Glaucoma is the leading cause of irreversible blindness in the world. The need to diagnose glaucoma early in its natural history before extensive sight loss occurs cannot be overemphasised. However, glaucoma is largely asymptomatic in the early stages of the disease making it complex to diagnose clinically and requires the support of technology. The objective of this scoping review is to determine the nature and extent of the evidence for use of portable devices in the diagnosis of glaucoma.

We will consider studies conducted in all healthcare settings using portable devices for the detection of all type of adult glaucoma. We will also include any systematic reviews or scoping reviews, which relate to this topic. Searches will be conducted in MEDLINE, Embase, CENTRAL on the Cochrane Library and Global Health databases, from their inception to the present. Reference lists from publications identified in the searches will also be reviewed. Two authors will independently screen titles and abstracts, followed by full-text screening to assess studies for inclusion. Any disagreements will be discussed and resolved with a third author. Tables accompanied by narrative descriptions will be employed to discuss results and show how it relates to review questions.

Ethical approval is not required in this review. Only published and publicly accessible data will be used. We will publish our findings in an open-access, peer-reviewed journal and develop an accessible summary of results and recommendations.

Individuals with dementia face an increased risk of falls. Falls can cause a decline in the individual’s overall functionality. All types of falls, including those that do not result in injury, can lead to psychosocial consequences, such as diminished confidence and a fear of falling. Projections indicate a rising trend in dementia diagnoses, implying an increase in fall incidents. Yet, there is a lack of evidence to support interventions for people living with dementia who have fallen. Our objective is to test the feasibility of a falls intervention trial for people with dementia.

This is a UK-based two-arm pilot cluster randomised controlled trial. In this study, six collaborating sites, which form the clusters, will be randomly allocated to either the intervention arm or the control arm (receiving treatment as usual) at a 1:1 ratio. During the 6 month recruitment phase, each cluster will enrol 10 dyads, comprising 10 individuals with dementia and their respective carers, leading to a total sample size of 60 dyads. The primary outcomes are the feasibility parameters for a full trial (ie, percentage consented, follow-up rate and cost framework). Secondary outcomes include activities of daily living, quality of life, fall efficacy, mobility, goal attainment, cognitive status, occurrence of falls, carer burden and healthcare service utilisation. Outcome measures will be collected at baseline and 28 weeks, with an additional assessment scheduled at 12 weeks for the healthcare service utilisation questionnaire. An embedded process evaluation, consisting of interviews and observations with participants and healthcare professionals, will explore how the intervention operates and the fidelity of study processes.

The study was approved by the NHS and local authority research governance and research ethics committees (NHS REC reference: 23/WA/0126). The results will be shared at meetings and conferences and will be published in peer-reviewed journals.

ISRCTN16413728.

Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size.

This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of the colonisation rate. The primary outcome of this study is to determine the optimal SPN3 dose and inoculation regime to establish the highest rates of NP colonisation in healthy adults. Secondary outcomes include determining density and duration of experimental SPN3 NP colonisation and characterising mucosal and systemic immune responses to SPN3 challenge.

This study is approved by the NHS Research and Ethics Committee (reference 22/NW/0051). Findings will be published in peer-reviewed journals and reports will be made available to participants.

Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%–20%. Several iNTS vaccine candidates are in early-stage assessment which—if found effective—would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis.

This double-blind, safety and dose-escalation study will randomise 40–80 healthy UK participants aged 18–50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%–75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host–pathogen interactions in response to infection.

Ethical approval has been obtained from the NHS Health Research Authority (London—Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants.

NCT05870150

There is an urgent need for scalable strategies for treating overweight and obesity in clinical settings. PROPS 2.0 (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0) aims to adapt and implement the combined intervention from the PROPS Study at scale, in a diverse cross-section of patients and providers.

We are implementing PROPS 2.0 across a variety of clinics at Brigham and Women’s Hospital, targeting enrolment of 5000 patients. Providers can refer patients or patients can self-refer. Eligible patients must be ≥20 years old and have a body mass index (BMI) of ≥30 kg/m² or a BMI of 25–29.9 kg/m² plus another cardiovascular risk factor or obesity-related condition. After enrolment, patients register for the RestoreHealth online programme/app (HealthFleet Inc.) and participate for 12 months. Patients can engage with the programme and receive personalized feedback from a coach. Patient navigators help to enrol patients, enter updates in the electronic health record, and refer patients to additional resources. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework is guiding the evaluation.

