Updates on the genetic variations of Norovirus in sporadic gastroenteritis in Chungnam Korea, 2009-2010

Previously, we explored the epidemic pattern and molecular characterization of noroviruses (NoVs) isolated in Chungnam, Korea in 2008, and the present study extended these observations to 2009 and 2010. In Korea, NoVs showed the seasonal prevalence from late fall to spring, and widely detected in preschool children and peoples over 60 years of age. Epidemiological pattern of NoV was similar in 2008 and in 2010, but pattern in 2009 was affected by pandemic influenza A/H1N1 2009 virus. NoV-positive samples were subjected to sequence determination of the capsid gene region, which resolved the isolated NoVs into five GI (2, 6, 7, 9 and 10) and eleven GII genotypes (1, 2, 3, 4, 6, 7, 8, 12, 13, 16 and 17). The most prevalent genotype was GII.4 and occupied 130 out of 211 NoV isolates (61.6%). Comparison of NoV GII.4 of prevalent genotype in these periods with reference strains of the same genotype was conducted to genetic analysis by a phylogenetic tree. The NoV GII.4 strains were segregated into seven distinct genetic groups, which are supported by high bootstrap values and previously reported clusters. All Korean NoV GII.4 strains belonged to either VI cluster or VII cluster. The divergence of nucleotide sequences within VI and VII intra-clusters was > 3.9% and > 3.5%, respectively. The "Chungnam(06-117)/2010" strain which was isolated in June 2010 was a variant that did not belong to cluster VI or VII and showed 5.8-8.2%, 6.2-8.1% nucleotide divergence with cluster VI and VII, respectively

Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug

BACKGROUND: Dose selection is an important step in pharmacokinetic (PK) studies of hemodialysis patients. We propose a simulation-based dose-selection method for PK studies of hemodialysis patients using a subpharmacological dose of oseltamivir as a model drug. METHODS: The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured by liquid chromatography-tandem mass spectrometry. To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study. After the dose was determined, a low dose study (n = 10) was performed, and the optimal dose required to reach the hypothetical target OC exposure (area under the concentration-time curve [AUC] of 60,000 ng · hr/mL) was simulated using a nonparametric superposition method. Finally, observed PKs at the optimal dose were compared to the simulated PKs to verify PK predictability. RESULTS: In the pilot low dose determination study, 2.5 mg of oseltamivir was determined to be the low dose. Subsequently, we performed a single-dose PK study with the low oseltamivir dose in an additional group of 10 hemodialysis patients. The predicted AUC(last) of OC following continuous oseltamivir doses was simulated, and 35 mg of oseltamivir corresponded to the hypothetical target AUC(last) of OC. The observed PK profiles of OC at a 35-mg oseltamivir dose and the simulated data based on the low dose study were in close alignment. CONCLUSION: The results indicate that the proposed method provides a rational approach to determine the proper PK dose in hemodialysis patients

Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Dose selection is an important step in pharmacokinetic (PK) studies of hemodialysis patients. We propose a simulation-based dose-selection method for PK studies of hemodialysis patients using a subpharmacological dose of oseltamivir as a model drug. Methods The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured by liquid chromatography-tandem mass spectrometry. To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study. After the dose was determined, a low dose study (n = 10) was performed, and the optimal dose required to reach the hypothetical target OC exposure (area under the concentration-time curve [AUC] of 60,000 ng · hr/mL) was simulated using a nonparametric superposition method. Finally, observed PKs at the optimal dose were compared to the simulated PKs to verify PK predictability. Results In the pilot low dose determination study, 2.5 mg of oseltamivir was determined to be the low dose. Subsequently, we performed a single-dose PK study with the low oseltamivir dose in an additional group of 10 hemodialysis patients. The predicted AUClast of OC following continuous oseltamivir doses was simulated, and 35 mg of oseltamivir corresponded to the hypothetical target AUClast of OC. The observed PK profiles of OC at a 35-mg oseltamivir dose and the simulated data based on the low dose study were in close alignment. Conclusion The results indicate that the proposed method provides a rational approach to determine the proper PK dose in hemodialysis patients

Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug

Background: Dose selection is an important step in pharmacokinetic (PK) studies of hemodialysis patients. We propose a simulation-based dose-selection method for PK studies of hemodialysis patients using a subpharmacological dose of oseltamivir as a model drug. Methods: The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured by liquid chromatography-tandem mass spectrometry. To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study. After the dose was determined, a low dose study (n = 10) was performed, and the optimal dose required to reach the hypothetical target OC exposure (area under the concentration-time curve [AUC] of 60,000 ng. hr/ mL) was simulated using a nonparametric superposition method. Finally, observed PKs at the optimal dose were compared to the simulated PKs to verify PK predictability. Results: In the pilot low dose determination study, 2.5 mg of oseltamivir was determined to be the low dose. Subsequently, we performed a single-dose PK study with the low oseltamivir dose in an additional group of 10 hemodialysis patients. The predicted AUC(last) of OC following continuous oseltamivir doses was simulated, and 35 mg of oseltamivir corresponded to the hypothetical target AUC(last) of OC. The observed PK profiles of OC at a 35-mg oseltamivir dose and the simulated data based on the low dose study were in close alignment. Conclusion: The results indicate that the proposed method provides a rational approach to determine the proper PK dose in hemodialysis patients.Y

Early Referral to a Nephrologist Improved Patient Survival: Prospective Cohort Study for End-Stage Renal Disease in Korea

<div><p>The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3±58.9 versus 2.9±3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27–4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73–13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.</p> </div

Kaplan-Meier survival curve by timing of referral.

<p>(A) Total patients, adjusted for age, gender, modified CCI, BMI, eGFR, serum hemoglobin, calcium, iPTH, uric acid, triglycerides, total cholesterol, and HDL cholesterol. (B) DM ESRD patients, adjusted for age, gender, modified CCI, BMI, eGFR, serum hemoglobin, calcium, iPTH, uric acid, triglycerides, total cholesterol, and HDL cholesterol.</p

Cause of death in patients.

<p>Cause of death in patients.</p