Medicine (RMH) - Research Publications
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ItemNo Preview AvailableImpact of epilepsy surgery on quality of life: Systematic review and meta-analysis(WILEY, 2023-07)Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug-resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes. We conducted a systematic review and meta-analysis using Medline, Embase, and Cochrane Central Register of Controlled Trials. All studies reporting pre- and post-epilepsy surgery QoL scores in adults with DRE via validated instruments were included. Meta-analysis assessed the postsurgery change in QoL. Meta-regression assessed the effect of postoperative seizure outcomes on postoperative QoL as well as change in pre- and postoperative QoL scores. A total of 3774 titles and abstracts were reviewed, and ultimately 16 studies, comprising 1182 unique patients, were included. Quality of Life in Epilepsy Inventory-31 item (QOLIE-31) meta-analysis included six studies, and QOLIE-89 meta-analysis included four studies. Postoperative change in raw score was 20.5 for QOLIE-31 (95% confidence interval [CI] = 10.9-30.1, I2 = 95.5) and 12.1 for QOLIE-89 (95% CI = 8.0-16.1, I2 = 55.0%). This corresponds to clinically meaningful QOL improvements. Meta-regression demonstrated a higher postoperative QOLIE-31 score as well as change in pre- and postoperative QOLIE-31 score among studies of cohorts with higher proportions of patients with favorable seizure outcomes. At an individual study level, preoperative absence of mood disorders, better preoperative cognition, fewer trials of antiseizure medications before surgery, high levels of conscientiousness and openness to experience at the baseline, engagement in paid employment before and after surgery, and not being on antidepressants following surgery were associated with improved postoperative QoL. This study demonstrates the potential for epilepsy surgery to provide clinically meaningful improvements in QoL, as well as identifies clinicodemographic factors associated with this outcome. Limitations include substantial heterogeneity between individual studies and high risk of bias.
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ItemProjecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis(SPRINGER, 2023-04)AIMS/HYPOTHESIS: Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs. METHODS: We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained. RESULTS: The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs. CONCLUSIONS/INTERPRETATION: At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.
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ItemThe effect of epilepsy surgery on productivity: A systematic review and meta-analysis(WILEY, 2022-04)OBJECTIVES: An important but understudied benefit of resective epilepsy surgery is improvement in productivity; that is, people's ability to contribute to society through participation in the workforce and in unpaid roles such as carer duties. Here, we aimed to evaluate productivity in adults with drug-resistant epilepsy (DRE) pre- and post-resective epilepsy surgery, and to explore the factors that positively influence productivity outcomes. METHODS: We conducted a systematic review and meta-analysis using four electronic databases: Medline (Ovid), EMBASE (Ovid), EBM Reviews - Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Library. All studies over the past 30 years reporting on pre- and post-resective epilepsy surgical outcomes in adults with DRE were eligible for inclusion. Meta-analysis was performed to assess the post-surgery change in employment outcomes. RESULTS: A total of 1005 titles and abstracts were reviewed. Seventeen studies, comprising 2056 unique patients, were suitable for the final quantitative synthesis and meta-analysis. Resective epilepsy surgery resulted in a 22% improvement in overall productivity (95% confidence interval [CI]: 1.07-1.40). The factors associated with increased post-surgery employment risk ratios were lower pre-surgical employment in the workforce (relative risk ratio [RRR] =0.34; 95% CI: 0.15-0.74), shorter follow-up duration (RRR = 0.95; 95% CI: 0.90-0.99), and lower mean age at time of surgery (RRR= 0.97; 95% CI: 0.94-0.99). The risk of bias of the included studies was assessed using Risk Of Bias In Non-randomised Studies - of Interventions and was low for most variables except "measurement of exposure." SIGNIFICANCE: There is clear evidence that resective surgery in eligible surgical DRE patients results in improved productivity. Future work may include implementing a standardized method for collecting and reporting productivity in epilepsy cohorts and focusing on ways to reprioritize health care resource allocation to allow suitable candidates to access surgery earlier. This will ultimately benefit individuals with DRE, their families, our communities, and the wider health care system.
