Clinical and economic burden of immune tolerance induction in entire patients with hemophilia A: Insights from a real-world Korean setting.

INTRODUCTION: The most notable challenge facing hemophilia A treatment is the development of inhibitors against factor VIII, resulting in increased clinical and socioeconomic burdens due to the need for expensive bypassing agents (BPAs). Although immune tolerance induction (ITI) is currently the primary approach for inhibiting and reducing the inhibitors, the lengthy duration of ITI necessitates the continued use of BPA to manage bleeding episodes. In this study, we aimed to obtain real-world evidence on the clinical and economic aspects and associated burdens experienced by patients with hemophilia A with inhibitors undergoing ITI in Korea. METHODS: Claims data from January 1, 2007, to December 31, 2020, were used in this study. The study cohort comprised patients with hemophilia A undergoing ITI, who were categorized into three groups: successful, failed, or continuation of ITI. We evaluated clinical and economic burdens, including monthly healthcare visits, medication costs, and total medical expenses. RESULTS: The study involved 33 cases of ITI across 32 patients. Excluding seven continuation cases where success could not be determined at the observation point, the estimated success rate of ITI was 80.8 %. The median duration of ITI for all patients was 25.7 months. While no significant disparities were noted in the ITI duration between successful and unsuccessful cases (24.51 vs. 25.66 months), substantial discrepancies were observed in the duration of BPA usage (11.10 vs. 25.66 months) and the number of prescribed BPAs (1.79 vs. 2.97). CONCLUSION: Successful ITI reduced both clinical and economic burdens, resulting in decreased monthly medication expenses and overall medical costs.

Expert survey on real-world data utilization and real-world evidence generation for regulatory decision-making in drug lifecycle in Korea.

As the importance of utilizing real-world data (RWD)/real-world evidence (RWE) for supporting regulatory scientific decision-making continues to grow, experiences and inputs from experts become crucial for developing a systematic and practice-oriented plan for the use of fit-for-purpose RWD/RWE. This study aimed to survey relevant experts from government agencies, industries, and academia to identify prerequisites for the drug life cycle in Korea. The questionnaire comprised the following: (A) the definition and categories of RWD/RWE, (B) the suitability and feasibility of using RWD/RWE at each authorization stage by the types of RWD, and (C) the challenges and solutions for the use of RWD/RWE. A total of 46 respondents completed the online survey, with 89.1% of them having prior experience with RWD/RWE usage. A majority of respondents agreed that RWD can be obtained from various sources. Among these sources, the registry was the most suitable source. It is suitable to compensate for the limitations of randomized control trials and ensure quality in data collection. Though there was consensus among the respondents for the use of RWD/RWE in post-marketing surveillance, the use of such data in new drug application (NDA) was disagreeable. Respondents considered it necessary to write a protocol in advance for RWD collection and RWE generation, for all RWD types. In conclusion, this study examined the perceptions of experts for RWD/RWE use at each approval stage of drugs. The results suggest that guidelines for the fit-for-purpose use of RWD/RWE should be developed via careful deliberation among experts in the future.

Cost-Effectiveness of Intravascular Imaging-Guided Complex PCI: Prespecified Analysis of RENOVATE-COMPLEX-PCI Trial.

