Yeon-Yong Kim

Transcription factor decoy for AP-1 reduces mesangial cell proliferation and extracellular matrix production in vitro and in vivo

Diabetic nephropathy is characterized by an expansion of glomerular mesangium, caused by mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins, which eventually leads to glomerulosclerosis and renal failure. Activator protein-1 (AP-1), a transcription factor, is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation and ECM production. This investigation was undertaken to test the hypothesis that AP-1 plays an important role in ECM gene expression, and to develop a molecular therapeutic strategy based on decoy oligodeoxynucleotides (ODN). In this report, we show that transfection with AP-1 decoy ODN strongly inhibits high glucose- and angiotensin II-induced cell proliferation and expression of ECM genes in cultured mesangial cells in vitro. Administration of AP-1 decoy ODN into streptozotocin-induced diabetic rat kidney in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually abolished TGF-β1 and plasminogen activator inhibitor-1 expression. Our results collectively indicate that AP-1 activation is crucial for mesangial cell proliferation and ECM production in response to high glucose and angiotensin II. Moreover, use of stable AP-1 decoy ODN combined with the highly effective HVJ-liposome method provides a novel potential molecular therapeutic strategy for the prevention of diabetic nephropathy.

Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter

Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats with hemagglutinating virus of Japan-envelope (HVJ-E) vectors containing Epstein–Barr virus (EBV) plasmids encoding the genes for insulin and the GLUT 2 transporter. Efficient delivery of the genes was achieved with the HVJ-E vector, and the use of the EBV replicon vector led to prolonged hepatic gene expression. Blood glucose levels were normalized for at least 3 weeks as a result of the gene therapy. Cotransfection of GLUT 2 with insulin permitted the diabetic rats to regulate their blood glucose levels upon exogenous glucose loading in a physiologically appropriate manner and improved postprandial glucose levels. Moreover, cotransfection with insulin and GLUT 2 genes led to in vitro glucose-stimulated insulin secretion that involved the closure of KATP channels. The present study represents a new way to efficiently deliver insulin gene in vivo that is regulated by ambient glucose level with prolonged gene expression. This may provide a basis to overcome limitations of insulin gene therapy in humans.

Data Analytic Process of a Nationwide Population-Based Study on Obesity Using the National Health Information Database Presented by the National Health Insurance Service 2006-2015

Background In Korea, the prevalence of obesity has steadily increased, and the socioeconomic burden of obesity has increased along with it. In 2015, the National Health Insurance Service (NHIS) signed a memorandum of understanding with the Korean Society for the Study of Obesity (KSSO), providing limited open access to its databases so that the status of obesity and obesity management could be investigated. Methods Using NHIS databases, we analyzed nationwide population-based studies for obesity using the definition of obesity (body mass index ≥25 kg/m2) in subjects over the age of 20. Age and sex standardization were used for all data. Results The KSSO released the ‘Obesity Fact Sheet 2016’ using the 2006–2015 NHIS Health Checkup database. The prevalence of obesity steadily increased from 28.7% in 2006 to 32.4% in 2015, and the prevalence of abdominal obesity also steadily increased from 18.4% in 2009 to 20.8% in 2015. The prevalence of class II obesity steadily increased from 2006 to 2015, such that the total prevalence was 4.8% in 2015 (5.6% in men and 4.0% in women). The highest prevalence of obesity was found in Jeju Island, while the lowest prevalence was found in Daegu City. The highest prevalence of abdominal obesity was also found in Jeju Island, while the lowest prevalence was found in Gwangju City. Conclusion Based on the Obesity Fact Sheet 2016, a strategy for reducing the prevalence of obesity is needed, especially in Korean men.

Factors Affecting the Downward Mobility of Psychiatric Patients: A Korean Study of National Health Insurance Beneficiaries

Objectives: The purpose of this study is to examine the magnitude of and the factors associated with the downward mobility of first-episode psychiatric patients. Methods: This study used the claims data from the Korean Health Insurance Review and Assessment Service. The study population included 19 293 first-episode psychiatric inpatients diagnosed with alcohol use disorder (International Classification of Diseases, 10th revision [ICD-10] code F10), schizophrenia and related disorders (ICD-10 codes F20-F29), and mood disorders (ICD-10 codes F30-F33) in the first half of 2005. This study included only National Health Insurance beneficiaries in 2005. The dependent variable was the occurrence of downward mobility, which was defined as a health insurance status change from National Health Insurance to Medical Aid. Logistic regression analysis was used to assess factors associated with downward drift of first-episode psychiatric patients. Results: About 10% of the study population who were National Health Insurance beneficiaries in 2005 became Medical Aid recipients in 2007. The logistic regression analysis showed that age, gender, primary diagnosis, type of hospital at first admission, regular use of outpatient clinic, and long-term hospitalization are significant predictors in determining downward drift in newly diagnosed psychiatric patients. Conclusions: This research showed that the downward mobility of psychiatric patients is affected by long-term hospitalization and medical care utilization. The findings suggest that early intensive intervention might reduce long-term hospitalization and the downward mobility of psychiatric patients.

