospitals in Singapore.

3999 adults hospitalised from 2020 to 2022 with a first heart failure-related admission and left ventricular ejection fraction ≤40%. Patients with absolute contraindications to specific GDMT classes were excluded from eligibility calculations.

Primary outcomes were the proportions of eligible patients prescribed each GDMT class and quadruple therapy at discharge. Secondary outcomes were 6-month prescription patterns, dose attainment and predictors of quadruple therapy use.

Among eligible patients, 80%–99% met criteria for each GDMT drug class, yet only 29% received quadruple therapy at discharge in 2022. Prescription rates for ACEi/ARB/ARNI (67%), beta-blockers (89%), MRAs (40%), and SGLT2 inhibitors (46%) remained suboptimal despite high eligibility. At discharge, over 90% of patients on ACEi/ARB/ARNI and beta-blockers received ≤50% of target doses. By 6 months, prescription rates declined by 16% for ACEi/ARB/ARNI, 26% for beta-blockers and 7% for MRAs, while SGLT2 inhibitor use increased. Older age (OR 0.97, 95% CI 0.96 to 0.98) and chronic kidney disease stage 3a–4 (OR 0.65 to 0.04) were associated with lower odds of receiving quadruple therapy, while significant institutional variation was observed.

Despite high eligibility, uptake and optimisation of GDMT remain poor in Singapore, with substantial treatment gaps driven by underprescription, inadequate dosing and discontinuation. Interventions targeting clinician awareness, postdischarge support and institutional practice variation may improve adherence to guideline-recommended therapy.

Hand osteoarthritis (OA) is a prevalent and debilitating joint disorder that impairs daily functioning and quality of life. Current treatments are often inadequate in managing the symptoms and progression of the disease. The cytokine interleukin (IL)-17 has been implicated in the inflammatory processes associated with OA, making it a potential target for therapeutic intervention. This trial aims to evaluate the efficacy of vunakizumab, an IL-17A inhibitor, in reducing pain and improving functional outcomes in patients with erosive hand OA.

This multicentre, randomised, placebo-controlled, double-blind trial will enrol 150 participants aged 30–80 years with symptomatic erosive hand OA. Participants will be randomised in a 1:1 ratio to receive either vunakizumab 120 mg or placebo subcutaneously every 4 weeks for 24 weeks, with a loading dose injection period during the first 4 weeks. The primary outcome is the change in hand pain assessed by the Visual Analogue Scale at 28 weeks. Secondary outcomes include changes in physical function measured by the Functional Index for Hand Osteoarthritis, the Quick Disabilities of the Arm, Shoulder and Hand questionnaire and the Health Assessment Questionnaire, as well as changes in grip strength and radiographic and MRI evaluations of the hands.

Written informed consent will be obtained from all participants. The study was approved by the Ethics Committee of Shanghai Sixth People’s Hospital (2024–217) and will adhere to the Declaration of Helsinki. Research results will be published in peer-reviewed journals.

ChiCTR2500101031; https://www.chictr.org.cn/showproj.html?proj=264789.

To examine inpatient benzodiazepine receptor agonists prescribing patterns and assess how hospitalisation affects use at discharge.

Subanalysis of the WEsleep trial, a cluster-randomised controlled single-centre study conducted at Amsterdam University Medical Center (Amsterdam UMC) (two locations) between July 2023 and March 2024. Twelve departments (six medical, six surgical) were matched and randomised to intervention or standard care. On intervention wards, multiple measures to improve sleep were implemented, including minimising nighttime disruptions.

Amsterdam UMC, across medical and surgical hospital departments.

Adult patients admitted for ≥2 nights (medical) or undergoing elective non-cardiac surgery in a surgical department.

Benzodiazepine use was classified as no use, pre-admission use or new in-hospital initiation. Prescribing patterns were summarised descriptively according to type, timing, indication and discharge status.

Of 746 patients, 187 (25%) used benzodiazepines: 80 (43%) had pre-admission use, and 107 (57%) were newly initiated during their hospital stay. Among pre-admission users, two discontinued and five had adjustments at discharge. Among newly initiated users, 94 (88%) had their benzodiazepine discontinued at discharge. Approximately half of pre-admission prescriptions and one-third of in-hospital prescriptions lacked a documented indication.

Although most newly initiated benzodiazepine treatments were discontinued during hospitalisation, pre-existing use was rarely reassessed and nearly 10% of new users were discharged with a prescription. Structured deprescribing protocols, better documentation of indications and improved discharge planning are needed to promote safer and more rational benzodiazepine use.

