Cost-effectiveness of the anti-vascular endothelial growth factor intravitreal injection and panretinal photocoagulation for patients with proliferative diabetic retinopathy in South Korea.

BACKGROUND: We determined the cost-effectiveness of the anti-vascular endothelial growth factor (VEGF) intravitreal injection versus panretinal photocoagulation (PRP) for patients with proliferative diabetic retinopathy (PDR) in South Korea. METHODS: We simulated four treatment strategies using PRP and the anti-VEGF injection by constructing a Markov model for a hypothetical cohort of 50-year-old PDR patients: (1) PRP only; (2) anti-VEGF injection only; (3) PRP first; and (4) anti-VEGF injection first. RESULTS: In this cost-effectiveness analysis, compared with only-PRP, the incremental cost-effectiveness ratio was $95,456 per quality-adjusted life-year (QALY) for PRP first, $34,375 per QALY for anti-VEGF injection first, and $33,405 per QALY for anti-VEGF injection only from a healthcare perspective. From the societal and payer perspective, strategy (2) was more cost-saving and effective than (1). In the probabilistic sensitivity analysis, only-PRP was cost-effective up to the willingness-to-pay (WTP) of about $42,000, while anti-VEGF injection only was cost-effective from a healthcare perspective. From the societal and payer perspectives, regardless of the value of WTP, anti-VEGF injection only was the most cost-effective strategy. CONCLUSION: In our study, the anti-VEGF injection for PDR was cost-effective from the payer and societal perspectives.

Gastric Cancer Incidence and Mortality After Endoscopic Resection of Gastric Adenoma: A Nationwide Cohort Study.

INTRODUCTION: Gastric adenoma is a precursor lesion of gastric cancer. We investigated whether the removal of gastric adenoma prevented gastric cancer incidence and its mortality. METHODS: Using the linkage of nationwide databases, we assessed gastric cancer incidence and mortality among patients who had gastric adenomas removed between 2011 and 2013 in Korea. These outcomes were compared primarily with those of the Korean general population by estimating the standardized incidence and mortality ratio and secondarily with internal control subjects who did not have gastric neoplasm after esophagogastroduodenoscopy and were matched for age, sex, and calendar year by calculating hazard ratios (HR) with the Cox proportional hazards model. RESULTS: We identified 44,405 adenoma removal patients. During a median follow-up of 8.4 years, 1,038 (2.34%) of them were given a diagnosis of gastric cancer and a total of 524 gastric cancers were expected for a standard incidence ratio of 1.98 (95% confidence interval [CI], 1.84-2.13). A total of 199 deaths from gastric cancer were expected and 99 were observed for a standard mortality ratio of 0.50 (95% CI, 0.40-0.60). Compared with the nonadenoma cohort (n = 39,826), the adenoma removal patients had a higher risk of gastric cancer (HR, 2.84; 95% CI, 2.51-3.21) and associated mortality (HR, 1.66; 95% CI, 1.19-2.31). DISCUSSION: Removal of gastric adenoma resulted in lower-than-expected mortality but higher-than-expected incidence due to gastric cancer than that in the general population. Our analyses indicated the importance of follow-up strategy after removal of gastric adenoma.

Real-World Outcomes of On- vs Off-pump Coronary Bypass Surgery: Result From Korean Nationwide Cohort.

