Association between dietary supplements and frailty: a cross-sectional study using national survey data in South Korea.

We aimed to examine the association between the use of specific types of dietary supplements and frailty using cross-sectional, nationally representative survey data. Adults aged ≥50 years in the Korea National Health and Nutrition Examination Survey 2018-2020 were included. We calculated a 46-item frailty index to assess frailty. In total, 27,384 older adults were included (mean age: 62.47 years; median frailty index: 0.12). Among them, 72% used at least one dietary supplement. The prevalence of dietary supplement use was higher among women than among men and in participants with higher socioeconomic status. Compared to non-users, users of dietary supplements had a healthier diet and nutrient intake, and lower levels of frailty. After adjusting for socioeconomic and dietary factors, users of vitamin C, red ginseng or calcium were found to be significantly less frail. Our findings indicate promising results concerning dietary supplement intake in managing frailty among older Korean adults.

Impact of aging on acute myeloid leukemia epidemiology and survival outcomes: A real-world, population-based longitudinal cohort study.

Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated the epidemiology and survival rates of patients diagnosed with de novo acute myeloid leukemia in South Korea from Jan 1, 2011, to Aug 31, 2020. We used real-world data from the Health Insurance Review and Assessment Service database. We observed an increase in the number of acute myeloid leukemia cases, with age-specific incidence rates escalating in older patients. In contrast a long-term decrease from 1.94 to 1.77 per 100,000 individuals was found in the age-standardized incidence rates. Meanwhile, age-standardized prevalence rates ascended from 8.93 to 9.67 per 100,000 individuals, with a remarkable increase in the age-specific prevalence rate for those aged 80 years and above. Survival rates were notably better in younger or treated patients, and in those who underwent Hematopoietic stem cell transplantation. The time of diagnosis did not affect the survival of patients younger than 65 years. However, the most recent survival rates were significantly lower for patients 65 or older, as shown in the unadjusted Cox survival analysis. After adjustments in the analysis, it was found that the overall survival rates of the most recently diagnosed group improved significantly compared with those diagnosed earlier, with a hazard ratio of 0.90 (95% confidence interval, 0.84-0.97). This improvement may potentially be influenced by the enhanced treatment alternatives available for newly diagnosed older patients aged 65 years or older. In conclusion, aging appears to fuel an increase in the number of acute myeloid leukemia cases and mortality. Further studies are warranted to understand the impact of aging on acute myeloid leukemia treatment outcomes and devise efficacious care strategies for older patients.

The Risk of Venous Thromboembolism and Ischemic Stroke Stratified by VTE Risk Following Multiple Myeloma: A Korean Population-Based Cohort Study.

Background: Multiple myeloma (MM) is associated with high morbidity and mortality, with elevated rates of arterial thrombosis and venous thromboembolism (VTE) and ischemic stroke (IS). We aimed to estimate the incidence of VTE and IS categorized by the VTE risk grade among individuals with MM in Korea. Additionally, we explored the potential of the IMPEDE VTE score as a tool for assessing IS risk in patients with MM. Methods: This retrospective cohort study comprised 37,168 individuals aged ≥ 18 years newly diagnosed with MM between January 2008 and December 2021 using the representative claims database of the Korean population. The risk of the incidence of VTE and IS within 6 months after MM diagnosis was stratified based on high-risk (IMPEDE VTE score ≥ 8) and low-risk (<8) categories. The hazard ratios (HRs) were estimated using Cox proportional hazard models. Results: The VTE incidence was 120.4 per 1000 person-years and IS incidence was 149.3 per 1000 person-years. Statistically significant differences were observed in the cumulative incidence rates of VTE between groups with high and low VTE scores (p < 0.001) and between individuals aged ≤ 65 years (p < 0.001) and those with a Charlson comorbidity index (CCI) ≥ 3 compared to lower scores (p < 0.001). Additionally, the cumulative incidence rate of IS differed significantly across all groups (p < 0.001). The HR for the high-risk group in VTE and IS occurrence was 1.59 (95% CI, 1.26-2.00) and 3.47 (95% CI, 2.99-4.02), respectively. Conclusions: It is important to screen and manage high-risk groups for the early development of VTE or IS in patients with newly diagnosed MM.