NCT05683483.

Within the UK there are 33 deaths every day from prostate cancer, second only to lung cancer as the most common cause of cancer death in males in the UK. Of the 55 000 new cases each year, up to 50% of these patients will receive radiotherapy either alone or after prostatectomy. Although there have been significant improvements in the accuracy of radiotherapy delivery leading to better tumour targeting and a reduction in dose to normal tissues, significant permanent genito-urinary or gastrointestinal-related side effects are all too common. With nearly 80% of patients with prostate cancer surviving for 10 years or more, minimising life-limiting radiation damage to normal tissues is vitally important. However, at present, it is not possible to identify which patients will suffer a poorer outcome after radiotherapy. The aim of this study, improving radiotherapy in PROState cancer using EleCtronic population-based healthCAre data (PROSECCA), is to do this by using the existing information in a patient’s digital healthcare record. By linking primary, secondary and tertiary clinical data, including digital image information, with radiotherapy treatment plans and outcome data, the PROSECCA study will identify de novo predictive biomarkers of radiation response and provide clinicians with a tool to individualise a radiotherapy dose and plan to maximise cure and minimise toxicity.

The PROSECCA study is a large multidisciplinary project, the purpose of which is to analyse healthcare records from up to 15 000 patients with prostate cancer who underwent radiotherapy in the treatment of their cancer in Scotland between 2010 and 2022. Through the linkage of data obtained specifically for radiotherapy and data held within each patient’s unique electronic health record (EHR), the factors that indicate why some patients have a poor response to treatment, or an increased risk of side effects from radiation, will be identified. This will be made possible by the use of artificial intelligence and machine learning (AL/ML), which will help to identify at-risk patients earlier and allow adaptation of their treatment accordingly.

The study is being conducted in accordance with the ethical principles set out in the Declaration of Helsinki and Good Clinical Practice that respects and protects the rights, and maintains confidentiality, of all trial participants. The study protocol (V.1.0) was reviewed by the South Central Oxford A Research Ethics Committee (REC) on 13 December 2021 and received a favourable opinion subject to each National Health Service (NHS) organisation confirming permission for patients treated within their area. Approval for the use of unconsented healthcare record data for patients included in the study and treated at one of the five Scottish Cancer Centres required an application to the NHS Scotland Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP). Full approval from the HSC-PBPP panel was received on 1 July 2024, which covered the use of pseudoanonymised EHR data for all patients participating in the study. The study is publicly listed on the NHS Health Research Authority site, with IRAS ID 306245 and REC reference 21/SC/0402. Dissemination of the study findings will take place through field-leading cancer, radiation oncology and medical physics journals. All manuscripts will be approved by the main study team and authorship determined by mutual agreement.

NCT06714630.

Large-scale stroke registries can provide critical insights into disease mechanisms, progression and healthcare needs, informing prevention and care. However, few collect detailed demographic, brain imaging, and comprehensive long-term follow-up data. To address this, we established the prospective Stroke Investigation Group in North And central London (SIGNAL) registry in 2017.

The SIGNAL registry included 3931 adults aged ≥18 years with confirmed acute stroke (cerebral ischaemia or intracerebral haemorrhage (ICH)) admitted to the University College London Hospital hyperacute stroke unit between January 2017 and 2020, drawn from an ethnically diverse North and Central London population (~1.6 million). Baseline data included demographic, clinical, brain imaging and next-of-kin information. Six month follow-up included measures of functional status and non-motor outcomes (anxiety, depression, fatigue, sleep, pain, language, continence, social participation, cognition) via face-to-face, telephone or postal follow-up methods.

The mean age of individuals included in the SIGNAL registry was 72.1 years, and 1806 (45.9%) were female. The ethnic distribution comprised 2365 (60%) white, 649 (16.5%) black and 511 (13%) Asian. Stroke diagnoses included 3371 (85.8%) with cerebral ischaemia and 560 (14.2%) with ICH. On admission, 2240 individuals (57.0%) had a National Institutes of Health Stroke Scale score >4, indicating moderate stroke severity. At hospital discharge, the median functional outcome, measured by the modified Rankin Scale, was 3 (IQR 1–4), indicating moderate disability. At 6 months, functional outcomes measured with mRS were available for 3755 individuals (95.6%) with a median score of 1 (IQR=0–3) and non-motor outcomes were available for 3080 individuals (92.3%). The most prevalent adverse non-motor outcomes were fatigue 1756 (57%), reduced social participation 1694 (55%) and sleep disturbance 1663 (54%).

