Population pharmacodynamic modeling without plasma concentrations of rocuronium in children.

Using the pharmacodynamic model without plasma concentrations described by Bragg et al, an individual approach resulted in highly variable parameters for rocuronium. Using a population approach of the model, the time course of the effect of an IV bolus dose of 400, 600, and 800 microg/kg of rocuronium was studied. Response was measured by accelerometry (TOF-Guard) in 45 low-risk surgical children, ages 2 to 14 years, who were receiving general anesthesia with isoflurane. Using a Bayesian approach and the software P-PHARM, response (the first twitch of the TOF) was modeled. The apparent rate constant of elimination, the rate constant for equilibrium between plasma and the effect compartment, the sigmoidicity factor of the relationship between drug concentration in the effect compartment and the effect, and the infusion rate that produces 50% of the effect at steady state were obtained. Population and individual post hoc parameters were similar among groups and variability was reduced.     

Effect of Icodextrin on Heart Rate Variability in Diabetic Patients on Peritoneal Dialysis

♦ Introduction: Spectral analysis of heart rate variability is a noninvasive method for evaluating autonomic cardiovascular dysfunction under various clinical conditions, such as in dialysis patients, in whom an imbalance between the sympathetic and parasympathetic nervous system appears to be an important risk factor for sudden cardiovascular death and arrhythmia.♦ Objective: We compared the effect of icodextrin-based dialysis solution, an option that allows for better metabolic and fluid overload control, with that of glucose-based dialysis fluid on sympathetic and parasympathetic activity in the heart, as assessed by heart rate variability, in diabetic patients on peritoneal dialysis (PD).♦ Methods: This secondary analysis uses data from a randomized controlled trial in diabetic PD patients with high or high-average peritoneal transport using icodextrin-based (ICO group, n = 30) or glucose-based (GLU group, n = 29) solutions for the long dwell. All patients underwent 24-hour electrocardiographic Holter monitoring at baseline, and at 6 and 12 months of follow-up.♦ Results: We observed no significant differences between the groups in most of the variables analyzed, although values were, in general, below reference values. In the ICO group, total power and both low- and high-frequency power in normalized units increased, but the percentage of RR intervals with variation of more than 50 ms declined over time; in the GLU group, all those values declined. Plasma catecholamine levels were higher at baseline and declined over time.♦ Conclusions: These results indicate a partial recovery of sympathetic activity in the ICO group, probably because of better extracellular fluid control and lower exposure to glucose with the use of icodextrin-based dialysis solutions.     

Molecular epidemiology of a hepatitis C virus outbreak in a hemodialysis unit in Italy

Hemodialysis patients are at increased risk of hepatitis C virus (HCV) infection. The aim of this study was to investigate a HCV outbreak in a hemodialysis unit using epidemiological and molecular methods. Between April 2003 and October 2003, anti-HCV seronconversion was detected in four patients attending the unit. These cases were added to 10 patients already anti-HCV positive upon admission in the unit. All 14 anti-HCV patients were tested for HCV RNA and HCV genotype. NS5B and HVR1/ E2 genomic regions were amplified and sequenced in all HCV RNA positive patients and phylogenetic analysis was performed. Furthermore, clinical-epidemiological records obtained from all patients were examined. All four patients newly infected harbored genotype 2c. Genotype 2c was also detected in 2 of 10 patients already anti-HCV positive upon admission. Phylogenetic analysis showed that all newly HCV infected patients harbored very closely related viral isolates that clustered together with the 2c isolate found in one of the two 2c chronic infected patients. All HCV-2c infected patients had no other risk factors except hemodialysis. Three of four newly HCV-2c infected patients and the one HCV-2c chronically infected involved in the outbreak received dialysis on the same day and same shift but used different machines. The remaining HCV-2c newly infected patient and one of the above cited three received dialysis on the same day during different shifts but used the same machine. The outbreak was probably due to breaks of infection control procedures although a related-machine transmission cannot be excluded in one of the cases.     

Organochlorine pesticide exposure in rural and urban areas in Mexico

The objective of this study was to determine the level of organochlorine pesticides in maternal milk of women living in urban and rural areas in central Mexico. High levels of the DDT (1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane) and metabolites, p,p'-DDT (1.83, 0.66 and 3.13 mg/kg) and p,p'-DDE (2.49, 4.28 and 13.32 mg/kg), were encountered for Mexico City, Cuemavaca and rural Morelos, respectively. As was expected, the highest levels of exposure to these pesticides were found in the rural areas of the State of Morelos.     

Ten daily fractions for partial breast irradiation. Long‐term results of a prospective phase II trial

Partial breast irradiation (PBI) is an effective adjuvant treatment after breast conservative surgery for selected early‐stage breast cancer patients. However, the best fractionation scheme is not well defined. Hereby, we report the 5‐year clinical outcome and toxicity of a phase II prospective study of a novel regimen to deliver PBI, which consists in 40 Gy delivered in 10 daily fractions. Patients with early‐stage (pT1‐pT2, pN0‐pN1a, M0) invasive breast cancer were enrolled after conservative surgery. The minimum age at diagnosis was 60 years old. PBI was delivered with 3D‐conformal radiotherapy technique with a total dose of 40 Gy, fractionated in 10 daily fractions (4 Gy/fraction). Eighty patients were enrolled. The median follow‐up was 67 months. Five‐year local control (LC), disease‐free survival (DFS), and overall survival (OS) were 95%, 91%, and 96%, respectively. Grade I and II subcutaneous fibrosis were documented in 23% and 5% of cases. No grade III late toxicity was observed. PBI delivered in 40 Gy in 10 daily fractions provided good clinical results and was a valid radiotherapy option for early‐stage breast cancer patients.