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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., (© 2022. The Author(s).)

Lipid-lowering medications comprise standard of care in the prevention of cardiovascular disease. This study examined the trends in the utilization of statin and non-statin medications in the Australian general population between 2013 and 2019. Pharmacoepidemiological analyses were performed using pharmacy dispensing data from Australian Pharmaceutical Benefits Scheme. One-year prevalence and incidence of statin and non-statin prescribing patterns were reported, and relative variations in prescribing examined via Poisson regression modelling. The one-year prevalence of statins' prescriptions decreased between 2013-2019 by 5.5% (from 25.0%-19.5%). Females were less likely than males to be prescribed statins (rate ratio [RR]=0.90, 95% confidence interval [CI] 0.89-0.91). The one-year prevalence of ezetimibe alone, and in combination with statins, increased consistently from 2013-2019 from 1.5%-3.6% (P<0.01) and 0.1%-1.1% (P<0.01), respectively. The prevalence was higher among those aged 61-80 years (RR=1.20, 95%CI 1.10-1.21) and those aged older than 80 years (RR=1.34, 95%CI 1.22-1.47), when compared to people aged <60 years. The incidence of ezetimibe prescriptions was highest in people aged 61-80 years (RR=1.36, 95%CI 1.31-1.41) compared to those aged <60 years. The one-year prevalence of proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions was highest among those aged 46-60 years (RR=1.24, 95%CI 0.97-4.97) compared to people aged <46 and >60 years. Females were less likely than males to be prescribed a proprotein convertase subtilisin/kexin type 9 inhibitor (RR=0.87, 95%CI 0.75-0.98). Statins remain the most prevalent lipid-lowering medication prescribed in Australia. The prescribing of non-statin medications remains low, but is increasing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Little is known about the attainment of low-density lipoprotein cholesterol (LDL-C) targets in patients treated with statins in Australian primary healthcare setting that are at increased risk of cardiovascular disease. A retrospective cohort study was conducted using data from electronic medical records of patients treated by general practitioners across Australia. LDL-C target attainment was defined as LDL-C levels ≤ 2 mmol/L for all risk groups, in line with Australian guidelines. Multivariable logistic regression was used to identify the factors associated with LDL-C target attainment. Overall, 61,407 patients were included in the analysis. The mean age was 65 years (± standard deviation [SD] 12.1); 52.0% were males.. Overall, the median LDL-C level was 2.3 mmol/L (IQR = 1.8 - 2.8) and 36.0% of the study population met therapeutic targets. Increased likelihood to achieve LDL-C targets was observed in patients diagnosed with type 2 diabetes (OR 2.07, 95% CI 1.92 - 2.24), stroke (OR = 1.58, 95% CI 1.39 - 1.79, P < 0.001) or chronic heart disease (OR = 1.67, 95% CI 1.55 - 1.81, P < 0.001). Patients diagnosed with dyslipidemia (OR = 0.59, 95% CI 0.55 - 0.64, P < 0.001), hypertension (OR = 0.91, 95% CI 0.83 - 1.00, P < 0.05) and current smokers (OR = 0.71, 95% CI 0.71 - 1.00, P < 0.05), were less likely to attain LDL-C targets, regardless of the type, intensity and length of use of the prescribed statin. Longer duration and higher intensity statin were associated with more patients achieving targeted LDL-C goal, however nearly two thirds of Australians still failed to achieve targeted outcome even after 24 months of statin therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in real-world settings among patients receiving combination lipid-lowering therapy (LLT, statins plus non-statins) is not well characterised., Objective: To evaluate LDL-C levels and LDL-C goal attainment in patients treated with combination LLT in real-world primary care settings., Methods: A retrospective cohort study of patients treated with combination LLT. Data were drawn from general practitioner electronic medical records across Australia from 2013 to 2019. The on-treatment goal for LDL-C was < 2 mmol/L (77 mg/dL), as per Australian guidelines., Results: The cohort analysed included 9,173 individuals treated with combination LLT. The mean age was 65.8 years (standard deviation [SD] 11.5), 60.1% were males, and 56.7% had at least one cardiovascular risk factor. The median on-treatment LDL-C was 2.1 mmol/L (IQR 1.6-2.8), and overall 45.4% of the cohort met LDL-C goals, with individuals on fixed-dose combination of statins plus ezetimibe having the highest rates of achievement (49.8%). In multivariable logistic regression analyses, factors associated with LDL-C goal achievement were male sex (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.3-1.6, p < 0.001), aged >80 years (OR 4.2, 95% CI 1.5 - 6.6, p = 0.006), and a history of T2DM (OR 1.7; 95% CI 1.5-1.9, p < 0.001) or coronary heart disease (OR 1.4, 95% CI 1.2 - 1.6, p < 0.001)., Conclusions: More than half of Australians on combination LLT did not achieve LDL-C goals. Urgent measures are needed to address this gap in clinical practice to minimise negative health outcomes., Competing Interests: Declaration of Competing Interest CM, SVT, MP, ST, DA and ZA have nothing to declare; SL and DT are employed by Amgen Australia Pty Ltd or other Amgen subsidiaries; GS is employed by IQVIA; EZ declares grants from Amgen, AstraZeneca, Pfizer and Shire, outside the submitted work; DL declares grants from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Pfizer and Sanofi, and past participation in advisory boards and/or receipt of honoraria from Abbvie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Edwards Lifesciences, Novartis, Pfizer, Sanofi and Shire, outside the submitted work., (Copyright © 2022. Published by Elsevier Inc.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown to reduce cardiovascular events and mortality in patients with type 2 diabetes mellitus (T2DM), but they are currently not used as first-line therapy in clinical practice. This study sought to evaluate the cost-effectiveness of first-line empagliflozin plus standard care for patients with newly diagnosed T2DM and existing cardiovascular disease (CVD). A decision-analytic Markov model with one-year cycles and a lifetime time horizon was developed from the perspective of the Qatari healthcare system to compare first-line empagliflozin combined with metformin versus metformin monotherapy for patients aged 50 to 79 years with T2DM and existing CVD. Two health states were considered: 'Alive with CVD and T2DM' and 'Dead'. Patients could experience non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular or non-cardiovascular death. Model inputs were ascertained from published and publicly available sources in Qatar. Costs and outcomes were discounted at 3% per annum. Sensitivity analyses were conducted to evaluate parameter uncertainty. The model predicted that adding empagliflozin to current standard care led to additional 1.9 years of life saved (YoLS) and 1.5 quality-adjusted life year (QALYs) per person, and an incremental cost of QAR 56,869 (USD 15,619), which equated to an incremental cost-effectiveness ratio of QAR 30,675 (USD 8,425) per YoLS and QAR 39,245 (USD 10,779) per QALY. Sensitivity analyses showed the findings to be robust. First-line empagliflozin combined with metformin appears to be a cost-effective therapeutic option for patients with T2DM and CVD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia., Methods and Results: A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion., Conclusion: Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

People with epilepsy have variable and dynamic trajectories in response to antiseizure medications. Accurately modelling long-term treatment response will aid prognostication at the individual level and health resource planning at the societal level. Unfortunately, a robust model is lacking. We aimed to develop a Markov model to predict the probability of future seizure-freedom based on current seizure state and number of antiseizure medication regimens trialled. We included 1795 people with newly diagnosed epilepsy who attended a specialist clinic in Glasgow, Scotland, between July 1982 and October 2012. They were followed up until October 2014 or death. We developed a simple Markov model, based on current seizure state only, and a more detailed model, based on both current seizure state and number of antiseizure medication regimens trialled. Sensitivity analyses were performed for the regimen-based states model to examine the effect of regimen changes due to adverse effects. The model was externally validated in a separate cohort of 455 newly diagnosis epilepsy patients seen in Perth, Australia, between May 1999 and May 2016. Our models suggested that once seizure-freedom was achieved, it was likely to persist, regardless of the number of antiseizure medications trialled to reach that point. The likelihood of achieving long-term seizure-freedom was highest with the first antiseizure medication regimen, at approximately 50%. The chance of achieving seizure-freedom fell with subsequent regimens. Fluctuations between seizure-free and not seizure-free states were highest earlier on but decreased with chronicity of epilepsy. Seizure-freedom/recurrence risk tables were constructed with these probability data, similar to cardiovascular risk tables. Sensitivity analyses showed that the general trends and conclusions from the base model were maintained despite perturbing the model and input data with regimen changes due to adverse effects. Quantitative comparison with the external validation cohort showed excellent consistency at Year 1, good at Year 3 and moderate at Year 5. Quantitative models, as used in this study, can provide pertinent clinical insights that are not apparent from simple statistical analysis alone. Attaining seizure freedom at any time in a patient's epilepsy journey will confer durable benefit. Seizure-freedom risk tables may be used to individualize the prediction of future seizure control trajectory., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

