Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown.

The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population.

The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries.

Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025

Oxaliplatin, a key drug in the treatment of colorectal cancer (CRC), can cause oxaliplatin-induced peripheral neuropathy (OIPN) in a dose-dependent manner. These symptoms can severely affect daily life, and chronic OIPN often limits treatment continuation because of its correlation with the cumulative dose of oxaliplatin. Currently, effective preventive measures are unavailable. However, surgical glove compression therapy may reduce paclitaxel-induced neuropathy, suggesting its potential in preventing OIPN.

This multicentre, randomised, open-label, phase II/III trial evaluates surgical glove compression therapy to investigate the possible preventive effects of OIPN in patients with CRC receiving adjuvant capecitabine plus oxaliplatin chemotherapy. Patients with stage III CRC undergoing curative surgery will be enrolled and randomised into two groups. The intervention group will wear two layers of tight-fitting surgical gloves from 30 min before to 30 min after oxaliplatin infusion, whereas the control group will receive standard care. The primary endpoint is the incidence of grade ≥2 chemotherapy-induced peripheral neuropathy (CIPN) based on the Common Terminology Criteria for Adverse Events criteria. Secondary endpoints include quality of life assessments (Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity-12 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-item), duration and extent of OIPN as assessed using the Debiopharm Neurologic and Sensory Toxicity Criteria, chemotherapy completion rates, and adverse events. To detect a significant reduction in the incidence of CIPN, 170 patients will be enrolled (36% in the control group vs 15% in the intervention group). The planned case enrolment period is from 1 November 2024 to 31 October 2026.

This trial was approved by the Institutional Review Board of Hiroshima University, Japan (approval no. CRB2024-0008), and has been registered with the Japan Registry of Clinical Trials (jRCTs062240066). The results of this study will be submitted for publication in a peer-reviewed journal and shared with the scientific community at international conferences.

jRCTs062240066

Venous leg ulcers (VLUs) are complex, chronic wounds that often recur after healing. The ongoing use of compression hosiery is the primary strategy to reduce the risk of VLU recurrence. However, adherence to this prophylactic treatment is low, undermining treatment effectiveness and placing a substantial burden on individuals with a history of VLUs and on healthcare systems. Understanding the factors influencing people’s adherence to compression hosiery for secondary VLU prevention is essential to support approaches to promote uptake.

The study aimed to (1) draw on the Capabilities, Opportunities and Motivations of Behaviour (COM-B) model and the Theoretical Domains Framework (TDF) to explore factors influencing individuals’ use of prophylactic compression hosiery for the secondary prevention of VLUs and (2) use the behaviour change wheel to identify intervention strategies to support the ongoing use of prophylactic compression hosiery by individuals after VLU healing.

A descriptive, interpretive qualitative study involving individuals with a history of healed VLUs. Semistructured interviews were conducted with people who had experienced healed VLUs. The interviews were guided by the COM-B model. Framework analysis was conducted using deductive coding informed by the TDF and inductive coding to capture emerging themes linked to barriers to and enablers of the target behaviour (ongoing compression use). Data management was aided by NVivo software, and coding was conducted by two researchers.

Interventions were conducted in person, by telephone or online, based on participants’ preferences, at community leg clubs or in their homes, from April 2024 to January 2025.

Participants with experience of healed VLUs were recruited from three National Health Service (NHS) trusts and community leg clubs in the North of England.

A total of 15 participants were interviewed, comprising 4 males and 11 females aged between 49 and 89 years. Our analysis identified six factors that may influence individuals’ use of prophylactic compression hosiery following VLU healing: knowledge, skills, environmental context and resources, emotion, social influences and beliefs about consequences. Deficits in knowledge, skills and resources, such as limited availability of prophylactic compression sizes, delays in prophylactic compression delivery and limited access to NHS services after healing, were primary barriers to people’s use of compression hosiery in this context. Conversely, positive beliefs about the benefits of ongoing use of prophylactic compression hosiery were a strong enabler. Emotion and social influences were identified as both barriers and enablers: fear of recurrence and social support encouraged adherence, while stigma and negative feelings hindered it. We identified six intervention functions (education, training, persuasion, environmental restructuring, modelling and enablement) and eight linked behaviour change techniques that could be explored further to support people’s ongoing use of prophylactic compression therapy. These techniques include providing information about antecedents, discussing health and emotional consequences, instruction, demonstration, rehearsal, social support, framing/reframing and vicarious reinforcement.

