Explore the vast range of titles available.

Unintentional injuries are a leading cause of hospitalisation for children. This study investigated the incidence and associated risk factors for unintentional injury hospitalisation (UIH) among Aboriginal and non-Aboriginal children aged under 5 years in Australia's Northern Territory. This was a retrospective cohort study using linked data from a perinatal register, hospital admissions, school enrolment and child protection services. The outcome variable was a first UIH. Potential risk factors included gender, pregnancy and birth outcomes, maternal education level, child protection service contact and geographic remoteness. Modified Poisson regression was used for multivariate modelling. A cohort of 21,189 children (54.0% Aboriginal) born between 2000 and 2010 were followed to the age of 5 years. The overall incidence of first UIH was 25.8 per 1,000 person-years, which was 28.6% higher among Aboriginal than non-Aboriginal children (28.8 and 22.4 per 1000 person-years, respectively). Risk factors identified in the full model included: being male (incidence rate ratio (IRR) 1.26, 95%CI: 1.17-1.36); living in a remote (IRR 1.26, 95%CI: 1.14-1.40) or very remote area (IRR 1.44, 95%CI: 1.29-1.59); having a notification or substantiated notification for abuse (IRR 1.42, 95%CI: 1.27-1.58 and IRR 1.60, 95%CI: 1.41-1.82, respectively); or neglect (IRR 1.32, 95%CI: 1.17-1.48 and IRR 1.28, 95%CI: 1.11-1.47, respectively). After adjustment, there was no difference in UIH rates between Aboriginal and non-Aboriginal children. In both stratified models, being male, living in remote or very remote areas and having a notification or substantiated notification for child maltreatment were identified as risk factors. Our study found high UIH incidence rates and evidence for an association between UIH and child maltreatment. This suggests child maltreatment and UIH have shared determinants and points to the need for clinicians to be aware of the overlap between these conditions and the importance of cross-agency collaboration in prevention and management.

Background Congregate settings may serve as institutional amplifiers of tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB). We analyze spatial, epidemiological, and pathogen genetic data prospectively collected from neighborhoods surrounding a prison in Lima, Peru, where inmates experience a high risk of MDR-TB, to investigate the risk of spillover into the surrounding community. Methods Using hierarchical Bayesian statistical modeling, we address three questions regarding the MDR-TB risk: (i) Does the excess risk observed among prisoners also extend outside the prison? (ii) If so, what is the magnitude, shape, and spatial range of this spillover effect? (iii) Is there evidence of additional transmission across the region? Results The region of spillover risk extends for 5.47 km outside of the prison (95% credible interval: 1.38, 9.63 km). Within this spillover region, we find that nine of the 467 non-inmate patients (35 with MDR-TB) have MDR-TB strains that are genetic matches to strains collected from current inmates with MDR-TB, compared to seven out of 1080 patients (89 with MDR-TB) outside the spillover region ( p values: 0.022 and 0.008). We also identify eight spatially aggregated genetic clusters of MDR-TB, four within the spillover region, consistent with local transmission among individuals living close to the prison. Conclusions We demonstrate a clear prison spillover effect in this population, which suggests that interventions in the prison may have benefits that extend to the surrounding community.