HIV-related stigma and discrimination have been a significant barrier to accessing health care, hence contributing to poor health outcomes. This study aimed to investigate factors associated with HIV-related stigma and discrimination and health-related quality of life (HRQoL) among people living with HIV in rural Thailand setting. A cross-sectional convenience sample of 161 HIV-positive Thai patients was recruited from a single rural district hospital using a self-administered questionnaire entailing sociodemographic information, the 12-item stigma scale, the Medical Outcomes Study HIV Health Survey (MOS-HIV), and the EuroQoL 5-Dimension 5-Level (EQ-5D-5L). Linear regression and the multi-variable analyses were used to investigate factors associated with stigma and HRQoL, whereas the correlations between stigma and quality of life variables were tested by Pearson correlations. Being married and duration of antiretroviral therapy were negatively correlated with HIV stigma, while increased age was inversely associated with HRQoL. Being employed and having sufficient money for living contributed positively to predict HRQoL. HIV stigma was negatively associated with mental health summary (MHS) and visual analog scale (VAS) score, whereas duration diagnosed with HIV and the use of two nucleoside reverse transcriptase inhibitors in combination with protease inhibitor regimen were negative factors associated with VAS and health utility, respectively. The findings confirm complex and inseparable associations of factors relating to HIV-related stigma and HRQoL. The development of effective interventions tailored at individual level is warranted to address this gap.

Background: There is limited evidence about lifetime burden of child malnutrition. This study aimed to estimate the lifetime impact of being underweight or overweight/obese during childhood in Vietnam., Methods: We developed a life table model in combination with a Markov model for Vietnamese children aged 5-19 years and simulated until they reached 75 years of age or died using published data. The starting year was 2019 and the model estimated number of deaths, years of life lived and quality-adjusted life years (QALY) with an annual discount rate of 3%. We performed scenario, one-way, and probabilistic sensitivity analyses to assess the impact of uncertainties in input parameters., Results: The model estimated 9.68 million deaths (6.44 million men and 3.24 million women), 622 million years of life lived (317 million men and 305 million women), and 601 million QALYs (308 million men and 293 million women). Scenario analyses showed that the reduction in either underweight or overweight/obesity alone, and reduction in both underweight and overweight/obesity resulted in fewer deaths, more years of life lived and more QALYs gained. In the scenario where everyone was a healthy weight, the model estimated 577,267 fewer deaths (6.0% less), 2 million more years of life lived (0.3% more), and 3 million QALYs gained (0.6% more) over base-case results which represents current situation in Vietnam., Conclusions: Our results suggest that addressing underweight and overweight/obesity will contribute to reducing deaths and increasing years of life lived and QALYs. Policies and interventions in alignment with Sustainable Development Goals to address underweight and overweight/obesity are necessary to achieve health for all., (© 2022. The Author(s).)

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., (© 2022 International League Against Epilepsy.)

Background: Socioeconomic status has an important effect on cardiovascular disease (CVD). Data on the economic implications of CVD by socioeconomic status are needed to inform healthcare planning., Objectives: The aim of this study was to project new-onset CVD and related health economic outcomes in Australia by socioeconomic status from 2021 to 2030., Methods: A dynamic population model was built to project annual new-onset CVD by socioeconomic quintile in Australians aged 40-79 years from 2021 to 2030. Cardiovascular risk was estimated using the Pooled Cohort Equation (PCE) from Australian-specific data, stratified for each socioeconomic quintile. The model projected years of life lived, quality- adjusted life-years (QALYs), acute healthcare medical costs, and productivity losses due to new-onset CVD. All outcomes were discounted by 5% annually., Results: PCE estimates showed that 8.4% of people in the most disadvantaged quintile were at high risk of CVD, compared with 3.7% in the least disadvantaged quintile (p < 0.001). From 2021 to 2030, the model projected 32% more cardiovascular events in the most disadvantaged quintile compared with the least disadvantaged (127,070 in SE 1 vs. 96,222 in SE 5). Acute healthcare costs in the most disadvantaged quintile were Australian dollars (AU$) 183 million higher than the least disadvantaged, and the difference in productivity costs was AU$959 million. Removing the equity gap (by applying the cardiovascular risk from the least disadvantaged quintile to the whole population) would prevent 114,822 cardiovascular events and save AU$704 million of healthcare costs and AU$3844 million of lost earnings over the next 10 years., Conclusion: Our results highlight the pressing need to implement primary prevention interventions to reduce cardiovascular health inequity. This model provides a platform to incorporate socioeconomic status into health economic models by estimating which interventions are likely to yield more benefits in each socioeconomic quintile., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: Lifestyle interventions during pregnancy improve maternal and infant outcomes. We aimed to compare the cost-effectiveness of 4 antenatal lifestyle intervention types with standard care., Methods: A decision tree model was constructed to compare lifestyle intervention effects from a novel meta-analysis. The target population was women with singleton pregnancies and births at more than 20 weeks' gestation. Interventions were categorized as diet, diet with physical activity, physical activity, and mixed (lacking structured diet and, or, physical activity components). The outcome of interest was cost per case prevented (gestational diabetes, hypertensive disorders in pregnancy, cesarean birth) expressed as an incremental cost-effectiveness ratio (ICER) from the Australian public healthcare perspective. Scenario analyses were included for all structured interventions combined and by adding neonatal intensive care unit costs. Costs were estimated from published data and consultations with experts and updated to 2019 values. Discounting was not applied owing to the short time horizon., Results: Physical activity interventions reduced adverse maternal events by 4.2% in the intervention group compared with standard care and could be cost saving. Diet and diet with physical activity interventions reduced events by 3.5% (ICER = A$4882) and 2.9% (ICER = A$2020), respectively. Mixed interventions did not reduce events and were dominated by standard care. In scenario analysis, all structured interventions combined and all interventions when including neonatal intensive care unit costs (except mixed) may be cost saving. Probabilistic sensitivity analysis showed that for physical activity and all structured interventions combined, the probability of being cost saving was 58% and 41%, respectively., Conclusions: Governments can expect a good return on investment and cost savings when implementing effective lifestyle interventions population-wide., (Copyright © 2021 ISPOR–The International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Economic evaluation is crucial for cost-effective resource allocation to improve child nutrition in low and middle-income countries (LMICs). However, the quality of published economic evaluations in these settings is not well understood. This systematic review aimed to assess the quality of existing economic evaluations of child nutrition interventions in LMICs and synthesize the study characteristics and economic evidence. We searched 9 electronic databases, including MEDLINE, with the following concepts: economic evaluation, children, nutrition, and LMICs. All types of interventions addressing malnutrition, including stunting, wasting, micronutrient deficiency, and overweight, were identified. We included economic evaluations that examined both costs and effects published in English peer-reviewed journals and used the Drummond checklist for quality appraisal. We present findings through a narrative synthesis. Sixty-nine studies with diverse settings, perspectives, time horizons, and outcome measures were included. Most studies used data from sub-Saharan Africa and South Asia and addressed undernutrition. The mortality rate, intervention effect, intervention coverage, cost, and discount rate were reported as predictors among studies that performed sensitivity analyses. Despite the heterogeneity of included studies and the possibility of publication bias, 81% of included studies concluded that nutrition interventions were cost-effective or cost-beneficial, mostly based on a country's cost-effectiveness thresholds. Regarding quality assessment, the studies published after 2016 met more criteria than studies published before 2016. Most studies had well-stated research questions, forms of economic evaluation, interventions, and conclusions. However, reporting the perspective of the analyses, justification of discount rates, and describing the role of funders and ethics approval were identified as areas needing improvement. The gaps in the quality of reporting could be improved by consolidated guidance on the publication of economic evaluations and the use of appropriate quality appraisal checklists. Strengthening the evidence base for child malnutrition across different regions is necessary to inform cost-effective investment in LMICs. Trial registration: PROSPERO CRD42020194445., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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.

