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.

Early-onset chronic liver disease (CLD) and its subsequent clinical progression have systemic impact. Its trajectory coincides with critical periods of brain development. In this study, we will test the hypothesis that early-onset CLD is associated with neurodevelopmental and psychiatric symptoms and delineate their neurobiological underpinnings through multimodal neuroimaging.

This study will recruit 100 patients with biliary atresia and 50 patients with other types of early-onset CLD, aged between 6 and 30 years, under the primary care of Paediatric Liver Services at King’s College Hospital, London, UK. Cognitive performance and autism-related behaviours will be evaluated with neurodevelopmental assessments. Participants and their parents will complete questionnaires addressing neurodevelopmental and psychiatric outcomes in everyday life, and quality of life. Multimodal neuroimaging will be conducted using electroencephalography (EEG); eye-tracking; structural, functional and diffusion MRI; and magnetic resonance spectroscopy (MRS). Clinical information will be collected from patients’ medical records and bio samples. Data of 222 neurotypical controls and 307 neurodivergent controls without CLD will be pooled from the Longitudinal European Autism Project with a similar study protocol. Neurodevelopmental and psychiatric outcomes will be compared with normative values and between groups. Associations with clinical risk factors will be explored using multivariable regression. Neuroimaging markers will be compared between groups and associations with neurodevelopmental outcomes and clinical risk factors will be tested using multivariable regression. Individual deviation from normal brain development will be quantified using Bayesian modelling and will be associated with neurodevelopmental outcomes.

This study was approved by the National Health Service Health Research Authority’s ethical committee (REC reference: 22/PR/1587). Findings from this study will be published in peer-reviewed journals, presented at national and international conferences and shared with patients and their families for widespread dissemination of the results.

Falls are a critical problem for older people, including those from ethnically diverse communities, who are under-represented in research. The aim of this pilot trial is to evaluate (1) the implementability of a co-designed intervention developed to support the sustained uptake of tailored exercise to reduce falls (MOVE Together: Reduce Falls) and (2) the feasibility of conducting a randomised controlled trial (RCT) in older people from Italian, Arabic, Cantonese or Mandarin-speaking communities.

Investigator and assessor-blinded pilot two-arm parallel RCT. 60 older people at risk of falls from Italian, Arabic, Cantonese or Mandarin speaking communities will be recruited, with the option to enrol on their own or with another participant (dyad). Participants or dyads will be randomly assigned to the experimental or control arm. The experimental arm will receive MOVE Together: Reduce Falls, which provides up to 12 sessions with a physiotherapist over 12 months and supports participants to engage in individualised exercises. Both arms will receive educational resources in the participant’s preferred language. The primary outcome is implementability of the co-designed intervention, MOVE Together: Reduce Falls; operationalised as fidelity (>70% of intended sessions delivered), feasibility (> 95% of sessions delivered with no serious adverse events related or likely related to the intervention) and acceptability (>50% acceptability score). The secondary outcome is feasibility of the RCT protocol, which will be evaluated quantitatively (eg, recruitment and retention rates, completion of clinical outcome data including prospective collection of falls data for 12 months via falls calendars) and qualitatively (eg, barriers and enablers to data collection).

Ethical approval has been granted for this study (HREC/106010/MH-2024). Study findings will be published in peer-reviewed journals and presented at relevant conferences and community forums.

ACTRN12624000658516.

Intraoperative anaesthesia handoffs represent a risk point in the care of surgical patients. Although often necessary to prevent fatigue, improve vigilance and optimise operational efficiency, critical information can be lost, potentially leading to postoperative complications. Structured handoffs can increase the transfer of knowledge during intraoperative anaesthesia handoffs, improving their quality. We therefore propose to test the primary hypothesis that a semi-structured intraoperative anaesthesia handoff cognitive aid reduces the number of serious 30-day complications in surgical patients.

