1.Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis
Po-Yao HSU ; Yu-Ju WEI ; Jia-Jung LEE ; Sheng-Wen NIU ; Jiun-Chi HUANG ; Cheng-Ting HSU ; Tyng-Yuan JANG ; Ming-Lun YEH ; Ching-I HUANG ; Po-Cheng LIANG ; Yi-Hung LIN ; Ming-Yen HSIEH ; Meng-Hsuan HSIEH ; Szu-Chia CHEN ; Chia-Yen DAI ; Zu-Yau LIN ; Shinn-Cherng CHEN ; Jee-Fu HUANG ; Jer-Ming CHANG ; Shang-Jyh HWANG ; Wan-Long CHUANG ; Chung-Feng HUANG ; Yi-Wen CHIU ; Ming-Lung YU
Clinical and Molecular Hepatology 2021;27(1):186-196
		                        		
		                        			 Background/Aims:
		                        			Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. 
		                        		
		                        			Methods:
		                        			The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. 
		                        		
		                        			Results:
		                        			Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). 
		                        		
		                        			Conclusions
		                        			HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs. 
		                        		
		                        		
		                        		
		                        	
2.Extrapyramidal Signs and Risk of Progression from Mild Cognitive Impairment to Dementia: A Clinical Research Center for Dementia of South Korea Study.
Woojae MYUNG ; Jin Hong PARK ; Sook Young WOO ; Seonwoo KIM ; Sang Ha KIM ; Jae Won CHUNG ; Hyo Shin KANG ; Shinn Won LIM ; Junbae CHOI ; Duk L NA ; Seong Yoon KIM ; Jae Hong LEE ; Seol Heui HAN ; Seong Hye CHOI ; Sang Yun KIM ; Bernard J CARROLL ; Doh Kwan KIM
Psychiatry Investigation 2017;14(6):754-761
		                        		
		                        			
		                        			OBJECTIVE: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia. METHODS: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline. RESULTS: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53–0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30–17.39, p < 0.001). CONCLUSION: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.
		                        		
		                        		
		                        		
		                        			Alzheimer Disease
		                        			;
		                        		
		                        			Dementia*
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Korea*
		                        			;
		                        		
		                        			Mild Cognitive Impairment*
		                        			;
		                        		
		                        			Neurologic Examination
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
3.Association between the BDNF Val66Met Polymorphism and Chronicity of Depression.
Yujin LEE ; Shinn Won LIM ; Soo Yeon KIM ; Jae Won CHUNG ; Jinwoo KIM ; Woojae MYUNG ; Jihae SONG ; Seonwoo KIM ; Bernard J CARROLL ; Doh Kwan KIM
Psychiatry Investigation 2013;10(1):56-61
		                        		
		                        			
		                        			OBJECTIVE: Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD). METHODS: Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences. RESULTS: Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives. CONCLUSION: BDNF genotyping may be informative for anticipating chronicity in major depression.
		                        		
		                        		
		                        		
		                        			Age of Onset
		                        			;
		                        		
		                        			Alleles
		                        			;
		                        		
		                        			Amino Acid Substitution
		                        			;
		                        		
		                        			Biological Factors
		                        			;
		                        		
		                        			Brain-Derived Neurotrophic Factor
		                        			;
		                        		
		                        			Codon
		                        			;
		                        		
		                        			Depression
		                        			;
		                        		
		                        			Depressive Disorder
		                        			;
		                        		
		                        			Depressive Disorder, Major
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			
		                        		
		                        	
4.First report of furuncular myiasis caused by the larva of botfly, Dermatobia hominis, in a Taiwanese traveler.
Je-Ming HU ; Chih-Chien WANG ; Li-Lian CHAO ; Chung-Shinn LEE ; Chien-Ming SHIH
Asian Pacific Journal of Tropical Biomedicine 2013;3(3):229-231
		                        		
		                        			
		                        			A case of furuncular myiasis was reported for the first time in a 29-year-old young Taiwanese traveler returning from an ecotourism in Peru. Furuncle-like lesions were observed on the top of his head and he complained of crawling sensations within his scalp. The invasive larva of botfly, Dermatobia hominis, was extruded from the furuncular lesion of the patient. Awareness of cutaneous myiasis for clinicians should be considered for a patient who has a furuncular lesion and has recently returned from a botfly-endemic area.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Diptera
		                        			;
		                        		
