Acute lower limb ischaemia (ALI) is a life- and limb-threatening vascular emergency requiring urgent intervention. Despite advancements in therapeutic strategies, outcome reporting for ALI remains inconsistent, limiting evidence synthesis and guideline development. The CORE-ALI study aims to develop a Core Outcome Set (COS) to standardise outcome reporting and ensure the inclusion of both clinical and patient-centred metrics.

CORE-ALI will use a structured, multi-phase methodology guided by the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Core Outcome Set-STAndards for Reporting (COS-STAR) guidelines. Phase 1 involves stakeholder engagement through semi-structured interviews with patients, clinicians and policymakers from diverse European healthcare systems. Qualitative data will be analysed using thematic analysis to generate a preliminary list of outcomes. In Phase 2, a multi-round Delphi survey (anticipated two to three rounds) will prioritise and refine outcomes through consensus building, with quantitative data analysed using descriptive and non-parametric statistical methods. Phase 3 will culminate in a consensus meeting to finalise the COS. Multilingual accommodations will ensure inclusivity, and General Data Protection Regulation (GDPR)-compliant platforms will secure data handling.

The study has received ethics approval from the Ethics Committee of the Medical University of Innsbruck (EK Nr: 1082/2025) on 20/05/2025. Additional local ethics approvals are required and will be obtained at all participating sites prior to the initiation of recruitment. The final Core outcome set will be disseminated through peer-reviewed publications, presentations at international conferences and engagement with professional societies and patient organisations.

COMET initiative (Registration No. 3346).

Patient safety is a central pillar of healthcare quality. However, with repeated examples of failure emerging across healthcare, there is an ongoing need to better understand how the safety of care can be improved for patients. Evidence suggests that some population groups are more likely to inequitably experience healthcare harm. This review will look at what evidence exists on understanding patient safety harm and its causes and impact on different population groups and particularly those from marginalised backgrounds. It will also focus on what actions can be taken to address patient safety disparities and service improvements, including with patient and public involvement.

A scoping review of empirical and grey literature will be conducted following the Joanna Briggs Institute guidance. Medical databases such as Medline, EMBASE, PsycINFO will be searched for peer-reviewed articles and grey literature sources such as BASE, institutional and government repositories will be searched for reports, independent reviews, confidential enquiries, etc. These will be searched from 2001 to present for publications in English. Title and abstract and full text screening will be undertaken by one or more people acting as first reviewers and validated by a second reviewer. A data extraction form will be used to extract data including equity considerations following the PRO EDI framework. Data will be grouped thematically and analysed using a narrative approach.

Ethics approval is not required for this work as the information used is publicly available. The findings of the review will be disseminated through stakeholder meetings, a peer-reviewed publication and conference presentations.

osf.io/4mfus.

Rheumatoid arthritis (RA) is a heterogeneous disease, which current treatment guidelines insufficiently accommodate, as they predominantly emphasise the suppression of disease activity. However, a step towards personalised medicine is preferred to further optimise treatment and requires homogeneous subgroups with similarities in pathophysiological mechanisms and treatment responses. Prior research has already demonstrated notable differences in the pathophysiology of patients with autoantibody-positive and autoantibody-negative RA, as well as differences in treatment responses, which may serve as a strong basis for personalised medicine. Additionally, there is evidence suggesting that an early treatment response is indicative of future courses. Based on these findings, we designed a personalised medicine trial in RA that compares the effectiveness and cost-effectiveness of a tailor-made approach with routine care.

