Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

First Nations communities in Canada are disproportionately impacted by prenatal opioid exposure (POE) and neonatal abstinence syndrome (NAS). In response, we developed a research partnership with 13 First Nations communities in Ontario. Phase I of the research project, initiated in 2018, included the development of mixed-methods reports on the impact of POE for each community. This protocol outlines the evaluation of phase II, during which nine communities individually co-designed and implemented community-specific knowledge mobilisation (KMb) plans informed by findings from phase I. The evaluation aims to assess advisory working group engagement, KMb implementation and perceived community-level impacts.

This mixed-methods evaluation integrates survey and qualitative data to assess First Nations-led KMb products and activities. The Public and Patient Engagement Evaluation Tool, a validated survey instrument, will be administered to advisory group members and analysed descriptively. Focus groups and interviews will be conducted to explore advisory working group members’ experiences and analysed using phenomenological methods. Qualitative findings will be mapped to the Engage with Impact framework to assess outcomes across engagement domains.

Ethics approval has been granted by Vancouver Island University. All community contacts and advisory working group members will provide informed consent prior to data collection. Phase II activities are governed by formal community agreements. In alignment with First Nations Principles of OCAP (Ownership, Control, Access and Possession), First Nations community partners retain ownership of their KMb products and are actively involved in the design, implementation and dissemination of the project evaluation. Results will be shared through peer-reviewed publications, community reports and knowledge-sharing events.

Childhood cancer survivors (CCSs) experience educational disruptions during and following treatment, yet robust, longitudinal evidence on educational performance remains limited. We will investigate differences in educational outcomes between CCSs and non-cancer peers during primary and secondary school. We will also explore how sociodemographic factors and age at diagnosis contribute to potential differences in General Certificate of Secondary Education (GCSE) examinations, a critical indicator of future academic and employment prospects.

We will use the Education and Child Health Insights from Linked Data (ECHILD) to capture linked health and education data for children born in National Health Service (NHS)-funded hospitals in England. We will generate birth cohorts spanning September 1997 to August 2015 (estimated sample size: ~10 million), formed of pupils expected to have undertaken national curriculum assessments between academic years 2004/2005 and 2021/2022 including Key Stage (KS) 1, 2 and 4, corresponding to ages 7, 11 and 16 respectively. Cancer diagnosis will be identified from inpatient hospital records, using International Classification of Diseases, 10th Revision codes (ICD-10). We will investigate differences between CCS and their non-cancer peers in terms of their sociodemographic characteristics and describe trends in educational performances at all KSs, recorded Special Educational Needs and Disabilities (SEND) and school absences. Differences in KS4 (GCSE) performances between CCS and non-cancer peers will be quantified, according to and accounting for geographic region, sex, deprivation, ethnicity and birth characteristics. To assess whether cancer diagnosis disrupts academic trajectories, we will restrict analysis to those with KS2 attainment data and investigate KS4 performance. We will finally explore the influence of age at diagnosis on educational performance at KS4.

Ethics approval was granted by NHS Health Research Authority Research Ethics Committee (20/EE/0180). Findings will be shared with academics, policymakers, children and families affected by childhood cancer, and published in journals. Code/metadata will be shared on ECHILD GitHub repository.

Older age is one of the greatest risk factors of dementia, and the rural demographic is ageing in Canada. Compared with their urban counterparts, rural older adults often face unique challenges in accessing cognitive healthcare, which is exacerbated by a shortage of healthcare specialists, public transportation, finances, education, services and dispersed geography. This scoping review protocol outlines the methodology that will be used to examine the literature about the care priorities, service needs and lived experiences from the perspectives of rural older adults living with cognitive impairment and dementia in Canada.

Our scoping review protocol will follow the guidance of Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extensions for Scoping Reviews checklist. Our search strategy will identify relevant peer-reviewed literature in databases including Cumulated Index in Nursing and Allied Health Literature (CINAHL), EMBASE, PsycINFO, PubMed, Web of Science and Scopus. The database search dates for this scoping review will be from 1 January 2015 to 1 January 2025. The data will be charted by two reviewers using a standardised data extraction table. Inductive content analysis will be performed using a three-step process.

Given this scoping review will be an examination of the published literature, human subjects will not be included in this research. Therefore, ethics approval is not required. Knowledge mobilisation and dissemination strategies will include peer-reviewed journal articles, conference presentations, community workshops, newsletter articles and webinars. This study may provide valuable information for healthcare practitioners, community leaders and policymakers working to support people living with cognitive impairment and dementia in rural communities.

Dysregulated immunity may account for an increased risk of infection and other adverse outcomes among frail hospitalised persons. The primary objective of this study is to examine whether baseline frailty is associated with the risk of developing ventilator-associated pneumonia (VAP) or other intensive care unit (ICU)-acquired infections among invasively ventilated adults. Additional objectives are to examine the relationship between frailty and hospital length of stay, discharge to a long-term care facility and vital status. We hypothesise that persons with frailty compared with others would have an increased risk of VAP and other infections, a longer hospital stay, higher probability of discharge to a long-term care facility and higher mortality.