BACKGROUND: Although clinical benefits of intravascular imaging-guided percutaneous coronary intervention (PCI) in patients with complex coronary artery lesions have been observed in previous trials, the cost-effectiveness of this strategy is uncertain. METHODS: RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance vs Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) was conducted in Korea between May 2018 and May 2021. This prespecified cost-effectiveness substudy was conducted using Markov model that simulated 3 states: (1) post-PCI, (2) spontaneous myocardial infarction, and (3) death. A simulated cohort was derived from the intention-to-treat population, and input parameters were extracted from either the trial data or previous publications. Cost-effectiveness was evaluated using time horizon of 3 years (within trial) and lifetime. The primary outcome was incremental cost-effectiveness ratio (ICER), an indicator of incremental cost on additional quality-adjusted life years (QALYs) gained, in intravascular imaging-guided PCI compared with angiography-guided PCI. The current analysis was performed using the Korean health care sector perspective with reporting the results in US dollar (1200 Korean Won, ₩=1 dollar, $). Willingness to pay threshold was $35 000 per QALY gained. RESULTS: A total of 1639 patients were included in the trial. During 3-year follow-up, medical costs ($8661 versus $7236; incremental cost, $1426) and QALY (2.34 versus 2.31; incremental QALY, 0.025) were both higher in intravascular imaging-guided PCI than angiography-guided PCI, resulting incremental cost-effectiveness ratio of $57 040 per QALY gained within trial data. Conversely, lifetime simulation showed total cumulative medical cost was reversed between the 2 groups ($40 455 versus $49 519; incremental cost, -$9063) with consistently higher QALY (8.24 versus 7.89; incremental QALY, 0.910) in intravascular imaging-guided PCI than angiography-guided PCI, resulting in a dominant incremental cost-effectiveness ratio. Consistently, 70% of probabilistic iterations showed cost-effectiveness of intravascular imaging-guided PCI in probabilistic sensitivity analysis. CONCLUSIONS: The current cost-effectiveness analysis suggests that imaging-guided PCI is more cost-effective than angiography-guided PCI by reducing medical cost and increasing quality-of-life in complex coronary artery lesions in long-term follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03381872.

Recent updates on treatment patterns in patients with treated attention-deficit/hyperactivity disorders from a nationwide real-world database in South Korea.

The prevalence of attention-deficit/hyperactivity disorder (ADHD) is steadily increasing across Korea. We analyzed ADHD patients with ADHD medications (Rx) characteristics and treatment patterns compared to patients without Rx and identified the differences between pediatric-/adult- and active-/transient-patients with Rx. Using a nationwide claims dataset from 2020 to 2021, we conducted a prevalence-based cross-sectional study and analyzed the recent patients' characteristics and patterns among ADHD patients. Among 132 017 ADHD patients with Rx, differences from 20 312 without Rx across all characteristics except sex. We found significant differences in characteristics and treatment patterns between pediatric-/adult- and active-/transient-patients with Rx. Age-specific sex ratios notably diverged in pediatric patients (61.2%), but remained similar in adults, revealing significant psychiatric comorbidities differences. Active-patients peaked at 6-11 years (41.4%), while transient-patients at 18-30 years (36.1%). Predominantly, methylphenidate (89.7%), atomoxetine (27.8%), and clonidine (2.8%) were prescribed, with 85% experiencing treatment changes within methylphenidate formulations. In pediatric patients, extended-release methylphenidate was preferred (56.1%), adults favored oral delivery system methylphenidate (71.5%), and active-patients had higher treatment rates than transient-patients across all patterns, with low monotherapy rates. This study provides epidemiologic insights into recent characteristics and treatment patterns of ADHD patients with Rx in Korea, providing valuable evidence for identifying those actively receiving ADHD treatment in future healthcare policy decisions.

Cost-Effectiveness of Fractional Flow Reserve-Guided Treatment for Acute Myocardial Infarction and Multivessel Disease: A Prespecified Analysis of the FRAME-AMI Randomized Clinical Trial.

