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.

Associations of unspecified pain, idiopathic pain and COVID-19 in South Korea: a nationwide cohort study.

Background: Few studies have investigated unspecified or idiopathic pain associated with COIVD-19. This study aimed to provide the incidence rates of unspecified pain and idiopathic pain in patients with COVID-19 for 90 days after COVID-19 diagnosis. Methods: A propensity score matched cohort was used, including all patients with COVID-19 in South Korea, and analyzed their electronic medical records. The control group consisted of those who had not had tests for COVID-19 at all. Unspecified pain diagnoses consisted of diagnoses related to pain included in the ICD-10 Chapter XVIII. Idiopathic pain disorders included fibromyalgia, temporomandibular joint disorders, headaches, chronic prostatitis, complex regional pain syndrome, atypical facial pain, irritable bowel syndrome, and interstitial cystitis. Results: After matching, the number of participants in each group was 7,911. For most unspecified pain, the incidences were higher in the COVID-19 group (11.7%; 95% confidence interval [CI], 11.0-12.5) than in the control group (6.5%; 95% CI, 6.0-7.1). For idiopathic pain, only the headaches had a significantly higher incidence in the COVID-19 group (6.6%; 95% CI, 6.1-7.2) than in the control group (3.7%; 95% CI, 3.3-4.1). However, using a different control group that included only patients who visited a hospital at least once for any reasons, the incidences of most unspecified and idiopathic pain were higher in the control group than in the COVID-19 group. Conclusions: Patients with COVID-19 might be at a higher risk of experiencing unspecified pain in the acute phase or after recovery compared with individuals who had not had tests for COVID-19.

Association of Chronic Hepatitis B Infection and Antiviral Treatment With the Development of the Extrahepatic Malignancies: A Nationwide Cohort Study.

PURPOSE: Epidemiologic studies suggest that chronic hepatitis B (CHB) is a risk factor for various primary extrahepatic malignancies. Our aim was to evaluate the associations of CHB and nucleos(t)ide analog (NA) treatment with the risk of the development of extrahepatic malignancies. PATIENTS AND METHODS: We conducted an 18-month landmark analysis using nationwide claims data from the National Health Insurance Service of South Korea. Patients newly diagnosed with CHB in 2012-2014 (n = 90,944) and matched-controls (n = 685,436) were included. Patients with CHB were further classified as the NA-treated (CHB+/NA+, n = 6,539) or the NA-untreated (CHB+/NA-, n = 84,405) group. Inverse probability of treatment weighting analysis was applied to balance the treatment groups. Time-varying Cox analysis was performed to evaluate time-varying effect of NA treatment. The primary outcome was the development of any primary extrahepatic malignancy. Development of intrahepatic malignancy and death were considered as competing events. RESULTS: During the study period (median = 47.4 months), 30,413 patients (3.9%) developed any extrahepatic malignancy. The CHB+/NA- group had a higher overall risk of extrahepatic malignancy than the CHB+/NA+ group (adjusted subdistribution hazard ratio [aSHR] = 1.28; 95% CI, 1.12 to 1.45; P < .001) or controls (aSHR = 1.22; 95% CI, 1.18 to 1.26; P < .001). There was no difference in the risk of extrahepatic malignancy between the CHB+/NA+ group and the controls (CHB+/NA+ v control: aSHR = 0.96; 95% CI, 0.84 to 1.08; P = .48). In time-varying Cox analysis, the CHB+/NA- patients were associated with a higher risk of extrahepatic malignancy than the CHB+/NA+ patients (aSHR = 1.37; 95% CI, 1.23 to 1.52; P < .001). CONCLUSION: Patients with CHB have an elevated risk of developing primary extrahepatic malignancy. Long-term NA treatment was associated with a lower risk of extrahepatic malignancy development among patients with CHB.

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.

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients.

PURPOSE: This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. MATERIALS AND METHODS: We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. RESULTS: Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)-negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). CONCLUSION: Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

Patterns of percutaneous transthoracic needle biopsy (PTNB) of the lung and risk of PTNB-related severe pneumothorax: A nationwide population-based study.

BACKGROUND: As percutaneous transthoracic needle biopsy (PTNB) of the lung is a well-established diagnostic method for the evaluating pulmonary lesions, evidence of safety based on representative data is limited. This study investigated the practice patterns of PTNB of the lung and assessed the incidence and risk factors of PTNB-related severe pneumothorax in Korea. METHODS: We used a national-level health insurance database between January 1, 2007 and December 31, 2015. Patients who underwent PTNB of the lung were identified using procedure codes for organ biopsy, fluoroscopy, computed tomography, chest radiography, and lung-related diagnosis codes. The annual age-/sex-standardized rate of PTNB and the incidence of PTNB-related severe pneumothorax were calculated. We defined severe pneumothorax as the pneumothorax requiring intervention. The odds ratios of risk factors were assessed by a generalized estimating equation model with exchangeable working correlation matrix to address clustering effect within institution. RESULTS: A total of 66,754 patients were identified between 2007 and 2015. The annual age-/sex-standardized rate of PTNB per 100,000 population was 19.6 in 2007 and 22.4 in 2015, and it showed an increasing trend. The incidence of severe pneumothorax was 2.4% overall: 2.5% in men and 1.2% in women, and 2.6%, 2.7%, 2.1%, 2.1%, 1.9%, 2.4%, and 2.4% from 2009 to 2015. Older age (≥60), male sex, presence of chronic obstructive pulmonary disease, receiving treatment in an urban or rural area versus a metropolitan area, and receiving treatment at a general hospital were significantly associated with the risk of severe pneumothorax. CONCLUSIONS: Considering the increasing trend of PTNB, more attention needs to be paid to patients with risk factors for severe pneumothorax.

