Pulmonary embolism (PE) is a potentially fatal condition requiring timely diagnosis and treatment. CT pulmonary angiography (CTPA) is the gold standard for diagnosis and indicates PE severity through radiological markers of right heart strain. However, accurate interpretation and communication of these findings is often suboptimal in real-world practice. Artificial intelligence (AI) could alleviate pressure on radiology services by supporting PE identification, risk stratification and worklist prioritisation. Before widespread adoption, AI tools must be rigorously validated for diagnostic accuracy, safety and clinical impact.

This pragmatic single-centre, non-randomised quasi-experimental study will evaluate the diagnostic accuracy, feasibility, and clinical-cost impact of AI-assisted PE detection and risk stratification using AIDOC and IMBIO software. We will recruit two consecutive cohorts of adult patients undergoing CTPAs for suspected PE: a comparator cohort (12 months pre-AI implementation) and an intervention cohort (12 months post-AI implementation). AI will be applied retrospectively to the comparator cohort, while in the intervention cohort, radiologists will have contemporaneous access to the AI’s interpretation of CTPA images.

A subset of retrospective scans, both PE-positive and PE-negative, will undergo expert thoracic radiologist review to establish a reference standard. Data on patient demographics, clinical management and outcomes will be collected. Clinical management pathways and patient outcomes will be compared between cohorts to assess AI’s influence on acute PE management. Health economic modelling will assess the cost-effectiveness of integrating AI technology within the diagnostic workflow of acute PE.

This study was approved by the UK Healthcare Research authority (IRAS 311735, 10 May 2023). Ethical approval was granted by West of Scotland Research Ethics Service (23/WS/0067, 3 May 2023). Results will be shared with stakeholders, presented at national and international conferences, and published in open-access peer-reviewed journals.

NCT06093217.

Gestational weight gain (GWG) is an important indicator of maternal nutrition to be monitored during pregnancy. However, there is no evidence-based tool that can be used to monitor it across all geographic locations and pre-pregnancy body mass index (BMI) categories. The WHO is undertaking a project to develop GWG charts by pre-pregnancy BMI category, and to identify GWG ranges associated with the lowest risks of adverse maternal and infant outcomes. This protocol describes all the steps that will be used to accomplish the development of these GWG charts.

This project will involve the analysis of individual participant data (researcher-collected or administrative). To identify eligible datasets with GWG data, a literature review will be conducted and a global call for data will be launched by the WHO. Eligible individual datasets obtained from multiple sources will be harmonised into a pooled database. The database will undergo steps of cleaning, data quality assessment and application of individual-level inclusion criteria. Heterogeneity of maternal weight and GWG will be assessed to verify the possibility of combining datasets from multiple sources and regions into a single database. Generalized Additive Models for Location, Scale and Shape will be applied for the construction of the centile curves. Diagnostic measures, internal and external validation procedures will also be performed.

This project will include an analysis of existing study de-identified data. To be included in the pooled database, each included study should have received ethics approvals from relevant committees. Manuscripts will be submitted to open-access journals and a WHO document will be published, including the GWG charts and cut-offs for application in antenatal care.

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract distinguished by progressive bowel damage with a risk of structuring and penetrating complications. It is characterised by focal or segmental transmural inflammation that disrupts intestinal mucosal integrity and favours the development of abscesses and fistulas. Perianal fistula develops in 13%–39% of patients with CD. Their care is difficult but improves with medical and surgical treatment to preserve anal continence and avoid a maximum proctectomy. Combined treatment with seton placement and concomitant anti-TNF (infliximab, adalimumab) allows wound healing in 40%–70% of cases. The currently available treatments are not curative and fail to provide a long-term resolution. The injection of adipose stromal cells is currently being evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischaemia, osteoarthritis, systemic sclerosis, etc). Immunoregulatory and anti-inflammatory properties of AdMSC (adipose-derived stroma/stem cells) are responsible for accelerating healing and represent an innovative approach for treating perianal fistulas associated with CD.

This phase I/IIa study is designed to assess the treatment of complex perianal fistulas linked with CD after failure of conventional treatment by injection of AdMSC (CellReady) into the fistula. Two doses of associated AdMSC will be tested for a dose escalation (5x10⁷ and 10x10⁷ cells) and injected into the wall of the fistula. Those eligible for inclusion include patients with controlled luminal CD characterised by a Harvey-Bradshaw score below or equal to eight and diagnosed on clinical, endoscopic, histological and/or radiological criteria, a colonoscopy dating back less than 1 year without ulcer in the rectum and presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports. All patients must have social security insurance or equivalent social protection. The aim of this study is to determine the optimal dose corresponding to maximum efficacy 6 months after injection of cells with a treatment-related adverse event rate of 20%.

