A Multicenter Retrospective Study of Vancomycin Dosing by Weight Measures in Children.

OBJECTIVE: Vancomycin carries risks of treatment failure and emergent resistance with underexposure and renal toxicity with overexposure. Children with overweight or obesity may have altered pharmacokinetics. We aimed to examine how body weight metrics influence vancomycin serum concentrations and to evaluate alternative dosing strategies. METHODS: This was a multicenter retrospective cohort study across 3 large, academic hospitals. Patients aged 2 to 18 years old who received ≥3 doses of intravenous vancomycin were included. Weight metrics included total body weight, adjusted body weight, ideal body weight, body surface area, and allometric weight. Outcomes included vancomycin concentration and ratios of area under the curve (AUC) to minimum inhibitory concentration (MIC). Regression analyses were used to examine which body-weight identifier predicted outcomes. RESULTS: Of the 1099 children, 45% were girls, mean age was 9.0 (SD = 5.4) years, 14% had overweight, and 17% had obesity. Seventy-five percent of children had vancomycin concentrations in the subtherapeutic range by trough <10 µg/mL, and 63% had a ratio of AUC to MIC <400 µg-hr/mL. Three percent had a supratherapeutic initial trough >20 µg/mL or ratio of AUC to MIC >600 µg-hr/mL. Serum vancomycin concentrations were higher in children with overweight or obesity compared with children who were at a normal weight or underweight; the mean ratio of AUC to MIC also trended higher in the groups with overweight or obesity. CONCLUSIONS: Most children received vancomycin regimens that produced suboptimal trough levels. Children with overweight or obesity experienced higher vancomycin trough levels than children of normal weight despite receiving lower total body weight dosing. Using the ratio of AUC to MIC was a better measure of drug exposure.

Shear wave elastography reveals a high prevalence of liver fibrosis in overweight or obese Hispanic youth.

Background: Obesity, prediabetes, and type 2 diabetes are risk factors for nonalcoholic fatty liver disease. Inflammation and hepatocellular damage associated with nonalcoholic fatty liver disease lead to progressive non-alcoholic steatohepatitis, fibrosis and cirrhosis. Current tests to identify fibrosis (liver biopsy) are invasive and not conducive to serial examination. For that reason, we used the newer technique of shear wave elastogrophy (SWE) to detect fibrosis in overweight or obese Hispanic youth and sought to determine if carbohydrate tolerance or insulin resistance were associated with fibrosis in this high risk population. Methods: A total of 67 Hispanic youth (8-18 years of age) with overweight or obesity who were referred for multidisciplinary evaluation were included. SWE was used to identify those with suspected fibrosis. Results of SWE were then compared with glycohemoglobin (A1c), insulin resistance (homeostatic model of insulin resistance), and biochemical parameters. Results: The prevalence of suspected fibrosis (SWE >5.10 kPa) in overweight or obese Hispanic youth was 62.7% (42/67). Patients with suspected fibrosis (SWE ≥5.10 kPa) had significantly higher levels of serum aspartate aminotransferase, alanine aminotransferase and the aminotransferase to platelet ratio index when compared to patients without significant fibrosis (SWE <5.01 kPa). However, there were no significant differences between the groups in body mass index, A1c, or homeostatic model of insulin resistance. Conclusions: SWE detected a high prevalence (62.7%) of suspected hepatic fibrosis in a group of high risk, overweight or obese Hispanic youth suggesting that SWE is a useful tool for surveillance and longitudinal studies.

Relationship Between Parental Diabetes and Presentation of Metabolic and Glycemic Function in Youth With Type 2 Diabetes: Baseline Findings From the TODAY Trial.

OBJECTIVE: Children whose parents have diabetes are at increased risk for developing type 2 diabetes. This report assessed relationships between parental diabetes status and baseline demographics, anthropometrics, metabolic measurements, insulin sensitivity, and ß-cell function in children recently diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: The sample included 632 youth (aged 10-17 years) diagnosed with type 2 diabetes for <2 years who participated in the TODAY clinical trial. Medical history data were collected at baseline by self-report from parents and family members. Youth baseline measurements included an oral glucose tolerance test and other measures collected by trained study staff. RESULTS: Youth exposed to maternal diabetes during pregnancy (whether the mother was diagnosed with diabetes prior to pregnancy or had gestational diabetes mellitus) were diagnosed at younger ages (by 0.6 years on average), had greater dysglycemia at baseline (HbA1c increased by 0.3% [3.4 mmol/mol]), and had reduced ß-cell function compared with those not exposed (C-peptide index 0.063 vs. 0.092). The effect of maternal diabetes on ß-cell function was observed in non-Hispanic blacks and Hispanics but not whites. Relationships with paternal diabetes status were minimal. CONCLUSIONS: Maternal diabetes prior to or during pregnancy was associated with poorer glycemic control and ß-cell function overall but particularly in non-Hispanic black and Hispanic youth, supporting the hypothesis that fetal exposure to aberrant metabolism may have long-term effects. More targeted research is needed to understand whether the impact of maternal diabetes is modified by racial/ethnic factors or whether the pathway to youth-onset type 2 diabetes differs by race/ethnicity.

Pediatric obesity epidemiology.

PURPOSE OF REVIEW: To provide updated summary of recently published data regarding pediatric obesity epidemiology. RECENT FINDINGS: There is a burgeoning literature of pediatric obesity epidemiology, with type 2 diabetes trends serving as the harbinger for obesity related diseases in children. The National Health and Nutrition Examination Survey and Pediatric Nutrition Surveillance System report a tripling of the prevalence of BMI at least 95% (obesity) among US school-age children and adolescents over the past three decades. Recent updates provide insight into infants and toddler obesity and explore the impact of ethnicity, socioeconomic status, school setting and geographic variations. International data confirm similar upward shifts in pediatric BMI distribution, especially in countries undergoing economic transitions favoring industrialized, western urban lifestyles. SUMMARY: The health and financial consequences of this epidemic are a complex global public health dilemma. International efforts are underway to reverse these obesity trends. On-going analysis of obesity prevalence and exploration of potential causal associations are required to implement and assess the effectiveness of interventions and policies.