Seungho Ryu

Comparison of Guaiac-Based and Quantitative Immunochemical Fecal Occult Blood Testing in a Population at Average Risk Undergoing Colorectal Cancer Screening

OBJECTIVES:Although some studies have shown that the quantitative, immunochemical fecal occult blood test (FOBT) (qFIT) has better performance characteristics than the standard guaiac-based FOBT (GT) for identifying advanced colorectal neoplasia (ACRN), there is limited information on test performance of these tests in average-risk populations.METHODS:Seven hundred seventy consecutive average-risk patients from four centers who were undergoing screening colonoscopy also provided stool samples. Stool specimens from three consecutive bowel movements were applied to a hemoccult II test card (Beckman Coulter, Fullerton, CA) and OC-SENSA MICRO (Eiken Chemical, Tokyo, Japan) sampling probes at the same time. We measured the diagnostic value of the qFIT for detecting an ACRN by using three criteria: sensitivity, specificity, and likelihood ratios. A receiver operating characteristic curve for determining the qFIT cutoff values and the number of tests that best discriminated between ACRNs and other findings were determined.RESULTS:Seventy-eight ACRNs were identified during colonoscopy. At all hemoglobin thresholds, the sensitivity of the qFIT was higher than that of the GT for cancer or ACRN. The sensitivity and specificity of the GT for detecting advanced adenomas, cancer, and ACRNs were 13.6%/92.4%, 30.8%/92.4%, and 16.7%/92.9%, respectively. Using the 100 ng/ml cut point and three-sample qFIT results, the sensitivity and specificity of the qFIT for detecting advanced adenomas, cancer, and ACRNs were 33.9%/90.6%, 84.6%/89.8%, and 43.7%/91.9%, respectively. The area under the curve for cancer indicated that using either 2 or 3 tests provided the best discrimination for cancer.CONCLUSIONS:The qFIT provides a higher sensitivity for detecting ACRN and cancer than the GT, and has an acceptable specificity that significantly reduces the need for colonoscopic evaluation in the screened population.

Characteristics of Excessive Cellular Phone Use in Korean Adolescents

Abstract The objective of this study was to evaluate the possible psychological problems related to excessive cellular phone use in adolescents. Results from 595 participants showed that the potentially excessive user group had a tendency to identify themselves with their cellular phones and to have difficulties in controlling usage. They expressed more depressive symptoms, higher interpersonal anxiety, and lower self-esteem. A positive correlation was also observed between excessive cellular phone use and Internet addiction.

Metabolically-healthy obesity and coronary artery calcification.

OBJECTIVES The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women. BACKGROUND The risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as MHO, is controversial. METHODS We conducted a cross-sectional study of 14,828 metabolically-healthy adults with no known cardiovascular disease who underwent a health checkup examination that included estimation of CAC scores by cardiac tomography. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. RESULTS MHO individuals had a higher prevalence of coronary calcification than normal weight subjects. In multivariable-adjusted models, the CAC score ratio comparing MHO with normal-weight participants was 2.26 (95% confidence interval: 1.48 to 3.43). In mediation analyses, further adjustment for metabolic risk factors markedly attenuated this association, which was no longer statistically significant (CAC score ratio 1.24; 95% confidence interval: 0.79 to 1.96). These associations did not differ by clinically-relevant subgroups. CONCLUSIONS MHO participants had a higher prevalence of subclinical coronary atherosclerosis than metabolically-healthy normal-weight participants, which supports the idea that MHO is not a harmless condition. This association, however, was mediated by metabolic risk factors at levels below those considered abnormal, which suggests that the label of metabolically healthy for obese subjects may be an artifact of the cutoff levels used in the definition of metabolic health.

A nationwide survey on the prevalence of dementia and mild cognitive impairment in South Korea.

