Cardiac allograft vasculopathy (CAV) is a critical predictor of the long-term success of heart transplantation and once it is established, progression to graft dysfunction and loss is inevitable, despite adherence to immunosuppression and medications that ameliorate cardiac risk factors. Regulatory T cells (Tregs) are key for maintaining immune balance in the periphery. Studies investigating adoptive transfer of ex vivo expanded Tregs isolated from blood have been shown to be feasible and safe with good evidence for Tregs reducing CAV lesions in animal models of transplantation. Here, we describe the protocol for the ATT-Heart Study which is a phase I clinical trial investigating autologous thymus-derived Treg cell therapy in nine paediatric heart transplant recipients.

Patients will be recruited from the heart transplant waiting list at Great Ormond Street Hospital. Individualised autologous thymus-derived and expanded Tregs (TR006) will be injected into patients 3–6 months after transplant and follow-up will be conducted as per the post-transplant standard of care protocol with no wean of standard of care immunosuppression. Primary endpoint includes occurrence of Dose-limiting Toxicities in patients receiving TR006. Further data from blood tests, endomyocardial biopsy tissue, coronary imaging and clinical follow-up will be collected.

This article is based on the ATT-Heart study Protocol (V.1.1; dated 19 December 2024). The ATT-Heart trial has received a favourable ethical opinion from the Health Research Authority and South-Central Oxford A Research Ethics Committee (IRAS Number: 1008875/REC reference: 24/SC/0333). Clinical trials authorisation approval from UK Medicines and Healthcare products Regulatory Agency has also been received. The clinical trial will be conducted in accordance with the principles of Good Clinical Practice and following the guidelines set as part of the Research Governance Framework for Health and Social Care and all applicable necessary local policies. It is intended that the findings of the clinical trial will be presented at national/international conferences and using social media and through patient groups for dissemination among their members. The results will also be published in international peer-reviewed journals.

ISRCTN15374803.

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

Population-based retrospective cohort study.

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

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

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

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

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

Food retail outlets in sports and recreation facilities often fail to support healthy eating, despite aligning with healthy lifestyles and goals of local governments (LGs) that often own or manage them. LGs face barriers to implementing facility changes including inadequate staffing, training and incentives. The Promoting CHANGE initiative was co-designed to support LGs in improving and sustaining healthier food and drink offerings in these settings.

A 3-year, type 2 effectiveness-implementation hybrid cluster randomised controlled trial will evaluate the Promoting CHANGE capacity-building and support package in three Intervention and four Control LGs in Victoria, Australia (August 2023–July 2026). The co-designed initiative includes human resource support, training, tools, technical assistance, community-of-practice groups, feedback based on food outlet audit and sales data and small grant incentives. Using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) evaluation framework, the trial’s co-primary outcomes are the percentage of least healthiest food and drinks (1) displayed (implementation) and (2) sold weekly (effectiveness). Key secondary outcomes are effectiveness (sales and revenue); facility-level adoption, implementation, maintenance of healthy changes; cost-effectiveness (within-trial modelled economic evaluation). Findings will provide evidence of the initiative’s effectiveness and scalability, informing recommendations for advancing healthier food environments in over 6000 community-based food outlets across 500 Australian LGs, with implications globally.

This study has received approval from the Deakin University Human Research Ethics Committee (reference number HEAG-H 92_2023). The results will be published in scientific peer-reviewed journals along with plain language summaries for participants.

ACTRN12621001120864.

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).

Endometriosis affects 5–10% of women during reproductive years, with a 20–30% incidence among those with infertility. Deep infiltrating endometriosis (DIE) affects 10–15% of women of childbearing age and 50% of infertile women. When hormonal therapy and conservative surgery prove ineffective, total hysterectomy with or without bilateral salpingo-oophorectomy may be the ultimate therapeutic option. Laparoscopic surgery is the gold standard for treating endometriosis, offering effective disease eradication, safety, reduced pain, shorter hospital stay and faster recovery compared with laparotomy. However, patients undergoing total laparoscopic hysterectomy with DIE have higher risks of complications and organ damage, particularly urinary tract damage. Robot-assisted laparoscopic hysterectomy has emerged as a promising alternative, with a significantly lower conversion rate than total laparoscopic hysterectomy in patients with endometriosis. This study evaluates the safety and efficacy of robot-assisted total laparoscopic hysterectomy (RATLH) versus total laparoscopic hysterectomy (TLH) in the management of DIE. We hypothesise that robot-assisted laparoscopic hysterectomy will result in fewer complications and better outcomes compared with total laparoscopic hysterectomy in DIE patients.

The ENDORAS trial is a prospective, multicentre, open-label, randomised controlled trial conducted in French reference hospitals specialising in endometriosis surgery. A total of 224 adult women patients will be enrolled in this study if they have DIE with adenomyosis, and without digestive tract involvement as confirmed by MRI. Participants will be randomised to undergo either RATLH or TLH. The primary outcome will be the intraoperative and postoperative complication rates, classified according to the Clavien-Dindo classification (grade 2 or above) at the 3-month postoperative follow-up. Among the secondary outcomes, we will evaluate the quality of life using various questionnaires, including the Endometriosis Health Profile-30, the Short Form-306 and the Female Sexual Function Index.

The ENDORAS trial will be conducted in accordance with the International Council on Harmonization Good Clinical Practice guidelines. All trial documents and procedures have been reviewed and approved by the Ethics Committee Ile de France II (approval ID number: 24.01408.000300). Informed consent will be obtained during the preoperative check-up by the operating gynaecologist. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, broadcast media, print media and the internet.

NCT06445179. Registered on 14 November 2024.

To assess the comparative effectiveness of educational interventions in neurological disease for healthcare workers and students.