The PeRsonalIsed Medicine in RA (PRIMERA) trial is a multicentre, open-label, randomised controlled trial that includes 300 adult patients with newly diagnosed, DMARD-naïve RA, according to 2010 American College of Rheumatology/EULAR criteria. Patients are randomised into either routine care or a tailor-made approach. Both management approaches use a treat-to-target strategy, aiming for low disease activity (LDA, Disease Activity Score using 44 joints (DAS) ≤2.4). In routine care, initial treatment consists of methotrexate along with a single intramuscular dose of glucocorticoids (GCs) and treatment can be intensified after 3, 7 and 10 months if LDA is not reached. Conversely, initial treatment in the tailor-made approach depends on the presence of autoantibodies, with patients with autoantibody-positive and autoantibody-negative RA starting with hydroxychloroquine or methotrexate together with a single intramuscular dose of GCs, respectively. Medication intensifications will be allowed at months 1, 3, 4, 7 and 10. Intensifications at months 1 and 4 depend on whether patients have an early sufficient response to GCs and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively. The tailor-made approach is superior to routine care if no more biological DMARDs (bDMARDs) or tsDMARDs are used after 10 months of treatment, while the mean DAS over time is lower. Our primary outcome is the proportional difference in bDMARD or tsDMARD usage after 10 months of treatment between routine care and the tailor-made approach. Secondary outcomes are DAS over time, time to achieve LDA, cost-effectiveness and patient-reported outcome measurements over time.

Ethical approval has been granted by Erasmus MC Medical Ethics Review Committee (MEC-2020-0825). The results will be disseminated through peer-review journals and medical congresses.

ISRCTN16170070.

To evaluate the association between asthma-related emergency department (ED) visits and weather, air quality, monsoons, haze and cultural festivals in Singapore.

Retrospective cohort study.

A public healthcare cluster that covers 20% of the nation’s adult asthma population.

2617 adult patients accounting for 5337 asthma ED visits between 2016 and 2024.

Temperature, rainfall, wet bulb temperature (WBT), wind speed and Pollution Standards Index (PSI) were correlated with asthma ED counts at 0–7 day lags. Associations between ED visits and monsoons, transboundary haze and cultural festivals were evaluated using one-way analysis of variance. Weekly seasonal ARIMA models with exogenous regressors were fitted, incorporating PSI as a covariate and adjusting for demographic, clinical and socioeconomic factors.

Asthma ED visits were positively correlated with PSI (lag 0: r=0.142; 95% CI 0.107 to 0.178) and inversely correlated with rainfall (lag 3: r=–0.062; 95% CI –0.099 to –0.026) and WBT (lag 1: r=–0.067; 95% CI –0.104 to –0.031). Wind speed (lag 2: r=–0.049; 95% CI –0.086 to –0.013) and ambient temperature (lag 6: r=–0.045; 95% CI –0.081 to –0.008) showed weaker inverse associations. Mean PSI was higher during haze (82.67 vs 51.46, p

PSI–ED association peaked on the same day of exposure but was no longer significant after adjusting for demographic and clinical factors. Pollution-linked festivals, transboundary haze and the Northeast monsoon were associated with increased asthma ED visits

This proof-of-concept study explored the feasibility and acceptability of research cafés as a community-based model to engage racially minoritised communities in health research, with a focus on mental health.

Adopting a community peer research approach, a research team led by researchers from racially minoritised backgrounds, partnered with four voluntary organisations to conduct four research cafés. A mixed-methods feasibility design combined descriptive quantitative questionnaire data with thematic analysis of discussion notes to evaluate the impact of these cafés in South West London.

The study took place in Wandsworth, Kingston, Croydon and Sutton, in community venues provided by the voluntary organisations.

A total of 75 participants from racially minoritised backgrounds attended the sessions. Participants were intentionally selected based on age, ethnicity, location, mental well-being experiences and willingness to engage in mental health research.

Quantitative data were collected on participant attendance, demographics and feedback. Qualitative data captured participant perceptions and experiences related to healthcare and research.

The study took place between October 2023 and March 2024. Out of the 112 individuals who registered, 75 people attended with 74 contributing to the analysis (excluding one on the day sign-up). Participants were predominantly Asian/Asian British (62%) and Black/Black British (31%). All participants reported feeling comfortable and respected. Understanding of research improved for 96% and 95% expressed interest in further research involvement, most commonly the idea of joining a peer research network (64%). Participants also highlighted a need for training in research methods and communication skills for ongoing involvement. Five main themes emerged from the café discussions: (1) systemic barriers to accessing safe healthcare and mistrust of UK healthcare systems; (2) the need for cultural competence and sensitivity in healthcare and research; (3) research as a positive step for change; (4) barriers to research participation and (5) the importance of incentives and feedback for research participation.