		                        			growth & development
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Larva
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Myiasis
		                        			;
		                        		
		                        			diagnosis
		                        			;
		                        		
		                        			parasitology
		                        			;
		                        		
		                        			Taiwan
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
5.An Association Study between Various Adrenergic Alpha 2 Receptor Polymorphisms and Treatment Response to Mirtazapine in Major Depression.
Jin Woo KIM ; Shinn Won LIM ; Hong CHOI ; Su Yeon KIM ; Woo Jae MYUNG ; Yu Jin LEE ; Ji Hye SONG ; Jae Won CHUNG ; Doh Kwan KIM
Journal of Korean Geriatric Psychiatry 2010;14(1):20-26
		                        		
		                        			
		                        			OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.
		                        		
		                        		
		                        		
		                        			Antidepressive Agents
		                        			;
		                        		
		                        			Depression
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Logistic Models
		                        			;
		                        		
		                        			Mianserin
		                        			;
		                        		
		                        			Pharmacogenetics
		                        			;
		                        		
		                        			Polymorphism, Genetic
		                        			;
		                        		
		                        			Polymorphism, Single Nucleotide
		                        			;
		                        		
		                        			Receptors, Adrenergic
		                        			;
		                        		
		                        			Stress, Psychological
		                        			
		                        		
		                        	
6.An Association Study between Various Adrenergic Alpha 2 Receptor Polymorphisms and Treatment Response to Mirtazapine in Major Depression.
Jin Woo KIM ; Shinn Won LIM ; Hong CHOI ; Su Yeon KIM ; Woo Jae MYUNG ; Yu Jin LEE ; Ji Hye SONG ; Jae Won CHUNG ; Doh Kwan KIM
Journal of Korean Geriatric Psychiatry 2010;14(1):20-26
		                        		
		                        			
		                        			OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.
		                        		
		                        		
		                        		
		                        			Antidepressive Agents
		                        			;
		                        		
		                        			Depression
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Logistic Models
		                        			;
		                        		
		                        			Mianserin
		                        			;
		                        		
		                        			Pharmacogenetics
		                        			;
		                        		
		                        			Polymorphism, Genetic
		                        			;
		                        		
		                        			Polymorphism, Single Nucleotide
		                        			;
		                        		
		                        			Receptors, Adrenergic
		                        			;
		                        		
		                        			Stress, Psychological
		                        			
		                        		
		                        	
7.Comparative Study of Serum Brain-Derived Neurotrophic Factor in Acute and Chronic Depression.
Seung Youn LEE ; Jae Won CHUNG ; Shinn Won LIM ; Su Yeon KIM ; Doh Kwan KIM
Korean Journal of Psychopharmacology 2009;20(5):254-261
		                        		
		                        			
		                        			OBJECTIVE: The aim of this study was to compare the serum brain-derived neurotrophic factor (BDNF) in acute depression with that in chronic depression. METHODS: Eighty subjects who met criteria for major depressive disorder (MDD) were recruited. Patients experiencing at least their fourth episode or an episode of at least 24 months in duration were defined as chronically depressed (n=21). Other patients were classified as acutely depressed (n=59). Antidepressant medications were administered for 6 weeks. Serum BDNF and Hamilton rating scale for depression (HAM-D) scores were measure before and after the administration of medication. RESULTS: We found significant differences in serum BDNF between the two groups. Serum BDNF was significantly higher among those with chronic depression than among those with acute depression both at baseline and after medication. CONCLUSION: This study suggested that serum BDNF might constitute a potential biological marker for chronic depression.
		                        		