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ItemIntegrating the Biology of Cardiovascular Disease into the Epidemiology of Economic Decision Modelling via Mendelian Randomisation(ADIS INT LTD, 2022-11)Health economic analyses are essential for health services research, providing decision-makers and payers with evidence about the value of interventions relative to their opportunity cost. However, many health economic approaches are still limited, especially regarding the primary prevention of cardiovascular disease (CVD). In this article, we discuss some limitations to current health economic models and then outline an approach to address these via the incorporation of genomics into the design of health economic models for CVD. We propose that when a randomised clinical trial is not possible or practical, health economic models for primary prevention of CVD can be based on Mendelian randomisation analyses, a technique to assess causality in observational data. We discuss the advantages of this approach, such as integrating well-known disease biology into health economic models and how this may overcome current statistical approaches to assessing the benefits of interventions. We argue that this approach may provide the economic argument for integrating genomics into clinical practice and the efficient targeting of newer therapeutics, transforming our approach to the primary prevention of CVD, thereby moving from reactive to preventive healthcare. We end by discussing some limitations and potential pitfalls of this approach.
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ItemEstimating the benefits of obesity prevention on productivity: an Australian perspective(SPRINGERNATURE, 2022-08)BACKGROUND/OBJECTIVES: Obesity poses one of the biggest public health challenges globally. In addition to the high costs of obesity to the healthcare system, obesity also impacts work productivity. We aimed to estimate the benefits of preventing obesity in terms of years of life, productivity-adjusted life years (PALYs) and associated costs over 10 years. SUBJECTS/METHODS: Dynamic life table models were constructed to estimate years of life and PALYs saved if all new cases of obesity were prevented among Australians aged 20-69 years from 2021 to 2030. Life tables were sex specific and the population was classified into normal weight, overweight and obese. The model simulation was first undertaken assuming currently observed age-specific incidences of obesity, and then repeated assuming all new cases of obesity were reduced by 2 and 5%. The differences in outcomes (years of life, PALYs, and costs) between the two modelled outputs reflected the potential benefits that could be achieved through obesity prevention. All outcomes were discounted by 5% per annum. RESULTS: Over the next 10 years, 132 million years of life and 81 million PALYs would be lived by Australians aged 20-69 years, contributing AU$17.0 trillion to the Australian economy in terms of GDP. A 5% reduction in new cases of obesity led to a gain of 663 years of life and 1229 PALYs, equivalent to AU$262 million in GDP. CONCLUSIONS: Prevention of obesity is projected to result in substantial economic gains due to improved health and productivity. This further emphasises the need for public health prevention strategies to reduce this growing epidemic.
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ItemProspective multisite cohort study of patient-reported outcomes in adults with new-onset seizures(WILEY, 2022-03)OBJECTIVE: New-onset seizures affect up to 10% of people over their lifetime, however, their health economic impact has not been well-studied. This prospective multicenter study will collect patient-reported outcome measures (PROMs) from adults with new-onset seizures seen in six Seizure Clinics across Melbourne, Australia and The University of Colorado, USA. METHODS: Approximately 450 eligible patients will be enrolled in the study at or following their initial attendance to Seizure Clinics at the study hospitals. Inclusion criteria for the study group are those with new-onset acute symptomatic seizures, new-onset unprovoked seizures, and new-onset epilepsy. Inclusion criteria for the three comparator groups are those with noncardiac syncope, those with psychogenic nonepileptic seizures, as well as published PROMs data from the Australian general population. Exclusion criteria are those aged less than 18 years, those with a preexisting epilepsy diagnosis, and those with intellectual disabilities or other impairments which would preclude them from comprehending and completing the questionnaires. Patients will complete eight online questionnaires regarding the effect that their seizures (or seizure mimics) have had on various aspects of their life. These questionnaires will be readministered at 6 and 12 months. Patients with new-diagnosis epilepsy will also be asked to share the reasons why they have accepted or declined antiseizure medications. ANALYSIS: Primary outcome measures will be quality of life, work productivity, informal care needs, and mood, at baseline compared to 6 and 12 months later for those with new-onset seizures and comparing these outcomes to those in the three comparator groups. Secondary outcomes include mapping of QoLIE-31 to the EQ-5D-5L in epilepsy, modelling indirect costs of new-onset seizures, and exploring why patients may or may not wish to take antiseizure medications. SIGNIFICANCE: These data will form an evidence-base for future studies that examine the effectiveness of various healthcare interventions for new-onset seizure patients. ETHICS AND DISSEMINATION: This study is approved by the Alfred Health Human Research Ethics Committee (SERP: 52 538, Alfred HREC: 307/19), the Austin Health Human Research Ethics Committee (HREC/59148/Austin-2019), and the Colorado Multiple Institutional Review Board (COMIRB) (COMIRB #20-3028). ANZCTR TRIAL REGISTRATION NUMBER: ACTRN12621000908831.
