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Background: Fluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3-4 (≥ G3) toxicities that require hospital-based management ± intensive care admission. Approximately 1% of patients die secondary to FP toxicities. Prospective screening for DPYD gene variants (encoding the key enzyme for FP catabolism) can identify patients at risk of ≥ G3 toxicity and allow for dose adjustment prior to first FP exposure. Evidence supports this as a cost-effective method of improving patient safety and reducing healthcare burden internationally; however, no Australian data confirms its feasibility on a large scale., Method: This investigator-led, single-arm study will determine large scale feasibility of prospective DPYD genotyping, confirming patient safety and cost-effectiveness within the Australian health care system. 5000 patients aged 18 years and older with solid organ cancers requiring FP chemotherapy will be consented and genotyped prior to commencing treatment, and early toxicity (within 60 days) post-FP exposure will be determined. Toxicity data for DPYD variant carriers who have dose adjustments will be compared to the wild-type cohort and historical cohorts of carriers who did not undergo genotyping prior to FP exposure, and prospective variant carriers who do not undergo dose-adjustment. Prevalence of the four standard DPYD gene variants will be confirmed in an Australian population. Additionally, health economic analysis, implementation research via semi-structured interviews of patients and clinicians, and feasibility of UGT1A1 genotyping will be conducted., Discussion: This study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing., Trial Registration: This trial was registered with the Australian and New Zealand Cancer Trials Registry on 13th Dec 2023, ACTRN12623001301651., (© 2024. The Author(s).)

Aim: To explore the utilization of permanent residential aged care (PRAC), healthcare costs, and mortality for frail compared with non-frail individuals following their first assessment by an aged care assessment team (ACAT) for a government-funded home care package., Methods: The study involved people aged 65 years and over who completed their first ACAT assessment in 2013 and were followed for up to 36 months. Frail and non-frail study participants were matched through caliper matching without replacement to adjust for potential unobserved confounders. Poisson regression estimated the impact of frailty on PRAC admission and mortality rates. Healthcare costs, encompassing hospital admissions, emergency department presentations, primary care consultations, and pharmaceutical use, from ACAT assessment to end of follow-up, PRAC entry or death were summarized monthly by frailty status., Results: 13 315 non-frail controls were matched with up to three frail individuals (52 678 total). Frail individuals experienced higher mortality (incidence rate ratio [IRR] = 1.76; 95% confidence interval [CI] 1.70-1.83) and greater likelihood of entering PRAC (IRR = 1.73; 95% CI 1.67-1.79) compared with non-frail individuals. Total healthcare costs over the 3-year post-assessment period for 39 363 frail individuals were $1 277 659 900, compared with expected costs of $885 322 522 had they not been frail. The primary contributor to the mean monthly excess cost per frail individual (mean = $457, SD = 3192) was hospital admissions ($345; 75%)., Conclusions: Frailty is associated with higher rates of mortality and of entering PRAC, and excess costs of frailty are substantial and sustained over time. These findings emphasize the potential economic value of providing home care for older people before they become frail. Geriatr Gerontol Int 2024; 24: 939-947., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Serving in the military can have significant impacts on the mental health of veterans and their families. Military personnel can be exposed to a range of physical stressors, psychological trauma, risky lifestyle factors, a regimented military culture, and inadequate support when transitioning out of service. This article reviews research on interventions designed to improve the mental health of Australian military veterans in order to synthesise current knowledge and identify gaps in the literature. Our scoping review followed PRISMA recommendations and comprised peer-reviewed literature published since 2000. The review demonstrates a dominance of psychologically driven research paradigms and interventions and a neglect of the importance of social factors in shaping veteran mental health. There is a wide range of interventions available; however, the literature is narrow and limited. We found little evidence that the lived experience of veterans had been harnessed in program design or delivery. We argue the need for a holistic approach that moves beyond psychological and biological understandings of health and wellbeing to incorporate social and cultural determinants. Future research could adopt a stronger multidisciplinary approach, increased socio-cultural understanding, and greater consideration of the lived experience of veterans and their families.

