In current practice, fluid volumes administered to children following kidney transplant vary widely. Up to 52% of children experience fluid overload-related complications. Current fluid guidelines are not evidence-based and the optimal amount of fluid for children after transplant is not known. The aim of Randomised multiple centre trial of conservative versus LIberal fluid adMInisTration for children receiving a kidney tranSplant (LIMITS) is to determine whether relative limitation of fluid volume administered to children receiving kidney transplants is superior to liberal fluid volume administration.

LIMITS is a pragmatic, open-label, UK-based, multicentre randomised controlled trial, with an internal pilot phase and integrated economic evaluation. A total of 140 children receiving kidney transplants will be randomised to receive either conservative postoperative fluid administration (maximum of 150 mL/m²/hour for no longer than 18 hours, followed by a fixed daily target of maximum 1.5 L/m²/day thereafter) versus the comparator of liberal postoperative fluid administration (fluid volume administered to replace urine output and insensible losses for at least 48 hours with target urine output >2 mL/kg/hour). The primary outcome is mean days at home in the first 30 days after kidney transplant. The primary outcome will be analysed using a mixed linear regression model adjusted for donor type (living vs deceased donor) and participant weight (

The trial received Health Research Authority approval on 20 August 2025 (REC reference: 25/EE/0161, IRAS project ID: 354370). Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain.

ISRCTN21516608.

Empathic healthcare improves patient satisfaction with care, anxiety and pain, while reducing practitioner burnout. Artificial intelligence (AI) is continuously advancing and changing the context of empathy in healthcare. While AI may improve diagnostic accuracy or help streamline processes to reduce workload, there is a concern about how AI will impact human patient–practitioner relationships. However, patient and practitioner experiences of AI in healthcare are underexplored. We therefore aimed to synthesise the findings of qualitative studies which explore patient and practitioner experiences of empathy in AI-supported encounters in healthcare.

We will include any qualitative study in which patient or practitioner experiences of empathy with AI-assisted healthcare are explored. Secondary studies, quantitative studies and those exploring other stakeholders’ experiences will be excluded. The search will include records from database inception in any language. The search strategy is based on the Population, Phenomenon of Interest, Context framework, built around the keywords: artificial intelligence, empathy, healthcare professionals and patients. The following databases will be searched: MEDLINE, Scopus, APA PsycINFO and CINAHL. Additionally, grey literature searches in BASE and OpenAIRE. Forward and backward citation chasing will also be conducted. Records will be screened by two independent reviewers, data extraction will be conducted by one reviewer and checked by another. The risk of bias assessment will be conducted in duplicate using the Joanna Briggs Institute appraisal tool for qualitative studies. The results will be synthesised using thematic synthesis. The number of records identified from the search and the exclusions to reach the total number of included records will be presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The included studies will be listed, along with summaries of relevant study characteristics and risk of bias assessments. Confidence in the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation - Confidence in the Evidence from Reviews of Qualitative research framework.

The systematic review will include only previously anonymised data from primary studies. For this reason, ethical approval is not required for this study. Dissemination of the findings of the final systematic review will occur through publishing in a peer-reviewed journal.

CRD420261301427.

In many low-income and lower-middle-income countries (LMICs), palliative care services are limited and much of the care for adults with advanced cancer is provided by family caregivers. This review aims to explore the family caregiver experience in providing palliative care to adult patients with cancer in LMICs.

This qualitative systematic review will be conducted using a comprehensive search strategy on PubMed (MEDLINE), Embase, CINAHL and PsycINFO without language or date restrictions. The COnnecting REpositories (CORE) database of the Open University will be searched for grey literature. Review questions will follow the PICo framework (Population, Phenomena of Interest and Context). Qualitative or mixed-method studies on the experience of family caregivers of adult patients with cancer (above 18 years) receiving palliative care in LMICs will be included. Study quality will be assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. Findings will be synthesised using meta-aggregation or with a narrative synthesis if pooling is not feasible. The review process will follow the JBI methodology for systematic reviews of qualitative evidence and will be reported according to the ENhancing Transparency in REporting the synthesis of Qualitative research (ENTREQ) framework.

No ethical approval is required as the study involves secondary data analysis of published literature. Ethical principles of accurate reporting and transparency will be upheld. Findings will be published in peer-reviewed open-access journals and presented at academic conferences. Recommendations will be shared with policymakers and healthcare organisations responsible for the provision of palliative care for patients with cancer in LMICs.

CRD420251010556.

Aboriginal women in the remote Northern Territory (NT) experience high rates of adverse pregnancy outcomes related to hyperglycaemia in pregnancy. Oral glucose tolerance test (OGTT) screening was recommended in early pregnancy but barriers to uptake exist.

To examine uptake of screening for hyperglycaemia in pregnancy among Aboriginal women in remote NT communities and explore adverse pregnancy outcome rates among women who did not have early OGTT screening compared with women who did undergo screening in early pregnancy and those with pre-existing diabetes.

Retrospective observational cohort study of pregnancies among Aboriginal women in remote NT clinics from January 2017 to December 2019. Screening for hyperglycaemia in pregnancy included having an early OGTT (

Among 1191 pregnancies in 52 remote communities, pre-existing type 2 diabetes (T2D) was diagnosed in 6.4% (n=76) and gestational diabetes mellitus (GDM) was diagnosed in 13% (154/1191). Excluding women with pre-existing diabetes, 226 (20%) had an early OGTT. Guideline-directed screening (with either (a) an early OGTT diagnosing GDM or (b) a negative early OGTT followed by a routine OGTT) occurred in 14% of pregnancies (n=158). Compared with women who had an early pregnancy OGTT, the combined adverse pregnancy outcome was more common among women with pre-existing T2D (89% vs 54%, adjusted OR 6.06 (95% CI 2.75 to 13.35)) and similar among women who did not undergo early OGTT (50%, adjusted OR 0.97 (95% CI 0.71 to 1.32)).

Uptake of guideline-directed screening in Aboriginal women in remote NT was low, although there was no difference in pregnancy outcomes for women who were and were not screened with an early OGTT. Rates of adverse pregnancy outcomes were concerningly high in women with pre-existing T2D, highlighting a need to strengthen diabetes care for these women.

Remote consultations (video, telephone, text) have become integral to the delivery of primary care and are promoted by government initiatives. While many find these more convenient, they may also discriminate against those with lower digital literacy and present a barrier to empathy by removing some non-verbal communication. The aim of this realist review is to understand how therapeutic empathy can be effectively expressed during remote consultations in general practice across different situations and for different people.

This realist review will follow the methodological framework proposed by Pawson and colleagues, which includes the following five steps: (1) identify existing theories to develop an initial programme theory; (2) systematically search bibliographic databases to identify relevant literature; (3) select, extract and organise data; (4) synthesise evidence to develop context-mechanism-outcome configurations; (5) refine and finalise programme theory. This iterative process will be guided by a Content Expert Group consisting of patients, carers, clinical staff working in general practice and representatives from national stakeholder groups. The final programme theory will inform the development of evidence-based recommendations to help clinical staff working in general practice express empathy during remote consultations.

This review does not require ethics approval. Findings will be disseminated through peer-reviewed journals, national and international conferences and through relevant professional associations and primary care networks in the UK.

CRD420261306014.

Deficiencies in non-technical skills—including communication and leadership—are well-established causes of clinical errors in healthcare. Healthcare students and professionals increasingly use high-fidelity and virtual reality (VR) simulation to replicate clinical practice, through immersive and realistic scenarios in a risk-free teaching setting. However, there is no up-to-date, high-quality synthesis of the effects of high-fidelity and VR simulation on non-technical skills for healthcare students and professionals. A systematic review and meta-analysis of this literature is required to enhance the current knowledge.

This protocol has been reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. We will include randomised trials and other controlled studies that report differences in non-technical skills between high-fidelity and VR simulation. We will search MEDLINE, Scopus, EMBASE, ERIC and CINAHL, from database inception. We will also search reference lists and contact experts to identify additional studies. Two independent reviewers will screen titles and abstracts, review full texts, and extract data. Discrepancies will be resolved through discussion, with a third reviewer if necessary. For randomised trials, we will use the Cochrane Risk-of-Bias 2.0 (RoB2) tool to evaluate the risk of bias in the included studies. For non-randomised studies, we will use the Risk Of Bias In Non-randomized Studies (ROBINS-1) assessment tool. If appropriate, meta-analysis will be performed. We will analyse continuous outcomes using weighted mean differences (with 95% CIs) or standardised mean differences (with 95% CIs) if different measurement scales are used. We will use subgroup and sensitivity analyses to explore heterogeneity. The overall certainty of evidence will be assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) tool.

Ethical approval is not applicable for this study because no primary data have been collected. This review will be disseminated through peer-reviewed publication and presented at conferences to inform ongoing educational practises.

CRD420251136479.

To assess the prevalence of dyslipidaemia and associated risk factors, and evaluate low-density lipoprotein cholesterol (LDL-C) target attainment among adults in the Western Province of Sri Lanka.

Cross-sectional epidemiological study.

Western province, Sri Lanka.

Participants were recruited through a community-based survey of non-institutionalised adults aged ≥20 years residing in the Western Province for at least 1 year (n=1800), using multistage stratified random cluster sampling.

Dyslipidaemia was defined according to the National Cholesterol Education Programme/Adult Treatment Panel III guidelines. Prevalence estimates are presented with 95% CIs. Multiple logistic regression results are reported as adjusted ORs with 95% CIs.

Cardiovascular risk in participants aged ≥40 years was assessed using the WHO laboratory-based cardiovascular disease (CVD) risk chart for South-East Asia. Achievement of LDL-C targets was evaluated according to the Sri Lankan guidelines on management for dyslipidaemia management.

Data from 1333 subjects were analysed. Mean age was 49.8 (±14.9) years. The majority were females (63.6%). The age-sex standardised prevalence of any form of dyslipidaemia was 73.3% (95% CI 70.9% to 75.7%). Age standardised prevalence in females was 77.1% (95% CI 74.3% to 79.9) and males was 69.3% (95% CI 65.3% to 73.3%). The most prevalent type of dyslipidaemia was low high-density lipoprotein cholesterol (HDL-C) (46.6%, 95% CI 43.9% to 49.3%), followed by high LDL-C (32.5%, 95% CI 30.0% to 35.0%) and high triglycerides (21.7%, 95% CI 19.5% to 23.9%). Low HDL-C was positively associated with smoking (OR: 1.89, 95% CI 1.16 to 3.18) and inversely with male sex (OR: 0.29, 95% CI 19 to 0.45) and physical activity (OR: 0.71, 95% CI 0.51 to 0.99). Elevated LDL-C was associated with male sex (OR: 1.84, 95% CI 1.2 to 2.89), diabetes (OR: 5.34, 95% CI 3.53 to 8.08), and hypertension (OR: 1.62, 95% CI 1.18 to 2.23). Male sex (OR: 1.85, 95% CI 1.08 to 3.18), diabetes (OR: 1.9, 95% CI 1.4 to 2.58) and hypertension (OR: 1.81, 95% CI 1.12 to 2.91) were positively associated with elevated triglycerides, whereas urban sector (OR: 0.54, 95% CI 0.32 to 0.91) was protective. Physical activity (OR: 0.65, 95% CI 0.44 to 0.98) and male sex (OR: 0.52, 95% CI 0.31 to 0.89) inversely associated with any form of dyslipidaemia, whereas diabetes (OR: 7.08, 95% CI 3.99 to 12.55), hypertension (OR: 1.93, 95% CI 1.36 to 2.73), and body mass index (OR: 1.06, 95% CI 1.01 to 1.2) were positively associated. The majority of participants (66.6%) had a

Three-fourths of adults in Western Province, Sri Lanka had any form of dyslipidaemia, more common in females. Low HDL-C was the most frequent abnormality. Most participants aged above 40 years were at low cardiovascular risk, yet two-thirds failed to meet LDL-C targets. Non-communicable disease prevention in Sri Lanka should expand through population-wide strategies, including awareness campaigns, promoting self-monitoring, targeted education and surveillance to evaluate interventions.

