Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Statin use and incidence and mortality of breast and gynecology cancer: A cohort study using the National Health Insurance claims database.

Previous studies have reported inconsistent findings concerning the impact of statin use on cancer prevention. Our study examined the association between statin use and cancer incidence and mortality related to breast and gynecologic cancers in South Korea. A population-based cohort study was conducted using the National Health Insurance claims database. Women aged 45 to 70 years old who had taken statins for at least 6 months were compared to statin non-users of the same age from January 2005 to June 2013. The primary outcomes were cancer incidence and mortality related to breast cancer, total gynecologic cancers, cervix uteri cancer and ovarian cancer. Cox proportional hazards regression was conducted to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). Out of 587 705 women, there were 3591 cases of breast cancer, 2239 cases of gynecologic cancers and 565 breast and total gynecologic cancer deaths during 7.6 person-years. The aHRs for the association between the risk of each cancer and statin use were 0.88 (95% CI 0.79-0.97) for breast cancer and 0.83 (95% CI 0.67-0.99) for cervix uteri cancer. Statin use was associated with decreased breast cancer mortality (HR = 0.65, 95% CI 0.43-0.99) and total gynecologic cancer mortality (HR = 0.70, 95% CI 0.50-0.98). A dose-response relationship was only found for all-cancer mortality. Statin use for at least 6 months was significantly associated with a lower risk of breast and cervix uteri cancer incidence, and with lower mortality of breast and gynecologic cancers. Further research on these associations will be needed.

First-trimester exposure to benzodiazepines and risk of congenital malformations in offspring: A population-based cohort study in South Korea.

BACKGROUND: Benzodiazepines are frequently prescribed during pregnancy; however, evidence about possible teratogenicity is equivocal. We aimed to evaluate the association between first-trimester benzodiazepine use and the risk of major congenital malformations. METHODS AND FINDINGS: Using Korea's nationwide healthcare database, we conducted a population-based cohort study of women who gave birth during 2011 to 2018 and their live-born infants. The exposure was defined as one or more benzodiazepine prescriptions during the first trimester. We determined the relative risks (RRs) and confidence intervals (CIs) of overall congenital malformations and 12 types of organ-specific malformations. Infants were followed from birth to death or 31 December 2019, whichever came first (up to 8 years of age). Propensity score fine stratification was employed to control for 45 potential confounders. Among a total of 3,094,227 pregnancies, 40,846 (1.3%) were exposed to benzodiazepines during the first trimester (mean [SD] age, 32.4 [4.1] years). The absolute risk of overall malformations was 65.3 per 1,000 pregnancies exposed to benzodiazepines versus 51.4 per 1,000 unexposed pregnancies. The adjusted RR was 1.09 (95% CI 1.05 to 1.13, p < 0.001) for overall malformations and 1.15 (1.10 to 1.21, p < 0.001) for heart defects. Based on mean daily lorazepam-equivalent doses, the adjusted RRs for overall malformations and heart defects were 1.05 (0.99 to 1.12, p = 0.077) and 1.12 (1.04 to 1.21, p = 0.004) for <1 mg/day and 1.26 (1.17 to 1.36, p < 0.001) and 1.31 (1.19 to 1.45, p < 0.001) for >2.5 mg/day doses, respectively, suggesting a dose-response relationship. A small but significant increase in risk for overall and heart defects was detected with several specific agents (range of adjusted RRs: 1.08 to 2.43). The findings were robust across all sensitivity analyses, and negative control analyses revealed a null association. Study limitations include possible exposure misclassification, residual confounding, and restriction to live births. CONCLUSIONS: In this large nationwide cohort study, we found that first-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest. The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT04856436.

High-Cost Users of Prescription Drugs: National Health Insurance Data from South Korea.