BACKGROUND: Although several randomized trials have shown conflicting results regarding the comparative effectiveness of on- and off-pump coronary artery bypass grafting (CABG), research on long-term outcomes in large-scale, real-world clinical settings are limited. The study sought to examine the comparative effectiveness of on- and off-pump CABG in a real-world clinical setting. METHODS: Using the nationwide claims database of the Korean National Health Insurance Service, the study identified patients who underwent isolated CABG from 2004 to 2013. Propensity-score matching with multivariable adjustment was used to assemble a cohort of patients with similar baseline characteristics. RESULTS: Among 23 828 patients, 12 639 in the off-pump group (53.0%) and 11 189 in the on-pump group (47.0%) were enrolled. After matching, 6483 pairs were included in the final analysis. At 30 days, there was no significant difference in adjusted mortality between the off- and on-pump groups (hazard ratio [HR], 1.00; 95% CI, 0.87-1.16). During long-term follow-up (100% complete; median, 5.3 years; maximum, 13.2 years), however, off-pump CABG was associated with a higher risk of mortality than on-pump CABG (HR, 1.09; 95% CI, 1.03-1.15). The risks of myocardial infarction (HR, 1.3; 95% CI, 1.16-1.45) and repeat revascularization (HR, 1.50; 95% CI, 1.37-1.63) were also significantly higher in the off-pump CABG group than in the on-pump CABG group, whereas the stroke risk was similar between the groups (HR, 0.99; 95% CI, 0.87-1.13). CONCLUSIONS: In this contemporary, nationwide, clinical practice claim registry, off-pump CABG was associated with higher long-term risks of mortality, myocardial infarction, and repeat revascularization than on-pump CABG.

Underutilisation of Physical Rehabilitation Therapy by Cancer Patients in Korea: a Population-based Study of 958,928 Korean Cancer Patients.

BACKGROUND: Advanced cancers are associated with more severe symptoms and greater impairment. Although most patients with metastatic cancer would benefit from rehabilitation, few patients receive appropriate rehabilitation therapy. We explored the use of rehabilitation therapy by cancer patients. Our data represented the entire population of Korea. The analyses were performed according to cancer type and stage. METHODS: We extracted rehabilitation utilization data of patients newly diagnosed with cancer in the period of 2011-2015 from the Korea Central Cancer Registry, which is linked to the claims database of the National Health Insurance Service (n = 958,928). RESULTS: The utilisation rate increased during the study period, from 6.0% (11,504) of 192,835 newly diagnosed patients in 2011 to 6.8% (12,455) of 183,084 newly diagnosed patients in 2015. Patients with central nervous system (28.4%) and bone (27.8%) cancer were most likely to undergo physical rehabilitation. The rehabilitation rate was higher in patients with metastatic than localised or regional cancer (8.7% vs. 5.3% vs. 5.5%). CONCLUSION: This claims-based study revealed that rehabilitation therapy for cancer patients is underutilised in Korea. Although patients with metastasis underwent more intensive rehabilitation than patients with early stage cancer, those without brain and bone tumours (the treatment of which is covered by insurance) were less likely to use rehabilitation services. Further efforts to improve the use of rehabilitation would improve the outcomes of cancer patients.

The Korean Hypertension Cohort study: design and baseline characteristics.

BACKGROUND/AIMS: Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. METHODS: The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. RESULTS: This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. CONCLUSION: The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.

Tenofovir disoproxil fumarate on the risk of hepatocellular carcinoma in chronic hepatitis B patients with failure to preceding treatments: A nationwide cohort study.

Tenofovir disoproxil fumarate (TDF) monotherapy is recommended for the treatment of chronic hepatitis B (CHB) patients who are refractory to other drugs. Yet, little data are available for the effectiveness of TDF monotherapy compared with TDF-based combination therapy on the risk of hepatocellular carcinoma (HCC) and death/transplantation. This nationwide population-based cohort study included 11,289 CHB patients who initiated TDF rescue therapy after failure of preceding treatments between 2012 and 2014 in Korea. The risks of HCC and death/transplantation were compared between TDF combotherapy (n = 2,499) and TDF monotherapy (n = 8,790) groups. The findings were validated in a hospital cohort of 1,163 CHB patients. In the nationwide cohort, during 44.2 months of overall treatment duration, 529 patients developed HCC and 190 died or received transplantation. In the 2,499 propensity score-matched pairs, compared with TDF combotherapy, TDF monotherapy showed no significantly different risks of HCC (1.11/100 person-year [PY] vs. 1.32/100 PY; HR 1.23, 95% CI 0.95-1.60, p = .12) and death/transplant (0.43/100 PY vs. 0.42/100 PY; HR 1.04, 95% CI 0.67-1.60, p = .87). However, in the 469 propensity score-matched pairs of cirrhosis subcohort, TDF monotherapy was associated with a higher risk of HCC than TDF combotherapy (HR 1.46, 95% CI 1.002-2.12, p = .049). In the validation hospital cohort, TDF monotherapy was not associated with significantly different risks of HCC and death/transplant in the entire cohort and cirrhosis subcohort. In CHB patients with failure to preceding treatments, TDF monotherapy showed no higher risks of HCC and death/transplantation compared with TDF combotherapy. However, the comparative effectiveness of rescue TDF monotherapy should be further clarified in cirrhotic patients since the findings were not consistent in the nationwide and hospital cohorts.

