Medicine (RMH) - Research Publications

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    Relationship Between Urinary Phosphate and All-Cause and Cardiovascular Mortality in a National Population-Based Longitudinal Cohort Study
    Toussaint, ND ; Damasiewicz, MJ ; Holt, SG ; Lu, ZX ; Magliano, DJ ; Atkins, RC ; Chadban, SJ ; Shaw, JE ; Polkinghorne, KR (W B SAUNDERS CO-ELSEVIER INC, 2022-09)
    OBJECTIVES: High dietary phosphate intake may lead to adverse outcomes including cardiovascular disease (CVD). Urinary phosphate excretion, a marker of intestinal phosphate absorption, may be a more reliable marker of phosphate homeostasis in steady state than serum phosphate. Studies report good agreement between urine phosphate-to-creatinine ratio (uPiCr) and 24-hour urinary phosphate; however, whether uPiCr is associated with increased risk of CVD or mortality remains uncertain. This study aimed to assess the relationship between uPiCr and all-cause and CVD mortality. DESIGN AND METHODS: This is an observational longitudinal cohort study using data from the population-based national Australian Diabetes, Obesity and Lifestyle study (n = 10,014 participants). Non-linear association between uPiCr and all-cause and CVD mortality was assessed using fractional polynomial transformations. Cox proportional hazards regression models were used to estimate adjusted hazard ratios for all-cause and CVD mortality. RESULTS: Median age [interquartile range] was 50 [41-62] years, and 46% were male. Median uPiCr was 1.38 [1.02-1.79] mmol/mmol. Median follow-up time was 16.9 years with 1,735 deaths. uPiCr was associated with all-cause and CVD mortality in univariate models and when adjusted for age and gender. However, associations were not significant in multivariate models. Sensitivity analyses excluding participants with chronic kidney disease (CKD) revealed a significant J-shaped association between uPiCr and all-cause mortality. Urine phosphate alone showed an association with increased all-cause mortality in a similar J-shape relationship. CONCLUSION: Although no association between uPiCr and all-cause and CVD mortality was observed in multivariate analyses in the whole cohort, a significant relationship between uPiCr and mortality in those without CKD suggests that uPiCr may have predictive validity for future adverse outcomes in people with no CKD.
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    Projecting 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
    Morton, J ; Marquina, C ; Shaw, JE ; Liew, D ; Polkinghorne, KR ; Ademi, Z ; Magliano, DJ (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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    The Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes
    Menon, K ; de Courten, B ; Magliano, DJ ; Ademi, Z ; Liew, D ; Zomer, E (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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    Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies
    Koye, DN ; Shaw, JE ; Reid, CM ; Atkins, RC ; Reutens, AT ; Magliano, DJ (WILEY, 2017-07)
    AIMS: The aim was to systematically review published articles that reported the incidence of chronic kidney disease among people with diabetes. METHODS: A systematic literature search was performed using MEDLINE, Embase and CINAHL databases. The titles and abstracts of all publications identified by the search were reviewed and 10 047 studies were retrieved. RESULTS: A total of 71 studies from 30 different countries with sample sizes ranging from 505 to 211 132 met the inclusion criteria. The annual incidence of microalbuminuria and albuminuria ranged from 1.3% to 3.8% for Type 1 diabetes. For Type 2 diabetes and studies combining both diabetes types, the range was from 3.8% to 12.7%, with four of six studies reporting annual rates between 7.4% and 8.6%. In studies reporting the incidence of eGFR < 60 ml/min/1.73 m2 using the Modification of Diet on Renal Disease (MDRD) equation, apart from one study which reported an annual incidence of 8.9%, the annual incidence ranged from 1.9% to 4.3%. The annual incidence of end-stage renal disease ranged from 0.04% to 1.8%. CONCLUSIONS: The annual incidence of microalbuminuria and albuminuria is ~ 2-3% in Type 1 diabetes, and ~ 8% in Type 2 diabetes or mixed diabetes type. The incidence of developing eGFR < 60 ml/min/1.73 m2 is ~ 2-4% per year. Despite the wide variation in methods and study design, within a particular category of kidney disease, there was only modest variation in incidence rates. These findings may be useful in clinical settings to help understand the risk of developing kidney disease among those with diabetes.
