As the pharmaceutical industry in Korea is reaching the golden era of drug discovery due to increased investments in research and development and government funds, the need for a more efficient tool for the quantitative analysis has emerged. Therefore, the demand for pharmacometrics (PMx) consultancy services increased. Higher quality service suitable for regulatory submission and out-licensing deals were desired. In this analysis, we compiled and summarized 3 years of experiences of Q-fitter, the first PMx consultancy service company providing PMx analysis to the pharmaceutical industry in Korea. The projects were organized by companies, company types, indications, therapeutic areas, drug development stages, purposes, and scope of services. Within each category, we subcategorized the sections and assessed proportions and a year-over-year trend. As a result, we observed an increase in the number of projects in an average of ~170% per year, with the most frequent types of companies collaborated being the domestic pharmaceutical companies. Among the projects, ~72% involved modeling and simulation using population pharmacokinetic (PK) models, and the other included non-compartmental analysis (NCA), drug-drug interaction (DDI) prediction, and interpretation of the modeling results. The most sought-after purpose in PMx analysis was first-in-human (FIH) dose prediction followed by PK analysis, next clinical trial prediction, and scenario-based simulation. Oncology has been the top therapeutic area of interest every year consisting of ~38% of total projects, followed by Neurology (~13%). From this review, we were able to characterize the PMx service needs and spot the trend of current PMx practices in Korea.
Drug Discovery ; Drug Industry ; Financial Management ; Investments ; Korea ; Neurology

Objectives: The purpose of this study was to classify the users of a university counseling center and define their characteristics using the information from the service application written by them as one of the approaches to improve the efficiency of the center. Methods: The participants were a total of 300 users of the university counseling and affiliated psychiatry center in the local science and technology institute. The service application form used in this study contained questions on personal information, overall satisfaction with university life and interpersonal relationships, problem areas and symptoms, depression, anxiety, sleep, family history, suicidal thoughts, experiences of suicide/self-harm attempts, and a functional impairment questionnaire. First, a latent class analysis was performed to classify the layers and define them. Also, a tree-based model was used to confirm the characteristics of the service applications of the suicide/self-harm attempt experience group. Results: A total of 5 layers were found to be the most suitable fit. They were named the ‘health concern type,’ ‘relation problem type,’ ‘depression-sleep problem combined type,’ ‘complex problem type,’ and ‘sleep problem type.’ The variable that best discriminates the suicide/selfharm attempt experience group was question 5 of the Patient Health Questionnaire (PHQ-9). The frequency of selection in the impulsivity domain among the problem types and question 9 of the PHQ-9 was followed. Conclusion The results of this study indicate that five types of discriminatory interventions are possible based on the characteristics of the service application. The application can thus be used as basic data for increasing service efficiency in university counseling.

The prevalence of Atopic Dermatitis (AD), a non-infective chronic inflammatory skin disease, is increasing worldwide. Avoiding the allergen is the basic principle in the treatment of AD. However, when the allergen is food, excessive restriction can lead to nutrition deficiency. The objective of the study was to examine the status of the dietary restriction and compare the caregiver's restriction practice with doctor's recommendation in Korean children with AD. A total of 158 children diagnosed with Atopic Dermatitis were recruited for this study. Information about foods that aggravate AD symptoms and food restriction were collected from the mothers of 158 children aged 6 month-5 year with AD using questionnaires. Food restriction recommendation by doctor was collected through medical chart. McNemar and Margianl homogeneity tests were used to detect a relationship between food restriction recommended by doctor and current practice by mother. There were significant proportion differences of food restriction for each food between by doctor and mother. We found 75.9% of children were avoiding eggs although only 61.4% were recommended for egg restriction by a doctor. Children with restriction of more than 4 kinds of food were 53.2% compared to 13.3% by doctor. Excessive restrictors tended to be younger and diagnosed at younger age. The caregivers of excessive restrictors had trends of "being older" and "having higher income". Avoidance of common foods in children without food allergy could result in malnutrition or impaired growth. Nutrition education is needed for sound practice and nutrition care in children with Atopic Dermatitis as well as interactive communication between caregivers and experts.
Aged ; Caregivers ; Child ; Dermatitis, Atopic ; Eggs ; Food Hypersensitivity ; Humans ; Malnutrition ; Mothers ; Ovum ; Prevalence ; Surveys and Questionnaires ; Skin Diseases

