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Introduction: The correlation between body mass index (BMI) and utility in participants with obesity was assessed using health-related quality-of-life data collected in two weight loss intervention studies, SCALE and STEP 1., Methods: Short Form Health Survey 36-Item (SF-36) scores from SCALE and STEP 1 were mapped to EuroQoL-5 dimensions-3 levels (EQ-5D-3L) using an established algorithm to derive utilities for the UK. SF-36 scores from STEP 1 were converted into Short Form 6 dimension (SF-6D) utilities for Portugal using the tool developed by the University of Sheffield. The correlation between baseline BMI and utility was assessed by multiple linear regression analyses, controlling for demographic and clinical parameters., Results: A higher baseline BMI correlated with lower EQ-5D-3L and SF-6D utilities, although the trend was non-significant. Assuming linearity between BMI ranges 30-40 kg/m 2 , an additional unit of BMI correlated with 0.0041 and 0.0031 lower EQ-5D-3L scores in SCALE and 0.0039 and 0.0047 lower EQ-5D-3L and 0.0027 and 0.0020 lower SF-6D scores in STEP 1 for men and women, respectively., Conclusion: In individuals with comparable demographic characteristics and weight-related comorbidities, a 1 unit change in BMI leads to a difference of up to 0.005 in utility indices., Trial Registration: ClinicalTrials.gov identifiers: SCALE (NCT01272219) and STEP 1 (NCT03548935)., (© 2024. The Author(s).)

Objective: This study leveraged data from 11 independent international diabetes models to evaluate the impact of unrelated future medical costs on the outcomes of health economic evaluations in diabetes mellitus., Methods: Eleven models simulated the progression of diabetes and occurrence of its complications in hypothetical cohorts of individuals with type 1 (T1D) or type 2 (T2D) diabetes over the remaining lifetime of the patients to evaluate the cost effectiveness of three hypothetical glucose improvement interventions versus a hypothetical control intervention. All models used the same set of costs associated with diabetes complications and interventions, using a United Kingdom healthcare system perspective. Standard utility/disutility values associated with diabetes-related complications were used. Unrelated future medical costs were assumed equal for all interventions and control arms. The statistical significance of changes on the total lifetime costs, incremental costs and incremental cost-effectiveness ratios (ICERs) before and after adding the unrelated future medical costs were analysed using t-test and summarized in incremental cost-effectiveness diagrams by type of diabetes., Results: The inclusion of unrelated costs increased mean total lifetime costs substantially. However, there were no significant differences between the mean incremental costs and ICERs before and after adding unrelated future medical costs. Unrelated future medical cost inclusion did not alter the original conclusions of the diabetes modelling evaluations., Conclusions: For diabetes, with many costly noncommunicable diseases already explicitly modelled as complications, and with many interventions having predominantly an effect on the improvement of quality of life, unrelated future medical costs have a small impact on the outcomes of health economic evaluations., (© 2024. The Author(s).)

Objectives: The Mount Hood Diabetes Challenge Network aimed to examine the impact of model structural uncertainty on the estimated cost-effectiveness of interventions for type 2 diabetes., Methods: Ten independent modeling groups completed a blinded simulation exercise to estimate the cost-effectiveness of 3 interventions in 2 type 2 diabetes populations. Modeling groups were provided with a common baseline population, cost and utility values associated with different model health states, and instructions regarding time horizon and discounting. We collated the results to identify variation in predictions of net monetary benefit (NMB) and the drivers of those differences., Results: Overall, modeling groups agreed which interventions had a positive NMB (ie, were cost-effective), Although estimates of NMB varied substantially-by up to £23 696 for 1 intervention. Variation was mainly driven through differences in risk equations for complications of diabetes and their implementation between models. The number of modeled health states was also a significant predictor of NMB., Conclusions: This exercise demonstrates that structural uncertainty between different health economic models affects cost-effectiveness estimates. Although it is reassuring that a decision maker would likely reach similar conclusions on which interventions were cost-effective using most models, the range in numerical estimates generated across different models would nevertheless be important for price-setting negotiations with intervention developers. Minimizing the impact of structural uncertainty on healthcare decision making therefore remains an important priority. Model registries, which record and compare the impact of structural assumptions, offer one potential avenue to improve confidence in the robustness of health economic modeling., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Chronic disease progression models are available for several highly prevalent conditions. For chronic kidney disease (CKD), the scope of existing progression models is limited to the risk of kidney failure and major cardiovascular (CV) events. The aim of this project was to develop a comprehensive CKD progression model (CKD-PM) that simulates the risk of CKD progression and a broad range of complications in patients with CKD. A series of literature reviews informed the selection of risk factors and identified existing risk equations/algorithms for kidney replacement therapy (KRT), CV events, other CKD-related complications, and mortality. Risk equations and transition probabilities were primarily sourced from publications produced by large US and international CKD registries. A patient-level, state-transition model was developed with health states defined by the Kidney Disease Improving Global Outcomes categories. Model validation was performed by comparing predicted outcomes with observed outcomes in the source cohorts used in model development (internal validation) and other cohorts (external validation). The CKD-PM demonstrated satisfactory modeling properties. Accurate prediction of all-cause and CV mortality was achieved without calibration, while prediction of CV events through CKD-specific equations required implementation of a calibration factor to balance time-dependent versus baseline risk. Predicted annual changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio were acceptable in comparison to external values. A flexible eGFR threshold for KRT equations enabled accurate prediction of these events. This CKD-PM demonstrated reliable modeling properties. Both internal and external validation revealed robust outcomes.

Patients with cardiac disease exhibit exaggerated sympathoexcitation, pressor, and ventilatory responses to muscle metaboreflex activation (MMA). However, the effects of cardiac rehabilitation (CR) and especially resistance training (RT) modalities on MMA are not well known. This study investigated how CR impacts MMA in such patients, specifically examining the effects of two different resistance training (RT) protocols following 12 weeks of CR. In addition to endurance exercises, 32 patients were randomized into either a 3/7 RT modality (comprising 5 sets of 3-7 repetitions) or a control (CTRL) modality (involving 3 sets of 9 repetitions), with distinct inter-set rest intervals (15 s for 3/7 and 60 s for CTRL). MMA, gauged by blood pressure (BP) and ventilatory (Ve) responses during a handgrip exercise at 40% effort and subsequent post-exercise circulatory occlusion, demonstrated CR's significant impact. Systolic BP, initially at + 28 ± 23% pre-CR, improved to + 11 ± 15% post-CR (P = .011 time effect; P = .131 group effect). Diastolic BP showed a similar trend, from + 27 ± 23% to + 13 ± 15% (P = .099 time effect; P = .087 group effect). Ve, initially at + 60 ± 39%, reduced to + 14 ± 19% post-CR (P < .001 time effect; P = .142 group effect). Critical parameters-maximal oxygen consumption, lean mass, hand grip, and quadriceps strength-exhibited parallel increases in both 3/7 and CTRL groups (P < .05 time effect; P > .3 group effect). Ultimately, CR demonstrated comparable improvements in MMA across both RT modalities, indicating its positive influence on cardiovascular responses and physical performance in individuals with cardiac conditions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC)., Methods: Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m 2 , and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime., Results: From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained., Conclusion: Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis., (© 2024. The Author(s).)

Background: Obesity and overweight are a significant public health concern. Subcutaneous semaglutide 2.4 mg injection is a glucagon-like peptide-1 (GLP-1) analogue approved by the European Medicines Agency as an adjunct to a reduced calorie diet and increased physical activity (diet and exercise, D&E) for the treatment obesity and overweight in the presence of at least one weight related comorbidity. This study aimed to assess the cost-effectiveness of semaglutide 2.4 mg in combination with D&E compared to D&E alone for the Portuguese setting., Methods: Analysis were conducted using the Core Obesity Model (COM) version 18, a Markov state transition cohort model, to predict the health outcomes and costs of weight related complications based on changes in surrogate endpoints. Efficacy and safety data were sourced from the STEP trials (Body Mass Index, systolic blood pressure and glycemic status) from a cohort of adults aged on average 48 years with obesity (BMI ≥ 30 kg/m2) and ≥ 1 obesity-related comorbidities, over a time horizon of 40 years. Costs were estimated from the perspective of the Portuguese National Health Service. Sensitivity analyses were conducted to test the robustness of results across a range of assumptions., Results: On a patient level, Semaglutide 2.4 mg in addition to D&E compared to D&E alone, improved QALYs by 0.098 and yielded higher costs by 1,325 EUR over a 40-year time horizon, with an ICER of 13,459 EUR per QALY gained and 100% probability of cost-effectiveness at the given WTP. Semaglutide 2.4 mg remained cost-effective across all different scenarios and sensitivity analysis at a WTP of 20,000 EUR per QALY. Among the subpopulations examined, Semaglutide 2.4 mg yielded ICERs of 18,459 EUR for patients with BMI ≥ 30 kg/m2 and of 22,657 EUR for patients with BMI ≥ 35 kg/m2., Conclusions: Semaglutide 2.4 mg was cost-effective compared to D&E alone for patients with obesity (BMI ≥ 30 kg/m2) and weight related comorbidities in Portugal, over a 40-year time horizon., (© 2024. The Author(s).)