Objective: Sodium-glucose cotransporter 2 inhibitors have been shown to reduce cardiovascular events but are currently not used as the first-line therapy. This study was conducted to evaluate the cost-effectiveness of first-line empagliflozin plus metformin versus metformin monotherapy among Australians with type 2 diabetes mellitus (T2DM) and existing cardiovascular disease (CVD)., Methods: A Markov model with 1-year cycles and a 5-year time horizon was constructed to simulate the occurrence of recurrent cardiovascular events among Australians aged 50 to 84 years with T2DM and CVD. Efficacy results were derived from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose trial. Costs and utilities were drawn from published sources. The evaluation adopted both health care and societal perspectives, with the latter ascribing the Australian government's "value of statistical life year" (A$213 000) to each year lived by a person. Future outcomes were discounted at 5% annually. Sensitivity analyses were conducted to enhance the robustness of conclusions., Results: Compared with metformin monotherapy, first-line empagliflozin plus metformin reduced overall cardiovascular events by 0.82% and overall deaths by 7.72% over 5 years. There were 0.2 years of life saved per person and 0.16 quality-adjusted life years gained, at a net health care cost of A$4408. These equated to incremental cost-effectiveness ratios of A$22 076 per year of life saved and A$28 244 per quality-adjusted life year gained. The gains in the value of statistical life year equated to A$42 530 per person, meaning that from a societal perspective, the intervention was cost-saving., Conclusion: First-line empagliflozin plus metformin may represent a cost-effective strategy for the management of T2DM and CVD in Australia., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: Diabetes increases the risk of premature mortality and considerably impacts on work productivity. We sought to examine the impact of diabetes in India, in terms of excess premature mortality, years of life lost (YLL), productivity-adjusted life years (PALYs) lost, and its associated economic impact., Research Design and Methods: A life table model was constructed to examine the productivity of the Indian working-age population currently aged 20-59 years with diabetes, followed until death or retirement age (60 years). The same cohort was resimulated, hypothetically assuming that they did not have diabetes. The total difference between the two cohorts, in terms of excess deaths, YLL and PALYs lost reflected the impact of diabetes. Data regarding the prevalence of diabetes, mortality, labor force dropouts, and productivity loss attributable to diabetes were derived from published sources., Results: In 2017, an estimated 54.4 million (7.6%) people of working-age in India had diabetes. With simulated follow-up until death or retirement age, diabetes was predicted to cause 8.5 million excess deaths (62.7% of all deaths), 42.7 million YLL (7.4% of total estimated years of life lived), and 89.0 million PALYs lost (23.3% of total estimated PALYs), equating to an estimated Indian rupee 176.6 trillion (U.S. dollars 2.6 trillion; purchasing power parity 9.8 trillion) in lost gross domestic product., Conclusions: Our study demonstrates the impact of diabetes on productivity loss and highlights the importance of health strategies aimed at the prevention of diabetes., (© 2021 by the American Diabetes Association.)

Objective: To review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality., Design: Systematic review and meta-analysis., Data Sources: Medline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints)., Eligibility Criteria for Study Selection: Observational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality., Main Outcome Measures: The main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality., Data Synthesis: DerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran's Q test and the I 2 metrics, with two tailed P values., Results: 72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a "package of interventions." Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I 2 =12%), mask wearing (0.47, 0.29 to 0.75, I 2 =84%), and physical distancing (0.75, 0.59 to 0.95, I 2 =87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively., Conclusions: This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination., Systematic Review Registration: PROSPERO CRD42020178692., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/and declare: ET is supported by a Cancer Research UK Career Development Fellowship and XZ is supported by The Darwin Trust of Edinburgh; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Acute myeloid leukemia (AML) is a rare hematologic malignancy accounting for 0.8% of new cancer diagnoses in Australia. High mortality and morbidity affect work productivity through workforce dropout and premature death. This study sought to estimate the productivity loss attributable to AML in the Australian population over 10 years and to estimate the costs of this productivity loss. Productivity was measured using productivity-adjusted life years (PALYs), a similar concept to quality-adjusted life years, but adjusts for the productivity loss attributable to disease, rather than impaired health., Materials and Methods: Dynamic life tables modeled the Australian working population (age 15-65 years) between 2020 and 2029. The model population had two cohorts: those with and without AML. Differences in life years, PALYs, and costs represented the health and productivity impact of AML. Secondary analyses evaluated the impact of different scenarios., Results: Over the next 10 years, there will be 7,600 years of life lost and 7,337 PALYs lost because of AML, amounting to Australian dollars (AU$) 1.43 billion in lost gross domestic product ($971 million in US dollars). Secondary analyses highlight potential savings of approximately AU$52 million if survival rates were improved by 20% and almost AU$118 million in savings if the return-to-work rates increased by 20% on the current estimates., Conclusion: Our study demonstrates that even in low-incidence cancer, high mortality and morbidity translate to profound impacts on years of life, productivity, and the broader economy. Better treatment strategies are likely to result in significant economic gains. This highlights the value of investing in research for improved therapies., Competing Interests: Danny LiewConsulting or Advisory Role: Novartis, Pfizer, AstraZeneca, CSL BehringResearch Funding: AmgenTravel, Accommodations, Expenses: Novartis Andrew WeiHonoraria: Amgen, Servier, Novartis, Celgene, Abbvie/Genentech, Pfizer, Janssen Oncology, Astellas Pharma, Macrogenics, AstraZenecaConsulting or Advisory Role: Servier, Novartis, Amgen, Abbvie/Genentech, Celgene, Macrogenics, Pfizer, Astellas Pharma, AstraZeneca, JanssenSpeakers' Bureau: Abbvie/Genentech, Novartis, Celgene/Bristol Myers SquibbResearch Funding: Novartis, Celgene, Abbvie, AstraZeneca, Servier, Amgen, RochePatents, Royalties, Other Intellectual Property: A.W. is a former employee of the Walter and Eliza Hall Institute which receives milestone and royalty payments related to venetoclax, and is eligible for benefits related to these payments. A.W. receives payments from WEHI related to venetoclax Ella ZomerConsulting or Advisory Role: Amgen, AstraZeneca, Pfizer, ShireNo other potential conflicts of interest were reported.

Home-visiting interventions are used to improve outcomes for families experiencing disadvantage. As scarce resources must be allocated carefully, appropriate methods are required to provide accurate information on the effect of these programmes. We aimed to investigate: economic evaluation/analysis methods used in home-visiting programmes for children, young people and families, study designs and methods suitable in situations where randomised-controlled-trials are not feasible, and type of costs included in analyses, including any implementation costs stated. A systematic search and review was conducted of existing full economic evaluation/analysis methods in home-visiting programmes for children, young people and/or families. We included studies published in English between January 2000 and mid-November 2020. Of the 4,742 papers sourced, 60 were retained for full-text review, and 21 included. Economic-analysis methods found in the included studies were: within trial economic evaluation, economic evaluation using decision analytic modelling (i.e. cost-utility, cost-benefit analysis), cost comparison and cost-consequence. Studies incorporating return on investment and budget impact analysis were also found. Study designs suitable when randomisation was not feasible included parallel cluster randomised trials and using pre-post intervention data. Costs depended mainly on study context and only one study reported implementation costs. We hope this information will help guide future economic evaluations of home-visiting interventions., (© 2021 John Wiley & Sons Ltd.)

