The ‘time-limited trial’ for patients with critical illness is a collaborative plan made by clinicians, patients and families to use life-sustaining therapies for a defined duration. After this period, the patient’s response to therapy informs decisions about continuing recovery-focused care or transitioning to comfort-focused care. The promise of time-limited trials to help navigate the uncertain limits and benefits of life-sustaining therapies has been extensively discussed in the palliative and critical care literature, leading to their dissemination into clinical practice. However, we have little evidence to guide clinicians in how to conduct time-limited trials, leading to substantial variation in how and why they are currently used. The overall purpose of this study is to characterise the features of an optimal time-limited trial through a rich understanding of how they are currently shaping critical care delivery.

We are conducting an observational, multicentre, focused ethnography of time-limited trials in patients with acute respiratory failure receiving invasive mechanical ventilation in six intensive care units (ICUs) within five hospitals across the US. Study participants include patients, their surrogate decision makers and ICU clinicians. We are pursuing two complementary analyses of this rich data set using the open-ended, inductive approach of constructivist grounded theory and, in parallel, the structured, deductive methods of systems engineering. This cross-disciplinary, tailored approach intentionally preserves the tension between time-limited trials’ conceptual formulation and their heterogeneous, real-world use.

This study has been reviewed and approved by the University of Wisconsin Institutional Review Board (IRB) as the single IRB (ID: 2022-1681; initial approval date 23 January 2023). Our findings will be disseminated through peer-reviewed publication, conference presentations, and summaries for the public.

NCT06042621.

Artificial intelligence (AI)-based clinical decision support systems (CDSSs) are currently being developed to aid prescribing in primary care. There is a lack of research on how these systems will be perceived and used by healthcare professionals and subsequently on how to optimise the implementation process of AI-based CDSSs (AICDSSs).

To explore healthcare professionals’ perspectives on the use of an AICDSS for prescribing in co-existing multiple long-term conditions (MLTC), and the relevance to shared decision making (SDM).

Qualitative study using template analysis of semistructured interviews, based on a case vignette and a mock-up of an AICDSS.

Healthcare professionals prescribing for patients working in the English National Health Service (NHS) primary care in the West Midlands region.

A purposive sample of general practitioners/resident doctors (10), nurse prescribers (3) and prescribing pharmacists (2) working in the English NHS primary care.

The proposed tool generated interest among the participants. Findings included the perception of the tool as user friendly and as a valuable complement to existing clinical guidelines, particularly in a patient population with multiple long-term conditions and polypharmacy, where existing guidelines may be inadequate. Concerns were raised about integration into existing clinical documentation systems, medicolegal aspects, how to interpret findings that were inconsistent with clinical guidelines, and the impact on patient-prescriber relationships. Views differed on whether the tool would aid SDM.

AICDSSs such as the OPTIMAL tool hold potential for optimising pharmaceutical treatment in patients with MLTC. However, specific issues related to the tool need to be addressed and careful implementation into the existing clinical practice is necessary to realise the potential benefits.

People experiencing severe and multiple disadvantage (SMD: homelessness, substance use and criminal offending) have multiple intersecting unmet health and social care needs and high mortality rates, often due to street-drug overdose. Pilot randomised controlled trials (RCTs) suggest an integrated, holistic, collaborative outreach intervention (Pharmacy Homeless Outreach Engagement Non-medical Independent Prescribing Rx (PHOENIx)) involving generalist-trained pharmacists, nurses or General Practitioners accompanied by staff from third sector homeless organisations may improve outcomes, including reducing overdose.