Do Cardiac Rehabilitation Affect Clinical Prognoses Such as Recurrence, Readmission, Revascularization, and Mortality After AMI?: Systematic Review and Meta-Analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to analyze the effects of cardiac rehabilitation (CR) on post-discharge prognoses of patients with acute myocardial infarction (AMI). METHODS: A literature search was conducted through four international medical and two Korean databases. Primary outcomes for the effectiveness of CR included all-cause mortality, cardiovascular mortality, recurrence, revascularization, major adverse cardiovascular event, major adverse cardiocerebrovascular event, and readmission. We summarized and analyzed results of studies about CR for AMI, including not only randomized controlled trials (RCTs) but also non-RCTs. We calculated the effect size separately by the study type. RESULTS: Fourteen articles were finally selected. Of these, two articles were RCTs, while 12 were non-RCTs. In RCTs, the overall mortality rate was lower in the group that participated in CR than that in the conventional care group by 28% (relative risk=0.72; 95% confidence interval, 0.34-1.57). Among non-RCTs, CR participation significantly decreased the overall risk of mortality. Moreover, the rates of recurrence and major adverse cardiovascular events were lower in the group that participated in CR compared to those in the non-CR group. CONCLUSION: The meta-analysis shows that CR reduces the risk of re-hospitalization and all-cause mortality after AMI, compared to no participation in CR. This outcome was seen in RCTs as well as in non-RCTs. More studies are necessary for concrete conclusions about the beneficial effects of CR after AMI in various settings.

High level of medication adherence is required to lower mortality in patients with chronic hepatitis B taking entecavir: A nationwide cohort study.

It is unclear whether suboptimal adherence contributes to adverse clinical outcomes in patients with chronic hepatitis B (CHB). Moreover, there is no consensus regarding the optimal level of drug adherence. This was a population-based historical cohort study including 51 975 adult CHB patients treated with entecavir (0.5 mg/d orally). Data were obtained from the Korean national health insurance service claims database, which covers >99% of the entire population, between 2007 and 2015. Medication adherence was categorized as high (proportion of days covered [PDC], ≥90%; n = 32 089), intermediate (PDC, 80%-89%; n = 10 197) and low (PDC, <80%; n = 9689). During a median 4.5 years (maximal 9 years) of follow-up in 51 975 CHB patients treated with entecavir, multivariable analyses revealed that the risk of mortality/transplantation was significantly greater in the low-adherers (adjusted hazard ratio [HR], 1.38; P < .001) and intermediate-adherers (adjusted HR, 1.44; P < .001) than the high-adherers (P for trend < 0.001). The risk of renal failure in the low- and intermediate-adherence groups was also significantly higher than the high-adherence group (P for trend < 0.001). By contrast, the risk of hepatocellular carcinoma (HCC) was not significantly different between groups (P for trend = 0.70). The higher risk of mortality/transplantation and renal failure but similar risk of HCC for low- and intermediate-adherers compared with high-adherers was consistent in inverse probability treatment weighting analysis of the entire cohort and subcohorts with or without cirrhosis. In conclusion, high medication adherence (≥90%) is required to significantly lower risk of mortality and renal failure in patients with CHB during long-term treatment with entecavir.

Cardiac rehabilitation and 5-year mortality after acute myocardial infarction. Report from 11 tertiary hospitals in Korea (ETHIK Study).

