Persons with serious mental illness (SMI) often have coexisting medical conditions and experience a significantly reduced life expectancy compared with the general population. Peer support is considered an effective care approach for this population, and with rapid technological advancements, digital peer support, such as the DigiPer mobile application, can be a feasible self-management tool for persons with SMI. The study aims to assess the feasibility of DigiPer for persons with SMI in the Norwegian community mental health service settings.

This feasibility study will incorporate both qualitative and quantitative methods. The study consists of three phases: (1) simulation-based training among peer support workers using qualitative individual interviews; (2) pre–post study of DigiPer among peer support workers and service users using quantitative questionnaires and (3) process evaluation for peer support workers and service users using qualitative individual interviews. Peer support workers (n=5) and service users with SMI (n=15) will be recruited to evaluate the feasibility of DigiPer.

Ethics approval was granted from the Regional Committee for Medical Research Ethics (reference no. 853041), along with an assessment of processing of personal data by the Norwegian Agency for Shared Services in Education and Research (reference no. 810990). Findings will be disseminated through peer-reviewed publications and presentations at relevant national and international scientific conferences.

Streptococcus pneumoniae serotype 3 (SPN3) remains a significant contributor to invasive pneumococcal disease globally, despite its inclusion in widely administered vaccines. The next generation of pneumococcal vaccines may confer better protection against this serotype, reducing disease burden. We describe an ethically approved protocol for a double-blind randomised controlled trial assessing the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine (PCV15)) and 0.9% saline (placebo) on the acquisition, density and duration of SPN3 carriage using a controlled human infection model.

Healthy adults aged 18–50 years will be randomised 1:1 to receive PCV15 or placebo. Participants will be considered enrolled on the trial at vaccination. One month following vaccination, all participants will be intranasally inoculated with SPN3. Following inoculation, participants will be followed up on days 2, 7, 14 and 28 to monitor safety, SPN3 colonisation status, density and duration, as well as immune responses. The primary endpoint of the study is to assess the rate of SPN3 acquisition between vaccinated and unvaccinated participants defined by classical microbiological methods. Secondary endpoints will determine the density and duration of SPN3 colonisation and compare the immune responses between study groups. An exploratory cohort of 5 participants will be asked to consent to a nasal biopsy procedure during a screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will only receive PCV15 and will not be challenged. Through this exploratory cohort, we will explore gene expression changes induced by PCV15 vaccination and their visualisation (spatial location) within the nasal tissue.

This protocol has been reviewed by the sponsor, funder and external peer reviewers. The study is approved by the NHS Research and Ethics Committee (Reference: 24/SC/0388) and by the Medicines and Healthcare Products Regulatory Agency (Reference: CTA 21584/0485/001-0001).

NCT06731374 – ISRCTN91656864.

Cluster randomised trials (CRTs) can be at risk of bias driven by differential identification and recruitment of participants across treatments, posing a threat to the validity of findings. We explored the awareness and importance, among CRT researchers, of the recommended bias mitigation measures.

Qualitative interview study using semistructured interviews.

Participants were researchers involved in conducting CRTs, including investigators, statisticians and trial coordinators. 24 participants, including statisticians (n=13, 54.2%), clinical investigators (n=9, 37.5%) and trial coordinators (n=2, 8.3%), were interviewed; with representation from the UK (n=10, 41.7%), Australia (n=5, 20.8%) and the USA (n=4, 16.7%).

Participants exhibited differing levels of knowledge related to biases. Some participants demonstrated high levels of knowledge, but we also identified prevalent misconceptions, with some evidence of superficial knowledge. While some participants worked in collaborative teams, other teams’ responsibilities were delineated, and this impacted on how knowledge of biases was shared and acted on. Logistical and practical issues could prevent known solutions to mitigate biases being implemented. Biases also manifested because of a perception from participant recruiters that the purpose of research is for participant benefit rather than producing generalisable knowledge; and a normalisation or expectation that CRTs produce a lower level of evidence.

There is an urgent need to ensure that CRTs are free from risks of bias. Mitigation measures are either not known, not practical or unconsciously subverted. More education and collaborative working might help. Preventing subconscious bias during participant recruitment and dispelling the myth that CRTs produce lower levels of evidence would require a change in culture.

Knee osteoarthritis (OA) is a leading cause of disability in older adults, with health and economic impacts. Despite pharmacological advances, exercise continues to be a fundamental pillar in the management of OA, with lower limb strength training showing significant benefits. Virtual reality (VR)-based interventions have emerged as innovative tools, providing immersive environments to facilitate functional movement exercises. VR offers pain relief, improved functionality and reduced fall risks, although its efficacy in OA management requires further exploration. The main aim of the study is to assess whether a VR-based intervention provides superior improvements in pain, stiffness, physical function and movement biomechanics compared with conventional therapeutic exercise in adults aged 60 years and older with knee OA.

