Acute respiratory distress syndrome (ARDS) is a major public health problem, accounting for 23% of intubated patients and associated with high mortality rates. Although lifesaving, invasive mechanical ventilation can worsen lung injury when ventilator settings are poorly adjusted to lung physiology. We hypothesise that individualising ventilator settings via (1) the bedside assessment of lung recruitability using a one-breath derecruitment manoeuvre and measurement of airway opening pressure to set positive end-expiratory pressure (PEEP), (2) controlling the distending pressure and (3) controlling respiratory drive improves ARDS outcomes.

The CAreful Ventilation In ARDS trial is an investigator-led multicentre (33 centres in eight countries), open-label, randomised controlled basket trial comparing two ventilation strategies in two subpopulations of moderate-to-severe ARDS: induced or not by COVID-19. A total of 740 patients will be randomised (370 in each substudy) in a 1:1 ratio to individualised ventilator settings or to using traditional PEEP to inspired fraction of oxygen tables for PEEP setting. Indications for proning and weaning strategies are similar in both arms. The primary outcome is all-cause mortality at day 60. Secondary outcomes include duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital stay, organ dysfunction, barotrauma and mortality in ICU, at day 28 and in hospital.

Ethics approval has been obtained for all participating centres: Unity Health Toronto Research Ethics Board (for three centres: St Michael’s Hospital, Toronto General Hospital and Toronto Western Hospital); Comité de Ética de Investigación con Medicamentos del Hospital Universitari Vall d’Hebron; Comité de protection des personnes Ile de France III; Comité d'Ética de la Investigatción con Medicamentos de la Fundació de Gestió Sanitària del Hospital de la Santa Creu i Sant Pau; Comitato Etico—Fondazione Policlinico Gemelli; Comitato Etico di Area Vasta Emilia Centro; NYU Langone Health Institutional Review Board; Comité Ético Científico de Ciencias de la Salud; Il Comitato Etico Area 1 dell’Azienda Ospedaliero-Universitaria ‘Ospedali Riuniti’ di Foggia; HIGA ‘Eva Perón’ Comité de Bioética; Comité de Revisión Institucional del Hospital Británico Comité de Ética en Investigación; Complejo Médico Churruca-Visca Comité de Ética Biomédica; Comité de Ética SATI Comité de Ética en Investigación; Comité de Ética en Investigación del CEMIC; Comité de Ética SATI Comité de Ética en Investigación; Medical Research Ethics Committees United. Findings will be disseminated in peer review journals and conference presentations.

NCT03963622.

The National Institute for Health and Care Research (NIHR) has 20 Biomedical Research Centres (BRCs) and 28 Clinical Research Facilities (CRFs) that work with NHS organisations and universities to translate cutting-edge research into new interventions. As mandated by NIHR, all BRCs/CRFs have an Equality, Diversity and Inclusion (EDI) strategy which details how they will implement EDI through their practices, research and organisational systems. This UK-based study aimed to conduct a pilot qualitative analysis of EDI strategies to compare all 20 NIHR BRCs/CRFs, identify common priorities and improve inclusion across research infrastructures. The analysis was presented at the first in-person seminar for NIHR EDI professionals (Birmingham, October 2024).

Qualitative content analysis of publicly available EDI strategy documents.

48 research infrastructures (20 BRCs and 28 CRFs).

EDI strategies were collated into NVivo and Microsoft Excel where inductive coding and content analysis was executed for objectives, action plans and success measures. Both quantitative and qualitative content analyses were conducted to analyse the prevalence of categories and similarities or differences between them. Logic models were developed to map the process of implementing EDI for each main category generated.

The most common main category across objectives was ‘Cultural change in workplaces’ for BRCs and ‘Leadership, governance and policy’ for CRFs. For action plans, codes for ‘Collaborations and Networks’ and ‘Research development and delivery’ were most prevalent for BRCs—for CRFs, it was ‘Workforce culture change’ and ‘Research development and delivery’. Success measures for both BRCs and CRFs most often related to ‘Summary reports, feedback, audits and monitoring’. Differences between BRCs and CRFs reflected their organisational roles and strategic maturity, with BRCs tending to have more comprehensive, measurable strategies.