IMPORTANCE: In OECD countries, pharmaceutical spending reached around 800 billion USD in 2013, accounting for about 20% of total spending in the retail sector. Pharmaceutical expenditures are steadily increasing in South Korea, necessitating strategies to promote efficiency. OBJECTIVE: This study investigated factors associated with high-cost users (HCUs), who account for the majority of outpatient prescriptions in the total South Korean population. The top 20 frequently prescribed therapeutic subgroups were also investigated. DESIGN: This is an observational study performed using health insurance claims data in 2019. PARTICIPANTS: In total, 44,744,632 people (including 6,806,339 aged 65 years or older) who were prescribed outpatient medications were included. MAIN MEASURES: HCUs were defined as those for whom prescription drug costs were in the top 5%. Multivariate logistic regression analysis was performed using factors including age, insurance type, number of prescription drugs, outpatient visit days, prescription treatment days, and chronic diseases. RESULTS: HCUs accounted for 3.6 million (5% of the total population) and 1.4 million (21.1% of those 65 years or older). Furthermore, 4.1% of HCUs in the total population had few comorbidities. Male sex, older age, insurance (Medical Aid), comorbidities, chronic diseases, number of prescription drugs, outpatient visit days, and prescription days were all associated with an increased probability of being an HCU. The highest spending was found for B01 (antithrombotic agents) with 0.4 billion USD, followed by C10 (lipid-modifying agents) and A10 (drugs used in diabetes). The proportion of spending for HCUs among the general population was highest in L01 (antineoplastic agents), at 98.2%, and L04 (immunosuppressants), at 87.8%, whereas among the elderly, the highest proportions were found for B01 (antithrombotic agents), at 44.5%, and N06 (antidepressants), at 44.3%. CONCLUSION: Age and multiple chronic conditions were strongly associated with HCUs, and it seems necessary to reduce drug prescriptions in patients without complex comorbidities. Several measures should target those without multiple chronic conditions who are nonetheless HCUs.

Association Between Statins and the Risk of Kidney Cancer Incidence and Mortality Using the Korean National Health Insurance Claims Database.

BACKGROUND: Conflicting results have been reported regarding the potential preventive effects of statins on the risk of cancer. This study investigated the associations of statin use with the incidence and mortality of kidney cancer in South Korea. METHODS: In this retrospective population-based cohort study using the National Health Insurance claims database, we compared patients aged 45-70 years who had used statins for at least 6 months to non-statin users matched by age and sex from 2005 to June 2013. The main outcomes were kidney cancer incidence and mortality according to statin use. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). RESULTS: In the cohort of 1 008 101 people, the aHRs for the association between statin use and the outcomes were .84 (95% CI: 0.71-.99) for kidney cancer incidence and .65 (95% CI: 0.41-.98) for kidney cancer mortality. In the matched cohort of 337 578, the risk per 1000 people of cancer incidence and mortality was 1.63, 1.07, and .24, .17 in statin users and non-users, respectively. In matched cohort, the risk of kidney cancer incidence and mortality decreased, but it is not statistically significant. Also, there was no linear relationship with increased doses. CONCLUSION: Statin use might be associated with a decreased risk of kidney cancer incidence and mortality, but it showed no statistical significance. This study was a large-scale analysis, however, further studies that are larger and multinational in scope are needed to confirm the beneficial effects of statins on survival.

Ramucirumab plus paclitaxel as a second-line treatment in HER2-positive gastric cancer: subgroup analysis of a nationwide, real-world study in Korea (KCSG-ST19-16).

BACKGROUND: A subgroup analysis of data from a nationwide study (KCSG-ST19-16) was performed to evaluate the efficacy and safety of second-line ramucirumab plus paclitaxel treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma. METHODS: The KCSG-ST19-16 study enrolled a total of 1063 patients from 56 hospitals in South Korea with advanced gastric or GEJ adenocarcinoma, who had received second-line treatment with ramucirumab plus paclitaxel. HER2 status was known for 994 (93.5%) of these patients, who were thus included in the subgroup analysis. RESULTS: In total, 163 of 994 patients (16.4%), had HER2-positive gastric or GEJ adenocarcinoma. The objective response rate to ramucirumab plus paclitaxel treatment was significantly higher in patients with HER2-positive disease compared to those with HER2-negative disease (23.0% [95% confidence interval (CI), 15.9-30.1] vs. 15.1% [95% CI, 12.3-17.9], p = 0.025). The median progression-free survival was longer in patients with HER2-positive versus HER2-negative disease, but the difference was not statistically significant (4.3 months [95% CI, 3.7-5.3] vs 3.7 months [95% CI, 3.4-4.0], p = 0.054). There was no statistically significant difference in median overall survival (OS) between the groups (9.8 months [95% CI, 8.9-12.3] vs 10.1 months [95% CI, 9.2-10.9], p = 0.564). CONCLUSIONS: In patients with HER2-positive gastric or GEJ adenocarcinoma, the objective response rate to second-line treatment with ramucirumab plus paclitaxel was significantly higher compared to patients with HER2-negative disease. However, an increased response to treatment was not associated with an improvement in OS.

Development of the Korean Standardized Antimicrobial Administration Ratio as a Tool for Benchmarking Antimicrobial Use in Each Hospital.