Importance: Complete revascularization by non-infarct-related artery (IRA) percutaneous coronary intervention (PCI) in patients with acute myocardial infarction is standard practice to improve patient prognosis. However, it is unclear whether a fractional flow reserve (FFR)-guided or angiography-guided treatment strategy for non-IRA PCI would be more cost-effective. Objective: To evaluate the cost-effectiveness of FFR-guided compared with angiography-guided PCI in patients with acute myocardial infarction and multivessel disease. Design, Setting, and Participants: In this prespecified cost-effectiveness analysis of the FRAME-AMI randomized clinical trial, patients were randomly allocated to either FFR-guided or angiography-guided PCI for non-IRA lesions between August 19, 2016, and December 24, 2020. Patients were aged 19 years or older, had ST-segment elevation myocardial infarction (STEMI) or non-STEMI and underwent successful primary or urgent PCI, and had at least 1 non-IRA lesion (diameter stenosis >50% in a major epicardial coronary artery or major side branch with a vessel diameter of ≥2.0 mm). Data analysis was performed on August 27, 2023. Intervention: Fractional flow reserve-guided vs angiography-guided PCI for non-IRA lesions. Main Outcomes and Measures: The model simulated death, myocardial infarction, and repeat revascularization. Future medical costs and benefits were discounted by 4.5% per year. The main outcomes were quality-adjusted life-years (QALYs), direct medical costs, incremental cost-effectiveness ratio (ICER), and incremental net monetary benefit (INB) of FFR-guided PCI compared with angiography-guided PCI. State-transition Markov models were applied to the Korean, US, and European health care systems using medical cost (presented in US dollars), utilities data, and transition probabilities from meta-analysis of previous trials. Results: The FRAME-AMI trial randomized 562 patients, with a mean (SD) age of 63.3 (11.4) years. Most patients were men (474 [84.3%]). Fractional flow reserve-guided PCI increased QALYs by 0.06 compared with angiography-guided PCI. The total cumulative cost per patient was estimated as $1208 less for FFR-guided compared with angiography-guided PCI. The ICER was -$19 484 and the INB was $3378, indicating that FFR-guided PCI was more cost-effective for patients with acute myocardial infarction and multivessel disease. Probabilistic sensitivity analysis showed consistent results and the likelihood iteration of cost-effectiveness in FFR-guided PCI was 97%. When transition probabilities from the pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials were used, FFR-guided PCI was more cost-effective than angiography-guided PCI in the Korean, US, and European health care systems, with an INB of $3910, $8557, and $2210, respectively. In probabilistic sensitivity analysis, the likelihood iteration of cost-effectiveness with FFR-guided PCI was 85%, 82%, and 31% for the Korean, US, and European health care systems, respectively. Conclusions and Relevance: This cost-effectiveness analysis suggests that FFR-guided PCI for non-IRA lesions saved medical costs and increased quality of life better than angiography-guided PCI for patients with acute myocardial infarction and multivessel disease. Fractional flow reserve-guided PCI should be considered in determining the treatment strategy for non-IRA stenoses in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02715518.

Effects of the coronavirus disease outbreak on the development of neurological disorders in children: A comparison of the incidence of febrile seizure and epilepsy using an interrupted time-series approach.

BACKGROUND: With the outbreak of COVID-19, school closures and quarantines following social distancing have brought significant changes to children's lifestyles. Therefore, we aimed to compare the population-adjusted incidence of febrile seizures(FS) and epilepsy before and after the COVID-19 outbreak in Korea and to assess the effects of the COVID-19 outbreak on the incidence by region and age group. METHODS: A retrospective cohort study was conducted using nationwide claims data and covid data from January 2019 to December 2020. The incidence of diseases and difference in incidence before (Jan 20 to Dec 30, 2019) and after (Jan 20 to Dec 30, 2020) the COVID-19 outbreak was measured using rate ratio. An Interrupted time series analysis was used to identify the effect of COVID-19 on trends of FS and epilepsy. Subgroup analysis by age, sex, insurance, and risk of coronavirus by area were conducted. RESULTS: Following the onset of the pandemic, the number of newly diagnosed FS cases decreased sharply by 69 % (24,182 to 7238), whereas the incidence of epilepsy, increased to 1.02 times (30,286-29,312), when adjusted in proportion to the population. Notably, a greater decrease in the incidence of FS were found in the regions with high-risk of coronavirus. A result of segmented regression analysis proved the decrease was significant and made immediately after the pandemic started(p < 0.001). In contrast to the incidence of FS, that of epilepsy did not exhibit a significant month-to-month change during the baseline period, immediately after the pandemic started, and during the pandemic. CONCLUSIONS: The COVID-19 outbreak and resulting social distancing measures reduced the incidence of febrile seizure immediately rather than gradually. Unlike in the case of acute febrile seizure, the COVID-19 pandemic had no effect on the incidence of chronic epilepsy.