Multicentre, parallel group, prospective RCT with parallel economic and process evaluation. Set in six areas of Scotland, UK, 378 adults with SMD will be recruited and randomised (stratified by setting and previous non-fatal overdoses) to PHOENIx intervention in addition to usual care (UC) or UC. Aiming to meet participants weekly for 9–15 months, PHOENIx teams assess and address health and social care needs while referring onwards as necessary, co-ordinating care with wider health and third sector teams. During a person-centred consultation, in the participants’ choice of venue, and taking account of the participant’s priorities, the NHS clinician may prescribe, de-prescribe and treat, for example, wound care, and refer to other health services as necessary. The third sector worker may help with welfare benefit applications, social prescribing or advocacy, for example, securing stable housing. Pairings of clinicians and third sector workers support the same participants. The primary outcome is time to first fatal/non-fatal street-drug overdose at nine months. Secondary endpoints include health-related quality of life, healthcare use and criminal justice encounters. A health economic evaluation will assess cost per quality adjusted life year of PHOENIx relative to standard care. A parallel qualitative process evaluation will explore the perceptions and experiences of PHOENIx, by participants, stakeholders and PHOENIx staff.

The primary and other time-to-event secondary outcomes will be analysed by Cox proportional hazards regression.

IRAS number 345246, approved 23/10/2024 by North of Scotland Research Ethics Service. Results will be shared with participants, third sector homelessness organisations, health and social care partnerships, then peer-reviewed journals and conferences worldwide, from the first quarter of 2027.

ISRCTN12234059 registered on 20/2/2025 (ISRCTN).

Growing evidence points towards the integral role of both central and peripheral inflammation across all neurodegenerative diseases, including dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The immune alterations observed in these diseases may occur long before the onset of clinical and cognitive symptoms; however, the exact timing and role of inflammation in the pathogenesis of neurodegenerative disease remains unclear. Findings to date are conflicting, with most work focused on AD rather than other dementias and most studies from single sites and cross-sectional. Through longitudinally examining detailed phenotypes of the peripheral immune system using mass cytometry, the Immune Profiling in Early Cognitive Disorders study aims to uncover specific immune signatures in early AD and DLB, how these signatures change over time and how they relate to disease progression and cognitive changes.

Blood, cerebrospinal fluid, saliva and urine samples will be collected from a cohort of participants with either prodromal (mild cognitive impairment) or early dementia due to Lewy bodies or AD (MCI-LB and DLB; and MCI-AD and AD), alongside healthy controls. Through immunophenotyping with mass cytometry, detailed immune fingerprints will be identified for these groups. We will assess which key combinations of immune cell clusters are predictive of disease phenotype, cognitive decline and progression to dementia. Samples will also be evaluated with novel techniques to measure markers of degenerative pathology and inflammation.

This study was approved by the Preston North West Research Ethics committee (21/NW/0314) and is registered with the ISRCTN registry (ISRCTN62392656). The study is ongoing (since June 2022). Baseline visits are being undertaken, and follow-up visits have started for some participants. Full data analyses will be completed and submitted for publication upon conclusion of the study.

Saskatchewan is facing a public health crisis driven by high rates of HIV, syphilis and hepatitis C virus (HCV) infections, particularly among people who use drugs. Injection drug use is a major contributor to these syndemic infections, exacerbated by structural barriers such as stigma, poverty and limited culturally safe healthcare. Innovative, community-informed approaches are urgently needed to improve prevention, testing and linkage to care.

This study will implement a rapid assessment and response system in Regina, Saskatchewan, Canada, integrating geospatial mapping of community needle prevalence with pop-up interventions. Needle hotspot maps will be used to guide the deployment of community-based pop-up events offering point-of-care testing for HIV, syphilis and HCV, alongside education on pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP). A convergent participatory mixed-methods design will be used to evaluate feasibility, acceptability and effectiveness, guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Quantitative data will assess changes in knowledge of PrEP and PEP, satisfaction with the intervention and report new diagnoses and participant demographics descriptively. A qualitative substudy will include 30 participants and will explore experiences with the intervention, barriers to care and perceptions of service delivery.

Ethical approval has been obtained from the research ethics board of the Saskatchewan Health Authority (#24–91). Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. This study may provide a model of community-based geospatial testing and education that could be scaled up and adapted elsewhere.

Open Science Framework https://doi.org/10.17605/OSF.IO/HVK3B

Cellulitis is a common bacterial skin infection causing significant pain, swelling and impact on daily activities, frequently leading to emergency department presentations and hospital admissions. While antibiotics are the mainstay of treatment, they do not directly address inflammation, often resulting in persisting or worsening symptoms in the initial days. Corticosteroids, with their potent anti-inflammatory effects, have shown benefit in other acute infections but are not currently standard care for patients with cellulitis. This trial aims to determine if adjunctive oral dexamethasone can reduce pain and improve outcomes in adults with cellulitis presenting to UK urgent secondary care settings.