Aim: There is growing interest in novel insulin management systems that improve glycemic control. This study aimed to evaluate the cost-effectiveness of smart connected insulin re-usable pens or caps for disposable insulin pens versus pens without connected capabilities in the management of adult patients with Type 1 diabetes (T1DM) from a Canadian societal perspective. Materials & methods: The IQVIA Core Diabetes Model was utilized to conduct the analyses. Applying data from a non-interventional study, the connected insulin device arm was assumed to result in greater reductions (-0.67%) in glycated hemoglobin from baseline and fewer non-severe hypoglycemic events (-32.87 events/patient annually). Macro- and micro-vascular risks were predicted using the Epidemiology of Diabetes Interventions and Complications study data. Direct and indirect costs and utilities were sourced from literature. Key model outcomes included life years and quality-adjusted life-years (QALYs). Both costs and effects were annually discounted at 1.5% over a 60-year time horizon. Uncertainty was explored in scenario and probabilistic sensitivity analyses (PSA). Results: The connected insulin pen device was associated with lower mean discounted total costs (CAD221,943 vs 266,199; -CAD44,256), improvement in mean life expectancy (25.78 vs 24.29; +1.49 years) and gains in QALYs (18.48 vs 16.74; +1.75 QALYs) over the patient's lifetime. Most scenario analyses confirmed the base case results. The PSA showed dominance in 99.5% of cases. Conclusion: For adults with T1DM in Canada, a connected insulin pen device is likely to be a cost-effective treatment option associated with greater clinical benefits and lower costs relative to a standard re-usable or disposable pen.

Introduction: Type 2 diabetes mellitus (T2DM) is associated with huge clinical and economic burden in the Kingdom of Saudi Arabia (KSA) which can be curtailed by efficacious treatment. In order to achieve this, current treatment pathways for T2DM and associated costs need to be assessed., Methods: A longitudinal cohort review was conducted to collect country-specific and patient-specific clinical data, over a minimum observation period of 5 years in the KSA. Patient demographics, clinical characteristics and treatment patterns were recorded. The IQVIA Core Diabetes Model (CDM) version 9.5 Plus was used to assess the burden of illness, which included long-term projections of clinical (life expectancy [LE], quality-adjusted life-years [QALYs], event rates of diabetes-related complications) and direct medical cost (per-patient annual or lifelong [50 years]) outcomes of the most commonly used first-line (1st-line) regimens for T2DM from a payer perspective in the KSA., Results: Data were collected from a subpopulation of 638 patients from 15 participating centres. There was an equal gender representation with a majority of the patients belonging to Arabian/Saudi ethnicity (71.0%). Biguanides (81.5%), sulfonylureas (51.6%), dipeptidyl peptidase 4 (DPP4) inhibitors (26.2%) and fast-acting insulins (17.2%) were the most prescribed 1st-line agents. The most frequently used 1st-line regimens resulted in an estimated LE of 25-28 years, QALYs of 18-21 years and lifelong total cost of illness of 201,377-437,371 Saudi Arabian riyal (53,700-116,632 US dollars)., Conclusion: Our study addresses gaps in the current research by providing a complete landscape of baseline demographic, clinical characteristics and treatment patterns from a heterogeneous group of patients with T2DM in the KSA. Additionally, the burden of illness analysis using CDM showed substantially higher cost of T2DM care from a payer perspective in the KSA., (© 2024. The Author(s).)

Objective: The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) vs SoC alone in the treatment of CKD in the UK., Methods: A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes., Results: Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses., Limitations: This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression., Conclusions: Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.

Objective: To estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17Ai's, ixekizumab, and secukinumab, from the NHS Scotland perspective., Methods: The axSpA treatment-pathway was modeled using a decision tree followed by a lifetime Markov model. The pathway included first- and second-line biologic disease-modifying antirheumatic drugs (bDMARD), followed by best supportive care (bDMARD, nonbiologic). Bimekizumab followed by any bDMARD ("BKZ") was compared with IL-17Ai's: secukinumab 150 mg followed by a blend ("SEC") of dose up-titration to secukinumab 300 mg and any bDMARD, or ixekizumab followed by any bDMARD ("IXE"). Transition to the next therapy was triggered by Bath Ankylosing Spondylitis Disease Activity Index-50% (BASDAI50) non-response or any-cause discontinuation. A published network meta-analysis provided efficacy data. EuroQoL-5-dimensions utilities were derived by mapping from Ankylosing Spondylitis Disease Activity Score. Costs included disease management (linked to functional limitations), biologics acquisition (list prices), administration and monitoring (NHS 2021/22). Discounting was 3.5%/year. Probabilistic results from patients with non-radiographic axSpA and ankylosing spondylitis were averaged to reflect the axSpA disease spectrum. Scenario and sensitivity analyses were performed., Results: The incremental cost-effectiveness ratio (ICER) of BKZ was £24,801/quality-adjusted life-year (QALY) vs. SEC (95% credible interval £24,163-£25,895). BKZ had similar costs (Δ -£385 [-£15,239-£14,468]) and QALYs (Δ 0.039 [-0.748-0.825]) to IXE, with £1,523 (£862-£2,222) net monetary benefit. Conclusions remained unchanged in most scenarios. Results' drivers included BASDAI50 response rate and disease management cost., Limitations: Results were based on list prices. Data concerning up-titration to secukinumab 300 mg was scarce., Conclusions: The bimekizumab treatment-pathway represents a cost-effective option across the axSpA disease spectrum in Scotland. Bimekizumab is cost-effective compared to a secukinumab-pathway that includes dose up-titration, and has similar costs and QALYs to an ixekizumab-pathway.

The 3/7 resistance training (RT) method involves performing sets with increasing numbers of repetitions, and shorter rest periods than the 3x9 method. Therefore, it could induce more metabolic stress in people with heart failure with reduced ejection fraction (HFrEF) or coronary artery disease (CAD). This randomized cross-over study tested this hypothesis. Eleven individuals with HFrEF and thirteen with CAD performed high-intensity interval training (HIIT) for 30 min, followed by 3x9 or 3/7 RT according to group allocation. pH, HCO 3- , lactate, and growth hormone were measured at baseline, after HIIT, and after RT. pH and HCO 3- decreased, and lactate increased after both RT methods. In the CAD group, lactate increased more (6.99 ± 2.37 vs. 9.20 ± 3.57 mmol/L, p = 0.025), pH tended to decrease more (7.29 ± 0.06 vs. 7.33 ± 0.04, p = 0.060), and HCO 3- decreased more (18.6 ± 3.1 vs. 21.1 ± 2.5 mmol/L, p = 0.004) after 3/7 than 3x9 RT. In the HFrEF group, lactate, pH, and HCO 3- concentrations did not differ between RT methods (all p > 0.248). RT did not increase growth hormone in either patient group. In conclusion, the 3/7 RT method induced more metabolic stress than the 3x9 method in people with CAD but not HFrEF.