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    Association between type 2 diabetes mellitus and disability: What is the contribution of diabetes risk factors and diabetes complications?
    Tabesh, M ; Shaw, JE ; Zimmet, PZ ; Soderberg, S ; Koye, DN ; Kowlessur, S ; Timol, M ; Joonas, N ; Sorefan, A ; Gayan, P ; Alberti, KGMM ; Tuomilehto, J ; Magliano, DJ (WILEY, 2018-09)
    BACKGROUND: The aim of this study was to evaluate the association between type 2 diabetes and disability in Mauritius and to assess the extent to which the effect of diabetes is explained by diabetes risk factors and concomitant complications. METHODS: Data from a national survey in the multiethnic nation of Mauritius, which comprises South Asians and African Creoles, were analyzed. Disability was measured using the Katz activities of daily living questionnaire in participants aged >50 years. RESULTS: Among 3692 participants, 487 (13.2%) had some level of disability. Diabetes was associated with significantly higher risk of disability (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.34-2.08). After adjusting for demographic, behavioral, and metabolic factors, as well as comorbidities, disability was significantly associated with diabetes among African Creoles (OR 2.03; 95% CI 1.16-3.56), but not South Asians (OR 1.27; 95% CI 0.98-1.66). Obesity explained much of the association between diabetes and disability (excess percentage of risk: 26.3% in South Asians and 12.1% in African Creoles). Obesity, history of cardiovascular disease (CVD), asthma-like symptoms, and depression together explained 46.5% and 29.0% of the excess risk in South Asians and African Creoles, respectively. CONCLUSIONS: Diabetes is associated with a 67% increased risk of disability. Diabetes risk factors and comorbidities explain more of the association between diabetes and disability among South Asians than Africans. Obesity and history of CVD explained the largest percentage of the relationship between diabetes and disability, indicating that weight and CVD management may be helpful in controlling disability related to diabetes.
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    Educating junior doctors and pharmacists to reduce discharge prescribing of opioids for surgical patients: a cluster randomised controlled trial
    Hopkins, RE ; Thuy, B ; Konstantatos, AH ; Arnold, C ; Magliano, DJ ; Liew, D ; Dooley, MJ (WILEY, 2020-11)
    OBJECTIVES: To evaluate whether educating junior doctors and hospital pharmacists about analgesic prescribing improved discharge prescribing of opioids for opioid-naïve patients after surgical admissions. DESIGN: Cluster randomised controlled trial, undertaken during the first half of 2019. SETTING: The Alfred Hospital, a major Melbourne teaching hospital with 13 surgical units. PARTICIPANTS: Opioid-naïve patients discharged from surgical units after a stay of at least 24 hours. INTERVENTION: Surgical units were randomised to the intervention or control arms. Interns, residents, and clinical pharmacists assigned to intervention arm units attended education sessions, presented by the hospital analgesic stewardship pharmacist, about appropriate analgesic prescribing for patients in hospital surgical units. MAIN OUTCOME MEASURES: The patients prescribed slow release opioids on discharge from hospital during the baseline (1 February - 30 April 2018) and post-intervention periods (17 February - 30 April 2019). RESULTS: During the baseline period, 1369 intervention unit and 1014 control unit admissions were included in our analysis; during the evaluation period, 973 intervention unit and 706 control unit episodes were included. After adjusting for age, length of stay, pain score, acute pain service involvement, and use of immediate release opioids prior to admission, patients in the intervention group were prescribed slow release opioids at discharge less frequently than patients in the control group (adjusted odds ratio [aOR], 0.52; 95% CI, 0.35-0.77) and were more frequently discharged without any prescribed opioids following the intervention (aOR, 1.69; 95% CI, 1.24-2.30). Providing de-escalation plans was more frequent for intervention than control group patients prescribed slow release opioids on discharge post-intervention (OR, 2.36; 95% CI, 1.25-4.45). CONCLUSIONS: Specific education for clinicians and pharmacists about appropriate analgesic prescribing for surgical patients is effective in reducing prescribing of opioids at discharge. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618000876291 (prospective).