The Mass General Brigham Human Research Committee approved this protocol. An implementation guide will be created and disseminated, to help other sites adopt the intervention in the future.

NCT0555925.

Social prescribing (SP) is a non-medical intervention in which professionals refer patients to a link worker (LW), who connects them with appropriate support. Children and young people (CYP) with neurodisability often have unmet needs and may bypass community initiatives. We undertook a review of hospital-initiated SP for CYP with neurodisability.

Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance and using Mixed Methods Appraisal Tool.

Medline, PsycINFO, PsycARTICLES, Embase, CINAHL, Scopus, Web of Science and FutureNHS, searched from 1 January 2000 to 19 October 2023, with no language restrictions.

Studies describing SP interventions for CYP (ages 0–25 years) with neurodisability/neurodivergence. Exclusions: interventions outside of secondary care; with no description; or no LW.

Two researchers independently screened references. Data were charted, summarised, quality assessments performed and narratively reviewed.

After removal of duplicates, 518 references were identified. Following screening, eight articles (covering five SP schemes) were included. Rahi et al connected 68 families of CYP newly diagnosed with visual impairment to a community LW. Families needed information about social and educational services, and emotional support. Healthcare professionals had more time for clinical issues. Six papers described three different digital interventions supporting in total 86 CYP with traumatic brain injury and their families. Wade et al (2004, 2005a, 2005b) provided a website with core and individualised sessions, and weekly therapist support. Wade et al (2018) provided a smartphone application, website and weekly meetings with an online coach. These interventions boosted social behaviours. Wade et al (2014, 2015) found that online family problem-solving therapy improved overall child functioning compared with self-guided resources. Toutain et al (2009) provided non-medical support to 11 children with fetal alcohol syndrome and their mothers. No outcome data were provided. Studies reported benefits to health, well-being, healthcare usage, knowledge, skills, satisfaction and service delivery.

Literature describing hospital-initiated SP schemes for CYP with neurodisability, while sparse, suggests potential benefit.

CRD42022384188.

Globally, incidence, prevalence and mortality rates of skin cancers are escalating. Earlier detection by well-trained primary care providers in techniques such as dermoscopy could reduce unnecessary referrals and improve longer term outcomes. A review of reviews is planned to compare and contrast the conduct, quality, findings and conclusions of multiple systematic and scoping reviews addressing the effectiveness of training primary care providers in dermoscopy, which will provide a critique and synthesis of the current body of review evidence.

Four databases (Cochrane, CINAHL, EMBASE and MEDLINE Complete) will be comprehensively searched from database inception to identify published, peer-reviewed English-language articles describing scoping and systematic reviews of the effectiveness of training primary care providers in the use of dermoscopy to detect skin cancers. Two researchers will independently conduct the searches and screen the results for potentially eligible studies using ‘Research Screener’ (a semi-automated machine learning tool). Backwards and forwards citation tracing will be conducted to supplement the search. A narrative summary of included reviews will be conducted. Study characteristics, for example, population; type of educational programme, including content, delivery method, duration and assessment; and outcomes for dermoscopy will be extracted into a standardised table. Data extraction will be checked by the second reviewer. Methodological quality will be evaluated by two reviewers independently using the Critical Appraisal Tool for Health Promotion and Prevention Reviews. Results of the assessments will be considered by the two reviewers and any discrepancies will be resolved by team consensus.

Ethics approval is not required to conduct the planned systematic review of peer-reviewed, published articles because the research does not involve human participants. Findings will be published in a peer-reviewed journal, presented at leading public health, cancer and primary care conferences, and disseminated via website postings and social media channels.

CRD42023396276.

Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care.

Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of –2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.

The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40–50 UK ICUs.

The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines.

ClinicalTrials.gov NCT03653832.

Despite evidence for the efficacy and effectiveness of hand hygiene in reducing the transmission of infectious diseases, there are gaps in global normative guidance around hand hygiene in community settings. The goal of this review is to systematically retrieve and synthesise available evidence on hand hygiene in community settings across four areas: (1) effective hand hygiene; (2) minimum requirements; (3) behaviour change and (4) government measures.