Whereas exercise training, as part of multidisciplinary rehabilitation, is a key component in the management of patients with chronic coronary syndrome (CCS) and/or congestive heart failure (CHF), physicians and exercise professionals disagree among themselves on the type and characteristics of the exercise to be prescribed to these patients, and the exercise prescriptions are not consistent with the international guidelines. This impacts the efficacy and quality of the intervention of rehabilitation. To overcome these barriers, a digital training and decision support system [i.e. EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool], i.e. a stepwise aid to exercise prescription in patients with CCS and/or CHF, affected by concomitant risk factors and comorbidities, in the setting of multidisciplinary rehabilitation, was developed. The EXPERT working group members reviewed the literature and formulated exercise recommendations (exercise training intensity, frequency, volume, type, session and programme duration) and safety precautions for CCS and/or CHF (including heart transplantation). Also, highly prevalent comorbidities (e.g. peripheral arterial disease) or cardiac devices (e.g. pacemaker, implanted cardioverter defibrillator, left-ventricular assist device) were considered, as well as indications for the in-hospital phase (e.g. after coronary revascularisation or hospitalisation for CHF). The contributions of physical fitness, medications and adverse events during exercise testing were also considered. The EXPERT tool was developed on the basis of this evidence. In this paper, the exercise prescriptions for patients with CCS and/or CHF formulated for the EXPERT tool are presented. Finally, to demonstrate how the EXPERT tool proposes exercise prescriptions in patients with CCS and/or CHF with different combinations of CVD risk factors, three patient cases with solutions are presented., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: The purpose of this study was to determine and compare the effectiveness of three different resistance training (RT) methods for cardiac rehabilitation., Methods: Individuals with heart failure with reduced ejection fraction (HFrEF, n = 23) or coronary artery disease (CAD, n = 22) and healthy controls (CTRL, n = 29) participated in this randomized crossover trial of RT exercises at 70% of the one-maximal repetition on a leg extension machine. Peak heart rate (HR) and blood pressure (BP) were measured noninvasively. The three RT methods were five sets of increasing repetitions from three to seven (RISE), of decreasing repetitions from seven to three (DROP), and three sets of nine repetitions (USUAL). Interset rest intervals were 15 sec for RISE and DROP and 60 sec for USUAL., Results: Peak HR differed on average by <4 bpm between methods in the HFrEF and CAD groups ( P < .02). Rises in systolic BP (SBP) in the HFrEF group were comparable across methods. In the CAD group, mean SBP at peak exercise increased more in RISE and DROP than in USUAL ( P < .001), but the increase was ≤10 mm Hg. In the CTRL group, SBP was higher for DROP than for USUAL (152 ± 22 vs 144 ± 24 mm Hg, respectively; P < .01). Peak cardiac output and perceived exertion did not differ between methods., Conclusions: The RISE, DROP, and USUAL RT methods induced a similar perception of effort and similar increases in peak HR and BP. The RISE and DROP methods appear more efficient as they allow a comparable training volume in a shorter time than the USUAL method., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Infantile hemangiomas (IHs) can be part of PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies) syndrome when they are segmental, extensive, and located on the face or neck. The initial assessment is codified and well known, but there are no recommendations for the follow-up of these patients. The aim of this study was to assess the long-term prevalence of different associated abnormalities., Methods: Patients with a history of large segmental IHs of the face or neck. diagnosed between 2011 and 2016 were included in the study. Each patient underwent an ophthalmological, dental, ENT (ear, nose, and throat), dermatological, neuro-pediatric, and radiological assessment at inclusion. Eight patients including five with PHACE syndrome were prospectively evaluated., Results: After a mean follow-up of 8.5 years, three patients presented with an angiomatous aspect of the oral mucosa, two with hearing loss, and two with otoscopic abnormalities. No patients developed ophthalmological abnormalities. The neurological examination was altered in three cases. Brain magnetic resonance imaging follow-up was unchanged in three out four patients and revealed atrophy of the cerebellar vermis in 1 patient. Neurodevelopmental disorders were found in five of the patients and learning difficulties were observed in five patients. The S1 location appears to be associated with a higher risk of neurodevelopmental disorders and cerebellar malformations, while the S3 location was associated with more progressive complications, including neurovascular, cardiovascular, and ENT abnormalities., Conclusion: Our study reported late complications in patients with a large segmental IH of the face or neck, whether associated with PHACE syndrome or not, and we proposed an algorithm to optimize the long-term follow-up., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

BACKGROUND: A tubeless, on-body automated insulin delivery (AID) system (Omnipod 5 Automated Insulin Delivery System) demonstrated improved glycated hemoglobin A1c levels and increased time in range (70 mg/dL to 180 mg/dL) for both adults and children with type 1 diabetes in a 13-week multicenter, single-arm study. OBJECTIVE: To assess the cost-effectiveness of the tubeless AID system compared with standard of care (SoC) in the management of type 1 diabetes (T1D) in the United States. METHODS: Cost-effectiveness analyses were conducted from a US payer's perspective, using the IQVIA Core Diabetes Model (version 9.5), with a time horizon of 60 years and an annual discount of 3.0% on both costs and effects. Simulated patients received either tubeless AID or SoC, the latter being defined as either continuous subcutaneous insulin infusion (86% of patients) or multiple daily injections. Two cohorts (children: <18 years; adults: ≥18 years) of patients with T1D and 2 thresholds for nonsevere hypoglycemia (nonsevere hypoglycemia event [NSHE] <54 mg/dL and <70 mg/dL) were considered. Baseline cohort characteristics and treatment effects of different risk factors for tubeless AID were sourced from the clinical trial. Utilities and cost of diabetes-related complications were obtained from published sources. Treatment costs were derived from US national database sources. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Treating children with T1D with tubeless AID, considering an NSHE threshold of less than 54 mg/dL, brings incremental life-years (1.375) and quality-adjusted life-years (QALYs) (1.521) at an incremental cost of $15,099 compared with SoC, resulting in an incremental cost-effectiveness ratio of $9,927 per QALY gained. Similar results were obtained for adults with T1D assuming an NSHE threshold of less than 54 mg/dL (incremental cost-effectiveness ratio = $10,310 per QALY gained). Furthermore, tubeless AID is a dominant treatment option for children and adults with T1D assuming an NSHE threshold of less than 70 mg/dL compared with SoC. The probabilistic sensitivity analyses results showed that compared with SoC, in both children and adults with T1D, tubeless AID was cost-effective in more than 90% of simulations, assuming a willingness-to-pay threshold of $100,000 per QALY gained. The key drivers of the model were the cost of ketoacidosis, duration of treatment effect, threshold of NSHE, and definition of severe hypoglycemia. CONCLUSIONS: The current analyses suggest that the tubeless AID system can be considered a cost-effective treatment compared with SoC in people with T1D from a US payer's perspective. DISCLOSURES: This research was funded by Insulet. Mr Hopley, Ms Boyd, and Mr Swift are full-time Insulet employees and own stock in Insulet Corporation. IQVIA, the employer of Ms Ramos and Dr Lamotte, received consulting fees for this work. Dr Biskupiak is receiving research support and consulting fees from Insulet. Dr Brixner has received consulting fees from Insulet. The University of Utah has received research funding from Insulet. Dr Levy is a consultant with Dexcom and Eli Lilly and has received grant/research support from Insulet, Tandem, Dexcom, and Abbott Diabetes. Dr Forlenza conducted research sponsored by Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. He has been speaker/consultant/advisory board member for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly.

Cardiopulmonary exercise testing (CPET) was limited to peak oxygen consumption analysis (VO 2 peak), and now the ventilation/carbon dioxide production (VE/VCO 2 ) slope is recognized as having independent prognostic value. Unlike VO 2 peak, the VE/VCO 2 slope does not require maximal effort, making it more feasible. There is no consensus on how to measure the VE/VCO 2 slope; therefore, we assessed whether different methods affect its value. This is a retrospective study assessing sociodemographic data, left ventricular ejection fraction, CPET parameters, and indications of patients referred for CPET. The VE/VCO 2 slope was measured to the first ventilatory threshold (VT1-slope), secondary threshold (VT2-slope), and included all test data (full-slope). Of the 697 CPETs analyzed, 308 reached VT2. All VE/VCO 2 slopes increased with age, regardless of test indications. In patients not reaching VT2, the VT1-slope was 32 vs. 36 ( p < 0.001) for the full-slope; in those surpassing VT2, the VT1-slope was 29 vs. 33 ( p < 0.001) for the VT2-slope and 37 (all p < 0.001) for the full-slope. The mean difference between the submaximal and full-slopes was ±4 units, sufficient to reclassify patients from low to high risk for heart failure or pulmonary hypertension. We conclude that the method used for determining the VE/VCO 2 slope greatly influences the result, the significant variations limiting its prognostic value. The calculation method must be standardized to improve its prognostic value.

Background: Obesity might be a cause of limited aerobic exercise capacity. It is often associated with metabolic syndrome (MS) that includes cardiovascular comorbidities as arterial hypertension. Cardiopulmonary exercise testing (CPET) is the gold-standard to assess aerobic capacity and discriminate causes of dyspnea., Aim: To evaluate aerobic capacity in obesity and if MS or hypertensive treatment impacts on the CPET profile., Methods: CPET of 146 obese patients, whom 33 and 31 were matched for MS and antihypertensive medication, were analyzed. VO 2peak (mL/min/Kg) was reported in percentage of predicted value, or, divided by body weight, fat free mass (FFM) or body weight expected for a body mass index of 24 (BMI24)., Results: VO 2peak (20,8 ± 4,4 mL/min/Kg) was normal when expressed in percentage predicted for obesity (111 ± 22%pred) or divided by FFM and weight BMI24 (33,6 ± 5,6 and 30,6 ± 6,2 respectively). The latter correlated better with maximal work rate (r = 0,7168, p < 0,001). Obese patients showed normal ventilatory efficiency (ventilation to carbon dioxide production slope: 28 ± 4), VO 2 to work rate (10,2 ± 1,6 mLO 2 /Watt) and, slightly elevated heart rate to VO 2 slope (4,0 ± 1,1 bpm/mL/min/Kg). Compared to normotensives, hypertensive medicated patients had higher blood pressure at anaerobic threshold (142 ± 23 vs 158 ± 26 mmHg, p = 0,001) but not at maximal exercise (189 ± 31 vs 201 ± 23 mmHg, p = NS), and, had lower actual maximal heart rate (155 ± 23 vs 143 ± 25 bpm, p = 0,03). There was no difference between obese patients with or without MS., Conclusion: Obese people with or without MS present with similar and normal aerobic profile related to the excessive body weight. VO 2peak divided by weight BMI24 is an easy and clinical meaningful index for obese patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Beta-blockers are increasingly prescribed while the effects of beta-adrenergic receptor blockade on cardio-pulmonary exercise test (CPET)-derived parameters remain under-studied., Methods: Twenty-one young healthy adults repeated three CPET at the same time with an interval of 7 days between each test. The tests were performed 3 h after a random, double-blind, cross-over single-dose intake of placebo, 2.5 mg or 5.0 mg bisoprolol, a cardio-selective beta1-adrenoreceptor antagonist. Gas exchange, heart rate (HR) and blood pressure (BP) were measured at rest and during cyclo-ergometric incremental CPET., Results: Maximal workload and VO 2 max were unaffected by the treatment, with maximal respiratory exchange ratio > 1.15 in all tests. A beta-blocker dose-dependent effect reduced resting and maximal BP and HR and the chronotropic response to exercise, evaluated by the HR/VO 2 slope (placebo: 2.9 ± 0.4 beat/ml/kg; 2.5 mg bisoprolol: 2.4 ± 0.5 beat/ml/kg; 5.0 mg bisoprolol: 2.3 ± 0.4 beat/ml/kg, p < 0.001). Ventilation efficiency measured by the VE/VCO 2 slope and the ventilatory equivalent for CO 2 at the ventilatory threshold were not affected by beta1-receptor blockade. Post-exercise chronotropic recovery measured after 1 min was enhanced under beta1-blocker (placebo: 26 ± 7 bpm; 2.5 mg bisoprolol: 32 ± 6 bpm; 5.0 mg bisoprolol: 33 ± 6 bpm, p < 0.01)., Conclusion: The present results suggest that a single dose of bisoprolol does not affect metabolism, respiratory response and exercise capacity. However, beta-adrenergic blockade dose dependently reduces exercise hemodynamic response by lowering BP and the chronotropic response., (© 2022. The Author(s).)