		                        		
		                        		
		                        			Biomarkers
		                        			;
		                        		
		                        			Brain-Derived Neurotrophic Factor
		                        			;
		                        		
		                        			Depression
		                        			;
		                        		
		                        			Depressive Disorder, Major
		                        			;
		                        		
		                        			Humans
		                        			
		                        		
		                        	
8.Association of Adiponectin and Hepatic Steatosis in Adults with Normal Transaminase Levels.
Jeong Hyun MUN ; Seung Eun LEE ; Ji Hyun AHN ; Soon Hyun SHINN
Korean Diabetes Journal 2008;32(2):149-156
		                        		
		                        			
		                        			BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome including insulin resistance, hypertension, dyslipidemia, central obesity, type 2 diabetes, and cardiovascular disease. In NAFLD, insulin resistance plays an important role in the progression of liver damage. In this study, we evaluated insulin resistance, plasma adiponectin, hepatic steatosis, and their association in adults with normal liver transaminase concentrations. METHODS: We analyzed 111 subjects, aged over 20 years old, who visited the Health Management Center at Chung-Ang University Hospital between May 2006 and August 2006. They had neither history nor clinical evidence of diabetes, cardiovascular or liver disease. They were divided into three groups by the degree of hepatic steatosis based on ultrasound findings. Anthropometric parameters were measured and blood samples were drawn after eight hours of fasting. RESULTS: Hepatic steatosis had a positive correlation with body mass index, waist circumference, blood pressure, triglycerides, HOMA-IR, and QUICKI. Moreover, it had a negative correlation with high-density lipoprotein cholesterol and adiponectin. Triglycerides, Adiponectin, and QUICKI were independent variables in predicting the degree of hepatic steatosis. CONCLUSION: This finding suggests that triglycerides and plasma adiponectin are independent predictors of hepatic steatosis in adults with normal liver transaminase concentrations.
		                        		
		                        		
		                        		
		                        			Adiponectin
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Blood Pressure
		                        			;
		                        		
		                        			Body Mass Index
		                        			;
		                        		
		                        			Cardiovascular Diseases
		                        			;
		                        		
		                        			Cholesterol
		                        			;
		                        		
		                        			Dyslipidemias
		                        			;
		                        		
		                        			Fatty Liver
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypertension
		                        			;
		                        		
		                        			Insulin Resistance
		                        			;
		                        		
		                        			Lipoproteins
		                        			;
		                        		
		                        			Liver
		                        			;
		                        		
		                        			Liver Diseases
		                        			;
		                        		
		                        			Obesity, Abdominal
		                        			;
		                        		
		                        			Plasma
		                        			;
		                        		
		                        			Triglycerides
		                        			;
		                        		
		                        			Waist Circumference
		                        			
		                        		
		                        	
9.Clinical Analysis of Repeated Heart Valve Replacement.
Hyuck KIM ; Won Sang CHUNG ; Seung Hyuk NAM ; Jeong Ho KANG ; Young Hak KIM ; Chul Burm LEE ; Soon Ho CHON ; Sung Ho SHINN
The Korean Journal of Thoracic and Cardiovascular Surgery 2007;40(12):817-824
		                        		
		                        			
		                        			BACKGROUND: There are two choices for heart valve replacement-the use of a tissue valve and the use of a mechanical valve. Using a tissue valve, additional surgery will be problematic due to valve degeneration. If the risk of additional surgery could be reduced, the tissue valve could be more widely used. Therefore, we analyzed the risk factors and mortality of patients undergoing repeated heart valve replacement and primary replacement. MATERIAL AND METHOD: We analyzed 25 consecutive patients who underwent repeated heart valve replacement and 158 patients who underwent primary heart valve replacement among 239 patients that underwent heart vale replacement in our hospital from January 1995 to December 2004. RESULT: There were no differences in age, sex, and preoperative ejection fraction between the repeated valve replacement group of patients and the primary valve replacement group of patients. In the repeated valve replacement group, the previously used artificial valves were 3 mechanical valves and 23 tissue valves. One of these cases had simultaneous replacement of the tricuspid and aortic valve with tissue valves. The mean duration after a previous operation was 92 months for the use of a mechanical valve and 160 months for the use of a tissue valve. The mean cardiopulmonary bypass time and aortic cross clamp time were 152 minutes and 108 minutes, respectively, for the repeated valve replacement group of patients and 130 minutes and 89 minutes, respectively, for the primary valve replacement group of patients. These results were statistically significant. The use of an intra aortic balloon pump (IABP) was required for 2 cases (8%) in the repeated valve replacement group of patients and 6 cases (3.8%) in the primary valve replacement group of patients. An operative death occurred in one case (4%) in the repeated valve replacement group of patients and occurred in nine cases (5.1%) in the primary valve replacement group of patients. Among postoperative complications, the need for mechanical ventilation over 48 hours was different between the two groups. The mean follow up period after surgery was 6.5+/-3.2 years. The 5-year survival of patients in the repeated valve replacement group was 74% and the 5-year survival of patients in the primary valve replacement group was 95%. CONCLUSION: The risk was slightly increased, but there was little difference in mortality between the repeated and primary heart valve replacement group of patients. Therefore, it is necessary to reconsider the issue of avoiding the use of a tissue valve due to the risk of additional surgery, and it is encouraged to use the tissue valve selectively, which has several advantages over the use of a mechanical valve. In the case of a repeated replacement, however, the mortality rate was high for a patient whose preoperative status was not poor. A proper as sessment of cardiac function and patient status is required after the primary valve replacement. Subsequently, a secondary replacement could then be considered.
		                        		