Preliminary findings suggest that diverse and inclusive community-based partnerships are the basis for developing research cafés as a feasible and acceptable model for engaging racially minoritised communities in health research. They complement existing participatory approaches by creating inclusive, peer-facilitated spaces that build trust, improve awareness and generate high intention for future involvement and participation. Future studies are needed to test the model’s scalability across different geographic and demographic contexts and evaluate its long-term impact on research literacy, participation and equity.

In Tanzania, acute myocardial infarction (AMI) is underdiagnosed, and uptake of evidence-based care is suboptimal. Using an implementation science approach, an intervention was developed to address local barriers to care: the Multicomponent Intervention for Improving Myocardial Infarction Care in Tanzania (MIMIC).

This sequential cohort design trial was conducted in a single northern Tanzanian emergency department (ED). During the preintervention phase (February–August 2023) and the postintervention phase (September 2023–August 2024), adults presenting with chest pain and/or dyspnoea were prospectively enrolled and their ED care was observed. AMI was defined by the Fourth Universal Definition criteria. Telephone follow-ups were conducted to ascertain 30-day mortality. Pearson’s ² was used to compare care before and after MIMIC implementation.

A total of 275 participants were enrolled in the preintervention phase and 577 were enrolled in the postintervention phase. Following MIMIC implementation, significant increases were observed in ECG testing (89.4% of postintervention participants vs 55.3% preintervention, OR 6.82, 95% CI 4.79 to 9.79, p

The MIMIC intervention was associated with large increases in uptake of AMI testing, case identification and evidence-based treatment in a single Tanzanian ED. Multisite studies are needed to evaluate the effect of MIMIC on AMI care in diverse settings across Tanzania.

NCT04563546.

There is limited evidence on how to effectively treat individuals from marginalised populations with dependence on amphetamine and/or methamphetamine (collectively referred to hereafter as amphetamine dependence). The disease burden is extremely high in this population, especially related to psychiatric comorbidities, cardiovascular complications, injection-related infections and poor social functioning. ATLAS4Dependence is a multi-centre randomised, placebo-controlled, double-blind trial that will investigate the effectiveness and safety of substitution treatment with dextroamphetamine compared with placebo in people with amphetamine dependence.

The trial will recruit 226 adult patients in several outpatient clinics in Norway.Inclusion criteria comprise individuals with amphetamine dependence, defined as use on three or more days per week during the past 28 days, who currently inject or have formerly injected drugs. This includes individuals both with and without comorbid opioid dependence, as well as those currently receiving or not receiving opioid agonist treatment. Participants will be randomly assigned 1:1 to receive either dextroamphetamine or placebo for 12 weeks. Flexible doses within the range of 30–120 mg daily will be provided based on individual assessments. The participants in both arms will be offered standard psychosocial and medical follow-up in accordance with current clinical practice. The endpoint assessments will be conducted at 12 weeks with weekly self-reports and safety assessments and a follow-up assessment at 52 weeks. The primary objective of the study is to assess the impact of 12 weeks daily prescribed oral dextroamphetamine versus placebo on the use of illicit amphetamines as well as on the total amount of amphetamines used (including both illicit and prescribed sources). Secondary outcomes are the differences between the groups at 12 weeks regarding psychological distress, symptoms of psychosis, quality of life, cardiovascular risk factors, injection-related infections, executive functioning, attention-deficit hyperactivity disorder-related symptoms, sleep, violence risk, fatigue, symptoms of craving and withdrawal, treatment retention, days of use of illicit amphetamines and use at 4 weeks and 8 weeks during the intervention period, use of other illicit substances and alcohol, as well as a cost-effectiveness analysis (using private economy, criminal activity and health service utilisation) and a qualitative approach to assess overall experiences with the study intervention. Analysis and reporting will follow the Consolidated Standards of Reporting Trials guidelines. All tests will be two-sided. Descriptive results and the estimated effectiveness will be presented with 95% CIs. The difference between the groups at the primary time point (at the end of the 12-week trial) will be assessed using ² test (for use of illicit amphetamines measured by monthly urine tests) and Analysis of Covariance (ANCOVA) (for weekly self-reported total amount of amphetamines). Analyses for the primary endpoint will be undertaken on an intention-to-treat basis and reported on as such, but sensitivity analyses with per protocol analyses will also be presented.