This is a preplanned secondary analysis of the PROSPECT trial (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) which enrolled patients across 44 ICUs in three countries. We will use Cox proportional hazards regression analysis to assess the association of frailty with the clinical outcomes of interest, adjusting for other baseline variables. Baseline demographic and descriptive outcome data will be reported using descriptive statistics. Regression results will be presented as adjusted HRs or ORs with 95% CIs for the associations of each independent variable with the primary, secondary and tertiary outcomes.

Participating hospital research ethics board approved the PROSPECT trial and data collection. The protocol for this study was approved by the Hamilton Integrated Research Ethics Board on 20 August 2015 (Project ID:19128). This study will identify whether frailty is associated with risk of VAP and other healthcare-associated infections in invasively ventilated patients, adjusted for other baseline factors. Results may be useful to patients, their caregivers, clinicians and the design of future research. Findings will be disseminated to investigators at a meeting of the Canadian Critical Care Trials Group. We will present study results at an international conference in the fields of critical care and infectious diseases, to coincide with or precede open-access peer-review publication. To aid knowledge dissemination, we will use a variety of formats. For example, for traditional and social media, we will create two different visual abstracts and infographics of our results suitable to share on clinician-facing and public-facing platforms.

NCT02462590.

As of 2024, 123.2 million people had been forcibly displaced as a result of persecution, armed conflict or climate-related catastrophes, and these numbers are predicted to rise. There is a growing awareness of possible intergenerational effects of trauma on life-course health and well-being, however few studies have followed individuals longitudinally starting prenatally. This paper describes the first large prenatal birth cohort study in a refugee context in a lower middle-income country. This study aims to investigate the potential lifespan health and developmental implications of being born into a protracted humanitarian context, and what factors can buffer from the adversity posed by conflict and displacement.

We outline our approach of recruiting, consenting and gathering data from pregnant Rohingya refugee and host community women (N=2888; 80% Rohingya) over the course of 12 months in Cox’s Bazar, Bangladesh.

A fifth wave of data collection, when children were 6 months old, was completed in April 2025. Rohingya women were substantially less literate; were marrying and having children at slightly younger ages, were more likely to live in crowded, resource-limited households and exhibited higher rates of clinically significant post-traumatic stress disorder and anxiety than host community women.

There is a critical need for research in displaced populations in order to elucidate potentially lasting transgenerational impacts of experiencing conflict and displacement trauma, and the prenatal and postnatal factors that support health and development across the life span. The next follow-up is planned when the children turn 36 months of age (starting March 2026).

Public involvement in mental health research enhances research quality. The use of citizen science methods in mental health research has been described as a conclusion of a movement towards increased public involvement; however, this field is in its early stages of development. Our objective was to create a theory of change (ToC) for how citizen science can be used to enhance mental health research quality.

Iterative consultation with the stakeholders of an existing citizen mental health science study, that is, change for citizen science to achieve co-production at scale (C-STACS: https://www.researchintorecovery.com/research/c-stacs/)

We co-developed a ToC through an iterative consultation with C-STACS stakeholders who were (a) representatives of mental health community organisations (n=10), individuals with public involvement experience (n=2) and researchers (n=5). In keeping with established ToC practice, entities were identified, including long-term impacts, outcomes needed to create an impact, stakeholder assumptions and indicators for tracking progress.

A desired primary long-term impact of greater co-production of research was identified between researchers and members of the public, which would create a secondary impact of enhancing public capacity to engage in citizen mental health science. We proposed long-term outcomes needed to enable this impact: (1) greater co-production of research objectives and pathways between researcher and the public, (2) greater embedment of citizen mental health science into funder processes (eg, the creation of specific funding calls for citizen mental health science proposals, (3) greater clarity on the boundaries between citizen science and other participatory approaches (eg, so that there is not loss of impact due to conceptual confusion between these, (4) increased knowledge around effective frameworks to enable mass public participation and (5) greater availability of technology platforms, enabling safe and accessible engagement with citizen mental health science projects.

The proposed ToC is grounded in the C-STACS project, but intended to be broadly applicable. It allows the continued formation of a community of practice around citizen mental health science and should be reviewed, as greater knowledge is developed on how citizen mental health science creates change.

To assess the feasibility of conducting a definitive randomised controlled trial (RCT) to test the clinical and cost-effectiveness of a tailored exercise intervention compared with usual care for people aged 80 years and older with hip and/or knee osteoarthritis (OA) and comorbidities.

Two-arm, parallel-design, multicentre, pragmatic, feasibility RCT.

Four National Health Service outpatient physiotherapy services across England.

Adults aged 80 years and over with clinical hip and/or knee OA and ≥1 comorbidity.

Participants were randomised 1:1 via a central web-based system to be offered: (1) a 12-week tailored exercise programme or (2) usual care. Participants and outcome assessors were not blinded to treatment allocation.

(1) Ability to screen and recruit participants; (2) retention of participants at 14-week follow-up; (3) intervention fidelity (proportion of participants who received ≥4 intervention sessions as per protocol) and (4) participant engagement (assessed by home exercise adherence).