This study provides the first systematic analysis of EDI strategies across all NIHR BRCs and CRFs, offering a comprehensive mapping of how EDI priorities are articulated and operationalised across objectives, action plans and success measures. While both infrastructures align with NIHR’s inclusion goals, BRCs generally showed more strategic maturity than CRFs. As the analysis was based solely on publicly available strategy documents, it could not determine the extent to which any strategy had been implemented in practice. Future research is needed to examine implementation and impact. The contribution of this work lies in demonstrating systematically and for the first time the ways in which EDI commitments are framed across NIHR infrastructures and their varying levels of depth and maturity. Our findings support the development of more measurable EDI frameworks and highlight opportunities to strengthen inclusion across NIHR-funded research infrastructures.

To determine the safety and efficacy of ruxolitinib (RUX) and fostamatinib (FOS) compared with standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.

Adaptive multiarm, multistage, randomised, open-label trial (three arm, two stage).

Five hospitals in England between October 2020 and September 2022.

Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified WHO COVID-19 severity grade of 3 or 4.

Participants were randomly assigned 1:1:1 to receive RUX (10 mg two times per day for 7 days then 5 mg two times per day for 7 days), FOS (150 mg two times per day for 7 days then 100 mg two times per day for 7 days) or SOC.

Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAEs).

At stage 1, 181 patients were randomised, with 4 assessed as ineligible post randomisation. FOS was stopped early for futility with 16 participants (27.6%, n=58) developing severe COVID-19 pneumonia compared with 15 (25.0%, n=60) in the SOC arm (adjusted odds ratio (aOR) compared with SOC: 1.12; 95% CI 0.49 to 2.58; p=0.608). RUX progressed to stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, n=62) developed severe COVID-19 pneumonia in the RUX arm compared with 15 (24.6%, n=61) in the SOC arm (aOR: 0.63; 95% CI 0.25 to 1.57; p=0.161). Four (7.4%) participants in the FOS arm, none in the RUX arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported SAE and were numerically higher in the FOS (10, 17.2%) and RUX (10, 16.1%) arms compared with SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the RUX arm only.

We found no evidence that FOS was superior to SOC for the treatment of COVID-19 pneumonia in patients requiring hospital admission. Due to early stopping, the trial was underpowered to establish RUX’s effect in this population. Further study is needed.

NCT04581954; EUDRA-CT: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001750-22/GB.

Significant advances in systemic therapy have improved survival for patients with advanced-stage non-small cell lung cancer (NSCLC). However, the present treatment strategies and dose-fractionation for high-dose palliative radiotherapy (RT) are based on trials from the 1990s, when RT planning was simple with less precise delivery. Contemporary lung RT uses 4D-CT, volumetric modulated arc radiotherapy, aided by online verification using cone beam CT, which enables greater accuracy and better target volume coverage, while reducing doses to normal organs at risk. The Shortened High-dose Palliative Radiotherapy for Lung Cancer study aims to evaluate the safety and feasibility of reducing the number of RT fractions and RT duration, using contemporary planning, verification and delivery techniques.

This single-arm, multicentre, phase-II study will test the shortened hypofractionated accelerated palliative RT regimen of 30 Gy in 6 alternate-day fractions, with strict normal tissue dose constraints. We aim to recruit 37 patients across 4 sites within the West Midlands. Quality assurance for the RT is supported by the Radiotherapy Trials Quality Assurance Group (RTTQA). Patients with locally advanced or metastatic NSCLC, who are candidates for high-dose palliative RT, before or after first-line systemic therapy, are eligible for recruitment. The primary objective of this study is to assess the safety of the proposed dose-fractionation. Secondary objectives include evaluating toxicity profiles, patient-reported outcome measures, time to progression, feasibility and the National Health Service cost-saving.