The study is approved by European Medicines Agency, Clinical Trial Information System (CTIS). Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.

CTIS 2023-510404-44-00.

First post-contrAst SubtracTed (FAST) MRI, an abbreviated breast MRI scan, has high sensitivity for sub-centimetre aggressive breast cancer and short acquisition and interpretation times. These attributes promise effective supplemental screening. Until now, FAST MRI research has focused on women above population-risk of breast cancer (high mammographic density or personal history). DYAMOND aims to define the population within the population-risk NHS Breast Screening Programme (NHSBSP) likely to benefit from FAST MRI. The study population is the 40% of screening clients aged 50–52 who have average mammographic density (BI-RADS (Breast Imaging Reporting and Data System) B) on their first screening mammogram. DYAMOND will answer whether sufficient numbers of breast cancers, missed by mammography, can be detected by FAST MRI to justify the inclusion of this group in a future randomised controlled trial.

Prospective, multicentre, diagnostic yield, single-arm study with an embedded qualitative sub-study: all recruited participants undergo a FAST MRI. An internal pilot will assess the willingness of sites and screening clients to participate in the study. Screening clients aged 50–52, with a clear first NHSBSP mammogram and BI-RADS B mammographic density (by automated measurement) will be invited to participate (recruitment target: 1000). The primary outcome is the number of additional cancers detected by FAST MRI (missed by screening mammography). A Fleming’s two-stage design will be used as this allows for early stopping after stage 1, to save participants, funding costs and time continuing to the end of the study if the question can be answered earlier.

The NHSBSP Research and Innovation Development Advisory Committee and the Yorkshire and Humber–Sheffield Research Ethics Committee (23/YH/0268, study ID (IRAS): 330059) approved this research protocol. Participation involves a two-stage informed consent process, enabling screening for eligibility through automated mammographic density measurement. Patients with breast cancer helped shape the study design and co-produced participant-facing documents. They will disseminate the results to the public in a clear and meaningful way. Results will be published with open access in international peer-reviewed scientific journals.

ISRCTN74193022

The improved survival rates of children with cancer have heightened concerns about treatment-related chronic health conditions, including platinum-induced hearing loss (PIHL). Cisplatin and carboplatin, widely used in paediatric cancer therapies, frequently cause irreversible sensorineural hearing loss. PIHL affects 1.7–90.1% of patients exposed to these drugs, yet known risk factors—including age, cisplatin dosage, cranial radiation and co-treatment with ototoxic drugs—fail to fully explain interindividual variability. Genetic factors likely play a role in susceptibility to PIHL. Since genetic susceptibility in children may differ from adults, and given the critical window of auditory development, a focused investigation of paediatric genetic factors using quantitative methods is warranted to detect small to moderate effects and understand the polygenic nature of PIHL.

In this study, we will systematically review and conduct a meta-analysis of genetic polymorphisms associated with PIHL in individuals diagnosed before the age of 21 years. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, the review will include randomised controlled trials, cohort, case-control and cross-sectional studies that analyse the genetic influence on PIHL in paediatric populations treated with cisplatin and carboplatin. A comprehensive search of PubMed, EMBASE and Cochrane databases will be conducted, supplemented by backward citation searching. Data will be extracted on study design, treatment details, hearing loss assessment methods, genetic findings and covariates. We will use forest plots to present the results, and both Mantel-Haenszel fixed-effects model and random-effects model will be used for meta-analysis. Heterogeneity will be assessed with the I² index. The study will address potential heterogeneity, individual study quality, proportion of missing data and meta-analysis bias. The quality of the evidence of the meta-analysis will be assessed using the Grading quality of evidence and strength of Recommendations (GRADE) approach.

This systematic review will enhance our understanding of the genetic contribution to PIHL in children and serve as a basis for further research for improvement of personalised treatment strategies for paediatric cancer care.

CRD42024532664.

All the included patient’s data are already published with an ethics approval for each study, respectively. No original data will be collected.

Most research on the relationship between diabetes and cognitive health has used data from high-income countries. This study described this relationship in India, the world’s most populous country.