The EU CT number 2024-511821-75-00 was approved by the following Ethics Committee: CPP (committee for the protection of persons in French: comité de protection des personnes) Ouest 1 – Tours #2024UEMED-18 and ANSM (French Agency for the Safety of Health and Medicinal Products in French : Agence nationale de sécurité du médicament et des produits de santé) #2024-511821-75-00 (Sponsor number RC31/13/7030, protocol V2.1). The results will be disseminated through conventional scientific channels.

NCT06636032.

The results will be disseminated through conventional scientific channels.

Insomnia afflicts about half of outpatients with coronary heart disease (CHD) and worsens prognosis. We aimed to simulate the potential socioeconomic savings of integrating group cognitive–behavioural therapy for insomnia (gCBT-I) into cardiac outpatient care for patients with CHD compared with usual care.

Early health technology assessment using prospective and cross-sectional cohort data.

Secondary care for outpatients with CHD in Norway in a non-university hospital setting.

A hypothetical cohort of 100 outpatients with CHD and insomnia.

Weekly sessions of gCBT-I over 5 weeks versus usual care.

Potential savings related to possible effects on revascularisations and hospitalisations due to a recurrent CHD event, and reduced sick leave. Representative data on healthcare consumption and sick leave rates were collected from the NORwegian CORonary cohort study (n=528). Costs of productivity loss were drawn from public sources and calculated using a conservative human capital approach. Estimates of therapeutic effectiveness in conveying insomnia remission by gCBT-I were informed by results from randomised trials and meta-analyses.

Rates of healthcare consumption and sick leave were higher in outpatients with CHD and insomnia compared with those without insomnia. Our model indicated that treating 100 patients with gCBT-I would cost 2406. If patients treated with gCBT-I show similar rates of revascularisations and hospitalisations as those without insomnia, there is a maximum potential saving of 117,221 per 100 patients tied to healthcare consumption. Similarly, the maximum potential savings related to reduced productivity loss from sick leave range from 53,244 to 692,172.

Treating insomnia among outpatients with CHD has the potential for substantial reduction of socioeconomic costs related to healthcare consumption and sick leave. Implementation into routine outpatient care seems relevant, but randomised controlled trials investigating the effects of gCBT-I in this population are warranted.

Worldwide, one in three adults lives with multiple long-term conditions (MLTCs) and requires ongoing management and self-management. Socioeconomic deprivation exacerbates health inequalities due to limited resources and opportunities. In England, people living in deprived areas tend to develop MLTCs earlier and have a...

Shoulder osteoarthritis most commonly affects older adults, causing pain, reduced function and quality of life. Total shoulder replacements (TSRs) are indicated once other non-surgical options no longer provide adequate pain relief. Two main types of TSRs are widely used: anatomic TSR (aTSR) and reverse TSR (rTSR). It is not clear whether one TSR type provides better short- or long-term outcomes for patients, and which, if either, is more cost-effective for the National Health Service (NHS).

RAPSODI-UK is a multi-centre, pragmatic, two-parallel arm, superiority randomised controlled trial comparing the clinical- and cost-effectiveness of aTSR versus rTSR for adults aged 60+ with a primary diagnosis of osteoarthritis, an intact rotator cuff and bone stock suitable for TSR. Participants in both arms of the trial will receive usual post-operative rehabilitation. We aim to recruit 430 participants from approximately 28 NHS sites across the UK. The primary outcome is the Shoulder Pain and Disability Index (SPADI) at 2 years post-randomisation. Outcomes will be collected at 3, 6, 12, 18 and 24 months after randomisation. Secondary outcomes include the pain and function subscales of the SPADI, the Oxford Shoulder Score, health-related quality of life (EQ-5D-5L), complications, range of movement and strength, revisions and mortality. The between-group difference in the primary outcome will be derived from a constrained longitudinal data analysis model. We will also undertake a full health economic evaluation and conduct qualitative interviews to explore perceptions of acceptability of the two types of TSR and experiences of recovery with a sample of participants.

Ethics committee approval for this trial was obtained (London - Queen Square Research Ethics Committee, Rec Reference 22/LO/0617) on 4 October 2022. The results of the main trial will be submitted for publication in a peer-reviewed journal and using other professional and media outlets.