BACKGROUND: The Korea National Antimicrobial Use Analysis System (KONAS), a benchmarking system for antimicrobial use in hospitals, provides Korean Standardized Antimicrobial Administration Ratio (K-SAAR) for benchmarking. This article describes K-SAAR predictive models to enhance the understanding of K-SAAR, an important benchmarking strategy for antimicrobial usage in KONAS. METHODS: We obtained medical insurance claims data for all hospitalized patients aged ≥ 28 days in all secondary and tertiary care hospitals in South Korea (n = 347) from January 2019 to December 2019 from the Health Insurance Review & Assessment Service. Modeling was performed to derive a prediction value for antimicrobial use in each institution, which corresponded to the denominator value for calculating K-SAAR. The prediction values of antimicrobial use were modeled separately for each category, for all inpatients and adult patients (aged ≥ 15 years), using stepwise negative binomial regression. RESULTS: The final models for each antimicrobial category were adjusted for different significant risk factors. In the K-SAAR models of all aged patients as well as adult patients, most antimicrobial categories included the number of hospital beds and the number of operations as significant factors, while some antimicrobial categories included mean age for inpatients, hospital type, and the number of patients transferred from other hospitals as significant factors. CONCLUSION: We developed a model to predict antimicrobial use rates in Korean hospitals, and the model was used as the denominator of the K-SAAR.

Decreased Use of Broad-Spectrum Antibiotics During the Coronavirus Disease 2019 Epidemic in South Korea.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a concern over possible increase in antibiotic use due to coinfections among COVID-19 patients in the community. Here, we evaluate the changes in nationwide use of broad-spectrum antibiotics during the COVID-19 epidemic in South Korea. METHODS: We obtained national reimbursement data on the prescription of antibiotics, including penicillin with ß-lactamase inhibitors, cephalosporins, fluoroquinolones, and macrolides. We examined the number of antibiotic prescriptions compared with the previous 3 years in the same period from August to July. To quantify the impact of the COVID-19 epidemic on antibiotic use, we developed a regression model adjusting for changes of viral acute respiratory tract infections (ARTIs), which are an important factor driving antibiotic use. RESULTS: During the COVID-19 epidemic in South Korea, the broad-spectrum antibiotic use dropped by 15%-55% compared to the previous 3 years. Overall reduction in antibiotic use adjusting for ARTIs was estimated to be 14%-30%, with a larger impact in children. CONCLUSIONS: Our study found that broad-spectrum antibiotic use was substantially reduced during the COVID-19 epidemic in South Korea. This reduction can be in part due to reduced ARTIs as a result of stringent public health interventions including social distancing measures.

Familial risk of Behçet's disease among first-degree relatives: a population-based aggregation study in Korea.

OBJECTIVE: Previous studies have indicated that Behçet's disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship. METHODS: Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR. RESULTS: Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females. CONCLUSION: This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling-sibling) vs between generations (parent-offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD.

Incidence, mortality, and cardiovascular diseases in pituitary adenoma in Korea: a nationwide population-based study.

PURPOSE: Few nationally representative studies have evaluated the epidemiology of PA (pituitary adenoma). This South Korean study evaluated the incidence of different PA subtypes, cardiovascular disease (CVD), and related mortality. METHODS: This population-based study evaluated 31,898 patients with PA during 2005-2015. The incidence of PA, mortality, and CVD occurrence in PA cases were evaluated during a median follow-up of 5.3 years (range: 0-10 years). Cox regression analysis was used to evaluate the associations between CVD and mortality. RESULTS: The annual incidences (per 100,000 population) were 3.5 for non-functioning pituitary adenoma (NFPA), 1.6 for prolactinoma (PRL), 0.5 for growth hormone-secreting pituitary adenoma (GH), and 0.2 for adrenocorticotropic or thyroid-stimulating hormone-secreting pituitary adenoma (ACTH + TSH). The standardized mortality ratios were 1.9 for ACTH + TSH, 1.7 for NFPA with hypopituitarism, 1.4 for NFPA without hypopituitarism, 1.3 for GH, and 1.1 for PRL. During 2005-2015, the overall incidence of CVD among PA patients was 6.6% (2106 cases), and the standardized incidence ratios were 4.1 for hemorrhagic stroke, 3.0 for ischemic stroke, and 1.7 for acute myocardial infarction. The standardized incidence ratios for stroke were significantly higher in the ACTH + TSH and NFPA groups, which also had higher risks of CVD-related mortality, relative to the PRL and GH groups. CONCLUSION: South Korea had a relatively high incidence of NFPA. The incidence of stroke was highest for ACTH + TSH and NFPA, which was directly related to mortality during long-term follow-up. Patients with these types of PA should receive stroke prevention measures to reduce their risk of mortality.