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    Assessing the impact of smoking on the health and productivity of the working-age Indonesian population using modelling
    Satyana, RPU ; Uli, RE ; Magliano, D ; Zomer, E ; Liew, D ; Ademi, Z (BMJ PUBLISHING GROUP, 2020)
    OBJECTIVES: To estimate the impact of smoking in the working-age Indonesian population in terms of costs, years of life, quality-adjusted life years (QALYs) and productivity-adjusted life years (PALYs) lost. METHODS: Life table modelling of Indonesian smokers aged 15-54 years, followed up until 55 years (retirement age). Contemporary data on demographics, all-cause mortality, population attributable fractions and prevalence of smoking were derived from the Institute for Health Metrics and Evaluation. The quality of life and reduction in productivity due to smoking were derived from published sources. The analysis was repeated but with the assumption that the cohorts were non-smokers. The differences in results represented the losses incurred due to smoking. Gross domestic product (GDP) per equivalent full-time worker (US$11 765) was used for estimation of the cost of each PALY, and an annual discount rate of 3.0% was applied to all costs and outcomes. RESULTS: The prevalences of smoking among Indonesian working-age men and women were 67.2% and 2.16%, respectively. This study estimated that smoking caused 846 123 excess deaths, 2.9 million years of life lost (0.40%), 41.6 million QALYs lost (5.9%) and 15.6 million PALYs lost (2.3%). The total cost of productivity loss due to smoking amounted to US$183.7 billion among the working-age population followed up until retirement. Healthcare cost was predicted to be US$1.8 trillion. Over a 1-year time horizon, US$10.2 billion was lost in GDP and 117 billion was lost in healthcare costs. CONCLUSION: Smoking imposes significant health and economic burden in Indonesia. The findings stress the importance of developing effective tobacco control strategies at the macro and micro levels, which would benefit the country both in terms of health and wealth.
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    Diabetes Prevention and Treatment Strategies: Are we doing enough?
    Backholer, K ; Peeters, A ; Herman, WH ; Shaw, JE ; Liew, D ; Ademi, Z ; Magliano, DJ (AMER DIABETES ASSOC, 2013-09)
    OBJECTIVE: Effective interventions to prevent, delay, or remit diabetes are currently available. However, their impact on the prevalence of diabetes at the population level is unknown. This study aimed to estimate the impact of a range of diabetes interventions on the population prevalence of diabetes for Australian adults between 2010 and 2025. RESEARCH DESIGN AND METHODS: We used the Australian Diabetes Projection Model to estimate the impact of a population-wide strategy, high-risk prevention, surgical diabetes treatment, and a combination strategy on the future population prevalence of diabetes and to estimate the number of diabetes cases that could be potentially prevented in the year 2025. RESULTS: We estimate that a population-wide strategy would reduce the number of diabetes cases by 60,000-85,000 in 2025 from an estimated 2 million cases under the status quo scenario. A high-risk prevention strategy would result in 106,000 to 150,000 fewer cases of diabetes in 2025, and surgically induced weight loss would result in 3,000-6,000 fewer cases. No single intervention, or combination of interventions, reversed the increasing trend in diabetes prevalence over the next 15 years. CONCLUSIONS: To reverse upward trends in diabetes prevalence in future years, it is essential that current approaches to diabetes prevention and treatment are optimized and implemented and that alternative approaches to reduce the prevalence of diabetes at a population level are developed.