Objectives: Major depression in South Korea, which remains under-diagnosed and under-treated, increases the risk of premature death, and reduces quality of life and work productivity. The aim of this study was to quantify the depression-related health and productivity loss in South Korea in terms of life-years lost and productivity-adjusted life-years (PALYs) lost., Method: Age and sex-specific life table models simulated follow-up of South Koreans with depression aged 15 to 54 years, until 55 years. Depression was defined as major depression. Inputs were drawn from national datasets and published sources. Models were constructed for the cohort with depression and repeated assuming they had no depression. Differences in total deaths, years of life, and PALYs represented the impact of depression. PALYs were ascribed a financial value equivalent to total gross domestic product (GDP) divided by the number of equivalent full-time workers (KRW81,507,146 or USD74,748). All outcomes were discounted by 3% per annum., Results: In 2019, there were more than 500,000 people aged 15-54 years with major depression in South Korea. We predicted that until this cohort reached age 55 years, and assuming 22.2% of people with depression are treated, depression led to 12,000 excess deaths, more than 55,000 discounted years of life lost and 1.6 million discounted PALYs lost, equating to KRW133 trillion (USD122 billion) in lost GDP. Applying treatment-related response and remission rates of 11.8% and 42.1%, respectively, and a non-response/non-remission rate of 46.1%, increased the total number of PALYs lost by almost 6.0%., Conclusions: Our study highlights the considerable productivity loss attributable to depression among South Koreans over their working lifetime. Better prevention and treatment of depression is needed for long-term economic gains., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In the present study, we aimed to estimate the impact of hypertension in the working-age Japanese population. We developed life table models to estimate total deaths, years of life lived, and productivity-adjusted life years lived (a newly developed metric for quantifying the burden of acute and chronic health conditions on work productivity) among Japanese individuals with hypertension aged 20-64 years, with simulated follow-up until age 65 years. Data inputs were drawn from local population statistics and published sources. Gross domestic product per person employed, a measure of labor productivity, was used to assign an economic value to each productivity-adjusted life year lived. Outcomes and costs were discounted by 2% annually. In 2017, 26.3 million Japanese individuals aged 20-64 years (37.5%) had hypertension. Of these people, 23.7% were treated and had controlled blood pressure, 23.2% were treated but had uncontrolled blood pressure, and 53.1% were untreated. During the simulated follow-up until age 65 years, 335,342 deaths (28.0% of total deaths), 1.6 million years of life (0.8% of total), 3.1 million productivity-adjusted life years (1.9% of total), and US$242.9 billion or 28.3 trillion Japanese yen of gross domestic product were lost to hypertension. Our findings highlight the considerable economic burden of hypertension in Japan, as well as the importance of effective strategies for hypertension prevention and management, which are likely to deliver a significant return on investment., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: The Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilised from an Acute Heart Failure Episode (PIONEER-HF) trial demonstrated significant reductions in N-terminal pro-B-type natriuretic peptide. Our study explored the cost-effectiveness of the use of sacubitril-valsartan versus enalapril in acute decompensated heart failure from the Australian healthcare perspective., Methods: A Markov model was designed using data from the PIONEER-HF trial to model the clinical progress and costs of patients over a lifetime time horizon. The model consisted of three health states: 'alive and event-free', 'alive after non-fatal hospitalisation for acute decompensated heart failure' or 'dead'. Costs and utilities were estimated from published sources. The cost of sacubitril-valsartan (per the Australian pharmaceutical benefits schedule) was AU$7.08/day. Outcomes of interest were the incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year gained and cost per year of life saved. Cost and benefits were discounted at 5.0% per annum., Results: Compared to enalapril, sacubitril-valsartan was estimated to cost an additional AU$7464 (discounted) per person, but lead to 0.127 years of life saved (discounted) and 0.096 quality-adjusted life years gained (discounted) over a lifetime analysis. These equated to incremental cost-effectiveness ratios of AU$58,629/year of life saved (US$41,795, EU€58,629, GBP£32,001) and AU$77,889/quality-adjusted life year gained (US$55,526, EU€49,202, GBP£42,504). We have assumed a threshold of AU$50,000/quality-adjusted life year gained to suggest cost-effectiveness., Conclusions: At its current acquisition price, sacubitril-valsartan in comparison to enalapril is not likely to be cost-effective in the management of acute decompensated heart failure in Australia. A price reduction of more than 25% would confer cost-effectiveness., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aim: To assess the cost-effectiveness of dapagliflozin in addition to standard care versus standard care alone in patients with chronic heart failure and reduced ejection fraction., Methods: A Markov model was constructed based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial to assess the clinical outcomes and costs of 1000 hypothetical subjects with established heart failure and reduced ejection fraction. The model consisted of three health states: 'alive and event-free', 'alive after non-fatal hospitalisation for heart failure' and 'dead'. Costs and utilities were estimated from published sources. The main outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. An Australian public healthcare perspective was employed. All outcomes and costs were discounted at a rate of 5% annually., Results: Over a lifetime horizon, the addition of dapagliflozin to standard care in patients with heart failure and reduced ejection fraction prevented 88 acute heart failure hospitalisations (including readmissions) and yielded an additional 416 years of life and 288 quality-adjusted life-years (discounted) at an additional cost of A$3,692,440 (discounted). This equated to an incremental cost-effectiveness ratio of A$12,482 per quality-adjusted life-year gained, well below the Australian willingness-to-pay threshold of A$50,000 per quality-adjusted life-year gained. Subanalyses in subjects with and without diabetes resulted in similar incremental cost-effectiveness ratios of A$13,234 and A$12,386 per quality-adjusted life-year gained, respectively., Conclusion: Dapagliflozin is likely to be cost-effective when used as an adjunct therapy to standard care compared with standard care alone for the treatment of chronic heart failure and reduced ejection fraction., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: The Quality in Acute Stroke Care (QASC) protocol is a multidisciplinary approach to implement evidence-based treatment after acute stroke that reduces death and disability. This study sought to evaluate the cost-effectiveness of implementing the QASC protocol across Australia, from a healthcare and a societal perspective., Materials and Methods: A decision-analytic model was constructed to reflect one-year outcomes post-stroke, aligned with the stroke severity categories of the modified Rankin scale (mRS). Decision analysis compared outcomes following implementation of the QASC protocol versus no implementation. Population data were extracted from Australian databases and data inputs regarding stroke incidence, costs, and utilities were drawn from published sources. The analysis assumed a progressive uptake and efficacy of the QASC protocol over five years. Health benefits and costs were discounted by 5% annually. The cost of each year lived by an Australian, from a societal perspective, was based on the Australian Government's 'value of statistical life year' (AUD 213,000)., Results: Over five years, the model predicted 263,722 strokes among the Australian population. The implementation of the QASC protocol was predicted to prevent 1,154 deaths and yield a gain of 876 years of life (0.003 per stroke), and 3,180 quality-adjusted life years (QALYs) (0.012 per stroke). There was an estimated net saving of AUD 65.2 million in healthcare costs (AUD 247 per stroke) and AUD 251.7 million in societal costs (AUD 955 per stroke)., Conclusions: Implementation of the QASC protocol in Australia represents both a dominant (cost-saving) strategy, from a healthcare and a societal perspective., Competing Interests: Conflict of Competing Interest CM, ZA, RO and RT declare no conflict of interest. EZ declares grants from Amgen, AstraZeneca, Pfizer and Shire; outside the submitted work. DL declares grant support from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Pfizer and Sanofi and past participation in advisory boards and/or receipt of honoraria from Abbvie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Edwards Lifesciences, Novartis, Pfizer, Sanofi and Shire, outside the submitted work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to estimate the cost-effectiveness, from the perspective of the Australian public healthcare system, of icosapent ethyl in combination with statin therapy compared with statin alone for the prevention of cardiovascular disease., Methods and Results: A Markov model populated with data from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial was designed to predict the effectiveness and costs of icosapent ethyl in combination with statins compared with statins alone over a 20-year time horizon. Data inputs for costs and utilities were sourced from published sources. The annual costs of icosapent ethyl were assumed to be AUD1637 (USD2907) per person. All future costs and outcomes were discounted annually by 5%. The main outcome of interest was incremental cost-effectiveness ratios in terms of cost per quality adjusted life year (QALY) gained and per year of life saved (YoLS). Over a 20-year time horizon, compared with statin alone, icosapent ethyl in combination with statin was estimated to cost an additional AUD$13,022 per person, but led to 0.338 YoLS and 0.289 QALYs gained (all discounted). These equated to incremental cost-effectiveness ratios of AUD45,036 per QALY gained and AUD38,480 per YoLS. Sub-analyses for primary and secondary prevention were AUD96,136 and AUD35,935 per QALY gained, respectively. The results were sensitive to time-horizon, age related trends and the acquisition price of icosapent ethyl., Conclusion: Compared with statin alone, icosapent ethyl in combination with statin therapy is likely to be cost-effective in the prevention of cardiovascular disease assuming a willingness-to-pay threshold of AUD50,000 per QALY gained, especially in the secondary preventive setting., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The global health burden of chronic kidney disease is rapidly rising, and chronic kidney disease is an important risk factor for cerebrovascular disease. Proposed underlying mechanisms for this relationship include shared traditional risk factors such as hypertension and diabetes, uremia-related nontraditional risk factors, such as oxidative stress and abnormal calcium-phosphorus metabolism, and dialysis-specific factors such as cerebral hypoperfusion and changes in cardiac structure. Chronic kidney disease frequently complicates routine stroke risk prediction, diagnosis, management, and prevention. It is also associated with worse stroke severity, outcomes and a high burden of silent cerebrovascular disease, and vascular cognitive impairment. Here, we present a summary of the epidemiology, pathophysiology, diagnosis, and treatment of cerebrovascular disease in chronic kidney disease from the Kidney Disease: Improving Global Outcomes Controversies Conference on central and peripheral arterial disease with a focus on knowledge gaps, areas of controversy, and priorities for research.