Effect of nationwide concurrent drug utilization review program on drug-drug interactions and related health outcome.

BACKGROUND: A computerized drug utilization review (DUR) program has provided physicians and pharmacists with alerts on drug-drug interactions (DDIs), drug-age precautions and therapeutic duplication in Korea since 2010. OBJECTIVE: The purpose of this study was to evaluate the impact of the DUR program on health outcomes associated with DDIs. METHODS: An uncontrolled before-after study was performed to investigate the impact of the nationwide DUR program on DDIs and related health outcomes. The study population consisted of people who used two types of DDI pairs before DUR implementation (from January 2009 to December 2010) and post-DUR implementation (from January 2012 to December 2013); (i) benzodiazepines with concurrent use of metabolic enzyme inhibitors and (ii) QTc (heart-rate corrected QT interval) prolongation agents. The main outcome measures were all-cause and cause-specific hospitalization admissions or emergency department (ED) visits. RESULTS: This study included 107 874 people who used benzodiazepines with enzyme inhibitors and 8489 who received co-medication of QTc prolongation agents. For patients receiving a combination of benzodiazepines and enzyme inhibitors, both all-cause hospitalization and cause-specific hospitalization decreased after DUR implementation, from 43.2% to 41.7% and from 4.6% to 4.5% (adjusted odds ratio [OR] = 0.96; 95% confidence interval (CI), 0.93-0.98; OR = 0.89, 95% CI = 0.84-0.99, respectively). For patients receiving co-medication of QTc prolongation agents, all-cause hospitalization (54.2%) was lower than before (54.9%) (OR = 0.87, 95% CI = 0.79-0.96), but no significant change was found for cause-specific hospitalization and ED visits. CONCLUSION: Implementation of a DUR program may reduce the adverse health outcomes posed by DDIs in patients on combination of benzodiazepines and enzyme inhibitors potentially QTc-prolongation agents.

Familial Risk for Moyamoya Disease Among First-Degree Relatives, Based on a Population-Based Aggregation Study in Korea.

BACKGROUND AND PURPOSE: Genetic factors have been known to play a role in the etiology of moyamoya disease (MMD); however, population-level studies quantifying familial risk estimates are unavailable. We aimed to quantify familial incidence and risk for MMD in first-degree relatives (FDR) in the general population of Korea. METHODS: By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 study subjects constituting 12 million families with blood-related FDR and followed them for a familial occurrence of MMD from 2002 to 2017. Incidence risk ratios were calculated as MMD incidence in individuals with affected FDR compared with those without affected FDR, according to age, sex, and family relationships. RESULTS: Among total study subjects, there were 22 459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8/104 person-years. Overall, the familial risk for MMD was 132-fold higher in individuals with versus without affected FDR. Familial risk (incidence risk ratio; incidence/104 person-years) increased with the degree of genetic relatedness, being highest in individuals with an affected twin (1254.1; 230.0), followed by a sibling (212.4; 35.6), then mother (87.7; 14.4) and father (62.5; 10.4). Remarkably, there was no disease concordance between spouses. The risks were age-dependent and were particularly high in younger age groups. Familial risks were similar in males and females, and the risk of disease transmission was higher in same-sex parent-offspring and sibling pairs. CONCLUSIONS: Our study indicates that genetic predisposition is the predominant driver in MMD pathogenesis, with minimal contribution of environmental factors. These results could be utilized to direct future genetic studies and clinical risk counseling.

Development of Antibiotic Classification for Measuring Antibiotic Usage in Korean Hospitals Using a Modified Delphi Method.

In 2019, a project designed to develop a system for measuring and comparing antibiotic usage in hospitals was launched in Korea. As part of this project, we developed a means to classify antibiotic usage in Korean hospitals using a modified Delphi method. In results, the following categories of antibiotic classification were accepted for use in Korean hospitals: 1) broad-spectrum antibacterial agents predominantly used for hospital-onset infections in adults, 2) broad-spectrum antibacterial agents predominantly used for community-acquired infections in adults, 3) antibacterial agents predominantly used for resistant gram-positive infections in adults, 4) narrow-spectrum beta-lactam agents in adults, 5) antibacterial agents predominantly used for extensive antibiotic resistant gram-negative bacteria in adults, and 6) total antibacterial agents.