Further analyses of SIGNAL registry data will investigating associations between stroke mechanisms, subtypes and neuroimaging features and 6-month functional status, non-motor outcomes and cognitive impairment. Longer term follow-up of survivors for ~10 years is also planned.

Administering supplemental oxygen to prevent hypoxaemia is a fundamental treatment for patients hospitalised with acute injury or illness. However, the amount of oxygen administered frequently exceeds that needed to maintain normoxaemia, causing patients to experience hyperoxaemia and wasting supplemental oxygen. Closed-loop, autonomous oxygen titration systems are designed to optimise oxygen delivery by administering the lowest possible oxygen flow that maintains peripheral oxygen saturation (SpO₂) within a predefined range. For adults hospitalised with an acute injury or illness, it remains uncertain whether the use of a closed-loop, autonomous oxygen titration system safely increases the proportion of time spent in normoxaemia (SpO₂ 90%–96%) compared with usual care.

The Strategy to Avoid Excessive Oxygen using Autonomous Oxygen Titration Intervention trial is a multicentre, unblinded, parallel-group, randomised trial being conducted at four level 1 trauma centres in the USA. The trial compares an autonomous oxygen titration system versus usual care among 300 adults hospitalised for major trauma, burn, acute care surgery or acute respiratory illness. The primary outcome is the proportion of patient-time spent within the targeted normoxaemia range (SpO₂ 90%–96%) as measured by continuous non-invasive pulse oximetry, during the first 72 hours after randomisation. Secondary outcomes include the amount of supplemental oxygen administered and the proportion of time spent in hypoxaemia (SpO₂2 >96%). Specifying the protocol and statistical analysis plan before the conclusion of enrolment increases the rigour, reproducibility and interpretability of the trial. Enrolment began on 6 May 2024.

The trial protocol was approved by the single institutional review board at the University of Colorado School of Medicine and the Office of Human Research Oversight at the Department of Defense. We will present the results at scientific conferences and submit them for publication in a peer-reviewed journal.

NCT06374225.

Effect size and event rate estimation is necessary for sample size calculation in randomised clinical trials. Overestimation of the effect size and event rate can lead to inadequately powered studies and increased probability of false negative results. This is common in trials involving critically ill patients. However, such overestimation has not been systematically evaluated in trials involving neurocritical care. We aimed to conduct a systematic review of published randomised clinical trials involving critically ill neurological patients, to determine the accuracy of effect size and event rate estimation.

We will review randomised clinical trials involving adult critically ill neurological patients that were published from 2015 onwards in selected clinically useful and high-impact journals. We will include randomised clinical trials reporting a binary or time to event outcome, using two study groups, and a superiority design testing the efficacy of diagnostic, monitoring, therapeutic or process interventions. All eligible studies must report an estimated event rate in the control group and estimated effect size. All relevant studies will be identified through database searches. All study selection and data extraction will be conducted by two independent reviewers. We will use a random-effects model for pooling data. This review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Accuracy of effect size and event rate estimation will be evaluated by comparing the estimated and observed values. The association between the accuracy of the individual randomised clinical trial effect size and event rate estimation and rejection of the null hypothesis will be evaluated using logistic regression analysis. Multivariable linear regression analysis will be used to explore the factors associated with accuracy of effect size and event rate estimation. In addition, we will perform subgroup analysis by impact factor of the published journals, sample size of the studies and risk of bias.

As this systematic review will use data from previously published studies, it does not require ethics approval. Findings of this systematic review will be published in a peer-reviewed journal and will be presented at specialty-based conferences. The study will be included in the higher degree research thesis of the primary author.

CRD420251106394.

Transient ischaemic attack (TIA) and migraine can generate identical symptoms but have very different short-term risks of stroke. Uncertainty about the diagnosis may lead to missed opportunities to prevent stroke if TIA is treated as migraine, or overtreatment if migraine is treated as TIA. This project aims to define the risk of stroke for people with migrainous symptoms reviewed as suspected TIA and develop a risk assessment tool that could promote standardisation of care.

The project involves two interlinked studies:

(1) Study A: prospective observational cohort study.

Setting: NHS TIA and stroke services.

