Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.

Phase 2a randomised, placebo-controlled, double-blinded, trial.

Hospitals in Canada, Turkey and the USA.

A total of 61 subjects with moderate-to-severe COVID-19.

Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.

The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.

At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O₂ ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.

In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.

NCT04402957.

To explore whether large language models (LLMs) Generated Pre-trained Transformer (GPT)-3 and ChatGPT can write clinical letters and predict management plans for common orthopaedic scenarios.

Fifteen scenarios were generated and ChatGPT and GPT-3 prompted to write clinical letters and separately generate management plans for identical scenarios with plans removed.

Letters were assessed for readability using the Readable Tool. Accuracy of letters and management plans were assessed by three independent orthopaedic surgery clinicians.

Both models generated complete letters for all scenarios after single prompting. Readability was compared using Flesch-Kincade Grade Level (ChatGPT: 8.77 (SD 0.918); GPT-3: 8.47 (SD 0.982)), Flesch Readability Ease (ChatGPT: 58.2 (SD 4.00); GPT-3: 59.3 (SD 6.98)), Simple Measure of Gobbledygook (SMOG) Index (ChatGPT: 11.6 (SD 0.755); GPT-3: 11.4 (SD 1.01)), and reach (ChatGPT: 81.2%; GPT-3: 80.3%). ChatGPT produced more accurate letters (8.7/10 (SD 0.60) vs 7.3/10 (SD 1.41), p=0.024) and management plans (7.9/10 (SD 0.63) vs 6.8/10 (SD 1.06), p

This study shows that LLMs are effective for generation of clinical letters. With little prompting, they are readable and mostly accurate. However, they are not consistent, and include inappropriate omissions or insertions. Furthermore, management plans produced by LLMs are generic but often accurate. In the future, a healthcare specific language model trained on accurate and secure data could provide an excellent tool for increasing the efficiency of clinicians through summarisation of large volumes of data into a single clinical letter.

The objective of this study is to investigate the proportion of potentially low-value knee MRI in Norway and to provide an estimate of the related costs.

Register study based on conditional data extraction and analysis of data from Control and Reimbursement of Healthcare Claims registry in Norway.

MRI in public specialist healthcare with universal health coverage (Norway).

48 212 MRIs for 41 456 unique patients and 45 946 reimbursement claims.

Proportion of MRIs of the knee that (1) did not have a relevant tentative diagnosis prior to the knee MRI, (2) did not have a relevant alternative image of the knee before the MRI or (3) did not have a relevant code from the specialist care within 6 months after the MRI, and those that had combinations of 1, 2 and 3. Estimated costs for those that had combinations of 1, 2 and 3.

Very few patients (6.4%) had a relevant diagnosis code or prior imaging examination when having the MRI and only 14.6% got a knee-related diagnosis code from the specialist care within 6 months after the MRI. 21.8% of the patients had knee X-ray, CT or ultrasound within 6 months before the MRI. Between 58% and 85% of patients having knee MRIs in Norway have no relevant examinations or diagnoses six months prior to or after the MRI examination. These examinations are unlikely to benefit patients and they correspond to between 24 108 and 35 416 MRIs at a cost of 6.7–9.8 million per year.

A substantial proportion of MRIs of the knee in Norway have no relevant examinations or diagnoses before or after the MRI and are potentially of low value. Reducing low-value MRIs could free resources for high-value imaging, reduce waiting times, improve the quality of care and increase patient safety and professional integrity.

To identify barriers to hospital participation in controlled cluster trials of clinical decision support (CDS) and potential strategies for addressing barriers.

Qualitative descriptive design comprising semistructured interviews.

Five hospitals in New South Wales and one hospital in Queensland, Australia.

Senior hospital staff, including department directors, chief information officers and those working in health informatics teams.

20 senior hospital staff took part. Barriers to hospital-level recruitment primarily related to perceptions of risk associated with not implementing CDS as a control site. Perceived risks included reductions in patient safety, reputational risk and increased likelihood that benefits would not be achieved following electronic medical record (EMR) implementation without CDS alerts in place. Senior staff recommended clear communication of trial information to all relevant stakeholders as a key strategy for boosting hospital-level participation in trials.

Hospital participation in controlled cluster trials of CDS is hindered by perceptions that adopting an EMR without CDS is risky for both patients and organisations. The improvements in safety expected to follow CDS implementation makes it challenging and counterintuitive for hospitals to implement EMR without incorporating CDS alerts for the purposes of a research trial. To counteract these barriers, clear communication regarding the evidence base and rationale for a controlled trial is needed.

This study examined the prevalence of amphetamine use and its associated factors among in-school adolescents in Sierra Leone.