The identified intervention functions and behaviour change techniques provide theoretically informed insights for designing interventions to support sustained use of prophylactic compression hosiery following VLU healing. Key barriers to address include addressing gaps in individuals’ knowledge about prophylactic compression therapy, prioritising posthealing VLU services, ensuring timely access to appropriately fitted compression and enhancing social support networks.

Hypertension is the leading risk factor for death globally. Undiagnosed hypertension is common, but the incidence in hospitalised patients is unclear. There are calls for universal facility-based screening for hypertension among all attending patients. The hospital inpatient setting, where blood pressure (BP) is measured routinely and repeatedly, presents an ideal opportunity. However, international hypertension guidelines do not include inpatient BP thresholds for diagnostic or treatment purposes. We investigated the performance of current UK community BP thresholds for diagnosing hypertension in the hospital setting.

Investigate the diagnostic performance of the current UK ambulatory BP diagnostic thresholds for systolic and diastolic hypertension in the hospital setting against the reference test of community-based ambulatory BP monitoring (ABPM).

A prospective diagnostic accuracy study.

Hospital inpatients admitted to three UK centres were approached. Follow-up ABPM was delivered in the community.

Eligible patients were aged between 18 and 80 years, with no prior diagnosis of, or prescription for hypertension, and whose mean cumulative daytime BP was 120 mm Hg to 179 mm Hg systolic and ≤109 mm Hg diastolic from the 24th hour of their hospital admission.

Participants received 24-hour ABPM 4–26 weeks post-discharge, as the reference test for hypertension, with UK diagnostic thresholds of an average daytime BP of ≥135 mm Hg systolic and ≥85 mm Hg diastolic applied. Participants found to be severely hypertensive at the ABPM fitting appointment were also considered reference-test positive but did not proceed with ABPM.

The diagnostic performance of a mean daytime in-hospital BP of ≥135 mm Hg systolic or ≥85 mm Hg diastolic (index test) for the prediction of hypertension diagnosed on ABPM (reference test) was assessed using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) as primary outcome measures. Additionally, we explored the accuracy of a range of alternative in-hospital systolic and diastolic BP thresholds against the same reference test.

351 participants were enrolled and 206 completed the study protocol. The average age of the 206 participants was 53 years, 55% were male, and 91 (44%) had daytime community hypertension on ABPM reference testing. Of 107 participants with raised in-hospital daytime BP, 59 (55%) had daytime community hypertension. When assessing the performance of the index test for detecting daytime community hypertension, sensitivity was 65% (59/91, 54% to 75%) and specificity was 58% (67/115, 49% to 67%). The PPV was 55% (59/107, 45% to 65%) and NPV was 68% (67/99, 58% to 77%), respectively. A further 45/206 participants (23%) had night-time community hypertension when assessed using European diagnostic thresholds for nocturnal hypertension (120 mm Hg systolic or 70 mm Hg diastolic), while 25/107 of those with raised in-hospital daytime BP (23%) had night-time community hypertension. When assessing the performance of the index test for detecting either day or night-time community hypertension, sensitivity was 62% (84/135, 53% to 70%) and specificity was 68% (48/71, 55% to 78%). The PPV was 79% (84/107, 70% to 86%) and NPV was 48% (48/99, 38% to 59%).

Undiagnosed hypertension is common in hospitalised patients, particularly those with raised in-hospital BP. While in-hospital BP alone is an imperfect predictor and should not be used as a stand-alone diagnostic test, this could serve as a trigger for further assessment of BP in the community after discharge.

The study protocol was registered with the ISCTRN Registry (ISRCTN80586284).

