BACKGROUND: Multidisciplinary team care (MTC) is a collaborative approach to treatment plan and ongoing care. We aimed to evaluate the clinical effect of MTC on the regulation of chronic kidney disease-mineral and bone disorder (CKD-MBD) complications in dialysis patients. METHODS: This retrospective observational study was approved by the institutional review board. Among patients who have undergone dialysis at admission, the patients admitted to the nephrology ward were allocated to MTC group, and the others to usual care (UC) group. The MTC group had collaborative care by nephrologists, nurses, pharmacists, and nutritionists. The endpoints were the regulation of corrected calcium (cCa) and phosphate (P), the percent of patients in target level of cCa-P product (cCa×P), and the prescription rate of non-calcium based P-binders. RESULTS: A total of 163 patients were included from January to December 2009. A significant difference was shown in the percentage of patients in target cCa×P level at admission (MTC vs. UC, 81.40% vs. 91.67%; P = 0.038), but there was no significant difference at discharge. During admission, the cCa and P levels of patients in only UC group were significantly changed. In addition, compared with UC group, patients in MTC group were more likely prescribed appropriate P-binders, when they had higher cCa×P levels than 55 mg²/dL² (P <0.001). CONCLUSION: It was found that MTC had beneficial effect on improving the regulation of CKD-MBD and the appropriate phosphate binder uses. Therefore, application of the MTC is anticipated to enhance quality of clinical care in chronic diseases.
Calcium ; Chronic Disease ; Dialysis* ; Ethics Committees, Research ; Humans ; Kidney ; Miners* ; Nephrology ; Nutritionists ; Observational Study ; Pharmacists ; Prescriptions ; Renal Insufficiency, Chronic* ; Retrospective Studies

Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.
Adenocarcinoma ; Bile Ducts ; Carcinoma, Squamous Cell ; Cholangiocarcinoma ; Colon ; Epigenomics ; Genome* ; Individuality ; Kidney ; Liver ; Lung ; MicroRNAs* ; Pharmacogenetics ; RNA, Messenger

PURPOSE: Although many previous studies have attempted to identify differences between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused on the difference of each variable of lung function and airway inflammation. The aim of this study was to evaluate relationships between lung function, bronchial hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children with AA and NAA. METHODS: One hundred and thirty six asthmatic children aged 5-15 years and 40 normal controls were recruited. Asthma cases were classified as AA (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and serum total IgE were measured. RESULTS: The AA and NAA cases shared common features including a reduced small airway function and increased BHR to methacholine. However, children with AA showed higher BHR to AMP and eNO levels than those with NAA. When the relationships among these variables in the AA and NAA cases were evaluated, the AA group showed significant relationships between lung function, BHR to AMP or methacholine and eNO levels. However, the children in the NAA group showed an association between small airway function and BHR to methacholine only. CONCLUSIONS: These findings suggest that the pathogenesis of NAA may differ from that of AA during childhood in terms of the relationship between lung function, airway inflammation and BHR.
Asthma* ; Child* ; Eosinophils ; Humans ; Immunoglobulin E ; Inflammation ; Lung* ; Methacholine Chloride ; Nitric Oxide* ; Skin

