43 results on '"Donghwan Lee"'
Search Results
2. Author Correction: Comparing predictions among competing risks models with rare events: application to KNOW-CKD study—a multicentre cohort study of chronic kidney disease
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Jayoun Kim, Soohyeon Lee, Ji Hye Kim, Dha Woon Im, Donghwan Lee, and Kook-Hwan Oh
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Medicine ,Science - Published
- 2023
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Catalog
3. Deep learning-based virtual cytokeratin staining of gastric carcinomas to measure tumor–stroma ratio
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Yiyu Hong, You Jeong Heo, Binnari Kim, Donghwan Lee, Soomin Ahn, Sang Yun Ha, Insuk Sohn, and Kyoung-Mee Kim
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Medicine ,Science - Abstract
Abstract The tumor–stroma ratio (TSR) determined by pathologists is subject to intra- and inter-observer variability. We aimed to develop a computational quantification method of TSR using deep learning-based virtual cytokeratin staining algorithms. Patients with 373 advanced (stage III [n = 171] and IV [n = 202]) gastric cancers were analyzed for TSR. Moderate agreement was observed, with a kappa value of 0.623, between deep learning metrics (dTSR) and visual measurement by pathologists (vTSR) and the area under the curve of receiver operating characteristic of 0.907. Moreover, dTSR was significantly associated with the overall survival of the patients (P = 0.0024). In conclusion, we developed a virtual cytokeratin staining and deep learning-based TSR measurement, which may aid in the diagnosis of TSR in gastric cancer. more...
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- 2021
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4. Design and investigation of the effectiveness of a metatarsophalangeal assistive device on the muscle activities of the lower extremity.
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Jiyoun Kim, Jinkyu Lee, Donghwan Lee, Jiyoung Jeong, Pankwon Kim, and Choongsoo S Shin
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Medicine ,Science - Abstract
The metatarsophalangeal (MTP) joint is not considered in most current walking assistive devices even though it plays an important role during walking. The purpose of this study was to develop a new MTP assistive device and investigate its effectiveness on the muscle activities of the lower extremities during walking while wearing the device. The MTP assistive device is designed to support MTP flexion by transmitting force through a cable that runs parallel with the plantar fascia. Eight participants were instructed to walk at a constant speed on a treadmill while wearing the device. The muscle activities of their lower extremities and MTP joint kinematics were obtained during walking under both actuated and non-actuated conditions. Paired t-tests were performed to compare the differences in each dependent variable between the two conditions. The muscle activity of the MTP flexor was significantly reduced during walking under actuated conditions (p = 0.013), whereas no differences were found in the muscle activities of other muscles or in the MTP joint angle between actuated and non-actuated conditions (p > 0.05 for all comparisons). In conclusion, the cable-driven MTP assistive device is able to properly assist the MTP flexor without interfering with the action of other muscles in the lower extremities; as such, this MTP assistive device, when integrated into existing exoskeleton designs, has the potential to offer improved walking assistance by reducing the amount of muscle activity needed from the MTP flexor. more...
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- 2022
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5. Author Correction: Deep learning method for comet segmentation and comet assay image analysis
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Yiyu Hong, Hyo‑Jeong Han, Hannah Lee, Donghwan Lee, Junsu Ko, Zhen‑yu Hong, Ji‑Young Lee, Ju‑Hyung Seok, Hee Seon Lim, Woo‑Chan Son, and Insuk Sohn
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Medicine ,Science - Published
- 2022
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6. Urinary Exosomal and cell-free DNA Detects Somatic Mutation and Copy Number Alteration in Urothelial Carcinoma of Bladder
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Dong Hyeon Lee, Hana Yoon, Sanghui Park, Jeong Seon Kim, Young-Ho Ahn, Kihwan Kwon, Donghwan Lee, and Kwang Hyun Kim
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Somatic Mutation Analysis ,Urinary Exosomes ,Copy Number Aberrations ,Liquid Biopsy ,Normal Blood Samples ,Medicine ,Science - Abstract
Abstract Urothelial bladder carcinoma (UBC) is characterized by a large number of genetic alterations. DNA from urine is a promising source for liquid biopsy in urological malignancies. We aimed to assess the availability of cell-free DNA (cfDNA) and exosomal DNA (exoDNA) in urine as a source for liquid biopsy in UBC. We included 9 patients who underwent surgery for UBC and performed genomic profiling of tumor samples and matched urinary cfDNA and exoDNA. For mutation analysis, deep sequencing was performed for 9 gene targets and shallow whole genome sequencing (sWGS) was used for the detection of copy number variation (CNV). We analyzed whether genetic alteration in tumor samples was reflected in urinary cfDNA or exoDNA. To measure the similarity between copy number profiles of tumor tissue and urinary DNA, the Pearson’s correlation coefficient was calculated. We found 17 somatic mutations in 6 patients. Of the 17 somatic mutations, 14 and 12 were identified by analysis of cfDNA and exoDNA with AFs of 56.2% and 65.6%, respectively. In CNV analysis using sWGS, although the mean depth was 0.6X, we found amplification of MDM2, ERBB2, CCND1 and CCNE1, and deletion of CDKN2A, PTEN and RB1, all known to be frequently altered in UBC. CNV plots of cfDNA and exoDNA showed a similar pattern with those from the tumor samples. Pearson’s correlation coefficients of tumor vs. cfDNA (0.481) and tumor vs. exoDNA (0.412) were higher than that of tumor vs. normal (0.086). We successfully identified somatic mutations and CNV in UBC using urinary cfDNA and exoDNA. Urinary exoDNA could be another source for liquid biopsy. Also, CNV analysis using sWGS is an alternative strategy for liquid biopsy, providing data from the whole genome at a low cost. more...
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- 2018
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7. Healthcare resource use and costs of diabetic macular oedema for patients with antivascular endothelial growth factor versus a dexamethasone intravitreal implant in Korea: a population-based study
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SeungJin Bae, HyunJeong Cho, Kyung Seek Choi, Joo Yong Lee, Donghwan Lee, Nam-Kyong Choi, and YouKyung Lee
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Medicine - Abstract
Objectives To estimate the costs and healthcare resources of patients with diabetic macular oedema (DME) who received intravitreal antivascular endothelial growth factor (anti-VEGF) agents or a dexamethasone intravitreal implant (DEX-implant) in Korea.Design Retrospective cohort study.Setting The Korean National Health Insurance claim data from 1 January 2015 to 30 June 2017 were retrieved from the Health Insurance Review and Assessment Service.Participants Adult patients with DME who were diagnosed with diabetic retinopathy or DME and received ranibizumab, aflibercept or a DEX-implant in conjunction with intravitreal injection were included. Patients whose primary diagnoses were age-related macular degeneration or retinal vein occlusion were excluded.Main outcome measures Healthcare resource utilisation and costs related to DME in the 12-month postindex period.Results During the study period, 182 patients and 414 patients were identified in the anti-VEGF and DEX-implant groups, respectively, and there was no significant difference in the demographic characteristics between the two groups. The outpatient eye care-related medical costs were US$3002.33 for the anti-VEGF group vs US$2250.35 for the DEX-implant group (p more...
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- 2019
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8. Effect of High Glucose on Stress-Induced Senescence of Nucleus Pulposus Cells of Adult Rats
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Jae-Gwan Kong, Jong-Beom Park, Donghwan Lee, and Eun-Young Park
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Senescence ,Adult nucleus pulposus cells ,High glucose ,Intervertebral disc degeneration ,Medicine - Abstract
Study DesignIn vitro cell culture model.PurposeWe investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells.Overview of LiteratureDM is a major public health issue worldwide, especially adult-onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM-associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells.MethodsAdult NP cells were isolated from 24-week-old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence-associated-beta-galactosidase (SA-β-Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53-p21-pRB) and stress-induced premature senescence (p16-pRB) pathways.ResultsThe mean SA-β-Gal-positive percentage was increased in adult rat NP cells treated with high glucose in a dose- and time-dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations.ConclusionsThe current study demonstrated that high glucose accelerated stress-induced senescence in adult rat NP cells in a dose- and time-dependent manner. Accelerated stress-induced senescence in adult NP cells could be an emerging risk factor for intervertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM. more...
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- 2015
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9. Residue Dynamics of Streptomycin in Citrus Delivered by Foliar Spray and Trunk Injection and Effect on ‘Candidatus Liberibacter asiaticus’ Titer
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Zhiqian Pang, Vladimir G. Kolbasov, Donghwan Lee, Nicole Collins, Yixiao Huang, Jinyun Li, and Nian Wang
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0106 biological sciences ,0301 basic medicine ,Minimum bactericidal concentration ,Candidatus Liberibacter asiaticus ,fungi ,Trunk injection ,food and beverages ,social sciences ,Plant Science ,Biology ,01 natural sciences ,eye diseases ,03 medical and health sciences ,Titer ,Minimum inhibitory concentration ,Residue (chemistry) ,Horticulture ,030104 developmental biology ,Streptomycin ,medicine ,Agronomy and Crop Science ,geographic locations ,010606 plant biology & botany ,medicine.drug - Abstract
Streptomycin (STR) has been used to control citrus huanglongbing (HLB) caused by ‘Candidatus Liberibacter asiaticus’ (CLas) via foliar spray. Here, we studied the residue dynamics of STR and its effect on CLas titers in planta applied by foliar spray and trunk injection of 3-year-old citrus trees that were naturally infected by CLas in the field. After foliar spray, STR levels in leaves peaked at 2 to 7 days postapplication (dpa) and gradually declined thereafter. The STR spray did not significantly affect CLas titers in leaves of treated plants as determined by quantitative PCR. After trunk injection, peak levels of STR were observed 7 to 14 dpa in the leaf and root tissues, and near-peak levels were sustained for another 14 days before significantly declining. At 12 months after injection, moderate to low or undetectable levels of STR were observed in the leaf, root, and fruit, depending on the doses of STR injected, with a residue level of 0.28 µg/g in harvested fruit at the highest injection concentration of 2.0 µg/tree. CLas titers in leaves were significantly reduced by trunk injection of STR at 1.0 or 2.0 g/tree, starting from 7 dpa and throughout the experimental period. The reduction of CLas titers was positively correlated with STR residue levels in leaves. The in planta minimum effective concentration of STR needed to suppress the CLas titer to an undetectable level (cycle threshold ≥36.0) was 1.92 µg/g fresh weight. Determination of the in planta minimum effective concentration of STR against CLas and its spatiotemporal residue levels in planta provides the guidance to use STR for HLB management. more...