Association between selective serotonin reuptake inhibitor use and developing irritable bowel syndrome through retrospective analysis.

BACKGROUND AND AIM: Serotonin affects the balance and integrity of the gut microbiome; however, studies have confirmed the influence of selective serotonin reuptake inhibitors (SSRIs) on irritable bowel syndrome (IBS). We evaluated the association between SSRI use and subsequent IBS occurrence in a real-world setting. METHODS: A multivariate Cox proportional hazard model was adopted, and the National Health Insurance Service cohort claims database between 2010 and 2019 was used. Non-SSRI users were selected using the propensity score matching method. Subgroup analyses were performed using the point of use, cumulative dose, and duration of SSRI use. Additional analysis was performed using a control group without psychiatric medications. RESULTS: We included 2901 SSRI users and 2727 non-SSRI users. After adjusting covariates, the risk of developing IBS in SSRI users was 1.54 times that in non-SSRI users (95% confidence interval [CI]: 1.01-2.33). The hazard ratio (HR) of the recent, heavy, and short-term user groups were 3.19 (95% CI: 2.03-4.99), 2.22 (95% CI: 1.50-3.29), and 4.83 (95% CI: 3.02-7.73), respectively, compared with that of non-users. In patients without a history of psychiatric medications, the risk of IBS incidence after SSRI use increased significantly (HR: 1.61, 95% CI: 1.06-2.42), whereas HR was insignificant in patients with a history of psychiatric medications (HR: 1.25, 95% CI: 0.98-1.60). CONCLUSIONS: The risk of subsequent IBS occurrence following SSRI use was high in patients who initially took a heavy SSRI dose and those who did not have a history of psychiatric drug use.

Exploring the health literacy status of people with hearing impairment: a systematic review.

BACKGROUND: People with hearing impairment have many problems with healthcare use, which is associated with health literacy. Research on health literacy is less focused on people with hearing impairments. This research aimed to explore the levels of health literacy in people with hearing impairment, find the barriers to health literacy, and summarize methods for improving health literacy. METHODS: A systematic review was conducted using three databases (PubMed, Cochrane, and Embase) to search the relevant articles and analyze them. The studies were selected using pre-defined inclusion/exclusion criteria in two steps: first, selection by examining the title and abstract; and second, after reading the study in full. The Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) was used to assess the quality of the articles. RESULTS: Twenty-nine studies were synthesized qualitatively. Individuals with hearing impairment were found to have lower health literacy, when compared to those without impairment, which can lead to a higher medical cost. Most of the people with hearing impairment faced barriers to obtaining health-related information and found it difficult to communicate with healthcare providers. To improve their health literacy, it is essential to explore new ways of accessing health information and improving the relationship between patients and healthcare providers. CONCLUSIONS: Our findings show that people with hearing impairment have lower health literacy than those without. This suggests that developing new technology and policies for people with hearing impairment is necessary not to mention promoting provision of information via sign language. TRIAL REGISTRATION: OSF: https://doi.org/10.17605/OSF.IO/V6UGW . PROSPERO ID: CRD42023395556.

New Evidence of Oral Branched-Chain Amino Acid Supplementation on the Prognosis of Patients With Advanced Liver Disease.