Systematic review.

Medline, Embase and Cochrane through to 1 June 2025.

Studies evaluating neurological disease educational interventions with a comparator group (observational cohort/randomised controlled trial (RCT)) were included.

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted (PROSPERO: CRD42023461838). Knowledge acquisition and educational methodologies were collected from each study. Study outcomes were classified using the Kirkpatrick and Kirkpatrick four-level model (learner reaction, knowledge acquisition, behavioural change, clinical outcome).¹ Risk of bias was assessed using the Newcastle-Ottawa scale for non-randomised studies and the Cochrane Risk of Bias tool for RCTs.^{2 3}

A total of 67 studies involving 4728 participants were included. Of these, 36 were RCTs, and 31 were observational studies. Virtual interventions were the most common (67.2%, n=45 studies), primarily targeting either medical students (46.3%, n=31 studies) or specialists (40.3%, n=27 studies). Overall, 70.1% (n=47) of studies demonstrated outcomes in favour of the intervention. However, few studies used K&K level 3/4 outcomes, with two studies evaluating behaviour change (level 3) and three assessing clinical outcomes (level 4 combined with other levels). No study exclusively assessed level 4 outcomes. Meta-analysis of 22 RCTs with calculable standardised mean differences (SMDs) (n=1748) showed a significant benefit of interventions (SMD 0.75, 95% CI 0.22 to 1.27, p=0.0056).

This review highlights a growing body of research particularly focusing on virtual techniques, specialist audiences and treatment-oriented content. Few studies assessed changes in practice or patient care. Non-specialists remain underrepresented. Future studies should prioritise assessing the clinical impact of educational interventions within non-specialist audiences.

Tuberculosis (TB) is a major global cause of morbidity and mortality. Emerging evidence in high-burden settings suggests significant long-term sequelae among people surviving TB; however, evidence from high-income, low-TB burden settings like Canada is lacking. In a person with TB infection, provision of TB preventive treatment (TPT) can prevent TB disease and its sequelae, but remains underused. We propose the Functional Outcomes, Lung health and Livelihood Outcomes among people With Tuberculosis study, a multicentre, prospective cohort study in Canada to help improve our understanding of the impacts of TPT and TB disease on individuals.

This is a prospective cohort study taking place in Montreal and Vancouver, Canada. We aim to recruit and retain at least 120 people with microbiologically confirmed TB disease, 340 people treated for TB infection and 120 without TB disease or infection who will be considered our unexposed group. All participants must be ≥6 years of age. Participants with TB disease or infection will be recruited within 2 weeks of treatment initiation. We will follow-up unexposed participants and participants with TB disease for 24 months, and participants with TB infection for 12 months. Throughout follow-up, participants will complete assessments measuring lung health and function, quality of life, disability, dyspnoea, psychological distress, as well as changes in employment and direct and indirect costs incurred because of treatment. Among participants with TB disease, our primary outcome is the difference in quality-adjusted life years between participants with TB disease and those unexposed at 24 months. For participants with TB infection, our primary outcome is the identification of non-patient characteristics (eg, patient cost, quality of life) associated with participant decision to discontinue treatment. Patient partners have contributed to the design of the study and will be involved with the study through to its dissemination.

This study has been approved by institutional ethics review boards at The Research Institute of the McGill University Health Centre (2025–10344) and The University of British Columbia (H24-02071). All participants will provide informed consent (and assent, if required) prior to participating in the study. We will disseminate study results to participants, national and international organisations, and through open-access peer-reviewed academic journals and conferences.

Despite the known haemostatic action of emicizumab (Hemlibra) in haemophilia A patients, its role in the prevention and control of bleeding in high-demand haemostatic situations, such as major surgery, remains to be determined. Patients receiving regular emicizumab prophylaxis often require concomitant factor VIII (FVIII) therapy during major surgery to prevent uncontrolled bleeding and to promote postoperative healing. However, there are limited prospective surgical data relating to concomitant FVIII and emicizumab use. Simoctocog alfa (Nuwiq) is a B-domain deleted recombinant FVIII produced in a human cell line without chemical modification or protein fusion with proven efficacy as surgical prophylaxis in adult and paediatric patients. The Nuwiq for Perioperative management Of patients With haemophilia A on Emicizumab Regular prophylaxis (NuPOWER) study aims to examine perioperative efficacy and safety of simoctocog alfa in haemophilia A patients on emicizumab prophylaxis undergoing major surgery.

NuPOWER is a prospective, open-label, single-arm, multicentre study that will be conducted at approximately 15 centres worldwide. Up to 28 male patients ≥12 years with severe haemophilia A and no FVIII inhibitors will be recruited. All patients must be receiving regular emicizumab prophylaxis and scheduled to undergo a major surgical procedure during which concomitant simoctocog alfa will be administered. The primary endpoint is the overall haemostatic efficacy of simoctocog alfa, adjudicated by an independent data monitoring committee using a pre-defined algorithm, and will consider intraoperative and postoperative efficacy assessments by the surgeon and investigator, respectively. Secondary endpoints include intraoperative haemostatic efficacy, postoperative haemostatic efficacy, number of allogeneic blood products transfused, perioperative FVIII plasma levels (as measured by FVIII activity) and thrombin generation, and safety parameters. In the era of non-factor therapy, NuPOWER will generate valuable prospective data on concomitant use of simoctocog alfa and emicizumab prophylaxis in patients with severe haemophilia A undergoing major surgery.

Ethical approval has been received from institutional review boards/independent ethics committees, and the study will be conducted in compliance with the Declaration of Helsinki. This work will be disseminated by publication of peer-reviewed manuscripts and presentations at scientific meetings.

CT EU 2022-502060-21-00; NCT05935358.