Antidepressants and the Risk of Ischemic Stroke in Older Adults According to the Degree of Serotonin Reuptake Inhibition: A Retrospective Cohort Study.

OBJECTIVE: The effects of serotonin reuptake inhibition induced by antidepressants on ischemic stroke and its pathophysiology remain unclear despite the frequent use of antidepressants and high fatality of ischemic stroke. We estimated the risk of ischemic stroke associated with antidepressant use in older adults according to the degree of serotonin reuptake inhibition. DESIGN: Retrospective cohort study. PARTICIPANTS: The cohort consisted of older adult patients who were treated with antidepressants. MEASUREMENTS: We estimated the risk of ischemic stroke associated with antidepressant use in older adults according to the degree of serotonin reuptake inhibition using Korea's National Health Insurance System-Senior Cohort. Exposure to antidepressants was categorized by type (strong, intermediate, or weak serotonin reuptake inhibitors [SRIs]) and by the mean prescribed dose per day and treatment duration. The risk for the strong and intermediate SRIs group was compared with that of the weak SRIs group using a Cox proportional hazards regression model. RESULTS: Of 97,411 were weak SRIs users, and 107,152 and 18,783 were users of strong and intermediate SRIs. The risk of ischemic stroke was 1.192- and 1.057-fold higher in strong and intermediate SRI users, respectively than in weak SRI users. Hazard ratios were increased in higher dose and shorter duration user groups. The risk increased 1.753-fold in strong SRI users with anticonvulsants and 1.387-fold in intermediate SRI users with PPIs. CONCLUSION: The use of strong and intermediate SRIs should be considered carefully in older adult patients, especially when high-dose antidepressants are prescribed even for a short duration.

Effect of methylphenidate on height in pediatric attention-deficit hyperactivity disorder patients: a systematic review and meta-analysis.

Methylphenidate (MPH), a first-line treatment for attention-deficit hyperactivity disorder (ADHD) management, has been the focus of debate for decades regarding its effect on growth. The aim of this PRISMA meta-analysis was to determine the effect of MPH on height in children/adolescents with ADHD and its predictive factors based on literature reports. Available full-text articles were systematically reviewed to identify clinical studies of pediatric ADHD patients with height Z-score (HZS) data for monotherapy MPH-treated and non-treated groups. We estimated standardized mean differences (SMDs) of HZS or its changes from baseline (ΔHZS) between groups, then identified associated factors through subgroup analyses and meta-regression. For before-after treatment studies, the paired standard errors of ΔHZS were re-estimated to demonstrate in the forest plot. Risk of bias was analyzed using the Newcastle-Ottawa Scale. Among the 29 eligible studies, 26 reported ΔHZS with self-control groups, and ΔHZS or absolute HZS were compared to other external controls in 11 studies. A significant reduction was observed between post-MHP and pre-MPH use, with high heterogeneity (SMD = - 0.40; 95% confidence interval = [ - 0.54, - 0.27]; I2 = 91%). The study region, ADHD subtype, and stimulant-naïve status of patients at baseline may modify the effect on HZS. Because of the high clinical heterogeneity in observational studies, clinicians should consider the negative effect of MPH on height in ADHD patients by determining whether patients fulfill appropriate high-risk criteria. Further well-designed longitudinal studies are required to better quantify this effect, especially with prolonged treatment.

Treatment patterns and cost of exacerbations in patients with chronic obstructive pulmonary disease using multiple inhaler triple therapy in South Korea.

BACKGROUND: Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed. METHODS: This was a retrospective cohort study using the South Korea National Health Insurance database (2014-2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months' data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW). RESULTS: Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75-0.78); mean PPPY total healthcare costs were 2093 USD. CONCLUSIONS: Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.

Preoperative percutaneous needle lung biopsy techniques and ipsilateral pleural recurrence in stage I lung cancer.