This protocol entails a two-phased approach to identify relevant studies for multiple related systematic reviews. Phase 1 involves a broad search to capture all studies on hand hygiene in community settings. Databases, trial registries, expert consultations and hand searches of reference lists will be used to ensure an exhaustive search. A comprehensive, electronic search strategy will be used to identify studies indexed in PubMed, Web of Science, EMBASE, CINAHL, Global Health, Cochrane Library, Global Index Medicus, Scopus, PAIS Index, WHO IRIS, UN Digital Library and World Bank eLibrary published in English from January 1980 to March 2023. The outcome of phase 1 will be a reduced sample of studies from which further screening, specific to research questions across the four key areas can be performed. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Quantitative and qualitative data will be extracted following best practices. We will assess all studies using the Mixed Method Appraisal Tool. All effect measures pertaining to review outcomes will be reported and a narrative synthesis of all studies will be presented including ‘data-driven’ descriptive themes and ‘theory-driven’ analytical themes as applicable.

This systematic review is exempt from ethics approval because the work is carried out on published documents. The findings of the reviews will be disseminated in related peer-reviewed journals.

CRD42023429145.

Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.

The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.

The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.

Ethical approval for this study has been obtained from the South Central—Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.

EudraCT Number: 2020-000510-14.

Care home residents have experienced significant morbidity, mortality and disruption following outbreaks of SARS-CoV-2. Regular SARS-CoV-2 testing of care home staff was introduced to reduce transmission of infection, but it is unclear whether this remains beneficial. This trial aims to investigate whether use of regular asymptomatic staff testing, alongside funding to reimburse sick pay for those who test positive and meet costs of employing agency staff, is a feasible and effective strategy to reduce COVID-19 impact in care homes.

The VIVALDI-Clinical Trial is a multicentre, open-label, cluster randomised controlled, phase III/IV superiority trial in up to 280 residential and/or nursing homes in England providing care to adults aged >65 years. All regular and agency staff will be enrolled, excepting those who opt out. Homes will be randomised to the intervention arm (twice weekly asymptomatic staff testing for SARS-CoV-2) or the control arm (current national testing guidance). Staff who test positive for SARS-CoV-2 will self-isolate and receive sick pay. Care providers will be reimbursed for costs associated with employing temporary staff to backfill for absence arising directly from the trial.

The trial will be delivered by a multidisciplinary research team through a series of five work packages.

The primary outcome is the incidence of COVID-19-related hospital admissions in residents. Secondary outcomes include the number and duration of outbreaks and home closures. Health economic and modelling analyses will investigate the cost-effectiveness and cost consequences of the testing intervention. A process evaluation using qualitative interviews will be conducted to understand intervention roll out and identify areas for optimisation to inform future intervention scale-up, should the testing approach prove effective and cost-effective. Stakeholder engagement will be undertaken to enable the sector to plan for results and their implications and to coproduce recommendations on the use of testing for policy-makers.

The study has been approved by the London—Bromley Research Ethics Committee (reference number 22/LO/0846) and the Health Research Authority (22/CAG/0165). The results of the trial will be disseminated regardless of the direction of effect. The publication of the results will comply with a trial-specific publication policy and will include submission to open access journals. A lay summary of the results will also be produced to disseminate the results to participants.

ISRCTN13296529.

The objective of this study is to explore patient, relative/carer and clinician perceptions of barriers to early physical rehabilitation in intensive care units (ICUs) within an associated group of hospitals in the UK and how they can be overcome.

Qualitative study using semi-structured interviews and thematic framework analysis.

Four ICUs over three hospital sites in London, UK.

Former ICU patients or their relatives/carers with personal experience of ICU rehabilitation. ICU clinicians, including doctors, nurses, physiotherapists and occupational therapists, involved in the delivery of physical rehabilitation or decisions over its initiation.

Views and experiences on the barriers and facilitators to ICU physical rehabilitation.

Interviews were carried out with 11 former patients, 3 family members and 16 clinicians. The themes generated related to: safety and physiological concerns, patient participation and engagement, clinician experience and knowledge, teamwork, equipment and environment and risks and benefits of rehabilitation in intensive care. The overarching theme for overcoming barriers was a change in working model from ICU clinicians having separate responsibilities (a multidisciplinary approach) to one where all parties have a shared aim of providing patient-centred ICU physical rehabilitation (an interdisciplinary approach).

The results have revealed barriers that can be modified to improve rehabilitation delivery in an ICU. Interdisciplinary working could overcome many of these barriers to optimise recovery from critical illness.