Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). Conclusion Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

Background/Aims: Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than 0.7 using spirometry is the golden standard to diagnose airf low limitation of chronic obstructive pulmonary disease (COPD). Recently, measuring FEV6 has been suggested as an alternative to measure FVC. Studies about the cut-off value for FEV1/FEV6 to diagnose airflow limitation have shown variable results, with values between 0.7 and 0.8. The purpose of this study was to determine the best cut-off value of FEV1/FEV6 to detect airflow limitation using handheld spirometry. Methods: We recruited subjects over 40 years of age with smoking history over 10 pack-years. Participants underwent measurements with both handheld spirometry and conventional spirometry. We calculated the sensitivity and specificity of the value of FEV1/FEV6 using receiver-operating characteristic (ROC) curve analysis to obtain the diagnostic accuracy of handheld spirometry to detect airflow limitation. Results: A total of 290 subjects were enrolled. Their mean age and smoking amount were 63.1 years and 31.6 pack-years, respectively. According to our ROC curve analysis, when FEV1/FEV6 ratio was 73%, sensitivity and specificity were the maximum and the area under the ROC curve was 0.93, showing an excellent diagnostic accuracy. Sensitivity, specificity, positive predictive value, and negative predictive value were 86.7%, 89.7%, 88.0%, and 88.5%, respectively. Participants with FEV1/FEV6 ≤ 73% had lower FEV1 predicted value compared to those with FEV1/FEV6 > 73% (65.4% vs. 86.5%, p < 0.001). Conclusions In summary, we demonstrate that the value of 73% in FEV1/FEV6 using handheld spirometry has the best sensitivity and specificity to detect airflow limitation in subjects with risk of COPD.

Background/Aims: Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than 0.7 using spirometry is the golden standard to diagnose airf low limitation of chronic obstructive pulmonary disease (COPD). Recently, measuring FEV6 has been suggested as an alternative to measure FVC. Studies about the cut-off value for FEV1/FEV6 to diagnose airflow limitation have shown variable results, with values between 0.7 and 0.8. The purpose of this study was to determine the best cut-off value of FEV1/FEV6 to detect airflow limitation using handheld spirometry. Methods: We recruited subjects over 40 years of age with smoking history over 10 pack-years. Participants underwent measurements with both handheld spirometry and conventional spirometry. We calculated the sensitivity and specificity of the value of FEV1/FEV6 using receiver-operating characteristic (ROC) curve analysis to obtain the diagnostic accuracy of handheld spirometry to detect airflow limitation. Results: A total of 290 subjects were enrolled. Their mean age and smoking amount were 63.1 years and 31.6 pack-years, respectively. According to our ROC curve analysis, when FEV1/FEV6 ratio was 73%, sensitivity and specificity were the maximum and the area under the ROC curve was 0.93, showing an excellent diagnostic accuracy. Sensitivity, specificity, positive predictive value, and negative predictive value were 86.7%, 89.7%, 88.0%, and 88.5%, respectively. Participants with FEV1/FEV6 ≤ 73% had lower FEV1 predicted value compared to those with FEV1/FEV6 > 73% (65.4% vs. 86.5%, p < 0.001). Conclusions In summary, we demonstrate that the value of 73% in FEV1/FEV6 using handheld spirometry has the best sensitivity and specificity to detect airflow limitation in subjects with risk of COPD.

Background: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. Methods: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. Results: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. Conclusion The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