Objective: This novel study sought to understand lived experience and carer perspectives on the use of adaptive trials to evaluate interventions for eating disorders, in addition to understanding the factors and outcomes of most importance in eating disorder research and treatments from a lived experience perspective., Method: A total of 73 people with either lived or carer experience consented, 70 started the questionnaire, and 36 (51%) completed all questions. Participants were asked Likert scale and open-ended questions to understand what factors and outcomes of eating disorder interventions were most important to them and understand their pre-existing knowledge of clinical trials. Two videos were then used to explain randomized controlled trials (RCTs) and adaptive trials and participants were asked their opinions, including perceived benefits and concerns, of each trial type., Results: The thematic analysis found two key themes regarding factors important in eating disorder treatment: Person-centred care and Evidence-based and effective treatment; and two key themes regarding outcomes of treatment: Sustained, full recovery and The bigger picture. Both RCTs and adaptive trials were viewed favorably, however, there was a slight preference for adaptive trials. Key themes for both demonstrated perceived benefits and ethical, practical, and scientific considerations unique to each., Discussion: Findings demonstrate the support of adaptive trials in eating disorder interventions from people with lived experience and their carers. It is recommended that researchers consider the use of adaptive designs and the incorporation of lived experience perspectives when designing future intervention trials., Public Significance: This novel study found that the use of adaptive trials in eating disorder intervention research is supported by people with lived experience and carers. Furthermore, the factors and outcomes of most importance to participants in this study are comparable to those previously identified in the emerging literature. The use of adaptive designs and the incorporation of lived experience are recommended in further clinical trials., (© 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Objective: This scoping review sought to map the breadth of literature on the use of adaptive design trials in eating disorder research., Method: A systematic literature search was conducted in Medline, Scopus, PsycInfo, Emcare, Econlit, CINAHL and ProQuest Dissertations and Theses. Articles were included if they reported on an intervention targeting any type of eating disorder (including anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified feeding or eating disorders), and employed the use of an adaptive design trial to evaluate the intervention. Two independent reviewers screened citations for inclusion, and data abstraction was performed by one reviewer and verified by a second., Results: We identified five adaptive design trials targeting anorexia nervosa, bulimia nervosa and binge-eating disorder conducted in the USA and Australia. All employed adaptive treatment arm switching based on early response to treatment and identified a priori stopping rules. None of the studies included value of information analysis to guide adaptive design decisions and none included lived experience perspectives., Discussion: The limited use of adaptive designs in eating disorder trials represents a missed opportunity to improve enrolment targets, attrition rates, treatment outcomes and trial efficiency. We outline the range of adaptive methodologies, how they could be applied to eating disorder research, and the specific operational and statistical considerations relevant to adaptive design trials., Public Significance: Adaptive design trials are increasingly employed as flexible, efficient alternatives to fixed trial designs, but they are not often used in eating disorder research. This first scoping review identified five adaptive design trials targeting anorexia nervosa, bulimia nervosa and binge-eating disorder that employed treatment arm switching adaptive methodology. We make recommendations on the use of adaptive design trials for future eating disorder trials., (© 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Background: Emergency service personnel perform roles associated with high levels of trauma exposure and stress, and not surprisingly experience greater risk for poor mental health including posttraumatic stress disorder (PTSD), depression, anxiety, and substance use relative to the general population. Although programs exist to minimise the risk of developing mental health problems, their efficacy to date has been limited or untested. We will test the efficacy of the three programs which form PEREI: Protecting Emergency Responders with Evidence-Based Interventions. PEREI consists of modified versions of internet-delivered cognitive training in resilience (iCT-R) for early career first responders, PEREI-S for supervisors, and Be Well for Significant Others (BW-SO). Method : Up to 450 members in their first 5 years of service across multiple agencies will be recruited, with their adult supports (significant others, friends) invited to participate. Up to 180 supervisors in the agencies will be recruited. Participants will be randomized to their respective program or to receive the standard practice for mental health offered by the service (or usual mental health support for significant others). Assessments will be conducted pre- and post-program, and at 6- and 12-month follow-up. Primary outcome is PTSD and depression severity and probable-diagnosis. Secondary measures will index hypothesized mediators and moderators of outcome and determine whether the programs are cost-effective. Conclusions : The results will provide evidence as to efficacious methods for reducing risk of mental health problems in high-risk occupations, a better understanding of how such interventions may work, and whether they are good value for money. Trial registration: www.anzctr.org.au (ACTRN12622001267741).