Visual Patient Predictive (VPP) is an AI-based extension of the Visual Patient Avatar (VPA) that integrates deep learning models to predict upcoming vital sign deviations and display them as dashed visual elements. By explicitly showing anticipated changes, the system aims to support level 3 situation awareness—the projection of future patient states. This multicentre simulation study will evaluate whether predictive algorithms and visualisations integrated into the VPA (resulting in VPP) improve clinicians’ ability to anticipate critical vital sign changes compared with conventional number-based and waveform-based monitoring and examine its effects on decision-making, confidence, workload and user acceptance.

This investigator-initiated, randomised, within-subjects crossover, computer-based simulation trial will be conducted at five academic centres in Switzerland, Germany and the United States. Medical professionals from anaesthesiology departments will complete scenario-based prediction tasks using both VPP (as the index test) and conventional monitoring (as the reference standard) in randomised order, with the same participant evaluating both modalities and the identical underlying clinical scenario used in each condition, following video-based training and a learnability test. The primary outcome is recall (true positive rate) of vital sign deviation predictions. Secondary outcomes include average lead time, precision, prediction confidence, number and correctness of proposed interventions, perceived workload (NASA-TLX) and qualitative usability feedback. Quantitative data will be analysed using a logistic generalised linear mixed model with random intercepts for centre and participant, and a random slope for the intervention effect. Qualitative interviews will undergo thematic analysis.

The leading ethics committee (Zurich, Switzerland; BASEC-Req-2023–00465) reviewed and approved the study protocol. Ethics committees at the other participating centres have obtained their respective approvals or waivers. Bonn: 2025–144-BO, Boston: 2025P000501, Heidelberg: S-376/2025, Munich: 2025–357 W-CB. As this simulation study involves only healthcare professionals performing prediction tasks based on simulated vital sign scenarios—without collection of patient data or any medically relevant personal data—it does not constitute human subjects research under applicable regulations. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

The WHO Safe Childbirth Checklist (SCC) has been implemented in diverse settings to improve the quality and safety of intrapartum care, but implementation strategies and their relationship with adoption and fidelity remain heterogeneous and incompletely described.

To describe the landscape of SCC implementation, map the implementation strategies used and explore how these strategies were reported in relation to adoption and fidelity.

We included primary studies reporting SCC implementation in healthcare settings that described at least one implementation strategy, with no restrictions on country or language. Studies that did not report implementation strategies or did not involve SCC use in real-world care settings were excluded.

We searched PubMed, Embase, CINAHL, Global Health and Global Index Medicus (June 2024), screened reference lists and consulted grey literature for the period 2009–2024.

This scoping review followed JBI methodology (Peters et al) and was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We extracted study characteristics and implementation findings, coded strategies using the Expert Recommendations for Implementing Change (ERIC) taxonomy and grouped them by clusters. Adoption (initial uptake) and fidelity (adherence to core components) were categorised following Proctor’s implementation outcomes. We created a descriptive implementation intensity score and conducted exploratory analyses (tertiles, boxplot).

34 studies described 19 SCC implementation projects across 16 countries. We identified 24 distinct ERIC strategies, with most projects using 5–11 strategies. Frequently reported strategies included educational meetings, audit and feedback, supervision, contextual adaptation and leadership or champions. Exploratory analyses did not show consistent associations between implementation intensity and adoption or fidelity. ‘Change infrastructure’ strategies (such as record system or equipment changes) were variably defined and warrant cautious interpretation. Adaptations (eg, translation and alignment with national guidelines) were common and aimed at improving local fit, but heterogeneous reporting limited cross-study comparability.

SCC implementation has relied on diverse, multicomponent strategies, yet reporting—especially of strategy content and adaptations—remains insufficient, constraining comparison and synthesis across settings. As a pragmatic bundle, implementers may prioritise brief team training, unit-level champions and leadership signals, point-of-care audit and feedback, light-touch SCC adaptation that preserves core content and structured supervision or peer coaching, combined with systematic inclusion of women and families through codesign and companion-mediated prompting. Using theory-informed frameworks (such as Exploration, Preparation, Implementation, and Sustainment and Consolidated Framework for Implementation Research [CFIR]) and standardised reporting tools (eg, Proctor’s outcomes; Template for Intervention Description and Replication / Standards for Reporting Implementation Studies [TIDieR/StaRI]) can make SCC implementation strategies more transparent, comparable and scalable.