Potentially inappropriate medication and hospitalization/emergency department visits among the elderly in Korea.

OBJECTIVE: To investigate the association between potentially inappropriate medicine (PIM) use, defined using the American Geriatric Society (AGS) 2012 Beers criteria, and the risk of hospitalization or emergency department (ED) visits in elderly patients, and to examine the most frequently used PIMs among patients with adverse outcomes. DESIGN/SETTING: This was a retrospective study using National Health Insurance claims data from 2010 to 2012. INTERVENTION(S): Elderly patients who took PIMs are compared to those who were not taking PIMs. STUDY PARTICIPANTS: Elderly patients (n = 79 552) who visited medical institutions in Jeju Island during 2011. MAIN OUTCOME MEASURE: Hospitalization and ED visits were evaluated according to whether the patients took PIMs during the study period. The most frequent medications used by the PIM group were also investigated. RESULTS: The likelihood of hospitalization was higher in older patients who took at least one PIM than in those who were not taking PIMs during the study period (odds ratio 2.25, 95% confidence interval 2.09-2.44). Patients taking PIMs were more likely to visit EDs (odds ratio 1.59, 95% confidence interval 1.50-1.67). Among patients who were hospitalized or visited EDs, 45.5% had taken at least one PIM on that day. The most commonly used PIMs included chlorpheniramine maleate, diazepam, metoclopramide HCl and diclofenac sodium. CONCLUSION: Our findings indicate that PIM use can lead to negative health consequences, providing further evidence of the inappropriateness of these medications. Thus, pharmaceutical policies regarding PIM use may need to be implemented for elderly adults in Korea.

Physicians' and pharmacists' perceptions on real-time drug utilization review system: a nationwide survey.

OBJECTIVE: To identify healthcare providers' experience and satisfaction for the drug utilization review (DUR) system, their impact on prescription changes following alerts, and difficulties experienced in the system by surveying primary healthcare centers and pharmacies. DESIGN: A cross-sectional nationwide survey. SETTING AND PARTICIPANTS: Approximately 2000 institutions were selected for the survey by a simple random sampling of nationwide primary healthcare centers and community pharmacy approximately practices, and 358 replied. MAIN OUTCOMES MEASURES: The questionnaire included questions on experience and recognition of DUR alerts, personal attitude and respondents' biographical information. Space was included for respondents to suggest improvements of the DUR system. RESULTS: The DUR system scored 71.5 out of 100 points for satisfaction by physicians and pharmacists, who reported that the alerts prevent medication-related errors; most respondents (96.6%) received the alerts. Several respondents (10.9%) replied that they prescribe or dispense prescriptions as they are without following the alerts. Physicians (adjusted odds ratio, 8.334; 95% confidence interval, 3.449-20.139) are more likely to change the prescription than pharmacists and persons with alert experience (4.605; 1.080-19.638). However, current practice in metropolitan areas (0.478; 0.228-1.000) and frequent alerts regarding co-administration incompatibilities within prescriptions (0.135; 0.031-0.589) negatively influence adherence to DUR alerts. CONCLUSIONS: Although most surveyed physicians and pharmacists receive the alerts, some do not or reported that they would not follow the alerts. To increase adherence, the DUR system should be improved to ensure a preferential and intensive approach to detecting potentially high-risk drug combinations.

Towards Actualizing the Value Potential of Korea Health Insurance Review and Assessment (HIRA) Data as a Resource for Health Research: Strengths, Limitations, Applications, and Strategies for Optimal Use of HIRA Data.

Health Insurance and Review Assessment (HIRA) in South Korea, also called National Health Insurance (NHI) data, is a repository of claims data collected in the process of reimbursing healthcare providers. Under the universal coverage system, having fee-for-services covering all citizens in South Korea, HIRA contains comprehensive and rich information pertaining to healthcare services such as treatments, pharmaceuticals, procedures, and diagnoses for almost 50 million beneficiaries. This corpus of HIRA data, which constitutes a large repository of data in the healthcare sector, has enormous potential to create value in several ways: enhancing the efficiency of the healthcare delivery system without compromising quality of care; adding supporting evidence for a given intervention; and providing the information needed to prevent (or monitor) adverse events. In order to actualize this potential, HIRA data need to actively be utilized for research. Thus understanding this data would greatly enhance this potential. We introduce HIRA data as an important source for health research and provide guidelines for researchers who are currently utilizing HIRA, or interested in doing so, to answer their research questions. We present the characteristics and structure of HIRA data. We discuss strengths and limitations that should be considered in conducting research with HIRA data and suggest strategies for optimal utilization of HIRA data by reviewing published research using HIRA data.