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- 2021
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10. Deep learning-based virtual cytokeratin staining of gastric carcinomas to measure tumor–stroma ratio
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Sang Yun Ha, Yiyu Hong, Kyoung-Mee Kim, Binnari Kim, Donghwan Lee, Insuk Sohn, You Jeong Heo, and Soomin Ahn
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Mathematics and computing ,Science ,Kaplan-Meier Estimate ,Risk Assessment ,Article ,Cytokeratin ,Deep Learning ,Engineering ,Text mining ,Gastrectomy ,Stomach Neoplasms ,Image Processing, Computer-Assisted ,medicine ,Humans ,Stage (cooking) ,Tumor stroma ,Aged ,Neoplasm Staging ,Observer Variation ,Multidisciplinary ,Receiver operating characteristic ,business.industry ,Carcinoma ,Stomach ,fungi ,Area under the curve ,Cancer ,Middle Aged ,medicine.disease ,Computational biology and bioinformatics ,Staining ,Treatment Outcome ,ROC Curve ,Oncology ,Keratins ,Medicine ,Female ,business ,Follow-Up Studies - Abstract
The tumor–stroma ratio (TSR) determined by pathologists is subject to intra- and inter-observer variability. We aimed to develop a computational quantification method of TSR using deep learning-based virtual cytokeratin staining algorithms. Patients with 373 advanced (stage III [n = 171] and IV [n = 202]) gastric cancers were analyzed for TSR. Moderate agreement was observed, with a kappa value of 0.623, between deep learning metrics (dTSR) and visual measurement by pathologists (vTSR) and the area under the curve of receiver operating characteristic of 0.907. Moreover, dTSR was significantly associated with the overall survival of the patients (P = 0.0024). In conclusion, we developed a virtual cytokeratin staining and deep learning-based TSR measurement, which may aid in the diagnosis of TSR in gastric cancer. more...
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- 2021
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11. Citrus Huanglongbing is an immune-mediated disease that can be treated by mitigating reactive oxygen species triggered cell death of the phloem tissues caused by Candidatus Liberibacter asiaticus
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Jin Xu, Zhiqian Pang, Donghwan Lee, Sheo Shankar Pandey, Wenxiu Ma, Jinyun Li, Connor Hendrich, Xiaoen Huang, Nian Wang, Fernanda Nogales da Costa Vasconcelos, Yixiao Huang, Wenting Wang, and Diann Achor more...
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chemistry.chemical_classification ,Reactive oxygen species ,Programmed cell death ,fungi ,Callose ,food and beverages ,Biology ,medicine.disease_cause ,Microbiology ,chemistry.chemical_compound ,Immune system ,chemistry ,medicine ,Gibberellin ,Phloem ,Citrus × sinensis ,Oxidative stress - Abstract
The immune system is critical for keeping animals and plants healthy from pathogens. However, immune-mediated diseases are also common for human. Immune-mediated diseases have not been reported for plants. Here, we present evidence that citrus Huanglongbing (HLB), caused by phloem-colonizing Candidatus Liberibacter asiaticus (CLas), is an immune-mediated disease. CLas infection of Citrus sinensis stimulated systemic and chronic immune response in the phloem tissues including reactive oxygen species (ROS) production as indicated by H2O2, callose deposition, and induction of immune related genes. Systemic cell death of companion and sieve element cells, but not surrounding parenchyma cells, was observed following ROS production triggered by CLas. ROS production triggered by CLas localized in phloem tissues. The H2O2 concentration in exudates extracted from phloem enriched bark tissue of CLas infected plants reached a threshold of killing citrus protoplast cells, which was suppressed by uric acid (a ROS scavenger) and gibberellin. Foliar spray of HLB positive citrus with antioxidants (uric acid and rutin) and gibberellin significantly reduced both H2O2 concentrations and cell death in phloem tissues induced by CLas and reduced HLB symptoms. RNA-seq analyses of CLas infected and health C. sinensis support that CLas causes oxidative stress. In sum, HLB is an immune-mediated disease and both mitigating ROS via antioxidants and promoting plant growth can reduce cell death of the phloem tissues caused by CLas, thus controlling HLB. more...
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- 2021
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12. The in Planta Effective Concentration of Oxytetracycline Against ‘Candidatus Liberibacter asiaticus’ for Suppression of Citrus Huanglongbing
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Donghwan Lee, Jinyun Li, Zhiqian Pang, Nian Wang, Vladimir G. Kolbasov, and Shuo Duan
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0106 biological sciences ,0301 basic medicine ,Cycle threshold ,Candidatus Liberibacter asiaticus ,Log reduction ,food and beverages ,Plant Science ,Oxytetracycline ,Biology ,01 natural sciences ,Disease control ,03 medical and health sciences ,Horticulture ,Minimum inhibitory concentration ,030104 developmental biology ,Greening ,medicine ,Agronomy and Crop Science ,010606 plant biology & botany ,Field conditions ,medicine.drug - Abstract
Huanglongbing (HLB) or greening currently is the most devastating citrus disease worldwide. The fastidious phloem-colonizing bacterium ‘Candidatus Liberibacter asiaticus’ (CLas) is the causal agent of citrus HLB in Florida. Bactericides containing the active ingredient oxytetracycline (OTC) have been used in foliar spray to control citrus HLB in Florida since 2016. However, the minimum concentration of OTC required to suppress CLas in planta remains unknown. We developed a new method for evaluating the effects of OTC treatment on CLas titers in infected plants and determined the relationship between OTC residue levels and control levels achieved for CLas using mathematical modeling in greenhouse and field experiments. In both greenhouse and field, OTC spray did not reduce the titers of CLas, and it produced undetectable or mild levels of OTC residue in leaves within 7 days post-application (DPA). In greenhouse, OTC injection at 0.05 g per tree decreased CLas titers to an undetectable level (cycle threshold value ≥ 36.0) from 7 to 30 DPA and produced a residue level of OTC at 0.68 to 0.73 µg/g of fresh tissue over this period. In the field, OTC injection at 0.50 g per tree resulted in the decline of CLas titers by 1.52 log reduction from 14 to 60 DPA, with residue levels of OTC at 0.27 to 0.33 µg/g of fresh tissue. In both trials, a first-order compart model of OTC residue dynamics in leaves of trunk-injected trees was specified for estimating the retention of effective concentrations. Furthermore, nonlinear modeling revealed significant positive correlations between OTC residue levels in leaves and the control levels for CLas achieved. The results suggested that the minimum concentrations of OTC required to suppress CLas populations in planta to below the detection limit are 0.68 and 0.86 µg/g and that the minimum concentrations of OTC required for initial inhibition of CLas growth in planta are ∼0.17 and ∼0.215 µg/g in leaf tissues under greenhouse and field conditions, respectively. This finding highlights that a minimum concentration of OTC should be guaranteed to be delivered to target CLas in infected plants for effective control of citrus HLB. more...
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- 2019
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13. Identification of Major Psychiatric Disorders From Resting-State Electroencephalography Using a Machine Learning Approach
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Su Mi Park, Boram Jeong, Da Young Oh, Chi-Hyun Choi, Hee Yeon Jung, Jun-Young Lee, Donghwan Lee, and Jung-Seok Choi
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medicine.medical_specialty ,RC435-571 ,resting-state brain function ,Electroencephalography ,Machine learning ,computer.software_genre ,psychiatric disorder ,mental disorders ,Medicine ,Psychiatry ,Original Research ,power spectrum density ,Resting state fMRI ,medicine.diagnostic_test ,Intelligence quotient ,business.industry ,functional connectivity ,medicine.disease ,Support vector machine ,Psychiatry and Mental health ,machine learning ,Mood disorders ,Binary classification ,classification ,Schizophrenia ,Anxiety ,Artificial intelligence ,medicine.symptom ,business ,computer ,electroencephalography - Abstract
We aimed to develop a machine learning (ML) classifier to detect and compare major psychiatric disorders using electroencephalography (EEG). We retrospectively collected data from medical records, intelligence quotient (IQ) scores from psychological assessments, and quantitative EEG (QEEG) at resting-state assessments from 945 subjects [850 patients with major psychiatric disorders (six large-categorical and nine specific disorders) and 95 healthy controls (HCs)]. A combination of QEEG parameters including power spectrum density (PSD) and functional connectivity (FC) at frequency bands was used to establish models for the binary classification between patients with each disorder and HCs. The support vector machine, random forest, and elastic net ML methods were applied, and prediction performances were compared. The elastic net model with IQ adjustment showed the highest accuracy. The best feature combinations and classification accuracies for discrimination between patients and HCs with adjusted IQ were as follows: schizophrenia = alpha PSD, 93.83%; trauma and stress-related disorders = beta FC, 91.21%; anxiety disorders = whole band PSD, 91.03%; mood disorders = theta FC, 89.26%; addictive disorders = theta PSD, 85.66%; and obsessive–compulsive disorder = gamma FC, 74.52%. Our findings suggest that ML in EEG may predict major psychiatric disorders and provide an objective index of psychiatric disorders. more...
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- 2021
14. Value Frameworks: Adaptation of Korean Versions of Value Frameworks for Oncology
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Hee Jun Kim, Sung Young Oh, Hyerim Ha, Hee Yeon Lee, Jin Hyoung Kang, Seung Jin Bae, Donghwan Lee, Green Bae, Dong Hoe Koo, Do Yeun Kim, Juhee Han, Jong Hwan Lee, and Hye Sook Han
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Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Intraclass correlation ,Computer science ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Analytic hierarchy process ,value frameworks ,Antineoplastic Agents ,Medical Oncology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Republic of Korea ,medicine ,Humans ,country adaptation ,030212 general & internal medicine ,Reliability (statistics) ,Clinical Oncology ,lcsh:R ,Public Health, Environmental and Occupational Health ,Reproducibility of Results ,Sample size determination ,030220 oncology & carcinogenesis ,oncology ,Value (mathematics) ,Value framework - Abstract
This study sought to adapt the existing value framework (VF) to produce a reliable and valid Korean oncology VF. Two VFs developed by The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) were selected for examination in the present study. Forward and backward translations were conducted for six high-priced drugs indicated for non-small-cell lung cancer and multiple myeloma. Inter-rater reliability was measured based on the intraclass correlation coefficient (ICC) and variation was described using the coefficient of variation. The relative weights of factors critically considered by Korean oncologists were derived following the analytic hierarchy process (AHP), and focus group interviews (FGIs) were used to obtain qualitative data regarding the applications of these two VFs in the Korean setting. The ICCs of the Korean VFs were 0.895 (0.654–0.983) for ASCO and 0.726 (0–0.982) for ESMO translations, suggesting excellent reliability for ASCO and good reliability for ESMO. AHP demonstrated that clinical benefit has the highest priority, which is consistent with the ASCO VF. The FGIs suggested that the result for AHP is acceptable and that both ESMO and ASCO VFs should be used complementarily. Although further evaluation with a larger sample size is needed, the Korean versions of ESMO/ASCO VFs are valid and reliable tools and are acceptable to Korean stakeholders, yet they should be applied with caution. more...