Data for the study was sourced from the 2017 Sierra Leone Global School-based Health Survey. Percentages with confidence intervals (CIs) were used to present the prevalence of amphetamine use among in-school adolescents. A multivariable binary logistic regression analysis was employed to examine the factors associated with amphetamine use. The results were presented using adjusted odds ratios (aORs) with 95% CIs.

Sierra Leone.

A weighted sample of 1,314 in-school adolescents in Sierra Leone.

Lifetime amphetamine use.

The prevalence of amphetamine use was 6.1% (3.9%–9.5%). In-school adolescents who planned suicide were more likely to use amphetamine compared with those who did not (aOR 2.54; 95% CI 1.02 to 6.31). Also, the odds of amphetamine use were higher among in-school adolescents who received support from their peers (aOR 3.19, 95% CI 1.71 to 5.96), consumed alcohol (aOR 4.85, 95% CI 2.61 to 9.03), and those who had previously used marijuana (aOR 13.31, 95% CI 6.61 to 28.78) compared with those who did not receive any support, never consumed alcohol, and never used marijuana, respectively.

Amphetamine use is prevalent among in-school adolescents in Sierra Leone. There is a need to implement comprehensive public health policies that extend beyond school-based psychobehavioural therapies. These policies should specifically address the considerable risk factors associated with amphetamine use among in-school adolescents in Sierra Leone.

Restorative sleep is critical in preventing hypertension and other chronic diseases. Limited research has explored the relationship between sleep quality and hypertension in Africa. This study investigated the association between sleep quality and blood pressure control among hypertensive patients in Southern Nigeria.

Cross-sectional study.

A rural tertiary hospital in Southern Nigeria, April to June 2023.

250 systematically selected hypertensive adults. Participants completed a validated semistructured interviewer-administered questionnaire to assess their sleep patterns, including sleep duration, self-reported trouble sleeping and a history of clinical diagnosis of sleep disorders. Sleep patterns were categorised as restorative (healthy) or non-restorative (unhealthy). The blood pressure of respondents was checked and categorised as controlled (

Quality of sleep and blood pressure control.

Respondents had a mean age of 51.5±10.0 years, with the majority being female (156, 62.4%), married (135, 54.0%) and belonging to the Esan tribe (125, 50.0%). The prevalence of restorative sleep was 36%, while the blood pressure control rate was 23.6%. An association was found between restorative sleep and blood pressure control (adjusted OR =4.38; 95% CI=2.37–8.10; p

The study found an association between poor quality sleep and poor blood pressure control. Incorporating sleep assessments and interventions into comprehensive hypertension management strategies could be explored as a possible approach to improve sleep quality and enhance blood pressure control.

PACTR202301917477205.

Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD).

DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies.

Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual’s body image can inform obesity prevention and management. This study’s objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension.

Research visits were completed in local research clinics in respective countries.

Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country).

Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg.

Most women and men from the USA and Seychelles had ‘Perceived minus Actual weight status Discrepancy’ scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size.

This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people’s perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.

Management controversy and clinical equipoise exist in treatments of long bone fractures and traumatic hip dislocation in paediatric patients due to the lack of high-quality clinical evidence. This protocol describes the effort of a large prospective global multicentre cohort study (registry) aiming at providing quality data to assist evidence-based treatment decision-making.

Eligible paediatric patients (N=750–1000) with open physes suffering from proximal humerus fractures, distal humerus fractures, proximal radius fractures, forearm shaft fractures, traumatic hip dislocations, femoral neck fractures or tibial shaft fractures will be recruited over a period of 24–36 months. Hospitalisation and treatment details (including materials and implants) will be captured in a cloud-based, searchable database. Outcome measures include radiographic assessments, clinical outcomes (such as range of motion, limb length discrepancies and implant removal), patient-reported outcomes (Patient Reported Outcomes Of Fracture, Patient-Reported Outcomes Measurement Information System (PROMIS) and EuroQol-5D (EQ-5D-Y)) and adverse events.

Aside from descriptive statistics on patient demographics, baseline characteristics, types of fractures and adverse event rates, research questions will be formulated based on data availability and quality. A statistical analysis plan will be prepared before the statistical analysis.

Ethics approval will be obtained before patients are enrolled at each participating site. Patient enrolment will follow an informed consent process approved by the responsible ethics committee. Peer-reviewed publication is planned to disseminate the study results.

NCT04207892.

Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM.

BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent’s three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival.

BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines.

ISRCTN60524.

Older adults constitute a heterogeneous group, and the focus of the individual physical exercise is often subject to the reasoning and experience of health professionals or exercise physiologists who prescribe them. Thus, this is the first effort to explicitly conceptualise the planning of individualised physical exercise training (IPET) for older adults in an outpatient setting and investigate individual exercise preferences.

The concept of IPET was developed by researchers, exercise physiologists and health professionals from a real-life outpatient setting using an iterative approach. Health indicators assessing aerobic capacity, strength, balance and musculoskeletal pain/discomfort sites form the basis of physical exercise recommendations. A cross-sectional study was conducted to assess the basis of implementing IPET.