Prevalence and predictors of non-steroidal anti-inflammatory drug/analgesic therapeutic duplication in the South Korean ambulatory care setting.

PURPOSE: Therapeutic duplication (TD) in prescriptions is a common cause of inappropriate drug use. This study aimed to determine the prevalence of TD in the Korean ambulatory setting and to determine the patient and prescriber characteristics that were associated with TD of non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. METHODS: Ambulatory care cases with NSAID/analgesic prescriptions were extracted from the National Health Insurance database for January­March 2011. The Korean TD classification (64 ingredients) was used to define cases of TD. Multivariate logistic regression was used to determine the predictors of TD. The independent variables in the regression model included patient characteristics (sex, age, insurance type, comorbidity, diagnosis, and number of prescribed drugs) and prescriber characteristics (type of medical institution and specialty). RESULTS: Among 21 million patients, we identified 59,636,222 ambulatory care visits with NSAID/analgesic prescriptions; 13.3 % of these cases involved TD. The most frequent duplications were diclofenac/aceclofenac (12.4 % of TDs), diclofenac/talniflumate (11.2 %), and diclofenac/loxoprofen sodium (10.7 %). Male sex, older age, and a Charlson comorbidity index of ≥1 were associated with an increased likelihood of TD. Arthritis, injection administration (OR 3.676, 95 % CI 3.670­3.683), and the number of drugs per prescription were associated with an increased likelihood of TD. Orthopedic and pediatric specialties were associated with an increased likelihood of TD. CONCLUSIONS: This study is the first to determine the prevalence of NSAID TD and the factors that were associated with its occurrence in South Korea. These results may help prevent TD and improve appropriate medication use.

Potentially inappropriate medication use at ambulatory care visits by elderly patients covered by National Health Insurance in Korea.

OBJECTIVES: Potentially inappropriate medication (PIM) use is an important and preventable safety concern in the care of elderly patients and has been associated with adverse drug reactions, hospitalization, and mortality. Although PIM use for the elderly is a common and serious public health issue worldwide, there are few studies examining PIM use in the ambulatory care setting in Korea. METHODS: To examine the prevalence and risk factors of PIM use from ambulatory care visits by elderly patients covered by National Health Insurance (NHI) in Korea, the nationwide prescription claims data of elderly patients' ambulatory care visits in 2006 were analyzed. RESULTS: Potentially inappropriate prescriptions were identified using extensive criteria that included Beers', Zhan's, and Canadian criteria. In 2006, 3,770,978 elderly patients received 40,995,267 prescriptions. 36.7% of the total prescriptions for elderly patients who visited ambulatory care clinics were identified as PIM use. Findings in this study indicated that the strongest risk factors for PIM prescriptions were the number of drugs prescribed and visit characteristics. CONCLUSION: Therefore, it is necessary to develop the explicit criteria of PIM prescription in Korea that can be included in the Drug Utilization Review (DUR) system, which is expected to lead to more appropriate and judicious prescribing.

Physicians' and pharmacists' acceptance of online, real-time "drug combinations to avoid" messages.

UNLABELLED: Drug-induced prolongation of the electrocardiogram QT interval, a risk factor for ventricular arrhythmia and death, has been observed for some small drugs with masses < 1 kDa. Over the last two decades, patient exposure to large molecule monoclonal antibody drugs with masses > 40 kDa has increased dramatically; hence, the aim of this study was to systematically review the scientific literature for evidence of QT prolongation induced by these drugs. METHODS: The PubMed and Embase databases were searched for cases indicative of drug-induced QT prolongation for 28 pre-identified monoclonal antibody drugs authorized in Europe. Cases were identified by applying a standardized search string and a subsequent text search and manual review. In parallel, the public European Medicines Agency (EMA) database was searched for reported frequencies of adverse events indicative of QT prolongation. RESULTS: A valid case of drug-induced QT prolongation, caused indirectly by hypocalcaemia, could be identified for only 1 out of 28 monoclonal antibody drugs (denosumab) from the PubMed and Embase search. The EMA database showed no hits for denosumab. Considering that hypocalcaemia-mediated QT prolongation is an already-identified and labelled risk for denosumab, the current study did not identify any additional evidence of QT prolongation caused by monoclonal antibody drugs.