INTRODUCTION: Oral branched-chain amino acids (BCAAs) might benefit patients with advanced liver disease. We assess its effects on prognosis compared with control from the meta-analysis. METHODS: Study end points were development of hepatic encephalopathy (HE), hepatocellular carcinoma (HCC), mortality, and overall liver-related events (LREs). Risk ratios (RRs) and hazard ratios (HRs) were calculated using random effects model and heterogeneity using I 2 statistic. RESULTS: Twenty-eight studies were included in this meta-analysis; 1,578 and 1,727 patients in oral BCAAs and control groups, respectively. From studies using RRs as outcome measures, oral BCAAs were better in preventing HE and LRE than controls, with RRs 0.684 (95% confidence interval [CI] 0.497-0.941; P = 0.019) and 0.788 (95% CI 0.585-0.810; P < 0.001), respectively. Oral BCAAs had marginal effect on preventing HCC compared with control, with RR 0.791 (95% CI 0.619-1.011; P = 0.061); no significant difference in mortality was detected. From studies using HRs as outcome measures, oral BCAAs were superior to control in preventing LRE with adjusted HR 0.497 (95% CI 0.321-0.770; P = 0.002). In subgroups undergoing HCC resection, oral BCAAs had beneficial effect in preventing HE (RR 0.716, 95% CI 0.514-0.996; P = 0.047) and LRE (RR 0.716, 95% CI 0.595-0.860; P < 0.001). DISCUSSION: Oral BCAAs could afford clinical benefits in reducing HE and LRE risks, especially among patients undergoing HCC resection.

Comparison of Netarsudil/Latanoprost Therapy with Latanoprost Monotherapy for Lowering Intraocular Pressure: A Systematic Review and Meta-analysis.

PURPOSE: Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma. METHODS: We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy. RESULTS: Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each. CONCLUSIONS: Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.

Real-world clinical features, health-care utilization, and economic burden in decompensated cirrhosis patients: A national database.

BACKGROUND: Patients with decompensated cirrhosis are well known to experience morbidity and mortality. AIM: We assessed clinical characteristics, health-care utilization, and economic burden according to the type, number, and combination of decompensation-related complications. METHODS: We used recent nationally representative sample data from 2016 to 2018, covering approximately 13% of hospitalized patients in South Korea annually. Decompensation-related complications included ascites, hepatic encephalopathy (HE), gastroesophageal variceal (GEV) bleeding, and hepatorenal syndrome (HRS). RESULTS: Among 14 601 patients with decompensated cirrhosis, 11 201 (76.7%) experienced ≥ 1 decompensation-related complications, and approximately three-quarters underwent hospitalization. The most prevalent decompensation-related complications were ascites (54.8%), GEV bleeding (33.2%), HE (27.4%), and HRS (3.6%). Patients with GEV bleeding exhibited the highest hospitalization rate (95.7%), and patients with HE or HRS underwent hospitalization for 4 weeks/year due to decompensated cirrhosis. Hospitalization costs were 1.9 times higher in patients with HRS than in those with ascites alone ($9022 vs $4673; P < 0.01). Once patients developed decompensation-related complications, 41.3% had ≥ 2 types of decompensation-related complications. As the number of decompensation-related complications increased from 0 to ≥ 3, health-care utilization and economic burden significantly increased in a stepwise manner; patients with ascites, GEV bleeding, and HE visited medical institutions 2.2 times more (11 vs 5/year; P < 0.01) and incurred 6.4 times greater medical expenditure ($11 060 vs $1728/year; P < 0.01) than those with ascites only. CONCLUSION: A substantial proportion of patients had multiple decompensation-related complications and socioeconomic burdens for decompensated cirrhosis considering admission rate, hospital stay, and costs increased markedly, depending on the number of decompensation-related complications.

Cost-effectiveness of antiviral therapy in untreated compensated cirrhosis patient with serum HBV-DNA level < 2000 IU/mL.