We investigated the prevalence of dementia and mild cognitive impairment (MCI) and the factors associate with risk of dementia from a representative nationwide sample of Korean elders. 8,199 randomly-sampled Koreans aged 65 years or older were invited to participate in the Phase I screening assessment using Mini-Mental State Examination by door-to-door home visit, and 6,141 subjects (response rate = 74.9%) responded. Among them, 2,336 subjects were invited to participate in the Phase II diagnostic assessment for dementia and MCI, and 1,673 subjects responded (response rate = 71.6%). Diagnostic assessments were administered using the Korean version of the Consortium to Establish a Registry for Alzheimers Disease Assessment Packet (CERAD-K) Clinical Assessment Battery. The CERAD-K Neuropsychological Assessment Battery was used for diagnosing MCI. Age-, gender-, education-, and urbanicity-standardized prevalence of dementia was estimated to be 8.1% (95% CI = 6.9-9.2) for overall dementia and 24.1% (95% CI = 21.0-27.2) for MCI. Alzheimers disease (AD) was the most prevalent type (5.7%) followed by vascular dementia (2.0%). Amnestic subtype (20.1%) was much more prevalent than nonamnestic subtype in MCI (4.0%). Older age, being male, lower education level, illiteracy, smoking, and histories of head trauma or depression were associated with increased dementia risk, and alcohol use and moderately intense exercise were associated with decreased dementia risk. We expect numbers of dementia patients to double every 20 years until 2050 in Korea and expect AD to account for progressively more dementia cases in the future.

Association between a G-protein β3 subunit gene polymorphism and the symptomatology and treatment responses of major depressive disorders

ABSTRACTThe genes involved in signal transduction are major candidates in association studies on affective disorders and responses to antidepressants. We investigated whether the C825T polymorphism of the β3 subunit of G protein (GNB3) gene is associated with the symptom severity or treatment response of major depressive disorders (MDDs) in a Korean sample of 106 MDD patients; our study also included 133 healthy controls. Hypertensive subjects were excluded from the study because association between GNB3 variants and hypertension has been reported in previous studies. We found significantly more carriers of the 825T allele in MDD patients than in normal controls (χ2=6.37, P=0.012; OR=2.19, 95% CI 1.18–4.05). The T-allele carriers showed higher scores than those with the CC genotype in the baseline total and in some subcategories of the Hamilton Depression Rating Scale (P<0.05). We also found a statistically significant association between T-allele carriers and antidepressant treatment response (P<0.05). These results suggest that the T allele of the C825T polymorphism in the GNB3 gene is associated with MDD. It was also demonstrated that MDD patients bearing the T allele had a severe symptomatology and a better response to antidepressant treatment than patients without the T allele.

Metabolically Healthy Obesity and Development of Chronic Kidney Disease: A Cohort Study.