Aim: Home care packages (HCPs) facilitate older individuals to remain at home, with longer HCP wait times associated with increased mortality risk. We analyze healthcare cost data pre- and post-HCP access to inform hypotheses around the effects of healthcare use and mortality risk., Methods: Regression models were used to assess the impact of delayed HCP access on healthcare costs and to compare costs whilst waiting and in the 6- and 12 month periods post-HCP access for 16 629 older adults., Results: Average wait time for a HCP was 89.7 days (SD = 125.6) during the study period. Wait-time length had no impact on any healthcare cost category or time period. However, total per day healthcare costs were higher in the 6 and 12 months post-receipt of a HCP (AU$61.5, AU$63, respectively) compared with those in the time waiting for a HCP (AU$48.1). Inpatient care accounted for a higher proportion of total healthcare costs post-HCP (AU$45.1, AU$46.3, respectively) compared with in the wait time (AU$30.6), whilst spending on medical services and pharmaceuticals reduced slightly in the 6 month (AU$7.1, AU$6.3) and 12 month (AU$7.2, AU$6.3) post-HCP periods compared with in the wait time (AU$7.9, AU$7.1)., Conclusions: Increased spending post-HCP on inpatient care or non-health support afforded by HCPs may offer protective effects for mortality and risk of admission to aged care. Further research should explore the association between delayed access to inpatient care for geriatric syndromes and mortality to inform recommendations on extensions to residential care outreach services into the community to improve the timely identification of the need for inpatient care. Geriatr Gerontol Int 2023; 23: 899-905., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Purpose: Improved health outcomes for individuals ever diagnosed with cancer require comprehensive, coordinated care that addresses their supportive care needs. Implementing interventions to address these is confounded by a lack of evidence on population needs and a large pool of potential interventions. This systematic review estimates the point prevalence of different supportive care needs stratified by the tool used to measure needs and cancer type in Australia., Methods: We searched MEDLINE, Embase, and Scopus from 2010 to April 2023 to identify relevant studies published on the prevalence of supportive care needs in Australia., Results: We identified 35 studies that met the inclusion criteria. The highest prevalent unmet need across all cancers was 'fear of cancer spreading' (20.7%) from the Supportive Care Needs Survey Short-Form 34 (SCNS-SF34), ranging from 9.4% for individuals ever diagnosed with haematological cancer to 36.3% for individuals ever diagnosed with gynaecological cancer, and 'concerns about cancer coming back' (17.9%) from the Cancer Survivors' Unmet Needs (CaSUN), ranging from 9.7% for individuals ever diagnosed with prostate cancer to 37.8% for individuals ever diagnosed with breast cancer. Two studies assessed needs in Aboriginal and Torres Strait Islander populations, reporting the highest needs for financial worries (21.1%)., Conclusions: Point prevalence estimates presented here, combined with estimates of the costs and effects of potential interventions, can be used within economic evaluations to inform evidence-based local service provision to address the supportive care needs of individuals ever diagnosed with cancer., Implications for Cancer Survivors: Local health services can use local evidence to prioritise the implementation of interventions targeted at unmet needs., (© 2023. The Author(s).)

Cancer is a leading cause of global morbidity and mortality, accounting for 250 Disability-Adjusted Life Years and 10 million deaths in 2019. Minimising unwarranted variation and ensuring appropriate cost-effective treatment across primary and tertiary care to improve health outcomes is a key health priority. There are few studies that have used linked data to explore healthcare utilisation prior to diagnosis in addition to post-diagnosis patterns of care. This protocol outlines the aims of the DaLECC project and key methodological features of the linked dataset. The primary aim of this project is to explore predictors of variations in pre- and post-cancer diagnosis care, and to explore the economic and health impact of any variation. The cohort of patients includes all South Australian residents diagnosed with cancer between 2011 and 2020, who were recorded on the South Australian Cancer Registry. These cancer registry records are being linked with state and national healthcare databases to capture health service utilisation and costs for a minimum of one-year prior to diagnosis and to a maximum of 10 years post-diagnosis. Healthcare utilisation includes state databases for inpatient separations and emergency department presentations and national databases for Medicare services and pharmaceuticals. Our results will identify barriers to timely receipt of care, estimate the impact of variations in the use of health care, and provide evidence to support interventions to improve health outcomes to inform national and local decisions to enhance the access and uptake of health care services.