We will enrol adults having non-cardiac surgery who are scheduled to have an intraoperative anaesthesia handoff for operational reasons. We plan a cluster randomised trial (enrolling over 18 months, anticipated sample size approximately 4500 patients) that will compare the Epic Electronic Health Record intraoperative anaesthesia handoff cognitive aid to routine handoffs. Our primary outcome will be the number of serious postoperative complications within 30 days. Our secondary outcomes will be: (1) the number of minor complications; and (2) the duration of postoperative hospitalisation. Bayesian analysis with generalised linear multilevel modelling will be used to estimate the effect of structured handoffs on the primary and secondary outcomes.

This study has been approved by the local institutional review board with a waiver of informed consent. Results will be disseminated in the medical literature with de-identified data available on request.

NCT06533111.

Insomnia is a common complaint among patients with opioid use disorder (OUD) maintained on buprenorphine (BUP). However, people with OUD have historically been excluded from insomnia clinical trials, leaving clinicians without evidence-based treatment options for this patient population. Lemborexant, the Food and Drug Administration (FDA)-approved dual orexin receptor antagonist for the treatment of insomnia, was recently shown to be safe and tolerable among a sample of patients with insomnia who were maintained on BUP. We hypothesise that pharmacologically antagonising the orexin system with lemborexant may improve insomnia symptoms in individuals with OUD and also enhance BUP treatment benefits by improving performance in neurofunctional domains identified in the National Institute on Drug Abuse Phenotyping Assessment Battery.

Participants with insomnia and OUD who have been stabilised on BUP for at least 4 weeks will be randomly assigned to receive either lemborexant (n=50) or placebo (n=50) for 8 weeks. Participants will complete assessments at baseline, during the 8-week intervention, postintervention and at a 2-week follow-up. Primary outcomes are insomnia severity and impulsivity. Secondary measures include objective sleep metrics (total sleep time, sleep efficiency, sleep onset latency and wake after sleep onset) and performance in the neurofunctional domains of negative emotionality and metacognition.

The study was approved by the Virginia Commonwealth University Institutional Review Board in April 2025 (protocol number HM20031777). Data collection began in May 2025 and is expected to be completed by May 2029. The trial is conducted under FDA IND no. 154797 (FGM). The dissemination plan for the trial includes presentations at local and national conferences, submission of primary and secondary outcome manuscripts for publication in peer-reviewed journals and circulation of findings to popular media outlets, as available. Results will also be shared with interested participants and clinical collaborators upon completion of the trial.

NCT06981195.

Genomic diagnostics have accelerated therapeutic and preventative breakthroughs in oncology and cancer genetics. Despite increased access, the implementation of genomics-based care faces serious fragmentation and scalability issues due to a lack of system support. The Precision Care Initiative aims to develop a novel and scalable Precision Care Clinic (PCC). It is designed to coordinate precision medicine in oncology and streamline decision support for referring oncologists and geneticists. The PCC will enhance quality of care through multifaceted, patient-centred communication. It will also improve translational capacity by integrating team expertise in precision oncology, implementation science, clinical informatics, cancer genetics, health economics and patient-reported measures.

This programme uses a type I and type II hybrid effectiveness-implementation trial design sequentially. The complex clinical intervention is precision oncology—matching the targeted treatment or risk management strategy to the right patient, based on their genomic, cancer staging, environmental, lifestyle and biological characteristics, etc. The service intervention is the PCC, providing centralised multidisciplinary review to facilitate shared decision-making with clinicians for the provision of optimal precision oncology care for their patients. The implementation intervention is the co-designed implementation platform—applying evidence-based implementation approaches and Learning Health System principles to enhance feasibility and sustainability. All adult patients across Australia referred to the PCC (n=est. 100–150/year), and healthcare professional interest holders involved in the delivery of precision oncology services, are eligible to participate. Over the study course, phase I involves using a mixed-methods approach to inform iterative co-design and pilot testing of the first PCC with an accompanying implementation platform, and a suite of outcome measures to assess effectiveness; phase II (hybrid type I) includes the implementation of the PCC and evaluation of the outcome measures designed in phase I; phase III (hybrid type II) involves a co-design of local adaptations and testing the effectiveness of the PCC model nationally.

The study received ethical approval from the St Vincent’s Hospital Human Research Ethics Committee (2023/ETH00373). Study results will be presented at relevant conferences and published in peer-reviewed journals.

NCT06077110

This study explored how Structured Medication Reviews (SMRs) are being undertaken and the challenges to their successful implementation and sustainability.