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- 2021
15. Medication Adherence and Persistence of Open-Angle Glaucoma Patients in Korea: A Retrospective Study Using National Health Insurance Claims Data
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Nam Kyong Choi, Seung Jin Bae, Donghwan Lee, Donghyun Jee, and Yunjeong Jang
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Male ,medicine.medical_specialty ,Intraocular pressure ,Open angle glaucoma ,genetic structures ,National Health Programs ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Medication adherence ,Glaucoma ,open-angle glaucoma ,Logistic regression ,Article ,Persistence (computer science) ,Medication Adherence ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Republic of Korea ,medicine ,Humans ,030212 general & internal medicine ,claim database ,Antihypertensive Agents ,Retrospective Studies ,business.industry ,lcsh:R ,Public Health, Environmental and Occupational Health ,Retrospective cohort study ,Odds ratio ,persistence ,medicine.disease ,030221 ophthalmology & optometry ,Female ,business ,Glaucoma, Open-Angle - Abstract
This study aimed to analyze medication adherence and persistence among open-angle glaucoma patients in Korea. A retrospective study was conducted using the Korean National Health Insurance (NHI) claims database from 2016 to 2019. Newly diagnosed open-angle glaucoma patients who were prescribed with the intraocular pressure (IOP)-lowering eyedrops were included. Adherence was measured using the medication possession ratio (MPR), and persistence was measured using the duration of therapy during the 24 month follow-up period. During the study period, 14,648 open-angle glaucoma patients were identified, and 3118 (21.3%) and 4481 patients (30.6%) were adherent to and persistent with their glaucoma treatment, respectively. The mean MPR was 48.8%, and the mean duration of therapy was 357.2 days. Logistic regression analysis showed that patients who are older, female, using prostaglandins as the index medication, and visiting secondary or tertiary hospitals were significantly associated with greater rates of adherence (odds ratio (OR) = 1.21, 1.12, 1.27, and 1.73, respectively) and persistence (OR = 1.11, 1.17, 1.16, 1.17, and 1.36, respectively) during the study period. Patients with open-angle glaucoma in Korea had substandard medication adherence and discontinued their treatment. Ophthalmologists should pay more attention to younger, male patients to improve adherence. more...
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- 2021
16. A Meta-Regression Analysis of Utility Weights for Breast Cancer: The Power of Patients’ Experience
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Seung Jin Bae, Ji Ryoun Gong, Donghwan Lee, and Juhee Han
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Cost-Benefit Analysis ,Health, Toxicology and Mutagenesis ,MEDLINE ,lcsh:Medicine ,Breast Neoplasms ,Disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Quality of life ,meta-regression ,medicine ,Humans ,Meta-regression ,Stage (cooking) ,preferences ,business.industry ,030503 health policy & services ,lcsh:R ,Multilevel model ,Public Health, Environmental and Occupational Health ,Middle Aged ,medicine.disease ,quality of life ,utility ,030220 oncology & carcinogenesis ,Respondent ,Linear Models ,Regression Analysis ,0305 other medical science ,business ,Demography - Abstract
To summarize utility estimates of breast cancer and to assess the relative impacts of study characteristics on predicting breast cancer utilities. We searched Medline, Embase, RISS, and KoreaMed from January 1996 to April 2019 to find literature reporting utilities for breast cancer. Thirty-five articles were identified, reporting 224 utilities. A hierarchical linear model was used to conduct a meta-regression that included disease stages, assessment methods, respondent type, age of the respondents, and scale bounds as explanatory variables. The utility for early and late-stage breast cancer, as estimated by using the time-tradeoff with the scales anchored by death to perfect health with non-patients, were 0.742 and 0.525, respectively. The severity of breast cancer, assessment method, and respondent type were significant predictors of utilities, but the age of the respondents and bounds of the scale were not. Patients who experienced the health states valued 0.142 higher than did non-patients (P <, 0.001).&rdquo, Besides the disease stage, the respondent type had the highest impact on breast cancer utility. more...
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- 2020
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17. Incidence, cost and gender differences of oropharyngeal and noncervical anogenital cancers in South Korea
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Seung Jin Bae, Kyung-Bok Son, Inseon Choi, and Donghwan Lee
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Adult ,Male ,medicine.medical_specialty ,Vaginal Neoplasms ,Cost ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Noncervical anogenital cancer ,Internal medicine ,Republic of Korea ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Sex Distribution ,Papillomaviridae ,Penile Neoplasms ,Retrospective Studies ,Oropharyngeal cancer ,Vulvar Neoplasms ,business.industry ,Incidence ,lcsh:Public aspects of medicine ,Incidence (epidemiology) ,Public health ,Papillomavirus Infections ,Burden of disease ,Public Health, Environmental and Occupational Health ,Cancer ,lcsh:RA1-1270 ,Retrospective cohort study ,Health Care Costs ,Middle Aged ,Anus Neoplasms ,medicine.disease ,Oropharyngeal Neoplasms ,National health insurance ,030220 oncology & carcinogenesis ,Female ,Biostatistics ,business ,Urogenital Neoplasms ,Oropharyngeal Cancers ,Research Article - Abstract
Background Human papillomavirus (HPV) is associated with a significant public health burden, yet few studies have been conducted in Asia, especially on noncervical cancers. We estimated the incidence and cost of oropharyngeal and noncervical anogenital (anal, vulvar, vaginal, penile) cancer in Korea. Methods We conducted a retrospective cohort study using Korea’s National Health Insurance (NHI) claim database from 2013 to 2016. The main outcome measures were the number of respective cancer incidences during the study period and the annual costs per patient in the first year after diagnosis, which was adjusted by relevant variables based on the regression analysis. Results During the study period, 8022 patients with these cancers were identified, and oropharyngeal cancer comprised 46% of them. The crude incidence rate for male oropharyngeal cancer was significantly higher than that of females (3.1 vs. 0.7 per 100,000 as of 2016, respectively). Additionally, the crude incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The mean annual incidence-based cost per patient in 2016 was highest for oropharyngeal cancers (21,870 USD), and it was significantly higher in males than in females based on then regression analysis (p Conclusions Oropharyngeal cancer comprises the highest number of HPV-associated noncervical cancer incidences in Korea, and the incidence and cost of oropharyngeal cancer was significantly higher among males than females. More aggressive public health policy toward males may decrease gender gap of oropharyngeal cancer. more...
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- 2020
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18. Clinical Case of a Transfusion-Associated Canine Mycoplasma haemocanis Infection in the Republic of Korea: A Case Report
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Jun-Gu Kang, Daseul Chun, Jihu Kim, Hyeona Bae, Eun-Chae Yoon, Dong-In Jung, Donghwan Lee, and Do-Hyeon Yu
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Hemolytic anemia ,Male ,Blood transfusion ,040301 veterinary sciences ,Anemia ,medicine.medical_treatment ,030231 tropical medicine ,Case Report ,blood transfusion ,law.invention ,Mycoplasma haemocanis ,0403 veterinary science ,03 medical and health sciences ,0302 clinical medicine ,Dogs ,Mycoplasma ,law ,Republic of Korea ,Medicine ,Animals ,Mycoplasma Infections ,Dog Diseases ,Polymerase chain reaction ,donor ,hemolytic anemia ,Doxycycline ,business.industry ,Transfusion Reaction ,04 agricultural and veterinary sciences ,medicine.disease ,Basophilic ,Infectious Diseases ,Treatment Outcome ,Immunology ,Parasitology ,Clinical case ,Anemia, Hemolytic, Autoimmune ,business ,medicine.drug - Abstract
This report describes the first clinical case of a transfusion-associated Mycoplasma haemocanis infection in a dog in Korea. A 6-year-old male Maltese underwent a red blood cell transfusion for idiopathic immune-mediated hemolytic anemia. Eighteen days after the blood transfusion, the recipient’s packed cell volume decreased and basophilic organisms were found on erythrocytes. A polymerase chain reaction and sequential analysis showed that both the donor dog and recipient dog had M. haemocanis. Six weeks after doxycycline administration, no organisms were detected and the recipient’s anemia had improved. more...
- Published
- 2020
19. Are Recently Evaluated Drugs More Likely to Receive Positive Reimbursement Recommendations in South Korea? 11-year Experience of the South Korean Positive List System
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Kyung Min Lim, Seung Jin Bae, Ji Ryoun Gong, and Donghwan Lee
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Pharmacology ,Government ,business.industry ,Cost-Benefit Analysis ,Budget impact ,Logistic regression ,Insurance, Pharmaceutical Services ,Drug Costs ,Health Services Accessibility ,Reimbursement Mechanisms ,Environmental health ,Economic evaluation ,Republic of Korea ,Medicine ,Humans ,Pharmacology (medical) ,business ,Reimbursement - Abstract
The South Korean government in 2014 introduced various policies to enhance accessibility of pharmaceuticals. This study sought to examine whether positive reimbursement recommendations of pharmaceuticals have increased since 2014.Industry submissions evaluated from January 2007 to December 2018 were identified, and characteristics relevant to reimbursement recommendations were extracted. Logistic regression analyses with robust SEs were used to quantify the likelihood of positive recommendations for pharmaceuticals, after controlling for relevant factors influencing the recommendations.During the study period, 355 (72.9%) of 487 submissions were positively recommended; the drugs evaluated after 2014 (77.8%) were significantly more likely to receive positive reimbursement recommendations than the drugs evaluated before 2014 (69.5%). In the multivariable logistic regression analysis, several factors (labeled a noncancer drug, priced less than alternatives, considered clinically superior, and having budget impact10 billion South Korean won) were significantly associated with positive recommendations (P 0.05). When considering interaction effects between evaluation year and other variables, only the interaction between comparative clinical benefit and evaluation year was significant. Specifically, clinically noninferior drugs evaluated after 2014 had 2.85 times the odds of receiving positive recommendations compared with the clinically noninferior drugs evaluated earlier.Recently evaluated drugs are more likely to receive positive reimbursement recommendations, especially those drugs whose comparative clinical benefits are noninferior. more...
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- 2020
20. Associations of personality and clinical characteristics with excessive Internet and smartphone use in adolescents: A structural equation modeling approach
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Jung Seok Choi, Bo Mi Kim, Donghwan Lee, Youngjo Lee, Boram Jeong, Eunmin Park, Jun Gun Kwon, Daijin Kim, and Ji Yoon Lee
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Adolescent ,media_common.quotation_subject ,education ,Medicine (miscellaneous) ,Anger ,Toxicology ,Affect (psychology) ,Structural equation modeling ,Surveys and Questionnaires ,mental disorders ,Republic of Korea ,medicine ,Personality ,Humans ,media_common ,Internet ,Aggression ,Addiction ,Behavior, Addictive ,Psychiatry and Mental health ,Clinical Psychology ,Mood ,Latent Class Analysis ,Anxiety ,Smartphone ,medicine.symptom ,Psychology ,Clinical psychology - Abstract
Adolescent Internet addiction is an important social issue entailing extensive use of Internet and smartphones and its side effects. This study identified relevant psychological factors that affect excessive Internet use (EIU) and excessive smartphone use (ESU) in adolescents using structural equation modeling (SEM). A sample of 714 individuals drawn from lists of middle school students in South Korea completed self-administered questionnaires, including Young's Internet Addiction Test (Y-IAT), the Smartphone Addiction Scale (SAS), and various clinical and psychological scales measuring depression, anxiety, attention deficit/hyperactivity disorder (ADHD), aggression, expression of anger, and the behavioral inhibition system (BIS)/activation system (BAS). The final model, fitted using SEM, showed that both clinical characteristics, including ADHD symptoms, aggression, expression of anger, depression, and anxiety, and personality characteristics, represented by BIS/BAS, played important roles in the severity of EIU or ESU. In particular, affective components such as depression and anxiety were significantly associated with both EIU and ESU, whereas aggression, the expression of anger, and ADHD symptoms affected only EIU. Furthermore, the association between ESU and EIU was significant. Although personality characteristics measured by the BIS and BAS scores did not have direct effects on addiction, they were associated with clinical features and might be risk factors for addiction. The model revealed significant pathways from personality and clinical features to EIU and ESU in adolescents and informed our basic understanding of the meaningful predictors of these addictions and their direct and indirect influences. more...
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- 2020
21. Genomic alterations in signet ring and mucinous patterned colorectal carcinoma
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Hyunchul Kim, Donghwan Lee, Eun Shin, and Bo-Hyung Kim
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0301 basic medicine ,Adult ,Male ,Colorectal cancer ,Biology ,medicine.disease_cause ,Pathology and Forensic Medicine ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Signet ring cell carcinoma ,medicine ,Mucinous carcinoma ,Humans ,Aged ,Aged, 80 and over ,Mutation ,Signet ring cell ,Cancer ,Cell Biology ,Genomics ,Middle Aged ,medicine.disease ,Adenocarcinoma, Mucinous ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,Female ,Microsatellite Instability ,Colorectal Neoplasms ,Carcinoma, Signet Ring Cell ,Proto-oncogene tyrosine-protein kinase Src - Abstract
The genetic alterations (GAs) in two specific histological subtypes of colorectal cancer (CRC), signet ring cell colorectal carcinoma (SRC) and mucinous colorectal carcinoma (MC), are not well known. In the present study, we employed next-generation sequencing to perform genetic profiling of SRC and MC, and compared the spectrum of GAs with the alterations found in conventional type colorectal cancer (CON).We selected 46 CRCs comprising 17 SRCs and mucinous carcinoma with signet ring cell component (SRCCs), 17 MCs, and 12 CONs with microsatellite stability or microsatellite instability-low. Deep sequencing was performed using a targeted cancer panel composed of 171 cancer-related genes. SMAD4 protein expression was evaluated by immunohistochemical staining.We detected 108 mutations in 18 different genes. Overall, 2.34 GAs were detected per tumor (range, 0-14). The overall frequency of GA and alteration in targetable genes was less prevalent in SRC/SRCC compared to the frequency of alteration in MC/CON (p = 0.040 and p 0.001, respectively). The GA profile of SRC/SRCC included TP53 (8/17, 47.1%), SMAD4 (5/17, 29.4%), KRAS (4/17.23.5%), APC (4/17.23.5%), PIK3CA, ATM, BRAF, and PIK3R1 (1/17, 5.9%, each). KRAS mutation was significantly less prevalent in SRC/SRCC compared to the number of KRAS mutations in MC (12/17, 70.6%) and CON (9/12, 75.0%) (p = 0.015 and 0.01, respectively). Compared to the 152 non-hypermutated CONs from TCGA database, SMAD4 alteration was predominant in SRC/SRCC (p = 0.045) with aberrant loss of SMAD4 expression (13/17, 76.5%) compared to the SMAD4 alterations in CON (5/15, 33.3%) (p = 0.031). Accordingly, KRAS (12/17, 70.6%), APC (6/17, 35.3%), SMAD4, TP53 (4/17, 23.5%, each), PIK3CA (3/17, 17.6%), AKT1, ATM, BRAF, EGFR, and EZH2 (1/17, 5.9%, each) were altered in MC. APC and TP53 mutations were less frequent in MC compared to those in TCGA-CON (p 0.001 and 0.003, respectively) whereas KRAS mutation was prevalent (p = 0.041).Alterations of known cancer associated genes and targetable genes in SRC/SRCC are infrequent. The profile of GAs in SRC/SRCC and MC differs from the GA profile of CON. Specifically, SMAD4 mutation and loss of SMAD4 expression is frequently found in SRC/SRCC. The genetic profiles revealed in the present study may aid in developing precision medicine for CRC treatment based on histological subtype. more...
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- 2019
22. Analysis of multi-center bladder cancer survival data using variable-selection method of multi-level frailty models
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Bohyeon Kim, Il Do Ha, and Donghwan Lee
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Survival data ,Bladder cancer ,Computer science ,Statistics ,medicine ,Feature selection ,Center (algebra and category theory) ,medicine.disease - Published
- 2016
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23. Pharmacokinetic comparison between a fixed-dose combination of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg and a corresponding loose combination of fimasartan/amlodipine 60/25 mg and hydrochlorothiazide 25 mg in healthy subjects
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Soyoung Lee, Jihyun Jung, In-Jin Jang, Jaeseong Oh, Seung-Hwan Lee, Donghwan Lee, and Kyung Sang Yu
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business.industry ,Fixed-dose combination ,Area under the curve ,Cmax ,Bioequivalence ,Pharmacology ,Hydrochlorothiazide ,Pharmacokinetics ,Fimasartan ,medicine ,Original Article ,Pharmacology (medical) ,Amlodipine ,business ,Fixed-dose Combination ,medicine.drug - Abstract
For the treatment of hypertension, fixed-dose combinations (FDCs) of antihypertensive drugs can provide complementary benefits from improved compliance and cost-effectiveness compared with loose combinations of corresponding drugs. A new FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg is undergoing clinical development. A randomized, open-label, single-dose, 3-period, 3-sequence, partially replicated crossover phase 1 study was conducted to compare the pharmacokinetics (PKs) between the FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg and a loose combination of a dual-combination FDC (fimasartan/amlodipine 60/10 mg) and hydrochlorothiazide 25 mg. Sixty healthy subjects were randomized, and 55 subjects completed the study. Serial blood samples were collected, and plasma concentrations of fimasartan, amlodipine and hydrochlorothiazide were measured to analyze PK parameters. The PK profiles of the FDC were similar to those of the loose combinations. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to loose combinations for the maximum plasma concentration (Cmax) and area under the curve until the last measurable time point (AUClast) were within the conventional bioequivalent range of 0.80 to 1.25. The GMRs and 90% CIs of fimasartan, amlodipine and hydrochlorothiazide were 1.0163 (0.8681–1.1898), 0.9595 (0.9256–0.9946), and 1.1294 (1.0791–1.1821) for Cmax and 1.0167 (0.9347–1.1059), 0.9575 (0.9317–0.9841), and 1.0561 (1.0170–1.0967) for AUClast, respectively. Both the FDC and loose combinations were well tolerated. In conclusion, the FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg showed similar PK profiles to those of the corresponding loose combination, and both treatments were well tolerated. more...
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- 2021
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24. Urinary Exosomal and cell-free DNA Detects Somatic Mutation and Copy Number Alteration in Urothelial Carcinoma of Bladder
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Kwang Hyun Kim, Young Ho Ahn, Jeong Seon Kim, Donghwan Lee, Kihwan Kwon, Sanghui Park, Dong Hyeon Lee, and Hana Yoon
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Adult ,Male ,0301 basic medicine ,DNA Copy Number Variations ,Science ,DNA Mutational Analysis ,Urinary Bladder ,Copy Number Aberrations ,Biology ,Cystectomy ,Exosomes ,Article ,Deep sequencing ,Circulating Tumor DNA ,03 medical and health sciences ,Germline mutation ,CDKN2A ,Biomarkers, Tumor ,Carcinoma ,medicine ,Humans ,PTEN ,Prospective Studies ,Copy-number variation ,Liquid biopsy ,Somatic Mutation Analysis ,Urinary Exosomes ,Aged ,Carcinoma, Transitional Cell ,Multidisciplinary ,Whole Genome Sequencing ,Liquid Biopsy ,Middle Aged ,medicine.disease ,030104 developmental biology ,Normal Blood Samples ,Urinary Bladder Neoplasms ,Cell-free fetal DNA ,Mutation ,Cancer research ,biology.protein ,Medicine ,Feasibility Studies - Abstract
Urothelial bladder carcinoma (UBC) is characterized by a large number of genetic alterations. DNA from urine is a promising source for liquid biopsy in urological malignancies. We aimed to assess the availability of cell-free DNA (cfDNA) and exosomal DNA (exoDNA) in urine as a source for liquid biopsy in UBC. We included 9 patients who underwent surgery for UBC and performed genomic profiling of tumor samples and matched urinary cfDNA and exoDNA. For mutation analysis, deep sequencing was performed for 9 gene targets and shallow whole genome sequencing (sWGS) was used for the detection of copy number variation (CNV). We analyzed whether genetic alteration in tumor samples was reflected in urinary cfDNA or exoDNA. To measure the similarity between copy number profiles of tumor tissue and urinary DNA, the Pearson’s correlation coefficient was calculated. We found 17 somatic mutations in 6 patients. Of the 17 somatic mutations, 14 and 12 were identified by analysis of cfDNA and exoDNA with AFs of 56.2% and 65.6%, respectively. In CNV analysis using sWGS, although the mean depth was 0.6X, we found amplification of MDM2, ERBB2, CCND1 and CCNE1, and deletion of CDKN2A, PTEN and RB1, all known to be frequently altered in UBC. CNV plots of cfDNA and exoDNA showed a similar pattern with those from the tumor samples. Pearson’s correlation coefficients of tumor vs. cfDNA (0.481) and tumor vs. exoDNA (0.412) were higher than that of tumor vs. normal (0.086). We successfully identified somatic mutations and CNV in UBC using urinary cfDNA and exoDNA. Urinary exoDNA could be another source for liquid biopsy. Also, CNV analysis using sWGS is an alternative strategy for liquid biopsy, providing data from the whole genome at a low cost. more...
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- 2018
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25. DEP domain-containing mTOR-interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease
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Pal Pacher, Yu Li, Mengwei Zang, Jian-Gao Fan, Feng Liu, Jinyan Han, Bingbing Jiang, Bin Gao, Allison Nocon, Donghwan Lee, Leonard Guarente, Alex Sherban, Nicolas Musi, Feng Shen, Hanqing Chen, Hua Wang, Mingjiang Xu, Xianliang Rui, Amrita Kamat, Na Li, Farnaz Keyhani-Nejad, and Massachusetts Institute of Technology. Department of Biology more...
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0301 basic medicine ,Liver injury ,medicine.medical_specialty ,Alcoholic liver disease ,Hepatology ,Fatty liver ,P70-S6 Kinase 1 ,mTORC1 ,medicine.disease ,DEPTOR ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Internal medicine ,Lipogenesis ,medicine ,Alcoholic fatty liver ,biological phenomena, cell phenomena, and immunity - Abstract
Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation, and liver injury. Chronic-plus-binge ethanol feeding led to hyperactivation of mTORC1, as evidenced by increased phosphorylation of mTOR and its downstream kinase S6 kinase 1 (S6K1) in hepatocytes. Aberrant activation of mTORC1 was likely attributed to the defects of the DEP domain-containing mTOR-interacting protein (DEPTOR) and the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1) in the liver of chronic-plus-binge ethanol-fed mice and in the liver of patients with ALD. Conversely, adenoviral overexpression of hepatic DEPTOR suppressed mTORC1 signaling and ameliorated alcoholic hepatosteatosis, inflammation, and acute-on-chronic liver injury. Mechanistically, the lipid-lowering effect of hepatic DEPTOR was attributable to decreased proteolytic processing, nuclear translocation, and transcriptional activity of the lipogenic transcription factor sterol regulatory element-binding protein-1 (SREBP-1). DEPTOR-dependent inhibition of mTORC1 also attenuated alcohol-induced cytoplasmic accumulation of the lipogenic regulator lipin 1 and prevented alcohol-mediated inhibition of fatty acid oxidation. Pharmacological intervention with rapamycin alleviated the ability of alcohol to up-regulate lipogenesis, to down-regulate fatty acid oxidation, and to induce steatogenic phenotypes. Chronic-plus-binge ethanol feeding led to activation of SREBP-1 and lipin 1 through S6K1-dependent and independent mechanisms. Furthermore, hepatocyte-specific deletion of SIRT1 disrupted DEPTOR function, enhanced mTORC1 activity, and exacerbated alcoholic fatty liver, inflammation, and liver injury in mice. Conclusion The dysregulation of SIRT1-DEPTOR-mTORC1 signaling is a critical determinant of ALD pathology; targeting SIRT1 and DEPTOR and selectively inhibiting mTORC1-S6K1 signaling may have therapeutic potential for treating ALD in humans. (Hepatology 2018). more...
- Published
- 2018
26. Effect of High Glucose on Stress-Induced Senescence of Nucleus Pulposus Cells of Adult Rats
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Donghwan Lee, Jae-Gwan Kong, Eun-Young Park, and Jong-Beom Park
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Senescence ,medicine.medical_specialty ,Pathology ,lcsh:Medicine ,Degeneration (medical) ,Internal medicine ,Diabetes mellitus ,medicine ,Orthopedics and Sports Medicine ,business.industry ,lcsh:R ,Intervertebral disc ,Basic Study ,medicine.disease ,Adult nucleus pulposus cells ,Staining ,Endocrinology ,medicine.anatomical_structure ,High glucose ,Surgery ,Intervertebral disc degeneration ,business ,Nucleus ,Fetal bovine serum - Abstract
Study Design: In vitro cell culture model. Purpose: We investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells. Overview of Literature: DM is a major public health issue worldwide, especially adult‑onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM‑associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells. Methods: Adult NP cells were isolated from 24‑week‑old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence ‑associated‑beta‑galactosidase (SA‑β‑Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53–p21–pRB) and stress‑induced premature senescence (p16–pRB) pathways. Results: The mean SA‑β‑Gal‑positive percentage was increased in adult rat NP cells treated with high glucose in a dose‑ and time‑ dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations. Conclusions: The current study demonstrated that high glucose accelerated stress‑induced senescence in adult rat NP cells in a dose‑ and time‑dependent manner. Accelerated stress‑induced senescence in adult NP cells could be an emerging risk factor for inter‑ vertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM. more...
- Published
- 2015
27. LMI-based robust sampled-data stabilization of polytopic LTI systems: A truncated power series expansion approach
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Young Hoon Joo and Donghwan Lee
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Power series ,Discretization ,medicine.medical_treatment ,Computer Science Applications ,Matrix (mathematics) ,Control and Systems Engineering ,Control theory ,Norm (mathematics) ,Bounded function ,Homogeneous polynomial ,medicine ,Remainder ,Relaxation technique ,Mathematics - Abstract
For continuous-time linear time-invariant (LTI) systems with polytopic uncertainties, we develop a robust sampled-data state-feedback control design scheme in terms of linear matrix inequalities (LMIs). Truncated power series expansions are used to approximate a discretized model of the original continuous-time system. The system matrices obtained by using the power series approximations are then expressed as homogeneous polynomial parameter-dependent (HPPD) matrices of finite degrees, and conditions for designing the controller are formulated as a HPPD matrix inequality, which can be solved by means of a recent LMI relaxation technique to test the positivity of HPPD matrices with variables in the simplex. To take care of the errors induced by the remainder terms of the truncated power series, the terms are considered as norm bounded uncertainties and then incorporated into the proposed LMI conditions. Finally, examples are used to illustrate the approach. more...
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- 2015
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28. Pharmacokinetic Interaction Between Rosuvastatin and Telmisartan in Healthy Korean Male Volunteers: A Randomized, Open-label, Two-period, Crossover, Multiple-dose Study
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Jinju Guk, Hyerang Roh, Su Youn Nam, Yukyung Kim, Mijeong Son, Kyungsoo Park, Donghwan Lee, Hankil Son, and Seong Bok Jang
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Adult ,Male ,medicine.medical_specialty ,Administration, Oral ,Type 2 diabetes ,Pharmacology ,Benzoates ,Gastroenterology ,Young Adult ,Asian People ,Pharmacokinetics ,Internal medicine ,Republic of Korea ,medicine ,Humans ,Drug Interactions ,Pharmacology (medical) ,Rosuvastatin ,Telmisartan ,Rosuvastatin Calcium ,Adverse effect ,Antihypertensive Agents ,Cross-Over Studies ,business.industry ,Incidence (epidemiology) ,nutritional and metabolic diseases ,medicine.disease ,Healthy Volunteers ,Metformin ,Cough ,Area Under Curve ,Benzimidazoles ,Drug Therapy, Combination ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Dyslipidemia ,medicine.drug - Abstract
Purpose Rosuvastatin is indicated for hypercholesterolemia or dyslipidemia and metformin mainly for type 2 diabetes. These 2 drugs are frequently prescribed in combination due to the high comorbidity of the 2 diseases. However the nature of pharmacokinetic interaction between the 2 drugs has not been previously investigated. The purpose of our study was to investigate the pharmacokinetic interaction between rosuvastatin and metformin in healthy Korean male volunteers. Methods This was a randomized, open-label, 6-sequence, 3-period, crossover, multiple-dose study. Eligible subjects, aged 20 to 50 years and within 20% of the ideal body weight, received 1 of the following 3 treatments for each period once daily for 5 consecutive days with a 10-day washout period between the treatments: monoadministration of rosuvastatin 10 mg tablet, monoadministration of metformin 750 mg tablet, and coadministration of rosuvastatin 10 mg tablet with metformin 750 mg tablet. Blood samples were collected up to 72 hours after the last dose and pharmacokinetic parameters for rosuvastatin and metformin were compared between combination and monotherapy. Adverse events were investigated and evaluated based on subject interviews and physical examinations. Findings Among the 36 enrolled subjects, 31 completed the study. The coadministration of rosuvastatin with metformin produced a significant pharmacokinetic interaction in rosuvastatin C ss,max , with the 90% CI for the geometric mean ratio (coadministration:monoadministration) being 110.27% to 136.39% ( P = 0.0029), whereas no significant interaction was observed in rosuvastatin AUC tau , yielding the 90% CI of 104.41% to 118.95%. When metformin was coadministered with rosuvastatin, no significant pharmacokinetic interaction was observed for C ss,max and AUC tau of metformin, yielding the 90% CIs of the geometric mean ratio for coadministration to monoadministration as 87.38% to 102.54% and 86.70% to 99.08%, respectively. Overall, 19 mild and 1 moderate adverse events occurred in 12 subjects, with no significant differences in the incidence among the 3 treatments. Implications Although the C ss,max of rosuvastatin was significantly influenced by coadministration with metformin, the degree of interaction seen was considered clinically insignificant, with no significant interaction observed in the other pharmacokinetic measures between the 2 drugs. These results imply that drug effects of rosuvastatin and metformin will also not be significantly influenced by coadministration of the 2 drugs. All treatments were well tolerated and no serious adverse events occurred. ClinicalTrials.gov identifier: NCT01526317. more...
- Published
- 2014
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29. Healthcare resource use and costs of diabetic macular oedema for patients with antivascular endothelial growth factor versus a dexamethasone intravitreal implant in Korea: a population-based study
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Hyun Jeong Cho, You Kyung Lee, Seung Jin Bae, Nam Kyong Choi, Kyung Seek Choi, Donghwan Lee, and Joo Yong Lee
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Male ,Vascular Endothelial Growth Factor A ,genetic structures ,cost of illness ,Angiogenesis Inhibitors ,Dexamethasone ,Cohort Studies ,0302 clinical medicine ,Health care ,Occlusion ,Dexamethasone Intravitreal Implant ,030212 general & internal medicine ,Original Research ,Aflibercept ,Drug Implants ,Health Care Costs ,General Medicine ,Diabetic retinopathy ,Middle Aged ,population-based study ,Intravitreal Injections ,Health Resources ,Female ,Public Health ,diabetic macular edema ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Recombinant Fusion Proteins ,agencies regulation ,Macular Edema ,Young Adult ,03 medical and health sciences ,Ranibizumab ,Internal medicine ,Republic of Korea ,medicine ,Humans ,Aged ,Retrospective Studies ,Diabetic Retinopathy ,Korea ,business.industry ,Retrospective cohort study ,Macular degeneration ,medicine.disease ,resource utilization ,Receptors, Vascular Endothelial Growth Factor ,030221 ophthalmology & optometry ,business ,Facilities and Services Utilization - Abstract
ObjectivesTo estimate the costs and healthcare resources of patients with diabetic macular oedema (DME) who received intravitreal antivascular endothelial growth factor (anti-VEGF) agents or a dexamethasone intravitreal implant (DEX-implant) in Korea.DesignRetrospective cohort study.SettingThe Korean National Health Insurance claim data from 1 January 2015 to 30 June 2017 were retrieved from the Health Insurance Review and Assessment Service.ParticipantsAdult patients with DME who were diagnosed with diabetic retinopathy or DME and received ranibizumab, aflibercept or a DEX-implant in conjunction with intravitreal injection were included. Patients whose primary diagnoses were age-related macular degeneration or retinal vein occlusion were excluded.Main outcome measuresHealthcare resource utilisation and costs related to DME in the 12-month postindex period.ResultsDuring the study period, 182 patients and 414 patients were identified in the anti-VEGF and DEX-implant groups, respectively, and there was no significant difference in the demographic characteristics between the two groups. The outpatient eye care-related medical costs were US$3002.33 for the anti-VEGF group vs US$2250.35 for the DEX-implant group (pConclusionThe average annual eye-related medical cost of the DEX-implant group was significantly lower than that of the anti-VEGF group during the study period, which was mainly due to decreased utilisation of eye care-related injections. Further long-term studies are needed. more...
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- 2019
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30. Pharmacokinetics of Rosuvastatin/Olmesartan Fixed-Dose Combination: A Single-Dose, Randomized, Open-Label, 2-Period Crossover Study in Healthy Korean Subjects
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Chohee Yun, Hankil Son, Donghwan Lee, Hee-Chul Chang, Hyerang Roh, Kim Jun-Ku, and Kyungsoo Park
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Adult ,Male ,medicine.medical_specialty ,Fixed-dose combination ,Urology ,Administration, Oral ,Tetrazoles ,Pharmacology ,Bioequivalence ,Young Adult ,Pharmacokinetics ,medicine ,Humans ,Pharmacology (medical) ,Rosuvastatin ,Rosuvastatin Calcium ,Sulfonamides ,Cross-Over Studies ,business.industry ,Imidazoles ,Middle Aged ,Desmethyl ,Crossover study ,Healthy Volunteers ,Fluorobenzenes ,Drug Combinations ,Pyrimidines ,Drug Therapy, Combination ,Olmesartan ,business ,Combination drug ,medicine.drug - Abstract
Background Rosuvastatin, a lipid-lowering agent, has been widely used with olmesartan, a long-acting angiotensin II receptor blocker, indicated for the treatment of dyslipidemia accompanied by hypertension. A fixed-dose combination (FDC) tablet of these 2 drugs was recently developed to enhance the dosing convenience and to increase patient compliance while yielding pharmacokinetic profiles comparable to coadministration of each drug as individual tablets. Objective The goal of present study was to compare the pharmacokinetic profiles of single-dose administration of an FDC tablet containing rosuvastatin/olmesartan 20/40 mg (test formulation) with coadministration of a rosuvastatin 20-mg tablet and a olmesartan 40-mg tablet (reference formulation) in healthy Korean male volunteers, for the purpose of determining bioequivalence. Methods This single-dose, randomized, open-label, 2-period crossover study enrolled subjects aged 20 to 50 years and within 20% of ideal body weight. Each subject received a single dose of the test and reference formulations orally in a fasted state, with a 7-day washout period between the administrations. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite ( N -desmethyl rosuvastatin), and olmesartan. Bioequivalence was concluded if the 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters were within the predetermined range of 80% to 125%. Adverse events (AEs) were evaluated based on subject interviews and physical examinations. Results Among the 58 enrolled subjects, 54 completed the study. The 90% CIs of the geometric mean ratios of the primary pharmacokinetic parameters were as follows: rosuvastatin: AUC last , 85.60% to 97.40% and C max , 83.16% to 98.21%; N -desmethyl rosuvastatin: AUC last , 82.08% to 93.45% and C max , 79.23% to 93.41%; and olmesartan: AUC last , 97.69% to 105.69% and C max , 100.35% to 109.42%. The most frequently noted AE was headache, occurring in 3 and 6 patients with the test and reference formulations, respectively. All of the AEs were expected, and there was no significant difference in the prevalences of AEs between the 2 formulations. Conclusions The pharmacokinetic properties of the newly developed FDC tablet of rosuvastatin/olmesartan 20/40 mg suggest that it is bioequivalent to co-administration of each drug as individual tablets in these healthy Korean male subjects. The two formulations were well tolerated, with no serious AEs observed. ClinicalTrials.gov identifier: NCT01823900. more...
- Published
- 2013
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31. Pharmacokinetic Comparison of 2 Fixed-Dose Combination Tablets of Amlodipine and Valsartan in Healthy Male Korean Volunteers: A Randomized, Open-Label, 2-Period, Single-Dose, Crossover Study
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Hankil Son, Mijeong Son, Donghwan Lee, Kyungsoo Park, Hyerang Roh, Yukyung Kim, Mi Young Bahng, and Dongwoo Chae
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Adult ,Male ,medicine.medical_specialty ,Fixed-dose combination ,Urology ,Administration, Oral ,Tetrazoles ,amlodipine ,Bioequivalence ,Pharmacology ,valsartan ,Dosage form ,Young Adult ,Asian People ,Pharmacokinetics ,Humans ,Medicine ,Pharmacology (medical) ,Amlodipine ,pharmacokinetic ,combination drug ,Cross-Over Studies ,business.industry ,Valine ,Middle Aged ,Crossover study ,Healthy Volunteers ,Drug Combinations ,Valsartan ,Drug Therapy, Combination ,business ,Tablets ,Combination drug ,medicine.drug - Abstract
Background Amlodipine and valsartan have different mechanisms of action, and it is known that the combination therapy with the 2 drugs increases treatment effects compared with the monotherapy with each drug. A fixed-dose combination (FDC) drug is a formulation including fixed amounts of active drug ingredients combined in a single dosage form that is expected to improve medication compliance. Objective The goal of this study was to compare the pharmacokinetic profiles of single administration of a newly developed FDC tablet containing amlodipine orotate 10 mg and valsartan 160 mg (test formulation) with the conventional FDC tablet of amlodipine besylate 10 mg and valsartan 160 mg (reference formulation) in healthy male Korean volunteers. Methods This was a randomized, open-label, single-dose, 2-way crossover study. Eligible subjects were between the ages of 20 and 50 years and within 20% of their ideal weight. Each subject received a single dose of the reference and the test formulations, with a 14-day washout period between formulations. Blood samples were collected up to 144 hours after the dose, and pharmacokinetic parameters were determined for amlodipine and valsartan. Adverse events were evaluated based on subject interviews and physical examinations. Results Forty-eight of the 50 enrolled subjects completed the study. For both amlodipine and valsartan, the primary pharmacokinetic parameters were included in the range for assumed bioequivalence, yielding 90% CI ratios of 0.9277 to 0.9903 for AUC 0–last and 0.9357 to 1.0068 for C max in amlodipine, and 0.9784 to 1.1817 for AUC 0–last and 0.9738 to 1.2145 for C max in valsartan. Dizziness was the most frequently noted adverse event, occurring in 4 subjects with the test formulation, followed by oropharyngeal pain occurring in 1 subject with the test formulation and 3 subjects with the reference formulation. All other adverse events occurred in Conclusions These findings suggest that the pharmacokinetics of the newly developed FDC tablet of amlodipine and valsartan did not differ significantly from the conventional FDC tablet in these healthy Korean male subjects. Both formulations were well tolerated, with no serious adverse events observed. ClinicalTrials.gov identifier: NCT01823913. more...
- Published
- 2013
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32. Effect ofHMGCRVariant Alleles on Low-Density Lipoprotein Cholesterol-Lowering Response to Atorvastatin in Healthy Korean Subjects
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Yoon Jung Lee, Donghwan Lee, Kyungsoo Park, Lay Ahyoung Lim, Sung Kweon Cho, Eun Sil Oh, Seong Bok Jang, Jae Yong Chung, and Min Soo Park
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Adult ,Male ,medicine.medical_specialty ,Genotype ,Atorvastatin ,Reductase ,Pharmacology ,Young Adult ,Basal (phylogenetics) ,Asian People ,Pharmacokinetics ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,Pyrroles ,Pharmacology (medical) ,Hypolipidemic Agents ,Polymorphism, Genetic ,biology ,Cholesterol, LDL ,Endocrinology ,Heptanoic Acids ,HMG-CoA reductase ,biology.protein ,Female ,Hydroxymethylglutaryl CoA Reductases ,lipids (amino acids, peptides, and proteins) ,Creatine kinase ,Pharmacogenetics ,medicine.drug - Abstract
The investigators quantified the relationship between the genetic polymorphism of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and the low-density lipoprotein cholesterol (LDL-C)-lowering effects of atorvastatin in a prospective clinical study. Twenty-four healthy participants were grouped into HMGCR rs3846662 GG (n = 13) and AA (n = 11) genotypes and given atorvastatin (20 mg/d) for 14 days. Serum levels of LDL-C, high-density lipoprotein cholesterol, total cholesterol, triglycerides, and creatinine kinase (CK) were measured before (day 1) and 7, 13, 14, 15, 16, 21, and 28 days after dosing initiation. Blood samples for pharmacokinetics were taken on days 14 through 16. The levels of LDL-C in the GG group were significantly higher than in the AA group at all observation times, with mean differences of 18% to 33% (P < .05). The area under the LDL-C-time curve and the minimum value of LDL-C in the GG group were 24% and 23% higher than in the AA group, respectively (P < .01). There was no significant difference in other lipids, CK, and pharmacokinetic parameters. The HMGCR rs3846662 GG genotype was quantitatively documented to be a significant determinant for higher LDL-C level in basal state and possibly in response to atorvastatin. more...