This is a pragmatic, multicentre, double-blind, placebo-controlled, randomised, parallel group, phase 3 superiority trial, with an internal pilot and parallel health economic evaluation. Adult patients (≥16 years) with a clinical diagnosis of cellulitis (at any body site except the orbit) presenting to urgent secondary care will be screened for eligibility. 450 participants will be randomised (1:1) to receive either two 8 mg doses of oral dexamethasone or matched placebo, administered approximately 24 hours apart, in addition to standard antibiotic therapy. The primary outcome is total pain experienced over the first 3 days postrandomisation, calculated using the standardised area under the curve from pain scores (Numerical Rating Scale 0–10) across up to seven timepoints. Secondary outcomes include health-related quality of life (EuroQol 5 Dimension 5 Level), patient global impression of improvement, analgesia and antibiotic usage, hospital (re)admissions, complications, unscheduled healthcare use, cellulitis recurrence and cost-effectiveness at 90 days. The primary estimand will apply a treatment policy approach to intercurrent events.

The trial has received ethical approval from South Central—Oxford B Research Ethics Committee (reference: 24/SC/0289) and will be conducted in compliance with Good Clinical Practice and applicable regulations. Informed consent will be obtained from all participants. A model consent form can be seen in . Findings will be disseminated through peer-reviewed publications and conference presentations, and to patient groups and relevant clinical guideline committees.

ISRCTN76873478.

The COVID-19 pandemic has made long-standing nursing workforce challenges apparent on an international scale. Decision-makers must develop multi-pronged approaches to foster the development and maintenance of a strong nursing workforce to support health systems. These approaches require attendance to recruitment and retention initiatives that show promise for stabilising the nursing workforce now and into the future.

Searches were conducted across MEDLINE, Embase, CINAHL and Scopus from January 2014 up to 11 March 2024. This rapid umbrella review protocol is guided by the Joanna Briggs Institute scoping review methodology and adheres to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. The research question guiding this review is: what structures have healthcare systems put in place to stabilise, support and sustain the nursing workforce? This review will include existing reviews of nursing workforce initiatives with outcomes that impact nursing recruitment and retention. Results will support local health transformation including the development of a jurisdictional nursing workforce stabilisation strategy. Findings from this review will be relevant for the design, refinement and implementation of nursing workforce sustainability strategies in countries around the globe and may apply to strategies for other healthcare workers.

Institutional research ethics board exemption was received. The research team is supported by an advisory group that includes provider and patient partners. The results from this study will inform the Nursing Workforce Strategy for the province of Nova Scotia as part of a larger Canadian Institutes of Health Research-funded project. They will also inform broader planning and strategy in Canada through integration with other evidence-generation activities such as comparative policy analyses and workforce planning exercises. Finally, the results will be published in a peer-reviewed journal.

Registered through Open Science Framework: https://doi.org/10.17605/OSF.IO/CUJYK

Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disease characterised by cognitive, behavioural and motor problems. Motor symptoms are highly disabling, while cognitive and behavioural changes have a major impact on carer burden, quality of life and prognosis. Apathy and impulsivity are very common, often coexistent in PSP, and negatively predict survival. In preclinical models and other diseases, apathy and impulsivity are associated with noradrenergic deficits, which can be severe in PSP.

Noradrenaline for Progressive Supranuclear Palsy Syndromes trial is a randomised, double-blind, placebo-controlled, crossover design, Phase IIb clinical trial to evaluate the efficacy and safety of oral atomoxetine for the treatment of cognitive and behavioural changes in PSP. Participants receive atomoxetine 40 mg (10 mg/mL oral solution) once daily or a matched placebo solution, in random order, each for 8 weeks. An ‘informant’, who knows the patient with PSP well, is co-recruited to complete some of the trial outcome measures. Participants remain in the trial for 22 weeks after randomisation. The primary objectives are to assess (1) safety and tolerability and (2) efficacy versus placebo on challenging behaviours as reported in a subscale of the Cambridge Behavioural Inventory. Secondary and exploratory measures relate to cognition, the PSP Rating Scale, mood and potential baseline predictors of individual response to atomoxetine computed from imaging, genetic and cognitive measures at baseline.