Open Science Framework: https://doi.org/10.17605/OSF.IO/RWY27.

To evaluate the cost-effectiveness of implementing a penicillin allergy assessment pathway (PAAP) versus usual care within the NHS.

A decision tree analysis over a 5-year time-period, informed by a randomised controlled trial (RCT) of PAAP and systematic review. Value of information analysis was also conducted to estimate the value of conducting a new trial.

Model inputs were informed by the ALABAMA RCT participants included in the primary analysis, 811 adults with penicillin allergy labels and recent antibiotic prescriptions, and data from published literature.

Participants in the ALABAMA trial included in the primary analysis: PAAP (n=401) and usual care (n=410).

Costs are presented in GBP (£) at 2022–2023 prices, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, incremental net monetary benefit (INMB), the probability of cost-effectiveness at the £20,000 and £30,000 per QALY threshold, and the cost effectiveness of a new follow-on trial.

PAAP had incremental costs of £–83 (probability of cost saving 47.5%) and incremental QALYs of 0.036 (probability of positive benefits 47.5%). The INMBs (probability of cost-effectiveness) were £806 (48%) and £1167 (48%) under the decision thresholds of £20,000 and £30,000 per QALY, respectively. PAAP was more cost-effective among females, people aged >65 years, and more frequent antibiotic users. A new follow-on trial involving 1267 participants was estimated to cost £2.4 million and, by reducing uncertainty in the evidence, would avoid £19.6 million in costs of incorrect management decisions for eligible patients over the next 10 years.

The PAAP was considered cost-effective, but significant uncertainty remained. Future trials with adequate power and longer follow-up are needed to determine the most cost-effective models for penicillin allergy testing.

ISRCTN20579216.

Shared decision-making (SDM) requires that individuals are correctly and smoothly supported to make decisions. However, in Japan, development of decision aids (DAs) to support implementation of SDM is lagging behind Western countries, and there are few reports focused on breast reconstruction. Thus, it is unclear if SDM using a DA in the context of the unique national character and medical culture in Japan is useful in decision-making for breast reconstruction, including whether or not to undergo reconstruction. The aim of this multicentre collaborative study is to investigate the clinical effectiveness of SDM using a DA for patients with breast cancer considering reconstruction, from the perspectives of decisional conflict and postoperative quality of life.

A multisite trial will be conducted at 12 facilities certified by the Japanese Society of Breast Oncoplastic Surgery. A cluster-randomised controlled trial is planned at centres that have implemented SDM with DAs and those that have not implemented SDM, but use a conventional surgical explanation and informed consent to make decisions about reconstruction methods. The study participants will be female patients aged ≥20 years with newly diagnosed stage 0–III breast cancer who are interested in breast reconstruction. Data collection includes baseline and follow-up patient surveys and medical record review. The effectiveness of the DA at reducing conflict and regret in decision-making (primary outcome) will be evaluated using the decision conflict scale.

This protocol has been approved by the Kyoto University Central Institutional Review Board, and permission for performance of the study has been obtained from the Ethics Review Board at each participating centre. We plan to disseminate the findings through journal publications and national meetings, including a presentation of the research results at the Japanese Society of Breast Oncoplastic Surgery. Our findings will advance the science of medical decision-making and have the potential to reduce socioeconomic health disparities.

UMIN000052161.

Preterm infants are at risk of developmental impairment, especially those born before 33 weeks gestational age. Many studies have shown a positive impact of early interventions on medical outcomes during hospitalisation, long-term cognitive development and parental anxiety. Infant Behavioral Assessment and Intervention Program (IBAIP) has shown positive effects on cognitive development but also on motor impairment in a Dutch cohort. We aim to confirm these results in a multicentric, cluster randomised controlled trial in a French setting.