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    Health and productivity burden of coronary heart disease in the working Indonesian population using life-table modelling
    Uli, RE ; Satyana, RPU ; Zomer, E ; Magliano, D ; Liew, D ; Ademi, Z (BMJ PUBLISHING GROUP, 2020)
    OBJECTIVES: The impact of coronary heart disease (CHD) and its effect on work productivity at a population level remains unknown in Indonesia. This study estimates the health and productivity lost to CHD in terms of years of life, quality-adjusted life years (QALYs) and productivity-adjusted life years (PALYs). SETTING AND PARTICIPANTS: A life-table model was constructed to simulate the experiences of Indonesians currently aged 15-54 years (working age) with CHD, followed-up to 55 years (retirement age). The life-table analysis was then repeated assuming that the cohort did not have CHD. Differences in the results reflected the impact of CHD. Demographical, prevalence and mortality data were based on the 2017 Global Burden of Disease study and 2018 Indonesian National Health Survey. Costs, productivity indices and utilities were derived from published sources. The cost of each PALY was assumed to be equivalent to gross domestic product per equivalent full-time worker (US$11 765). Future costs and outcomes were discounted by 3% annually. PRIMARY AND SECONDARY OUTCOME MEASURES: Differences in total deaths, years of life and PALYs represented the impact of CHD. RESULTS: At present, 1 954 543 (1.45%) Indonesians of working-age have CHD. By retirement age, it was estimated that CHD resulted in 32 492 (36.6%) excess deaths, 128 132 (0.5%) years of life lost, 2 331 495 (10.5%) QALYs lost and 1 589 490 (6.9%) PALYs lost. The economic impact of lost productivity amounted to US$33.3 billion, and healthcare costs to US$139 billion. CONCLUSION: The health and economic burden of CHD in Indonesia looms large. This highlights the importance of its prevention and control, strategies for which, if effective, will deliver financial return.
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    The impact of diabetes on the productivity and economy of Bangladesh
    Afroz, A ; Hird, TR ; Zomer, E ; Owen, A ; Chen, L ; Ademi, Z ; Liew, D ; Magliano, DJ ; Billah, B (BMJ PUBLISHING GROUP, 2020-06)
    AIMS: To estimate the impact of type 2 diabetes in terms of mortality, years of life lost (YLL) and productivity-adjusted life years (PALY) lost in Bangladesh. METHODS: A life table model was constructed to estimate the productivity of the Bangladeshi population of current working age (20-59 years) with diabetes. Follow-up to 60 years (retirement age) was simulated. The life table analysis was then repeated assuming that the cohort did not have diabetes, with subsequent improvement in productivity. Differences in the results of the two analyses reflected the impact of diabetes on health and productivity. Demographic and the prevalence of diabetes data were sourced from the International Diabetes Foundation estimates for 2017 and mortality data were based on the 2017 Global Burden of Disease study. Relative risk and productivity indices were based on an Indian and Bangladeshi study, respectively. The cost of each PALY was assumed to be equivalent to gross domestic product (GDP) per equivalent full-time worker (US$8763). Future costs and years of life, and PALYs lived were discounted at an annual rate of 3%. RESULTS: Assuming a follow-up of this population (aged 20-59 years) until age 60 years or death, an estimated 813 807 excess deaths, loss of 4.0 million life years (5.5%) and 9.2 million PALYs (20.4%) were attributable to having diabetes. This was equivalent to 0.7 YLL, and 1.6 PALYs lost per person. The loss in PALYs equated to a total of US$97.4 billion lost (US$16 987 per person) in GDP. The results of the scenario analysis showed that the estimation was robust. CONCLUSION: In Bangladesh, the impact of diabetes on productivity loss and the broader economy looms large, and poses a substantial risk to the country's future prosperity. This highlights the critical importance of health strategies aimed at the control of diabetes.