Between 12 May 2022 and 26 January 2023, 133 potential participants were screened, of whom 94 were eligible. The main reasons for ineligibility were symptoms not consistent with hip or knee OA (10/39, 25.6%) or already having had a physiotherapy appointment (8/39, 20.5%). 51 of 94 (54%) eligible participants were recruited. Participants had a mean age of 84 years (SD 3.5), 31 (60.8%) were female and 96.1% reported their ethnicity as White British (n=49/51). 45 of 51 participants (88%) provided outcome data at the 14-week follow-up time point. Four or more intervention sessions were attended by 13/25 (52%) participants. Home exercise log completion declined over time: 6/23 participants (26.1%) returned completed exercise logs for all 12 weeks. The median number of days home exercises were recorded each week was 5 (range 0–7).

This study demonstrated that a definitive trial would be feasible. Before proceeding, modifications to ensure recruitment of a diverse population and intervention fidelity should be addressed.

ISRCTN75983430.

There are estimated to be 3.4 million patients in the UK living after a diagnosis of cancer. We know very little about their quality of life or healthcare usage. Patient-reported outcome measures (PROMs) are tools which help to translate a patient’s quality of life into measurable categories, but how to do this at scale remains underexplored. The study employs a randomised design to assess different engagement strategies for optimising participation, data linkage and questionnaire completion in Northwest London and then nationally, with appropriate research approvals.

We have designed and implemented an online, patient-completed, randomised observational trial. We will pilot it in Northwest London before national roll-out, using initially the General Practice (GP) record of a cancer diagnosis and then exploring the use of social media. The primary objective is to explore the feasibility of recruiting participants via self-identification or contact from the primary care research network and obtaining consent to link participants’ PROMs responses to their cancer registry records. Data collection occurs through a secure platform, with participants directly responsible for data entry. There is no formal target sample size because this is a feasibility study, and we want to explore how many patients we can recruit. Analyses will be conducted using descriptive statistics, repeated measures multilevel modelling and machine learning techniques. If a substantial difference in responses between randomisation arms is detected, ineffective strategies will be removed. If no clear difference is observed, recruitment will continue with periodic reviews based on response rates and data completeness.

The Study Coordination Centre has obtained approval from the London—Surrey Research Ethics Committee and Health Research Authority. We will publish and disseminate the results in local, national and international meetings, in peer-reviewed journals, on social media and on websites.

It has been registered under ‘Investigating Digital Outcomes for Cancer Survivors in the Community’ (NCT06095024).

NCT06095024: Investigating Digital Outcomes for Cancer Survivors in the Community.

There are structural and functional modifications that occur to the neonatal heart immediately after birth. While a number of studies recently have assessed cardiac function in the newborn, there is a dearth of data on diastolic function in the neonatal period during transition and into infancy. The objective of this study is to assess diastolic function in a large cohort of infants to provide normative reference values and to assess the influence of predefined maternal and infant characteristics.

This is a single-centre observational study of babies born at 35 weeks of gestation and above, involving echocardiography in the first 2 DOL and longitudinal follow-up of these infants up to 18 months of age. The echocardiographic measurements to assess diastolic function used in this study include conventional echo measures, novel echo measures using tissue Doppler imaging and deformation measures using 2D speckle tracking echocardiography.

The protocol was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The findings from this study will be disseminated in peer-reviewed journals and during scientific conferences.

NCT06200519.

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.

To assess the impact of opening a large community-based asynchronous review ophthalmic clinic on attendance delays among patients with stable chronic eye disease attending a London teaching eye hospital network.

Interrupted time-series analysis of routine electronic health records of appointment attendances.

A large eye hospital network with facilities across London, UK, between June 2018 and April 2023.

We analysed 69 257 attendances from 39 357 patients, with glaucoma and medical retina accounting for 62% (n=42 982) and 38% (n=26 275) of visits, respectively. Patients over 65 made up 54% (n=37 824) of attendances, while 53% (n=37 014) were from the more deprived half of the population, and 51% (n=35 048) were males.

An asynchronous review clinic opened in a shopping centre in London, in autumn 2021, following the COVID-19 lockdown in spring 2020.

Average attendance delays (days), calculated as the difference between follow-up attendance date and the latest clinically appropriate date determined at the preceding attendance.

Pre-COVID-19, attendance delays for chronic eye disease monitoring were increasing by 0.9 days per week (95% CI, 0.8 to 0.9) on average, worsening to 2.0 days per week (95% CI, 2.0 to 2.0) after the first COVID-19 national lockdown, mid-March 2020. Opening the asynchronous review clinic increased appointment capacity, with delays decreasing on average by 8.1 days per week (95% CI, 8.1 to 8.2) shortly after opening. The rate of decrease slowed to 0.3 days per week (95% CI, 0.3 to 0.3) after 5 months. We found no significant differences in average attendance delays by age, gender or level of deprivation.

The asynchronous review clinic significantly reduced attendance delays across the hospital network, addressing pre-existing backlog for stable chronic eye diseases. The reduction appeared to be maintained after the initial backlog had been cleared.