Aims: To determine the impact of preventing new (incident) cases of coronary heart disease (CHD) on years of life and productivity, using the novel measure 'productivity-adjusted life year' (PALY), over the next 10 years., Methods and Results: A dynamic life table model was constructed for the total Australian working-age population (15-69 years) over 10 years (2020-2029), separated by CHD status. Productivity estimates were sourced from the literature. The PALY was ascribed a financial value in terms of gross domestic product (GDP) per equivalent full-time worker. The total number of years lived, PALYs, and economic burden (in terms of GDP per PALY) were estimated. The model simulation was repeated assuming incidence was reduced, and the differences represented the impact of CHD prevention. All outcomes were discounted by 5% per annum. Over 10 years, the total projected years lived and PALYs in the Australian working-age population (with and without CHD) were 133 million and 83 million, respectively, amounting to A$17.2 trillion in GDP. We predicted more than 290 000 new (incident) CHD cases over the next 10 years. If all new cases of CHD could be prevented during this period, a total of 4 000 deaths could be averted, resulting in more than 8 000 years of life saved and 104 000 PALYs gained, equivalent to a gain of nearly A$21.8 billion (US$14.8 billion) in GDP., Conclusion: Prevention of CHD will prolong years of life lived and productive life years, resulting in substantial economic benefit. Policy makers and employers are encouraged to engage in preventive measures addressing CHD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Kidney disease is associated with impaired work productivity. However, the collective effect of missed work days, reduced output at work, and early withdrawal from the workforce is rarely considered in health-economic evaluations., Methods: To determine the effect on work productivity of preventing incident cases of kidney disease, using the novel measure "productivity-adjusted life year" (PALY), we constructed a dynamic life table model for the Australian working-age population (aged 15-69 years) over 10 years (2020-2029), stratified by kidney-disease status. Input data, including productivity estimates, were sourced from the literature. We ascribed a financial value to the PALY metric in terms of gross domestic product (GDP) per equivalent full-time worker and assessed the total number of years lived, total PALYs, and broader economic costs (GDP per PALY). We repeated the model simulation, assuming a reduced kidney-disease incidence; the differences reflected the effects of preventing new kidney-disease cases. Outcomes were discounted by 5% annually., Results: Our projections indicate that, from 2020 to 2029, the estimated number of new kidney-disease cases will exceed 161,000. Preventing 10% of new cases of kidney disease during this period would result in >300 premature deaths averted and approximately 550 years of life and 7600 PALYs saved-equivalent to a savings of US$1.1 billion in GDP or US$67,000 per new case avoided., Conclusions: Pursuing a relatively modest target for preventing kidney disease in Australia may prolong years of life lived and increase productive life years, resulting in substantial economic benefit. Our findings highlight the need for investment in preventive measures to reduce future cases of kidney disease., (Copyright © 2021 by the American Society of Nephrology.)

Objective: Diabetes imposes a heavy burden on both health and productivity. In this study, we sought to estimate the potential productivity gains associated with the prevention of type 2 diabetes over the next 10 years in Australia., Research Design and Methods: Dynamic life table models were constructed to estimate years of life lived and productivity-adjusted life-years (PALYs) lived by Australians aged 20-69 years over the period from 2020 to 2029. The models distinguished people with and without type 2 diabetes. PALYs were ascribed a financial value equivalent to gross domestic product (GDP) per full-time worker in Australia (∼200,000 Australian dollars [AUD]). The model simulation was first undertaken assuming currently expected trends in the incidence of type 2 diabetes and then repeated assuming hypothetically that the incidence was reduced. The difference between the modeled outputs reflected the impact of new cases of type 2 diabetes on productivity as well as the potential benefits of prevention. An annual 5% discount rate was applied to all outcomes., Results: Over the next decade, 140 million years of life and 87 million PALYs will be lived by Australians of working age, contributing AUD 18.0 trillion to the country's GDP. A 10% reduction in the incidence of type 2 diabetes would result in a gain of 2,510 PALYs and AUD 532 million in GDP., Conclusions: This study illustrates the health and economic impact of type 2 diabetes and the gains that could be potentially achieved from the implementation of effective prevention strategies. However, cost-effectiveness evaluations of these prevention strategies are needed., (© 2021 by the American Diabetes Association.)

Background: Streptoccocus suis (S.suis) infection is a neglected zoonosis disease in humans mainly affects men of working age. We estimated the health and economic burden of S.suis infection in Thailand in terms of years of life lost, quality-adjusted life years (QALYs) lost, and productivity-adjusted life years (PALYs) lost which is a novel measure that adjusts years of life lived for productivity loss attributable to disease., Methods: A decision-analytic Markov model was developed to simulate the impact of S. suis infection and its major complications: death, meningitis and infective endocarditis among Thai people in 2019 with starting age of 51 years. Transition probabilities, and inputs pertaining to costs, utilities and productivity impairment associated with long-term complications were derived from published sources. A lifetime time horizon with follow-up until death or age 100 years was adopted. The simulation was repeated assuming that the cohort had not been infected with S.suis. The differences between the two set of model outputs in years of life, QALYs, and PALYs lived reflected the impact of S.suis infection. An annual discount rate of 3% was applied to both costs and outcomes. One-way sensitivity analyses and Monte Carlo simulation modeling technique using 10,000 iterations were performed to assess the impact of uncertainty in the model., Key Results: This cohort incurred 769 (95% uncertainty interval [UI]: 695 to 841) years of life lost (14% of predicted years of life lived if infection had not occurred), 826 (95% UI: 588 to 1,098) QALYs lost (21%) and 793 (95%UI: 717 to 867) PALYs (15%) lost. These equated to an average of 2.46 years of life, 2.64 QALYs and 2.54 PALYs lost per person. The loss in PALYs was associated with a loss of 346 (95% UI: 240 to 461) million Thai baht (US$11.3 million) in GDP, which equated to 1.1 million Thai baht (US$ 36,033) lost per person., Conclusions: S.suis infection imposes a significant economic burden both in terms of health and productivity. Further research to investigate the effectiveness of public health awareness programs and disease control interventions should be mandated to provide a clearer picture for decision making in public health strategies and resource allocations., Competing Interests: The authors have declared that no competing interests exist.