A cross-sectional mixed methods online survey.

Primary care in England.

120 clinical pharmacists with experience in conducting SMRs in primary care.

Survey responses were received from clinical pharmacists working in 15 different regions. The majority were independent prescribers (62%, n=74), and most were employed by Primary Care Networks (65%, n=78), delivering SMRs for one or more general practices. 61% (n=73) had completed, or were currently enrolled in, the approved training pathway. Patient selection was largely driven by the primary care contract specification: care home residents, patients with polypharmacy, patients on medicines commonly associated with medication errors, patients with severe frailty and/or patients using potentially addictive pain management medication. Only 26% (n=36) of respondents reported providing patients with information in advance. The majority of SMRs were undertaken remotely by telephone and were 21–30 min in length. Much variation was reported in approaches to conducting SMRs, with SMRs in care homes being deemed the most challenging due to additional complexities involved. Challenges included not having sufficient time to prepare adequately, address complex polypharmacy and complete follow-up work generated by SMRs, issues relating to organisational support, competing national priorities and lack of ‘buy-in’ from some patients and General Practitioners.

These results offer insights into the role being played by the clinical pharmacy workforce in a new country-wide initiative to improve the quality and safety of care for patients taking multiple medicines. Better patient preparation and trust, alongside continuing professional development, more support and oversight for clinical pharmacists conducting SMRs, could lead to more efficient medication reviews. However, a formal evaluation of the potential of SMRs to optimise safe medicines use for patients in England is now warranted.

Inherited retinal diseases (IRDs) are a broad range of diseases associated with abnormalities/degeneration of retinal cells. We aimed to identify the top 10 Australian research priorities for IRDs to ultimately facilitate more meaningful and potentially cost-effective research.

We conducted a James Lind Alliance priority setting partnership that involved two Australian-wide surveys and online workshops.

Australia-wide.

Individuals aged 16 years or older were eligible to participate if they had an IRD, were caregivers of an individual with an IRD or were health professionals providing care to this community.

In Survey 1, we gathered participants’ unanswered questions about IRDs. We grouped these into summary questions and undertook a literature review to verify if they were truly unanswered (ie, evidence uncertainties). In Survey 2, participants voted for the uncertainties that they considered a priority. Top-ranked uncertainties progressed for discussion and final prioritisation in two workshops.

In Survey 1, we collected 223 questions from 69 participants. We grouped these into 42 summary questions and confirmed 41 as evidence uncertainties. In Survey 2, 151 participants voted, with the 16 uncertainties progressing to final prioritisation. The top 10 priorities, set by the 24 workshop participants, represented (1) treatment/cure; (2) symptoms and disease progression; (3) psychosocial well-being and (4) health service delivery. The #1 priority was for treatment to prevent, slow down or stop vision loss, followed by the #2 priority to address the psychological impact of having an IRD.

The top 10 research priorities highlight the need for IRD research that takes a whole-person, systems approach. Collaborations to progress priorities will accelerate the translation of research into real-world benefits.

There is an absence of real-world evidence, especially from low- and middle-income countries (LMICs), on the implementation successes and challenges of COVID-19 Test and Treat (T&T) programmes. In 2022, nirmatrelvir/ritonavir was provided as standard of care for mild to moderate COVID-19 treatment in eight LMICs (Ghana, Kenya, Laos, Malawi, Nigeria, Rwanda, Uganda and Zambia). This manuscript describes a research protocol to study novel drug introduction during the COVID-19 health emergency, with implications and learnings for future pandemic preparedness. The goal of the study is to provide simultaneous programme learnings and improvements with programme rollout, to fill a gap in real-world implementation data on T&T programmes of oral antiviral treatment for COVID-19 and inform programme implementation and scale-up in other LMICs.

This multiple methods implementation research study is divided into three components to address key operational research objectives: (1) programme learnings, monitoring and evaluation; (2) patient-level programme impact; and (3) key stakeholder perspectives. Data collection will occur for a minimum of 6 months in each country up to the end of grant. Quantitative data will be analysed using descriptive statistics for each country and then aggregated across the programme countries. Stakeholder perspectives will be examined using the Consolidated Framework for Implementation Research implementation science framework and semistructured interviews.

