Administration of antibiotics before incising the skin (‘surgical antimicrobial prophylaxis’) is a critical infection prevention strategy in surgery. Extending doses of prophylaxis into the postoperative period is a common practice in cardiac surgery; however, the benefit has not been clearly established and may lead to emergence of antimicrobial resistance and patient harm. We present the protocol for a large international multicentre, adaptive, pragmatic, double-blind, three-arm, placebo-controlled, randomised, non-inferiority clinical trial to compare the incidence of surgical site infection after three different durations of postoperative surgical antimicrobial prophylaxis in patients undergoing cardiac surgery.

This adaptive, multi-arm multistage non-inferiority trial will compare intraoperative only (Arm A), to intraoperative and 24 hours (Arm B) and, to intraoperative and 48 hours (Arm C) of intravenous cefazolin and placebo as surgical antimicrobial prophylaxis in 9180 patients undergoing cardiac surgery. The adaptive design allows for potential dropping of any of the three arms if clear inferiority is indicated at any of the scheduled interim analyses. The trial will evaluate the clinical and cost-effectiveness of the three different antibiotic prophylaxis durations.

Ethics approval will be obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. Patients and members of the public will also be involved in the dissemination and translation of the trial results.

NCT05447559.

Severe mental illness such as psychosis is among the most disabling illnesses worldwide, disproportionately affecting minoritised ethnic groups and those in socioeconomic disadvantage. In the UK, people from Black ethnic backgrounds are more likely to experience a first episode of psychosis and to be detained under the Mental Health Act than White British people. There is a clear need for mental health services to improve cultural awareness and understanding of the broader social needs of minoritised groups, as well as the need to improve mental health literacy (MHL) within Black communities to empower individuals to seek timely mental health support. This protocol describes our programme of work which aims to assess the feasibility, acceptability and cost-effectiveness of Co-STARS, which is a co-produced, culturally appropriate tiered training package.

We co-produced a culturally appropriate, place-based, tiered MHL training package (Co-STARS) to deliver within underserved Black communities and via an e-learning package implemented among staff within mental health trusts. The training will be evaluated in stages. First, a pilot cluster randomised controlled trial will assess the feasibility and acceptability (defined as participants’ perceptions of the training’s relevance, usefulness and delivery) of a lived experience-led MHL training package delivered by Black young people with experience of mental ill health, to underserved communities in Birmingham, UK. Acceptability will be quantified through participation and completion rates and explored qualitatively via focus groups and interviews. Second, a stepped-wedge cluster randomised trial will evaluate the feasibility of an e-learning training programme for mental health professionals. We will embed a process evaluation to explore change mechanisms and identify barriers and enablers for future implementation. Third, we will use realist-informed participatory systems mapping and novel epidemiological analyses to explore downstream effects (ie, improved care access for Black ethno-racial groups within the intervention areas). Last, a cost-effectiveness framework will be developed to assess whether the intervention is good value for money in future efficacy trials. In the cluster trial, eight clusters will be randomised to the intervention arm (face-to-face training in the community) and control arm (display of MHL materials) with pre- and post-assessments in 120 participants from 8 clusters, 3 weeks apart. In the stepped wedge trial, six clusters (clinical teams within NHS mental health trusts) including 120 NHS staff in total, will move from control phase to intervention phase in a stepped wedge manner, with pre-assessments and post-assessments.

This proposal was reviewed by the Research Governance of the University of Birmingham and UK Research and Innovation (UKRI) grant reviewers. Ethics approval was granted by East of Scotland Research Ethics Service. The findings will be communicated in research conferences, stakeholder meetings, via social media, through publication in peer-reviewed journals and as a policy document.

ISRCTN10517405.

To identify and prioritise research uncertainties regarding the assessment, management and rehabilitation of patients with problematic hip replacements through a national Priority Setting Partnership (PSP).

A national PSP using the James Lind Alliance (JLA) methodology.

UK.

Patients, carers and healthcare professionals (HCPs) involved in the care of patients with problematic hip replacements.

A steering group was established. The James Lind Alliance methodology was followed throughout. A nationwide survey was conducted to collect unanswered questions. These were refined, prioritised through an interim survey and ranked at a final consensus workshop.

The initial survey yielded 201 questions, refined to 32. The interim survey had 191 respondents, leading to 19 questions at the final workshop. The top 10 research priorities were agreed on.