Cross-sectional analysis of the baseline wave of the nationally representative Longitudinal Ageing Study in India, conducted from 2017 to 2019.

All 36 Indian states and union territories.

57 905 adults aged 45 years or older.

Scaled cognitive scores (mean of 0 and SD of 1) and cognitive impairment defined as a cognitive score 1.5 SD or below the age-matched and education-matched mean. Diabetes was defined as a self-report of a prior diabetes diagnosis made by a health professional or having a measured haemoglobin A1c ≥6.5%.

In age-adjusted and sex-adjusted models, people with diabetes had cognitive scores that were 0.24 SD higher (95% CI 0.22 to 0.26) and had a 1.2% (95% CI 0.6% to 1.7%) lower prevalence of cognitive impairment than people without diabetes. Differences persisted even when adjusting for demographic, socioeconomic and geographical characteristics. Rural versus urban residence modified the relationships of diabetes with cognitive score (p=0.001) and cognitive impairment (p=0.003). In fully adjusted models, rural respondents with diabetes had 0.05 SD (95% CI 0.03 to 0.07) greater cognitive scores and 1.6% (95% CI 0.9% to 2.4%) lower prevalence of cognitive impairment than those without diabetes. In urban areas, respondents with and without diabetes had similar cognitive scores and prevalence of cognitive impairment.

Middle-aged and older adults with diabetes living in India had better cognitive health than those without diabetes. Rural versus urban area of residence modified this relationship. Urban–rural differences, the nutrition transition and social conditions likely influenced the cross-sectional relationship between diabetes and cognitive health in India, leading to different associations than reported in other countries.

For patients with perihilar cholangiocarcinoma (pCCA), surgical resection remains the sole treatment modality that can potentially result in cure. Unfortunately, the majority of patients present with unresectable tumours or are excluded from surgical treatment due to complications like cholangitis affecting their performance status. In the Netherlands, recommended first-line treatment for patients with unresectable pCCA is palliative chemotherapy with gemcitabine and cisplatin. This regimen yields an estimated median overall survival (OS) of 11.7–15.2 months, highlighting the urgent need for novel treatment options. The STRONG I trial, a phase I study in patients with unresectable pCCA, was completed in 2020. Its aim was to assess the feasibility and toxicity profile of adding stereotactic body radiation therapy (SBRT) to chemotherapy. SBRT, delivered in 15 fractions of 4.0 Gray (Gy), was considered to be feasible and safe, with no dose-limiting toxicity being observed. The 1-year local tumour control rate was 80% and the 1-year OS rate 100%, with maintenance of quality of life (QoL). These results encouraged us to initiate the STRONG II trial, aiming to investigate the efficacy of adding SBRT to chemotherapy in a larger patient cohort.

STRONG II is a single-arm, multicentre phase II study. Patients with non-metastatic unresectable pCCA (T1-4, N0-2) are eligible. A total of 30 patients will be enrolled in six academic centres in the Netherlands and two in Belgium. SBRT will be delivered in 15 fractions of 4.0–4.5 Gy. The primary endpoint is local tumour control, defined by Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1. Secondary endpoints include toxicity, biliary stent-related events, progression-free survival, OS and QoL using the EuroQoL five-dimensional, five-level (EQ-5D-5L) questionnaire, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and the EORTC Biliary Module (QLQ-BIL21). In addition, we will explore the predictive value of the peripheral immunological status (immune-related proteins and serum functional immunological status assay) and its dynamics in determining survival outcomes. For this explorative translational study, two blood samples will be collected, one before the start of chemotherapy and another after completing chemotherapy.

Approval of the study was obtained on 5 June 2024 by the Medical Ethics Review Committee of Erasmus Medical Center Rotterdam, the Netherlands (ID: NL86210.078.24). The anticipated time frame for patient enrolment is July 2024 to December 2027. The main study findings will be published in peer-reviewed medical journals, and presented at national and international conferences.

NCT06493734 (ClinicalTrials.gov).