ISRCTN12216466.

Childhood cancer survivors (CCSs) experience educational disruptions during and following treatment, yet robust, longitudinal evidence on educational performance remains limited. We will investigate differences in educational outcomes between CCSs and non-cancer peers during primary and secondary school. We will also explore how sociodemographic factors and age at diagnosis contribute to potential differences in General Certificate of Secondary Education (GCSE) examinations, a critical indicator of future academic and employment prospects.

We will use the Education and Child Health Insights from Linked Data (ECHILD) to capture linked health and education data for children born in National Health Service (NHS)-funded hospitals in England. We will generate birth cohorts spanning September 1997 to August 2015 (estimated sample size: ~10 million), formed of pupils expected to have undertaken national curriculum assessments between academic years 2004/2005 and 2021/2022 including Key Stage (KS) 1, 2 and 4, corresponding to ages 7, 11 and 16 respectively. Cancer diagnosis will be identified from inpatient hospital records, using International Classification of Diseases, 10th Revision codes (ICD-10). We will investigate differences between CCS and their non-cancer peers in terms of their sociodemographic characteristics and describe trends in educational performances at all KSs, recorded Special Educational Needs and Disabilities (SEND) and school absences. Differences in KS4 (GCSE) performances between CCS and non-cancer peers will be quantified, according to and accounting for geographic region, sex, deprivation, ethnicity and birth characteristics. To assess whether cancer diagnosis disrupts academic trajectories, we will restrict analysis to those with KS2 attainment data and investigate KS4 performance. We will finally explore the influence of age at diagnosis on educational performance at KS4.

Ethics approval was granted by NHS Health Research Authority Research Ethics Committee (20/EE/0180). Findings will be shared with academics, policymakers, children and families affected by childhood cancer, and published in journals. Code/metadata will be shared on ECHILD GitHub repository.

Physical activity is crucial for young children’s health and development. Many young children do not meet the recommended 3 hours of daily physical activity, including 60 min of energetic play. Early childhood education and care (ECEC/childcare) is a key setting to intervene to improve children’s physical activity. The Play Active programme is a scalable evidence-informed ECEC-specific physical activity policy intervention with implementation support strategies to improve educators’ physical activity-related practices.

This hybrid type III effectiveness-implementation trial will use a quasi-experimental repeated measures design to assess the real-world effectiveness of Play Active’s scalable implementation support strategies in helping ECEC services adopt the practices included in the Play Active policy. Secondary aims will examine changes in educator-reported and device-measured children’s physical activity; assess the sustainability of the programme; identify effective dissemination strategies; assess cost-effectiveness; and involve comprehensive process evaluation. All ECEC services in Western Australia (n=776), Queensland (n=1744) and South Australia (n=445) will be invited to participate. Data will be collected at baseline, 6, 12, 18, 24 and 30 months.

Ethics approval has been provided by The University of Western Australia Human Research Ethics Committee (HREC) (2023/ET000187), the University of Queensland HREC (2024/HE000076) and the University of South Australia HREC (206023). This real-world trial of Play Active is vital for understanding its implementation in practice and to generate evidence for further scale-up and roll-out nationally. Key findings will be disseminated to stakeholders, collaborators, policy-makers as well as families and practitioners in the ECEC sector.

ACTRN12624000406505.

Continuous glucose monitoring (CGM) provides real-time glucose data for people with diabetes. However, detailed knowledge of its use in daily life remains limited. We aim to investigate the interaction between people with type 1 diabetes (T1D) and their CGM data and the impact of the interaction on glycaemia and diabetes distress.

This is a two-centre observational study of adults (n=500) with T1D using FreeStyle Libre 2. Over a period of 14 days, participants will continue their regular CGM use, record insulin doses and timing with smart insulin pens, track activity and sleep with an activity tracker, log all food intake in the LibreLink app and answer questions about quality of life and hypoglycaemia two times per day. Before the study period, the participants will complete a survey of 11 validated questionnaires assessing diabetes distress, hypoglycaemia awareness and other patient-reported outcomes (PROs). After the study period, the participants will complete two additional questionnaires assessing diabetes distress and health literacy.

The collected data will be used in two substudies with the overall aims of:

Substudy 1: to investigate how CGM is used in practice and the impact of the interaction on diabetes distress and glycaemia.

Substudy 2: to investigate whether and how CGM functions as a technological substitute for impaired awareness of hypoglycaemia, focusing on alarm data.

Endpoints will include CGM metrics, alarm data and PROs.