		                        		
		                        		
		                        			Aortic Valve
		                        			;
		                        		
		                        			Cardiopulmonary Bypass
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Heart Valve Diseases
		                        			;
		                        		
		                        			Heart Valves*
		                        			;
		                        		
		                        			Heart*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Mortality
		                        			;
		                        		
		                        			Postoperative Complications
		                        			;
		                        		
		                        			Reoperation
		                        			;
		                        		
		                        			Respiration, Artificial
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
10.The Effect-Site Concentration of Remifentanil for Prevention of Increase of Blood Pressure and Heart Rate to Tracheal Intubation during Propofol-Remifentanil Total Intravenous Anesthesia in Korean.
Helen Ki SHINN ; Hong Sik LEE ; Choon Soo LEE ; Chong Kweon CHUNG ; Doo Cheon CHA ; Hye Ha KIM ; Jang Ho SONG
Korean Journal of Anesthesiology 2006;51(3):312-317
		                        		
		                        			
		                        			BACKGROUND: Combination of propofol and remifentanil is an ideal regimen for total intravenous anesthesia. The purpose of this study is to determine the effect-site concentration of remifentanil for prevention of hemodynamic responses to tracheal intubation during fixed propofol infusion (4microgram/ml) and to find any sexual differences. METHODS: Thirty ASA physical status I-II patients undergoing general anesthesia were assigned to male (n = 15), and female (n = 15) group. All patients received a target controlled infusion (TCI) of propofol with a fixed effect-site concentration of 4microgram/ml. After target effect-site concentration of propofol and remifentanil was reached, tracheal intubation was performed. The hemodynamic changes (systolic/diastolic blood pressure, mean arterial pressure, and heart rate) were measured at 1 and 2 min before tracheal intubation (baseline), immediately after, 1, 2, 3, 4 and 5 min following tracheal intubation. In both groups, effect-site concentration of remifentanil was initiated with 3 ng/ml. Subsequent concentration of remifentanil was determined by hemodynamic responses of the previous patient to tracheal intubation based on up and down sequential allocation. RESULTS: The mean EC50 of remifentanil for prevention of hemodynamic responses to tracheal intubation were 1.37 ng/ml (95% CI, 0.95-1.81 microgram/ml) in male group and 1.05 microgram/ml (95% CI, 0.68-1.40 ng/ml) in female group, respectively. In addition, there were no statistical significant differences between two groups. CONCLUSIONS: Relatively small dosages of remifentanil (0.68-1.81 microgram/ml) for attenuation of hemodynamic responses to tracheal intubation was needed in Korean population in propofol TCI and there were no sexual differences.
		                        		
		                        		
		                        		
		                        			Anesthesia, General
		                        			;
		                        		
		                        			Anesthesia, Intravenous*
		                        			;
		                        		
		                        			Arterial Pressure
		                        			;
		                        		
		                        			Blood Pressure*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Heart Rate*
		                        			;
		                        		
		                        			Heart*
		                        			;
		                        		
		                        			Hemodynamics
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Intubation*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Propofol
		                        			;
		                        		
		                        			Sex Characteristics
		                        			
		                        		
		                        	
            
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