Many people with psychosis find the world very frightening. It can be difficult for them to do everyday things—for example, walking down a busy street, travelling on a bus or going to the shops. Sometimes, the fears are so great that individuals rarely leave their homes. gameChange virtual reality therapy is designed to reduce this agoraphobic avoidance. In gameChange, users practise going into computerised immersive versions of ordinary situations. A virtual therapist guides users through the programme. A mental health worker also supports people. People normally do six sessions of gameChange, but now they can do more as headsets can be left with many people. We originally tested gameChange with 346 patients with psychosis. People saw a significant reduction in their fears. People with the most severe problems made the biggest improvements. This led to gameChange receiving National Institute for Health and Care Excellence (NICE) Early Value Assessment (EVA) approval for its use with patients with psychosis who have severe agoraphobic avoidance. NICE EVA approval is conditional on further evidence generation. We aim to carry out a real-world trial of gameChange used in the NHS. The overall aim is to gather evidence on the four essential areas (clinical benefits on agoraphobia, level of engagement and adherence, healthcare resource use, adverse effects) and the two further supporting areas (health-related quality of life, generalisability) identified in the NICE evidence generation plan for gameChange.

200 patients with psychosis and severe agoraphobic avoidance will be randomised (1:1) to receive gameChange in addition to treatment as usual (TAU) or to a waitlist control group receiving TAU. Assessments will be conducted blind to group allocation at baseline, 8 weeks (end of treatment) and 26 weeks (follow-up). The trial will be embedded in services in at least seven National Health Service (NHS) trusts across England. The primary outcome is agoraphobic avoidance at 26 weeks assessed with the Oxford Agoraphobic Avoidance Scale. The secondary clinical outcomes are agoraphobic distress, paranoia and social contacts. There will be tests of moderation of the main clinical outcome. Treatment acceptability, adverse effects and cost-effectiveness will also be assessed. The target estimand is the treatment policy estimand and all primary and secondary analyses will be carried out incorporating data from all participants including those who do not complete treatment.

The trial has received ethical approval from the NHS Health Research Authority and Health and Care Research Wales (25/WA/0081). A key output will be the evidence needed for a NICE guidance update on gameChange and a clear recommendation concerning future routine use in the NHS.

ISRCTN79060696.

Although caesarean sections (CSs) are essential for the management of obstructed labour and other obstetric complications, postoperative pain, delayed recovery and complication risks continue to be significant challenges in perioperative management. Improvements in traditional medications and surgical techniques have helped, yet issues, including medication side effects and extended recovery times, persist. Therefore, it is particularly important to seek non-pharmacological interventions, such as acupoint stimulation, to optimise the perioperative management of CS. The aim of this systematic review protocol is to synthesise the available evidence and assess the effect of acupoint stimulation in the perioperative period of CS.

We plan to search PubMed, Web of Science, EMBASE, Scopus, the Cochrane Library and China National Knowledge Infrastructure, from their inception to August 2025. Primary outcome indicators will include pain, time to first defecation, time to first bowel movement and time to return of bowel sounds. Secondary outcome indicators will include postoperative complications, such as nausea and vomiting, bloating, anxiety and depression, as well as length of hospital stay and morphine consumption. Subgroup analyses, meta-regression and sensitivity analyses will be used to investigate the potential sources of heterogeneity and to test the stability of the results. Trial sequential analysis will be introduced to enhance the reliability of the evidence.

No ethical approval is required as this study synthesises the existing published data. Results will be disseminated through peer-reviewed publications and conference presentations. Any protocol amendments will be documented in PROSPERO and detailed in the final publication.

CRD42024558572.

Pain accounts for approximately 80% of emergency department admissions. While intravenous morphine titration is commonly used for severe pain, non-invasive alternatives that bypass intravenous access are needed. Nebulised fentanyl, combined with pupillometry for objective monitoring of opioid impregnation, may offer a rapid and safe alternative for pain management.

This phase I, open-label, randomised, exploratory, crossover, single-centre prospective controlled trial will employ pharmacokinetic–pharmacodynamic (PK–PD) modelling to assess the variability in bioavailability of nebulised fentanyl administered via intranasal route versus facial aerosol. 20 healthy volunteers will receive three repeated administrations of fentanyl over two visits. At each visit, blood samples (n=11) will be collected for fentanyl quantification by liquid chromatography–tandem mass spectrometry, and pupillary unrest in ambient light (PUAL) measurements (n=9) will be recorded. The resulting data will be analysed using Monolix 2024R1 to model PK–PD relationships, perform Monte Carlo simulations and determine the optimal dosing and timing required to achieve a reduction of more than 30% in PUAL, while also evaluating safety, comfort and tolerance.

The study has been approved by the Ethic Committee Île-de-France VII (approval reference number: 000216, February 2024) and will be conducted in accordance with the Declaration of Helsinki. Informed consent will be obtained from all participants. Study findings will be disseminated through peer-reviewed publications, conference presentations and appropriate data-sharing platforms to support further research and clinical application.

This trial is registered at ClinicalTrials.gov (Identifier: NCT06281951).

There are no validated paediatric-specific diagnostic criteria for complex regional pain syndrome (CRPS). As a result, diagnostic tools developed for adults (eg, Budapest Criteria, Japanese Diagnostic Criteria, Veldman Criteria) are frequently applied in the paediatric population. However, the clinical presentations and trajectories of children can differ from adults. Given that treatment outcomes are linked to early diagnosis and intervention, the lack of paediatric-specific screening or diagnostic tools is an important knowledge gap. We aim to identify the frequency of individual criteria used in diagnosing CRPS in children and adolescents in existing literature, summarise assessment methods used to establish the diagnosis, and provide recommendations for research and clinical application.

The following databases and platforms will be searched for articles published from 2003 (year the Budapest Criteria was developed) onward: CINAHL, CENTRAL, Embase, Ovid MEDLINE, PubMed, PsycINFO and Web of Science. Our search strategy will use subject headings and text words related to the concepts of CRPS in paediatric populations, with study inclusion criteria from birth up to 18 years old, and a diagnosis of CRPS. Data will be extracted by our multidisciplinary team and findings will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews.

This study does not involve human participants or unpublished data; therefore, approval from a human research ethics committee is not required. The findings of this scoping review will be disseminated through academic conferences and peer-reviewed publications.