The Danish Data Protection Agency approved the study (P-2024–15985), and the regional committee on health research ethics has granted an ethical waiver (H-24014662). All participants have signed written informed consent forms before participating. The results will be published in an international peer-reviewed scientific journal by the study investigators and shared via www.clinicaltrials.gov. Participants who agreed to receive information about the study will be sent the results after publication.

ClinicalTrials.gov (NCT06453434).

Video games have been linked to a range of positive and negative effects on the mental health of adolescents and young adults. However, to better understand how games affect the mental health of young people, their use and experiences must be situated in the sociocultural and personal life contexts of individuals. Drawing from a cultural-ecosocial approach, this study combines cross-sectional and digital phenotyping measures to examine the effects of video games on the mental health of youth.

Participants will be young people aged 16–25 years from the community and living in the province of Quebec, Canada. An initial sample of 1000 youth will complete a cross-sectional survey online, including measures of socio-demographic context, gaming practices and experiences, streaming practices and experiences, as well as personality and well-being. Qualitative questions will explore personal views on games and mental health. A subsample of 100 participants will be selected for digital phenotyping, including daily surveys of well-being, gaming, streaming and social experiences, combined with passive mobile sensing (eg, geolocation). Analyses will include regression and mixed models for quantitative data, reflexive thematic analysis for qualitative data, and an integration of quantitative and qualitative results using participatory methods.

The study received ethical approval from the Institutional Review Board of McGill University (24-02-015). The dissemination of results will be conducted in partnership with a multi-stakeholder advisory committee, including youth who play video games, and will involve peer-reviewed publications, presentations to policymakers in Quebec, and workshops for clinicians and researchers.

Dyspnoea frequently leads to admissions in the Emergency Department (ED). Rapid and accurate diagnosis, specifically to distinguish acute heart failure from pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD), is imperative to initiate appropriate therapy. This study aims to evaluate the feasibility and performance of the EMERgency ALgorithm efficiency for Dyspneic patient-UltraSound (EMERALD-US) algorithm using ultrasound (US) to diagnose the etiology of dyspnea in the ED-admitted patients.

225 patients of 50 years and above, presenting with acute non-traumatic dyspnoea, across six participating EDs will be enrolled. Patients will undergo a lung, a simplified four-chamber cardiac and a venous US. A physician, blinded to any clinical data or previous results, will execute the algorithm. The algorithm’s performance will be assessed using a receiver operating characteristic (ROC) curve. Secondary objectives include an evaluation of the protocol’s feasibility in the ED, an assessment of the concordance between the EMERALD-US algorithm diagnoses and results from other diagnostic tests (including laboratory work and imaging), as well as an evaluation of the algorithm’s performance in diagnosing other causes of dyspnoea, such as pulmonary embolism or pleural effusion, and the 30-day mortality rate.

The study protocol was approved by the French Committee for the Protection of Persons (CPP) (RCB n°2018-A02136-49). Misdiagnosis of dyspneic patients on ED admission has been associated with inappropriate treatment, prolonged hospital stays and increased mortality, particularly among elderly patients. The implementation of protocols like the EMERALD-US algorithm can help physicians in expedited decision-making and diagnosis without increasing ED visit durations.

NCT03691857.

An increasing number of teenagers and young adults (TYA) with chronic conditions and complex needs are transitioning from paediatric to adult services, including admission to intensive care units (ICUs). As these services are often ill-equipped to care for TYA, there is a risk of compromised care. Despite recent guidelines from the UK Paediatric Critical Care and Intensive Care Societies highlighting the importance and urgency of improving ICU transition, current recommendations are not evidence-based and established pathways for ICU transition remain limited.

This mixed-methods research study aims to generate evidence to underpin national policy on transition from paediatric to adult ICUs that will improve clinical care and patient experience. To do this, we will: (1) link and analyse UK national data (years 2017–2024) on paediatric and adult ICU admissions, hospital inpatient, outpatient and emergency care visits and survival status, to determine the clinical characteristics and healthcare resource utilisation from teenage years to early adulthood of people admitted to an ICU as a young person (admission aged 14 and 15), and how these relate to ICU admissions after age 16; (2) conduct semistructured interviews, online forums and surveys with TYA patients, carers and health professionals to understand their experience of transition in ICU services; and (3) synthesise these strands of evidence and use a structured process of stakeholder engagement to propose potential targeted improvements as appropriate.