Boron neutron capture therapy (BNCT) is a re-emerging technique for selectively killing tumor cells. Briefly, the mechanism can be described as follows: after the uptake of boron into cells, the thermal neutrons trigger the fission of the boron atoms, releasing the α-particles and recoiling lithium particles and high-energy photons that damage the cells. We performed a detailed study of the reactor dosimetry, cellular dose assessment, and radiobiological effects induced by BNCT in glioblastoma (GBM) cells. At maximum reactor power, neutron fluence rates were ϕ0 = 6.6 × 107 cm−2 s−1 (thermal) and θ = 2.4 × 104 cm−2 s−1 with a photon dose rate of 150 mGy·h−1. These values agreed with simulations to within 85% (thermal neutrons), 78% (epithermal neutrons), and 95% (photons), thereby validating the MCNPX model. The GEANT4 simulations, based on a realistic cell model and measured boron concentrations, showed that >95% of the dose in cells was due to the BNC reaction. Carboranylmethylbenzo[b]acridone (CMBA) is among the different proposed boron delivery agents that has shown promising properties due to its lower toxicity and important cellular uptake in U87 glioblastoma cells. In particular, the results obtained for CBMA reinforce radiobiological effects demonstrating that damage is mostly induced by the incorporated boron with negligible contribution from the culture medium and adjacent cells, evidencing extranuclear cell radiosensitivity.

Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive condition characterized by cortisol deficiency and excess androgen production. The current standard of care is glucocorticoid (GC) therapy, and sometimes mineralocorticoids, to replace endogenous cortisol deficiency; however, supraphysiologic GC doses are usually needed to reduce excess androgen production. Monitoring/titrating GC treatment remains a major challenge, and there is no agreement on assessment of treatment adequacy. This study surveyed expert opinions on current treatment practices and unmet needs in adults with classic CAH., Methods: A modified two-round Delphi process with adult endocrinologists was conducted via online questionnaire. Survey questions were organized into three categories: practice characteristics/CAH experience, GC management, and unmet needs/complications. Anonymized aggregate data from Round 1 were provided as feedback for Round 2. Responses from both rounds were analyzed using descriptive statistics. Consensus was defined a priori as: full consensus (100%, n=9/9); near consensus (78% to <100%, n=7/9 or 8/9); no consensus (<78%, n<7/9)., Results: The same nine panelists participated in both survey rounds; five (56%) were based in North America and four (44%) in Europe. Most panelists (78%) used hydrocortisone in the majority of patients, but two (22%) preferred prednisone/prednisolone. Panelists agreed (89%) that adequate control is best evaluated using a balance of clinical presentation and androgen/precursor laboratory values; no consensus was reached on optimal timing of collecting samples for androgen testing or laboratory values indicating good control. Despite lack of consensus on many aspects of CAH management, panelists agreed on the importance of many disease- and GC-related complications, and that there is a large unmet need for new treatments. With currently available treatments, panelists reported that 46% of classic CAH patients did not have optimized androgen levels, regardless of GC dose., Conclusions: The limited areas of consensus obtained in this study reflect the variability in treatment practices for adults with classic CAH, even among clinicians with expertise in treating this population. However, all panelists agreed on the need for new treatments for classic CAH and the importance of many disease- and GC-related complications, which are difficult to manage with currently available treatments., Competing Interests: MF, CO’D and CY were employed by Neurocrine Biosciences, Inc. MA, KC, and NT were employed by Evidera. ML, full-time employee of IQVIA. IQVIA received consulting fees for the advice of ML on this research. RA received research funding from Neurocrine Biosciences, Inc., Diurnal, LTD, and Spruce Biosciences; RA served as consultant for Neurocrine Biosciences, Inc., Crinetics Pharmaceuticals, OMass Therapeutics, H Lundbeck A/S, and Adrenas Therapeutics. HF served as consultant for Neurocrine Biosciences, Inc., Diurnal Ltd., Roche Diagnostics International Ltd., H Lundbeck A/S, and Adrenas Therapeutics. AL served as editor Adrenal Section, UpToDate. The authors declare that this study received funding from Neurocrine Biosciences, Inc. The funder had the following involvement in the study: Contracted with Evidera and IQVIA to conduct the Delphi surveys, collate data, perform statistical analyses, and assist with interpretation of data and preparation of the manuscript. Contracted with Prescott Medical Communications Group to assist with preparation of the manuscript., (Copyright © 2022 Auchus, Courtillot, Dobs, El-Maouche, Falhammar, Lacroix, Farrar, O’Donoghue, Anatchkova, Cutts, Taylor, Yonan, Lamotte and Touraine.)

Our aim was to evaluate the benefits of cardio-pulmonary rehabilitation on severe to moderate COVID-19 patients. 25 discharged COVID-19 patients underwent a cardio-pulmonary test (CPET), a spirometry test and a measure of carbon monoxide lung diffusion capacity (DLCO) at the beginning of their rehabilitation program and after 23 ± 5 rehabilitation sessions. This rehabilitation program combined interval training exercises on a bike and resistance exercises for major muscle groups. We then compared their progress in rehabilitation to that obtained with cardiac patients. At the beginning of their rehabilitation program, COVID-19 patients presented a reduced physical capacity with a maximal aerobic capacity (VO 2 max) at 71% of predicted value, a maximal workload at 70% of predicted value and an exercise hyperventilation measured by a higher VE/VCO 2 slope. Exercise was mainly limited by muscle deconditioning. After rehabilitation, the VO 2 max and maximal workload increased in COVID 19 patients by 18% and 26%, respectively. In patients with ischemic heart disease the post-rehabilitation gains in VO2 max and maximal workload were 22% and 25%, respectively. Moreover, exercise hyperventilation decreased by 10% in both groups. On the other hand, the intrinsic pulmonary function of COVID 19 patients improved following natural recovery. In conclusion, even if cardio-pulmonary rehabilitation is probably not the only parameter which explains the partial recovery of moderate to severe COVID-19 patients, it certainly helps to improve their physical capacity and reduce exercise hyperventilation.

Background: Structural uncertainty can affect model-based economic simulation estimates and study conclusions. Unfortunately, unlike parameter uncertainty, relatively little is known about its magnitude of impact on life-years (LYs) and quality-adjusted life-years (QALYs) in modeling of diabetes. We leveraged the Mount Hood Diabetes Challenge Network, a biennial conference attended by international diabetes modeling groups, to assess structural uncertainty in simulating QALYs in type 2 diabetes simulation models., Methods: Eleven type 2 diabetes simulation modeling groups participated in the 9th Mount Hood Diabetes Challenge. Modeling groups simulated 5 diabetes-related intervention profiles using predefined baseline characteristics and a standard utility value set for diabetes-related complications. LYs and QALYs were reported. Simulations were repeated using lower and upper limits of the 95% confidence intervals of utility inputs. Changes in LYs and QALYs from tested interventions were compared across models. Additional analyses were conducted postchallenge to investigate drivers of cross-model differences., Results: Substantial cross-model variability in incremental LYs and QALYs was observed, particularly for HbA1c and body mass index (BMI) intervention profiles. For a 0.5%-point permanent HbA1c reduction, LY gains ranged from 0.050 to 0.750. For a 1-unit permanent BMI reduction, incremental QALYs varied from a small decrease in QALYs (-0.024) to an increase of 0.203. Changes in utility values of health states had a much smaller impact (to the hundredth of a decimal place) on incremental QALYs. Microsimulation models were found to generate a mean of 3.41 more LYs than cohort simulation models ( P = 0.049)., Conclusions: Variations in utility values contribute to a lesser extent than uncertainty captured as structural uncertainty. These findings reinforce the importance of assessing structural uncertainty thoroughly because the choice of model (or models) can influence study results, which can serve as evidence for resource allocation decisions.HighlightsThe findings indicate substantial cross-model variability in QALY predictions for a standardized set of simulation scenarios and is considerably larger than within model variability to alternative health state utility values (e.g., lower and upper limits of the 95% confidence intervals of utility inputs).There is a need to understand and assess structural uncertainty, as the choice of model to inform resource allocation decisions can matter more than the choice of health state utility values.