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ItemThe Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes(MDPI, 2022-01)In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were 'Alive without type 2 diabetes', 'Alive with type 2 diabetes' and 'Dead'. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.
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ItemSynopsis of an integrated guidance for enhancing the care of familial hypercholesterolaemia: an Australian perspective(ELSEVIER, 2021-06)INTRODUCTION: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH. MAIN RECOMMENDATIONS: Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. There is a key role for general practitioners (GPs) working in collaboration with specialists with expertise in lipidology. Advice is given on genetic and cholesterol testing and risk notification of biological relatives undergoing cascade testing for FH; all healthcare professionals should develop skills in genomic medicine. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors, and appropriate use of low-density lipoprotein (LDL)-cholesterol lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recommendations on service design are provided in the full guidance. POTENTIAL IMPACT ON CARE OF FH: These recommendations need to be utilised using judicious clinical judgement and shared decision making with patients and families. Models of care need to be adapted to both local and regional needs and resources. In Australia new government funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of these recommendations. A broad implementation science strategy is, however, required to ensure that the guidance translates into benefit for all families with FH.
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ItemComparisons of direct and indirect utilities in adult epilepsy populations: A systematic review(WILEY, 2019-12)OBJECTIVE: Epilepsy is common and carries substantial morbidity, and therefore identifying cost-effective health interventions is essential. Cost-utility analysis is a widely used method for such analyses. For this, health conditions are rated in terms of utilities, which provide a standardized score to reflect quality of life. Utilities are obtained either indirectly using quality of life questionnaires, or directly from patients or the general population. We sought to describe instruments used to estimate utilities in epilepsy populations, and how results differ according to methods used. METHODS: We undertook a systematic review of studies comparing at least two instruments for obtaining utilities in epilepsy populations. MEDLINE, Embase, ScienceDirect, Cochrane Library, Google Scholar, and gray literature were searched from inception to June 2019. Mean utilities were recorded and compared for each method. RESULTS: Of the 38 unique records initially identified, eight studies met inclusion criteria. Utilities were highest for direct "tradeoff" methods, obtained via instruments including standard gamble (0.93) and time tradeoff (0.92), compared to indirect methods, obtained via instruments including EuroQoL five-dimensional form (range = 0.72-0.86) and Health Utilities Index Mark 3 (range = 0.52-0.71). Visual analog scale (VAS), a direct "nontradeoff" instrument, provided equal or lower utilities (range = 68.0-79.8) compared to indirect instruments. SIGNIFICANCE: Direct methods, with the important exception of VAS, may provide higher utilities than indirect methods. More studies are needed to identify the most appropriate utility instruments for epilepsy populations, and to investigate whether there is variation between utilities for different types of epilepsy and other patient- and disease-specific factors.
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ItemThe Health and Productivity Burden of Migraines in Australia(WILEY, 2020-11)OBJECTIVE: This study aimed to quantify the health and productivity burden of migraines in Australia, measured by quality-adjusted life years (QALYs), productivity-adjusted life years (PALYs, a novel measure of productivity), and associated health-care and broader economic costs. METHODS: A Markov state-transition model was constructed to simulate follow-up of Australians aged 20-64 years over the next 10 years. The model was first run using current prevalence estimates of migraine. It was then rerun assuming that people with migraine hypothetically did not have the condition. Differences in outcomes between the 2 model simulations represented the health and productivity burden attributable to migraine. All data inputs were obtained from published sources. Gross domestic product (GDP) per equivalent full-time worker in Australia was used to reflect the cost of each PALY (AU$177,092). Future costs and outcomes were discounted by 5% annually. RESULTS: Currently, 1,274,319 million (8.5%) Australians aged 20-64 years have migraine. Over the next 10 years, migraine was predicted to lead to a loss of 2,577,783 (95% confidence interval [CI] 2,054,980 to 3,000,784) QALYs among this cohort (2.02 per person and 2.43% of total QALYs), and AU$1.67 (95% CI $1.16 to $2.37) billion in health-care costs (AU$1313 per person, 95% CI $914 to $1862). There would also be 384,740 (95% CI 299,102 to 479,803) PALYs lost (0.30 per person and 0.53% of total PALYs), resulting in AU$68.13 (95% CI $44.42 to $98.25) billion of lost GDP (AU$53,467 per person, 95% CI $34,855 to $77,102). CONCLUSION: Migraines impose a substantial health and economic burden on Australians of working age. Funding interventions that reduce the prevalence of migraines and/or its effects are likely to provide sound return on investment.