Effectiveness of Acupotomy Combined with Epidural Steroid Injection for Lumbosacral Radiculopathy: A Randomized Controlled Pragmatic Pilot Study.

Background and Objectives: This pilot study aimed to evaluate the clinical effectiveness, cost-effectiveness, and safety of acupotomy combined with epidural steroid injection (ESI) in lumbosacral radiculopathy and examine its feasibility for the main study. Materials and Methods: This randomized, controlled, two-arm, parallel, assessor-blinded, pragmatic study included 50 patients with severe lumbosacral radiculopathy who had insufficient improvement after an ESI. Patients were randomized (1:1 ratio) into a combined treatment (acupotomy + ESI, experimental) and an ESI single treatment (control) group. Both groups underwent a total of two ESIs once every 2 weeks; the experimental group received eight additional acupotomy treatments twice a week for 4 weeks. Types of ESI included interlaminar, transforaminal, and caudal approaches. Drugs used in ESI comprised a 5-10 mL mixture of dexamethasone sodium phosphate (2.5 mg), mepivacaine (0.3%), and hyaluronidase (1500 IU). The primary outcome was the difference in changes from baseline in the Oswestry Disability Index (ODI) scores between the groups at weeks 4 and 8. The incremental cost-utility ratio (ICUR) was calculated to evaluate the cost-effectiveness between the groups. Adverse events (AEs) were assessed at all visits. Results: Mean ODI scores for the experimental and control groups were -9.44 (95% confidence interval [CI]: -12.71, -6.17) and -2.16 (95% CI: -5.01, 0.69) at week 4, and -9.04 (95% CI: -12.09, -5.99) and -4.76 (95% CI: -7.68, -1.84) at week 8, respectively. The difference in ODI score changes was significant between the groups at week 4 (p = 0.0021). The ICUR of the experimental group versus the control group was as economical as 18,267,754 won/quality-adjusted life years. No serious AEs were observed. Conclusions: These results demonstrate the potential clinical effectiveness and cost-effectiveness of acupotomy combined with ESI for lumbosacral radiculopathy and its feasibility for a full-scale study. Larger, long-term follow-up clinical trials are needed to confirm these findings.

Patient-Centered Economic Burden of Exudative Age-Related Macular Degeneration: Retrospective Cohort Study.

BACKGROUND: Exudative age-related macular degeneration (AMD), one of the leading causes of blindness, requires expensive drugs such as anti-vascular endothelial growth factor (VEGF) agents. The long-term regular use of effective but expensive drugs causes an economic burden for patients with exudative AMD. However, there are no studies on the long-term patient-centered economic burden of exudative AMD after reimbursement of anti-VEGFs. OBJECTIVE: This study aimed to evaluate the patient-centered economic burden of exudative AMD for 2 years, including nonreimbursement and out-of-pocket costs, compared with nonexudative AMD using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS: This retrospective cohort study was conducted using the OMOP CDM, which included 2,006,478 patients who visited Seoul National University Bundang Hospital from June 2003 to July 2019. We defined the exudative AMD group as patients aged >50 years with a diagnosis of exudative AMD and a prescription for anti-VEGFs or verteporfin. The control group was defined as patients aged >50 years without a diagnosis of exudative AMD or a prescription for anti-VEGFs or verteporfin. To adjust for selection bias, controls were matched by propensity scores using regularized logistic regression with a Laplace prior. We measured any medical cost occurring in the hospital as the economic burden of exudative AMD during a 2-year follow-up period using 4 categories: total medical cost, reimbursement cost, nonreimbursement cost, and out-of-pocket cost. To estimate the average cost by adjusting the confounding variable and overcoming the positive skewness of costs, we used an exponential conditional model with a generalized linear model. RESULTS: We identified 931 patients with exudative AMD and matched 783 (84.1%) with 2918 patients with nonexudative AMD. In the exponential conditional model, the total medical, reimbursement, nonreimbursement, and out-of-pocket incremental costs were estimated at US $3426, US $3130, US $366, and US $561, respectively, in the first year and US $1829, US $1461, US $373, and US $507, respectively, in the second year. All incremental costs in the exudative AMD group were 1.89 to 4.25 and 3.50 to 5.09 times higher in the first and second year, respectively, than those in the control group (P<.001 in all cases). CONCLUSIONS: Exudative AMD had a significantly greater economic impact (P<.001) for 2 years on reimbursement, nonreimbursement, and out-of-pocket costs than nonexudative AMD after adjusting for baseline demographic and clinical characteristics using the OMOP CDM. Although economic policies could relieve the economic burden of patients with exudative AMD over time, the out-of-pocket cost of exudative AMD was still higher than that of nonexudative AMD for 2 years. Our findings support the need for expanding reimbursement strategies for patients with exudative AMD given the significant economic burden faced by patients with incurable and fatal diseases both in South Korea and worldwide.