Primary biliary cholangitis (PBC) is a rare chronic cholestatic disease that despite current therapy has significant ongoing unmet needs, including risks of cirrhosis and life-impairing symptoms. The current treatment approach is a step-up model, wherein first-line therapy, ursodeoxycholic acid (UDCA), is given for a minimum of 12 months before the addition of second-line therapy is considered for non-responding patients. This ‘waiting to fail’ approach, focused on the needs of low-risk patients, allows, we postulate, a key process of biliary epithelial cell (BEC) senescence to become established, driving accelerated bile duct loss and aggressive disease. Preclinical mouse modelling has shown that early use of the farnesoid X receptor agonist obeticholic acid (OCA), currently only used as second-line therapy following UDCA failure, reverses BEC senescence, changing the clinical course of disease. Here, we describe the design of the Optimising Primary thErapy in pRimAry biliary cholangitis (OPERA) trial. The aim of OPERA is to explore a new paradigm for disease-modifying treatment of PBC: risk-informed early treatment stratification, with patients at increased risk offered UDCA and OCA combination with the goal of complete biochemical remission.

OPERA is a multicentre, randomised, double-blind, placebo-controlled trial of OCA in combination with UDCA, as first-line treatment for high-risk PBC. This is a multicentre trial in England, which will be undertaken in specialist clinics in secondary/tertiary referral centres (or as per local set up). These centres will be specialists in the area of PBC management and will manage patients from across their local region. OPERA will recruit and randomise 106 adults, within 6 months of PBC diagnosis, who are at an enhanced risk of non-response to standard first-line therapy, between either: (1) UDCA and OCA or (2) UDCA and matched placebo in a 1:1 ratio. The primary efficacy outcome measure is the percentage of participants showing normalisation of serum alkaline phosphatase and total bilirubin values at 26 weeks (disease remission).

Favourable ethical opinion was received from London – Riverside Research Ethics Committee (reference: 22/LO/0878). Potential participants will be fully informed of their rights and the benefits and harms of the trial by the research team before giving informed consent to participate in the trial. Results will be disseminated in peer-reviewed publications, at national and international conferences, in peer-reviewed journals and to participants and the public (using lay language).

ISRCTN17176388.

Stress and burnout are pervasive among physicians. Academic physicians who are female and physicians who are under-represented in medicine (URM) face inequities in the workplace and beyond. Understanding their experiences is crucial for workforce sustainability and diversity, especially given the disproportionate effects on these individuals and overall workforce capacity.

To qualitatively explore the perspectives of academic female and URM physicians and identify key themes affecting their careers and well-being.

Semi-structured interviews were conducted with 30 physicians at an urban academic health system. Interviews were audio-recorded, transcribed and thematically analysed using a general inductive approach. Interview guides were informed by prior literature and constructs.

None.

Female and URM physicians from a large, academic medical centre were recruited via email. Participants self-reported demographic information, including sex, race, ethnicity and tenure.

The primary outcomes encompassed the main themes identified through the analysis of interviews with female and URM physicians regarding their perspectives on well-being, mental health and academic medicine.

30 female or URM physicians were interviewed (27 (90%) female; 14 (47%) black, Asian or multi-racial). Thematic analysis revealed four key themes: physician identity (URM, female, family), well-being in the workplace (emotional health, staffing burden, non-clinical responsibilities), barriers to accessing well-being resources (workplace environment, culture, overgeneralisation) and facilitators to well-being (physician camaraderie, leadership support). Physicians discussed how their identities influenced their experiences of well-being. They highlighted emotional health challenges, staffing burdens and administrative tasks contributing to stress. Barriers to accessing resources included workplace culture and broad-based interventions, while supportive leadership and camaraderie were identified as facilitators of access.

Female and URM physicians face systemic challenges impacting their well-being and careers. These findings underscore the need to address systemic changes and specifically design programmes focused on promoting the well-being and inclusivity of female and URM physicians. Tailored interventions to these individuals, supportive leadership structures and collaborative working cultures are crucial for addressing these issues and sustaining a diverse physician workforce.

Previous reviews have investigated the relationship between empathy and burnout. However, these are now out of date, did not capture the effect of the pandemic, did not include healthcare professionals other than doctors and nurses or medical students, did not assess the impact of differences in profession and did not pool the data, which made estimating the strength of the association unclear. We therefore aim to address these shortcomings in an up-to-date, rigorous, systematic review and meta-analysis.