BACKGROUND: Due to stringent reimbursement criteria, significant numbers of patients with compensated cirrhosis (CC) and low-level viremia [LLV; serum hepatitis B virus (HBV)-DNA levels of 20-2000 IU/mL] remain untreated especially in the East Asian countries, despite potential risk of disease progression. We analyzed cost-effectiveness to assess rationales for antiviral therapy (AVT) for this population. METHODS: We compared cost and effectiveness (quality-adjusted life years, QALYs) in a virtual cohort including 10,000 54-year-old CC-LLV patients receiving AVT (Scenario I) versus no treatment (Scenario II). A Markov model, including seven HBV-related conditions, was used. Values for transition probabilities and costs were mostly obtained from recent real-world South Korean data. RESULTS: As per a simulation of a base-case analysis, AVT reduced costs by $639 USD and yielded 0.108 QALYs per patient for 5 years among CC-LLV patients compared to no treatment. Thus, AVT is a cost-saving option with lower costs and better effectiveness than no treatment. If 10,000 patients received AVT, 815 incident cases of hepatocellular carcinoma (HCC) and 630 HBV-related deaths could be averted in 5 years compared to no treatment. In case of 10-year observation, AVT was consistently dominant. Even when the transition probabilities from CC-LLV vs. maintained virological response to HCC were same, fluctuation of results also lied within willingness-to-pay in South Korea. In the probabilistic sensitivity analysis with the willingness-to-pay threshold, the probability of AVT cost-effectiveness was 100%. CONCLUSION: The extended application of AVT in CC-LLV patients may contribute positively to individual clinical benefits and national healthcare budgets.

Efficacy and Safety of Opicapone for Motor Fluctuations as an Adjuvant to Levodopa Therapy in Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy. OBJECTIVE: We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa. METHODS: We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups. RESULTS: Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = -71.39, -28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments. CONCLUSION: Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.

Cost-effectiveness of chronic hepatitis C screening and treatment.

Hepatitis C virus (HCV) infection is the second most common cause of chronic liver disease in South Korea, with a prevalence ranging from 0.6% to 0.8%, and HCV infection incidence increases with age. The anti-HCV antibody test, which is cheaper than the HCV RNA assay, is widely used to screen for HCV infections; however, the underdiagnosis of HCV is a major barrier to the elimination of HCV infections. Although several risk factors have been associated with HCV infections, including intravenous drug use, blood transfusions, and hemodialysis, most patients with HCV infections present with no identifiable risk factors. Universal screening for HCV in adults has been suggested to improve the detection of HCV infections. We reviewed the cost-effectiveness of HCV screening and the methodologies used to perform screening. Recent studies have suggested that universal HCV screening and treatment using direct-acting antivirals represent cost-effective approaches to the prevention and treatment of HCV infection. However, the optimal timing and frequency of HCV screening remain unclear, and further studies are necessary to determine the best approaches for the elimination of HCV infections.

Association between depression and antibiotic use: analysis of population-based National Health Insurance claims data.

BACKGROUND: Frequent exposure to antibiotic treatments may increase the risk of antibiotic resistance, which may threaten the effectiveness of future antibiotic treatments. Thus, it is important to identify the preventable risks in terms of antibiotic use. This study assessed the association between major depressive disorder (MDD) and antibiotic use by comparing the likelihood and extent of antibiotic use between patients with and without MDD. METHODS: This retrospective cross-sectional study utilized the National Patients Sample data from the 2017 Health Insurance Review and Assessment Service. We analyzed 16,950 patients with MDD, defined as those with at least two claims records stating a primary diagnosis of MDD (International Classification of Diseases, 10th revision codes F32-33) and 67,800 patients without MDD (1:4 propensity-score matched control group). Antibiotic use was compared between the patients with and without MDD based on three variables: the presence of antibiotic prescriptions, total prescription days of antibiotics per year, and total medication costs of antibiotics per year. RESULTS: The adjusted odds ratio obtained by multivariate regression analysis for the presence of prescription of antibiotics was 1.31 (95% confidence interval [CI]: 1.25-1.36). In the negative binomial model, the number of prescription days was 1.25 times (95% CI: 1.23-1.28) higher in patients with MDD than in those without MDD. Generalized linear model analysis showed a 1.39-fold (95% CI: 1.36-1.43) higher cost of antibiotic prescription in patients with MDD than in those without MDD. CONCLUSIONS: Our results suggest a potential association between MDD and the prescription of antibiotics, implying that patients with MDD are relatively vulnerable to infections. It is important to prevent as well as closely monitor the occurrence of infections when managing patients with MDD.

