Differences in life expectancy within and between countries: implications for domestic TAVI guidelines in Australia and Aotearoa New Zealand.

The advent of transcatheter aortic valve implantation (TAVI) has caused a paradigm shift in the management of aortic stenosis away from traditional surgical aortic valve replacement (SAVR). However, uncertainty remains about the long-term (>10 year) durability of TAVI valves, especially in younger patients. This viewpoint collates life expectancy data from Australia and Aotearoa New Zealand to propose sex-specific age-based recommendations for choice of SAVR versus TAVI in their respective general populations and among Aboriginal and Torres Strait Islander people in Australia and both Maori and Pacific peoples living in Aotearoa New Zealand.

'Joining the Dots: Linking Prenatal Drug Exposure to Childhood and Adolescence' - research protocol of a population cohort study.

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The Joining the Dots cohort study uses linked population data to understand the relationship between services, therapeutic interventions and outcomes of children with PDE. METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal social demographics or social determinants of health, and maternal physical and mental health comorbidities. Key outcome measures will include child mortality, academic standardised testing results, rehospitalisation and maternal survival. Data analysis will be conducted using Stata V.18.0. ETHICS AND DISSEMINATION: Approvals were obtained from the NSW Population and Health Services Research Ethics Committee (29 June 2020; 2019/ETH12716) and the Australian Capital Territory Health Human Research Ethics Committee (11 October 2021; 2021-1231, 2021-1232, 2021-1233); and the Aboriginal Health and Medical Research Council (5 July 2022; 1824/21), and all Australian educational sectors: Board of Studies (government schools), Australian Independent Schools and Catholic Education Commission (D2014/120797). Data were released to researchers in September 2022. Results will be presented in peer-reviewed academic journals and at international conferences. Collaborative efforts from similar datasets in other countries are welcome.

Clinicians' Experiences and Perspectives about a New Lung Cancer Referral Pathway in a Regional Health Service.

Introduction: Development and implementation of the Townsville Lung Cancer Referral Pathway [TLCRP] aims to reduce delays and improve referral patterns of people with suspected lung cancer in north Queensland, Australia. Reported in this paper is the experiences and perspectives of general practitioners [GPs] and specialists of the TLCRP. Methods: This was a descriptive qualitative study nested within a larger project evaluating TLCRP, utilising a broader implementation science framework. In-depth, semi-structured interviews with GPs and specialists were conducted. An iterative, inductive thematic analysis of interview transcripts was used to derive key codes, then grouped into themes regarding participant experiences and perceptions. Results: Data analysis identified two major themes and several sub-themes. The major themes were variation in the uptake of TLCRP and enhancing coordinated care and communication. Discussion: Several enablers and barriers to implementing TLCRP were identified. Barriers to adaptation of TLCRP included lack of clinical time, resistance to changing referral patterns, lack of familiarity or experience with HealthPathways and technology issues. Conclusion: Emerging themes from this study may be used to reduce the barriers and improve uptake of TLCRP and other health care pathways in the local health service and may have wider relevance in other settings.

The assessment of dietary carotenoid intake of the Cardio-Med FFQ using food records and biomarkers in an Australian cardiology cohort: a pilot validation.

Dietary carotenoids are associated with lower risk of CHD. Assessment of dietary carotenoid intake using questionnaires can be susceptible to measurement error. Consequently, there is a need to validate data collected from FFQs which measure carotenoid intake. This study aimed to assess the performance of the Cardio-Med Survey Tool (CMST)-FFQ-version 2 (v2) as a measure of dietary carotenoid intake over 12-months against plasma carotenoids biomarkers and 7-Day Food Records (7DFR) in an Australian cardiology cohort. Dietary carotenoid intakes (ß- and α-carotene, lycopene, ß-cryptoxanthin and lutein/zeaxanthin) were assessed using the 105-item CMST-FFQ-v2 and compared to intakes measured by 7DFR and plasma carotenoid concentrations. Correlation coefficients were calculated between each dietary method, and validity coefficients (VCs) were calculated between each dietary method and theoretical true intake using the 'methods of triads'. Thirty-nine participants aged 37-77 years with CHD participated in the cross-sectional study. The correlation between FFQ and plasma carotenoids were largest and significant for ß-carotene (0.39, p=0.01), total carotenoids (0.37, p=0.02) and ß-cryptoxanthin (0.33, p=0.04), with weakest correlations observed for α-carotene (0.21, p=0.21) and lycopene (0.21, p=0.21). The FFQ VCs were moderate (0.3-0.6) or larger for all measured carotenoids. The strongest were observed for total carotenoids (0.61) and ß-carotene (0.59), while the weakest were observed for α-carotene (0.33) and lycopene (0.37). In conclusion, the CMST-FFQ-v2 measured dietary carotenoids intakes with moderate confidence for most carotenoids, however, there was less confidence in ability to measure α-carotene and lycopene intake, thus further research is warranted using a larger sample.