PURPOSE: In elderly and patients with underlying diseases, mortality rate is increased when compared to rib fractures which occurred in other patients. Because there is a shortage of emergency physicians or real-time consultation with radiologists in many countries, it is necessary to receive a formal image reading remotely from an expert. We suggested the use of iPad in X-ray reading and compared the diagnostic validity of iPad, which was highly portable, with that of liquid crystal display (LCD) monitor. METHODS: Fifty four X-ray cases of rib fracture and 54 cases without rib fracture were randomized and reviewed by 10 emergency physicians. A total of 108 cases were divided 1st to 54th and 55th to 108th. Two sessions were separated with a four-week interval. If the reviewer interpreted the 1st to 54th with iPad, they did 55th to 108th with LCD monitor. Reviewers reported the presence of rib fracture, the number of fractured ribs, and diagnostic confidence of 5-scale. RESULTS: The interobserver agreement among reviewers in LCD and iPad was 0.551, 0.524 in Fleiss-kappa value. The intraobserver agreement between tools for each reviewer was 0.410-0.859 (Mean=0.628+/-0.150). Reviewers showed sensitivity over 0.810 regardless of the tool; 0.810- 0.966 (Mean=0.879+/- 0.054) in LCD, 0.828-1.000 (Mean=0.898+/-0.052) in iPad. The specificity was 0.520- 0.860 (Mean=0.750+/-0.117) in LCD and 0.560-0.880 (Mean=0.708+/-0.111) in iPad. Therefore, remote consultation of X-ray by iPad with a specialist was possible with minimized temporal and spatial limits in the emergency room. CONCLUSION: In our study, there was no statistical difference in the diagnosis of rib fracture by X-ray via iPad or LCD. Therefore, remote consultation of X-ray by iPad with a specialist in the emergency room was possible, with temporal and spatial limits by iPad.
Aged ; Diagnosis* ; Emergencies ; Emergency Service, Hospital ; Humans ; Liquid Crystals ; Mortality ; Remote Consultation ; Rib Fractures* ; Ribs* ; Sensitivity and Specificity ; Specialization ; Teleradiology

BACKGROUND: Levodropropizine is non-opioid agent whose peripheral antitussive action may result from its modulation of sensory neuropeptide levels. Currently, levodropropizine 60 mg is taken three-times daily. A controlled release formulation of levodropropizine (levodropropizine CR) 90 mg was developed, which can be taken twice daily. The aim of this study was to evaluate the safety and pharmacokinetic characteristics after multiple oral administrations of levodropropizine CR 90 mg tablets in healthy male volunteers. METHODS: A randomized, open-label, cross-over study was conducted in 24 healthy male volunteers. Each subject received levodropropizine syrup 60 mg three times daily or levodropropizine CR 90 mg twice daily for 3 days. Blood samples for pharmacokinetic analysis were collected pre-dose and up to 24 hours on day 4. Pharmacokinetic analysis was conducted by non-compartmental method. Safety assessments including monitoring adverse events, laboratory tests, vital signs, physical examinations and ECGs were performed throughout the study. RESULTS: A total of 20 male volunteers completed the study. The maximum steady-state plasma concentration (Css,max) of levodropropizine syrup and levodropropizine CR were 313.28 ng/mL and 285.31 ng/mL and time to reach Css,max (Tmax,ss) were 0.48 hr and 0.88 hr, respectively. The area under the concentration-time curve to the last measured concentration of two groups were 2345.36 hr x ng/mL and 2553.81 hr x ng/mL, respectively. There was no serious adverse event. CONCLUSION: Levodropropizine CR 90 mg tablet was safe and well-tolerated when administered twice daily for 3 days. No statistically significant differences were seen in Css,max and AUCss,24hr between the two formulations. This study provided pharmacokinetic evidences that the twice-daily dosing regimen of levodropropizine 90 mg may substitute the conventional 3-times-daily regimen of levodropropizine 60 mg.
Administration, Oral ; Cross-Over Studies ; Electrocardiography ; Humans ; Male* ; Methods ; Neuropeptides ; Pharmacokinetics* ; Physical Examination ; Plasma ; Tablets ; Vital Signs