Efficacy of complement inhibitors for patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan has revolutionized the management of PNH, leading to improvements in overall survival and quality of life for patients. Objectives: This systematic review aims to provide comprehensive evidence of the efficacy of complement inhibitors in relation to treatment duration. Design: This is a systematic review and meta-analysis. Data sources and methods: A thorough literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library up to 3 May 2022. We included all prospective interventional studies including single-arm trials. The primary outcomes of interest were lactate dehydrogenase (LDH) levels, hemoglobin (Hb) concentrations, transfusion avoidance, and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores. Results: Our study included a total of 27 studies, comprising 5 randomized controlled trials and 11 single-arm trials, with a total of 912 patients with PNH. We stratified the studies according to treatment duration, based on the most frequently reported period of 26 weeks. Our analysis showed that treatment-naïve patients who received complement inhibitors had a pooled estimate of a decrease in LDH levels from baseline by -1462.0 U/L (95% CI: -1735.6 to -1188.5) for treatment ⩽26 weeks and -1696.5 U/L (95% CI: -2122.7 to -1270.2) for treatment >26 weeks. The mean Hb levels were increased by 1.4 g/dL (95% CI: 0.5-2.3) and 1.9 g/dL (95% CI: 0.7-3.1) in each group. Treatment with any complement inhibitor prevented the need for transfusion in at least 50% of patients with PNH in all treatment periods. Clinically meaningful improvements in FACIT-F were observed both before and after 26 weeks, with a pooled estimate of 6.8 (95% CI: 6.0-7.6) and 9.5 (95% CI: 7.0-12.0), respectively. Conclusion: Our findings suggest that complement inhibitors can result in positive treatment outcomes and sustained benefits for patients with PNH.

Predicting Unmet Healthcare Needs in Post-Disaster: A Machine Learning Approach.

Unmet healthcare needs in the aftermath of disasters can significantly impede recovery efforts and exacerbate health disparities among the affected communities. This study aims to assess and predict such needs, develop an accurate predictive model, and identify the key influencing factors. Data from the 2017 Long-term Survey on the Change of Life of Disaster Victims in South Korea were analyzed using machine learning techniques, including logistic regression, C5.0 tree-based model, and random forest. The features were selected based on Andersen's health behavior model and disaster-related factors. Among 1659 participants, 31.5% experienced unmet healthcare needs after a disaster. The random forest algorithm exhibited the best performance in terms of precision, accuracy, Under the Receiver Operating Characteristic (AUC-ROC), and F-1 scores. Subjective health status, disaster-related diseases or injuries, and residential area have emerged as crucial factors predicting unmet healthcare needs. These findings emphasize the vulnerability of disaster-affected populations and highlight the value of machine learning in post-disaster management policies for decision-making.

Comparative Efficacy of Venetoclax-Based Combination Therapies and Other Therapies in Treatment-Naive Patients With Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy: A Network Meta-Analysis.