Reappraisal of sauropod dinosaur diversity in the Upper Cretaceous Winton Formation of Queensland, Australia, through 3D digitisation and description of new specimens.

Skeletal remains of sauropod dinosaurs have been known from Australia for over 100 years. Unfortunately, the classification of the majority of these specimens to species level has historically been impeded by their incompleteness. This has begun to change in the last 15 years, primarily through the discovery and description of several partial skeletons from the Cenomanian-lower Turonian (lower Upper Cretaceous) Winton Formation in central Queensland, with four species erected to date: Australotitan cooperensis, Diamantinasaurus matildae, Savannasaurus elliottorum, and Wintonotitan wattsi. The first three of these appear to form a clade (Diamantinasauria) of early diverging titanosaurs (or close relatives of titanosaurs), whereas Wintonotitan wattsi is typically recovered as a distantly related non-titanosaurian somphospondylan. Through the use of 3D scanning, we digitised numerous specimens of Winton Formation sauropods, facilitating enhanced comparison between type and referred specimens, and heretofore undescribed specimens. We present new anatomical information on the holotype specimen of Diamantinasaurus matildae, and describe new remains pertaining to twelve sauropod individuals. Firsthand observations and digital analysis enabled previously proposed autapomorphic features of all four named Winton Formation sauropod species to be identified in the newly described specimens, with some specimens exhibiting putative autapomorphies of more than one species, prompting a reassessment of their taxonomic validity. Supported by a specimen-level phylogenetic analysis, we suggest that Australotitan cooperensis is probably a junior synonym of Diamantinasaurus matildae, but conservatively regard it herein as an indeterminate diamantinasaurian, meaning that the Winton Formation sauropod fauna now comprises three (rather than four) valid diamantinasaurian species: Diamantinasaurus matildae, Savannasaurus elliottorum, and Wintonotitan wattsi, with the latter robustly supported as a member of the clade for the first time. We refer some of the newly described specimens to these three species and provide revised diagnoses, with some previously proposed autapomorphies now regarded as diamantinasaurian synapomorphies. Our newly presented anatomical data and critical reappraisal of the Winton Formation sauropods facilitates a more comprehensive understanding of the mid-Cretaceous sauropod palaeobiota of central Queensland.

Implementation of a programmatic assessment model in radiation oncology medical physics training.

PURPOSE: In 2019, a formal review and update of the current training program for medical physics residents/registrars in Australasia was conducted. The purpose of this was to ensure the program met current local clinical and technological requirements, to improve standardization of training across Australia and New Zealand and generate a dynamic curriculum and programmatic assessment model. METHODS: A four-phase project was initiated, including a consultant desktop review of the current program and stakeholder consultation. Overarching program outcomes on which to base the training model were developed, with content experts used to update the scientific content. Finally, assessment specialists reviewed a range of assessment models to determine appropriate assessment methods for each learning outcome, creating a model of programmatic assessment. RESULTS: The first phase identified a need for increased standardized assessment incorporating programmatic assessment. Seven clear program outcome statements were generated and used to guide and underpin the new curriculum framework. The curriculum was expanded from the previous version to include emerging technologies, while removing previous duplication. Finally, a range of proposed assessments for learning outcomes in the curriculum were generated into the programmatic assessment model. These new assessment methods were structured to incorporate rubric scoring to provide meaningful feedback. CONCLUSIONS: An updated training program for Radiation Oncology Medial Physics registrars/residents was released in Australasia. Scientific content from a previous program was used as a foundation and revised for currency with the ability to accommodate a dynamic curriculum model. A programmatic model of assessment was created after comprehensive review and consultation. This new model of assessment provides more structured, ongoing assessment throughout the training period. It contains allowances for local bespoke assessment, and guidance for supervisors by the provision of marking templates and rubrics.

