Body composition is associated with tacrolimus pharmacokinetics in kidney transplant recipients.

PURPOSE: A population pharmacokinetic (popPK) model may be used to improve tacrolimus dosing and minimize under- and overexposure in kidney transplant recipients. It is unknown how body composition parameters relate to tacrolimus pharmacokinetics and which parameter correlates best with tacrolimus exposure. The aims of this study were to investigate which body composition parameter has the best association with the pharmacokinetics of tacrolimus and to describe this relationship in a popPK model. METHODS: Body composition was assessed using bio-impedance spectroscopy (BIS). Pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM). Lean tissue mass, adipose tissue mass, over-hydration, and phase angle were measured with BIS and then evaluated as covariates. The final popPK model was evaluated using goodness-of-fit plots, visual predictive checks, and a bootstrap analysis. RESULTS: In 46 kidney transplant recipients, 284 tacrolimus concentrations were measured. The base model without body composition parameters included age, plasma albumin, plasma creatinine, CYP3A4 and CYP3A5 genotypes, and hematocrit as covariates. After full forward inclusion and backward elimination, only the effect of the phase angle on clearance (dOFV = - 13.406; p < 0.01) was included in the final model. Phase angle was positively correlated with tacrolimus clearance. The inter-individual variability decreased from 41.7% in the base model to 34.2% in the final model. The model was successfully validated. CONCLUSION: The phase angle is the bio-impedance spectroscopic parameter that correlates best with tacrolimus pharmacokinetics. Incorporation of the phase angle in a popPK model can improve the prediction of an individual's tacrolimus dose requirement after transplantation.

Psychological impact of short-term isolation measures in hospitalised patients.

Unintended negative effects, such as anxiety and depression, have been demonstrated in patients subjected to infection control strategies, such as isolation for long periods. Yet isolation precautions are mostly short-term. We therefore determined levels of anxiety, depression and quality of life in patients exposed to short-term isolation. In a cross-sectional matched cohort study, performed in a single university hospital, patients isolated for infection control were evaluated with the Hospital Anxiety and Depression Scale [HADS-A (Anxiety) and HADS-D (Depression)], Visual Analogue Scale of EQ-5D (EQ VAS) and an isolation evaluation questionnaire within 24-48 h after start of isolation. Two matched controls were selected for each isolated patient. Isolated patients (N=42) and control patients (N=84) had comparable HADS-A (4.5 vs 5.0), HADS-D (4.0 vs 5.0) and EQ VAS (65 vs 62) scores. In multiple regression analysis comorbidity was associated with EQ VAS outcome (P=0.005), whereas all other variables, including being in isolation, were unrelated to HADS and EQ VAS scores. Patients reported positive associations with isolation measures. The quality of care provided by physicians and nurses, as perceived by isolated patients, was not negatively affected in 74% and 71% of patients, respectively. In conclusion, short-term infection control measures do not influence hospitalised patients' levels of anxiety and depression and quality of life. Isolated patients had a positive attitude towards the precautions taken.

Epidemic gastroenteritis in Newfoundland during 1963 associated with E. coli 0111:4.

An epidemic of infantile gastroenteritis occurred in Newfoundland in the year 1963. Cases and deaths were reported from communities in widely separated geographic areas. A total of 1071 cases was reported and there were 100 deaths. The death rate was estimated at 600 per 100,000 live births and exceeded the highest rate noted during any of the preceding 15 years.During 1963 the Newfoundland Public Health Laboratories recorded a high incidence of enteropathogenic Escherichia coli isolations. Over 500 isolations were obtained, of which 76% were E. coli 0111:B4, indicating that this organism was the main offender. The majority of E. coli 0111:B4 isolates were resistant in vitro to chloramphenicol and neomycin.Important among efforts to control this widespread community outbreak was an educational program which made extensive use of television and radio.