Context The risk for chronic kidney disease (CKD) among obese patients without metabolic abnormalities is unknown. Contribution In this cohort study of South Korean men and women, metabolically healthy overweight and obese participants had increased incidence of CKD compared with normal-weight participants. Caution Body mass index was a marker of obesity and was assessed only once at baseline. Implication Physicians should monitor metabolically healthy obese and overweight patients for CKD and counsel them about maintaining a healthy weight and lifestyle. Chronic kidney disease (CKD) is a major clinical and public health problem (1). It is a precursor for end-stage renal disease and a strong risk factor for cardiovascular morbidity and mortality (2). Its prevalence is increasing worldwide along with the growing prevalence of obesity and metabolic disease (3). Indeed, obesitymediated by hypertension, insulin resistance, hyperglycemia, dyslipidemia, and other metabolic abnormalitiesis a major risk factor for CKD (4). Although the role of obesity-induced metabolic abnormalities in CKD development is well-established, metabolically healthy obese (MHO) persons, seem to have a favorable profile with no metabolic abnormalities (5, 6). The association between MHO and CKD, however, is largely unknown. The only study available found no association (7), but the comparison between MHO and normal-weight participants could be biased because the reference group included overweight participants, and metabolically healthy participants were defined as those with fewer than 2 metabolic components. Therefore, we examined the association between categories of body mass index (BMI) and CKD in a large sample of metabolically healthy men and women who had health screening examinations. Methods Study Population The Kangbuk Samsung Health Study is a cohort study of South Korean men and women aged 18 years or older who had a comprehensive annual or biennial health examination at the clinics of the Kangbuk Samsung Hospital Health Screening Centers in Seoul and Suwon, South Korea (8). More than 80% of participants were employees of various companies and local governmental organizations and their spouses. In South Korea, the Industrial Safety and Health Act requires all employees to receive annual or biennial health screening examinations, offered free of charge. The remaining participants registered for the screening examinations on their own. Our analysis included all persons who had comprehensive health examinations from 1 January 2002 to 31 December 2009 and had at least 1 other screening examination before 31 December 2013 (that is, they all had a baseline visit and 1 follow-up visit [n=175859]) (Figure 1). We excluded persons who had metabolic abnormalities (5, 9, 10) or evidence of kidney disease at baseline (n=108263). We excluded those with fasting glucose levels of 100 mg/dL or greater or who used glucose-lowering agents; blood pressure (BP) of 130/85 mm Hg or greater or who used BP-lowering agents; triglyceride levels of 150 mg/dL or greater or who used lipid-lowering agents; high-density lipoprotein (HDL) cholesterol levels less than 40 mg/dL in men or less than 50 mg/dL in women; insulin resistance, defined as homeostasis model assessment of insulin resistance (HOMA-IR) scores of 2.5 or greater (11); estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2; proteinuria; history of CKD; or history of cancer. Among eligible participants (n=67596), we further excluded those with missing values in any of the study variables (n=5347 [7.9%]). The final sample size was 62249 participants (Figure 1), all of whom were metabolically healthy and did not have markers of kidney disease at baseline. This study was approved by the Institutional Review Board of the Kangbuk Samsung Hospital, which exempted the requirement for informed consent because we only accessed deidentified data routinely collected as part of health screening examinations. Figure 1. Study flow diagram. CKD = chronic kidney disease; HDL = high-density lipoprotein. * Participants in the screening program could have >1 criterion that made them ineligible for the study. Eligible participants could have missing data in >1 study variable. Measurements Data on medical history, medication use, family history, physical activity, alcohol intake, smoking habits, and education level were collected by a standardized, self-administered questionnaire. Anthropometry data, BP, and blood samples were obtained by trained staff during the examinations (8, 12). Smoking status was categorized as never, former, or current. Alcohol consumption was categorized as none, moderate (20 g per day), or high (>20 g per day). The weekly frequency of moderate- or vigorous-intensity physical activity was also assessed. Sitting BP, height, and weight were measured by trained nurses. Height was measured to the nearest 1 cm with a stadiometer while the participant stood barefoot. Weight was measured to the nearest 0.1 kg on a bioimpedance analyzer (InBody 3.0 and Inbody 720, Biospace), which was validated for reproducibility and accuracy of body composition measurements (13) and calibrated every morning before testing started. Body mass index was calculated as weight in kilograms divided by height in meters squared and was classified according to Asian-specific criteria (14) (underweight, BMI <18.5 kg/m2; normal weight, BMI of 18.5 to 22.9 kg/m2; overweight, BMI of 23 to 24.9 kg/m2; and obese, BMI 25 kg/m2). Blood specimens were sampled from the antecubital vein after at least a 10-hour fast. The methods for measuring serum levels of glucose, uric acid, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, HDL cholesterol, aspartate aminotransferase, alanine aminotransferase, -glutamyltransferase, insulin, and high-sensitivity C-reactive protein (hsCRP) have been reported elsewhere (8, 12). The Department of Laboratory Medicine of the Kangbuk Samsung Hospital has been accredited by the Korean Society for Laboratory Medicine and the Korean Association of Quality Assurance for Clinical Laboratories and participates in the College of American Pathologists Proficiency Testing survey. Insulin resistance was assessed with the HOMA-IR equation (fasting insulin [uU/mL]fasting glucose [mmol/L] 22.5). An ultrasonographic diagnosis of fatty liver was defined as a diffuse increase of fine echoes in the liver parenchyma compared with the kidney or spleen parenchyma (15, 16). During the study period, serum creatinine levels were measured with the kinetic alkaline picrate method (Jaffe method) in an automated chemistry analyzer (from 2002 to 2009, we used the Advia 1650a Autoanalyzer [Bayer Diagnostics]; from 2010 to 2013, we used the Modular D2400 [Roche]). The within-batch and total coefficients of variation were 1.8% to 3.9% for low-level and 1.4% to 1.8% for high-level quality control specimens throughout the study. Because the laboratory method that was used to measure serum creatinine levels from 2002 to 2009 was not traceable to isotope-dilution mass spectrometry, we estimated GFR by using the 4-variable Modification of Diet in Renal Disease Study equation (17). The conclusions did not change if we used the Chronic Kidney Disease Epidemiology Collaboration equation (18) for GFR estimation (data not shown). Urine protein was measured semiquantitatively by urine dipstick (URiSCAN Urine test strips, YD Diagnostics) tested on fresh, midstream urine samples and was reported in the following 6 grades: absent, trace, 1+, 2+, 3+, and 4+ (corresponding to protein levels of undetectable, 10 mg/dL, 30 mg/dL, 100 mg/dL, 300 mg/dL, and 1000 mg/dL, respectively). Proteinuria was defined as a grade of 1+ or greater. Statistical Analysis Person-years of follow-up were calculated from the date of the baseline health examination until the date of CKD diagnosis or the last screening examination, whichever came first. The cumulative incidence of CKD for baseline BMI categories (<18.5, 18.5 to 22.9, 23.0 to 24.9, or 25.0 kg/m2) were standardized to the empirical distribution of baseline confounders in the overall study sample with inverse probability weighting (19, 20). We first fitted a multinomial logistic regression to estimate each participants probability of being in his or her own BMI category given the observed confounders. Stabilized weights were then calculated as the inverse of the estimated conditional probabilities of exposure, further rescaled by the overall proportion of participants in each BMI category to reduce variability of weights across groups and to avoid influential observations involving extremely obese persons (19). For risk analyses, we fitted a spline-based, parametric survival model (21) according to the stabilized weights and stratified by BMI category to obtain smooth estimates of the CKD cumulative incidence curves that would have been seen in the entire population if every participant had been in each category (20). This survival model parameterized stratum-specific log cumulative hazards as distinct natural cubic splines of log time with 3 internal knots at the 25th, 50th, and 75th percentiles; allowed for interval-censored events (incident CKD occurred at an unknown time point between the visit at which CKD was diagnosed and the previous visit); and used robust SEs for spline parameters that accounted for the correlation induced by weighting (21). For comparison, we also applied weighted KaplanMeier methods to estimate nonparametric cumulative incidence curves for each BMI category. We used the previously mentioned weighted, spline-based survival model to calculate adjusted differences in cumulative incidences of CKD at 2, 5, and 10 years of follow-up of normal-weight participants compared with those in the other BMI categories. We calculated 95% CIs by applying delta methods to the robust variance estimates of spline parameters. In addition to risk differences, we

Nonalcoholic fatty liver disease predicts chronic kidney disease in nonhypertensive and nondiabetic Korean men.

In the absence of significant research, we performed a prospective study to examine the association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The study cohort comprised a total of 8329 healthy men, with normal baseline kidney functions and no proteinuria, working in a semiconductor manufacturing company and its 13 affiliates. Alcohol intake was assessed with a self-reported questionnaire. Biochemical tests for liver and metabolic function and abdominal ultrasonography were done. Chronic kidney disease was defined as either the presence of proteinuria or a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2). Cox proportional hazards model was used to estimate hazard ratios in the model for CKD. During 26717.1 person-years of follow-up, 324 men developed CKD. Nonalcoholic fatty liver disease was associated with the development of CKD (crude relative risk, 2.18; 95% confidence interval [CI], 1.75-2.71); and this relationship remained significant even after adjustment for age, GFR, triglyceride, and high-density lipoprotein cholesterol (adjusted relative risk [aRR], 1.55; 95% CI, 1.23-1.95). The association between NAFLD and incident CKD was evident in the NAFLD group with elevated serum gamma-glutamyltransferase (GGT) (aRR, 2.31; 95% CI, 1.53-3.50), even after adjustment for age, GFR, triglyceride, and high-density lipoprotein cholesterol, but not in the NAFLD group without elevated GGT (aRR, 1.09; 95% CI, 0.79-1.50) (P = .008 for interaction). To summarize, NAFLD with elevated GGT concentration was associated with an increased CKD risk among nondiabetic, nonhypertensive Korean men, irrespective of metabolic syndrome.