THE ROLE OF SCHOOLS IN MENINGOCOCCAL CARRIAGE AMONG ADOLESCENTS AND YOUNG ADULTS IN SOUTH AUSTRALIA.

Neisseria meningitidis carriage peaks in adolescents. This secondary analysis of a randomized controlled trial (NCT03089086) assessing 4CMenB herd protection in South Australia ("B-Part-of-It" study) explored school attributes linked to baseline carriage in 34,489 adolescents prevaccination. Carriage was higher in students attending single-sex [adjusted odds ratio (aOR): 1.49; 95% confidence interval (CI): 1.14-1.93], boarding (aOR: 1.92; 1.13-3.27) and government schools (aOR: 1.32, 1.09-1.61).

First Isolation of Japanese Encephalitis Virus Genotype IV from Mosquitoes in Australia.

Introduction: Widespread transmission of Japanese encephalitis virus (JEV) genotype four (GIV) occurred across mainland Australia in 2022. This resulted in forty-five human cases, including seven deaths, and the identification of JEV infection in over 80 commercial piggeries. Materials and Methods: We collected mosquitoes which were trapped using CO2-baited light traps deployed near piggeries reporting disease or in regions linked to human cases in the Wide Bay region in the state of Queensland. Mosquitoes from four traps yielded JEV RNA by real-time RT-PCR. Pools containing RNA positive mosquitoes were inoculated onto mosquito cell monolayers. Discussion: A single isolate of JEV was obtained from a pool of mixed mosquito species. Near whole genome sequencing and phylogenetic analysis of the JEV isolate demonstrated its high genomic relatedness with JEV GIV pig sequences sampled from Queensland and the state of New South Wales in 2022. Conclusion: We report the first isolation of JEV GIV from mosquitoes collected in Australia. With only a few JEV GIV isolates available globally, the isolate we report will be essential for future research of JEV host interactions, evolution and disease markers, and development of effective therapies, vaccines, diagnostic assays, and mosquito control strategies.

Burden of depression in adolescents in the Western Pacific Region from 1990 to 2019: An age-period-cohort analysis of the Global Burden of Disease study.

BACKGROUND: Depression is a highly prevalent and disabling mental health condition among adolescents. The epidemiology of depression in adolescents has been changing over time, reflecting changes in risk factors as well as disease concepts and diagnosis. However, few studies have characterized the longitudinal epidemiology of depression in adolescents. Understanding trends of disease burden provides key insights to improve resource allocation and design targeted interventions for this vulnerable population. The Western Pacific Region (WPR) is home to over 1.3 billion people with tremendous diversity in culture and socioeconomic development. The epidemiology of adolescent depression in WPR remains largely unknown. In this study, we aimed to estimate trends of disease burden attributable to depressive disorders among adolescents aged 10-24 years in WPR countries between 1990 and 2019, and to investigate period and cohort effects using the Global Burden of Disease (GBD) study database. METHODS: The study utilized data from the Global Burden of Disease, Injuries, and Risk Factors Study 2019, concentrating on adolescents aged 10 to 24 years with depression. We conducted an in-depth analysis of depression, including its age-standardized prevalence, incidence, and Disability-Adjusted Life Years (DALYs), across diverse demographics such as regions, ages, genders, and socio-demographic indexes, spanning from 1990 to 2019. RESULTS: The analysis found decreasing trends in the prevalence, incidence, and DALYs of adolescent depression in the WPR between 1990-2019, although some countries like Australia and Malaysia showed increases. Specifically, the prevalence of adolescent depression in the region decreased from 9,347,861.6 cases in 1990 to 5,551,341.1 cases in 2019. The incidence rate declined from 2,508.6 per 100,000 adolescents in 1990 to 1,947.9 per 100,000 in 2019. DALYs decreased from 371.9 per 100,000 in 1990 to ASR 299.7 per 100,000 in 2019. CONCLUSION: This study found an overall decreasing trend in adolescent depression burden in the Western Pacific Region between 1990 and 2019, with heterogeneity across countries. For 30 years, the 20-24 age group accounted for the majority of depression among adolescents Widening inequality in depression burden requires policy attention. Further analysis of risk factors contributing to epidemiological trends is warranted to inform prevention strategies targeting adolescent mental health in the region.

Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving integrase strand-transfer inhibitors, tenofovir alafenamide, or both compared with other contemporary antiretroviral regimens: a multicentre, prospective observational study from the RESPOND consortium cohorts.

BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. METHODS: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. FINDINGS: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction=0·46 for hypertension; pinteraction=0·31 for dyslipidaemia). INTERPRETATION: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.

[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Paediatric medication incident reporting: a multicentre comparison study of medication errors identified at audit, detected by staff and reported to an incident system.

OBJECTIVES: To compare medication errors identified at audit and via direct observation with medication errors reported to an incident reporting system at paediatric hospitals and to investigate differences in types and severity of errors detected and reported by staff. METHODS: This is a comparison study at two tertiary referral paediatric hospitals between 2016 and 2020 in Australia. Prescribing errors were identified from a medication chart audit of 7785 patient records. Medication administration errors were identified from a prospective direct observational study of 5137 medication administration doses to 1530 patients. Medication errors reported to the hospitals' incident reporting system were identified and matched with errors identified at audit and observation. RESULTS: Of 11 302 clinical prescribing errors identified at audit, 3.2 per 1000 errors (95% CI 2.3 to 4.4, n=36) had an incident report. Of 2224 potentially serious prescribing errors from audit, 26.1% (95% CI 24.3 to 27.9, n=580) were detected by staff and 11.2 per 1000 errors (95% CI 7.6 to 16.5, n=25) were reported to the incident system. Although the prescribing error detection rates varied between the two hospitals, there was no difference in incident reporting rates regardless of error severity. Of 40 errors associated with actual patient harm, only 7 (17.5%; 95% CI 8.7% to 31.9%) were detected by staff and 4 (10.0%; 95% CI 4.0% to 23.1%) had an incident report. None of the 2883 clinical medication administration errors observed, including 903 potentially serious errors and 144 errors associated with actual patient harm, had incident reports. CONCLUSION: Incident reporting data do not provide an accurate reflection of medication errors and related harm to children in hospitals. Failure to detect medication errors is likely to be a significant contributor to low error reporting rates. In an era of electronic health records, new automated approaches to monitor medication safety should be pursued to provide real-time monitoring.

Treatment selection and real-world analysis of immunotherapy with or without chemotherapy in PD-L1-high metastatic non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death in Australia. Immunotherapy has improved outcomes in patients with metastatic non-small cell lung cancer (NSCLC). Pembrolizumab is approved in first-line treatment as single-agent immunotherapy (SAI) or combination chemoimmunotherapy (CIT). In metastatic NSCLC programmed death-ligand 1 (PD-L1) ≥50% either regimen may be used. AIMS: We aim to identify patient and tumour characteristics that influence treatment selection. METHODS: This is a retrospective observational study. Pharmacy records identified patients with metastatic/recurrent NSCLC receiving pembrolizumab at two metropolitan centres in Victoria, Australia, since 2018. Demographics, tumour characteristics, Charlson Comorbidity Index (CCI) and treatment data were collected. Descriptive and multivariate analyses were performed. RESULTS: Sixty-one patients had metastatic NSCLC PD-L1 ≥50% and received pembrolizumab with median age of 65.6 years, Eastern Cooperative Oncology Group 0-1 in 82%. CIT was administered to 23% (14) with no difference in rate of delivery between centres (P = 0.808). CCI mean score differed (3.38 SAI vs 2.36 CIT, P = 0.042). Patients with high CCI score (≥2) were less likely to receive CIT (OR = 0.15, P = 0.003, 95% confidence interval (CI) 0.04-0.57). Primary tumours over 5 cm were more likely to receive CIT (OR = 3.74, P = 0.043, 95% CI = 1.04-13.42). Site-specific metastases of liver, brain and pericardial effusion were not associated with CIT. CONCLUSIONS: Patients with higher comorbidity score were less likely to receive CIT, suggesting chemotherapy avoidance in comorbid patients. Larger tumours are associated with CIT use, indicating that oncologists may use tumour size as a surrogate of disease burden. Limitations include small sample size and data cut-off. Future prospective studies could incorporate comorbid status and a validated disease burden score to stratify patients.

Depressive symptoms and cognitive decline in older adults.