BACKGROUND: The participation rate for cardiac rehabilitation (CR) remains low in some Europe and Asia including Korea. AIM: To investigate effects of CR on prognosis improvements in terms of recurrence, readmission, revascularization, and mortality rates in patients with acute myocardial infarction (AMI) in Korea. DESIGN: A retrospective cohort study. SETTING: Eleven Tertiary Hospitals In Korea (ETHIK Study). POPULATION: Data from a total of 7299 patients between January 2012 and December 2015 were collected, of which data from 7136 patients were linked to insurance claims data. In the final analysis, 6743 patients were included. METHODS: Patients who participated in the CR program while receiving outpatient treatment were classified into CR group. Those who did not participate in CR programs were classified into the non-CR group. RESULTS: Kaplan-Meier survival analyses showed five-year survival rate of 96.9% in the CR group and 93.3% in the non-CR group. The hazard ratio (HR) for total 5-year mortality in the CR group was approximately 0.41 (95% CI: 0.27-0.63) times that of the non-CR group, indicating a reduction in the risk of mortality by approximately 59% in propensity score weighted cohort of 1878 patients. The HR for major adverse cardiac events (MACE) with respect to 5-year mortality, MI recurrence, revascularization, and readmission due to cardiovascular disease in CR group was 0.96 times that of non-CR group (95% CI: 0.83-1.12), without significant difference between the two groups. CONCLUSIONS: In this study, 5-year mortality decreased by 59% in patients with AMI who had participated in CR compared to those who did not. CLINICAL REHABILITATION IMPACT: This finding should be very helpful in emphasizing the need for CR in a country like Korea where CR has not yet been actively implemented.

Incidence and Outcomes of Sepsis in Korea: A Nationwide Cohort Study From 2007 to 2016.

OBJECTIVES: This study aimed to estimate the incidence and clinical outcomes of sepsis in Korea from 2007 to 2016. DESIGN: Retrospective observational study. SETTING: Nationwide study with population-based healthcare reimbursement claims database. PATIENTS: Using data from the National Health Insurance Service of Korea, patients who were hospitalized with a diagnosis of sepsis from 2007 to 2016 were analyzed. The incidence of sepsis was calculated using mid-year census population and analyzed according to year, age, and sex. The Elixhauser Comorbidity Index score was calculated to adjust for the impact of comorbidities on clinical outcome. In-hospital mortality, hospital length of stay, ICU admission rates, and risk factors for in-hospital mortality were also analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence of sepsis increased from 173.8 per 100,000 population in 2007 to 233.6 per 100,000 population in 2016. In-hospital mortality decreased from 30.9% in 2007 to 22.6% in 2016 (p < 0.0001). From 2007 to 2016, hospital length of stay and ICU admission rates associated with sepsis decreased from 26.0 ± 33.5 days to 21.3 ± 24.4 days (p < 0.0001) and from 16.2% to 12.7% (p < 0.0001), respectively. Male sex, age greater than 50 years, Elixhauser Comorbidity Index greater than 10, and mechanical ventilation were identified as risk factors for in-hospital mortality after adjusting for baseline characteristics. CONCLUSIONS: The incidence of sepsis in Korea increased from 2007 to 2016, while the associated in-hospital mortality, hospital length of stay, and ICU admission rates decreased.

Time- and Dose-Dependent Association of Statin Use With Risk of Clinically Relevant New-Onset Diabetes Mellitus in Primary Prevention: A Nationwide Observational Cohort Study.