Currently there is no secured ongoing funding in Australia for next generation sequencing (NGS) such as exome sequencing (ES) for adult neurological disorders. Studies have focused on paediatric populations in research or highly specialised settings, utilised standard NGS pipelines focusing only on small insertions, deletions and single nucleotide variants, and not explored impacts on management in detail. This prospective multi-site study performed ES and an extended bioinformatics repeat expansion analysis pipeline, on patients with broad phenotypes (ataxia, dementia, dystonia, spastic paraparesis, motor neuron disease, Parkinson's disease and complex/not-otherwise-specified), with symptom onset between 2 and 60 years. Genomic data analysis was phenotype-driven, using virtual gene panels, reported according to American College of Medical Genetics and Genomics guidelines. One-hundred-and-sixty patients (51% female) were included, median age 52 years (range 14-79) and median 9 years of symptoms. 34/160 (21%) patients received a genetic diagnosis. Highest diagnostic rates were in spastic paraparesis (10/25, 40%), complex/not-otherwise-specified (10/38, 26%) and ataxia (7/28, 25%) groups. Findings were considered 'possible/uncertain' in 21/160 patients. Repeat expansion detection identified an unexpected diagnosis of Huntington disease in an ataxic patient with negative ES. Impacts on management, such as more precise and tailored care, were seen in most diagnosed patients (23/34, 68%). ES and a novel bioinformatics analysis pipepline had a substantial diagnostic yield (21%) and management impacts for most diagnosed patients, in heterogeneous, complex, mainly adult-onset neurological disorders in real-world settings in Australia, providing evidence for NGS and complementary multiple, new technologies as valuable diagnostic tools., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Despite increasing prescription of sodium glucose co-transporter 2 (SGLT2) inhibitors, there is limited insight of the patterns of use among patients with diabetes prescribed these drugs. This study aimed to summarize available real-world data on the adherence and persistence to SGLT2 inhibitors., Materials and Methods: A systematic review for observational studies reporting the adherence and persistence to SGLT2 inhibitors was performed in Medline, Embase, and Web of Science from their inception to October 2019. Data were analysed via random-effects meta-analysis., Results: A total of 22 studies (31 cohorts) comprising 123 854 individuals prescribed SGLT2 inhibitors from eight countries were included. The pooled mean proportions of days covered [PDC] at six months and one year were 0.77 (95% confidence interval [CI] 0.72-0.82) and 0.72 (95% CI 0.66-0.77), respectively. The pooled proportions adherent (PDC ≥0.80) at six months and one year were 59.5% (95% CI 52.9-65.9) and 49.0% (95% CI 42.3-55.8), respectively. The pooled proportions of people persistent at six months, one year, and two years were 80.1% (95% CI 75.8-84.0), 61.8% (95% CI 57.8-65.7), and 45.9% (95% CI 35.5-56.5), respectively. When persistence was defined as the absence of ≥90-days gap, the equivalent pooled proportions persistent were 81.5% (95% CI 73.1-88.6), 58.9% (95% CI 53.1-64.6), and 34.7% (95% CI 33.6-35.8). Adherence and persistence appeared to vary across different SGLT2 inhibitors., Conclusions: Real-world adherence and persistence to SGLT2 inhibitors is poor. Hence, targets for improving treatment adherence and persistence need to be identified and appropriate interventions implemented., (© 2020 John Wiley & Sons Ltd.)

Aims: Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors., Methods: MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019. This was supplemented by manual screening of the references of included papers. Random-effects meta-analysis was performed., Results: Thirty-four cohort studies involving 594,138 patients with T2DM prescribed DPP4 inhibitors from ten countries were included. The pooled proportion adherent (proportion of days covered (PDC) or medication possession ratio (MPR) ≥ 0.80) was 56.9% (95% confidence interval [CI] 49.3-64.4) at one year and 44.2% (95% CI 36.4-52.1) at two years. The proportion persistent with treatment decreased from 75.6% (95% CI 71.5-79.5) at six months to 52.8% (95% CI 51.6-59.8) at two years. No significant differences in adherence and persistence were observed between individual DPP4 inhibitors. At one year, just 3.2% (95% CI 3.1-3.3) of patients switched from one DPP4 inhibitor to another. Switching from saxagliptin and alogliptin to others was commonest., Conclusions: Adherence to and persistence with DPP4 inhibitors is suboptimal but similar across all medications within the class. While in-class switching is uncommon, saxagliptin and alogliptin are the DPP4 inhibitors most commonly switched. Interventions to improve treatment adherence and persistence among patients with T2DM prescribed DPP4 inhibitors may be warranted.

Objective: To determine the health economic burden of epilepsy for Australians of working age by using life table modeling and to model whether improved seizure control may result in substantial health economic benefits., Methods: Life table modeling was used for working age Australians aged 15-69 years with epilepsy and the cohort was followed until age 70 years. Published 2017 population and epilepsy-related data regarding epilepsy prevalence, mortality, and productivity were used. This model was then re-simulated, assuming the cohort no longer had epilepsy. Differences in outcomes between these cohorts were attributed to epilepsy. Scenarios were also simulated in which the proportion of seizure-free patients increased from baseline 70% up to 75% and 80%., Results: In 2017, Australians of working age with epilepsy followed until age 70 years were predicted to experience over 14,000 excess deaths, more than 78,000 years of life lost, and over 146,000 productivity-adjusted life years lost due to epilepsy. This resulted in lost gross domestic product (GDP) of US $22.1 billion. Increasing seizure freedom by 5% and 10% would reduce health care costs, save years of life, and translate to US $2.6 billion and US $5.3 billion GDP retained for seizure freedom rates of 75% and 80%, respectively., Conclusions: Our study highlights the considerable societal and economic burden of epilepsy. Relatively modest improvements in overall seizure control could bring substantial economic benefits., (© 2020 American Academy of Neurology.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bempedoic acid is a novel adenosine triphosphate citrate lyase inhibitor shown to reduce low density lipoprotein cholesterol when used as an adjunct lipid-lowering therapy in patients with high cardiovascular disease (CVD) risk., Objective: Our analysis aimed to determine the price at which bempedoic acid would be cost-effective from the Australian health care perspective., Methods: A Markov model was designed using data from the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Harmony trial, to model the clinical outcomes and costs of 1000 patients treated with bempedoic acid over a lifetime horizon. Relevant health states were "Alive with CVD," "Alive with recurrent CVD," and "Dead." With annual cycles, patients were at risk of a nonfatal myocardial infarction, coronary revascularization, and death from CVD or non-CVD causes. Costs and utilities were obtained from published sources. Outcomes of interest were the incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year (QALY) gained and cost per year of life saved. Outcomes were discounted at 5% per annum., Results: Among 1000 individuals, bempedoic acid in addition to statin therapy was estimated to save 122 (discounted) years of life and 103 (discounted) QALYs compared with statin therapy alone. At an acquisition cost of AU$584.40 per year (USD$397.01), bempedoic acid would be considered cost-effective within the Australian setting, with an incremental cost-effectiveness ratio of AU$49,890 per QALY gained (USD$33,893) and AU$42,433 per year of life saved (USD$28,827)., Conclusions: Bempedoic acid may be cost-effective within the Australian health care setting at an annual acquisition price less than $600., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Familial hypercholesterolemia (FH) is a common inherited cause for premature coronary artery disease that increases suffering and disability in affected people. However, the extent to which FH impacts work productivity at a population level is unclear., Objective: We aimed to quantify the burden of heterozygous FH (HeFH) in terms of productivity-adjusted life years (PALYs) lost to HeFH in Australia., Methods: A life-table model was constructed to quantify years of life and PALYs lived by Australians with HeFH (prevalence 1 in 300) and of working age (aged 20-69 years). Follow-up was simulated until age 70 years. The model was then resimulated, but assuming the cohort did not have HeFH. Increased cardiovascular mortality and reduction in productivity attributable to HeFH were sourced from published data. Differences in total years of life, quality-adjusted life years, and PALYs lived by the "HeFH cohort" and the same cohort without HeFH ("non-HeFH cohort") reflected the quality-adjusted life years and PALYs lost due to HeFH. All future costs and outcomes were discounted by 5% annually., Results: In 2017, an estimated 51,587 people of working age in Australia (0.33%) had HeFH. Over their working lifetime, we predicted that 2950 excess cardiovascular deaths occurred in the current Australian population of working age individuals with HeFH, resulting in a loss of 24,727 years of life. In terms of productivity, HeFH led to the loss of 24,954 PALYs over the working lifetime. Based on gross domestic product (GDP) per full-time equivalent worker, this equated to a total of AUD 5.23 billion in lost GDP over the working lifetime, with an average of AUD 101,366 lost per person. A relative reduction of 20% in cardiovascular deaths (as can be achieved with adequate cholesterol control) would lead to 1113 PALYs and AUD 233 million in GDP saved in the HeFH cohort., Conclusion: The impact of HeFH on work productivity is significant. Screening and prevention strategies tailored early in life are likely to exert not only a positive impact on health but also the economy., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 American Headache Society.)