This study was approved by the East of England - Cambridge South Research Ethics Committee on 1 August 2024 (research ethics committee number 24/EE/0108), and the Health Research Authority Confidentiality Advisory Group (CAG) on 7 October 2024 (CAG number 24/CAG/0068). Study results will be actively disseminated through peer-reviewed journals, conference presentations and accessible lay texts and graphic summaries for the use of charities and patients including those with learning disabilities and neurodevelopmental disorders.

Despite growing evidence to characterise cancer-associated cognitive decline (CACD) in women with breast cancer, interventions to mitigate CACD are limited. Emerging evidence suggests aerobic exercise may enhance cognition after breast cancer diagnosis and treatment; yet, CACD remains an understudied outcome of exercise, and few high-quality studies have been conducted. In addition to knowledge gaps in effectiveness, the translation of exercise interventions to community settings remains challenging. The Breast cancer Reasoning and Activity INtervention (BRAIN) investigates the effectiveness of aerobic exercise training, delivered in a community-based setting, for improving cognitive function in women with breast cancer and gathers information on the implementation success of the intervention.

This Hybrid Type I effectiveness–implementation study is conducted at an academic medical centre in the southwestern United States in partnership with a non-profit, community health and wellness organisation. The study enrols 160 women diagnosed with stage I–IIIa breast cancer and within 3–36 months of treatment completion into a 1:1 randomised controlled trial. Individuals randomised to the exercise group receive a 6-month, individually tailored aerobic exercise programme delivered by exercise trainers employed at local community fitness centres. The programme is progressive in nature and designed to help participants achieve aerobic exercise levels consistent with guidelines for cancer survivors. Individuals randomise to the control group receive a 6-month health education control intervention delivered virtually by hospital-based health educators. Cognitive performance (primary), self-reported cognition, patient-reported outcomes, physical activity and cardiorespiratory fitness are measured at baseline, 6 months (postintervention) and 12 months (follow-up). Brain structure and function are measured via magnetic resonance imaging (MRI) at baseline and 6 months. Implementation outcomes are defined by the RE-AIM framework, which includes reach, effectiveness, adoption, implementation and maintenance. RE-AIM outcomes are measured at baseline, 6 months, 12 months and ongoing during the study.

This study was approved by the Mayo Clinic Institutional Review Board (#23-000020). All participants provide informed consent prior to participation. Findings will be disseminated to scientific, clinical and community audiences through manuscripts, presentations and newsletters.

NCT04816006.

Most older adults living in residential aged care facilities (RACFs) have at least one marker of potentially suboptimal prescribing. Pharmacists play a crucial role in medication management, with their effectiveness enhanced by using computerised decision support tools. The Pharmacists Review to Optimise Medicines in Residential Aged Care (PROMPT-RC) study aims to optimise medicine use by providing pharmacists in RACFs with an electronic medicine management app with integrated decision support (AusTAPER App/Pathway) to use as part of medication reviews they undertake.

The PROMPT-RC study is a parallel cluster randomised controlled trial design involving Australian RACFs. It will assess if pharmacists’ use of the AusTAPER App/Pathway for medication reviews improves medication regimens for RACF residents compared with usual care. Pharmacists in RACFs randomised to the intervention arm will be trained to use the AusTAPER App/Pathway, which flags potentially inappropriate medicines (PIMs) across a person’s entire medicine regimen. Pharmacists in RACFs randomised to the control arm will not have access to the AusTAPER App/Pathway—they will continue to provide usual care. The primary outcome is the difference in the number of regular medicines between treatment arms at 12 months. Secondary outcomes will measure the number of regular and pro re nata medicines, PIMs, medicine administration times, medicine regimen complexity, use of antipsychotics, antidepressants, and benzodiazepines, quality of life, mortality, instances of physical restraint, and the number of falls, hospitalisations and general practitioner/health professional visits. The cost-effectiveness of the AusTAPER App/Pathway compared with usual care will be calculated. Data collection will occur at baseline, 3, 6, 9 and 12 months postrandomisation and 3 and 6 months prebaseline. We aim to recruit 668 participants to adjust for an estimated 10% loss to follow-up, giving 334 participants in each arm. Data analysis will follow an intention-to-treat approach using a linear mixed model.

Ethical approval was obtained from The University of Western Australia Human Research Ethics Committee (Reference: 2024/ET000525; approved 14 August 2024). Reciprocal approval was also obtained in other states. This study is registered on the Australian New Zealand Clinical Trials Registry (https://anzctr.org.au). Trial findings will be disseminated through national and international peer-reviewed publications and conferences.

ACTRN12624001409561.