Findings will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and flowchart.

We will search American Psychological Association (APA) PsycINFO, APA PsycArticles, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, PubMed and Scopus. We will also search ResearchSquare and Social Science Research Network (SSRN) for preprints; ProQuest Dissertations and Theses and Electronic Theses Online Service for relevant theses. Forward and backward citation searches will identify additional studies. Two independent reviewers will screen titles, abstracts and full texts and extract data. Two independent reviewers will assess risk of bias using Risk of Bias 2 (RoB 2) for randomised controlled trials, Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) for non-randomised interventional studies and Risk of Bias in Non-randomised Studies of Exposures (ROBINS-E) for observational studies.

For all included studies, we will summarise the study characteristics, including number of participants; health profession, specialty and career stage; country and gender. If data are suitable, we will pool results and conduct subgroup analyses (including by health profession, career stage and clinical specialty). We will also explore the relationships between subscales of empathy and burnout. We will use metaregression to explore the impact of theoretically derived factors (such as study design and profession) on the strength of the association. Sensitivity analyses will assess the impact of low-quality research. In our discussion, we will summarise results, the limitations and provide a general interpretation of the results and implications.

Ethical approval is not required for this review, as primary data will not be collected. The review will be disseminated through peer-reviewed publication and presentation at conferences.

CRD420251075618.

For adolescents living with higher body weight, changing lifestyle behaviours can be met with challenges due to psychosocial factors, such as mental health and emotional challenges. Few behavioural interventions have included skill development to manage these mental health and emotional challenges.

The feasibility of a dialectical behavioural therapy (DBT)–enhanced lifestyle intervention will be evaluated through a pilot randomised controlled trial. We will recruit 90 adolescents aged 14–17 years with a body mass index Z-score >1.4 and mild-to-moderate depressive symptoms to participate with a caregiver in the trial. Adolescents will be randomised 2:2:1 to one of the three study arms: (A) behavioural lifestyle intervention with DBT skills training, (B) behavioural lifestyle intervention alone (ie, without DBT skills training) or (C) control. The interventions will include two sessions weekly for 16 weeks that include (1) one modified DBT skills training with two facilitators, supervised by a clinical psychologist, combined with one behavioural lifestyle session delivered by a dietitian and/or a kinesiologist and (2) two behavioural lifestyle sessions alone. DBT skills training will consist of teaching mindfulness, emotion regulation, distress tolerance, interpersonal effectiveness and walking the middle path modules. Behavioural sessions will be guided by evidence-based practices for goal setting, dietary counselling, improving sleep, reducing screen time and structured physical activity. The main outcomes are enrolment rates, adherence to the intervention and retention rates for follow-up measurements. The secondary outcome will be changes in the quality of life (Pediatric Quality of Life Inventory) and daily physical activity levels between baseline and immediately post-intervention. Adolescents will participate in a focus group incorporating photo elicitation to explore satisfaction, acceptability and perceived benefits of the study arms.

This study has received ethical approval from the University of Manitoba’s Biomedical Research Ethics Committee (HS24295-H2020:427), Hamilton Health Sciences & McMaster University (HiREB 18159) and The Conjoint Health Research Ethics Board (CHREB), University of Calgary (REB24-1084). Results will be disseminated through publication in peer-reviewed journals and be relevant to researchers and clinicians involved in paediatrics and paediatric weight management.

NCT05338944.

Leptospirosis is a significant public health concern worldwide, as it imposes a substantial economic burden on the global economy. Despite a comprehensive search of the relevant literature, few studies evaluating the economic burden experienced by leptospirosis patients were identified. In particular, very few studies thoroughly examined the cost components, including direct, indirect and intangible costs. This paucity of evidence further motivates the need to conduct a more focused search using a systematic review approach. Thus, this study aims to systematically review the global literature on the magnitude and aspects of the direct, indirect and intangible costs incurred by leptospirosis patients and the methods available for assessing these costs.