Outpatient setting.

We included 115 older adults (70 females) from an outpatient setting with a median age of 74 years.

Health indicators assessing aerobic capacity, strength, balance and musculoskeletal pain/discomfort sites were collected and informed the concept of IPET that structures exercise programmes based on the individual citizen’s needs and physical exercise preferences. Exceeding a health indicator cut-point results in exercise content mitigating the risk associated with the health indicator.

We included 115 older adults (70 females) from an outpatient setting median age of 74 years. Approximately two-thirds of participants exceeded at least one health indicator cut-point for aerobic training. One-third of the participants exceeded the cut-point for upper extremity strength, and almost all participants >99% exceeded the cut-point for lower extremity strength. Approximately two-thirds of the participants exceeded the cut-point for functional/balance training. The most prevalent site of musculoskeletal pain was the lower extremities. Eight of 20 training combinations were used, clustering the 115 participants primarily in three main training combinations.

This study shows that older adults vary in physical functioning, indicating that exercise preferences and rehabilitation needs are individual.

NCT04862481.

Sickle cell disease (SCD) poses a significant global health burden, particularly affecting individuals in developing countries with constrained healthcare resources. While research on self-management in the context of SCD is emerging, it has predominantly focused on primary studies, and there is a notable dearth of evidence synthesis on SCD self-management in developing countries. This scoping review aims to identify and map self-management needs of individuals living with SCD, the strategies they employed to meet those needs, and the support systems available to them.

The review will be conducted following the Arksey and O’Malley’s (2005) 29 framework to comprehensively examine the landscape of SCD self-management research. Searches will be performed in PubMed, Scopus, Embase and Dimensions AI, with additional searches in other databases and grey literature. Indexed literature published in English from inception to January 2024 will be included. Reference list from included studies will also be searched manually. Two teams will be constituted to independently screen titles, abstracts and full text against the eligible criteria. Data will be extracted from included studies onto a customised data extraction form.

Ethical approval is not required for this review due to the fact that it synthesises information from available publications. The findings will be disseminated through publication in a peer-reviewed journal. Also, the findings will possibly be presented at relevant international and national conferences. This protocol has already been registered with the Open Science Framework. The study characteristics such as design and setting will be descriptively analysed and presented as graphs, tables and figures. Thematic analysis will also be conducted based on the study objectives and presented as a narrative summary.

Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control ‘on-demand’ arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental ‘systematic’ arm, VA-ECMO will be pre-emptively initiated. We hypothesise a ‘systematic’ strategy will increase the number of ventilatory-free days at day 28.

We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events.

The sponsor is the Assistance Publique–Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals.

NCT05664204.

This scoping review maps the extant literature on students’ and graduates’ mental health experiences throughout their university-to-work transitions. The current review investigates the methodological features of the studies, the main findings, and the theories that the studies draw on to conceptualise mental health and transitions.

This project used a scoping review methodology created and developed by Peters and colleagues and the Joanna Briggs Institute. The review searched academic databases and screened existing studies that met predetermined inclusion criteria.

Seven academic databases and Google Scholar were searched with sets of search terms.

The included studies examined participants who were final-year university students or those who had graduated from university within a 3-year period. Studies published in English since 2000 and from any country were included. The review included studies examining the negative dimensions of mental health. The review excluded studies focusing on medical students and graduates.

Basic information about the studies and their findings on mental health and university-to-work transitions was retrieved. The findings are presented in tables and in a qualitative thematic summary.

The scoping review included 12 studies. Mental health was often not explicitly defined and it’s theoretical foundations were not clearly articulated. The review identified factors, including a lack of social support and economic precarity, as sources of adverse mental health. Other protective factors in these studies—variables that guard against mental health problems—were identified, such as career preparedness and having a good job.

Despite the methodological focus on the negative aspects of mental health, people’s mental health experiences during university-to-work transitions are not uniformly negative. Clear conceptualisations of mental health in future studies will aid in developing resources to improve well-being.

This scoping review adhered to a protocol previously published in this journal and that is registered on the Open Science Framework website (https://osf.io/gw86x).

To evaluate the feasibility of using the NeuroMotion smartphone application for remote General Movements Assessment for screening infants for cerebral palsy in Kathmandu, Nepal.

Thirty-one term-born infants at risk of cerebral palsy due to birth asphyxia or neonatal seizures were recruited for the follow-up at Paropakar Maternity and Women’s Hospital, 1 October 2021 to 7 January 2022. Parents filmed their children at home using the application at 3 months’ age and the videos were assessed for technical quality using a standardised form and for fidgety movements by Prechtl’s General Movements Assessment. The usability of the application was evaluated through a parental survey.