Review of brief cognitive tests for patients with suspected dementia

Background: As the population ages, it is increasingly important to use effective short cognitive tests for suspected dementia. We aimed to review systematically brief cognitive tests for suspected dementia and report on their validation in different settings, to help clinicians choose rapid and appropriate tests. Methods: Electronic search for face-to-face sensitive and specific cognitive tests for people with suspected dementia, taking ≤ 20 minutes, providing quantitative psychometric data. Results: 22 tests fitted criteria. Mini-Mental State Examination (MMSE) and Hopkins Verbal Learning Test (HVLT) had good psychometric properties in primary care. In the secondary care settings, MMSE has considerable data but lacks sensitivity. 6-Item Cognitive Impairment Test (6CIT), Brief Alzheimers Screen, HVLT, and 7 Minute Screen have good properties for detecting dementia but need further validation. Addenbrookes Cognitive Examination (ACE) and Montreal Cognitive Assessment are effective to detect dementia with Parkinsons disease and Addenbrookes Cognitive Examination-Revised (ACE-R) is useful for all dementias when shorter tests are inconclusive. Rowland Universal Dementia Assessment scale (RUDAS) is useful when literacy is low. Tests such as Test for Early Detection of Dementia, Test Your Memory, Cognitive Assessment Screening Test (CAST) and the recently developed ACE-III show promise but need validation in different settings, populations, and dementia subtypes. Validation of tests such as 6CIT, Abbreviated Mental Test is also needed for dementia screening in acute hospital settings. Conclusions: Practitioners should use tests as appropriate to the setting and individual patient. More validation of available tests is needed rather than development of new ones.

Serum uric acid levels predict incident nonalcoholic fatty liver disease in healthy Korean men

The objective of the study was to assess the prospective association between serum uric acid levels and incident nonalcoholic fatty liver disease in a cohort of healthy Korean men. A cohort study was performed on 5741 Korean men, 30 to 59 years of age, with no evidence of fatty liver disease on liver ultrasound and with no major risk factors for liver disease at baseline. Study participants were followed in annual or biennial health examinations between 2002 and 2008. The presence of fatty liver was determined at each examination by ultrasound. Cox proportional hazards models were used to evaluate the association of baseline and time-dependent levels of serum uric acid with incident fatty liver, adjusted for potential confounders. During 23,995 person-years of follow-up, 1717 participants developed fatty liver on ultrasound examination. After adjustment for age, body mass index, smoking, and alcohol intake, the hazard ratios (95% confidence intervals) for incident fatty liver comparing quartiles 2 to 4 of serum uric acid to quartile 1 were 1.17 (1.01-1.37), 1.28 (1.11-1.48), and 1.51 (1.31-1.73), respectively (P for trend = .001). The adjusted hazard ratio comparing participants with hyperuricemia (serum uric acid ≥7.0 mg/dL) to those with normouricemia (<7.0 mg/dL) was 1.29 (1.14-1.46). A graded and statistically significant association persisted after adjusting for other cardiometabolic factors and also in time-dependent models. Serum uric acid was an independent risk factor of incident fatty liver detected by ultrasonography. Additional research should clarify the mechanisms underlying this association and the role of hyperuricemia in the development of fatty liver.

Cohort Study of Non-alcoholic Fatty Liver Disease, NAFLD fibrosis score, and the Risk of Incident Diabetes in a Korean population

OBJECTIVES:No study has evaluated an association between non-alcoholic fatty liver disease (NAFLD) severity and the incidence of diabetes. We examined whether NAFLD and its severity—using the NAFLD fibrosis score (NFS)—predict the development of diabetes.METHODS:A cross-sectional study was performed in 43,166 apparently healthy Koreans aged 30–59 years, who underwent a health checkup in 2005 and 2006. Of these, 38,291 subjects without diabetes were followed annually or biennially until December 2011 for the cohort study. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. The NFS was used to categorize the severity of fibrosis. Diabetes was defined as fasting serum glucose ≥126 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or medication use for diabetes.RESULTS:During 175,996 person-years of follow-up, 2,025 participants developed diabetes. An increase across NAFLD categories was positively associated with an increased risk of diabetes in both the cross-sectional and cohort studies in a dose–response manner (P-trend <0.001). In multivariate-adjusted models, the hazard ratios (95% confidence intervals) for diabetes comparing NAFLD with low NFS and NAFLD with intermediate or high NFS vs. no NAFLD were 2.00 (1.79–2.24) and 4.74 (3.67–6.13), respectively. This association remained significant even in subjects with fasting glucose <100 mg/dl and subjects with HbA1c <5.8%.CONCLUSIONS:In this cohort study of a healthy Korean population, NAFLD and its severity using NFS were independently and strongly associated with increased incidence of diabetes in men and women—even with a euglycemic range of glucose and HbA1c.