OBJECTIVES: This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and decitabine monotherapies and best supportive care (BSC) in adults with untreated acute myeloid leukemia ineligible for intensive chemotherapy. METHODS: A systematic literature review and feasibility assessment was conducted to select phase III randomized controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs) with higher values indicating a higher likelihood of being effective. RESULTS: A total of 1140 patients across 5 trials were included. VEN + LDAC (SUCRA 91.4%) and VEN + AZA (87.5%) were the highest ranked treatments for complete remission + complete remission with incomplete blood count recovery. VEN + LDAC was associated significantly higher response rates versus AZA (odds ratio 5.64), LDAC (6.39), and BSC (23.28). VEN + AZA was also associated significantly higher response rates than AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN + AZA (SUCRA: 95.2%) and VEN + LDAC (75.9%) were the highest ranked treatments. VEN + AZA was associated with significant improvements in OS compared with AZA (hazard ratio 0.66), LDAC (0.57), and BSC (0.37), and VEN + LDAC was associated with significant improvements in OS compared with LDAC (0.70) and BSC (0.46). CONCLUSIONS: VEN + AZA and VEN + LDAC demonstrated improved efficacy compared with alternative therapies among treatment-naive patients with acute myeloid leukemia ineligible for intensive chemotherapy.

Use of gastrointestinal prokinetics and the risk of parkinsonism: A population-based case-crossover study.

BACKGROUND: The disease burden of parkinsonism is extremely costly in the United States. Unlike Parkinson's disease, drug-induced parkinsonism (DIP) is acute and reversible; exploring the causative drug is important to prevent DIP in patients at high-risk of parkinsonism. OBJECTIVE: To examine whether the use of gastrointestinal (GI) prokinetics is associated with an increased risk of parkinsonism. METHODS: We conducted a case-crossover study using nationally representative data. We included patients who were newly diagnosed with parkinsonism (ICD-10 G20, G21.1, G25.1) between January 1, 2007 and December 1, 2015. The first prescription date of G20, G21.1, or G25.1 diagnoses was defined as the index date (0 day). Patients with prior extrapyramidal and movement disorders or brain tumors were excluded. We assessed the exposure within the risk (0-29 days) and control periods (60-89 days), before or on the index date. Conditional logistic regression estimated the adjusted odds ratio (aOR) for parkinsonism. RESULTS: Overall, 2268 and 1674 patients were exposed to GI prokinetics during the risk and control periods, respectively. The use of GI prokinetics significantly increased the occurrence of parkinsonism (aOR = 2.31; 95% Confidence Interval [CI], 2.06-2.59). The use of GI prokinetics was associated with a higher occurrence of parkinsonism in elderly patients (≥65 years old; aOR = 2.69; 95% CI, 2.30-3.14) than in younger patients (aOR = 1.90; 95% CI, 1.59-2.27). CONCLUSIONS: The use of GI prokinetics was significantly associated with higher occurrences of parkinsonism, necessitating close consideration when using GI prokinetics.

Early impact of COVID-19 social distancing on social determinants of health and their effects on mental health and quality of life of Korean undergraduate students.

Introduction: This study aimed to investigate the association between social determinants of health and perception of COVID-19 social distancing/mental health/quality of life during COVID-19 social distancing in Korean undergraduate students using online survey data augmented with natural language processing. Methods: An online cross-sectional survey including sociodemographic characteristics, students' perceptions of COVID-19 social distancing, and social determinants of health was conducted between July and November in 2020. We conducted logistic regression analysis to investigate the relationship between social determinants of health (independent variables) and perceptions of COVID-19 social distancing, mental health, and quality of life (dependent variables). This association was augmented using sentiment analysis and word clouds by visualizing open-ended comments on COVID-19 social-distancing policies. Results: Data were collected from 1,276 undergraduate students. Participants who experienced negative impacts on their social-networking activities due to COVID-19 social distancing were at significantly higher odds to perceive COVID-19 social distancing as not being beneficial [odds ratio (OR) = 1.948, 95% confidence interval (CI) 1.254-3.027], to have increased stress levels (OR = 1.619, 95% CI 1.051-2.496), and to experience decreased quality of life over 5 weeks (OR = 2.230, 95% CI 1.448-3.434) against those who answered neutrally. In contrast, Participants who reported positive perceptions of social-networking activities during the COVID-19 pandemic had lower odds of feeling depressed or anxious (OR = 0.498, 95% CI 0.278-0.894) and reporting a low quality of life over 5 weeks (OR = 0.461, 95% CI 0.252-0.842) compared to those who reported neutral perceptions. Furthermore, the results of the word cloud and sentiment analyses showed that most students perceived social distancing negatively. Conclusions: The government's social-distancing policy to prevent the spread of COVID-19 may have had a negative impact, particularly on undergraduate students' social-networking activities. This highlights the need for greater social support for this population, including access to psychotherapeutic resources, and improvements in policies to prevent infectious diseases while still maintaining social connections.