Epidemiological Features and Economic Burden of Guillain-Barré Syndrome in South Korea: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: Guillain-Barré syndrome (GBS) is rare, but its symptoms are severe and they occasionally lead to long-term disability. Country-specific epidemiological evidence is useful for detecting potential problems at the population level. This study investigated the epidemiological and economic characteristics of GBS in South Korea. METHODS: The Korean National Health Insurance Service claims data from 2010 to 2016 were used to identify incident cases as newly hospitalized patients with a primary diagnosis of GBS (the 10th revision of the International Classification Disease code of G61.0). New cases were defined as patients not having claim records for GBS within one year prior to the hospital admission for GBS. RESULTS: The incidence rate increased by 45.6% between 2010 and 2016, from 1.28 to 1.82 per 100,000 population. All age groups other than <20 years showed increasing trends. The incidence rate was highest in those aged 65 years to 74 years. Approximately 72% of the incident GBS cases had antecedent infection within 42 days before GBS was diagnosed. Children younger than 10 years constituted the highest proportion of antecedent infections (93.7%). The average length of stay per GBS hospitalization was 33.5 days. Patients had an average of 7.48 outpatient visits for GBS treatment per year. The economic burden from a societal perspective of treating GBS during the first year was USD 16,428. CONCLUSIONS: The increasing incidence trend and substantial economic burden of GBS strongly advocate the development of effective strategies for preventing and managing GBS.

Cost-Effectiveness Analysis of Antiviral Therapy for Untreated Minimally Active Chronic Hepatitis B to Prevent Liver Disease Progression.

INTRODUCTION: Antiviral therapy (AVT) for chronic hepatitis B (CHB) can prevent liver disease progression. Because of its stringent reimbursement criteria, significant numbers of patients with untreated minimally active (UMA)-CHB exist, although they are still subject to disease progression. We thus performed a cost-effectiveness analysis to assess the rationale for AVT for UMA-CHB. METHODS: We compared cost and effectiveness (quality-adjusted life years, QALYs) in virtual UMA-CHB cohorts of 10,000 50-year-olds receiving AVT (scenario 1) vs no treatment (scenario 2) for 10 years. A Markov model, including 7 health states of CHB-related disease progression, was used. Values for transition probabilities and costs were mostly obtained from recent South Korean data. RESULTS: The simulation of AVT vs no treatment predicted $2,201 incremental costs and 0.175 incremental QALYs per patient for 10 years, with an incremental cost-effectiveness ratio (ICER) of $12,607/QALY, suggesting cost-effectiveness of AVT. In sum, if 10,000 patients received AVT, 720 incident hepatocellular carcinoma and 465 CHB-related more deaths could be averted in 10 years relative to no treatment. When the simulated analysis period was extended to 20 years, AVT was also highly cost-effective with an ICER of $2,036/QALY. Although hepatocellular carcinoma-related mortality was a major factor influencing ICER, its fluctuation can be accepted within willingness to pay of $33,000 in South Korea. According to probabilistic sensitivity analysis with the threshold of willingness to pay, the probability of AVT cost-effectiveness was 83.3%. DISCUSSION: Long-term AVT for patients with UMA-CHB may contribute positively toward individual clinical benefit and national health care budget.

Cost-utility analysis of emicizumab prophylaxis in haemophilia A patients with factor VIII inhibitors in Korea.