Prevalence of Overweight and Income Gaps in 245 Districts of Korea: Comparison Using the National Health Screening Database and the Community Health Survey, 2009–2014

Background We compared age-standardized overweight prevalence and their income gaps at the level of district in Korea using the National Health Screening Database (NHSD) and the Community Health Survey (CHS). Methods We analyzed 39,093,653 subjects in the NHSD and 926,580 individuals in the CHS between 2009 and 2014. For the comparison of body mass index (BMI) distributions, data from 26,100 subjects in the Korea National Health and Nutrition Examination Survey (KNHANES) were also analyzed. We calculated the age-standardized overweight prevalence and its interquintile income gap at the district level. We examined the magnitudes of the between-period correlation for age-standardized overweight prevalence. The differences in overweight prevalence and its income gap between the NHSD and the CHS were also investigated. Results The age-adjusted mean BMI from the CHS was lower than those from the NHSD and the KNHANES. The magnitudes of the between-period correlation for overweight prevalence were greater in the NHSD compared to the CHS. We found that the district-level overweight prevalence in the NHSD were higher in all districts of Korea than in the CHS. The correlation coefficients for income gaps in overweight prevalence between the two databases were relatively low. In addition, when using the NHSD, the district-level income inequalities in overweight were clearer especially among women than the inequalities using the CHS. Conclusion The relatively large sample size for each district and measured anthropometric data in the NHSD are more likely to contribute to valid and reliable measurement of overweight inequality at the district level in Korea.

Level of Agreement and Factors Associated With Discrepancies Between Nationwide Medical History Questionnaires and Hospital Claims Data

Objectives The objectives of this study were to investigate the agreement between medical history questionnaire data and claims data and to identify the factors that were associated with discrepancies between these data types. Methods Data from self-reported questionnaires that assessed an individual’s history of hypertension, diabetes mellitus, dyslipidemia, stroke, heart disease, and pulmonary tuberculosis were collected from a general health screening database for 2014. Data for these diseases were collected from a healthcare utilization claims database between 2009 and 2014. Overall agreement, sensitivity, specificity, and kappa values were calculated. Multiple logistic regression analysis was performed to identify factors associated with discrepancies and was adjusted for age, gender, insurance type, insurance contribution, residential area, and comorbidities. Results Agreement was highest between questionnaire data and claims data based on primary codes up to 1 year before the completion of self-reported questionnaires and was lowest for claims data based on primary and secondary codes up to 5 years before the completion of self-reported questionnaires. When comparing data based on primary codes up to 1 year before the completion of self-reported questionnaires, the overall agreement, sensitivity, specificity, and kappa values ranged from 93.2 to 98.8%, 26.2 to 84.3%, 95.7 to 99.6%, and 0.09 to 0.78, respectively. Agreement was excellent for hypertension and diabetes, fair to good for stroke and heart disease, and poor for pulmonary tuberculosis and dyslipidemia. Women, younger individuals, and employed individuals were most likely to under-report disease. Conclusions Detailed patient characteristics that had an impact on information bias were identified through the differing levels of agreement.

Factors associated with the specialty choice of Korean medical students: a cross-sectional survey

BackgroundAn imbalance of physician supply by medical specialty has been observed in most countries. In Korea, there is a greater tendency to avoid surgical specialties and specialty choices in nonclinical medicine, such as the basic science of medicine. In this study, we identified factors affecting the specialty choice of physicians in order to provide a basis for policies to address this problem.MethodsWe used the results of a 2013 nationwide survey of 12 709 medical students (82.7 % responded) to analyze the data of 9499 students after excluding missing data. Descriptive analyses of all students’ specialty choice were performed. Logistic regression was performed by selecting gender, age, grade level, type of medical school, hometown, and the location of the medical school as the independent variables. Medical specialty was the dependent variable. The dependent variable, or specialty of medicine, was categorized into three groups: nonclinical/clinical medicine, surgical-medical specialty, and controllable lifestyle specialty.ResultsThe order of preferred medical specialties was internal medicine, psychiatry, and pediatrics; for surgical specialties, the order was orthopedic surgery, general surgery, and ophthalmology. Medical specialties were most favored by women and students in the third (men) and second (women) year of the medical program, whereas surgical specialties were most preferred by men and students in the first year of the program. Students in the third year mostly favored nonclinical medicine. Medical college students had a stronger preference for nonclinical medicine (odds ratio [OR] 1.625, 95 % confidence interval [CI] 1.139–2.318) than graduate medical school students. Surgical specialties were more favored by men (OR 2.537, 95 % CI 2.296–2.804) than by women. However, they were favored less by medical college students (OR 0.885, 95 % CI 0.790–0.991) than by graduate medical school students and by medical students in metropolitan areas (OR 0.892, 95 % CI 0.806–0.988) than by medical students in nonmetropolitan areas. A controllable lifestyle specialty was less favored by men (OR 0.802, 95 % CI 0.730–0.881) than by women.ConclusionsBased on these results, we can evaluate the effectiveness of the government’s educational policies for solving the imbalance of physician supply and provide empirical evidence to understand and solve this problem.