BACKGROUND: Understanding the burden of disease is important to establish cost-effective treatment strategies and to allocate healthcare resources appropriately. However, little reliable information is available regarding the overall economic burden imposed by chronic obstructive pulmonary disease (COPD) in Korea. METHODS: This study is a multicenter observational research on the COPD burden in Korea. Total COPD costs were comprised of three categories: direct medical, direct non-medical, and indirect costs. For direct medical costs, institutional investigation was performed at 13 medical facilities mainly based on the claims data. For direct non-medical and indirect costs, site-based surveys were administered to the COPD patients during routine visits. Total costs were estimated using the COPD population defined in the recent report. RESULTS: The estimated total costs were approximately 1,245 million US dollar (1,408 billion Korean won). Direct medical costs comprised approximately 20% of the total estimated costs. Of these, formal medical costs held more than 80%. As direct non-medical costs, nursing costs made up the largest percentage (39%) of the total estimated costs. Costs for COPD-related loss of productivity formed four fifths of indirect costs, and accounted for up to 33% of the total costs. CONCLUSION: This study shows for the first time the direct and indirect costs of COPD in Korea. The total costs were enormous, and the costs of nursing and lost productivity comprised approximately 70% of total costs. The results provide insight for an effective allocation of healthcare resources and to inform establishment of strategies to reduce national burden of COPD.
Delivery of Health Care ; Efficiency ; Health Care Costs ; Humans ; Korea* ; Nursing ; Pulmonary Disease, Chronic Obstructive*

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.
Activating Transcription Factor 3 ; Adipocytes ; Adiponectin ; Adipose Tissue, White ; Animals ; Diet* ; Insulin Resistance ; Metabolic Diseases* ; Mice ; Mice, Obese* ; Microarray Analysis ; Obesity* ; RNA, Messenger

PURPOSE: Asthma is a common disease that is expensive and burdensome for patients. Inhaled corticosteroids (ICS) are the most important drugs for asthma treatment and are often prescribed long-term. However, the use of ICS has been reported to increase pneumonia, though this remains controversial. We evaluated whether the use of ICS increases the risk of pneumonia in asthmatic patients using the Health Insurance Review and Assessment Service (HIRA) database in Korea. METHODS: The Asthma Management Adequacy Assessment was performed by the HIRA in Korea. Patients with claimed insurance benefits for asthma disease codes and who were prescribed asthma medications more than 2 times were enrolled. Patient demographics, asthma medications, healthcare use, and complications were analyzed. RESULTS: The total number of asthma patients was 831,613. Patients using ICS were older and had more comorbidities than those not using ICS; they also visited outpatient clinics and emergency departments, and were more often hospitalized. Pneumonia and other complications occurred more often in patients using ICS, and they used more respiratory medications, except for theophylline. Multiple logistic regression analysis showed that ICS prescription was associated with pneumonia (odds ratio, 1.38; 95% confidence interval, 1.36-1.41). Age, sex, medical care, use of secondary and tertiary hospitals, and hospitalization due to asthma in the previous year were also associated with pneumonia. CONCLUSIONS: ICS use was associated with increasing pneumonia in asthmatic patients in Korea. Therefore, it is critical to acknowledge that the use of ICS may increase the risk of pneumonia and should be meticulously monitored in asthmatics.
Adrenal Cortex Hormones ; Ambulatory Care Facilities ; Asthma ; Comorbidity ; Delivery of Health Care ; Demography ; Emergency Service, Hospital ; Hospitalization ; Humans ; Insurance Benefits ; Insurance, Health ; Korea ; Logistic Models ; Pneumonia ; Prescriptions ; Steroids ; Tertiary Care Centers ; Theophylline

OBJECTIVE: This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS: We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20–60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. RESULTS: Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08–2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P < 0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01–17.00). CONCLUSION: The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.
Atypical Squamous Cells of the Cervix* ; Cohort Studies* ; Epidemiology ; Female ; Follow-Up Studies ; Human papillomavirus 16* ; Human Papillomavirus DNA Tests ; Humans ; Logistic Models ; Papillomaviridae ; Risk Factors* ; Smoking ; Squamous Intraepithelial Lesions of the Cervix

OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Alphapapillomavirus/genetics ; *Atypical Squamous Cells of the Cervix/pathology/virology ; Cell Adhesion Molecules/genetics ; *DNA Methylation ; Female ; Genotype ; Humans ; Immunoglobulins/genetics ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics ; Paired Box Transcription Factors/genetics ; Papanicolaou Test ; Pituitary Adenylate Cyclase-Activating Polypeptide/genetics ; ROC Curve ; Squamous Intraepithelial Lesions of the Cervix/*genetics/pathology/virology ; Uterine Cervical Neoplasms/*genetics/pathology/virology ; Vaginal Smears