Background: Hybrid closed-loop systems may offer improved HbA1c levels, more time-in-range, and less hypoglycemia than alternative treatment strategies. However, it is unclear if glycemic improvements offset this technology's higher acquisition costs. Among adults with type 1 diabetes in Australia, we sought to evaluate the cost-effectiveness of a hybrid closed-loop system in comparison with the current standard of care, comprising insulin injections and capillary glucose testing. Methods: Cost-effectiveness analysis was performed using decision analysis in combination with a Markov model to simulate disease progression in a cohort of adults with type 1 diabetes and compare the downstream health and economic consequences of hybrid closed-loop therapy versus current standard of care. Transition probabilities and utilities were sourced from published studies. Costs were considered from the perspective of the Australian health care system. A lifetime horizon was considered, with annual discount rates of 5% applied to future costs and outcomes. Uncertainty was assessed with probabilistic and deterministic sensitivity analyses. Results: Use of a hybrid closed-loop system resulted in an incremental cost-effectiveness ratio of Australian dollars (AUD) 37,767 per quality-adjusted life year (QALY) gained. This is below the traditionally cited willingness to pay a threshold of $50,000 per QALY gained in the Australian setting. Sensitivity analyses that varied baseline glycemic control, treatment effects, technology costs, age, discount rates, and time horizon indicated the results to be robust. Conclusions: For adults with type 1 diabetes, hybrid closed-loop therapy is likely to be cost-effective compared with multiple daily injections and capillary glucose testing in Australia.

Background: New pharmacological therapies for the treatment of cardiovascular disease (CVD) have emerged in recent years. The high rates of CVD and the need for long-term treatment to decrease risk factors makes cost-effectiveness crucial for their successful long-term implementation., Objective: This study assessed cost-effectiveness studies of novel pharmacological treatments (ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, omega-3 polyunsaturated fatty acids [n-3 PUFAs], and the cardiovascular polypill) compared with standard care for the secondary prevention of CVD., Methods: We searched seven databases and the reference list of selected literature reviews for eligible cost-effective analyses (CEA) published between January 2009 and January 2020 that evaluated the above novel treatments versus standard care. Two independent reviewers performed the screening and evaluation in accordance with the Consolidated Health Economic Evaluation Reporting Standards statement. Cost results were adapted to 2018 US dollars (US$) to facilitate comparisons between studies. Consideration of cost-effectiveness was based on the original study criteria., Results: Thirty-two studies were included in this review, most of them adopting a healthcare perspective. Studies evaluating ezetimibe, PCSK9 inhibitors and n-3 PUFAs assessed their addition to standard care compared with standard care alone, while studies analysing the polypill evaluated the replacement of multiple monotherapies for a fixed-dose combination. Ten studies reported on ezetimibe, fifteen evaluated PCSK9 inhibitors, five focused on n-3 PUFAs and seven on the polypill. From a healthcare perspective, ezetimibe was cost effective in 62.5% of the studies (incremental cost-effectiveness ratios [ICERs] ranged from US$27,195 to US$204,140), n-3 PUFAs in 60% (ICERs from US$57,128 to US$139,082) and the cardiovascular polypill in 100% (ICERs from dominant to US$30,731) compared with standard care. Conversely, only 10% of the studies considered PCSK9 inhibitors cost effective compared with standard care from a healthcare perspective (ICERs ranged from US$231,119 to US$1,223,831). Additionally, ezetimibe was cost effective in 50% of the studies, PCSK9 inhibitors in 33% and the polypill in 50% of the studies adopting a societal perspective. The key model-related parameters predicting cost-effectiveness included drug cost, time horizon, and the baseline risk of cardiovascular events., Conclusions: Based on current pricing and willingness-to-pay thresholds, most CEA studies considered ezetimibe, n-3 PUFAs and the polypill to be cost effective compared with standard care but not PCSK9 inhibitors for secondary prevention of CVD.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9). The comparison of inclisiran with statin versus statin alone in the ORION-10 trial demonstrated significant reductions in low-density lipoprotein cholesterol (LDL-C). Our study explored whether the use of inclisiran with statin versus statin alone for secondary prevention of cardiovascular events is cost effective from the Australian healthcare perspective, based on the price of currently available PCSK9 inhibitors., Methods: A Markov model was developed based on the ORION-10 trial to model outcomes and costs incurred by patients over a lifetime analysis. The three health states were 'alive with cardiovascular disease (CVD)', 'alive with recurrent CVD', and 'dead'. Cost and utilities were estimated from published sources. The cost of inclisiran was estimated from the annual cost of evolocumab, a PCSK9 inhibitor currently available in Australia (AU$6334, based on 2020 data). Outcomes of interest were incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life-year (QALY) and cost per year of life saved (YoLS). All costs, QALYs and YoLS were discounted at 5% per annum in line with Australian standards., Results: Among 1000 subjects followed-up over a lifetime analysis, inclisiran with statin compared with statin alone prevented 235 non-fatal myocardial infarctions (NFMIs; 151 NFMI and 84 repeat NFMI cases) and 114 coronary revascularisation cases, and increased years of life by 0.549 (discounted) and QALYs by 0.468 (discounted). At an annual price of AU$6334, the net marginal cost was AU$58,965 per person. The above values equated to ICERs of AU$107,402 per YoLS and AU$125,732 per QALY gained. Assuming a willingness-to-pay threshold of AU$50,000, inclisiran would have to be priced 60% lower than other available PCSK9 inhibitors to be considered cost effective., Conclusions: As an adjunct therapy to statin treatment in those who have persistently elevated LDL-C despite optimal statin therapy, inclisiran is effective in reducing cardiovascular events in patients with atherosclerotic CVD. Inclisiran is not cost effective from the Australian healthcare perspective, assuming acquisition costs of current PCSK9 inhibitors. The cost of inclisiran would have to be 60% lower than that of evolocumab.