Background Given that statins are increasingly being used for primary-prevention, the public concerns regarding the risk of new-onset diabetes mellitus associated with statin use may be an issue. Methods and Results Using healthcare data from the national health insurance examinees, our study comprised a cohort of adults aged ≥40 years with hypercholesterolemia who would be eligible for statin therapy for primary prevention from 2005 to 2012. The primary outcome was the occurrence of clinically relevant new-onset diabetes mellitus requiring medical therapy. Among 2 162 119 adults with hypercholesterolemia who might be eligible for statin therapy, 638 625 (29.5%) ever used statins and 1 523 494 (70.5%) never used statins. In the propensity-matched cohort of 518 491 pairs, during mean follow-up of 3.9 years, being an ever-user of statin was significantly associated with diabetes mellitus risk compared with being a never-user of statin (13.4 versus 6.9 per 1000 person-years; adjusted hazard ratio [ HR ], 1.88; 95% CI , 1.85-1.93). With increasing duration of statin use, the risk of diabetes mellitus was proportionally increased ( HR 1.25 <1 year, HR 2.22 for 1-2 years, and HR 2.62 >2 years). An excess risk of diabetes mellitus was also associated with a higher intensity ( HR 1.75 for low-to-moderate potency and HR 2.31 for high potency) and a cumulative dosing of statin ( HR 1.06 for low-tertile, HR 1.74 for middle-tertile, and HR 2.52 for high-tertile of defined-daily-disease). Conclusions In patients receiving statin therapy for primary prevention, there was a time- and dose-dependent association of statin use with an increasing risk of new-onset diabetes mellitus.

Procalcitonin-Guided Treatment on Duration of Antibiotic Therapy and Cost in Septic Patients (PRODA): a Multi-Center Randomized Controlled Trial.

BACKGROUND: The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. METHODS: In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. RESULTS: The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6-10 days vs. 14 days; IQR, 12-21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. CONCLUSION: PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02202941.

Risk of Hepatocellular Carcinoma in Patients Treated With Entecavir vs Tenofovir for Chronic Hepatitis B: A Korean Nationwide Cohort Study.

Importance: Entecavir and tenofovir disoproxil fumarate have comparable efficacy in achieving surrogate end points, including virologic response, and are equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). However, it is unclear whether treatment with these drugs is associated with equivalent clinical outcomes, especially development of hepatocellular carcinoma (HCC). Objective: To compare entecavir and tenofovir in terms of the risk of HCC and death or liver transplant in patients with CHB infection. Design, Setting, and Participants: A nationwide historical population cohort study involving treatment-naive adult patients with CHB who started treatment with entecavir (n = 11 464) or tenofovir disoproxil fumarate (n = 12 692) between January 1, 2012, and December 31, 2014, using data from the Korean National Health Insurance Service database. As validation, a hospital cohort of patients with CHB treated with entecavir (n = 1560) or tenofovir (n = 1141) in a tertiary referral center between January 1, 2010, and December 31, 2016, were analyzed. Nationwide cohort data were retrieved from January 1, 2010, to December 31, 2016, and hospital cohort data from January 1, 2010, to October 31, 2017. Main Outcomes and Measures: Cumulative incidence rates of HCC and death and transplant rates. Results: Among the population cohort of 24 156, the mean (SD) age was 48.9 (9.8) years, and 15 120 patients (62.6%) were male. Among the hospital cohort of 2701, the mean (SD) age was 48.8 (10.5) years and 1657 patients (61.3%) were male. In the population cohort, the annual incidence rate of HCC was significantly lower in the tenofovir group (0.64 per 100 person-years [PY]) than in the entecavir group (1.06 per 100 PY). By multivariable-adjusted analysis, tenofovir therapy was associated with a significantly lower risk of HCC (hazard ratio [HR], 0.61; 95% CI, 0.54-0.70) and all-cause mortality or transplant (HR, 0.77; 95% CI, 0.65-0.92) compared with entecavir. The tenofovir group also showed a significantly lower risk of HCC in the 10 923-pair propensity score-matched population cohort (HR, 0.62; 95% CI, 0.54-0.70) and 869-pair propensity score-matched hospital cohort (HR, 0.68; 95% CI, 0.46-0.99) compared with the entecavir group. Conclusions and Relevance: This study suggests that tenofovir treatment was associated with a significantly lower risk of HCC compared with entecavir treatment in a population-based cohort of adults with CHB; these findings were validated in a hospital cohort. Given the poor prognosis of patients with HCC, these findings may have considerable clinical implications in prevention of this cancer in patients with CHB infection.