Population: adults with migrainous symptoms undergoing review for suspected TIA by a TIA/stroke service and the initial specialist clinician symptom-based diagnosis is either possible migraine or possible TIA with migrainous symptoms.

Data collection: baseline clinical characteristics, investigations and treatments. Stroke, TIA and migraine events within 90 days.

Sample size: 2709 participants.

Main analyses: analysis of stroke risk, development of stroke risk prediction model, preparation of visual tools to represent the risk model.

(2) Study B: qualitative co-design study.

Setting and population: clinicians from NHS TIA and stroke services.

Data collection: focus groups/interviews exploring views about the potential role for a risk assessment tool, the most appropriate visualisation for the risk tool and barriers/facilitators for implementation.

Sample size: approximately 16 clinicians.

Analyses: framework approach using the Implementation Research Logic Model.

This study has ethical, Health Research Authority and participating NHS Trust approvals. Dissemination of study results will include presentations at national and international conferences and events, publication in peer-reviewed journals, and plain English summaries for patient/public engagement activities.

ISRCTN16775533.

Diabetes is a widespread chronic disease, with steadily rising prevalence in most countries. In 2019, the global prevalence of diabetes was estimated at 9.3%, affecting 463 million people. This figure is projected to rise to 10.2% by 2030 and 10.9% by 2045.2 All people with type 1 diabetes and many people...

Persistent somatic symptoms and functional disorders are conditions requiring a biopsychosocial approach to care, often from multiple professionals. The fragmentation of care common in most health systems results in unsatisfactory and challenging care experiences. Collaborative care networks form an important route towards improving outcomes and the overall experience of care for patients and professionals. While we have a good idea of what such collaborative care networks can look like, we lack knowledge on the practicalities of implementing change in such networks.

The core objective of this study is to implement change in a collaborative care network for persistent somatic symptoms and functional disorders care. Our questions were twofold: first, what are examples of realistic action processes to improve such collaborative care networks? Second, what are, in our experience, conditions for an effective change process in such a collaborative care network?

Participatory action research approach embedded within an active regional network between May 2023 and May 2024. The process was led by an action group who selected objectives and related actions with the aim of improving the network, leading to better care for people with persistent somatic symptoms and functional disorders as well as improving satisfaction among professionals.

ALK Netwerk Salland, a regional network of professionals and experts-by-experience, focused on care of persistent somatic symptoms. This network is based in the Salland region in the east of the Netherlands, centred around the city of Deventer.

The action group was made up of local stakeholders including experts-by-experience and health and social care professionals, facilitated by a researcher-in-residence. Other participants included members of the regional network who provided input towards the different objectives.

Over the course of a year, three objectives were selected and enacted, including assessing the resources of the network, improving knowledge of treatment options and improving the shared vision of care. The process faced some challenges, such as changes in action group members and a lack of resources and time to enact changes. However, by having a trusted and engaged team, working with an active network, we were able to enact significant changes to the network, which may be sustained and built on through the ongoing action group.

Future participatory action research studies would benefit from a trusted and embedded researcher-in-residence, meaningful involvement early in the process of experts-by-experience, and serious consideration of realistic outcome measures to monitor for evaluation of changes made.

Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) is associated with future major adverse cardiac events and may reflect residual ischaemia and suboptimal stent result (SSR). Post-PCI FFR should therefore be considered to identify patients at high risk. Whether abnormal post-PCI FFR and non-hyperaemic pressure ratios, including resting full-cycle ratio (RFR), represent SSR after PCI remains to be determined, especially after chronic total occlusion (CTO) PCI. In addition, little is known about the association between post-PCI intracoronary physiology and SSR with residual anginal complaints.

The physioLogy to evaluaTe procedural Result After percutaneous coronary intervention of Chronic Total Occlusion study is a prospective, multicentre, exploratory, mechanistic, investigator-initiated, single-arm study with a non-inferiority design. A total of 200 patients, undergoing CTO PCI, with FFR and RFR measured in all patients, will be included at two study sites in the Netherlands. The primary endpoint is the area under the curve (AUC) of post-PCI RFR, in comparison to the AUC of post-PCI FFR, for prediction of optical coherence tomography-detected SSR and its individual components.

The study is approved by the local ethical review board (‘Medisch Ethische Toetsing Commissie Isala Zwolle’). Written informed consent will be obtained from all patients before enrolment. The outcomes of this study are intended to be disseminated in a peer-reviewed journal.

NCT04780971.