This study was approved by the Duke University Institutional Review Board (Pro00111388). The study was also approved by the local institutional review boards in each country participating in individual-level data collection (objectives 2 and 3): Ghana, Malawi, Rwanda, Nigeria and Zambia. The study’s findings will be published in peer-reviewed journals and disseminated through dialogue events, national and international conferences and through social media.

NCT06360783.

To compare the quality and time efficiency of physician-written summaries with customised large language model (LLM)-generated medical summaries integrated into the electronic health record (EHR) in a non-English clinical environment.

Cross-sectional non-inferiority validation study.

Tertiary academic hospital.

52 physicians from 8 specialties at a large Dutch academic hospital participated, either in writing summaries (n=42) or evaluating them (n=10).

Physician writers wrote summaries of 50 patient records. LLM-generated summaries were created for the same records using an EHR-integrated LLM. An independent, blinded panel of physician evaluators compared physician-written summaries to LLM-generated summaries.

Primary outcome measures were completeness, correctness and conciseness (on a 5-point Likert scale). Secondary outcomes were preference and trust, and time to generate either the physician-written or LLM-generated summary.

The completeness and correctness of LLM-generated summaries did not differ significantly from physician-written summaries. However, LLM summaries were less concise (3.0 vs 3.5, p=0.001). Overall evaluation scores were similar (3.4 vs 3.3, p=0.373), with 57% of evaluators preferring LLM-generated summaries. Trust in both summary types was comparable, and interobserver variability showed excellent reliability (intraclass correlation coefficient 0.975). Physicians took an average of 7 min per summary, while LLMs completed the same task in just 15.7 s.

LLM-generated summaries are comparable to physician-written summaries in completeness and correctness, although slightly less concise. With a clear time-saving benefit, LLMs could help reduce clinicians’ administrative burden without compromising summary quality.

Paediatric major trauma patients with more severe injuries and physiological or biochemical abnormalities as a result of the injury are more likely to require invasive management in the form of an operation/interventional radiology (IR). Adverse psychological outcomes, such as post-traumatic stress disorder, anxiety, depression and adjustment disorder, are frequently observed in paediatric patients with major trauma. Similarly, it is recognised that children and adolescents who have invasive management are also at an increased risk of adverse psychological outcomes. However, it is not known to what extent major trauma patients requiring invasive management are at risk of adverse psychological outcomes compared with those managed conservatively. This study aims to determine whether paediatric major trauma patients who require an operation/IR have increased odds of having an adverse psychological outcome compared with those who are managed conservatively.

The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines will be used to construct this review. The databases Medline (via Ovid), Embase (via Ovid), PsycInfo (via Ebscohost) and Cinahl (via Ebscohost) will be searched from inception to February 2025. Both title and abstract screening and full-text screening will be done by two reviewers, with an adjudicating third reviewer. For randomised controlled trials, the Cochrane Risk of Bias Tool will be employed, while for non-randomised studies, the Newcastle-Ottawa Quality Assessment Scale will be used. We will assess bias using contoured funnel plots (with p set at 0.01, 0.05 and 0.10), non-parametric trim-fill analysis, leave-one-out analysis and Galbraith plotting. We will execute formal (Egger) testing for funnel plot asymmetry and also calculate prediction intervals if sufficient study N of 10 is accrued. Certainty and confidence in cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Ethical review is not required as no original data will be collected. Results will be disseminated through peer-reviewed publications and at academic conferences.

CRD42025643459.

Pharmacist prescribing has evolved to meet healthcare system needs, but the effectiveness, mechanisms and contextual factors influencing education programmes remain poorly understood. Realist approaches are fairly novel in pharmacy practice research. This realist synthesis aims to answer the question: to what extent do pharmacy prescribing education programs work (or not), for whom and under what circumstances, and why?