Treatment Changes and Prognoses in Patients with Incident Drug-Induced Parkinsonism Using a Korean Nationwide Healthcare Claims Database.

This retrospective cohort study assessed treatment changes and prognoses after incident drug-induced parkinsonism (DIP). We used the National Health Insurance Service's National Sample Cohort database in South Korea. We selected patients diagnosed with incident DIP and given prescriptions to take offending drugs (antipsychotics, gastrointestinal (GI) motility drugs, or flunarizine) for a period of time that overlapped with the time of DIP diagnosis during 2004-2013. The proportion of patients experiencing each type of treatment change and prognosis was assessed for 2 years after DIP diagnosis. We identified 272 patients with incident DIP (51.9% of patients were aged ≥ 60 years and 62.5% of them were women). Switching (38.4%) and reinitiation (28.8%) were the most common modifications in GI motility drug users, whereas dose adjustment (39.8%) and switching (23.0%) were common in antipsychotic users. The proportion of persistent users was higher among antipsychotic users (7.1%) than that among GI motility drug users (2.1%). Regarding prognosis, 26.9% of patients experienced DIP recurrence or persistence, the rate being the highest in persistent users and the lowest in patients who discontinued the drug. Among patients with incident DIP diagnoses, the patterns of treatment change and prognosis differed across the types of offending drugs. Over 25% of patients experienced DIP recurrence or persistence, highlighting the need for an effective strategy to prevent DIP.

A population-based study on the risk of prescription opioid abuse in patients with chronic opioid use and cost-effectiveness of prescription drug monitoring program using a patient simulation model in South Korea.

BACKGROUND: Concerns regarding the burden of inappropriate opioid use are growing. We examined the association between prescription opioid abuse and patient characteristics and estimated the cost-effectiveness of the prescription drug monitoring program (PDMP) implemented in South Korea, considering patient-level information. METHODS: A retrospective cohort study was conducted to explore the association between opioid abuse and patient characteristics using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. We selected non-cancer patients with chronic opioid use and investigated the incidence of opioid abuse between 2010 and 2015. The association between opioid abuse and patient characteristics was assessed using the Cox proportional hazards model. The cost-effectiveness of the PDMP was assessed using discrete event simulation (DES) with a time horizon of 30 years from a societal perspective. Time-to-event data and event costs were obtained from the NHIS-NSC database. The abuse rate was adjusted for each patient based on the baseline characteristics and history of abuse experienced in the model. Program effectiveness, program costs, and health-state utilities were obtained from the published literature. The incremental cost-utility ratio (ICUR) was estimated at a discount rate of 5% for both costs and quality-adjusted life-years (QALYs). RESULTS: We identified 22,524 patients with chronic opioid use in the NHIS-NSC database. Every one-year increase in age (hazard ratio: 1.002 [95% CI: 1.000-1.003]), medical aid program (1.130 [95% CI: 1.072-1.191]), high Charlson Comorbidity Index (1.054 [95% CI: 1.044-1.065]), and history of opioid abuse (1.501 [95% CI: 1.391-1.620] and 3.005 [95% CI: 2.387-3.783] for 1-2 and ≥3 abuse events, respectively) significantly increased the risk of opioid abuse. In the DES, the PDMP was cost-effective, with an estimated ICUR of $2,227/QALY, which was most affected by the program's effectiveness. CONCLUSION: Patient characteristics and history of opioid abuse affected the risk of opioid abuse. Considering patient-level information, the PDMP implemented in South Korea is likely to be cost-effective.