Background: Lifestyle interventions (diet, physical activity and/or behavioural) to optimise gestational weight gain can prevent adverse maternal outcomes such as gestational diabetes, pre-eclampsia and caesarean section., Objective: We aimed to model the cost effectiveness of lifestyle interventions during pregnancy on reducing adverse maternal outcomes., Methods: Decision tree modelling was used to determine the cost effectiveness of lifestyle interventions compared with usual care on preventing cases of gestational diabetes and hypertensive disease in pregnancy. Participants were pregnant women receiving routine antenatal care in secondary and tertiary care hospitals. The main outcome measures were cases of gestational diabetes and/or hypertensive disease in pregnancy prevented, costs, and incremental cost-effectiveness ratios. Analysis was conducted from the perspective of the Australian healthcare system, with a time horizon of early pregnancy to discharge after birth., Results: Women in the intervention group were 2.25% less likely to have gestational diabetes and/or hypertensive disease in pregnancy (9.53%) compared with the control group (11.78%). Intervention costs were Australian dollars (AUD) 228 per person. Costs were AUD33 per person higher in the intervention group (AUD8281) than the control group (AUD8248). The incremental cost-effectiveness ratio was AUD1470 per case prevented. Sensitivity analysis showed that base-case results were robust. In the probabilistic sensitivity analysis, 44.8% of data points fell within the north-east quadrant, and 52.2% in the south-east quadrant (cost saving), with a 95% confidence interval ranging from AUD - 50,018 to 32,779 per case prevented., Conclusions: While there is no formally accepted cost-effectiveness threshold for willingness-to-pay to prevent an adverse maternal event, the cost per person receiving a lifestyle intervention compared with controls was close to neutral, and therefore likely to be cost effective. Exploration of the cost effectiveness of different lifestyle delivery modes across various models of antenatal care is now required. Future cost-effectiveness studies should investigate longer time horizons, quality-adjusted life-years and productivity loss., Trial Registration: Not applicable.

Background: Pneumococcal diseases were estimated to cause 1.6 million deaths annually worldwide in 2008, with approximately half of these occurring in children aged under 5 years. The consequences and deaths adversely impact individuals' and caregivers' work productivity., Objectives: This study aimed to quantify the potential lifetime productivity loss due to pneumococcal diseases among the pediatric population in Thailand using productivity-adjusted life years (PALYs)., Methods: A decision analytic model was used to estimate the burden of pneumococcal diseases among the current Thai population aged 0-5 years and followed up until aged 99 years or death. Base-case analysis compared years of life and PALYs lost to pneumococcal diseases. Scenario analyses investigated the benefits of prevention with pneumococcal conjugated vaccine 13 (PCV 13). All health outcomes were discounted at 3% per annum., Results: The base-case analysis estimated that 453,401 years of life and 457,598 PALYs would be lost to pneumococcal diseases, equating to a loss of US$5586 (95% CI 3338-10,302) million. Vaccination with PCV13 at birth was estimated to save 82,609 years of life and 93,759 PALYs, which equated to US$1144 (95% CI 367-2591) million in economic benefits. The incidence of pneumonia in those aged 0-4 years, vaccine efficacy, and the assumed period of protection were key determinants of the health economic outputs., Conclusions: The disease and financial burden of pneumococcal diseases in Thailand is significant, but a large proportion of this is potentially preventable with vaccination.

Background and Aims: There are no studies that have specifically investigated the cost-effectiveness of cascade screening of children for heterozygous familial hypercholesterolemia (FH) and treatment of affected individuals with statins to prevent coronary heart disease (CHD). This study explores the cost-effectiveness of this strategy from the perspective of the Australian public healthcare system., Methods: A lifetime Markov model with four health states (Alive without CHD, Alive with CHD, Dead from fatal CHD, and Dead from other causes) was developed to simulate the progression of ten-year-old children screened for FH and treated immediately with statins if found to have FH. The underlying prevalence of FH in this target population was assumed to be 56.8%, and the sensitivity and specificity of testing were 100%. The comparator was usual care, which assumed that subjects started statins spontaneously at a later point or when they experienced a cardiovascular event. The effect of reducing low-density lipoprotein cholesterol (LDL-C) on the risk of a first event at each age assumed that risk was proportional to total lifetime exposure and was implemented using Mendelian randomisation analysis data. Cost and other outcome data were sourced from published sources. Outcome of interests were costs in Australian dollars (AUD), life years gained (LYG) and quality-adjusted life years (QALYs) gained, as well as incremental cost-effectiveness ratios (ICERs) of costs per LYG and per QALY gained. All future costs and outcomes were discounted by 5% annually., Results: Undiscounted results showed that compared with usual care, cascade screening of ten year-old children for FH and initiation of treatment of affected individuals saved 7.77 LYG and 7.53 QALYs per person over a lifetime. With 5% annual discounting, there were 0.97 LYG and 1.07 QALYs gained per person, at net reduction cost of -$1134. The cascade screening of ten-year-old children for FH and initiation of treatment compared to usual case was a cost saving approach. In 51.2% of iterations, screening and initiation with statin were cost saving and in 48.8% of iterations were cost-effective. In most of the one-way sensitivity and scenario analyses, the ICER stayed within the accepted Australian threshold., Conclusions: Compared to usual care, cascade screening of ten-year-old children for FH and treating affected individuals are likely to be cost saving., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Patients with chronic kidney disease (CKD) are commonly treated with renin-angiotensin-aldosterone system inhibitors (RAASi) in order to delay progression of renal disease. However, research has shown that RAASi in CKD patients increases hyperkalaemia (HK) prevalence, which leads to RAASi discontinuation or dose reduction with the loss of benefits on the kidney. Patiromer is a novel therapy for HK treatment and may enable patients to remain on their RAASi regimen. This study aimed to assess the cost-effectiveness of patiromer from a Swedish healthcare perspective., Methods: A Markov model was developed to evaluate the economic outcomes of patiromer versus no patiromer in HK patients with stage 3-4 CKD taking RAASi. The model consisted of six health states reflecting disease progression and hospitalisations. The analysis mainly considered clinical data from the OPAL-HK trial and national costs. The main outcomes of interest were incremental costs (euro [EUR] 2016) and quality-adjusted life years (QALYs), discounted at 3%, and the incremental cost-effectiveness ratio (ICER). Extensive uncertainty analyses were performed., Results: In comparison to no patiromer, a patiromer patient gained 0.14 QALYs and an incremental cost of EUR 6109 (Swedish krona [SEK] 57,850), yielding an ICER of EUR 43,307 (SEK 410,072)/QALY gained. The results were robust to a range of sensitivity analyses. At a willingness-to-pay threshold of EUR 52,804 (SEK 500,000)/QALY, patiromer had a 50% chance of being cost-effective., Conclusions: The results indicate that patiromer may demonstrate value for money in Swedish patients with stage 3-4 CKD, by enabling RAASi treatment. However, there is a considerable degree of uncertainty.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cancer patients are vulnerable to complications of respiratory viruses. This systematic review and meta-analysis sought to examine the prevalence of cancer and its association with disease severity in patients with novel coronavirus disease 2019 (COVID-19). Searches were performed in MEDLINE, EMBASE and ScienceDirect from their inception until 28 April 2020. Severe disease was considered to encompass cases resulting in death or as defined by the primary study authors. Meta-analysis was performed using random-effect models. We included 20 studies involving 32,404 patients from China, the United Kingdom, the United States, Italy, Singapore, Thailand, France, India and South Korea. The pooled prevalence of cancer was 3.50% (95% confidence interval (CI) 1.70 to 5.80). The pooled prevalence was not moderated by study mean age, proportion of females or whether the study was conducted in/outside of China. Patients with cancer were more likely to experience severe COVID-19 disease compared to patients without cancer (pooled risk ratio 1.76, 95% CI 1.39 to 2.23). Our findings reiterate the need for additional precautionary measures to ensure that patients with cancer are not exposed to COVID-19, and if they become infected, extra attention should be provided to minimise their risk of adverse outcomes., Competing Interests: None., (© the authors; licensee ecancermedicalscience.)