This study is conducted in accordance with the International Council for Harmonisation Good Clinical Practice (ICH GCP) guidelines and all applicable regulatory frameworks, including, but not limited to, the UK policy framework for health and social care research, as well as the Health Research Authority and Health and Care Research Wales regulations. Approval for the study was granted on 18 April 2024 (IRAS project ID: 332998; REC reference: 24/WM/0032). The chief investigator is responsible for obtaining informed consent from participants. Any individual delegated this responsibility is thoroughly authorised, trained and competent to conduct the informed consent process. On completion of the trial, the results will be shared with participants in a plain language summary and will be submitted for publication in a peer-reviewed journal. If successful, this study will inform a phase III randomised controlled trial to assess efficacy. For updates on the study, visit the study web page (https://research.mededcoventry.org/About-Us/Meet-The-Team/TMU/Ship-Rt).

NCT06483308.

Recent advances in treatment and care have improved survival rates for children and young adults with severe blood disorders such as sickle cell disease (SCD), transfusion-dependent beta-thalassaemia (TDT) and acute leukaemia. However, their quality of life and reproductive and psychosocial outcomes are not yet well studied. For SCD and TDT, robust survival data are mainly limited to North America. Thus, there is a need to fill these knowledge gaps to guide improvements in care, address unmet clinical needs and rigorously assess the efficacy of emerging novel therapies.

This is an observational population-based mixed-methods study of individuals diagnosed with SCD, TDT or acute leukaemia when under the age of 18 in England, involving a data linkage component and a patient-reported outcomes measures survey. Data linkage-eligible participants will be identified from national and regional databases, including the Hospital Episode Statistics, Yorkshire Specialist Register of Cancer in Children & Young People and the National Congenital Anomaly and Rare Diseases Registration Service. Data linkage will be processed within the NHS England and the University of Leeds’ secure, trusted research environments. Data will be accessed without consent under section 251 and approval by the confidentiality advisory group. It will assess survival rates for SCD and TDT as well as clinical, educational and mental health outcomes for SCD, TDT and acute leukaemia diagnosed in childhood.

Survey-eligible participants for SCD, TDT and acute leukaemia cohorts will be checked for their suitability to participate by the North of England clinical care teams. An NHS-approved survey provider will facilitate data checks with the NHS National Data Opt-Out Service. Consent is required for participation in the survey and for subsequent data linkage to existing databases. Surveys are conducted in various formats (online, paper and phone), with reminders sent after 21 days. The survey will assess quality of life and psychosocial and reproductive outcomes. Participants can withdraw at any time, and support is available via telephone helplines.

The study has received ethical and information governance approval from the Health Research Authority (Reference 24/YH/0186) and the Confidentiality Advisory Group (CAG 24/CAG/0138) to process identifiable data without consent. Study results will be available to patients, physicians, researchers, stakeholders and others through open-access publishing, results sharing via media platforms and presentations at conferences and meetings.

We aimed to determine whether UCLP-PRIMROSE (a care innovation to reduce physical health inequalities for people with severe mental illness) could be set up in the current UK National Health Service (NHS) context and identify the processes, barriers and facilitators to implementation.

We employed a convergent mixed methods approach, combining interviews, ethnographic site visits and the collection of meeting notes and uptake data for core model components. Interview transcripts were analysed using reflexive thematic analysis, and all qualitative data, including interview transcripts, were analysed using the Consolidated Framework for Implementation Research. Qualitative work and insights from implementation uptake frequencies were integrated using Normalisation Process Theory.

We evaluated implementation in Yorkshire and three London boroughs, mainly within general practices.

We conducted interviews with 39 staff members who were implementing and/or delivering UCLP-PRIMROSE.

UCLP-PRIMROSE is an integrated evidence-based care pathway developed to reduce cardiovascular disease risk and mental health relapse in people with severe mental illness.