Motivating factors of compliance to government's COVID-19 preventive guidelines: An investigation using discrete choice model.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) has resulted in a worldwide pandemic. We aimed to identify the factors that motivate public compliance with the government's COVID-19 preventive recommendations. METHODS: Focus group interviews were conducted to identify influencing factors. The relative importance of each factor was investigated through a survey, based on a discrete choice model, from February to June, 2021 in South Korea. RESULTS: "Severity of COVID-19 symptoms" (relative importance [magnitude of attribute coefficients]: 28.40%) and "risk of infection" (27.50%) were the most influential health-related factors, followed by social consequences of infection, including "cessation of social activities due to self-quarantine" (19.77%), "risk of personal information being disclosed when infected and social criticism on the infected person" (15.78%), and "risk of spreading infection" (8.55%). Respondents behaved differently based on their socioeconomic characteristics and COVID-19 experience. DISCUSSION: The perceived severity of symptoms was a strong motivator among fragile individuals, such as women and older adults. "Cessation of social activities" was the most influential factor for those infected with COVID-19, while "risk of infection" was for those whose acquaintances were infected. CONCLUSIONS: The provision of information regarding COVID-19 to the public must be tailored based on an understanding of behavioral differences.

Exploring the prevalence and characteristics of adverse drug events among older adults in South Korea using a national health insurance database.

Background: Adverse drug events (ADEs) in the elderly frequently occur because of their multiple chronic diseases and complexity of drug therapy. To better understand adverse drug events, the prevalence and characteristics of adverse drug events in elderly South Korean patients were assessed. Methods: The National Health Insurance databases for 2015 and 2016 were used for the analysis. We included patients aged ≥65 years that had at least one claim with the diagnosis codes 'drug-induced,' 'poisoning by drug,' and 'vaccine-associated' each year for the base-case analysis. To minimize the underestimation of adverse drug event prevalence, we also used an extended definition analysis by adding the 'adverse drug event very likely' codes. We estimated the prevalence of adverse drug events by sex, age group, and type of insurance and examined the frequent types of adverse drug events in 2015 and 2016. Results: In the base-case analysis, adverse drug event prevalence in individuals aged 65 years and older was 2.75% in 2015 and 2.77% in 2016. With advanced age, the prevalence of adverse drug event tended to increase, peaking in the age group of 75-79 years. In addition, the adverse drug event prevalence was higher in females and Medical Aid enrollees. The most frequently occurring adverse drug event was 'allergy, unspecified,' followed by 'other drug-induced secondary parkinsonism,' and 'generalized skin eruption due to drugs and medicaments.' When we examined the extended definition analysis, the prevalence of adverse drug events was 4.47% in 2015 and 4.52% in 2016, which significantly increased from those estimated in the base-case analysis. Conclusion: Among the older adults, the prevalence of adverse drug event was higher in advanced age, females, and Medical Aid enrollees. In particular, allergy and drug-induced secondary parkinsonism frequently occurred. This study provides evidence that health policies addressing the prevention and management of adverse drug events should be a priority for the most vulnerable elderly patients.

Economic burden of opioid misuse focused on direct medical costs.

Background: Since their development, synthetic opioids have been used to control pain. With increased opioid use, problematic opioid prescription has also increased, resulting in a growing economic burden. However, there is a paucity of research studies on the economic burden of prescription opioid misuse in Asia, especially South Korea. Objectives: To estimate the incremental economic burden of prescription opioid misuse for the South Korean population. Methods: The National Health Insurance Service-National Sample Cohort database, covering 2% of the South Korean population between 2010 and 2015, was analyzed. Outpatients aged 18 or older who took one or more prescription opioids were selected. Based on their opioid prescription patterns, patients were classified into opioid misuse and non-misuse groups. The direct medical costs per person per year (PPPY) and the incremental economic burden of the opioid misuse group were explored using an exponential conditional model with a suitable distribution and log link function. All analyses were performed using SAS® Enterprise Guide version 9.4, and p < 0.05 was considered statistically significant. Results: The number of patients who had ≥1 opioid prescription was 345,020 including 84,648 (24.53%) in the opioid misuse group and 260,372 (75.47%) in the non-misuse group. The adjusted mean direct medical costs PPPY were estimated to be USD 401 for the opioid misuse group, which is 1.49 times significantly higher than that for the non-misuse group (p < 0.0001). The incremental economic burden of the opioid misuse group in the South Korean population was estimated to be approximately USD 0.52 billion for the period 2010-2015. Conclusion: Prescription opioid misuse was significantly associated with the increased economic burden. Along with proper policies for using opioids, it is necessary to monitor opioid prescription patterns to prevent opioid misuse and reduce the related economic burden.