Purpose: This study evaluated epidermal cyst elasticity using multiple parameters of strain elastography (SE) and shear wave elastography (SWE) and assessed the reproducibility of each parameter. Methods: This retrospective study included 73 patients with epidermal cysts who underwent SE and SWE. SE scores were classified as 1-4 according to elasticity. The strain ratio was evaluated using the elasticity ratio of lesions and adjacent subcutaneous fat tissue. For SWE, the shear wave velocity (m/s), elasticity (kPa) according to the Young modulus, velocity ratio, and elasticity ratio were evaluated. All values were measured twice. The reproducibility of SE and SWE measurements was assessed. The relationships among SE and SWE measurements were evaluated. Results: The strain ratio on SE images showed good reproducibility (intra-class correlation coefficient [ICC]=0.789), and SE scores showed substantial reproducibility (kappa=0.753 and kappa=0.758 for readers 1 and 2, respectively). Moderate reproducibility was found for shear wave velocity and elasticity (ICC=0.750 and ICC=0.648, respectively), as well as for the shear wave velocity of the reference tissue and velocity ratio (ICC=0.747 and ICC=0.713, respectively). All SE scores were positively correlated with the strain ratio (P<0.001). The strain ratio in the second SE session was significantly correlated with the elasticity ratio and velocity ratio in the first SWE session (r=0.245, P=0.037; r=0.243, P=0.038, respectively). Other variables were not correlated. Conclusion SE and SWE parameters of epidermal cysts showed moderate to good reproducibility. The strain ratio on SE showed good reproducibility and could provide relatively objective and consistent measurements of epidermal cyst elasticity.

OBJECTIVE: Multi-regional clinical trials have been widely used for accelerating global drug development by multinational pharmaceutical companies. In this study, we aimed to review and analyze the international trends in regulations and guidelines on multi-regional clinical trials by regulatory authorities and international organizations, such as International Conference on Harmonisation, for referring to policies, including development of domestic guidelines for multi-regional clinical trials. METHODS: The policies, regulations, and guidelines published by the US Food and Drug Administration, European Medicines Agency, Pharmaceuticals and Medical Devices Agency (Japan), and China Food and Drug Administration were searched, and the International Conference on Harmonisation E17 draft guideline was reviewed. RESULTS: The regulatory authorities in developed countries have developed and implemented regulations and guidelines on multi-regional clinical trials to promote simultaneous global drug development and evaluate the regional differences in drug safety and efficacy. International Conference on Harmonisation developed the draft guideline for planning/designing of multi-regional clinical trials in 2016, which recommends the general principles for strategy-related issues and design of multi-regional clinical trials, and for protocol-related issues, such as consideration of regional variability, subject selection, dose selection, endpoints, comparators, overall sample size, allocation to regions, collecting information on efficacy and safety, and statistical analysis. CONCLUSION: It is important to understand the international regulatory requirements for designing and planning of multi-regional clinical trials for global drug development. Moreover, it is necessary to prepare multi-regional clinical trial guidelines in accordance with the Korean regulation for clinical trials and drug administration.
China ; Developed Countries ; Sample Size ; Social Control, Formal* ; United States Food and Drug Administration

Purpose: The present study investigated and compared the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) activity-predicting ability of the serum concentrations of the four interleukin (IL)-12 family cytokines including IL-23, IL-27, IL-35, and IL-39 in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: The present study included 70 patients with MPA and GPA. Clinical and laboratory data, particularly Birmingham Vasculitis Activity Score (BVAS), at the time of blood collection were obtained. The serum concentrations of IL-23, IL-27, IL-35, and IL-37 were measured using sera stored at -80°C. Patients were divided into two groups: the upper half of BVAS (BVAS ≥12) and the lower half of BVAS (BVAS <12). Results: The serum concentrations of IL-23 and IL-27 reflected AAV activity. Patients with the upper half of BVAS exhibited significantly higher serum concentrations of IL-23 and IL-27 than those without. Patients with the serum concentrations of IL-23 ≥132.1 pg/mL or IL-27 ≥684.7 pg/mL exhibited higher frequency and risk for the upper half of BVAS than those without [relative risks (RR) 5.143 and RR 4.091, respectively]. The serum concentrations of IL-27 were associated with age ≥65 years and proteinase 3-ANCA (or C-ANCA) negativity, whereas, those of IL-23 were associated with MPA. However, the serum concentrations of IL-35 and IL-39 were not useful in predicting AAV activity in this study. Conclusion The present study is the first to demonstrate that among the various members of IL-12 family cytokines, the serum concentrations of IL-23 and IL-27 possess AAV activity-predicting ability.

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.