Introduction: International and Danish guidelines recommend the use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors already in second line in the management of type 2 diabetes (T2D). The objective of this study was to evaluate the long-term cost-effectiveness (CE) of subcutaneous (SC) semaglutide (GLP-1 RA) versus empagliflozin (SGLT-2 inhibitor) in individuals with T2D uncontrolled on metformin alone from a Danish payer's perspective., Methods: Cost-effectiveness analyses (CEA) were conducted from a Danish payer's perspective, using the IQVIA Core Diabetes model (CDM 9.5), with a time horizon of 50 years and an annual discount of 4% on costs and effects. Patients received either SC semaglutide or empagliflozin, in addition to metformin, until HbA1c threshold of 7.5% (58 mmol/mol) was reached, following which treatment intensification with insulin glargine in addition to empagliflozin or SC semaglutide plus metformin was considered. Baseline cohort characteristics and treatment effects were sourced from a published CEA. Utilities and cost of diabetes-related complications were also obtained from published sources. Treatment costs were derived from Danish official sources. Scenario analyses were also performed to test the accuracy of the base case results., Results: Individuals with T2D on SC semaglutide plus metformin gained 0.065 life-years (LYs) and 0.130 quality-adjusted LYs (QALYs), respectively, at an incremental cost of DKK 96,923 (€ 13,031) compared to empagliflozin plus metformin, resulting in an incremental cost-effectiveness ratio (ICER) of DKK 745,561(€ 100,239) per QALY gained. The probabilistic sensitivity analysis (PSA) results showed that the SC semaglutide plus metformin was cost-effective in 19% of simulations assuming a willingness-to-pay (WTP) threshold of DKK 357,100 (€ 48,011)/QALY gained. Duration of therapy with SC semaglutide seems the key driver of results., Conclusion: The current analyses suggest that SC semaglutide plus metformin is not cost-effective compared to empagliflozin plus metformin from a Danish payer's perspective., (© 2022. The Author(s).)

Aim: To evaluate the cost-effectiveness of oral semaglutide+metformin versus empagliflozin+metformin in people with Type 2 diabetes uncontrolled on msetformin alone. Materials and methods: The IQVIA Core Diabetes Model was populated with efficacy data from a head-to-head study between oral semaglutide+metformin and empagliflozin+metformin. Danish costs and quality-of-life data were sourced from literature. Price per day was Danish Krone (DKK) 25.53 for oral semaglutide and DKK11.40 for empagliflozin. Discounting was fixed at 4%. Scenario and sensitivity analyses were performed. Results: Over a lifetime, Core Diabetes Model projected 8.78 and 8.75 quality-adjusted life-years and a total cost of DKK 447,633 and DKK 387,786, thereby generating an incremental cost-effectiveness ratio of DKK 1,930,548 for oral semaglutide+metformin versus empagliflozin+metformin. Scenario and sensitivity analyses showed the robustness of the outcomes. Duration of treatment with oral semaglutide is the key driver of the analyses. Conclusion: Oral semaglutide+metformin seems not cost effective versus empagliflozin+metformin in patients uncontrolled on metformin in Denmark.

Introduction: The fixed-ratio combinations (FRCs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and basal insulin, insulin glargine 100 U/mL plus lixisenatide (iGlarLixi), and insulin degludec plus liraglutide (iDegLira), have demonstrated safety and efficacy in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on GLP-1 RAs. However, a comparative cost-effectiveness analysis between these FRCs from a UK Health Service perspective has not been conducted., Methods: The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes in patients with T2DM receiving iGlarLixi (based on the LixiLan-G trial) versus iDegLira (based on relative treatment effects from an indirect treatment comparison using data from DUAL III). Utilities, medical costs, and costs of diabetes-related complications were derived from literature. Model outputs included costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated with a local willingness-to-pay threshold of £20,000 per QALY. Extensive scenario, one-way sensitivity, and probabilistic sensitivity analyses were conducted to evaluate the robustness of the model., Results: iGlarLixi was less costly (iGlarLixi, £30,011; iDegLira, £40,742), owing to lower acquisition costs, and similar in terms of QALYs gained (iGlarLixi, 8.437; iDegLira, 8.422). Extensive scenario and sensitivity analyses supported the base case findings., Conclusion: In patients with T2DM and inadequate glycemic control despite GLP-1 RAs, use of iGlarLixi was associated with substantial cost savings and comparable utility outcomes. iGlarLixi can be considered as cost-effective versus iDegLira from the UK Health Service perspective., (© 2021. The Author(s).)

Introduction: Frequent glucose monitoring is essential to obtain glucose control. This is done by periodic self-monitoring of blood glucose (SMBG) using finger-prick testing, or by using continuous glucose monitoring devices, wherein a sensor records interstitial glucose data automatically. This study assessed the cost-effectiveness of using the FreeStyle Libre Flash Continuous Glucose Monitoring System (FSL) compared to SMBG in individuals with type 2 diabetes (T2D) treated with insulin from a Swedish societal perspective., Methods: Cost-effectiveness analysis was conducted using the IQVIA Core Diabetes model v9.5, with demographic and clinical inputs from a real-world study using Swedish National Diabetes Register data. Two cohorts of individuals with T2D were considered based on baseline HbA1C (HbA1c: 8-9% [64-75 mmol/mol]; HbA1c: 9-12% [75-108 mmol/mol]). HbA1c reductions with FSL were - 0.41% (- 4 mmol/mol; SD: 0.94%-10 mmol/mol) and - 1.30% (- 14 mmol/mol; SD: 1.40%-15 mmol/mol) for the two cohorts, respectively. Utilities, treatment costs and diabetes-related complication costs were obtained from published sources. Analyses were conducted over a lifetime horizon, applying annual discounting of 3% on costs and effects. Scenario analyses and probabilistic sensitivity analyses were performed., Results: Individuals with T2D who had a baseline HbA1c of 8-9% (64-75 mmol/mol) and 9-12% (75-108 mmol/mol) and used FSL gained 0.50 and 0.57 quality-adjusted life-years (QALYs), respectively, at an incremental cost of SEK109,957 and SEK82,170 compared to SMBG, generating an incremental cost-utility ratio of SEK219,127 and SEK144,412 per QALY gained. Assuming a willingness-to-pay threshold of SEK300,000 per QALY gained, FSL use was considered cost-effective compared to SMBG for the majority of the individuals in both the lower and higher HbA1c cohorts. The key driver identified was the additional quality-of-life benefit that applied to FSL use., Conclusion: The FreeStyle Libre Flash Continuous Glucose Monitoring System is a cost-effective glucose monitoring alternative to SMBG for individuals with T2D in Sweden who are treated with insulin but are not reaching their glycaemic goals., (© 2021. The Author(s).)

Background: In several cardiovascular outcome trials (CVOTs), empagliflozin (SGLT-2 inhibitor), sitagliptin (DPP-4 inhibitor) and liraglutide (GLP-1 receptor agonist) + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and liraglutide + SoC based on the respective CVOT., Methods: The IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease (HbA1c, BMI, blood pressure, lipids) were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and liraglutide + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk adjustments to calibrate the CDM were obtained after a trial and error process to match as closely the observed and CDM-predicted outcomes. The drug-specific treatment effects were considered up until HbA1c reached 8.5% and treatment switch occurred. After this switch, the United Kingdom Prospective Diabetes Study 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal bolus insulin were applied. The analysis was conducted from the perspective of the Chinese healthcare system applying 3% discounting. The time horizon was lifelong., Results: Empagliflozin + SoC provides additional Quality Adjusted Life years (QALY + 0.564) for an incremental cost of 42,497RMB (US$6053) compared to sitagliptin + SoC, resulting in an Incremental Cost Utility Ratio of 75,349RMB (US$10,732), thus below the willingness-to-pay threshold of 212,676RMB, corresponding to three times the Gross Domestic Product in China (2019). Compared to liraglutide + SoC, empagliflozin + SoC use leads to 0.211QALY gained and cost savings of 71,427RMB (US$10,173) and is as such dominant. Scenario and probabilistic sensitivity analyses demonstrated the robustness of the results., Conclusion: Results suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and liraglutide + SoC at a willingness-to-pay threshold of 212,676RMB ($30,292)/QALY., (© 2021. The Author(s).)