Evaluation of Factors Associated with Adverse Drug Events in South Korea Using a Population-Based Database.

This retrospective study aims to investigate the factors associated with the occurrence of ADEs using nationally representative claims data. All patients with at least one claim with diagnosis codes denoting potential ADE between 1 July 2015 and 31 December 2015 were included. Potential ADE was defined as ADE identified in the claims data, because it was not verified. The index date was defined as the date of the first claim with potential ADEs. Demographic data were collected at the index date, while data on comorbidities and number of medications used were collected six months before the index date. Multivariate logistic regression was used to explore the association between potential ADEs and several factors, including sex, age group, insurance type, comorbidities, and number of prescribed medications. Patients with potential ADEs were older, had more chronic diseases, and used more medications than those without potential ADEs. In the multivariate analysis, occurrence of potential ADEs was associated with age (≥65 years, odds ratio [OR] 1.15, 95% confidence interval [CI] 1.08-1.21), Medical Aid program (OR 1.37, 95% CI 1.27-1.47), Charlson Comorbidity Index scores (≥5, OR 2.87, 95% CI 2.56-3.20), and use of six or more medications (6-10 medications, OR 1.89, 95% CI 1.79-1.99). Age, Medical Aid program, comorbidities, and number of medications were associated with occurrence of potential ADEs.

The impact of migraine and probable migraine on productivity loss in Korea: A cross-sectional online survey.

Migraine is an enormous burden on society, but relevant studies are limited. The population of interest of this study was migraine or probable migraine (PM) in Korea. In this population, we aimed to assess the productivity loss through the level of severity defined by monthly migraine days (MMD) and analgesic frequency and to estimate costs and associated factors of productivity loss. We conducted an online survey of adults with migraine symptoms. We defined migraine and PM using the modified International Classification of Headache Disorders, second edition. Severity level was defined by subgroups of MMD (0-3, 4-14, and ≥15 days) and analgesic frequency (0, 1, 2, 3, and ≥4 per week). Productivity loss was assessed using the Work Productivity and Activity Impairment questionnaire and consisted of absenteeism, presenteeism, overall work productivity loss, and activity impairment. The costs of productivity loss due to absenteeism and presenteeism were calculated in 2020 USD. We used negative binomial regression to identify the factors associated with the costs of productivity loss. We identified 362 respondents with migraine or PM. Mean age was 41.7 years, 75.7% were female (N = 274), and 73.2% (N = 265) were employed. On average, productivity losses due to absenteeism and presenteeism were 8.1% and 39.7%, respectively. As MMD increased, there was a trend toward increased activity impairment, presenteeism, and overall work productivity loss. The mean overall productivity loss cost was USD 44.61 per person per day. Duration of migraine attacks was significantly associated with higher absenteeism costs. The results of this study indicate that the higher the MMD, the greater the productivity loss in patients with migraine or PM in Korea. We also found that patients with low-frequency migraine and PM experienced substantial productivity loss. This study provides comprehensive evidence of the burden of migraine in Korea using a representative sample.

Impact of Integrating Machine Learning in Comparative Effectiveness Research of Oral Anticoagulants in Patients with Atrial Fibrillation.