OBJECTIVE: Although tuberculous lymphadenitis and Kikuchi disease are common causes of cervical lymphadenopathy in Asians and exhibit similar clinical manifestations, their treatment strategies are totally different. The purpose of this study was to identify ultrasonographic features that distinguish these two diseases. MATERIALS AND METHODS: This study was approved by the Institutional Review Board. The study included 77 patients with tuberculous lymphadenitis and 135 patients with Kikuchi disease. The sex and age distributions of the patients were analyzed. The size and shape of lymph nodes (LNs), presence of conglomeration, increased perinodal echogenicity, echogenic hilum, posterior neck involvement, internal calcification, patterns of internal necrosis, laterality of involved LNs, and hilar vascular patterns on ultrasonography were compared between the two groups. Multiple logistic regression analysis was conducted to identify independent findings to discriminate tuberculous lymphadenitis from Kikuchi disease. Finally, diagnostic accuracies were calculated using the independent findings. RESULTS: The presence of an echogenic hilum, internal calcification, patterns of internal necrosis, and LN hilar vascular structures on power Doppler ultrasonography were independent findings that discriminated tuberculous lymphadenitis from Kikuchi disease. The diagnostic accuracy of each of these four factors was 84.9% (181/212), 76.9% (163/212), 84% (178/212), and 89.2% (189/212), respectively. A combination of internal calcification and hilar vascular structures showed the best accuracy of 89.6% (190/212) (sensitivity, 86.7% [117/135]; specificity, 94.8% [73/77]) for diagnosing Kikuchi disease. CONCLUSION: The presence of an echogenic hilum, internal calcification, pattern of internal necrosis, and LN hilar vascular structures are useful ultrasonographic findings to differentiate tuberculous lymphadenitis from Kikuchi disease.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Biopsy ; Calcinosis/pathology ; Child ; Child, Preschool ; Female ; Histiocytic Necrotizing Lymphadenitis/pathology/*ultrasonography ; Humans ; Lymph Nodes/pathology/*ultrasonography ; Male ; Middle Aged ; Neck/ultrasonography ; Necrosis/pathology ; Sensitivity and Specificity ; Tuberculosis, Lymph Node/pathology/*ultrasonography ; Ultrasonography, Doppler ; Young Adult

To investigate the effects of maternal hyperthermia on early odontogenesis,pregnant Hsp70 knock-out and wild type mice at embryonic day (ED)8.5 were immersed in a 43 degrees C water bath until their core body temperature reached that temperature,and then given a further 5 min of hyperthermia.Untreated Hsp70 WT mice fetuses were used as the control group.Fetuses were collected at EDs 13.5,15.5 and 17.5.Developing teeth in the mandible were processed for histological and immunohistochemical studies.Tissue sections were immunostained for FGF-8 and FGF -4 and observed using light microscopy.In the controls, FGF-8 immunolocalization was observed in cells within the dental lamina and in apically located dental epithelium at ED 13.5.However,a few cells were immunopositive in the heat shocked (HS)group.At EDs 15.5 and 17.5 of the control group,the basal lamina adjacent to the dental pulp showed positive immunostaining.In contrast,most of the dental epithelium was immunopositive at ED 15.5 in the HS group and inner and outer dental epithelial cells were continuously immunopositive by ED 17.5.FGF-4 immunolocalization was found in apical dental epithelium at ED 13.3 in the control group,but no such positive reaction was observed in the HS group.At ED 15.5 in the controls,basal lamina and dental epithelium near the cervical loop were immunopositive.In contrast,early cap-stage teeth had cells near the mouth of the dental bud and cervical loop that were immunopositive to FGF-4 in the HS group.In controls at ED 17.5,cells near the future secondary enamel knot were immunopositive,whereas most of the dental epithelium except for cells in the mouth of the dental lamina was negative in the HS group.Thus,maternal hyperthermia may inhibit normal odontogenesis through sustained production of FGF-8 and downregulation of FGF-4.
Animals ; Basement Membrane ; Baths ; Body Temperature ; Dental Enamel ; Dental Pulp ; Down-Regulation ; Epithelial Cells ; Epithelium ; Fetus* ; Fever* ; Hot Temperature ; Immunohistochemistry ; Mandible ; Mice ; Mice, Knockout* ; Mouth ; Odontogenesis* ; Shock ; Tooth