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- 2012
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33. Comprehensive landscape of subtype-specific coding and non-coding RNA transcripts in breast cancer
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Chen Suo, Setia Pramana, Yudi Pawitan, Trung Nghia Vu, Donghwan Lee, and Stefano Calza
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0301 basic medicine ,Gene isoform ,Proteomics ,subtype-specific isoforms ,Breast Neoplasms ,Computational biology ,Biology ,Bioinformatics ,Receptor, Angiotensin, Type 1 ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Molecular classification ,breast cancer ,microRNA ,medicine ,Humans ,RNA, Neoplasm ,Gene ,Gene Expression Profiling ,subtype co-expression ,RNA ,RNA sequencing ,Non-coding RNA ,medicine.disease ,Prognosis ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Area Under Curve ,non-coding RNAs ,Female ,RNA, Long Noncoding ,Algorithms ,Research Paper - Abstract
// Trung Nghia Vu 1, * , Setia Pramana 1, * , Stefano Calza 1, 2, * , Chen Suo 1 , Donghwan Lee 1, 3 , Yudi Pawitan 1 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE 17177 Stockholm, Sweden 2 Department of Molecular and Translational Medicine, University of Brescia, 25125 Brescia, Italy 3 Department of Statistics, Ewha Womans University, Seodaemun-gu, Seoul 120-750, South Korea * These authors have contributed equally to this work Correspondence to: Yudi Pawitan, email: Yudi.Pawitan@ki.se Keywords: breast cancer, RNA sequencing, subtype-specific isoforms, subtype co-expression, non-coding RNAs Received: June 30, 2016 Accepted: August 24, 2016 Published: September 13, 2016 ABSTRACT Molecular classification of breast cancer into clinically relevant subtypes helps improve prognosis and adjuvant-treatment decisions. The aim of this study is to provide a better characterization of the molecular subtypes by providing a comprehensive landscape of subtype-specific isoforms including coding, long non-coding RNA and microRNA transcripts. Isoform-level expression of all coding and non-coding RNAs is estimated from RNA-sequence data of 1168 breast samples obtained from The Cancer Genome Atlas (TCGA) project. We then search the whole transcriptome systematically for subtype-specific isoforms using a novel algorithm based on a robust quasi-Poisson model. We discover 5451 isoforms specific to single subtypes. A total of 27% of the subtype-specific isoforms have better accuracy in classifying the intrinsic subtypes than that of their corresponding genes. We find three subtype-specific miRNA and 707 subtype-specific long non-coding RNAs. The isoforms from long non-coding RNAs also show high performance for separation between Luminal A and Luminal B subtypes with an AUC of 0.97 in the discovery set and 0.90 in the validation set. In addition, we discover 1500 isoforms preferentially co-expressed in two subtypes, including 369 isoforms co-expressed in both Normal-like and Basal subtypes, which are commonly considered to have distinct ER-receptor status. Finally, analyses at protein level reveal four subtype-specific proteins and two subtype co-expression proteins that successfully validate results from the isoform level. more...
- Published
- 2016
34. Optimal likelihood-ratio multiple testing with application to Alzheimer’s disease and questionable dementia
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Donghwan Lee, Heejung Kim, Yu Kyeong Kim, Dong Soo Lee, Hye Jin Kang, Hyekyoung Lee, Eunkyung Kim, and Youngjo Lee
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False discovery rate ,Epidemiology ,Multiple hypotheses ,Health Informatics ,Disease ,computer.software_genre ,Hippocampus ,Sensitivity and Specificity ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,Voxel ,Statistics ,medicine ,Humans ,Dementia ,Computer Simulation ,Questionable dementia ,Independence (probability theory) ,Likelihood Functions ,Brain ,Reproducibility of Results ,nutritional and metabolic diseases ,medicine.disease ,Frontal Lobe ,nervous system diseases ,Positron-Emission Tomography ,Multiple comparisons problem ,Psychology ,Neuroscience ,computer ,Research Article - Abstract
Background: Controlling the false discovery rate is important when testing multiple hypotheses. To enhance the detection capability of a false discovery rate control test, we applied the likelihood ratio-based multiple testing method in neuroimage data and compared the performance with the existing methods. Methods: We analysed the performance of the likelihood ratio-based false discovery rate method using simulation data generated under independent assumption, and positron emission tomography data of Alzheimer's disease and questionable dementia. We investigated how well the method detects extensive hypometabolic regions and compared the results to those of the conventional Benjamini Hochberg-false discovery rate method. Results: Our findings show that the likelihood ratio-based false discovery rate method can control the false discovery rate, giving the smallest false non-discovery rate (for a one-sided test) or the smallest expected number of false assignments (for a two-sided test). Even though we assumed independence among voxels, the likelihood ratio-based false discovery rate method detected more extensive hypometabolic regions in 22 patients with Alzheimer's disease, as compared to the 44 normal controls, than did the Benjamini Hochberg-false discovery rate method. The contingency and distribution patterns were consistent with those of previous studies. In 24 questionable dementia patients, the proposed likelihood ratio-based false discovery rate method was able to detect hypometabolism in the medial temporal region. Conclusions: This study showed that the proposed likelihood ratio-based false discovery rate method efficiently identifies extensive hypometabolic regions owing to its increased detection capability and ability to control the false discovery rate. more...
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- 2015
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35. Population pharmacokinetic analysis of diurnal and seasonal variations of plasma concentrations of cilostazol in healthy volunteers
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Hankil Son, Lay A. Lim, Donghwan Lee, and Kyungsoo Park
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Male ,Metabolic Clearance Rate ,Population ,Physiology ,Administration, Oral ,Tetrazoles ,Models, Biological ,Pharmacokinetics ,Covariate ,Healthy volunteers ,Medicine ,Humans ,Pharmacology (medical) ,Dosing ,education ,Pharmacology ,education.field_of_study ,business.industry ,Diurnal temperature variation ,Healthy Volunteers ,Cilostazol ,Circadian Rhythm ,Population model ,Female ,Seasons ,business ,medicine.drug - Abstract
The background of this study was (1) to examine factors influencing cilostazol pharmacokinetics by developing a population model incorporating diurnal variation and other covariate effects and (2) to assess the feasibility of applying the developed model to determine the optimal dosing times.Data obtained from a cilostazol pharmacokinetic study consisting of 2 clinical trials (a single twice-a-day (BID) dosing trial in winter and a multiple BID dosing trial in summer) conducted in healthy Korean subjects were used for model building. A basic model was built, followed by a diurnal variation model, and then a final model was built incorporating covariates, including a seasonal difference. The optimal morning and evening dosing times were determined from simulations.Diurnal variation in cilostazol pharmacokinetics was explained by the morning absorption rate constant being faster than in the evening, yielding values of 0.278 versus 0.234/h in summer, when 24- and 12-hour circadian rhythms were included in the model. The seasonal variation was explained by a 26.9% and a 31.8% decrease in the absorption rate constant and clearance, respectively, in winter compared with summer. Based on twice-a-day (BID) dosing, dosing times of 9 AM and 5 PM in summer and 10 AM and 7 PM in winter were expected to produce the smallest peak-to-peak fluctuations in cilostazol concentration, possibly minimizing unwanted effects of the drug.This study demonstrated the intraday and interseasonal time-varying nature of cilostazol pharmacokinetics using a population modeling approach and developed a strategy for optimizing dosing times. It is suggested that these methods can be similarly applied to analyses and controls of other drugs that exhibit characteristics of time-varying pharmacokinetics. more...
- Published
- 2014
36. Pharmacokinetic interaction between rosuvastatin and olmesartan: a randomized, open-label, 3-period, multiple-dose crossover study in healthy Korean male subjects
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Kyungsoo Park, Hee-Chul Chang, Chohee Yun, Hyerang Roh, Hankil Son, and Donghwan Lee
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Adult ,Male ,Administration, Oral ,Tetrazoles ,Pharmacology ,Young Adult ,Pharmacokinetics ,Asian People ,Republic of Korea ,medicine ,Humans ,Pharmacology (medical) ,Rosuvastatin ,Drug Interactions ,Rosuvastatin Calcium ,Adverse effect ,Active metabolite ,Antihypertensive Agents ,Cross-Over Studies ,business.industry ,Imidazoles ,nutritional and metabolic diseases ,Desmethyl ,Middle Aged ,Crossover study ,Healthy Volunteers ,Area Under Curve ,Drug Therapy, Combination ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Olmesartan ,business ,medicine.drug - Abstract
Purpose Rosuvastatin has been widely used in combination with olmesartan for the treatment of dyslipidemia accompanied by hypertension. With no information currently available on the interaction between the 2 drugs, a pharmacokinetic study was conducted to investigate the influence of rosuvastatin on olmesartan and vice versa when the 2 drugs were coadministered. The purpose of this study was to investigate the pharmacokinetic profile of coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet and the associated drug–drug interaction in healthy Korean male volunteers. Methods This was a randomized, open-label, 3-period, multiple-dose crossover study. Eligible subjects were aged 20 to 50 years and within 20% of their ideal body weight. After being randomly assigned to 6 groups of equal number, subjects received each of the following 3 formulations once a day for 7 consecutive days with an 8-day washout period between the formulations: rosuvastatin 20-mg tablet, olmesartan 40-mg tablet, and coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite ( N -desmethyl rosuvastatin), and olmesartan. Adverse events were evaluated based on subject interviews and physical examinations. Findings Among the 36 enrolled subjects, 34 completed the study (mean [range] age, 28.6 [23–49] y; mean [range] weight, 66.4 [52.2–78.7] kg). The 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters for the coadministration of the 2 drugs to the mono-administration of each drug were 85.14% to 96.08% for AUC τ and 81.41% to 97.48% for C ss,max for rosuvastatin, and 77.55% to 89.48% for AUC τ and 75.62% to 90.12% for C ss,max for N -desmethyl rosuvastatin; those values were 95.61% to 102.57% for AUC τ and 91.73% to 102.98% for C ss,max for olmesartan. Dizziness was the most frequently noted adverse drug reaction, occurring in 1 subject receiving mono-administration of rosuvastatin, 1 subject receiving mono-administration of olmesartan, and 4 subjects receiving coadministration of rosuvastatin and olmesartan. All the adverse events were expected, and there was no significant difference in the incidence between the 2 formulations. Implications This study suggests that rosuvastatin and olmesartan did not significantly influence each other's pharmacokinetics when coadministered. Although the pharmacokinetics of N -desmethyl rosuvastatin were influenced by olmesartan, such interactions were considered clinically insignificant. All 3 formulations were well tolerated, and no serious adverse events or drug reactions were noted. more...
- Published
- 2014
37. Development of a pharmacokinetic interaction model for co-administration of simvastatin and amlodipine
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Hyerang Roh, Hankil Son, Donghwan Lee, Lay Ahyoung Lim, Seong Bok Jang, and Kyungsoo Park
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Drug ,Adult ,Male ,Simvastatin ,Genotype ,Metabolite ,media_common.quotation_subject ,Pharmaceutical Science ,Administration, Oral ,Biological Availability ,Pharmacology ,Models, Biological ,chemistry.chemical_compound ,Republic of Korea ,polycyclic compounds ,Medicine ,Cytochrome P-450 CYP3A ,Humans ,Pharmacology (medical) ,Drug Interactions ,cardiovascular diseases ,Amlodipine ,media_common ,Cross-Over Studies ,Polymorphism, Genetic ,CYP3A4 ,business.industry ,organic chemicals ,Body Weight ,Age Factors ,nutritional and metabolic diseases ,Drug interaction ,Middle Aged ,Calcium Channel Blockers ,Crossover study ,Healthy Volunteers ,Bioavailability ,Phenotype ,chemistry ,Polypharmacy ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,medicine.drug - Abstract
A model for drug interaction between amlodipine and simvastatin was developed using concentration data obtained from a multiple-dose study consisting of single- and co-administration of amlodipine and simvastatin conducted in healthy Koreans. Amlodipine concentrations were assumed to influence the clearance of simvastatin and simvastatin acid, which as well as the oral bioavailability was allowed to vary depending on genetic polymorphisms of metabolic enzymes. Covariate effects on drug concentrations were also considered. The developed model yielded a 46% increase in simvastatin bioavailability and a 13% decrease in simvastatin clearance when amlodipine 10 mg was co-administered. When CYP3A4/5 polymorphisms were assessed by a mixture model, extensive metabolizers yielded a decrease in simvastatin bioavailability of 81% and a decrease in simvastatin clearance by 4.6 times as compared to poor metabolizers. Sixty percent of the usual dose was the optimal simvastatin dose that can minimize the interaction with amlodipine 10 mg. Age and weight had significant effects on amlodipine concentrations. In conclusion, this study has quantitatively described the pharmacokinetic interaction between simvastatin and amlodipine using a modeling approach. Given that the two drugs are often prescribed together, the developed model is expected to contribute to more efficient and safer drug treatment when they are co-administered. more...