OBJECTIVES: A recent meta-analysis of individual patient data revealed that preoperative percutaneous transthoracic needle lung biopsy (PTNB) was associated with an increased risk of ipsilateral pleural recurrence in stage I lung cancer. This study aimed to examine whether particular PTNB techniques reduced the risk of pleural recurrence. METHODS: We retrospectively included 415 consecutive patients with stage I lung cancer who underwent preoperative PTNB and curative resection from 2009 through 2016. Detailed information was collected, including clinical, PTNB technique, radiologic, and pathologic characteristics of lung cancer. Cox regression analyses were performed to identify risk factors for pleural recurrence before and after propensity score matching. RESULTS: The overall follow-up period after PTNB was 62.1 ± 23.0 months, and ipsilateral pleural recurrence occurred in 40 patients. Before propensity score matching, age (p = 0.063), microscopic pleural invasion (p = 0.065), and pathologic tumor size (p = 0.016) tended to be associated with pleural recurrence in univariate analyses and subsequently were matched using a propensity score. After propensity score matching, multivariate analysis revealed that ipsilateral pleural recurrence was associated with a larger target size on computed tomography (hazard ratio [HR] = 1.498; 95% CI, 1.506-2.125; p = 0.023) and microscopic lymphatic invasion (HR = 3.526; 95% CI, 1.491-8.341; p = 0.004). However, no PTNB techniques such as needle gauge, biopsy, or pleural passage numbers were associated with a reduced risk of recurrence. CONCLUSIONS: No particular PTNB techniques were associated with reduced pleural seeding after PTNB in stage I lung cancer. Regardless of the technique, PTNB needs to be cautiously applied when early lung cancer is suspected, followed by curative treatment. KEY POINTS: • Age, microscopic pleural invasion, and pathologic tumor size tended to be associated with pleural recurrence in stage I lung cancer before propensity matching. • After propensity matching, pre-biopsy CT target size and microscopic lymphatic invasion were associated with pleural recurrence. • No particular PTNB techniques were associated with reduced pleural seeding in stage I lung cancer before and after propensity matching.

Cardiovascular risk of nonsteroidal anti-inflammatory drugs in dialysis patients: a nationwide population-based study.

BACKGROUND: Given the cardiovascular risk of nonsteroidal anti-inflammatory drugs (NSAIDs), it is essential to identify the relationship between NSAIDs and cardiovascular outcomes in dialysis patients who have elevated cardiovascular risk. METHODS: A case-crossover study was conducted to assess the association of NSAIDs with major adverse cardiac and cerebrovascular events (MACCEs) and mortality using the Korean Health Insurance dataset. The case period was defined as 1-30 days prior to the event date and the control periods were defined as 61-90 days and 91-120 days prior to the event date. RESULTS: There were 3433 and 8524 incident dialysis patients who experienced MACCEs and mortality, respectively, after exposure to NSAIDs within 120 days before each event. NSAIDs significantly increased the risk of MACCEs {adjusted odds ratio [aOR] 1.37 [95% confidence interval (CI) 1.26-1.50]} and mortality [aOR 1.29 (95% CI 1.22-1.36)]. Nonselective NSAIDs, but not selective cyclooxygenase-2 inhibitors, significantly increased the risk of MACCEs and mortality. However, the MACCE and mortality risk did not increase in a dose-dependent manner in the analysis according to the cumulative defined daily dosage of NSAIDs. The incidence of MACCEs in the case period tended to be more common in patients who had recent exposure to NSAIDs than in patients who did not have recent exposure to NSAIDs. CONCLUSIONS: Clinicians should be particularly cautious when prescribing NSAIDs to dialysis patients considering the associations of NSAIDs with cardiovascular outcomes and mortality, which might occur independent of the dose and duration of exposure.

Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea: a retrospective cohort study.

BACKGROUND: Real-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS). METHODS: This was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD). RESULTS: Overall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C < 70 mg/dL in patients with stroke, ACS, CHD and PAD; and LDL-C < 100 mg/dL in patients with DM and AAD). Statin use was observed in relatively low proportions of subjects (21.5% [known high-risk], 34.4% [newly defined high-risk]). LDL-C goal attainment from 2009 to 2015 steadily increased but the goal-achiever proportion of newly defined high-risk patients with ACS remained reasonably constant (38.7% in 2009; 38.1% in 2015). CONCLUSIONS: LDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.

Cost analysis of depression using the national insurance system in South Korea: a comparison of depression and treatment-resistant depression.

BACKGROUND: The incidence and burden of depressive disorders are increasing in South Korea. There are many differences between pharmaceutically treated depression (PTD) and treatment-resistant depression (TRD), including the economic consequences; however, to our knowledge, the economic burden of depression is understudied in South Korea. Therefore, the objective of the present study was to calculate the different economic costs of PTD and TRD in South Korea, specifically by comparing several aspects of medical care. METHODS: This study comprised patients aged 18 and over who were newly prescribed antidepressants for more than 28 days with a depression code included from January 1, 2012, to December 31, 2012, by the Health Insurance Review and Assessment Service (HIRA). TRD was classified as more than two antidepressant regimen failures in PTD patients. The cost was calculated based on the cost reflected on the receipt registered with HIRA. RESULTS: Of the 834,694 patients with PTD, 34,812 patients (4.17%) were converted to TRD. The cost of medical care for TRD (6,610,487 KRW, 5881 USD) was approximately 5 times higher than the cost of non-TRD (1,273,045 KRW, 1133 USD) and was significantly higher for patients with or without depression and suicide codes. Medical expenses incurred by non-psychiatrists were roughly 1.7 times higher than those incurred by psychiatrists. CONCLUSIONS: TRD patients had significantly higher healthcare costs than PTD patients. Identifying these financial aspects of care for depression can help to establish a more effective policy to reduce the burden on mentally ill patients.

Prognostic Impact of Pregnancy in Korean Patients with Breast Cancer.

BACKGROUND: Pregnancy concurrent with, shortly before, or after breast cancer poses unique challenges because hormonal changes in pregnancy potentially interact with breast cancer outcomes. MATERIALS AND METHODS: We studied a cohort of 3,687 female patients of reproductive age (<50 years) with breast cancer, linking a large institutional database and the nationwide claims database to comprehensively capture exposure status and tumor characteristics. Exposures included breast cancer during pregnancy, postpartum breast cancer (<12 months after delivery), and pregnancy after breast cancer. RESULTS: Forty-five patients with postpartum breast cancer were significantly more likely to have advanced stage, hormone receptor-negative tumor and to be younger than 35 years at diagnosis than those without postpartum breast cancer. This trend was not observed with 18 patients with breast cancer during pregnancy. The unadjusted 5-year survival rates were 77% versus 96% for patients with postpartum breast cancer versus their counterparts, 89% versus 96% for patients with breast cancer during pregnancy versus their counterparts, and 98% versus 96% for patients with pregnancy after breast cancer versus their counterparts, respectively. In the multivariable analyses, postpartum breast cancer exhibited hazard ratios for death of 1.57 (95% confidence interval [CI], 0.82-2.99), whereas those for breast cancer during pregnancy and pregnancy after breast cancer were 1.09 (95% CI, 0.15-7.91) and 0.86 (95% CI, 0.26-2.83), respectively. CONCLUSION: Postpartum breast cancer, but not breast cancer during pregnancy, was associated with advanced stage, younger age at diagnosis (<35 years), hormone receptor-negative disease, and poorer survival. Pregnancy after breast cancer did not compromise overall survival. IMPLICATIONS FOR PRACTICE: Although pregnancy around the time of diagnosis of breast cancer is expected to become increasingly common with maternal age at first childbirth on the rise, data on the prognostic impact of pregnancy have been inconsistent and rare from Asian populations. In this investigation of a Korean patient cohort with breast cancer, pregnancy-associated breast cancer was associated with advanced stage, younger age at diagnosis (<35 years), hormone receptor-negative disease, and poorer survival. This adverse impact of pregnancy on the prognosis was apparent with postpartum breast cancer but not observed with breast cancer during pregnancy. Pregnancy after breast cancer did not compromise overall survival.