This is a protocol for a randomised controlled trial comparing the effects of immersive VR interventions with conventional therapeutic exercises in individuals aged 60 years and older with knee OA. Participants are allocated 1:1 to experimental (VR) and control groups. The VR intervention involves 18 supervised sessions over 8 weeks, using Meta Quest 3 goggles to perform functional movements in virtual environments. The control group follows standard therapeutic exercise protocols per Osteoarthritis Research Society International guidelines. Outcomes include OA-related symptoms, kinematic performance, pain intensity, kinesiophobia and fall risk. Secondary measures assess cybersickness, depressive symptoms, medication use and comorbidities. Assessments occur at baseline, ninth week, sixth and ^12th months. Data analysis employs intention-to-treat principles, leveraging descriptive statistics, t-tests and multiple imputations for missing data.

This study was approved by the A Coruña-Ferrol Research Ethics Committee (reference: 2023/557), under the Galician Health Service. All participants will be required to provide written informed consent prior to their inclusion in the study. Participant data will be pseudonymised and securely stored. Additionally, anonymised datasets will be deposited in open-access repositories (Zenodo).

NCT06362785.

To quantify and describe the use of real-world data (RWD) in National Institute for Health and Care Excellence (NICE) oncology technology appraisal (TA) final appraisal determination documents.

A systematic literature review was conducted on pharmaceutical NICE oncology TAs published between April 2000 and March 2024 (covering financial years 2000/2001 to 2023/2024 inclusive) extracted on 22 August 2023 (2000/2001 - 2022/2023) and 8 August 2024 (2023/2024).

NICE TA final appraisal determination documents.

All pharmaceutical oncology TAs published between April 2000 and March 2024 (financial years 2000/2001 to 2023/2024) that did not go on to be terminated.

The data required for eligibility screening was extracted from an Excel file directly from the NICE website, where data related to each TA was extracted using an automated script derived from published sources. TAs were assessed based on prespecified review criteria covering whether an RWD submission was reported by the committee, and if so, which RWD sources were used, alongside the methods reported and any feedback from the committee regarding the use of RWD. Bias was not assessed as part of the study.

Of 310 TAs identified, 135 (48.0%) used RWD. A variety of RWD types were used, mostly from UK or US data sources. 47 TAs (34.8%) leveraged RWD from multiple sources. RWD was mostly used in comparisons of survival (41.5%), to inform utility values (26.7%) and to compare baseline characteristics (19.3%), with matched adjusted indirect comparisons (MAICs) and external control arms (ECAs), seen from 2015 and 2018, respectively. The committee expressed concerns around the RWD presented by the company in 53 TAs (39.2%), the most common being a lack of generalisability to the UK population and/or National Health Service practice and comprehensiveness of the RWD.

This study quantifies the increasing use of diverse RWD sources in NICE oncology TAs, as well as the shift towards more complex methods like MAICs and ECAs. The feedback of the NICE committee highlights key areas of improvement as the generalisability and maturity of the RWD presented.

Early and balanced replacement of blood products appears to be the key factor in improving outcomes of major bleeding patients including acute trauma, cardiac, obstetric and transplant surgery patients. Definitive clinical guidance regarding the optimal ratio of blood products, including those containing fibrinogen, is still lacking. Therefore, we tested the hypothesis that increasing the fibrinogen content to erythrocyte suspension ratio improves the mortality and functional outcomes of patients undergoing surgeries with expected major bleeding.

The Approximate Dose-Equivalent of Fibrinogen-to-Erythrocyte Suspension (ADEFES) ratio is a multicentre, prospective, observational, cohort study of patients undergoing major surgical procedures with expected major perioperative bleeding (ie, requiring packed red blood cells (PRBC)>4U/24 hours). For 5U of cryoprecipitate and 1.5 U of fresh frozen plasma (FFP), the approximate dose-equivalent for fibrinogen is considered as 1 gram of fibrinogen. Association of the ADEFES ratio at 24 hours will be assessed on the primary objective, which will consist of the composite of 30-day all-cause mortality, 30-day bleeding-specific mortality and the ‘highly-dependent scores’ of Katz index of independence in activities of daily living.

The study protocol was approved by the Ethics Committee of Ankara Bilkent City Hospital (approval no. E2-23-4265, dated 07 June 2023; Chair: Prof. Dr. F.E. Canpolat) and by the institutional review boards of all participating centres. The study will be conducted in accordance with the principles of the Declaration of Helsinki and the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, as well as in compliance with national regulations on data protection and Good Clinical Practice standards. Written informed consent will be obtained from all participants prior to inclusion in the study.

The results of this study will be disseminated through peer-reviewed scientific journals, presentations at national and international conferences, and communication with relevant stakeholders including clinical practitioners and healthcare institutions. If applicable, study outcomes will also be shared via institutional newsletters and digital platforms to reach a broader audience in the medical community.

NCT06021184.