The trial was approved by the South Central-Oxford B Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (REC reference: 20/SC/0416). Dissemination will include publication in peer-reviewed journals, presentations at academic and public conferences and engagement with patients, the public, policymakers and practitioners.

ISRCTN99462035; DOI: https://doi.org/10.1186/ISRCTN99462035; EudraCT (European Union Drug Regulating Authorities Clinical Trials Database)/CTIS (Clinical Trial Information System) number: 2019-004472-19; IRAS (Integrated Research Application System) number: 272063; Secondary identifying numbers: CPMS (Central Portfolio Management System) 44441.

An increasing number of teenagers and young adults (TYA) with chronic conditions and complex needs are transitioning from paediatric to adult services, including admission to intensive care units (ICUs). As these services are often ill-equipped to care for TYA, there is a risk of compromised care. Despite recent guidelines from the UK Paediatric Critical Care and Intensive Care Societies highlighting the importance and urgency of improving ICU transition, current recommendations are not evidence-based and established pathways for ICU transition remain limited.

This mixed-methods research study aims to generate evidence to underpin national policy on transition from paediatric to adult ICUs that will improve clinical care and patient experience. To do this, we will: (1) link and analyse UK national data (years 2017–2024) on paediatric and adult ICU admissions, hospital inpatient, outpatient and emergency care visits and survival status, to determine the clinical characteristics and healthcare resource utilisation from teenage years to early adulthood of people admitted to an ICU as a young person (admission aged 14 and 15), and how these relate to ICU admissions after age 16; (2) conduct semistructured interviews, online forums and surveys with TYA patients, carers and health professionals to understand their experience of transition in ICU services; and (3) synthesise these strands of evidence and use a structured process of stakeholder engagement to propose potential targeted improvements as appropriate.

This study was approved by the East of England - Cambridge South Research Ethics Committee on 1 August 2024 (research ethics committee number 24/EE/0108), and the Health Research Authority Confidentiality Advisory Group (CAG) on 7 October 2024 (CAG number 24/CAG/0068). Study results will be actively disseminated through peer-reviewed journals, conference presentations and accessible lay texts and graphic summaries for the use of charities and patients including those with learning disabilities and neurodevelopmental disorders.

Spinal manipulative therapy (SMT) is a common manual therapy intervention provided by healthcare providers for patients with low back pain (LBP). Responses to SMT are influenced by interactions between the patient and provider. Contextual factors may be specific to the patient, provider, patient-provider relationship or environment in which treatment is provided, with all capable of influencing clinical outcomes. The overall goal of this study is to gain a deeper understanding of contextual factors associated with manual therapy utilisation, perception and outcomes, from both patient and provider perspectives. A better understanding of modifiable contextual factors will inform future studies testing the impact on how SMT is delivered to patients influences clinical outcomes that could potentially advance the clinical science of manual therapy.

A prospective, single-arm study design with follow-up measures assessed up to 26 weeks after initiation of physical therapy for LBP will be used to assess relationships between physical therapy clinical outcomes and contextual factors related to the patient (preference, expectation, pain beliefs, pain associated distress and prior manual therapy experiences), the provider (equipoise, expectation, pain beliefs and clinical experience) and the interaction between the two (therapeutic alliance). Multimodal treatment approach of SMT (required during initial three treatment sessions within a 2week period), exercise and education supported by recent clinical practice guidelines will be encouraged for this study.

Ethics approval for the study was obtained from the University of Florida Institutional Review Board. Informed consent is required for physical therapist and patient participant enrolment in this project. The results of this study will be disseminated at professional scientific conferences and submitted for publication in peer-reviewed journals. Reference or approval number: IRB#: IRB202301700

NCT06590116.