Background: When healthcare budgets are exogenous, cost-effectiveness thresholds (CETs) used to inform funding decisions should represent the health opportunity cost (HOC) of such funding decisions, but HOC-based CET estimates have not been available until recently. In recent years, empirical HOC-based CETs for multiple countries have been published, but the use of these CETs in the cost-effectiveness analysis (CEA) literature has not been investigated. Analysis of the use of HOC-based CETs by researchers undertaking CEAs in countries with different decision-making contexts will provide valuable insights to further understand barriers and facilitators to the acceptance and use of HOC-based CETs., Objectives: We aimed to identify the CET values used to interpret the results of CEAs published in the scientific literature before and after the publication of jurisdiction-specific empirical HOC-based CETs in four countries., Methods: We undertook a scoping review of CEAs published in Spain, Australia, the Netherlands and South Africa between 2016 (2014 in Spain) and 2020. CETs used before and after publication of HOC estimates were recorded. We conducted logit regressions exploring factors explaining the use of HOC values in identified studies and linear models exploring the association of the reported CET value with study characteristics and results., Results: 1171 studies were included in this review (870 CEAs and 301 study protocols). HOC values were cited in 28% of CEAs in Spain and in 11% of studies conducted in Australia, but they were not referred to in CEAs undertaken in the Netherlands and South Africa. Regression analyses on Spanish and Australian studies indicate that more recent studies, studies without a conflict of interest and studies estimating an incremental cost-effectiveness ratio (ICER) below the HOC value were more likely to use the HOC as a threshold reference. In addition, we found a small but significant impact indicating that for every dollar increase in the estimated ICER, the reported CET increased by US$0.015. Based on the findings of our review, we discuss the potential factors that might explain the lack of adoption of HOC-based CETs in the empirical CEA literature., Conclusions: The adoption of HOC-based CETs by identified published CEAs has been uneven across the four analysed countries, most likely due to underlying differences in their decision-making processes. Our results also reinforce a previous finding indicating that CETs might be endogenously selected to fit authors' conclusions., (© 2021. The Author(s).)

Purpose: Individuals diagnosed with cancer have a range of supportive care needs that are often unmet despite substantial evidence supporting interventions to address them. Addressing this knowledge-translation gap represents a significant opportunity to improve health outcomes. A scoping review of reviews was conducted to map the breadth of evidence for interventions, highlighting those with an existing evidence base, as well as those requiring further research., Methods: Systematic or meta-analytic reviews that examined interventions targeting supportive care needs of adults and children with cancer published between 2009 and 2019 were identified via searches in Medline, PsycINFO, CINAHL, Scopus and Cochrane., Results: Five hundred fifty-one systematic reviews, including 250 meta-analyses, of interventions addressing supportive care needs, were included. Most reviews focused on interventions to address the physical and psychosocial needs of individuals with few reviews identified to address practical needs. Interventions using mental health therapies and physical activity were most commonly used to address all supportive care needs, followed by the use of pharmaceutical and medical devices, complementary and alternative therapies, information and education resources, dietary information and specific spirituality and return-to-work interventions., Conclusion: This scoping review of reviews presents the first broad overview of the literature addressing the supportive care needs of people living with or beyond cancer. It provides a database that health service providers can search to identify appropriate interventions. Results highlight specific research gaps, particularly for practical needs, where reviews are needed. It highlights where a substantial evidence base exists that researchers and policy-makers can consider when implementing interventions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Many health technology assessment committees have an explicit or implicit reference value (often referred to as a 'threshold') below which new health technologies or interventions are considered value for money. The basis for these reference values is unclear but one argument is that it should be based on the health opportunity costs of funding decisions. Empirical estimates of the marginal cost per unit of health produced by a healthcare system have been proposed to capture the health opportunity costs of new funding decisions. Based on a systematic search, we identified eight studies that have sought to estimate a reference value through empirical estimation of the marginal cost per unit of health produced by a healthcare system for England, Spain, Australia, The Netherlands, Sweden, South Africa and China. We review these eight studies to provide an overview of the key methodological approaches taken to estimate the marginal cost per unit of health produced by the