Background Understanding how and why de-implementation of low-value practices is sustained remains unclear. The Paediatric Research in Emergency Departments International CollaboraTive (PREDICT) Bronchiolitis Knowledge Translation (KT) Study was a cluster randomised controlled trial conducted in 26 Australian and New Zealand hospitals (May-November 2017). Results showed targeted, theory-informed interventions (clinical leads, stakeholder meetings, train-the-trainer workshop, targeted educational package, audit/feedback) were effective at reducing use of five low-value practices for bronchiolitis (salbutamol, glucocorticoids, antibiotics, adrenaline and chest x-ray) by 14.1% in acute care settings. The primary aim of this study is to determine the sustainability (continued receipt of benefits) of these outcomes at intervention hospitals two-years after the removal of study supports. Secondary aims are to determine sustainability at one-year after removal of study support at intervention hospitals; improvements one-and-two years at control hospitals; and explore factors that influence sustainability at intervention hospitals and contribute to improvements at control hospitals. Methods A mixed-methods study design. The quantitative component is a retrospective medical record audit of bronchiolitis management within 24 hours of emergency department (ED) presentations at 26 Australian ( n  = 20) and New Zealand ( n  = 6) hospitals, which participated in the PREDICT Bronchiolitis KT Study. Data for a total of 1800 infants from intervention and control sites (up to 150 per site) will be collected to determine if improvements (i.e., no use of all five low-value practices) were sustained two- years (2019) post-trial (primary outcome; composite score); and a further 1800 infants from intervention and control sites will be collected to determine sustained improvements one- year (2018) post-trial (secondary outcome). An a priori definition of sustainability will be used. The qualitative component will consist of semi-structured interviews with three to five key emergency department and paediatric inpatient medical and nursing staff per site (total n  = 78-130). Factors that may have contributed to sustaining outcomes and/or interventions will be explored and mapped to an established sustainability framework. Discussion This study will improve our understanding of the sustainability of evidence-based bronchiolitis management in infants. Results will also advance implementation science research by informing future de-implementation strategies to reduce low-value practices and sustain practice change in paediatric acute care. Trial registration Australian and New Zealand Clinical Trials Registry No: ACTRN12621001287820.

IntroductionSepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes.Methods and analysisThis prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures.Ethics and disseminationEthics approval was received from the Royal Children’s Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences.Trial registration numberACTRN12621000920897; Pre-results.

The comparison of Mycobacterium tuberculosis bacterial genotypes with phenotypic, demographic, geospatial and clinical data improves our understanding of how strain lineage influences the development of drug-resistance and the spread of tuberculosis. To investigate the association of Mycobacterium tuberculosis bacterial genotype with drug-resistance. Drug susceptibility testing together with genotyping using both 15-loci MIRU-typing and spoligotyping, was performed on 2,139 culture positive isolates, each from a different patient in Lima, Peru. Demographic, geospatial and socio-economic data were collected using questionnaires, global positioning equipment and the latest national census. The Latin American Mediterranean (LAM) clade (OR 2.4, p<0.001) was significantly associated with drug-resistance and alone accounted for more than half of all drug resistance in the region. Previously treated patients, prisoners and genetically clustered cases were also significantly associated with drug-resistance (OR's 2.5, 2.4 and 1.8, p<0.001, p<0.05, p<0.001 respectively). Tuberculosis disease caused by the LAM clade was more likely to be drug resistant independent of important clinical, genetic and socio-economic confounding factors. Explanations for this include; the preferential co-evolution of LAM strains in a Latin American population, a LAM strain bacterial genetic background that favors drug-resistance or the \"founder effect\" from pre-existing LAM strains disproportionately exposed to drugs.

RationaleSevere acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only.ObjectivesTo identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma.MethodsRetrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS).Measurements and main resultsOf 14 029 children (median age 3 (IQR 1–3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3–63.2 hours) than children without escalation 6.7 hours, IQR 3.5–16.3 hours; p<0.001). The most common treatment escalations were respiratory support alone (400; 2.9%, 95% CI 2.6% to 3.1%), parenteral bronchodilator treatment alone (380; 2.7%, 95% CI 2.5% to 3.0%) and both respiratory support and parenteral bronchodilator treatment (209; 1.5%, 95% CI 1.3% to 1.7%). Respiratory support was predominantly nasal high-flow therapy (99.0%). The most common intravenous medication regimens were: magnesium alone (50.4%), magnesium and aminophylline (24.6%) and magnesium and salbutamol (10.0%).ConclusionsOverall, 7.3% children with acute severe asthma received some form of escalated treatment, with 4.2% receiving parenteral bronchodilators and 4.3% respiratory support. There is wide variation treatment escalation.

The first synthesis of Luffarin I, sesterterpenolide isolated from sponge Luffariella geometrica, has been accomplished from commercially available sclareol. The key strategy involved in this synthesis is the diastereoselective reduction of an intermediate ketone. Luffarin I against human solid tumor cell lines showed antiproliferative activities (GI50) in the range 12–17 μM.