OBJECTIVES: Few studies have examined the impact of late-life depression trajectories on specific domains of cognitive function. This study aims to delineate how different depressive symptom trajectories specifically affect cognitive function in older adults. DESIGN: Prospective longitudinal cohort study. SETTING: Australia and the United States of America. PARTICIPANTS: In total, 11,035 community-dwelling older adults with a mean age of 75 years. MEASUREMENTS: Depressive trajectories were modelled from depressive symptoms according to annual Centre for Epidemiological Studies Depression Scale 10 (CES-D-10) surveys. Four trajectories of depressive symptoms were identified: low ("nondepressed"), consistently mild ("subthreshold depression"), consistently moderate ("persistent depression"), and initially low but increasing ("emerging depression"). Global cognition (Modified Mini-Mental State Examination [3MS]), verbal fluency (Controlled Oral Word Association Test [COWAT]), processing speed (Symbol Digit Modalities Test [SDMT]), episodic memory (Hopkins Verbal Learning Test - Revised [HVLT-R]), and a composite z-score were assessed over a subsequent median 2 years. RESULTS: Subthreshold depression predicted impaired performance on the SDMT (Cohen's d -0.04) and composite score (-0.03); emerging depression predicted impaired performance on the SDMT (-0.13), HVLT-R (-0.09), 3 MS (-0.08) and composite score (-0.09); and persistent depression predicted impaired performance on the SDMT (-0.08), 3 MS (-0.11), and composite score (-0.09). CONCLUSIONS: Depressive symptoms are associated with later impaired processing speed. These effects are small. Diverse depression trajectories have different impacts on cognitive function.

Applying Social Practice Theory to Explore Australian Preschool Children's Oral Health.

INTRODUCTION: Despite substantial research and provision of dental care, significant morbidity remains for children's oral health. Guided by social practice theory (SPT), this research moves away from the often-ineffective focus on changing individual behavior to rethinking the centrality of the social world in promoting or undermining oral health outcomes. We define social practice as a routinized relational activity linking and integrating certain elements (competence, materials, and meanings) into the performance of a practice that is reproduced across time and space. OBJECTIVE: To investigate oral health in preschool children in Perth, Western Australia, using social practice theory. METHODS: With no definitive methodology for investigating SPT, we chose focused ethnography as a problem-focused, context-specific approach using mainly interviews to investigate participants' experience caring for their children's oral health. The focus of analysis was the practice of oral health care, not individual behavior, where themes identified from participants' transcripts were organized into categories of elements and performance. RESULTS: Eleven parents, all of whom were married or partnered, were interviewed in 2021. Findings identified social practices relevant to oral health within parenting and family relations linked to routine daily activities, including shopping, consumption of food and beverages, and toothbrushing. Oral health literacy was reflected in integrating competence, materials, and meanings into performing oral health care, notably preferences for children to drink water over sugary beverages and information often being sourced from social media and mothers' groups rather than health providers. CONCLUSION: Focusing on social practices as the unit of analysis offers a more layered understanding of elements in young children's oral health care that can indicate where the problem may lie. Findings provide an opportunity to consider future research and policy directions in children's oral health. KNOWLEDGE TRANSFER STATEMENT: Examining social practices related to young children's oral health care identifies parents/carers' knowledge about, for example, toothbrushing, the resources required, and why toothbrushing is important. Analyzing these separate elements can reveal both enablers and barriers to oral health care. This provides researchers, clinicians and policymakers an opportunity to focus on not changing individual behavior but understanding how social context impacts parents/carers' capacity to make optimum decisions around young children's oral health.

Using the Tasmanian Palliative and End of Life Care Policy Framework (2022) to assess service delivery in a rural general practice.

