Risk of tacrolimus toxicity in CYP3A5 nonexpressors treated with intravenous nicardipine after kidney transplantation.

BACKGROUND: Tacrolimus is commonly prescribed for immunosuppression, yet it can cause acute and chronic kidney injury. Continuous intravenous nicardipine (CIVN), prescribed for posttransplant hypertension, inhibits tacrolimus metabolism by cytochrome P450 (CYP) 3A4 and could lead to tacrolimus overexposure in patients genetically lacking the alternative pathway for tacrolimus metabolism, CYP3A5. METHODS: We compared maximum 12-hr tacrolimus trough levels (MaxC0) and dose-adjusted MaxC0 in 12 cases treated with CIVN immediately after kidney transplantation with 26 controls (no CIVN). CYP3A5 genotype was determined for all cases. RESULTS: Eight cases not expressing CYP3A5 (CYP3A5*3/*3) had higher median MaxC0 (24.3 ng/mL) than four cases expressing CYP3A5 (CYP3A5*1/*1; 13.9 ng/mL, P=0.028) and controls (14.6 ng/mL, P=0.003). Compared with the other two groups combined, CYP3A5*3/*3 cases had higher median dose-adjusted MaxC0 (330 vs. 175, P=0.012), less time to MaxC0 (42 vs. 72 hr, P<0.001), and more scheduled tacrolimus doses held per patient (1.75 vs. 0.4, P=0.007). Six of eight (75%) CYP3A5*3/*3 cases had potentially toxic MaxC0 (>20 ng/mL) compared with none of four CYP3A5*1/*1 cases and 3 of 26 (11.5%) controls (P<0.001, CYP3A5*3/*3 cases vs. all others). CONCLUSION: CYP3A5 nonexpressors simultaneously treated with tacrolimus and CIVN may be at increased risk for tacrolimus toxicity.

Breast milk feeding rates of mothers of multiples compared to mothers of singletons.

OBJECTIVE: Over 3% of infants born annually in the United States are from a multiple gestation pregnancy, yet there is little data published about the feeding practices of their mothers. The objectives of this study were to determine and compare the rates of breast milk feeding of mothers of multiples and mothers of singletons. METHODS: Stratified random sampling (n = 686) on the basis of plurality of pregnancy and gestational age at delivery was performed on a 1999 birth certificate database in the greater Cincinnati area. We collected information about infant feeding during the first 6 months of life using a retrospective, self-administered questionnaire and phone interview from mothers of term singletons (TS), preterm singletons (PS), term multiples (TM), and preterm multiples (PM). Data were analyzed using chi-square and logistic or multiple regression. RESULTS: We obtained feeding information from 346 mothers (n = 81 TS, 80 PS, 90 TM, and 95 PM). By 3 days postpartum, PM provided breast milk less often than all other groups: TS = 69%, PS = 66%, TM = 73%, PM = 57% (P =.035). Among mothers who initiated breast milk feeding, the geometric mean duration of at least some breast milk feeding was significantly shorter for PM than for all other groups: TS = 23 weeks, PS = 19 weeks, TM = 24 weeks, and PM = 12 weeks (P =.002). CONCLUSIONS: Further evaluation of the potential causes for the lower breast milk feeding rates among PM is needed to develop effective intervention strategies and increase the number of preterm multiple gestation infants receiving breast milk.

Health-related quality of life in urban elementary schoolchildren.

BACKGROUND: Health disparities between children from urban minority backgrounds and children from more affluent backgrounds are well-recognized. Few studies specifically address urban children's perceptions of their health-related quality of life (HRQOL) or the factors that contribute to these perceptions. Since schools are pivotal to children's intellectual, social, and emotional development, school connectedness may be a factor that contributes to their perception of HRQOL. OBJECTIVE: To examine children's perceptions of HRQOL in an elementary school-based population of urban children. METHODS: The study population consisted of 2nd, 3rd, and 5th graders from 6 urban kindergarten to 8th grade schools and their parents. Children completed a survey that included questions on HRQOL and school connectedness. Parents completed a telephone survey that assessed demographics, the child's health, health care usage, and parental health status. Data on school absences and mobility from the computerized school database were linked to survey data. Bivariate analyses were used to evaluate the association between child report of HRQOL and collected variables, including school connectedness. Multivariable linear regression was conducted to identify the factors best predicting HRQOL in these urban children. RESULTS: Of the 1150 eligible students, parent and child survey data were available for 525 (45.6%). Fifty-one percent of students were male and 89% were black. Ninety-four percent of parents were female, 29% were married, and 62% had family incomes below 20,000 dollars per year. The mean total score for HRQOL was 67.2, with a possible range of 0 to 100 (higher scores reflecting better HRQOL). In the multivariable analysis, child grade, the relationship of the " parent" to the child, employment, family income, type/presence of insurance, and school connectedness were significantly associated with the HRQOL total score. CONCLUSIONS: Young urban children self-report low HRQOL scores and do so as early as the 2nd grade. These low scores, which reflect children's own perceptions of impaired psychological and physical health, have potential implications for the success of urban children in their learning environments. The association between HRQOL and school connectedness might suggest that health and educational programs that improve a child's attachment to school could result in improved perceptions of health by urban children.