We aimed to compare the ability to balance baseline covariates and explore the impact of residual confounding between conventional and machine learning approaches to derive propensity scores (PS). The Health Insurance Review and Assessment Service database (January 2012-September 2019) was used. Patients with atrial fibrillation (AF) who initiated oral anticoagulants during July 2015-September 2018 were included. The outcome of interest was stroke/systemic embolism. To estimate PS, we used a logistic regression model (i.e., a conventional approach) and a generalized boosted model (GBM) which is a machine learning approach. Both PS matching and inverse probability of treatment weighting were performed. To evaluate balance achievement, standardized differences, p-values, and boxplots were used. To explore residual confounding, E-values and negative control outcomes were used. In total, 129,434 patients were identified. Although all baseline covariates were well balanced, the distribution of continuous variables seemed more similar when GBM was applied. E-values ranged between 1.75 and 2.70 and were generally higher in GBM. In the negative control outcome analysis, slightly more nonsignificant hazard ratios were observed in GBM. We showed GBM provided a better ability to balance covariates and had a lower impact of residual confounding, compared with the conventional approach in the empirical example of comparative effectiveness analysis.

Clinical and economic impact of changing reimbursement criteria for statin treatment among patients with type 2 diabetes mellitus in South Korea.

Aim: Patients with type 2 diabetes mellitus (T2DM) in South Korea can be reimbursed for statins if they have a low-density lipoprotein cholesterol (LDL-C) level of ≥100 mg/dL. We aimed to explore the clinical and economic benefit received by T2DM patients when easing the current criteria for statin treatment by lowering the LDL-C threshold from 100 mg/dL to 70 mg/dL. Methods: We used a static course model with a 5-year period to compare the following two scenarios in T2DM patients with no history of cardiovascular (CV) events: the current criteria covering LDL-C ≥100 mg/dL and the revised criteria covering LDL-C ≥70 mg/dL. The number of target patients was estimated based on previous Korean studies on patients with T2DM. The current mix of treatments used for T2DM and costs involving CV events were estimated using the National Health Insurance Service-National Health Screening Cohort database. The baseline CV event rates and case fatality were estimated using NHIS Customized database, including 50% patients who were prescribed atorvastatin and 100% who were not prescribed statins between 2009 and 2012 among patients with T2DM in the entire Korean population. After propensity score matching, patients with T2DM not prescribed statins were followed up until 2018 to estimate the incidence rates of coronary heart disease (CHD) and stroke. The efficacy of atorvastatin for the primary prevention of CV events in patients with T2DM was derived from a pivotal clinical trial. The outcome measures were the number of CV events prevented after the change in criteria and the consequent cost savings. Results: In South Korea, the current and revised criteria covered 2,434,379 and 3,446,149 patients with T2DM, respectively. The change in criteria resulted in the prevention of 726 CV events and cost savings of US dollars (USD) 5.5 million at the national level and USD 0.0089 per member per month in the fifth year. Conclusion: Easing the reimbursement criteria for statin treatment among patients with T2DM was associated with a reduction in CV events and their related costs; therefore, changing the reimbursement criteria is worth further consideration to mitigate the burden of CV disease.

Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses.

We conducted systematic reviews and meta-analyses to evaluate the efficacy of melatonin versus placebo or other hypnotic agents in improving sleep quality and quantity in patients with chronic insomnia. A literature search on Ovid-MEDLINE, EMBASE, and the Cochrane Library was performed up to November 2020. Sleep onset latency, total sleep time, sleep efficiency, sleep quality and quality of life were examined as outcomes. We identified 24 randomized controlled trials of chronic insomnia including four studies of patients with comorbid insomnia. All studies were compared with placebo. Due to heterogeneity, we conducted subgroup analyses by age group. In non-comorbid insomnia, melatonin was only significantly effective in sleep onset latency and total sleep time in children and adolescents. In adults group, melatonin was not significantly effective in improving sleep onset latency, total sleep time, and sleep efficiency. In comorbid insomnia, melatonin significantly improved sleep onset latency in all age groups, but there was only one study in adults group. In conclusion, melatonin did not appear to be effective in adults but might be effective in children and adolescents with chronic insomnia for both comorbid insomnia and non-comorbid insomnia. Further studies are needed to establish the efficacy and safety of melatonin by age groups.