AIMS: This commentary uses the Tasmanian Palliative and End of Life Care Policy Framework (2022; the TPE Framework) to reflect upon palliative care services delivered by a rural Tasmanian general practice. CONTEXT: Rural populations have challenges in accessing many healthcare services, including palliative care. General practitioners (GPs) and other primary healthcare workers are frequently relied upon to deliver palliative care in rural Australia. Palliative care is often needed before the end-of-life phase and patients prefer this to be delivered in the community or at home. GPs face challenges and barriers in continuing to deliver home-based palliative care services. APPROACH: All Medical Benefit Scheme billings for after-hours or home-based palliative care provided by the practice, between September 2021 and August 2022, were identified and patient demographic and clinical details collated. To further understand this data, nine GPs were surveyed to explore their attitudes to provision of palliative care service to the local rural communities they serve. These data highlighted several priority areas of the TPE Framework. The TPE Framework is used here to add to the shared understanding of palliative care service delivery in a rural community, and to see if GP's responses align with the priorities of the TPE Framework. Of the 258 after-hours and home-visits delivered over a 12-month period, almost 58% (n = 150) were for palliative care. Patients receiving palliative care were generally older than non-palliative patients visited (79.9 years vs. 72.0 years respectively; p = 0.004). Patients not at imminent risk of death (64.0%) were more frequently recipients of home-visits. Of the nine GPs responding to the survey, most intended to continue home visits for palliative patients. Disincentives to providing palliative care during home visits included a lack of time during the day (or after hours), low levels of interdisciplinary coordination or role-definition, and inadequate remuneration. CONCLUSION: Existing frameworks can be used as an implementation and evaluation guide to help understand local palliative care services. Using a Framework, a rural general practice in Tasmania reflected on their provision of palliative care services. Providing holistic palliative care services from a rural general practice is desirable and achievable with a coordinated, team-based approach. Access to and integration with specialist services remains a key component of community-based palliative care pathways.

Corneal Neurotization for Neurotrophic Keratopathy: A Multicentre Experience.

PURPOSE: Corneal neurotization is an emerging technique that offers potential for visual rehabilitation in neurotrophic keratopathy. This study reports on a multicenter experience and outcomes for both direct and indirect methods of corneal neurotization. METHODS: Retrospective case series. Sixteen patients with neurotrophic keratopathy who underwent corneal neurotization across 5 centers in Australia and Israel were identified for inclusion. Corneal neurotization was performed via direct neurotization from the ipsilateral or contralateral supraorbital/supratrochlear nerve or by the use of an interpositional sural nerve graft. Change in corneal sensitivity (measured in millimeters by the Cochet-Bonnet aesthesiometer), visual acuity, and corneal health. RESULTS: Over a mean follow-up period of 31.3 months (range: 3 months-8 years), mean corneal sensitivity improved from 3.6 mm (range: 0-25 mm) to 25.3 mm (range: 0-57 mm). Visual acuity improved on average from 20/380 to 20/260. Twelve of 16 patients (75.0%) improved in at least 2 out of the 3 main outcome measures. Nine patients (56.3%) showed an improvement in visual acuity; 13 (81.3%) showed an improvement in average corneal sensitivity; and 11 (68.8%) showed an improvement in corneal health. There were no intraoperative or postoperative complications. CONCLUSIONS: Corneal neurotization is an emerging surgical treatment option for the management of neurotrophic keratopathy. With appropriate case selection, outcomes are favorable and complication rates are low, for a condition that is otherwise challenging to manage. Patients with severe neurotrophic keratopathy should be considered for this surgical treatment option.

Patients' perceptions of participating in self-directed activities outside supervised occupational and physiotherapy within inpatient and home-based rehabilitation settings: a qualitative study.

PURPOSE: To investigate patients' perceptions of participating in self-directed activities, outside supervised occupational and physiotherapy, within rehabilitation settings. METHODS: Semi-structured interviews were undertaken with 16 patients and in three instances, their carers, from three health services in Victoria, Australia, two offering inpatient and one offering home-based rehabilitation care. A thematic analysis was performed using a framework approach. RESULTS: Themes identified included the role of the clinicians in encouraging patients and instilling confidence, giving feedback and "just being there"; considerations in program delivery, including different formats, support from peers and relatives, and program familiarity and flexibility; patients' different intrinsic driving and limiting forces, including following orders, seeing results, desiring autonomy and having an "inner athlete"; and the environment, including functional activities, space, equipment, time and availability. CONCLUSIONS: Patients and their carers reported positive experiences of participating in self-directed therapy programs within rehabilitation settings, with programs perceived as beneficial in optimising recovery. Patients reported a range of driving and limiting factors in relation to completing self-directed activities. Understanding these factors, relating to the patient, their environment and other people, is critical for clinicians so that they can modify their delivery accordingly, ensuring uptake and sustained implementation of self-directed activities in rehabilitation care.

Patients and their carers reported positive experiences of participating in self-directed therapy programs within rehabilitation settings.Self-directed therapy programs were seen to be beneficial in optimising recovery and helping patients return to previous levels of function.Understanding patients' specific driving and limiting factors in relation to completing self-directed activities, is critical for clinicians so that they can modify their delivery accordingly, ensuring uptake and sustained implementation of self-directed therapy in rehabilitation care.