Bo Ram Yang

The Incidence and Prevalence of Diabetes Mellitus and Related Atherosclerotic Complications in Korea: A National Health Insurance Database Study

Aims/Introduction The incidence and prevalence of type 2 diabetes mellitus (T2DM) and related macrovascular complications in Korea were estimated using the Health Insurance Review and Assessment (HIRA) database from 2007–2011, which covers the claim data of 97.0% of the Korean population. Materials and Methods T2DM, coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral artery disease (PAD) were defined according to ICD-10 codes. We used the Healthcare Common Procedure Coding System codes provided by HIRA to identify associated procedures or surgeries. When calculating incidence, we excluded cases with preexisting T2DM within two years before the index year. A Poisson distribution was assumed when calculating 95% confidence intervals for prevalence and incidence rates. Results The prevalence of T2DM in Korean adults aged 20–89 years was 6.1–6.9% and the annual incidence rates of T2DM ranged from 9.5–9.8/1,000 person-year (PY) during the study period. The incidence rates of T2DM in men and women aged 20–49 years showed decreasing patterns from 2009 to 2011 (P<0.001); by contrast, the incidence in subjects aged 70–79 years showed increased patterns from 2009 to 2011 (P<0.001). The incidence rates of CAD and CVD in patients newly diagnosed with T2DM were 18.84/1,000 PY and 11.32/1,000 PY, respectively, in the year of diagnosis. Among newly diagnosed individuals with T2DM who were undergoing treatment for PAD, 14.6% underwent angioplasty for CAD during the same period. Conclusions Our study measured the national incidences of T2DM, CAD, CVD, and PAD, which are of great concern for public health. We also confirmed the relatively higher risk of CAD and CVD newly detected T2DM patients compared to the general population in Korea.

Risk and Risk Periods for Stroke and Acute Myocardial Infarction in Patients with Central Retinal Artery Occlusion.

PURPOSE To investigate the risk of stroke and acute myocardial infarction (AMI) in patients with incident central retinal artery occlusion (CRAO). DESIGN A self-controlled case series (SCCS) study. PARTICIPANTS Patients with incident CRAO from the entire Korean population of 48 million individuals. METHODS We used the Korean national claim database (2007-2011) for analyses. After identifying patients with incident CRAO, the relative incidence rate ratios (IRRs) for stroke and AMI in risk periods were measured in these patients using a SCCS method. MAIN OUTCOME MEASURES The IRRs of stroke and AMI by risk periods. RESULTS Of 1655 patients with incident CRAO in 2009-2010, 165 had stroke/AMI (ischemic stroke in 139, hemorrhagic stroke in 13, and AMI in 15) in the observation period spanning 365 days before and after the occurrence of CRAO. The IRR of stroke/AMI 1 to 30 days after CRAO occurrence significantly increased (14.0; 95% confidence interval [CI], 8.90-22.00); the IRR peaked during the 1 to 7 days after CRAO occurrence (44.51; 95% CI, 27.07-73.20), and the increased risk was present for the first 30 days. The IRR of stroke/AMI also significantly increased 1 to 30 days (6.82; 95% CI, 4.01-11.60) and 31 to 90 days (2.86; 95% CI, 1.66-4.93) before CRAO occurrence. Subanalysis for only ischemic stroke showed similar, magnified IRRs in the risk periods compared with all events. The IRRs were not significantly different between sexes or age groups (<65 vs. ≥65 years). CONCLUSIONS Patients with incident CRAO are at increased risk of ischemic stroke just after CRAO occurrence, and the risk is particularly increased during the first week immediately after the CRAO occurrence. The results suggest that patients with incident CRAO require immediate neurologic evaluation and preventive treatment to reduce mortality and morbidity.

Risk of stroke in retinal vein occlusion.

Objective: To investigate risk and risk periods for stroke and acute myocardial infarction (AMI) with incident retinal vein occlusion (RVO). Methods: Data from the Korean national claims database (2007–2011) was analyzed, which covers the entire Korean population (48 million). Of the incident RVO cases, RVO cases with incident stroke/AMI during the observation period (RVO occurrence ±365 days) were identified. In this self-controlled case series, the risks of incident stroke/AMI were compared between the control and risk periods by calculating the relative incidence rate ratios (IRRs) for stroke/AMI. Results: Of the 44,603 patients with incident RVO in 2009–2010, 1,176 patients experienced incident stroke/AMI (853 ischemic strokes, 163 hemorrhagic strokes, 172 AMIs) during their observation period. The risk of stroke/AMI increased throughout the entire risk period; the IRR was highest during the first 30 days after RVO occurrence (2.66; 95% confidence interval, 2.06–3.43). Analysis limited to ischemic stroke resulted in similar findings. Analysis limited to hemorrhagic stroke showed an increased risk during the first 30 days after RVO occurrence (IRR, 3.45; 95% confidence interval, 1.80–6.59) as well as the 31 to 90 days before and 91 to 180 days after RVO occurrence. However, the risk was not increased during any risk periods in the analysis limited to AMI. Conclusions: The present study provides new evidence that patients with incident RVO are at increased risk of stroke just after RVO occurrence. Immediate risk evaluation and proper treatment of stroke risk factors in patients with RVO are needed to reduce stroke-related mortality and morbidity.

Tuberculosis is frequently diagnosed within 12 months of diabetes mellitus.