Migrants and refugees with low language proficiency (LLP) in the dominant language of their host country have a higher risk of suffering from certain mental health disorders compared with non-migrant populations. They are also more likely to experience a lack of access to mental healthcare due to language-related and culture-related barriers. As part of the MentalHealth4All project, a digital multilingual communication and information platform was developed to promote access to mental healthcare for LLP migrants and refugees across Europe. This paper describes the study protocol for evaluating the platform in practice, among both health and/or social care providers (HSCPs) and LLP migrants and refugees.

We will conduct a pretest–post-test cross-national survey study to evaluate the platform’s effect evaluation (primary objective) and process evaluation (secondary objective). The primary outcomes (measured at T0, T2 and T3) are four dimensions of access to mental healthcare services: availability, approachability, acceptability and appropriateness of mental healthcare. Secondary outcomes (measured at T2) are: actual usage of the platform (ie, tracking data), perceived ease of use, usefulness of content, comprehensibility of information, attractiveness of content and emotional support. Participants will be recruited from nine European countries: Belgium, Germany, Italy, Lithuania, the Netherlands, Poland, Slovakia, Spain and the UK. Using convenience sampling through professional networks/organisations and key figures, we aim to include at least 52 HSCPs (ie, 6–10 per country) and 260 LLP migrants (ie, 30–35 per country). After completing a pretest questionnaire (T0), participants will be requested to use the platform, and HSCPs will participate in an additional personalised training (T1). Next, participants will fill out a post-test questionnaire (T2) and will be requested to participate in a second post-test questionnaire (T3, about 6–8 weeks after T2) to answer additional questions on their experiences through a brief phone interview (T3 is optional for migrants/refugees).

For all nine countries, the ethical review board of the participating university (hospital) has assessed and approved the protocol. If successful, the MentalHealth4All platform will be made publicly available to help improve access to mental healthcare services, as well as HSCPs’ cultural competencies in delivering such services, for any LLP migrants and refugees across Europe (and beyond). Findings will also be disseminated through peer-reviewed journals and conferences.

The ‘MHealth4All project’ was prospectively registered on Open Science Framework, DOI: 10.17605/OSF.IO/U4XSM.

This study aimed to evaluate the utility of optical sensor-based technology in mitigating the frequency and severity of peripheral intravenous infiltration and/or extravasation (PIVIE) in neonates.

Single-centre, retrospective, observational cohort study.

Tertiary-level neonatal intensive care unit (NICU) (112 cots) at the Women’s Wellness and Research Centre (WWRC), Hamad Medical Corporation (HMC), Doha, Qatar, January 2019–December 2022.

All neonates admitted to the NICU requiring intravenous therapy via a neonatal short peripheral intravenous catheter (n-SPC) were included. Participants were excluded if the insertion was unsuccessful, if they had incomplete data, or if they received intravenous therapy exclusively through alternative vascular access devices.

The study analysed two cohorts representing different clinical practices over two distinct periods. In the conventional cohort (Phase 1, 2019–2020), PIVIE detection relied solely on periodic ‘Touch Look Compare (TLC)’ assessments. In the ivWatch cohort (Phase 2, 2021–2022), continuous optical sensor-based monitoring using the ivWatch system was implemented alongside TLC assessments. This sequential design allowed for a comparison of outcomes between the two phases.

The primary outcomes were the occurrence and severity of PIVIE. Secondary outcomes included the influence of patient demographics, vascular access characteristics, and management details on PIVIE incidence and severity.

Over the 4-year data collection period, 32 713 peripheral intravenous catheters were analysed across two cohorts. PIVIE was the most common reason for unplanned device removal. In the conventional cohort (Phase 1, 2019–2020), 4941 infiltration events were reported (29.9%), compared with 4872 events (30.1%) in the ivWatch cohort (Phase 2, 2021–2022). However, severity measures using the Intravenous Extravasation Grading Scale (IEGS) revealed a marked reduction in severe PIVIE cases, with severe events decreasing from 243 (4.9%) in the conventional cohort to 54 (1.1%) in the ivWatch cohort (p

PIVIE remains a frequent complication in neonatal vascular access. Continuous site monitoring with optical sensor technology was associated with earlier detection of PIVIE events and reduced IEGS severity scores. These findings highlight the potential of integrating sensor-based monitoring with traditional observational methods to improve patient outcomes in neonatal care.