This PSP identified key research priorities for problematic hip replacements, focusing on diagnosis, pain management, perioperative optimisation and infection. These priorities can inform researchers and funders to improve outcomes for affected patients.

The second phase of the Chiba Study of Mother and Child Health (C-MACH) was initiated to investigate how environmental exposures from the fetal period to early childhood influence maternal and child health outcomes. The sub-cohort focuses specifically on detailed assessments of indoor environmental factors and neighbourhood-built and social environments. By integrating environmental metrics with biological, behavioural and sociodemographic data, the study aims to elucidate their role in the development of allergies, neurodevelopmental disorders and other non-communicable diseases in early life.

Between June 2021 and April 2023, 505 pregnant women were enrolled in the second phase of the C-MACH main study. Of these, 298 participants consented to join the sub-cohort study, including 258 in the sleep and physical activity monitoring option (Option 1) and 148 in the indoor allergen exposure sub-study (Option 2). The study includes biological sampling, environmental monitoring and repeated questionnaire surveys. At baseline, 253 live births were recorded from 251 pregnancies.

Of the 298 women, 272 completed early pregnancy questionnaires. The mean maternal age was 33.1 years (SD 4.6); 97.8% were married. University-level education was reported by 51.0% of mothers and 53.7% of fathers. Most households had an annual income of 6 to

Longitudinal follow-up will continue until the children reach age 15. Future analyses will examine associations between environmental exposures and allergic, developmental, endocrine/metabolic and obesity-related outcomes.

High costs of screening and diagnostic tests remain a major barrier to timely tuberculosis (TB) identification in resource-limited settings. Evidence on the cost-effectiveness of scalable screening algorithms is limited. Start4All is a research project aimed at developing and evaluating algorithmic approaches to TB screening and diagnosis, with the goal of optimising technical and allocative efficiency when expanding diagnostic coverage to primary healthcare and community settings.

Five screening and diagnostic tests will be evaluated: a capillary blood-based assay (C-reactive protein (CRP)), sputum-based rapid molecular tests (PCR; individual and pooled Xpert MTB/RIF Ultra assay (Xpert Ultra, Cepheid®, California, USA)), a lateral-flow urine-based test for lipoarabinomannan (LF-LAM), and digital chest X-rays with artificial intelligence-based computer-aided detection (CXR-CAD). A microbiological reference standard of positive culture using the mycobacteria growth indicator tube will be used to confirm TB disease.

We will compare the cost and effectiveness of concurrent and sequential positive serial combinations (screening algorithms) of CRP, CXR-CAD, LF-LAM, individual and pooled Xpert Ultra. Diagnostic performance will be estimated using sensitivity, specificity, predictive values and proportions of positive results, with Bayesian inference used to derive these estimates. The analysis will include adults (15 years and older) only and will be stratified by HIV status and level of care, including facility and community-based case finding. Effectiveness will be assessed based on the number of people with TB detected. Cost analysis will be conducted from the provider perspective, incorporating commodity and implementation costs. A decision tree model will be developed to assess the cost per number of persons with confirmed TB detected across all countries. Probabilistic sensitivity analysis will be conducted to account for uncertainty in model parameters, incorporating willingness-to-pay and willingness-to-accept thresholds.

WHO ethical review committee approval ERC.0003921. Data will be available on reasonable request to the principal investigator of the consortium.

NCT05845112.

Group A Streptococcus (Strep A) causes a wide spectrum of diseases, ranging from pharyngitis and impetigo to severe invasive infections and immune-mediated conditions such as acute rheumatic fever, rheumatic heart disease and acute post-streptococcal glomerulonephritis. Contemporary data on the global burden of Strep A diseases are lacking. The proposed study aims to use administrative data from numerous jurisdictions to estimate age-specific incidence or prevalence of Strep A diseases, with an emphasis on severe clinical endpoints. Depending on the availability of data, a secondary objective will be to estimate the economic burden of Strep A diseases.

This population-based descriptive study will use routine health data obtained from different low-income and middle-income and high-income countries through international research collaborations to estimate the country-level and global burden of Strep A diseases. Data will be primarily obtained and collated from hospital or national health laboratory databases for individuals across all age groups, along with emergency department, primary care and microbiological datasets where available. Strep A disease endpoints will be identified using International Classification of Diseases 10th Revision or other relevant coding systems and microbiological diagnosis. Age-specific incidence and prevalence rates will be computed using population denominators, and country-level age-adjusted rates will be applied to standard global reference populations to estimate the number of cases globally.