Fluoxetine and Risk of Bleeding in Patients Aged 60 Years and Older Using the Korea Adverse Event Reporting System Database: A Case/Noncase Study.

BACKGROUND: Depression, the leading cause of nonfatal disease burden, has a strong correlation with suicide and affects approximately 7% of the general elderly population. Adverse drug reactions in older patients are particularly important because of reduced drug metabolism, polypharmacy, drug-drug interactions, and drug-disease interactions. Fluoxetine is the first representative selective serotonin reuptake inhibitor but is associated with the possibility of hemorrhage based on its mechanism of action. Serious cases of gastrointestinal bleeding and cerebral hemorrhage have been reported, raising concerns about the safety of this drug. METHODS: We detected signals of bleeding risk associated with fluoxetine in an elderly population using the Korea Adverse Event Reporting System database. Reporting odds ratios and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 16,517 adverse events related to antidepressants were reported. The reporting odds ratios for fluoxetine were 2.34 (95% CI, 1.03-5.34) for total bleeding, 4.41 (95% CI, 1.60-12.15) for major bleeding, 2.06 (95% CI, 0.28-15.03) for gastrointestinal bleeding, and 6.12 (95% CI, 2.14-22.60) for brain hemorrhage compared with those of all other antidepressants. CONCLUSIONS: We detected safety signals with total bleeding, major bleeding, and brain hemorrhage related to fluoxetine. For patients with a high risk of bleeding, such as the elderly population, prescribing antidepressants other than fluoxetine can be considered. The results of this study provide preliminary evidence of a relationship between fluoxetine and hemorrhage but have wide 95% CIs. Further pharmacoepidemiological studies will be needed to confirm the risk of bleeding associated with fluoxetine.

Risk of pleural recurrence after percutaneous transthoracic needle biopsy in stage I non-small-cell lung cancer.

OBJECTIVES: To determine whether percutaneous transthoracic needle biopsy (PTNB) increased the risk of pleural recurrence in stage I non-small-cell lung cancer (NSCLC). METHODS: In this retrospective study, we reviewed 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010. Cox regression analyses with propensity score matching were performed to identify risk factors for pleural recurrence. RESULTS: Of 830 patients, 540 (65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative bronchoscopic biopsy or intraoperative wedge resection for a pathological diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI, 3.8-6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1-4.6]; 20 [3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis after matching, only visceral pleural invasion was associated with concomitant pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262-8.986; p=0.015) and isolated pleural recurrence (HR=3.216; 95% CI, 1.037-9.978; p=0.043), while PTNB was associated with neither concomitant nor isolated pleural recurrence (p=0.605 and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural approach did not have a significant association with pleural recurrence (p=0.539 and p=0.313, respectively); instead, visceral pleural invasion and microscopic lymphatic invasion were significantly associated with concomitant pleural recurrence, and microscopic lymphatic invasion was associated with isolated pleural recurrence (p<0.05). CONCLUSION: PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. KEY POINTS: • PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • The transfissural approach in PTNB did not increase the risk of pleural recurrence. • PTNB can be performed for the confirmatory diagnosis of peripheral stage I lung cancer without concern for the risk of pleural recurrence.

Online registry for nationwide database of Helicobacter pylori eradication in Korea: Correlation of antibiotic use density with eradication success.

BACKGROUND: The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. MATERIALS AND METHODS: We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. RESULTS: Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication. CONCLUSION: There was no relationship between the eradication rate and antibiotic use density in Korea.

The association between antidepressant use and deaths from road traffic accidents: a case-crossover study.