Effect of medication adherence on long-term all-cause-mortality and hospitalization for cardiovascular disease in 65,067 newly diagnosed type 2 diabetes patients

This study determined the effects of anti-diabetic medication adherence on the long-term all-cause mortality and hospitalization for cerebrovascular disease and myocardial infarction among newly diagnosed patients. The study used retrospective cohort from the National Health Insurance Service. Study participants were 65,076 newly diagnosed type 2 diabetes mellitus patients aged ≥40 years. The medication adherence was evaluated from the proportion of days covered (PDC) between 2006 and 2007. Outcome variables were mortality, newly diagnosed cerebrovascular disease (CVD) and myocardial infarction (MI) in 2008–2017. Cox-proportional hazard regression analysis was performed. After adjusting for sex, age, monthly contribution, insurance type, medical institution type, Charlson comorbidity index score, disability, hypertension, and active ingredients of oral hypoglycemic agents, the adjusted hazard ratio (aHR) for all-cause-mortality of the lowest PDC group (<0.20) was 1.45 (95% confidence interval [CI] = 1.36–1.54) as compared to the highest PDC (≥0.8). The aHR for all-cause-mortality associated with PDC levels of 0.60–0.79, 0.40–0.59, and 0.20–0.39 were 1.19, 1.26, and 1.34, respectively (Ptrend < 0.001). Compared to the highest PDC group, diabetic patients with the lowest PDC had elevated risk for CVD (aHR = 1.41; 95% CI = 1.30–1.52; Ptrend < 0.001). Improving anti-diabetic medication adherence among newly diagnosed type 2 diabetes mellitus patients is essential to the reduce risk for cardiovascular disease and long-term all-cause mortality.

Comparison of District-level Smoking Prevalence and Their Income Gaps from Two National Databases: the National Health Screening Database and the Community Health Survey in Korea, 2009–2014

Background We compared age-standardized prevalence of cigarette smoking and their income gaps at the district-level in Korea using the National Health Screening Database (NHSD) and the Community Health Survey (CHS). Methods Between 2009 and 2014, 39,049,485 subjects participating in the NHSD and 989,292 participants in the CHS were analyzed. The age-standardized prevalence of smoking and their interquintile income differences were calculated for 245 districts of Korea. We examined between-period correlations for the age-standardized smoking prevalence at the district-level and investigated the district-level differences in smoking prevalence and income gaps between the two databases. Results The between-period correlation coefficients of smoking prevalence for both genders were 0.92–0.97 in NHSD and 0.58–0.69 in CHS, respectively. When using NHSD, we found significant income gaps in all districts for men and 244 districts for women. However, when CHS was analyzed, only 167 and 173 districts for men and women, respectively, showed significant income gaps. While correlation coefficients of district-level smoking prevalence from two databases were 0.87 for men and 0.85 for women, a relatively weak correlation between income gaps from the two databases was found. Conclusion Based on two databases, income gaps in smoking prevalence were evident for nearly all districts of Korea. Because of the large sample size for each district, NHSD may provide stable district-level smoking prevalence and its income gap and thus should be considered as a valuable data source for monitoring district-level smoking prevalence and its socioeconomic inequality.

Effects of patients’ motives in choosing a provider on determining the type of medical institution

Background Primary care is relatively weak in the Republic of Korea. As the referral system is not well established, patients can freely choose from among clinics, hospitals, and tertiary hospitals. This study was conducted to determine the factors influencing patients’ choice of providers. Methods A survey was conducted of 999 Korean adults aged 19–59 years. An exploratory factor analysis was performed on nine factors influencing their motives in choosing a medical provider. The factors derived from this analysis and the types of medical institutions were used as the independent and dependent variables, respectively, in logistic regression analysis. Adjustments were made for region, gender, age, educational level, income, type of insurance, and chronic diseases. Results The results showed that patients preferred clinics when considering the importance of accessibility, staff kindness, and patient-centeredness; they preferred hospitals when considering cleanliness; and tertiary hospitals when considering the reputation and structural factors. When considering structural factors, clinics and hospitals were less preferred; however tertiary hospitals were less preferred when considering accessibility, staff kindness, and patient-centeredness. Conclusion It is necessary to provide more accessible and patient-centered services in order to strengthen the primary health care role of clinics. In addition, efforts are needed to improve the quality of health care of tertiary hospitals in order to meet patient expectations.