Ethical approval to conduct this study was obtained from the Human Research Ethics Committee at the University of Western Australia (reference: #2024/ET000401) and governance approval was obtained from The Kids Research Institute Australia. The findings from this study will be published in peer-reviewed journals and presented at Strep A Vaccine Global Consortium collaborative meetings.

Patient-reported experience measures (PREMs) are measures of patients’ perceptions of care they receive. PREMs are critical in developing and evaluating programmes that aim to improve patient healthcare experiences and quality of care (QoC) according to patient-defined needs. This review aims to map key domains of PREMs across distinct healthcare technical areas and life stages from globally available literature.

A scoping review adapting Arksey and O’Malley’s framework and Joanna Briggs Institute’s guidelines for the conduct of scoping reviews.

Google Scholar, PubMed, WHO, US Academy of Medicine and USAID Momentum.

PREMs literature from electronic repositories of grey and peer-reviewed publications, published in English historically up to September 2023.

Two lead reviewers with support from the technical working group co-created a review framework of healthcare technical areas, life stages and PREMs domains. We screened eligible articles, prioritising reviews except for technical areas with no reviews, where we then selected individual studies. We charted, analysed and synthesised data from 52 eligible articles.

PREMs literature has recently increased, especially in low-income and middle-income countries (LMICs), although studies in high-income countries (HICs) dominate in proportion (n=38; 73.1%). Out of 52 eligible articles, technical areas with most publications were sexual and reproductive health (n=21; 40.4%) and general outpatient care (n=11; 21.2%). Studies in adulthood (n=24; 46.2%) and from pregnancy and birth to postnatal (n=16; 30.8%) were most represented. PREMs studies reported mostly on communication and rapport (n=33; 63.5%) and respect and dignity (n=42; 80.8%) domains. Nearly a quarter (n=12; 23.1%) of the articles included only validated tools; the rest included a combination of validated and unvalidated measures. Of the tools relating to life stages of babies, younger children and older adults, the majority (n=17; 94.4%) included patient proxies.

PREMs, as an important component of QoC measurement, are increasing across several healthcare technical areas and life stages with commonalities and notable distinctions in measurement domains and tools. Evidence on PREMs largely comes from HICs. Evidence on critical, yet sometimes overlooked domains, highlights key QoC implementation gaps. The adaptation and utilisation of PREMs in programmes, especially in LMICs and under-represented technical areas, present opportunities to close the QoC disparities in those settings. Strategic, concerted efforts towards the harmonisation of PREMs tools across multiple life course stages and technical areas are critically needed in high-level quality improvement efforts.

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

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

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

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

Major haemorrhage is the leading cause of preventable death in trauma, and prehospital blood transfusion may improve survival and outcomes for patients with prolonged out-of-hospital times. Globally, there is increasing interest in the use of whole blood in the prehospital environment, with randomised controlled trials ongoing. However, the results of these studies may not be generalisable to the longer out-of-hospital times seen in the Canadian trauma environment. The aim of this trial is to determine the feasibility of performing a randomised clinical trial evaluating the use of leukocyte-reduced whole blood transfusion compared with component blood transfusion in the Canadian prehospital environment. The secondary objective is to explore whether whole blood transfusion is better in reducing the proportion of patients who die or require massive transfusion within 24 hours.

This is a multi-centre, open-label, randomised controlled feasibility trial. Patients aged 16 years or older will be eligible if they have suffered a major traumatic haemorrhage, are attended by the provincial air ambulance service and require a prehospital blood transfusion. The primary outcome is feasibility as measured by the following metrics: proportion of patients enrolled with full data collection, proportion of patients who received at least one prehospital transfusion prior to arriving at the receiving trauma centre, proportion of patients who completed transfusion of all assigned blood units, number of patients unable to be enrolled due to lack of whole blood availability and number of whole blood units produced for the study that were wasted or expired. The secondary outcome is a composite outcome of death (all-cause mortality) or receipt of massive transfusion (receipt of 10 units of blood or more) within the first 24 hours from randomisation. We plan to recruit 60 patients, with an anticipated post-randomisation exclusion of ~10 patients for traumatic cardiac arrest or who do not meet eligibility criteria.

Provincial ethics approval was obtained (Clinical Trials Ontario REB ID: CTO-4921). An opt-out consent model will be employed for participants. The SWiFT Canada trial will recruit 60 patients through the provincial air ambulance organisation in Ontario who are transported to one of the six participating lead trauma centres. It will investigate the feasibility of a pre-hospital transfusion clinical trial in Canada to compare the effectiveness of whole blood compared with component blood therapy in a future definitive trial.

ClinicalTrials.gov: NCT06495294 (https://clinicaltrials.gov/study/NCT06495294), Clinical Trials Ontario: CTO-4921.

To examine how cultural health brokers, as trusted intermediaries between formal systems and diverse ethnocultural communities, help navigate decisional conflict and misinformation regarding COVID-19 vaccination and to identify how their work contributes to system resilience in crisis contexts.

A community-based participatory action sensemaking research project to capture the real-time work of cultural health brokers in helping people navigate decisional conflict for vaccination.

Multicultural Health Broker Cooperative in Edmonton, Alberta where brokers speak 54 languages and serve more than 10 000 people from diverse ethnolinguistic communities. 28 cultural health brokers (9 male; experience 4–25 years) contributed to data collection and analysis between 16 September 2021 and 16 December 2021.

The brokers captured real-time reflections and self-interpretations in the SenseMaker platform through a theoretically informed, codesigned, mixed-method data collection tool. The team engaged in 13 weekly, 90 minute, audio-recorded and transcribed sessions: seven focused on understanding and action planning and five reflecting on the SenseMaker data, the focus of the thematic analysis. Data were managed in NVivo (QSR International, Version 12, 2018).

Brokers collected 277 narratives and conducted 13 sensemaking sessions. Understanding and purpose were identified in 68% of narratives as key to achieving coherence; 81% of narratives highlighted trust as crucial to what was needed for action; 62% of narratives reflected on a potential risk, with loss of trust a concern in 70% of them. A rich understanding of the sources of decisional conflict and misinformation was achieved and managed through outreach. There were four entwined components to navigation of the evolving complexity of COVID-19 vaccination: (1) building and sustaining trust; (2) strengthening relationships; (3) creating safe spaces for collective sensemaking and solution finding; and (4) leveraging cultural and social capital to address barriers. Through these mechanisms, brokers reduced decisional conflict and misinformation, supporting informed, values-congruent decisions.

Cultural health brokers, embedded within communities and linked to formal systems, play a critical role in crisis response by fostering trust, mobilising resources and enabling collective sensemaking. This study demonstrates how these intermediaries’ contextually and culturally attuned work provides a model for building system resilience for future crisis response.

Value-based healthcare (VBHC) strives to improve the healthcare system by focusing on value of care, that is, patient relevant outcomes relative to the costs for achieving these outcomes. Within VBHC, patient participation is crucial to identify patient relevant outcomes and value improvement potential. However, patient participation in VBHC initiatives remains limited. Therefore, we aimed to improve patient participation within VBHC teams with the ultimate aim to develop a practical guide for patient participation in VBHC.

An action research study.

This study was conducted in seven collaborating Dutch hospitals from March 2023 to November 2024.

Seven VBHC teams were selected to participate in the cyclical action research steps, that is, orientation, planning, implementation, and evaluation, in which patient participation was implemented or improved. These included the following patient groups: prostate cancer, vulnerable elderly, breast cancer, diabetes, maternity care, colorectal cancer and chronic kidney disease.

Both qualitative and quantitative data were collected. Qualitative data included observations and minutes of meetings with the intervention teams. Quantitative data included responses to the Public and Patient Engagement Evaluation Tool (PPEET) by multiple members of the intervention (n=7) and control teams (n=94) at three time points (T1=6 months, T2=12 months, T3=end of study). Qualitative data were thematically analysed and quantitative data were analysed descriptively. Finally, the data were triangulated to create an overview of lessons learnt in improving patient participation.

Patient participation goals varied across teams, leading to diverse actions, such as establishing a diabetes patient panel and distributing questionnaires to patients with colorectal cancer. PPEET results show that 71% of intervention team members reported that patient participation had an impact on the team’s outcomes compared with 44% in control teams (T3). Furthermore, 80% of the intervention team members initially wanted training in patient participation (T1), which dropped to 29% at T3. Overall, 22 lessons in improving patient participation in multidisciplinary project teams were identified and compiled into a practical guide.

The action research process improved the process and impact of patient participation in the intervention teams. Furthermore, the results indicate that the action research process enhanced the team members’ knowledge and skills on patient participation. The practical guide developed in this study can be used to support implementation of patient participation in VBHC.

Couples diagnosed with unexplained subfertility are advised to start mild ovarian hyperstimulation and intrauterine insemination (MOH-IUI) as a primary treatment. Natural feedback mechanisms and hormone release are affected by artificially stimulated cycles and induced ovulation. Additional luteal support could positively affect progesterone patterns in the luteal phase. The LUMO study evaluates whether the addition of exogenous progesterone in the luteal phase following MOH-IUI treatment cycle will improve pregnancy and live birth rates.

A multicentre randomised, double-blind, controlled trial will be conducted in Dutch fertility clinics, academic and non-academic hospitals. There are two treatment arms: group A progesterone luteal phase support; group B placebo, without crossover. All initiated MOH-IUI cycles within 6 months after randomisation are included (study period). Participants will start study medication, applying a daily dosage of 2dd 300 mg progesterone (Utrogestan) or 2dd 300 mg placebo in vaginal capsules on the second day after the IUI procedure. Treatment is continued until the onset of menstruation, a negative pregnancy test (IUI+14 days), a miscarriage or until 7 weeks of gestation in case of a viable pregnancy. Follow-up ends at 12 months after the end of study period (18 months after study randomisation). The primary outcome is cumulative pregnancy rate, achieved within 6 months after randomisation, leading to live birth. A total of 1008 patients (504 patients in each group) will be included.

The study was approved by the Central Committee on Research Involving Human Subjects on 30 January 2023. All participating sites have the approval of the local Board of Directors to participate in the LUMO study. An informed consent form will be signed by all participants. Study results will be presented at (inter)national conferences and published in peer-reviewed journals. It is expected that the results of this trial will be used to draft national guidelines on this issue.

The study is registered in the EU CTIS trial register (2022-501534-33-00), the Dutch trial registry (registration number: LTR 24508), ClinicalTrials.gov (NCT05080569) and the WHO registry (universal trial number: U1111-1280-9461).

Healthcare workers (HCWs) report overwhelming demands and experience crisis levels of burnout and unique challenges that further impair their mental health. Promotion of mental health among HCWs using information and communication technology (ICT) has received little empirical research attention and interventions for improving mental health resilience in HCWs are not well established.

Scoping review to map existing evidence and identify gaps for future research regarding the main barriers and facilitators of the acceptance of ICT-based interventions for improving resilience and mental health among HCWs working in all healthcare settings.

This protocol was developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive bibliographic search will be conducted between October 2024 and October 2025 in Pubmed, Web of Science, PsycINFO, Scopus, Cochrane Library and CINAHL Ultimate (MedicLatina, Psychology and Behavioural Sciences Collection), with the assistance of a qualified research librarian, to retrieve studies describing data on the main barriers and facilitators to the acceptance of ICT-based interventions for improving resilience and mental health among HCWs working in healthcare settings. There will be no restrictions based on date of publication or language. Inclusion and exclusion criteria will be defined for each element of the PICO(D) framework, and both quantitative and qualitative data will be extracted. Quality will be assessed using the mixed methods assessment tool. Two independent investigators will perform the eligibility assessment and data extraction, and any disagreements will be resolved by a third reviewer. The main results will be narratively synthesised and analysed.

Since secondary data will be analysed, no ethical approval is required. The results will be disseminated through publications subject to peer review.

https://doi.org/10.17605/OSF.IO/5R36Q.

To determine what drives participation in clinical trials with decentralised elements and to estimate trial participation probabilities for trials with different degrees of decentralisation.

Patient preference study using a discrete choice experiment.

Recruitment in primary, secondary, tertiary care and other settings in the Netherlands (NL), Austria (AT) and Germany (DE).

People with type 2 diabetes mellitus (T2DM) aged ≥18 years. A total of 787 people (NL n=276, AT n=265, DE n=246) participated in the study.

Preferences for participation in clinical trials with different options for location and type of contact with the study team, activities to perform by participant, use of digital technologies by participant, number of scheduled contacts, trial duration, known safety and efficacy of the drug.

How much was known about the safety and efficacy of the drug was the most important element in the decision whether to participate in a clinical trial in all countries. The trial duration, location and type of contact with the study team, and number of scheduled contacts were other important elements. Participation probabilities for hypothetical trial scenarios differed between countries, with the highest rates for a decentralised trial involving video contact (NL: 89%; AT: 99%; DE: 84%).

People with T2DM prefer to take part in clinical trials with decentralised approaches. Information on preferences can help trialists and protocol developers to design and plan future trials that integrate patients’ needs and thus reduce barriers to participation.

Duchenne and Becker muscular dystrophies (DMD and BMD) are devastating conditions characterised by progressive muscle degeneration and weakness. Despite advances in understanding their pathogenetic processes, there is a critical need for reliable biomarkers to aid in patient stratification and inform clinical decision-making, predict disease progression and evaluate therapeutic responses. Several promising protein biomarkers have been investigated as potential diagnostic/prognostic tools, but, to date, this evidence has not been systematically synthesised. We aim to comprehensively and critically review and summarise published studies reporting the use of protein signatures of muscular damage in DMD and BMD.

We will systematically search Ovid MEDLINE (PubMed), OVID Embase, OVID Evidence-Based Medicine Reviews and Cochrane Library to retrieve all relevant articles. For ongoing trials, we will search WHO International clinical trials registry and ClinicalTrials.gov registry. We will include studies that measure circulating and urine levels of established and/or promising protein biomarkers associated with skeletal muscular damage and disease progression, such as creatine kinase, myoglobin, skeletal troponin I fast-twitch (type II), myostatin, creatine/creatinine ratio, creatinine and titin. We will consider randomised controlled trials, observational studies and longitudinal cohort studies with serial sampling, without restrictions on sample size, geographic location or language, while excluding animal and in vitro studies. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria and extract data of retained articles. A third author will be consulted in case of disagreement. The approach recommended by the Agency for Healthcare Research and Quality’s Methods Guide for Effectiveness and Comparative Effectiveness Reviews will be used. The risk of bias and reporting quality will be assessed with standardised scales. The analysis will involve a structured narrative synthesis and evidentiary tables. If a meta-analysis is possible, biomarker data for each outcome will be pooled using random effects models. Subgroup analyses have been planned as a function of age, genetic mutation, disease severity, imaging and clinical assessment, length of the observation and risk of bias.

Ethics approval is not required for this study as no original data will be collected. The findings will be shared through peer-reviewed publications and conference presentations. Additionally, this systematic review will guide the recommendations of the Duchenne Regulatory Science Consortium. This work will provide a rigorous, exhaustive and accessible evidence synthesis to identify candidate biomarkers of potential clinical value. Furthermore, it is expected that these results could be used to facilitate the development of future research strategies and guidelines, inform resource allocation decisions and accelerate the route towards clinical implementation of biomarkers for DMD and BMD.

CRD42024549471. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024549471

Infections caused by carbapenemase-producing organisms have become a major problem during the treatment of secondary bloodstream infection in patients with severe intra-abdominal infection (sIAI). Early detection and identification of potential carbapenemases by colloidal gold immunochromatography assay kit can provide information about the susceptibility of pathogenic bacteria before conventional microbial testing results are obtained. This study aims to evaluate the effects of rapid carbapenemase detection-guided antibiotic therapy on patients with sIAI.

The RAPID study is a multicentre, single-blinded, randomised controlled trial. All patients with intra-abdominal infection will be screened for eligibility on any given day that the first gram-negative bacilli-positive blood culture is detected. In total, 640 eligible study participants assigned informed consent will be randomised to either carbapenemase detection-directed antimicrobial treatment or the conventional group, receiving antimicrobial agents based on different bacterial identification and susceptibility tests. Patients will be followed until discharge or death within a follow-up 28 days after randomisation. The primary outcome is all-cause 28-day mortality. Secondary outcomes include antibiotic duration, length of stay in the hospital and intensive care unit and bacterial clearance. The desirability of outcome ranking and response adjusted for duration of antibiotic risk will also be used to comprehensively assess treatment effectiveness at 28 days.

The study has been approved by the Ethics Committee of Jinling Hospital (2023DZKY-069–01) and all participating centres. Written informed consent will be obtained from all participants or their legal representatives. The results of this trial will be disseminated through peer-reviewed publications and presented at national and international scientific conferences.

ChiCTR2300076159.

Internationally, the vision of a ‘Digital Trustworthy Evidence Ecosystem’ is being pursued with clinical practice guidelines (CPGs) as one element of such a system. Consequently, CPGs and CPG repositories need to be digitalised.

The objective of this prospective, before-after study is to evaluate the impact of digitalising a quality-assured CPG registry using the international data format standard ‘Fast Healthcare Interoperability Resources’ (FHIR). This includes the architecture of the registry, the format of individual guidelines and application programming interfaces to import and export CPG content. The study is guided by a scoping review.

The primary outcome is the usability of the digitalised CPG registry and CPG content for different user groups comprising CPG developers, CPG administrators, health care professionals and patients—including at the point of care in in- and outpatient settings—and technical professionals as users of CPG content in digital applications.

For the before-after comparison, semi-quantitative (surveys) and qualitative (focus groups) methods are applied. All user groups will be involved in a baseline analysis to assess user expectations and technical requirements. According to the results, the digitalised guideline registry will be implemented. The intervention comprises the testing of the digitalised registry with guideline content by all user groups. Analysis of outcomes will include formative and summative evaluation. Final results and further research needs will be discussed in a World Café with all stakeholders.

The Ethics Committee of the Berlin chamber of physicians, in accordance with its code of conduct §15 section 1 (Eth-KB-24-11) confirmed that no ethical approval is needed for this study. The study is registered in the German Clinical Trials Registry (No: DRKS00034111). Results will be presented at national and international conferences, published in peer-reviewed journals and on the website of the funding institution.

German Clinical Trials Registry (No: DRKS00034111).

Subarachnoid haemorrhage (SAH) is relatively frequent, accounting for 5% of strokes and affects a young population. Arterial vasospasm is a frequent complication of SAH, with an estimated incidence as high as 70%. Vasospasm is responsible for cerebral ischaemia which in turn is potentially responsible for severe morbidity (neurological deficit, neuropsychiatric disorders), poor quality of life (institutionalisation, inability to return to work) and increased mortality. Treatment with intravenous milrinone, an arterial vasodilator, has been proposed, but no randomised controlled study exists. We hypothesised that an intravenous infusion of milrinone would improve the neurological recovery of patients with vasospasm following aneurysmal SAH at 3 months.

The MiVAR (Milrinone Infusion for VAsospam treatment in subarachnoid hemoRrhage) study is an investigator-initiated, phase III multicentre, randomised placebo-controlled, double-blinded, superiority trial evaluating the effect of intravenous milrinone versus placebo (saline), in patients with cerebral vasospasm following aneurysmal SAH. Patients will be included within 6 hours of the confirmation of vasospasm diagnosis by a CT angiography and randomised to receive either milrinone (initial bolus of 0.1 mg/kg over 30 min—max 10 mg—followed by a continuous infusion at 1 µg/kg/min rate for at least 48 hours) or placebo. Milrinone (or placebo) could be increased to 1.5 µg/kg/min. The dose is adapted according to the clinical and/or transcranial Doppler response. 360 patients are expected to be included. The primary endpoint is the proportion of patients with a good neurological outcome at 3 months, defined as a modified Rankin score ≤2, obtained through a centralised standardised telephone interview (done by a unique trained team). The study started in August 2020, and the expected final follow-up is the last quarter of 2025. Analyses of the intention-to-treat and per-protocol populations are planned.

The MiVAR trial protocol has been approved by an ethics committee (Comité de Protection des Personnes Ouest V), by the Agence Nationale de Sécurité du Médicament (ANSM, Number 160 828A-21, approval date 26 December 2019) and by the ‘Commission Nationale Informatique et Liberté’ (CNIL, decision DR-2020-076, approval date 21 February 2020). The study will be conducted according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The MiVAR study will be the first multicentre randomised study to evaluate the efficacy of intravenous milrinone in improving the neurological outcomes at 3 months in patients with vasospasm following aneurysmal SAH.

NCT04362527, EudractCT number 2019-002145-37.