This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines. The Population, Intervention, Comparison, Outcomes, Study Design framework was used to develop the review questions. The search strategy will comprise two key term blocks: ‘Leptospirosis’ and ‘Economic cost’. A comprehensive literature search will be conducted in PubMed, Web of Science, Scopus, MEDLINE, CINAHL, the Cochrane Library, EconStor and IDEAS to collect publications from inception to July 2025. The search will be limited only to English-language and peer-reviewed publications. The Mixed Methods Appraisal Tool will be used to assess the quality of eligible studies. Extracted cost data will be categorised into direct, indirect and intangible costs. A meta-analysis will be conducted to quantify the magnitude of these costs if sufficient methodological and contextual homogeneity exists. Moreover, a narrative synthesis will be performed to analyse the qualitative data related to intangible costs.

As this study will use secondary data, ethical approval is not required. The systematic review’s findings will be published in a scientific journal and presented at relevant conferences to address the knowledge gap regarding the economic burden (including direct, indirect and intangible costs) faced by leptospirosis patients. The results of this systematic review will guide policies for prioritising prevention, improving surveillance and efficiently allocating resources to control leptospirosis.

PROSPERO CRD 42024585056.

Paediatric palliative care (PPC) improves the quality of life of children with life-limiting and life-threatening conditions, with caregivers playing an important role. Providing PPC in low-income and lower-middle-income countries (LMICs) is challenging due to limited resources, inadequate access to specialised care, financial constraints, and cultural or religious beliefs. This study aims to synthesise qualitative research on the experiences of primary care givers caring for children with cancer receiving palliative care in LMICs.

A systematic search will be conducted using electronic databases: MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, CINAHL (Cumulative Index to Nursing and Health Literature), Web of Science, and PsycINFO. Additional articles will be searched in the reference list of the selected articles. Review questions will be framed into different components according to the Population, phenomena of Interest, Context, and Outcome (PICO) framework. Primary caregivers of children with cancer will be the population of interest. Both title and abstract screening and full-text screening will be done by two independent reviewers. The quality of included studies will be assessed using the Joanna Briggs Institute critical appraisal checklist for qualitative research. The thematic synthesis approach will be followed as it will allow a transparent summarising of the qualitative data.

This study is not subject to ethics approval, as the work is carried out on published documents. The findings of this review will be disseminated among a broader audience through scientific channels, including publication in open-access journals and presentations at both national and international forums.

CRD420251065491.

Severe pectus excavatum (PE) may impair cardiopulmonary and physical function. The effectiveness of surgical treatment to correct PE and restore physical function is widely debated due to a lack of high-quality comparative evidence. The RESTORE trial aims to determine the clinical and cost-effectiveness of corrective surgery for severe PE compared with conservative management for the first time in a randomised controlled trial (RCT).

RESTORE is a pragmatic, multicentre, RCT with an embedded observational cohort. 200 participants aged ≥12 years with severe PE will be recruited at around 12 National Health Service cardiothoracic surgical centres in England. Participants will be randomised 1:1 to receive either surgery within 3 months of randomisation (intervention arm) or no surgery until after the primary outcome measurement at 1 year (comparator arm). The primary outcome is change in physical functioning from baseline to 1 year as measured by the Short Form Health Survey (SF-36v2) physical function score. The primary economic outcome is cost-effectiveness. The key secondary outcome is change in % predicted VO_2peak at 1 year measured by cardiopulmonary exercise test (CPET). Outcomes will be assessed at 1 year post-randomisation in the comparator arm and 1 year post-surgery in the intervention arm. The primary analyses will be undertaken on an intention-to-treat population using a linear mixed-effects model, adjusted for stratification variables via a binary covariate. Other secondary outcomes will include change from baseline of cardiopulmonary function (CPET and spirometry), health-related quality of life using the EuroQol 5 Dimension 5 Level (EQ-5D-5L) and SF-36v2 questionnaires, Hospital Anxiety and Depression Scale and disease specific symptoms (Phoenix Comprehensive Assessment for Pectus Excavatum Symptoms and Pectus Excavatum Evaluation Questionnaire). Adverse events, complications from surgery and operative technical success (Haller and Compression Indices from preoperative and postoperative CT scans) will also be assessed. Health economic analysis will estimate the incremental cost per quality adjusted life year at 1 year.

The trial was approved by East of Scotland Research and Ethics Service (24/ES/0034). Participants who are ≥16 years of age will be required to provide written informed consent. For participants

ISRCTN11359779.

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.