Eight French neonatal intensive care units (NICUs) will be randomised before study initiation to intervention or control group. We aim to include 240 infants born between 25 weeks and 33 weeks gestational age. IBAIP intervention comprises monthly home visits with a trained professional from hospital discharge until 6 months corrected age. Both groups receive standard care according to local organisation. The primary endpoint is composite cognitive score at 2 years corrected age using Bayley Scale of Infant Development Fourth Edition (BSID IV). Secondary endpoints include BSID IV subscores, Ages and Stages Questionnaire scores and parental stress. Analysis is in intention to treat. Univariate and multivariate analysis will be performed on primary and secondary endpoints.

Informed consent from one or both parents will be necessary for all patients. Study results will be published in peer-reviewed scientific journals. If our hypothesis is confirmed, IBAIP could be implemented on a nationwide scale. The study was registered with clinicaltrials.gov (ID: 29BRC17.0219).

NCT04685356.

To identify the factors influencing professionals’ implementation of the National Institute for Health and Care Excellence (NICE) guidelines on self-harm.

A rapid review evidence synthesis

Five electronic databases (ASSIA, CINAHL, EMBASE, MEDLINE, PsycINFO) and five indexing databases (Science Citation Index Expanded (SCIE), Social Sciences Citation Index (SSCI), Arts and Humanities Citation Index (AHCI), Emerging Sources Citation Index (ESCI) and Conference Proceedings Citation Index (CPCI)), using the Web of Science platform, were searched in December 2023 and repeated in July 2024.

We included quantitative and qualitative studies that investigated professionals’ knowledge and implementation of NICE guidelines on self-harm, that were in English language and published between 2004 and July 2024.

One reviewer used standardised methods to search, screen, select, quality assess and synthesise the included studies, to accelerate the review. Quality assessment was conducted using the Mixed Methods Appraisal Tool. Data were extracted and synthesised thematically using NICE guidance implementation priorities.

The review included 10 studies. Six were conducted in accident and emergency (A&E) settings, two in general practice, one in a burns and plastic surgery hospital department and one involved cross-sectoral health professionals. Key findings indicate that awareness and implementation of self-harm guidelines is low among health professionals. Systemic barriers include lack of staff training, negative staff attitudes towards people who self-harm and lack of resources.

There is a need to develop and implement regular training on self-harm, incorporating NICE guidance and measures, to integrate knowledge and mobilise practice changes. Further research into the implementation of NICE guidelines in children who self-harm is needed, and in a wider variety of health and social care settings. The absence of studies from the social care sector into professionals’ awareness and implementation of NICE guidelines on self-harm is a key limitation.

Despite advancements in biomedical and healthcare research, the translation of evidence into routine practice within healthcare systems often lags, perpetuating inefficiencies and disparities in care delivery. Learning health systems (LHS), which integrate internal data and external evidence for continuous improvement, hold promise for addressing these gaps. Implementation science (IS), focused on promoting the systematic uptake of evidence-based practices, offers a robust framework to drive sustainable improvements within LHS. However, the practical application of IS principles in LHS remains underexplored. This scoping review aims to systematically map the literature on the application of IS in LHS, highlighting themes, gaps and opportunities for advancing future practices.

This review will follow the Joanna Briggs Institute (JBI) methodology for scoping reviews, supported by the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR) checklist. The review employs a population-concept-context framework, focusing on studies engaged in LHS activities and the application of IS principles in various healthcare settings. Relevant literature will be searched across multiple databases, including OVID/Medline, Embase, Web of Science Core Collection and Health Policy Reference Center. Eligible studies will be screened, and data will be extracted and synthesised using both quantitative and qualitative methods. Key outcomes include characterising IS applications in LHS, evaluating barriers and facilitators, exploring equity integration, and identifying knowledge gaps.

As this study does not involve primary data collection, ethical approval is not required. Findings will be disseminated through peer-reviewed publications and conference presentations to inform future research and practice.

This protocol has been registered on the Open Science Framework (DOI: 10.17605/OSF.IO/BMQ6J).