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.

Survival rates following medical intensive care unit admission from 2003 to 2013: An observational study based on a representative population-based sample cohort of Korean patients.

The decision as to whether patients should be admitted to a medical intensive care unit (ICU), in the absence of information concerning survival rates or prognostic factors in survival, is often challenging. We analyzed survival trends in relation to hospital discharge and examined patient and hospital characteristics associated with survival following ICU care, using a sample of nationwide claims data in Korea from 2002 through 2013. The Korean government implements a compulsory social insurance program that covers the country's entire population, and the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) data from 2002 based on this program were used for this study. The NHIS-NSC is a stratified random sample of 1,025,340 subjects selected from around 46 million Koreans. We evaluated annual survival trends using the Kaplan-Meier test. Analyses of the relationship between survival and patient and hospital characteristics were performed using Cox regression analyses. Employing a multivariate model, variables were selected using the forward selection method to consider the multicollinearity of variables. A total of 32,553 patients admitted to an ICU between 2002 and 2013 were identified among the eligible beneficiaries. The number of patients who had histories of ICU admission steadily increased throughout the study period, and patients older than 80 years constituted a progressively increasing proportion of ICU admissions, from 7.3% in 2002 to 16.9% in 2007 to 23.1% in 2013. The mean number of mechanical equipment items applied consistently increased, while no difference was observed in the trend for overall 1-year survival in patients following ICU treatment across the study period: the 1-year survival rate ranged from 66.7% (year 2003) to 64.2% (year 2010). Advanced age, cancer, renal failure, pneumonia, and influenza were all associated with heightened risk of mortality within 1 year. Our results should prove useful to older patients and their clinicians in their decisions regarding whether to seek ICU care, with the goals of improving the end-of life care and optimizing resource utilization.

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.

Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study.

Simultaneous competition for cytochrome P450 (CYP) 2C19 and CYP3A4 might diminish clopidogrel's antiplatelet effect by impacting its metabolic activation. This pharmacoepidemiologic study investigated whether proton pump inhibitors (PPIs) and CYP3A4-metabolized statins individually and jointly increase thrombotic events by attenuating clopidogrel's effectiveness. From Korean nationwide claims data (2007-2015), we selected 59,233 patients who initiated clopidogrel and statins after coronary stenting and compared thrombotic risks by PPI or CYP3A4-metabolized statin use or both. PPIs were associated with increased thrombotic risks (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45), unlike CYP3A4-metabolized statins (HR 1.03, 95% CI 0.98-1.07). PPIs with high CYP2C19-inhibitory potential were more relevant than those with low potential (HR 1.28, 95% CI 1.02-1.61). Joint effects of PPIs and CYP3A4-metabolized statins were nonsignificant (relative excess risk due to interaction -0.14, 95% CI -0.34 to 0.07). Concurrent PPIs were associated with increased thrombotic risks in patients receiving clopidogrel and statins; CYP3A4-metabolized statins did not exacerbate PPI-associated risks.

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.

Prevalence of extraintestinal manifestations in Korean inflammatory bowel disease patients.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) in South Korea is increasing. Although extraintestinal manifestations (EIMs) are an important factor in the clinical outcomes of IBD patients, EIMs have not yet been investigated in Korea. Thus, we conducted a cross-sectional study to assess the prevalence of EIMs in Korean IBD patients. METHODS: The 2014 claims data from the National Health Insurance System (NHIS) of Korea were used. IBD patients were identified by codes for Crohn disease (CD) and ulcerative colitis (UC) in the NHIS registration system for rare or intractable diseases. International Classification of Diseases, Tenth Edition codes were used to identify EIM cases. To estimate the prevalence of EIMs in the general population of Korea, we used national sample data. Standardized prevalence ratios (SPRs) were calculated to compare the prevalence rates of EIMs among IBD patients to those among the general population of Korea. RESULTS: A total of 13,925 CD patients and 29,356 UC patients were identified. CD and UC patients were different in terms of demographics and utilization of medication. Among the 17 EIMs investigated, pyoderma gangrenosum, osteomalacia, Sweet syndrome, and scleritis were observed in very few patients. The SPRs were greater than 1 for all EIMs. Aphthous stomatitis, rheumatoid arthritis, and osteoporosis were highly prevalent in both CD and UC patients, but the SPRs of the EIMs were not high. CONCLUSION: The study confirmed that EIMs are more prevalent among IBD patients than among the general population of Korea. The prevalence of EIMs in IBD patients suggests the need for greater attention and effort in clinical practice.

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.