Adaptation and delivery varied in completeness and consistency across 24 general practices and their wider care teams. Factors outside the implementation teams’ influence challenged the embedding of UCLP-PRIMROSE. Factors included the impact from the immaturity of NHS integrated care systems, unintended consequences of the incentivised NHS severe mental illness physical health check and limited capacity for implementing in a system facing resourcing challenges. Drivers of successful implementation included staff being aligned with the values of the UCLP-PRIMROSE model and system leaders acting as champions. Supportive foundational processes acted as facilitators: these included protected and prioritised time for reflection, learning and problem solving.

Implementation of UCLP-PRIMROSE was moderately successful in a relatively short period of time. At the end of the research, all teams wanted to sustain delivery. However, further pathway simplification and additional resources are required to spread UCLP-PRIMROSE beyond early pockets of good practice.

The commercial determinants of health (CDoH) are a rapidly growing field of research and global health priority. Despite being disproportionately affected, Indigenous Peoples’ voices and perspectives are conspicuously absent from CDoH research and policy. This article outlines the protocol for Addressing Commercial Health determinants: Indigenous Empowerment and Voices for Equity (ACHIEVE), an Aboriginal and Torres Strait Islander-led project in Australia.

ACHIEVE integrates four research streams, using a novel combination of methods. The first three streams will (i) conceptualise the CDoH using Indigenous yarning methodology, (ii) evaluate the effectiveness and cost-effectiveness of policies to reduce exposure to harmful marketing and (iii) assess the impacts of specific commercial entities on Aboriginal and Torres Strait Islander health using case studies. The final stream will consolidate findings from streams 1–3 and work with Aboriginal Community Controlled Health Organisations (ACCHOs) to co-create strategies for addressing the commercial determinants of Aboriginal and Torres Strait Islander health.

Ethical approval for streams 1–3 has been granted by Deakin University Human Research Ethics Committee. ACHIEVE is guided by a governance model that prioritises Indigenous data sovereignty, community and ACCHO partnerships, capacity building and knowledge translation. Findings will be shared with participants, ACCHOs and policymakers to maximise research impact.

Patient-reported experience measures (PREMs) are measures of patients’ perceptions of care they receive. PREMs are critical in developing and evaluating programmes that aim to improve patient healthcare experiences and quality of care (QoC) according to patient-defined needs. This review aims to map key domains of PREMs across distinct healthcare technical areas and life stages from globally available literature.

A scoping review adapting Arksey and O’Malley’s framework and Joanna Briggs Institute’s guidelines for the conduct of scoping reviews.

Google Scholar, PubMed, WHO, US Academy of Medicine and USAID Momentum.

PREMs literature from electronic repositories of grey and peer-reviewed publications, published in English historically up to September 2023.

Two lead reviewers with support from the technical working group co-created a review framework of healthcare technical areas, life stages and PREMs domains. We screened eligible articles, prioritising reviews except for technical areas with no reviews, where we then selected individual studies. We charted, analysed and synthesised data from 52 eligible articles.

PREMs literature has recently increased, especially in low-income and middle-income countries (LMICs), although studies in high-income countries (HICs) dominate in proportion (n=38; 73.1%). Out of 52 eligible articles, technical areas with most publications were sexual and reproductive health (n=21; 40.4%) and general outpatient care (n=11; 21.2%). Studies in adulthood (n=24; 46.2%) and from pregnancy and birth to postnatal (n=16; 30.8%) were most represented. PREMs studies reported mostly on communication and rapport (n=33; 63.5%) and respect and dignity (n=42; 80.8%) domains. Nearly a quarter (n=12; 23.1%) of the articles included only validated tools; the rest included a combination of validated and unvalidated measures. Of the tools relating to life stages of babies, younger children and older adults, the majority (n=17; 94.4%) included patient proxies.

PREMs, as an important component of QoC measurement, are increasing across several healthcare technical areas and life stages with commonalities and notable distinctions in measurement domains and tools. Evidence on PREMs largely comes from HICs. Evidence on critical, yet sometimes overlooked domains, highlights key QoC implementation gaps. The adaptation and utilisation of PREMs in programmes, especially in LMICs and under-represented technical areas, present opportunities to close the QoC disparities in those settings. Strategic, concerted efforts towards the harmonisation of PREMs tools across multiple life course stages and technical areas are critically needed in high-level quality improvement efforts.

To characterise long-term trajectory of recovery in individuals with long covid.

Prospective cohort.

Single-centre, specialist post-COVID service (London, UK).

Individuals aged ≥18 years with long covid (hospitalised and non-hospitalised) from April 2020 to March 2024.

Routine, prospectively collected data on symptoms, quality of life (including Fatigue Assessment Scale (FAS) and EuroQol 5 Dimensions (EQ-5D), return to work status and healthcare utilisation (investigations, outpatient and emergency attendances). The primary outcome was recovery by self-reported >75% of ‘best health’ (EQ-5D Visual Analogue Scale) and was assessed using Cox proportional hazards regression models over 4 years. Linked National Health Service England registry data provided secondary care healthcare utilisation and expenditure.

We included 3590 individuals (63.3% female, 73.5% non-hospitalised, median age 50.0 years, 71.9% with ≥2 doses of COVID-19 vaccination), who were followed up for a median of 136 (0–346) days since first assessment and 502 (251–825) days since symptom onset. At first assessment, 33.2% of employed individuals were unable to work. Dominant symptoms were fatigue (78.7%), breathlessness (68.1%) and brain fog (53.5%). 33.4% of individuals recovered to >75% of best health prior to clinic discharge (recovery occurred median 202 (94–468) days from symptom onset). Vaccinated individuals were more likely to recover faster (pre: HR 2.93 (2.00–4.28) and post: HR 1.34 (1.05–1.71) COVID-19 infection), whereas recovery hazard was inversely associated with FAS (HR 0.37 (0.33–0.42)), myalgia (HR 0.59 (0.45–0.76)) and dysautonomic symptoms (HR 0.46 (0.34–0.62)). There was high secondary care healthcare utilisation (both emergency and outpatient care). Annual inpatient and outpatient expenditure was significantly lower in hospitalised individuals while under the service. When compared with the prereferral period, emergency department attendances were reduced in non-hospitalised patients with long covid, but outpatient costs increased.

In the largest long covid cohort from a single specialist post-COVID service to date, only one-third of individuals under follow-up achieved satisfactory recovery. Fatigue severity and COVID-19 vaccination at presentation, even after initial COVID-19 infection, was associated with long covid recovery. Ongoing service provision for this and other post-viral conditions is necessary to support care, progress treatment options and provide capacity for future pandemic preparedness. Research and clinical services should emphasise these factors as the strongest predictors of non-recovery.

Effective prevention of maternal-fetal transmission of hepatitis B virus (HBV) in highly endemic settings depends on targeting vaccination efforts to key priority groups, including pregnant women. However, the extent of HBV vaccination and determinants of uptake in sub-Saharan Africa (SSA) have not been systematically examined. This systematic review aims to estimate HBV vaccination among pregnant women in SSA and identify the broader factors influencing uptake.

This review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines. A comprehensive literature search will be conducted in MEDLINE, Embase, Web of Science, Scopus, African Journals Online and Google Scholar in November 2025. We will include published observational studies that assess HBV vaccination among pregnant women in SSA countries from database inception to October 2025. A meta-analysis will be conducted using random-effects models to pool estimates of HBV vaccination and multivariable-adjusted ORs for vaccination-associated factors. Statistical heterogeneity will be assessed using the I² statistic.

Ethical approval is not required as this review will not involve primary data collection. Findings will be published in a peer-reviewed journal, presented at regional and international public health conferences, and, where applicable, shared with policymakers and health authorities in SSA.

This protocol is registered with the International Prospective Register of Systematic Reviews, registration number CRD420251120357.