Introduction: The increasing financial burden associated with diabetes treatment presents a challenge to healthcare systems worldwide. Recently, clinical guidelines have focussed on patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and recommend a sodium-glucose co-transporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist as second-line treatment after metformin or independently of baseline glycated haemogloblin A1c (HbA1c). In Danish clinical guidelines, empagliflozin and liraglutide are highlighted owing to their positive impact on mortality. Thus, this study aimed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) versus liraglutide plus SoC in Danish patients with T2D and established CVD using a lifetime and 5-year horizon., Methods: The IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the clinical event rates observed in the cardiovascular outcome trial EMPA-REG OUTCOME. Network meta-analysis provided the relative risks for cardiovascular outcomes with empagliflozin versus liraglutide. Microvascular outcomes were predicted by standard CDM risk equations. The relative treatment effect was assumed for 9 years after which treatment was switched to basal-bolus therapy. The CDM was populated with Danish costs of events and drug costs at price-level 2019. Discounting of 4% was applied., Results: Over a lifetime horizon, CDM projected 9.858 and 9.667 life years, 6.162 and 5.976 quality-adjusted life years (QALY) and DKK 478,026 (€64,079) and DKK 500,025 (€67,027) in total costs for empagliflozin plus SoC and liraglutide plus SoC, respectively. For a 5-year horizon, the results were 4.189 and 4.140 life years, 2.746 and 2.655 QALY, as well as DKK 123,413 (€16,543) and DKK 161,783 (€21,687), respectively. Empagliflozin was the dominant treatment alternative. Sensitivity analyses showed the robustness of these results., Conclusion: The cost-effectiveness analysis suggests that empagliflozin plus SoC is dominant compared to liraglutide plus SoC in Denmark over both lifetime and 5-year horizons.

Objectives: Chronic obstructive pulmonary disease (COPD) exacerbations requiring hospitalisation are a considerable burden, both clinically and economically. Although long-acting maintenance therapy is recommended in both the GOLD (Global Initiative for Chronic Obstructive Lung Disease) and Chinese COPD guidelines, proper implementation is lacking. The objective of this study was to assess the clinical and economic impact of prescribing long-acting maintenance therapy to discharged patients with COPD after hospitalisation for an exacerbation in China by using an outcomes model., Design: This health economic analysis was conducted using a Markov cohort model from the Chinese healthcare payer perspective. Two health states (alive and dead) were modelled, and exacerbations were included as possible events., Setting: The target population was Chinese patients with COPD, >40 years of age, who were hospitalised for an exacerbation, with 1 year of follow-up. A recent COPD national prevalence study was referenced for population calculations., Intervention: A hypothetical future scenario, where 100% of patients would receive long-acting maintenance therapy after hospitalisation for an exacerbation, was compared with the current scenario, in which only 38.5% of patients are receiving long-acting maintenance therapy after hospitalisation., Outcome Measures: Number of exacerbations, deaths and medical costs were measured., Results: We estimated that there were approximately 4 million Chinese patients with COPD who were hospitalised annually due to an exacerbation. By prescribing long-acting maintenance therapy, our model predicted that 917 360 exacerbations and 4034 deaths could be avoided, translating into cost savings of ¥3.5 billion (US$0.5 billion). Scenario analysis also showed that if the rate of exacerbations requiring hospitalisation was higher than our base case analysis, cost savings could reach up to ¥10.7 billion (US$1.5 billion)., Conclusion: Administering long-acting maintenance therapy to more patients with COPD at hospital discharge could considerably reduce exacerbations and healthcare spending in China., Competing Interests: Competing interests: HH has provided professional training to AstraZeneca, outside the submitted work. HZ is a full-time employee of AstraZeneca. MR and ML are employees of IQVIA, and AS is a former employee of IQVIA., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The study assesses the cost-effectiveness of empagliflozin versus glimepiride in patients with Type 2 diabetes and uncontrolled by metformin alone in China, based on the EMPA-REG H2H-SU trial. Materials & methods: A calibrated version of the IQVIA Core Diabetes Model was used. Cost of complications and utility were taken from literature. The Chinese healthcare system perspective and 5% discounting rates were applied. Results: Empagliflozin+metformin provides additional quality-adjusted life-years (0.317) driven by a reduction in the number of cardiovascular and renal events, for an additional cost of $1382 (CNY9703) compared with glimepiride+metformin. Conclusion: Empagliflozin is cost-effective treatment versus glimepiride applying a threshold of $30,290 (CNY212,676).

Aims: Models are needed to quantify the economic implications of obesity in relation to health outcomes and health-related quality of life. This report presents the structure of the Core Obesity Model (COM) and compare its predictions with the UK clinical practice data., Materials and Methods: The COM is a Markov, closed-cohort model, which expands on earlier obesity models by including prediabetes as a risk factor for type 2 diabetes (T2D), and sleep apnea and cancer as health outcomes. Selected outcomes predicted by the COM were compared with observed event rates from the Clinical Practice Research Datalink-Hospital Episode Statistics (CPRD-HES) study. The importance of baseline prediabetes prevalence, a factor not taken into account in previous economic models of obesity, was tested in a scenario analysis using data from the 2011 Health Survey of England., Results: Cardiovascular (CV) event rates predicted by the COM were well matched with those in the CPRD-HES study (7.8-8.5 per 1000 patient-years across BMI groups) in both base case and scenario analyses (8.0-9.4 and 8.6-9.9, respectively). Rates of T2D were underpredicted in the base case (1.0-7.6 vs. 2.1-22.7) but increased to match those observed in CPRD-HES for some BMI groups when a prospectively collected prediabetes prevalence was used (2.7-13.1). Mortality rates in the CPRD-HES were consistently higher than the COM predictions, especially in higher BMI groups., Conclusions: The COM predicts the occurrence of CV events and T2D with a good degree of accuracy, particularly when prediabetes is included in the model, indicating the importance of considering this risk factor in economic models of obesity., Competing Interests: Sandra Lopes and Henrik H. Meincke are employees and shareholders of Novo Nordisk A/S. IQVIA, the employer of Mark Lamotte and Anamaria‐Vera Olivieri, received consulting fees from Novo Nordisk A/S for this study. Michael E.J. Lean has received departmental funding and contributed to advisory boards for Novo Nordisk.All authors contributed to the study design, data interpretation, and writing and critical review of manuscript content. Sandra Lopes, Mark Lamotte, and Anamaria‐Vera Olivieri were involved in performing and reviewing the data analysis., (© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Purpose: Depression and anxiety have been extensively associated with adverse outcomes in coronary heart disease patients. However, psychological and physiological processes underlying the persistence of these troubles in coronary heart disease patients attending cardiac rehabilitation are poorly investigated. Trait emotional competencies and heart rate variability could be some of these processes. Thus, the aim of this study was to assess the predictive value of trait emotional competencies and heart rate variability on depression and anxiety symptoms persistence in coronary heart disease patients., Methods: Eighty-four patients who recently presented a myocardial infarction were evaluated at the beginning of cardiac rehabilitation. Forty-two patients continued their rehabilitation program and were then assessed three months later. They completed the Profile of Emotional Competence as well as the Hospital Anxiety and Depression Scale and underwent a 5-minute resting heart rate variability measure., Results: Low trait emotional competencies score predicted depression symptoms persistence, but unexpectedly, high trait emotional competencies score was also associated with withdrawal from cardiac rehabilitation. Contrary to our expectations, heart rate variability did not predict depression or anxiety symptoms persistence and was not associated with trait emotional competencies., Conclusions: This study is the first to report an association between trait emotional competencies and depression symptoms persistence in coronary heart disease patients. However, heart rate variability was not associated with either depression or anxiety supporting the idea of mixed literature and highlighting the need of future research.

Background: Standard influenza vaccines are produced using egg-based manufacturing methods. Through the process, the resulting egg-adapted viral strains may differ from the selected vaccine strain. Cell-derived influenza vaccine manufacturing prevents egg-adaptation of the antigen which can improve vaccine effectiveness. We evaluated the cost-effectiveness of quadrivalent cell-derived influenza vaccine (QIVc) versus an egg-based quadrivalent influenza vaccine (QIVe) in preventing seasonal influenza from German societal and payer perspectives., Methods: Adapted version of the individual-based dynamic 4Flu transmission model was combined with a decision-tree to calculate the impact of QIVc versus QIVe on influenza over 20 seasons in Germany. Egg-adaptation, resulting in lower effectiveness of QIVe versus QIVc towards the H3N2 influenza strain, is sourced from a US retrospective study and assumed in 100% (base case) or 55% (conservative scenario) of years. Influenza-related probabilities of outpatient visits, hospitalizations, productivity loss, and mortality, with associated (dis)utilities/costs, were extracted from literature. Costs and outcomes were discounted 3.0%/year., Results: Replacing QIVe with QIVc in subjects aged ≥ 9 years can annually prevent 167,265 symptomatic cases, 51,114 outpatient visits, 2,091 hospitalizations, and 103 deaths in Germany. The annual number of quality-adjusted life-years (QALYs) increased by 1,628 and healthcare costs decreased by €178 M from societal perspective. From payer perspective, the incremental cost-effectiveness ratio was €2,285 per QALY. Scenario analyses confirmed results robustness., Conclusions: The use of QIVc compared to QIVe, in the German Immunization Program, could significantly prevent outpatient visits and hospitalizations and would enable substantial savings from a societal perspective.

Background: For economic models to be considered fit for purpose, it is vital that their outputs can be interpreted with confidence by clinicians, budget holders and other stakeholders. Consequently, thorough validation of models should be carried out to enhance confidence in their predictions. Here, we present results of external dependent and independent validations of the Core Obesity Model (COM), which was developed to assess the cost-effectiveness of weight management interventions., Objective: The aim was to assess the external validity of the COM (version 6.1), in line with best practice guidance from the International Society for Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making., Methods: For validation, suitable sources and outcomes were identified, and used to populate the COM with relevant inputs to allow prediction of study outcomes. Study characteristics were entered into the COM to replicate either the studies used to develop the model (dependent validation) or those not included in the model (independent validation). The concordance between predicted and observed outcomes was then assessed using established statistical methods and generation of mean error estimates., Results: For most outcomes, the predictions of the COM showed good linear correlation with observed outcomes, as evidenced by the high coefficients of determination (R 2 values). The independent validation revealed a degree of underestimation in predictions of cardiovascular (CV) disease and mortality, and type 2 diabetes., Conclusion: The predictions generated by the risk equations used in the COM showed good concordance both with the studies used to develop the model and with studies not included in the model. In particular, the concordance observed in the external dependent validation suggests that the COM accurately predicts obesity-related event rates observed in the studies used to develop the model. However, the impact of existing CV risk, as well as mortality, is a key area for future refinement of the COM. Our results should increase confidence in the estimates derived from the COM and reduce uncertainty associated with analyses using this model.

Objectives: The cardiovascular outcomes challenge examined the predictive accuracy of 10 diabetes models in estimating hard outcomes in 2 recent cardiovascular outcomes trials (CVOTs) and whether recalibration can be used to improve replication., Methods: Participating groups were asked to reproduce the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program. Calibration was performed and additional analyses assessed model ability to replicate absolute event rates, hazard ratios (HRs), and the generalizability of calibration across CVOTs within a drug class., Results: Ten groups submitted results. Models underestimated treatment effects (ie, HRs) using uncalibrated models for both trials. Calibration to the placebo arm of EMPA-REG OUTCOME greatly improved the prediction of event rates in the placebo, but less so in the active comparator arm. Calibrating to both arms of EMPA-REG OUTCOME individually enabled replication of the observed outcomes. Using EMPA-REG OUTCOME-calibrated models to predict CANVAS Program outcomes was an improvement over uncalibrated models but failed to capture treatment effects adequately. Applying canagliflozin HRs directly provided the best fit., Conclusions: The Ninth Mount Hood Diabetes Challenge demonstrated that commonly used risk equations were generally unable to capture recent CVOT treatment effects but that calibration of the risk equations can improve predictive accuracy. Although calibration serves as a practical approach to improve predictive accuracy for CVOT outcomes, it does not extrapolate generally to other settings, time horizons, and comparators. New methods and/or new risk equations for capturing these CV benefits are needed., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: International guidelines recommend treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist for treatment intensification in type 2 diabetes mellitus (T2DM) patients with progression on metformin. In the randomised, controlled, Peptide Innovation for Early Diabetes Treatment (PIONEER) 2 trial, the SGLT-2 inhibitor empagliflozin was compared with the GLP-1 receptor agonist oral semaglutide, in addition to metformin. The aim of the current study was to assess the long-term cost-effectiveness of empagliflozin 25 mg versus oral semaglutide 14 mg, in addition to metformin, for T2DM patients in the UK., Methods: Analyses were conducted from the UK healthcare payer perspective, using the IQVIA Core Diabetes model, with a time horizon of 50 years. Patients received either empagliflozin or oral semaglutide, in addition to metformin, until Hba1c threshold of 7.5% (58 mmol/mol) was exceeded, following which treatment intensification with insulin glargine in addition to empagliflozin or oral semaglutide plus metformin was assumed. Baseline cohort characteristics and 52-week treatment effects were derived from the PIONEER 2 trial. Treatment effects of empagliflozin and GLP-1 receptor agonists on hospitalisation for heart failure (hHF) were based on the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) real-world study. Utilities, treatment costs and costs of diabetes-related complications were obtained from published sources., Results: Direct costs for empagliflozin plus metformin were considerably lower than those for oral semaglutide plus metformin (by more than GBP 6000). Compared with oral semaglutide plus metformin, empagliflozin plus metformin was a cost-effective treatment for T2DM patients in all scenarios tested. Probabilistic sensitivity analysis showed cost-effectiveness in > 95% of the iterations using a threshold of 20,000 GBP/QALY., Conclusion: Empagliflozin 25 mg is a cost-effective treatment option versus oral semaglutide 14 mg, when used in addition to metformin, for the treatment of T2DM patients in the UK.

Aim: Cost-effectiveness (CE) analysis of empagliflozin+standard of care (SoC) compared with SoC and liraglutide+SoC, in patients with Type II diabetes and established cardiovascular disease, was conducted using evidence from cardiovascular outcomes trials. Methods: The IQVIA Core Diabetes Model was calibrated to predict same outcomes observed in EMPA-REG OUTCOME and LEADER trials. Three-year observed cardiovascular events of SoC, empagliflozin+SoC and liraglutide+SoC were derived from EMPA-REG OUTCOME trial and an indirect comparison. Time horizon was 50 years and the UK payer perspective was taken. Results: Empagliflozin+SoC dominated liraglutide+SoC with greater quality-adjusted life years and reduced costs. Base-case incremental CE ratio of 6428 GBP/QALY was observed for empagliflozin+SoC versus SoC. Conclusion: Results suggest that empagliflozin+SoC is cost effective versus SoC and liraglutide+SoC.

Between October 2017 and May 2019, measurements of tritium in rainwater were carried out at several sites in north-west France. Tritium is an important tracer for hydroclimatic studies and this work provided up-to-date data that we compared with Global Network for Isotopes in Precipitation (GNIP) measurements. Of the various sites studied, some could potentially be affected by atmospheric gaseous emissions from the nuclear industries in the region (reprocessing plant, nuclear power plant). On our reference site, the activities measured in rainwater are often below the decision threshold (<0.15 Bq.L -1 ). Two other sites with little impact from nuclear industries have mean activities of less than 0.7 Bq.L -1 . At the two Cherbourg sites closer to the nuclear industries, the activities in rainwater are slightly higher on average, though still close to 1 Bq.L -1 , but the activities are more variable when the rainfall accompanies an air mass from the Orano La Hague nuclear site. Using existing GNIP data and a simple model to simulate predicted data up to 2019, it is shown that all our measured data are comparable with the predicted activities for GNIP stations with a marine influence, in the case of the reference site and the sites with little impact from nuclear industries, and for GNIP stations with a continental influence, in the case of the other sites. Seasonal variation in activities was detected, with greater activities in the spring-summer period corresponding to the well known 'spring leak' phenomenon. This study also reveals significant differences between the activities measured on the western side of France (influenced by the Atlantic Ocean) and those measured in a continental zone. The mean levels of tritium in rainwater in France, excluding any nuclear influence, can be estimated on average at less than 0.3 Bq.L -1 in the western marine zone, and at around 1 Bq.L -1 in the continental zones., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: In the cardiovascular outcome trials (CVOT) EMPA-REG OUTCOME, TECOS and SAVOR-TIMI 53, empagliflozin [sodium/glucose cotransporter 2 (SGLT2) inhibitor], sitagliptin and saxagliptin [both dipeptidyl peptidase 4 (DPP4) inhibitors] + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and saxagliptin + SoC based on the respective CVOT., Methods: The IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease [glycated haemogloblin A1c (HbA1c), body mass index (BMI), blood pressure, lipids] were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and saxagliptin + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk (RR) adjustments to calibrate the CDM were estimated after consecutive attempts of running the model until the observed and CDM-predicted outcomes matched closely. The drug-specific treatment effects were considered up until treatment switch (when HbA1c reached 8.5%), after which, the United Kingdom Prospective Diabetes Study (UKPDS) 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal-bolus insulin were applied. The analysis was conducted from the perspective of the UK National Health Service. Costs and quality of life data were derived from UK national sources and published literature. A 50-year time horizon and discount rate of 3.5% were applied., Results: The CDM projected quality-adjusted life years (QALYs) of 6.408, 5.917 and 5.704 and total costs of 50,801 GBP, 47,627 GBP and 48,071 GBP for empagliflozin + SoC, sitagliptin + SoC and saxagliptin + SoC, respectively. The incremental CE ratio (ICER) of empagliflozin + SoC versus sitagliptin + SoC and saxagliptin + SoC was 6464 GBP/QALY and 3878 GBP/QALY, respectively. One-way and probabilistic sensitivity analyses demonstrated the robustness of the results., Conclusion: Results suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and saxagliptin + SoC at a willingness to pay threshold of 20,000 GBP/QALY., Funding: Boehringer Ingelheim International GmbH.

Transparency in health economic decision modelling is important for engendering confidence in the models and in the reliability of model-based cost-effectiveness analyses. The Mount Hood Diabetes Challenge Network has taken a lead in promoting transparency through validation with biennial conferences in which diabetes modelling groups meet to compare simulated outcomes of pre-specified scenarios often based on the results of pivotal clinical trials. Model registration is a potential method for promoting transparency, while also reducing the duplication of effort. An important network initiative is the ongoing construction of a diabetes model registry (https://www.mthooddiabeteschallenge.com). Following the 2012 International Society for Pharmacoeconomics and Outcomes Research and the Society of Medical Decision Making (ISPOR-SMDM) guidelines, we recommend that modelling groups provide technical and non-technical documentation sufficient to enable model reproduction, but not necessarily provide the model code. We also request that modelling groups upload documentation on the methods and outcomes of validation efforts, and run reference case simulations so that model outcomes can be compared. In this paper, we discuss conflicting definitions of transparency in health economic modelling, and describe the ongoing development of a registry of economic models for diabetes through the Mount Hood Diabetes Challenge Network, its objectives and potential further developments, and highlight the challenges in its construction and maintenance. The support of key stakeholders such as decision-making bodies and journals is key to ensuring the success of this and other registries. In the absence of public funding, the development of a network of modellers is of huge value in enhancing transparency, whether through registries or other means.

Background: International guidelines recommend using basal insulin in patients with type-2 diabetes mellitus if glycaemic target cannot be attained on non-insulin anti-diabetic drugs. Available choices of basal insulin include intermediate-acting neutral protamine Hagedorn (NPH) insulin and long-acting insulin analogues like insulin glargine U100. Despite clear advantages of glargine U100, the existing practice in Hong Kong still favours NPH insulin due to lower immediate drug costs., Objectives: The objective of this study was to assess the cost-effectiveness of insulin glargine U100 compared to NPH insulin in patients with type-2 diabetes uncontrolled with non-insulin anti-diabetic agents alone in Hong Kong., Methods: The IQVIA™ Core Diabetes Model (CDM) v9.0 was used to conduct the cost-effectiveness analysis of glargine U100 versus NPH. Baseline characteristics were collected from the Hong Kong Diabetes Registry. Efficacy rates were extracted from a published study comparing glargine U100 and NPH in Asia, utilities from published literature, and costs constructed using the Hong Kong Hospital Authority (HA) Gazette (public healthcare setting). The primary outcome was an incremental cost-effectiveness ratio (ICER)., Results: Insulin glargine U100 resulted in an ICER of HKD 98,663 per Quality Adjusted Life Year (QALY) gained. The incremental gains in QALY and costs were 0.217 years and HKD 21,360 respectively. Results from scenario and probabilistic sensitivity analyses were consistent with that from base case analysis., Conclusion: Insulin glargine U100 is a cost-effective treatment for patients with type 2 diabetes compared to NPH insulin in setting in Hong Kong. This was mainly driven by the significantly lower rates of hypoglycaemia of insulin glargine U100 than NPH insulin., Competing Interests: Competing interestsAL received a research grant from Sanofi Limited for conducting this study. Sanofi had no role in study design, data collection, analysis, or interpretation of the data.

Aims: The aim of this study was to estimate patient and caregiver productivity loss and indirect costs following an acute coronary syndrome (ACS) or a stroke in Europe., Methods: A cross-sectional study was conducted in seven European countries. A validated questionnaire was used during a cardiologist/neurologist visit 3-12 months post event. We included patients who returned to work ( ≥ 4 weeks prior to recruitment), given specific interest in presenteeism. Patient absenteeism, presenteeism and caregiver loss in the past four weeks were pro-rated to one year and combined with time-off due to initial hospitalisation/sick-leave. Hours lost were valued according to country labour cost (2018 euros)., Results: The analysis included 196 ACS (86% myocardial infarction) and 198 stroke (99% ischaemic, 77% modified Rankin Scale 0-1) patients. Mean age in ACS and stroke patients was 53 years, 86% and 78% respectively were men, 28% and 25% had previous cardiovascular event or established cardiovascular disease. Mean (country range) total productivity time loss was 70 (47-91) workdays for ACS and 68 (45-88) workdays for stroke (25% of annual workdays). Particularly, ACS patient lost 59 (37-79) workdays, and caregivers lost 11 (0-16) workdays, with total mean indirect cost per case €13,953 (€6641-23,160). After stroke, 56 (42-70) workdays were lost by patient plus 12 (3-20) days by caregiver, amounting to €13,773 (€10,469-20,215). Patients with previous events or established cardiovascular disease lost 80 (ACS) and 73 (stroke) workdays, costing €16,061 and €14,942 respectively., Conclusions: Our results suggest that lost productive time and indirect costs following ACS/stroke are substantial, with indirect costs comparable to direct costs.

Background: Recent estimates from the International Diabetes Federation Diabetes Atlas have quantified the total annual expenditure for diabetes in China to be between 354 and 611 billion Chinese yuan (¥) (2015)., Objectives: To use a modeling approach to assess the current and possible future diabetes burden in China on the basis of the current standard of type 2 diabetes (T2D) management (status quo [SQ]) and a series of hypothetical improved management strategies., Methods: The IQVIA CORE Diabetes Model was used to evaluate the economic burden of T2D in China on the basis of assumptions reflecting the current SQ of T2D management and a number of stepwise improvements. SQ was defined as a scenario in which T2D diagnosis is delayed by 4 years, treatment escalation to maintain glucose control occurs at a 9% glycated hemoglobin (HbA 1c ) threshold, and there is an overall 60% adherence rate. Stepwise improvements considered immediate diagnosis, declining levels of HbA 1c escalation thresholds to 7.0%, and improvements in adherence rate to 80% and 100%. The CORE Diabetes Model was applied on per-capita level to project lifetime costs and clinical outcomes of newly diseased T2D individuals in the Chinese setting. Model outcomes were subsequently annualized and extrapolated to Chinese national level considering the total number of diagnosed individuals with T2D in China., Results: The total annual direct costs attributable to diagnosed T2D in China reflecting current SQ management were estimated at ¥621 billion. Scenarios exploring stepwise improvements from SQ estimated annual net savings of ¥35, ¥35, ¥60, ¥71, ¥75, and ¥106 billion for scenarios exploring immediate diagnosis, HbA 1c threshold reductions to 8.0% and 7.0%, adherence rate increase to 80% and 100%, and cardiovascular risk factor control in concordance with clinical guidelines, respectively. Net savings resulted from reduced costs to treat diabetes complications (¥38, ¥67, ¥124, ¥141, ¥161, and ¥212 billion) and excess treatment costs alongside stepwise management improvements (¥4, ¥32, ¥65, ¥69, ¥86, and ¥107 billion). Per-capita life expectancy was increased by 0.26, 0.68, 1.33, 1.47, 1.69, and 3.21 years, respectively., Conclusions: Improved T2D management strategies can help to decrease the financial burden of the disease and increase life expectancy of individuals with T2D., (Copyright © 2018 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Objective: Transcatheter aortic valve implantation (TAVI) has become the therapy of choice for treating severe aortic stenosis in patients at high-risk for surgery or where it is considered too risky to attempt. This uptake varies across geographies however, and its cost or value has frequently been cited as the reason for this. We sought to evaluate the potential cost and clinical impact of TAVI in intermediate risk patients from a French collective perspective., Materials and Methods: The analysis was performed using a novel Markov model with data derived from the PARTNER II randomized controlled trial for survival, clinical event rates, and quality-of-life. The simulated time horizon was 15 years, costs were from French sources and presented in 2016 Euros. Discounting of all outcomes was at 4% annually and the effect of uncertainty in model parameters was explored by deterministic and probabilistic sensitivity analysis (PSA)., Results: In comparison to surgery, TAVI resulted in improved clinical outcomes (life expectancy and quality-adjusted life expectancy) and lower costs over a lifetime time horizon. The base case results showed increases of 0.42 years and 0.41 QALYs with lifetime cost savings of €439 for TAVI compared to surgery. PSA results showed a >50% likelihood of cost-effectiveness at €0 willingness-to-pay and a 100% likelihood at ∼€15,000., Limitations: Clinically, survival projections are based on limited follow-up data and introduce uncertainty into the outcomes from the model. Economically, procedure costs are derived from a heterogeneous mix of patient risk groups, although this is much more likely to bias against TAVI and under-estimate overall cost savings., Conclusions: In our analyses of intermediate risk patients, TAVI is associated with superior clinical outcomes compared to surgery and is cost saving. It could be expected that cost savings are conservative and likely to increase over time.