- Published
- 2013
38. Pharmacokinetic comparison of an orally disintegrating film formulation with a film-coated tablet formulation of sildenafil in healthy Korean subjects: a randomized, open-label, single-dose, 2-period crossover study
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Kyu Jeong Yeon, Hyun Soo Kim, Hohyun Kim, Hyerang Roh, Hankil Son, Donghwan Lee, and Kyungsoo Park
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Adult ,Male ,Sildenafil ,Administration, Oral ,Bioequivalence ,Piperazines ,Sildenafil Citrate ,law.invention ,chemistry.chemical_compound ,Young Adult ,Pharmacokinetics ,Randomized controlled trial ,law ,Reference Values ,Republic of Korea ,Medicine ,Humans ,Pharmacology (medical) ,Dosing ,Sulfones ,Active metabolite ,Pharmacology ,Cross-Over Studies ,business.industry ,Desmethyl ,Middle Aged ,Phosphodiesterase 5 Inhibitors ,Crossover study ,chemistry ,Purines ,Anesthesia ,business ,Tablets - Abstract
An orally disintegrating film (ODF) formulation of sildenafil was recently developed in Korea. This formulation is expected to enhance dosing convenience and increase patient compliance while yielding pharmacokinetics comparable to those of the conventional film-coated tablet (FCT) formulation.The goal of this study was to compare the pharmacokinetic profiles of a newly developed ODF formulation with those of a FCT formulation of sildenafil in healthy Korean male volunteers.This was a randomized, open-label, single-dose, 2-period crossover study conducted in 2 parts. Eligible subjects were between the ages of 20 and 50 years and within 20% of their ideal weight; subjects were equally divided into parts 1 and 2. Each subject received a single dose of the ODF and FCT formulations of sildenafil orally in a fasted state (part 1, 50 mg; part 2, 100 mg), with a 7-day washout period between the formulations. Blood samples were collected up to 24 hours postdosing. Pharmacokinetic parameters were determined for sildenafil and its active metabolite (N-desmethyl sildenafil). Adverse events (AEs) were evaluated based on subject interviews and physical examinations.Among the 120 enrolled subjects (60 subjects for each part), 110 completed the study (part 1, n = 53; part 2, n = 57). In both parts, all the primary pharmacokinetic parameters were included in the range for assumed bioequivalence in sildenafil, yielding 90% CI ratios of 91.07% to 120.67% for AUC0-last and 86.68% to 122.93% for Cmax in part 1, and 101.68% to 114.78% for AUC0-last and 93.76% to 109.76% for Cmax in part 2. In part 1, headache was the most frequently noted AE, occurring in 3 subjects with both the test and the reference formulations. All other AEs occurred in3 subjects. In part 2, nasal congestion was the most frequently observed AE (7 with the test formulation and 1 with the reference formulation), followed by abnormal vision (4 with the test formulation and 4 with the reference formulation), headache (4 with the test formulation and 4 with the reference formulation), and rhinorrhea (5 with the test formulation). All other AEs occurred in3 subjects.The study findings suggest that the pharmacokinetics of the ODF formulation of sildenafil do not differ significantly from those of the conventional FCT formulation (50 and 100 mg) in these healthy Korean male subjects. The 2 formulations were well tolerated in both parts of the study, with no serious AEs observed. ClinicalTrials.gov identifier: NCT01769638. more...
- Published
- 2013
39. The association between some endocrine disruptors in human plasma and the occurrence of congenital hypothyroidism
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Yonghee Hong, Hyunju Jung, Kijung Pang, Donghwan Lee, and Yunje Kim
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endocrine system ,medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,Phthalic Acids ,Genistein ,Mothers ,Endocrine Disruptors ,Toxicology ,Gas Chromatography-Mass Spectrometry ,chemistry.chemical_compound ,Phenols ,Reference Values ,Internal medicine ,Diethylhexyl Phthalate ,medicine ,Congenital Hypothyroidism ,Endocrine system ,Humans ,Benzhydryl compounds ,Benzhydryl Compounds ,Pharmacology ,Endocrine disease ,Daidzein ,Infant, Newborn ,Infant ,Reproducibility of Results ,General Medicine ,Equol ,Isoflavones ,medicine.disease ,Congenital hypothyroidism ,Endocrinology ,chemistry ,Child, Preschool ,Female ,hormones, hormone substitutes, and hormone antagonists - Abstract
Congenital hypothyroidism is a common pediatric endocrine disease. Endocrine disruptors are indicated as a possible cause of congenital hypothyroidism. We investigated the associations between endocrine disruptors and the occurrence of congenital hypothyroidism and passage of target compounds from the mother. The levels of phthalates (DEHP, MEHP, DBP, MBP and PA), alkylphenols (n-NP and t-OP), bisphenol, and isoflavones (equol, daidzein and genistein) were determined by gas chromatography-mass spectrometry (GC-MS) in infants. t-OP and PA concentrations in the patient group were significantly higher than in normal infants. Genistein concentrations in normal infants were significantly higher than in patients. We compared the plasma levels of target compounds in infants with their mothers. There was no correlation with the passage of endocrine disruptors and isoflavones from the mothers, except for t-OP, which was weakly correlated between mother and infant. more...
- Published
- 2012
40. Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study
- Author
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Jin Woo Park, Kiyoon Kim, Yoon Jung Lee, Min Soo Park, Seong Bok Jang, Donghwan Lee, Lay Ahyoung Lim, Jae Yong Lee, Hosang Yoon, Jae Yong Chung, Kyungsoo Park, and Jong Rak Choi
- Subjects
Adult ,Male ,Metabolic Clearance Rate ,Chemistry, Pharmaceutical ,Administration, Oral ,Tetrazoles ,Bioequivalence ,Pharmacology ,Models, Biological ,law.invention ,Food-Drug Interactions ,Young Adult ,Randomized controlled trial ,Pharmacokinetics ,Asian People ,law ,Republic of Korea ,Medicine ,Humans ,Pharmacology (medical) ,Adverse effect ,FOOD EFFECT ,Cross-Over Studies ,business.industry ,Cardiovascular Agents ,Middle Aged ,Crossover study ,Cilostazol ,Bioavailability ,Therapeutic Equivalency ,Area Under Curve ,Delayed-Action Preparations ,Female ,business ,medicine.drug - Abstract
A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation.The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency.This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations.Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P0.0001), yielding geometric mean ratios of 3.2879, 2.9894, and 3.0592 for C(max) and 1.7001, 1.7689, and 1.6976 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213. In part 3, only the C(ssmax) of clilostazol in the reference formulation did not satisfy the criterion for assumed bioequivalence, yielding 90% CI ratios of 1.2693 to 1.4238 and 1.2038 to 1.3441, respectively. When each dose was normalized, the C(max) for the SR formulation was significantly lower (P0.005 for cilostazol). Headache was the most frequently noted adverse effect (part 1, a total of 14 subjects with the IR formulation and 14 with the SR formulation; part 2, a total of 10 without food and 23 with a high-fat meal; part 3, a total of 10 with the IR formulation and 24 with the SR formulation), followed by nausea (part 1, none; part 2, only 1 without food and 3 with a high-fat meal; part 3, a total of 3 with the IR formulation and 3 with the SR formulation), and then dizziness (parts 1 and 2, none; part 3, a total of 4 with the IR formulation and 5 with the SR formulation). All other AEs, including fever, cough, vomiting, palpitation, diarrhea, and epigastric pain, occurred in3 subjects.These findings suggest that in this select group of healthy Korean volunteers, the SR formulation of cilostazol was not significantly different in AUC compared with that of the IR formulation, although it did display a significantly lower C(max) per dose in both the single- and multiple-dose groups. Food significantly increased the bioavailability of the SR formulation. The cilostazol SR and IR formulations were well tolerated in all parts of the study, with no serious adverse events reported. ClinicalTrials.gov identifier: NCT01455558. more...
- Published
- 2011
41. Assessment of statistical power for covariate effects in data from phase I clinical trials
- Author
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Yukyung Kim, Hankil Son, Mijeong Son, Donghwan Lee, Kyungsoo Park, and Young-A Heo
- Subjects
medicine.medical_specialty ,Clinical pharmacology ,business.industry ,Statistical power ,law.invention ,NONMEM ,Clinical trial ,law ,Covariate ,medicine ,Econometrics ,Pharmacology (medical) ,Medical physics ,Medical science ,business - Abstract
Yukyung Kim, Hankil Son, Mijeong Son, Donghwan Lee, Young-A Heo and Kyungsoo Park* Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Korea, Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul 120-752, Korea, Department of Clinical Pharmacology and Therapeutics, Inje University Pusan Paik Hospital, Busan 614-735, Korea *Correspondence: K. S. Park; Tel: +82-2-2228-1735, Fax: +82-2-313-1894, E-mail: kspark@yuhs.ac more...
- Published
- 2015
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42. The Safety and the Pharmacokinetics and Pharmacodynamics of a Pegylated Interferon Alpha-2a Formulation, Dong-A's DA-3021
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Seong Bok Jang, Donghwan Lee, Kyungsoo Park, Hankil Son, Jae Yong Chung, Yoon Jung Lee, and Lay Ahyoung Lim
- Subjects
Pharmacokinetics ,business.industry ,Pharmacodynamics ,Pegylated interferon alpha 2a ,PEGylation ,Medicine ,Pharmacology (medical) ,Pharmacology ,business ,Interferon Alpha 2a - Published
- 2010
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43. Physiological Dual Chamber Pacemaker Implantation (VDD Type, a Report of 2 Cases)
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Woonji Lee, Donghwan Lee, Yangha Kim, and Hyerin Kim
- Subjects
Dual Chamber Pacemaker ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,business - Published
- 1985
- Full Text
- View/download PDF
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