Plasma ionized calcium (Ca2+) concentrations are tightly regulated in the body and maintained within a narrow range; thus it is challenging to quantify calcium absorption under normal physiologic conditions. This study aimed to develop a mechanistic model for the parathyroid hormone (PTH) response after calcium intake and indirectly compare the difference in oral calcium absorption from PTH responses. PTH and Ca2+ concentrations were collected from 24 subjects from a clinical trial performed to evaluate the safety and calcium absorption of Geumjin Thermal Water in comparison with calcium carbonate tablets in healthy subjects. Indirect response models (NONMEM Ver. 7.2.0) were fitted to observed Ca2+ and PTH data, respectively, in a manner that absorbed but unobserved Ca2+ inhibits the secretion of PTH. Without notable changes in Ca2+ levels, PTH responses were modeled and used as a marker for the extent of calcium absorption.
Absorption ; Calcium Carbonate ; Calcium* ; Parathyroid Hormone* ; Plasma ; Tablets ; Water

OBJECTIVE: The systemic inflammatory response syndrome (SIRS) criteria used in the triage scale have been implemented incompletely without laboratory data, such as the white blood cell (WBC) count, so the validity of SIRS as a triage tool has been uncertain. This study assessed the validity of the Korean Triage and Acuity Scale (KTAS) in applying SIRS with or without a WBC count. METHODS: The KTAS level was simulated by the number of SIRS criteria. This new KTAS level that did not apply the WBC count was defined as the partial-simulated KTAS (PS-KTAS), and the KTAS level including the WBC count was called the total-simulated KTAS (TS-KTAS). The authors used the intensive care unit (ICU), overall admission rate, and use of emergent interventions as the primary outcomes. RESULTS: A total of 1,077 patients with a suspected infection were triaged using the SIRS in KTAS. Multivariable logistic regression analysis showed that the odds ratio for overall admission was greater with a higher KTAS level than with KTAS level 4 in both the PS-KTAS and TS-KTAS. All areas under the curve of the PS- and TS-KTAS for ICU admission and emergent intervention rate both showed very low discriminant powers. CONCLUSION: Compared to TS-KTAS, PS-KTAS showed a similar or partially better relationship between the KTAS level and the use of critical medical resource. Future research is recommended to improve the matching between the SIRS scoring and each KTAS level to better classify the patient severity status and develop or discover new infection assessment tools that can be applied to KTAS.
Humans ; Intensive Care Units ; Leukocyte Count ; Leukocytes ; Logistic Models ; Odds Ratio ; Systemic Inflammatory Response Syndrome ; Triage

Objective: Subjective cognitive impairment (SCI) is associated with future cognitive decline. This study aimed to compare cortical thickness and local gyrification index (LGI) between individuals with SCI and normal control (NC) subjects. Methods: Forty-seven participants (27 SCI and 20 NC) were recruited. All participants underwent brain magnetic resonance imaging scanning and were clinically assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery of tests. We compared cortical thickness and LGI between the two groups and analyzed correlations between cortical thickness/LGI and scores on CERAD protocol subtests in the SCI group for region of interests with significant between-group differences. Results: Cortical thickness reduction in the left entorhinal, superior temporal, insular, rostral middle frontal, precentral, superior frontal, and supramarginal regions, and right supramarginal, precentral, insular, postcentral, and posterior cingulate regions was observed in the SCI compared to the NC group. Cortical thickness in these regions correlated with scores of constructional praxis, word list memory, word list recall, constructional recall, trail making test A, and verbal fluency under the CERAD protocol. Significantly decreased gyrification was observed in the left lingual gyrus of the SCI group. In addition, gyrification of this region was positively associated with scores of constructional praxis. Conclusion Our results may provide an additional reference to the notion that SCI may be associated with future cognitive impairment. This study may help clinicians to assess individuals with SCI who may progress to mild cognitive impairment and Alzheimer’s dementia.