AIMS: Haemophilia A patients with factor VIII inhibitors (HAPI) experience frequent spontaneous bleeding, approximately once a week, and require expensive bypassing agent (BPA) treatments to control bleeding over their lifetime. According to the HAVEN 1 trial, weekly emicizumab (Hemlibra®) prophylaxis injection reduces annualized bleeding rates (ABR) by 87% compared with BPA on-demand treatment (BPA-OD) administered at the time of bleeding. Our study aimed to assess the cost-effectiveness of emicizumab prophylaxis in HAPI in Korea. METHODS: Using a lifetime Markov model with health states of 'alive with bleeds' and 'dead', we simulated the experience of HAPI receiving emicizumab prophylaxis (treatment arm) or BPA-OD (control arm) and estimated expected clinical and economic outcomes under each treatment arm. Model parameters included comparative effectiveness, clinical and epidemiologic characteristics of Korean HAPI, costs of drug treatment and medical events and utility for 'alive with bleeds' state under each treatment. We utilized local data, including National Health Insurance claims data, national statistics, literature and expert surveys with haematologists. RESULTS: Base-case analysis results showed that compared with BPA-OD, lifetime emicizumab prophylaxis prevented 807 bleedings, extended 3.04 quality-adjusted life-years and reduced costs by 2.6 million US dollars. Thus, emicizumab prophylaxis is a dominant treatment option with better effectiveness and lower costs than BPA-OD. A series of one-way sensitivity analyses consistently showed dominant results, confirming that lifetime emicizumab prophylaxis is a cost-saving intervention for HAPI. CONCLUSION: Emicizumab prophylaxis is an excellent treatment choice reducing ABR, improving quality of life and reducing costs.

Assessing the effects of National Health Insurance reimbursement policy revisions for anti-osteoporotic drugs in Korean women aged 50 or older.

INTRODUCTION: The Korean National Health Insurance revised its reimbursement criteria to expand coverage for anti-osteoporotic drug treatments in 2011 (expanding diagnostic criteria and the coverage period for anti-osteoporotic therapy) and 2015 (including osteoporotic fracture patients regardless of bone mineral density). We examined whether the two revisions contributed to an increase in the prescription rates of anti-osteoporotic drugs in Korea. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Sample data from 2010 through 2016. A segmented regression analysis of interrupted time series was performed to assess changes in the monthly prescription rates of anti-osteoporotic drugs among women aged 50 or older, defined as the proportion of elderly women prescribed with anti-osteoporotic drugs. RESULTS: Both the levels (i.e., abrupt jump or drop) and the trends (i.e., slope) of the prescription rates of anti-osteoporotic drugs in the general population, osteoporotic patients, and osteoporotic fracture patients showed no significant changes after the first revision. However, there was a significant increase in the trends in the general population (ß = 0.0166, p = 0.0173) and in osteoporotic patients (ß = 0.1128, p = 0.0157) after the second revision. Women aged 65 to 79 years were the most significantly increased group in terms of the treatment proportion after the second revision because the trend was significant after the second revision in all three study populations (ß = 0.0300, 0.1212, 0.1392, respectively; p < 0.05). CONCLUSIONS: Although the two revisions expanded reimbursement coverage, only the second revision on reimbursing based on osteoporotic fracture regardless of bone mineral density was associated with increasing the proportion of post-menopausal women being treated with anti-osteoporotic drugs.

Cost-utility analysis of pralatrexate for relapsed or refractory peripheral T-cell lymphoma based on a case-matched historical control study along with single arm clinical trial.

BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) treated with pralatrexate have previously shown superior overall survival (OS) compared to those who underwent conventional chemotherapy (CC, 15.4 vs. 4.07 months). We conducted an economic evaluation of pralatrexate from a societal perspective in Korea based on data from the PROPEL phase II study. METHODS: Using a Markov model with a weekly cycle, we simulated the experience of patients with R/R PTCL receiving pralatrexate or CC for 15 years. The model consists of five health states; initial treatment, treatment pause, subsequent treatment, stem cell transplantation (SCT) success, and death. Comparative effectiveness was based on PROPEL phase II single-arm study and its matched historical control analysis. Costs included drug, drug administration, monitoring, adverse event management, and SCT costs. RESULTS: The incremental cost-effectiveness ratio of the base case was $39,153 per quality-adjusted life-year (QALY) gained. The results of one-way sensitivity analysis ranged from $33,949 to $51,846 per QALY gained, which remained within an implicit willingness-to-pay (WTP) threshold of anticancer drugs in Korea. CONCLUSIONS: Pralatrexate is a cost-effective intervention with improved OS and incremental costs within the WTP limit. Pralatrexate could function as a new therapeutic option for patients suffering from life-threatening R/R PTCL.