A realist methodology (realist synthesis) will be used to review the outcomes of programmes. Pawson’s key stages will be followed: (1) clarifying the scope; (2) determining the search strategy; (3) study selection; (4) extracting and analysing data; and (5) synthesising findings and drawing conclusions. The synthesis will follow Realist And Meta-narrative Evidence Syntheses–Evolving Standards publication guidelines. Data extracted will include the study characteristics, alongside the contexts, mechanisms and outcomes of varied pharmacy prescribing education programmes. The search strategy will include searching PubMed, Scopus, Web of Science and CINAHL Complete. An initial programme theory will use selected grey literature. Context-mechanism-outcome configurations will be identified, and recurring patterns will be synthesised to refine the initial programme theory.

Ethics approval is not required. Dissemination will be sought via peer-reviewed academic conferences and journals.

CRD420251056576.

Prescribing patterns for hyperopia in children vary widely among eye care providers worldwide. This scoping review aims to identify and map the current literature on optical correction and catalogue outcomes reported, particularly in the domains of vision, vision-related functional outcomes and quality of life (QoL) in school-aged children with hyperopia.

This protocol was developed in accordance with the Joanna Briggs Institute’s Manual for Evidence Synthesis. We will include studies involving school-aged children with hyperopia without restrictions on sex, gender, race, ethnicity, type of optical correction, length of intervention, publication date or country of origin. We will include studies with internal or external comparison groups. We will exclude studies associated with myopia control treatments, ocular and visual pathway pathologies affecting vision or visual function. We will search Cochrane CENTRAL, Embase.com and PubMed. Examples of data to be extracted include population demographics, visual acuity, study-specific definitions for refractive error, treatment regimens for optical correction, vision and vision-related functional outcomes and QoL (general or vision-related) as quantified by validated instruments.

Informed consent and Institutional Review Board approval will not be required, as this scoping review will only use published data. The results from the scoping review will be disseminated by publication in a peer-reviewed scientific journal and at professional conferences.

This scoping review aims to assess low-cost simulation methods used in nursing education, evaluating how they balance educational effectiveness with budget constraints.

Scoping review conducted in accordance with Arksey and O’Malley’s methodological framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines.

PubMed, Embase and CINAHL were systematically searched for relevant studies published between January 2000 and October 2023.

We included peer-reviewed primary studies involving nurses or nursing students, focused on the use of low-cost simulation in any healthcare setting. Studies had to describe the simulation strategy and its educational application.

Two reviewers independently screened titles, abstracts and full texts and extracted data using a standardised form. Findings were synthesised narratively and categorised by type of simulation, educational context and competencies addressed.

Out of 3332 records, 39 studies met the inclusion criteria. The reviewed studies covered various clinical areas, including critical care, emergency, neonatal, paediatric and obstetric nursing, as well as transversal competencies such as communication and clinical reasoning. Low-cost methods included task trainers, mannequins, computer-based tools, hybrid models and serious games. Only 38% of studies reported detailed cost information.

Low-cost simulation offers promising opportunities in nursing education but suffers from inconsistent cost reporting and a lack of standardisation. Further research is needed to evaluate its long-term effectiveness and support broader implementation.

Amoxicillin is recommended for children with uncomplicated severe acute malnutrition (SAM). However, some trials have shown no difference in amoxicillin for nutritional recovery in children with SAM compared with placebo. In addition, amoxicillin treatment requires two times per day dosing for 7 days, which may influence adherence. Azithromycin is a broad-spectrum antibiotic that can be provided as a single dose and has reduced mortality in children aged 1–59 months when provided by mass drug administration. The AMOUR trial is designed to assess amoxicillin, azithromycin and placebo as part of outpatient treatment of uncomplicated SAM.

This double-masked randomised controlled trial will enrol 3000 children over 3 years in an individually randomised 1:1:1 allocation to azithromycin, amoxicillin or placebo arms and follow them for 12 months. Children eligible to enrol in the study will be aged 6–59 months and have uncomplicated non-oedematous SAM as defined by weight-for-height Z-score

Ethical approval was obtained from the Institutional Review Board at the University of California, San Francisco (Protocol 23–39411) and the Comité d’Ethique pour la Recherche en Santé in Ouagadougou, Burkina Faso (Protocol 2024-01-08). The results of this study will be disseminated to the Ministry of Health, community stakeholders and via peer-reviewed publications and academic conferences.

NCT06010719.