MRI is increasingly recognised as a valuable tool for assessing prognosis and predicting outcomes following traumatic spinal cord injury (SCI). Several potential MRI biomarkers have been identified, but efforts are still needed to improve the accuracy and feasibility of these biomarkers in clinical practice. This study aims to build a national Canadian SCI imaging repository for storing and analysing imaging data for SCI, with the goal of improving SCI MRI biomarkers to predict outcomes and inform clinical management.

As a substudy of the Rick Hansen SCI Registry (RHSCIR), this retrospective multisite study includes individuals who sustained a traumatic cervical SCI between 2015 and 2021, were previously enrolled in RHSCIR, and had MRI scans acquired within 72 hours of injury and before any surgical intervention. Individuals with a penetrating trauma and/or with any prior spine surgery are excluded. The study principal investigator and research associates, experienced with data curation and with the standardised format and specifications of the Brain Imaging Data Structure standard, guide the site’s curator on the steps to perform image deidentification and curation to create standardised datasets across all sites. These datasets are transferred to a Digital Research Alliance of Canada (‘the Alliance’) server designated for this project and concatenated to form the national Canadian SCI imaging repository (Neurogitea). We are using a semiautomated processing pipeline to quantify lesion morphology, together with additional imaging measures that are manually extracted from the images (for instance, the relative maximal spinal cord compression and the maximum canal compromise). Through linkage to RHSCIR clinical and epidemiological data already available on eligible participants, regression analysis is planned to predict neurological outcomes at discharge, including the American Spinal Injury Association Impairment Scale grade, upper and lower extremity motor and sensory scores.

This protocol has been submitted by the participating sites to obtain ethics and institutional approvals prior to the study initiation at each site. All 12 sites across Canada have now obtained ethics and institutional approvals. Study results will be disseminated at local, national and international conferences and by journal publications.

Pain in patients with rheumatoid arthritis (RA) is an unmet clinical need. Targeting joint inflammation with disease-modifying antirheumatic drugs has not resulted in the anticipated reduction in pain for many patients. This can partly be explained by the concept of central sensitisation whereby spinal and supraspinal pathways have a lower threshold of activation, leading to increased perception of pain. Synovial stromal cells, such as fibroblasts, are also thought to play a role through peripheral sensitisation of nerves in the joint. Synovial fibroblasts are known to produce pro-algesic mediators such as interleukin 6 and nerve growth factor at the messenger RNA level. These pro-algesic mediators could activate sensory nerve fibres that send signals from the joint to the spinal cord, thereby driving persistent pain in RA. The purpose of this study is to evaluate which pro-algesic mediators are produced by lining versus sub-lining fibroblasts and whether the level of these mediators correlates with clinical measures of pain in patients with RA.

FiND-Pain RA is a multicentre observational study which will recruit 50 patients with seropositive RA who attend the rheumatology department of Guy’s and St Thomas’ Hospital, London, and the Nuffield Orthopaedic Centre, Oxford. Clinical examination, pain-focused patient-reported outcome measures, ultrasound examination and ultrasound-guided synovial biopsy of the knee will be performed. The levels of known and putative pro-algesic mediators will be measured in fibroblasts from the lining and sub-lining layer of the synovium. The location and spatial morphology of sensory nerve fibres and their proximity to lining and sub-lining fibroblasts will be characterised. The primary outcome will be to determine whether the knee pain scores of participants correlate with the level of leukaemia inhibitory factor, a novel putative pain-mediator expressed in sub-lining fibroblasts. The secondary outcomes will be to determine whether other pro-algesic mediators produced by lining or sub-lining fibroblasts correlate with clinical measures of pain and to assess the location and proximity of sensory nerve fibres to lining versus sub-lining fibroblasts.

The study is a sub-study of the PUMIA (Pain Phenotypes and their Underlying Mechanisms in Inflammatory Arthritis) study, which has been approved by the Bromley Research Ethics Committee (REC: 21/LO/0712). The findings of this study will be disseminated through open-access publications, as well as scientific and clinical conferences.