PURPOSE: Antidepressants are some of the most commonly used psychiatric medications, but little information is available about the effects of antidepressant treatment on the risk of traffic accidents across classes of antidepressants or associated with each substance individually. To investigate the relationship between exposure to antidepressants and risk of fatality in road traffic accidents. METHODS: We used a Korean national road traffic authority database linked with a national health insurance database between January 1, 2010 and December 31, 2014 and applied a case-crossover design. The study subjects were drivers in South Korea who died from traffic accidents and who had prescriptions for antidepressants within 1 year prior to the date of the accident. We compared the status of prescription for antidepressants with the hazard period and four matched control periods using conditional logistic regression, adjusting for other drug use. The trends of antidepressant utilization were described in terms of the number of prescriptions. A case-case-time-control design was applied to drugs with an increasing trend in use and a significant case-crossover odds ratio (OR). RESULTS: A total of 1250 antidepressant-using drivers were included, and an increased risk was observed during the 30-day hazard period (adjusted OR 1.30; 95% CI 1.03-1.63). Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) showed significant risks, but tricyclic antidepressants did not. However, the associations of all antidepressants, SSRIs, SNRIs, escitalopram, and duloxetine did not remain significant after adjusting for trends in utilization. Paroxetine and milnacipran were associated with increased risks, with no obvious increase in their utilization, but the possibility of confounding by indication could have affected the results for milnacipran. CONCLUSION: Considering the trends of antidepressant prescription and utilization, the use of paroxetine increased the risk of fatal traffic accidents.

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.

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 ß-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.

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.

Utilization patterns of disease-modifying antirheumatic drugs in elderly rheumatoid arthritis patients.

This study was conducted to investigate disease-modifying antirheumatic drug (DMARD) utilization in Korean elderly patients with rheumatoid arthritis (RA). We used data from January 1, 2005 to June 30, 2006 from the Health Insurance Review and Assessment Service claims database. The study subjects were defined as patients aged 65 yr or older with at least two claims with a diagnosis of RA. DMARD use was compared by the patients' age-group, gender, medical service, and geographic divisions. The patterns of DMARD use in mono- and combination therapy were calculated. RA medication use was calculated by the number of defined daily doses (DDD)/1,000 patients/day. A total of 166,388 patients were identified during the study period. DMARD use in RA patients was 12.0%. The proportion of DMARD use was higher in the younger elderly, females, and patients treated in big cities. Hydroxychloroquine was the most commonly used DMARD in monotherapy, and most of the combination therapies prescribed it with methotrexate. DMARD use in elderly RA patients was noticeably low, although drug prescriptions showed an increasing trend during the study period, clinicians may need to pay more attention to elderly RA patients.

Comparison of the safety of seven iodinated contrast media.

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.

Association of driving while intoxicated and suicide ideation and attempts in South Korea: a study in a nationally representative sample.

Evidence indicating driving as a means for suicide has been consistently reported. However, there have been few reported studies examining the association between driving while intoxicated (DWI) and suicide. We aimed to investigate the associations between DWI and suicide ideation and suicide attempts taking into account the frequency and amount of alcohol consumption. This cross-sectional study used data from semi-structured, face-to-face interviews conducted with a nationally representative sample of the Korea Community Health Survey in 2009, 2013, and 2017. The study included 267,457 adult participants who drank alcohol at least once and had driven a motor vehicle at least once in the preceding year. The DWI group comprised participants who had driven under the influence of alcohol at least once in the preceding year. The associations between DWI and suicide ideation and suicide attempts were examined using a logistic regression model, adjusting for the frequency and amount of alcohol consumption and history of depressive episodes in the preceding year. The role of DWI as a risk factor for suicide was also examined in an analysis stratified by the frequency and amount of alcohol consumption. The DWI group included 39,062 (14.6%) subjects, who were at higher risk for suicide ideation (adjusted odds ratio [aOR] = 1.91; 95% CI 1.81-2.01) and suicide attempts (aOR = 1.56; 1.27-1.92) than those not involved in DWI. Increased risks of suicide ideation and suicide attempts were observed in most strata in the stratified analysis. People who engage in DWI may have an increased risk of suicide ideation and suicide attempts; this relationship was generally observed regardless of the frequency and amount of alcohol consumption.

Association between weight loss agents and elevated liver enzymes: a population-based cross-sectional study.

The widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08-1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12-1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03-1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93-3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14-3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02-1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed.