Prognostic value of resting heart rate in predicting undiagnosed diabetes in adults: Korean National Health and Nutrition Examination Survey 2008-2018.

BACKGROUND AND AIM: Although resting heart rate (RHR) is associated with prevalence and incidence of diabetes, whether it is associated with undiagnosed diabetes is still unclear. We aimed to investigate whether the RHR is associated with the prevalence of undiagnosed diabetes in a large Korean national dataset. METHODS AND RESULTS: The Korean National Health and Nutrition Examination Survey data from 2008 to 2018 were used. After screening, 51,637 participants were included in this study. The odds ratios and 95% confidence intervals (CIs) for undiagnosed diabetes were calculated using multivariable-adjusted logistic regression analyses. Analyses showed that participants with a RHR of ≥90 bpm showed a 4.00- (95% CI: 2.77-5.77) and 3.21-times (95% CI: 2.01-5.14) higher prevalence of undiagnosed diabetes for men and women, respectively, than those with a RHR of <60 bpm. The linear dose-response analyses showed that each 10-bpm increment in RHR was associated with a 1.39- (95% CI: 1.32-1.48) and 1.28-times (95% CI: 1.19-1.37) higher prevalence of undiagnosed diabetes for men and women, respectively. In the stratified analyses, the positive association between RHR and the prevalence of undiagnosed diabetes was tended to be stronger among those who were younger (age: <40 years) and lean (BMI: <23 kg/m2). CONCLUSIONS: Elevated RHR was significantly associated with a higher prevalence of undiagnosed diabetes in Korean men and women, independent of demographic, lifestyle, and medical factors. Accordingly, the value of RHR as a clinical indicator and health marker, especially in reducing the prevalence of undiagnosed diabetes, is suggestible.

Cost-Effectiveness of Tiotropium in Elderly Patients with Severe Asthma Using Real-World Data.

BACKGROUND: Tiotropium has the potential to alleviate asthmatic symptoms caused by the aging of lungs. However, few studies have focused on specific treatments for elderly patients with asthma. OBJECTIVES: To estimate the cost-effectiveness of adding tiotropium to inhaled corticosteroids and long-acting beta-agonists in elderly patients with severe asthma using real-world data. METHODS: Phase I was a retrospective cohort study using the National Health Insurance claims data to measure clinical and economic outcomes. In phase II, a Markov model was constructed to evaluate cost-effectiveness from Korean health care system perspective, based on phase I, including 2 health states, and an asthma exacerbation event. We estimated cost given in 2018 US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Subgroup analyses for patients with poorly controlled symptoms (frequent short-acting beta-agonist users; frequent exacerbators) were performed. RESULTS: In elderly patients with severe asthma, the incremental cost and effectiveness in the tiotropium group compared with the inhaled corticosteroid and long-acting beta-agonist group were $2281 and 0.038 QALYs, respectively. The incremental cost-effectiveness ratio was $60,074/QALY, indicating that the addition of tiotropium is not a cost-effective alternative. Meanwhile, 2 subgroups with poorly controlled symptoms showed that adding tiotropium is a cost-effective alternative (frequent short-acting beta-agonist users $4078/QALY; frequent exacerbators $8332/QALY). CONCLUSIONS: Tiotropium shows a higher cost-effectiveness profile when applied to elderly patients with uncontrolled symptoms. These results using real-world evidence provide information beyond the clinical outcomes reported by randomized controlled trials, providing a complementary ground in establishing the reimbursement criteria of tiotropium for elderly patients with severe asthma.

Breath Acetone Measurement-Based Prediction of Exercise-Induced Energy and Substrate Expenditure.

The purpose of our study was to validate a newly developed breath acetone (BrAce) analyzer, and to explore if BrAce could predict aerobic exercise-related substrate use. Six healthy men ran on a treadmill at 70% of maximal oxygen consumption (VO2max) for 1 h after two days of a low-carbohydrate diet. BrAce and blood ketone (acetoacetate (ACAC), beta-hydroxybutyrate (BOHB)) levels were measured at baseline and at different time points of post-exercise. BrAce values were validated against blood ketones and respiratory exchange ratio (RER). Our results showed that BrAce was moderately correlated with BOHB (r = 0.68, p < 0.01), ACAC (r = 0.37, p < 0.01) and blood ketone (r = 0.60, p < 0.01), suggesting that BrAce reflect blood ketone levels, which increase when fat is oxidized. Furthermore, BrAce also negatively correlated with RER (r = 0.67, p < 0.01). In our multiple regression analyses, we found that when BMI and VO2max were added to the prediction model in addition to BrAce, R2 values increased up to 0.972 at rest and 0.917 at 1 h after exercise. In conclusion, BrAce level measurements of our BrAce analyzer reflect blood ketone levels and the device could potentially predict fat oxidation.

Economic burden of subsequent fracture in osteoporosis patients in South Korea.

OBJECTIVES: This study aimed to assess the economic burden of subsequent fracture in osteoporosis patients with incident fracture. METHODS: The authors conducted a retrospective cohort analysis of the South Korean national health insurance claims data. Study subjects included osteoporosis patients aged ≥50 with incident fracture (July 1, 2014-June 30, 2015). Fracture-related 1-year healthcare cost was evaluated after incident fracture for patients with and without subsequent fracture, defined as a fracture occurring within 2 years from incident fracture at a different site or at the same site after 6-months washout period. Per-patient-per-month (PPPM) cost was calculated by dividing each patient's cumulative healthcare cost until subsequent fracture with time-to-subsequent-fracture. For the patients without subsequent fracture, PPPM cost equaled 1-year monthly cost. A generalized linear model (GLM) was used to estimate the ratio of increase in healthcare cost to assess the economic impact of subsequent fracture. RESULTS: A total of 73,717 osteoporosis patients with incident fracture were identified, consisting of 52.1% vertebral, 1.9% hip, and 46.0% non-vertebral-non-hip fractures. Subsequent fracture occurred in 17.9% of patients with average time-to-subsequent-fracture of 256 days. Patients with subsequent fracture had significantly higher 1-year healthcare cost after incident fracture than those without subsequent fracture ($4,307 vs $1,721) and the difference was greater in PPPM cost ($930 vs $141). GLM analysis showed that having subsequent fracture increased both 1-year healthcare cost and PPPM cost by 1.91-fold (95% CI = 1.87-1.95) and 6.14-fold (95% CI = 5.99-6.28), respectively. CONCLUSIONS: Subsequent fracture imposes a substantial burden on osteoporosis patients and, therefore, more efforts are needed for preventing subsequent fracture among osteoporosis patients.

Cost-Utility Analysis of Sacubitril/Valsartan Use Compared With Standard Care in Chronic Heart Failure Patients With Reduced Ejection Fraction in South Korea.

PURPOSE: Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is a possible treatment option for chronic heart failure patients with reduced ejection fraction (HFrEF). The aim of this study was to estimate the cost-effectiveness of sacubitril/valsartan use in South Korea for treating patients with HFrEF compared with that of enalapril, an angiotensin-converting enzyme inhibitor, and with angiotensin receptor blockers (ARBs). METHODS: A Markov model was designed to estimate the lifetime cost-effectiveness of treatment for patients with HFrEF. Cohorts in the alive-state incurred a monthly risk of hospitalization because of deteriorated HF, adverse events (AEs), or death. Transition probabilities of sacubitril/valsartan and enalapril were estimated by using data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. The effectiveness of ARBs (eg, reduction in mortality and hospitalization rates) was assumed to be identical to that of enalapril, according to the results of the meta-analysis. However, there was no comparative evidence for AEs. We therefore conducted a Bayesian network meta-analysis and adjusted the incidence rate of AEs for ARBs. The utility for estimating quality-adjusted life years (QALYs) was elicited by the survey of the general South Korean population by using EuroQol-5 dimensions. We calculated the medical costs, including medication, monitoring, hospitalization, AEs, and terminal care, from the health care sector perspective. Costs and effectiveness were discounted by 5%. One-way sensitivity analyses and a probabilistic sensitivity analysis were conducted to determine the model robustness. FINDINGS: The total cost per patient for sacubitril/valsartan and enalapril was $25,832 and $18,295, respectively. Sacubitril/valsartan was associated with an ∼8- month longer life expectancy compared with enalapril and a QALY gain of 0.59. As a result, the incremental cost-effectiveness ratio for sacubitril/valsartan versus enalapril was $12,722 per QALY. The incremental cost-effectiveness ratio of sacubitril/valsartan versus ARB was $11,970 with an incurred cost of $18,741 for the ARB group. The main results and those of various sensitivity analyses were lower than a threshold of $20,000. IMPLICATIONS: From a health care sector perspective, sacubitril/valsartan is a cost-effective treatment for HFrEF compared with enalapril and ARBs. This finding could be helpful for cardiologists or decision makers in reaching cost-effective choices regarding the treatment selection process.

The Utility of 5 Hypothetical Health States in Heart Failure Using Time Trade-Off (TTO) and EQ-5D-5L in Korea.

BACKGROUND AND OBJECTIVE: Utility provides a preference for specific health state in economic evaluation, and they obtained from general population could be useful in respect of societal resource allocation. We aimed to investigate the utilities of health states for heart failure (HF), a major and growing public health problem, related to hospitalization and adverse drug effects by interrogating the general Korean population. METHODS: Five health states for patients with HF were developed based on literature reviews: stable chronic heart failure (SCHF), hospitalization, SCHF + cough, SCHF + hypotension, and SCHF + hyperkalemia. We selected 100 individuals from the general population through quota sampling by age, sex, and region, and conducted face-to-face interviews. We measured utilities for 5 hypothetical health states of HF using both time trade-off (TTO) and EuroQol-5 dimensions-5 levels (EQ-5D-5L). Repeated-measures analysis of variance compared the utilities between all health states for each instrument. To identify the factors affecting the utility, a linear mixed model (LMM) analysis was performed. RESULTS: The mean utility value for SCHF, SCHF + cough, SCHF + hypotension, SCHF + hyperkalemia, and hospitalization was calculated as 0.815, 0.732, 0.646, 0.548, and 0.360, respectively, by using TTO. The respective values using EQ-5D-5L were 0.871, 0.793, 0.710, 0.589, and 0.215. The utilities for HF significantly differed between all health states in each instrument (p < 0.001). In LMM analysis, hospitalization had a significantly negative effect on the utilities of both instruments. CONCLUSIONS: The utilities decreased in order of SCHF, SCHF + cough, SCHF + hypotension, SCHF + hyperkalemia, and hospitalization. These results can be useful for decision making in resource allocation for HF interventions.

Health Care Utilization and Direct Costs in Mild, Moderate, and Severe Adult Asthma: A Descriptive Study Using the 2014 South Korean Health Insurance Database.

PURPOSE: Although asthma exacerbation comprises a large burden of the total asthma-related costs, few studies have examined the frequency and cost of acute exacerbation according to asthma severity. This study investigated asthma-related health care utilization and costs according to the severity of asthma. METHODS: We conducted a descriptive study using the national health insurance claims database between January 1 and December 31, 2014. We included adult patients with asthma (18 years of age and older) who had ≥2 claims with for an asthma diagnosis and were prescribed ≥1 asthma medications. They were classified into 3 asthma severity levels (level 1 = mild, level 2 = moderate, and level 3 = severe), based on individual medication prescriptions. Acute exacerbation was defined as having a corticosteroid burst, an emergency department visit, or hospitalization. Health care utilization, acute exacerbation, and direct costs associated with asthma were compared according to asthma severity levels. FINDINGS: Of the 36,687 adult asthma patients, level 1 had the largest proportion of patients (81.2%), followed by level 2 (18.2%), and level 3 (0.6%). The average number of asthma-related outpatient visits was 4.5 for level 1, 7.2 for level 2, and 11.9 for level 3 (P < 0.01). The estimated asthma-related direct cost per patient was $174 for level 1, $634 for level 2, and $1635 for level 3 (P < 0.01). The number of patients who experienced acute exacerbation increased as asthma severity increased: level 1, 22.6%; level 2, 26.0%; and level 3, 48.7% (P < 0.01). Direct costs associated with asthma exacerbation dramatically increased and accounted for 15.1% of the total cost in level 1 patients, 19.5% in level 2 patients, and 40.8% in level 3 patients (P < 0.01). IMPLICATIONS: The direct costs of acute exacerbation increased as asthma severity increased. In patients with severe asthma, acute exacerbation and the relative cost ratio in South Korea were higher than those in other countries. Proper management is required to avoid acute exacerbations and to reduce the burden of asthma, particularly in patients with severe asthma.