Twenty families sent in altogether 46 videos out of which 35 had approved technical quality. Sixteen children had at least one video with approved technical quality. Three infants lacked fidgety movements. The level of agreement between assessors was acceptable (Krippendorf alpha 0.781). Parental answers to the usability survey were in general positive.

Engaging parents in screening of cerebral palsy with the help of a smartphone-aided remote General Movements Assessment is possible in the urban area of a South Asian lower middle-income country.

In critically ill children, pain management is complex owing to cognitive development and the nature of hospitalisation in paediatric intensive therapy units. Although there are many protocols and guidelines for pain control via pharmacological interventions, non-pharmacological practices should also be explored and disseminated for their potential benefit.

A systematic literature search will be performed using the following databases: Academic Search Premier, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Excerpta Medica Database, Virtual Health Library, Medical Literature Analysis and Retrieval System Online, ScienceDirect, Scopus, Web of Science Core Collection, Theses from Coordenacão de Aperfeicoamento de Pessoal de Nível Superior, Dart Europe, Open Access Theses and Dissertations and grey literature from Google Scholar. The research will consider quantitative and qualitative studies, mixed-method studies, systematic reviews, text articles, opinion articles, letters to editors and editorials in any language and from any database. The following will be eligible for inclusion: (1) newborns, infants, children and adolescents; and (2) non-pharmacological therapies used for pain in paediatric intensive care.

This study does not require ethical approval. The results of this research will be disseminated through social media channels and podcasts about pain in children.

This protocol has been registered with the Open Science Framework (DOI 10.17605/OSF.IO/DZHKT).

Namibia is a high tuberculosis (TB)-burden country with an estimated incidence of 460/100 000 (around 12 000 cases) per year. Approximately 4.5% of new cases and 7.9% of previously treated TB cases are multidrug resistant (MDR) and 47% of patients with MDR-TB are HIV coinfected. Published data suggest a clustering of MDR-TB transmission in specific areas. Identifying transmission clusters is key to implementing high-yield and cost-effective interventions. This includes knowing the yield of finding TB cases in high-transmission zones (eg, community hotspots, hospitals or households) to deliver community-based interventions. We aim to identify such transmission zones for enhanced case finding and evaluate the effectiveness of this approach.

H3TB is an observational cross-sectional study evaluating MDR-TB active case finding strategies. Sputum samples from MDR-TB cases in three regions of Namibia will be evaluated by whole genome sequencing (WGS) in addition to routine sputum investigations (Xpert MTB/RIF, culture and drug susceptibility testing). We will collect information on household contacts, use of community spaces and geographical map intersections between participants, synthesising these data to identify transmission hotspots. We will look at the feasibility, acceptability, yield and cost of case finding strategies in these hotspots, and in households of patients with MDR-TB and visitors of hospitalised patients with MDR-TB. A compartmental transmission dynamic model will be constructed to evaluate the impact and cost-effectiveness of the strategies if scaled.

Ethics approval was obtained. Participants will give informed consent. H3TB will capitalise on a partnership with the Ministry of Health and Social Services to follow up individuals diagnosed with MDR-TB and integrate WGS data with innovative contact network mapping, to allow enhanced case finding. Study data will contribute towards a systems approach to TB control. Equally important, it will serve as a role model for similar studies in other high-incidence settings.

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors.

Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses.

Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model.

National Mutual Acceptance ethical approval was obtained from the Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC). Local approvals were sought in each jurisdiction. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC.

Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.

Bronchiolitis is the most common viral lower respiratory tract infection in children under 2 years of age. Respiratory support with high-flow nasal cannula (HFNC) is increasingly used in this patient population with limited understanding of the patients most likely to benefit and considerable practice variability of use. This study aims to understand the factors associated with failure of HFNC support among patients with bronchiolitis and to describe the current practice variations of HFNC use in patients with bronchiolitis in Canadian hospitals including fluid management and parameters to initiate, escalate and discontinue HFNC support.

This is a multicentre retrospective cohort study including hospitalised patients aged 0–24 months with bronchiolitis requiring support with HFNC between January 2017 and December 2021. Clinical data will be collected from patient medical records from Canadian hospitals (n=12), including academic and community centres. HFNC failure will be defined as the need for escalation to non-invasive or invasive mechanical ventilation. Factors associated with HFNC failure will be analysed using logistic regression. Descriptive statistics will be used to describe practice variations of HFNC utilisation and management.

Approval from the Research Ethics Boards (REBs) has been obtained for each participating study site prior to onset of data collection including Clinical Trials Ontario for all Ontario hospital sites and REBs from British Columbia Children’s Hospital, Stollery Children’s Hospital, Montreal Children’s Hospital and CHU Sainte-Justine. Study results will be disseminated through presentation at national/international conferences and publication in high-impact, peer-reviewed journals.