BACKGROUND Evidence regarding the effects of tuberculosis (TB) screening among patients with diabetes mellitus (DM) in intermediate TB burden countries is insufficient, and the most appropriate time point for TB screening is unclear. OBJECTIVE To investigate trends in TB incidence among newly diagnosed DM patients. DESIGN A retrospective cohort study of the claims database of the Health Insurance Review and Assessment Service in Korea was performed. Participants were newly diagnosed with type 2 DM in 2009. The study outcome was TB incidence between 2009 and 2011 among participants according to duration of type 2 DM. RESULTS A cohort of 331,601 patients with newly diagnosed type 2 DM in 2009 was identified. During the 3-year follow-up period, 1533 patients were diagnosed with TB. The estimated incidence of TB among newly diagnosed type 2 DM patients was 18/10,000 patient-years (py) (95%CI 17.5-19.4). TB incidence was 33/10,000 py (95%CI 30.0-35.6) in the first 6 months, and 19/10,000 py (95%CI 16.5-20.6) in the following 6-month period. CONCLUSIONS The risk of developing TB was increased among DM patients, particularly during the first 12 months after DM diagnosis.

Co-Medication of Statins with Contraindicated Drugs

Background The concomitant use of cytochrome P450 3A4 (CYP3A4) metabolized statins (simvastatin, lovastatin, and atorvastatin) with CYP3A4 inhibitors has been shown to increase the rate of adverse events. Objective This study was performed to describe the co-medication prevalence of CYP3A4-metabolized statins with contraindicated drugs. Methods The patients aged 40 or older receiving CYP3A4-metabolized statin prescriptions in 2009 were identified using the national patient sample from a Korea Health Insurance Review and Assessment Service database. Contraindicated co-medication was defined as prescription periods of statins and contraindicated drugs overlapping by at least one day. Co-medication patterns were classified into 3 categories as follows: co-medication in the same prescription, co-medication by the same medical institution, and co-medication by different medical institutions. The proportion of co-medication was analyzed by age, gender, co-morbidities, and the statin’s generic name. Results A total of 2,119,401 patients received CYP3A4-metabolized statins and 60,254 (2.84%) patients were co-medicated with contraindicated drugs. The proportion of co-medication was 4.6%, 2.2%, and 1.8% in simvastatin, lovastatin, and atorvastatin users, respectively. The most frequent combination was atorvastatin-itraconazole, followed by simvastatin-clarithromycin and simvastatin-itraconazole. Among the co-medicated patients, 85.3% were prescribed two drugs by different medical institutions. Conclusion The proportion of co-medication of statins with contraindicated drugs was relatively lower than that of previous studies; however, the co-medication occurring by different medical institutions was not managed appropriately. There is a need to develop an effective system and to conduct outcomes research confirming the association between co-medication and the risk of unfavorable clinical outcomes.

Impact of the Health Insurance Coverage Policy on Oral Anticoagulant Prescription among Patients with Atrial Fibrillation in Korea from 2014 to 2016

Background To evaluate oral anticoagulant (OAC) utilization in patients with atrial fibrillation after the changes in the health insurance coverage policy in July 2015. Methods We used the Health Insurance Review and Assessment Service-National Patient Samples (HIRA-NPS) between 2014 and 2016. The HIRA-NPS, including approximately 1.4 million individuals, is a stratified random sample of 3% of the entire Korean population using 16 age groups and 2 sex groups. The HIRA-NPS comprises personal and medical information such as surgical or medical treatment provided, diagnoses, age, sex, region of medical institution, and clinician characteristics. The studied drugs included non-vitamin K antagonist OACs (NOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban, and were compared with warfarin. We analyzed drug utilization pattern under three aspects: person, time, and place. Results The number of patients with atrial fibrillation who were prescribed OACs was 3,114, 3,954, and 4,828; and the proportions of prescribed NOACs to total OACs were 5.1%, 36.2%, and 60.8% in 2014, 2015, and 2016, respectively. The growth rate of OACs prescription increased from 61.4 patients/quarter before June 2015 to 147.7 patients/quarter thereafter. These changes were predominantly in elderly individuals aged more than 70 years. The proportion of NOACs to OACs showed significant regional difference. Conclusion The change of health insurance coverage policy substantially influenced OACs prescription pattern in whole Korean region. But the impact has been significantly different among regions and age groups, which provides the evidence for developing standard clinical practice guideline on OACs use.

Regional differences in the incidence of tuberculosis among patients with newly diagnosed diabetes mellitus

There are regional differences in the burden of tuberculosis (TB). Although these differences might be explained by regional differences in the risk factors of TB, whether such risk factors are actually associated with the regional differences in the TB burden remains unclear. This study aimed to investigate the relationship between the risk factors of and regional differences in TB incidence.

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database

Purpose To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). Materials and Methods We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. Results There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinsons syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. Conclusion We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals.

Risk of motor vehicle collisions associated with medical conditions and medications: rationale and study protocol

Background Medical conditions and medications may be associated with motor vehicle collisions (MVCs), which pose a major public health problem worldwide. Further epidemiological assessment is necessary for certain diseases and medications. Moreover, since disease aetiology and patterns of medication use may differ among ethnicities and healthcare systems, a population-specific approach is necessary. The present epidemiological study is designed to assess the medical conditions and medications associated with the risk of fatal MVCs among at-fault drivers in the Korean population. Method and design A retrospective cohort will be constructed for individuals who died in MVCs between 2005 and 2014 in the Korean Traffic Accident Analysis System database, which is linked to the Korean National Health Insurance database between 2002 and 2014. In order to compare medical conditions and medication use among drivers who died in a fatal MVC with the general population, standardised prevalence ratios will be calculated. In the culpability study, we will identify conditions and drugs associated with MVCs, comparing drivers with higher levels of responsibility to those with lower levels of responsibility. In the case-crossover study, the transient effects of medical conditions and medications will be examined using a conditional logistic regression model that adjusts for confounders. Discussion The results of this study will help to characterise the associations of diseases and medications with fatal MVCs in an Asian population, with the goal of informing regulatory and clinical decision-making regarding patients with the relevant conditions and the establishment of strategies for improving traffic safety.

Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability.