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Phase II multicentre double-blind randomised controlled trial of a Bivalent VaccInation against Salmonella Typhi and Paratyphi A (BiVISTA) using a controlled human infection model of paratyphoid A infection: study protocol

Por: Paganotti Vicentine · M. · McCann · N. · Hennigan · O. · Maria · N. · Juarez Molina · C. I. · Koleva · S. · Islam · M. K. · Jones · E. · Flaxman · A. · Day · N. · MacDonald · A. · Adnan · M. · Singh · N. · Vernon · S. · Wilson · E. · Potey · A. V. · Dharmadhikari · A. · Gaidhane · S. · Kul
Introduction

Enteric fever, primarily caused by Salmonella enterica Typhi and Salmonella enterica Paratyphi A (SPA), is endemic mainly in South Asia, disproportionately affecting school-age children. Although typhoid conjugate vaccines (TCVs) are effective and implemented in many countries, no licensed vaccine exists against paratyphoid A. Bivalent vaccines targeting both S. Typhi and SPA may address this gap. Although field efficacy trials are not considered feasible, controlled human infection models (CHIMs) offer an alternative pathway for evaluating vaccine efficacy. This will be the first efficacy study of a bivalent vaccine against typhoid and paratyphoid A using a paratyphoid CHIM.

Methods and analysis

This is a phase II multicentre, double-blind, randomised controlled trial assessing the efficacy and immunogenicity of a bivalent conjugate vaccine candidate, Serum Institute of India Typhoid Conjugate Vaccine (Bivalent) (SII-TCV(B)), against SPA using a CHIM in healthy UK adults aged 18–55 years. A total of 192 participants will be randomised 1:1 to receive either SII-TCV(B) or a licensed Vi-polysaccharide typhoid vaccine (Vi-PS). All participants will be orally challenged with S. Paratyphi A (strain NVGH308) 28 days postvaccination. Participants will be monitored closely for 14 days and treated at 14 days postchallenge or promptly on diagnosis, according to prespecified criteria. The primary objective is to evaluate vaccine efficacy of SII-TCV(B) against paratyphoid infection using a CHIM. The coprimary immunogenicity objective is to assess non-inferiority of the typhoid IgG response compared with a licensed Vi-PS control.

Ethics and dissemination

The study has received ethical approval from the Berkshire Research Ethics Committee (24/SC/0309) and regulatory approval from the UK Medicines and Healthcare products Regulatory Agency. Results will be disseminated via peer-reviewed publications and scientific meetings.

Trial registration number

ISRCTN65855590.

Specialist PrE-hospital rEDirection for ischaemic stroke thrombectomY (SPEEDY): study protocol for a cluster randomised controlled trial with included health economic and process evaluations

Por: Shaw · L. · Allen · M. · Day · J. · Ford · G. A. · James · M. · McClelland · G. · McMeekin · P. · Mossop · H. · Pope · C. J. · Simmonds · R. L. · White · P. · Wilson · N. · Price · C. I.
Background

Outcome from large vessel occlusion stroke can be significantly improved by time-critical thrombectomy but treatment is only available in regional comprehensive stroke centres (CSCs). Many patients are first admitted to a local primary stroke centre (PSC) and require transfer to a CSC, which delays treatment and decreases the chance of a good outcome. Access to thrombectomy might be improved if eligible patients could be identified in the prehospital setting and selectively redirected to a CSC. This study is evaluating a new specialist prehospital redirection pathway intended to facilitate access to thrombectomy.

Methods and analysis

This study is a multicentre cluster randomised controlled trial with included health economic and process evaluations. Clusters are ambulance stations (or teams) which are work bases for ambulance practitioners. Intervention allocated ambulance practitioners use the Specialist PrE-hospital rEDirection for ischaemic stroke thrombectomY (‘SPEEDY’) pathway which comprises initiation according to specific criteria followed by contact with CSC staff who undertake a remote assessment to select patients for direct CSC admission. Control allocated ambulance practitioners continue to provide standard care which comprises admission to a local PSC and transfer to a CSC for thrombectomy if required. A co-primary outcome of thrombectomy treatment rate and time from stroke symptom onset to thrombectomy treatment will evaluate the impact of the pathway. Secondary outcomes include key aspects of emergency care including prehospital/hospital time intervals, receipt of other treatments including thrombolysis, and performance characteristics of the pathway. A broad population of all ambulance practitioner suspected and confirmed stroke patients across participating regions is being enrolled with a consent waiver. Data about SPEEDY pathway delivery are captured onto a study case record form, but all other data are obtained from routine healthcare records. Powered on a ‘primary analysis population’ (ischaemic stroke patients with pathway initiation criteria), 894 participants will detect an 8.4% difference in rate and data from 564 thrombectomy procedures will detect a 30 minute difference in time to treatment. The full study population is estimated to be approximately 80 000. Regression modelling will be used to examine primary and secondary outcomes in several analysis populations. The economic analyses will include cost-effectiveness and cost–utility analyses, and calculation of willingness to pay at a range of accepted threshold values. The process evaluation involves semi-structured interviews with professionals and patient/family members to explore views and experiences about the SPEEDY pathway.

Ethics and dissemination

This study has ethical, Health Research Authority and participating NHS Trust approvals.

Dissemination of study results will include presentations at national and international conferences and events, publication in peer-reviewed journals, and plain English summaries for patient/public engagement activities.

Trial registration number

ISRCTN77453332.

The clinical application of shared decision-making in emergency surgery: a scoping review protocol

Por: Bisset · C. N. · Keane · C. · McKee · T. · John-Charles · R. · Wells · C. I. · Moug · S. J.
Introduction

Shared decision-making (SDM) between clinicians and patients is considered ‘best practice’. There is limited evidence regarding SDM in surgery, particularly in the emergency setting. Emergency SDM may be particularly challenging due to: time pressures, the patient’s underlying condition and the nature of the patient-surgeon interaction. However, emergency surgery arguably has a greater need for SDM due to the likelihood of disparate outcomes from intervention, which is dependent on the various treatment options available. This is necessary for patients to make informed decisions regarding their treatment of surgical pathology. The primary objective of this scoping review is to understand the extent and type of evidence in relation to SDM in emergency surgery to determine methods for improving SDM.

Methods

Any studies reporting SDM in emergency surgery on adult patients (age >18 years) will be included. EMBASE, Medline, Cochrane, CINAHL and Scopus databases will be searched for articles with no language or date limits. Studies will be screened by two independent reviewers, with consensus met prior to data extraction. Data extracted to include study design, details of study population, tools used to measure SDM, prevalence of SDM and barriers and enablers for SDM.

A systematic narrative synthesis will be performed following JBI (Joanna Briggs Institute) guidance. These will summarise findings of included studies. The findings may inform future research into facilitating implementation of SDM in emergency surgery.

Ethics and dissemination

This study does not require ethical approval. Final findings will be submitted for peer-reviewed publication and presentation at surgical conferences.

10 years on from the landmark stroke thrombectomy trials, where are we now? A qualitative study examining professional views on the implementation of endovascular treatment for ischaemic stroke in England

Por: Simmonds · R. L. · Day · J. · James · M. · White · P. · Price · C. I. · Shaw · L. · Ford · G. · Pope · C. J.
Objective

To explore multiprofessional views about system-wide factors influencing (impeding or facilitating) the delivery of stroke mechanical thrombectomy (MT) services and/or improvements to this pathway in England.

Design

A pragmatic exploratory qualitative study using online focus groups and semi-structured interviews with National Health Service (NHS) professionals and those working in a stroke strategic/policy lead role. We thematically analysed the data using the Framework Approach to understand participants’ views on the challenges to improving current and future MT implementation.

Setting

NHS trusts and other key stroke strategic/policy organisations covering 10 geographical regions in England and a national perspective.

Participants

A total of 29 professionals, working in an NHS clinical and managerial position and/or a stroke strategic national/regional clinical/policy lead role, participated in five focus groups and six individual semi-structured interviews between April and June 2024.

Results

We identified five themes relating to MT implementation progress and challenges (1) workforce, (2) clinical care pathways, (3) service/system, (4) cross-cutting theme: communications and (5) cross-cutting theme: culture. Our analysis emphasised the increasing complexity and inter-related factors shaping the emergency stroke pathway for MT provision and a need to acknowledge key people-related, organisational and sociocultural factors during service planning.

Conclusions

Despite the challenges and complexity, professionals were optimistic that further progress would be made with MT delivery in England. However, ongoing improvement strategies are required, which also acknowledge wider cultural factors and system-wide relationships and are not just focused on care pathways and resources.

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