healthcare system with the aim to help inform future estimates for additional countries. The lead author for each of these papers was invited to contribute to the current paper to ensure all the key methodological issues encountered were appropriately captured. These included consideration of the key variables required and their measurement, accounting for endogeneity of spending to health outcomes, the inclusion of lagged spending, discounting and future costs, the use of analytical weights, level of disease aggregation, expected duration of health gains, and modelling approaches to estimating mortality and morbidity effects of health spending. Subsequent research estimates for additional countries should (1) carefully consider the specific context and data available, (2) clearly and transparently report the assumptions made and include stakeholder perspectives on their appropriateness and acceptability, and (3) assess the sensitivity of the preferred central estimate to these assumptions., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

There is limited empirical evidence of the nature of any relationship between health spending and health outcomes in Australia. We address this by estimating the elasticity of health outcomes with respect to public healthcare spending using an instrumental variable (IV) approach to account for endogeneity of healthcare spending to health outcomes. Results suggest that, based on the conditional mean, a 1% increase in public health spending was associated with a 2.2% (p < 0.05) reduction in the number of standardised Years of Life Lost (YLL). Sensitivity analyses and robustness checks supported this conclusion. Further exploration using IV quantile regression indicated that marginal returns on public health spending were significantly greater for areas with poorer health outcomes compared to areas with better health outcomes. On average, marginal increases in public health spending reduce YLL, but areas with poorer health outcomes have the greatest potential to benefit from the same marginal increase in public health spending compared to areas with better health outcomes. Understanding the relationship between health spending and outcomes and how this differs according to baseline health outcomes can help meet dual policy objectives to improve the productivity of the healthcare system and reduce inequity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Spending on new healthcare technologies increases net population health when the benefits of a new technology are greater than their opportunity costs-the benefits of the best alternative use of the additional resources required to fund a new technology., Objective: The objective of this study was to estimate the expected incremental cost per quality-adjusted life-year (QALY) gained of increased government health expenditure as an empirical estimate of the average opportunity costs of decisions to fund new health technologies. The estimated incremental cost-effectiveness ratio (ICER) is proposed as a reference ICER to inform value-based decision making in Australia., Methods: Empirical top-down approaches were used to estimate the QALY effects of government health expenditure with respect to reduced mortality and morbidity. Instrumental variable two-stage least-squares regression was used to estimate the elasticity of mortality-related QALY losses to a marginal change in government health expenditure. Regression analysis of longitudinal survey data representative of the general population was used to isolate the effects of increased government health expenditure on morbidity-related, QALY gains. Clinical judgement informed the duration of health-related quality-of-life improvement from the annual increase in government health expenditure., Results: The base-case reference ICER was estimated at AUD28,033 per QALY gained. Parametric uncertainty associated with the estimation of mortality- and morbidity-related QALYs generated a 95% confidence interval AUD20,758-37,667., Conclusion: Recent public summary documents suggest new technologies with ICERs above AUD40,000 per QALY gained are recommended for public funding. The empirical reference ICER reported in this article suggests more QALYs could be gained if resources were allocated to other forms of health spending.

Vitamin B12, folate and homocysteine have long been implicated in mental illness, and growing evidence suggests that they may play a role in positive mental health. Elucidation of these relationships is confounded due to the dependence of homocysteine on available levels of vitamin B12 and folate. Cross-sectional and longitudinal relationships between vitamin B12, folate, homocysteine and subjective well-being were assessed in a sample of 391 older, community-living adults without clinically diagnosed depression. Levels of vitamin B12, but not folate, influenced homocysteine levels 18 months later. Vitamin B12, folate and their interaction significantly predicted levels of positive affect (PA) 18 months later, but had no impact on the levels of negative affect or life satisfaction. Cross-sectional relationships between homocysteine and PA were completely attenuated in the longitudinal analyses, suggesting that the cross-sectional relationship is driven by the dependence of homocysteine on vitamin B12 and folate. This is the first study to offer some evidence of a causal link between levels of folate and vitamin B12 on PA in a large, non-clinical population.