BackgroundIn 2017, the PREDICT (Paediatric Research in Emergency Departments International Collaborative) network conducted a cluster randomised controlled trial (cRCT) at 26 Australian and New Zealand hospitals to improve bronchiolitis care. Findings demonstrated that targeted interventions significantly improved adherence with five evidence-based low-value bronchiolitis practices (no chest radiography, salbutamol, glucocorticoids, antibiotics and epinephrine) in the first 24 hours of hospitalisation (adjusted risk difference, 14.1%; 95% CI: 6.5% to 21.7%; p<0.001). During the intervention year (2017), intervention hospital (n=13) compliance was 85.1% (95% CI: 82.6% to 89.7%). This study aimed to determine if improvements in bronchiolitis management were sustained at intervention hospitals 2 years post-trial completion.MethodsInternational, multicentre follow-up study of hospitals in Australia and New Zealand that participated in a cRCT of de-implementation of low-value bronchiolitis practices, 1 year (2018) and 2 years (2019) post-trial completion, obtained retrospectively from medical audits. Sustainability was defined a priori as no more than a <7% decrease to any level of improvement in adherence for all five low-value practices (composite outcome) from the cRCT intervention year.ResultsOf the 26 hospitals, 11 intervention and 10 control hospitals agreed to participate in the follow-up study. Data were collected on 3299 infants with bronchiolitis 1 year (intervention and control hospitals) and 1689 infants 2 years post-trial (intervention hospitals). Adherence with no use of the five low-value practices 2 years post-trial completion was 80.9% (adjusted predicted adherence, 80.8%, 95% CI: 77.4% to 84.2%; estimated risk difference from cRCT outcome −3.9%, 95% CI: −8.6% to 0.8%) at intervention hospitals, fulfilling the a priori definition of sustainability.DiscussionTargeted interventions, delivered over one bronchiolitis season, resulted in sustained improvements in bronchiolitis management in infants 2 years later. This follow-up study provides evidence for sustainability in de-implementing low-value care in bronchiolitis management.Trial registration detailsAustralian and New Zealand Clinical Trials Registry No: ACTRN12621001287820.

BackgroundThe 2017 Paediatric Research in Emergency Departments International Collaborative (PREDICT) Bronchiolitis Knowledge Translation (KT) Study, a cluster randomised trial in 26 Australasian hospitals, found targeted interventions provided over one bronchiolitis season effectively de-implemented five low-value practices (salbutamol, glucocorticoids, chest radiography, antibiotics and epinephrine) by 14.1% (adjusted risk difference, 95% CI 6.5% to 21.7%; p<0.001). A 2-year follow-up study found de-implementation was sustained. This process evaluation aimed to identify factors that influenced sustainability of de-implementation of these five low-value practices in PREDICT Bronchiolitis KT Study intervention hospitals and examine fidelity and/or adaptation of the targeted interventions over 4 years post intervention delivery (sustainment).MethodsSemistructured qualitative interviews were conducted, over 2021 and 2022, with a purposive sample of emergency department (ED) and paediatric inpatient clinicians. Data were analysed thematically into facilitators and barriers using the Consolidated Framework for Sustainability Constructs in Healthcare (CFSCH). The Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies was used to explore fidelity and adaptation.Results50 clinicians (nurses: n=26; doctors: n=24) from 12 intervention hospitals were interviewed. Eight themes were identified and mapped to three CFSCH domains: (1) organisational setting; (2) initiative design and delivery and (3) people involved. Facilitators were a culture of evidence-based practice, ongoing multimodal education, strong clinical leadership as unofficial champions and the previous effectiveness of the PREDICT Bronchiolitis KT Study interventions. Barriers were lack of paediatric trained ED staff, assumptions by senior clinicians that junior doctors can provide evidence-based bronchiolitis management, bronchiolitis not a current improvement priority and lack of bronchiolitis education sessions. Use of the targeted interventions reduced over time and, when used, was adapted locally.ConclusionThis study provides insights into factors influencing the sustainability of de-implementation of low-value care in acute care settings. Fostering an evidence-based practice culture, supported by senior leadership and ongoing multimodal education, supports sustainability of improvements in this setting.Trial registration numberAustralian and New Zealand Clinical Trials Registry No: ACTRN12621001287820.

Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes. This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures. Ethics approval was received from the Royal Children's Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences. ACTRN12621000920897; Pre-results.