Urinary Sulfate, Kidney Failure, and Death in CKD: The African American Study of Kidney Disease and Hypertension.

Background: Sulfur is an important mineral element whose principal source is animal protein. Animal protein contributes to the daily acid load, which is associated with poor outcomes in individuals with chronic kidney disease (CKD). We hypothesized that higher urinary sulfate, as a reflection of the daily acid load, is associated with a greater risk of death and CKD progression. Methods: Urinary sulfate was measured in 1057 African American Study of Kidney Disease and Hypertension (AASK) participants at baseline. Participants were categorized by tertiles of daily sulfate excretion. The longitudinal outcome of interest was the composite of death, dialysis, or 50% reduction in measured glomerular filtration rate (GFR). Multivariable adjusted Cox regression models were fit to relate the composite outcome to daily sulfate excretion using the lowest tertile as the reference. Results: Participants in the highest urinary sulfate tertile were more likely to be men and have a higher body mass index, protein intake, measured GFR, and urinary ammonium and phosphate excretion, and lower urinary protein/creatinine. Compared with those in the lowest tertile of sulfate, those in the highest tertile had a 44% lower hazard (95% CI, 0.37 to 0.84), and those in the middle tertile had a 27% lower hazard (95% CI, 0.55 to 0.96) of death, dialysis, or 50% reduction in measured GFR during follow-up after adjusting for demographics, GFR, protein intake, and other potential confounders. Protein intake was not associated with risk of these events. Conclusions: Higher urinary sulfate excretion is associated with more favorable outcomes in Blacks who have CKD attributed to hypertension.

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.

Nonclinical Factors in Autism Diagnosis: Results From a National Health Care Provider Survey.

OBJECTIVE: The prevalence of autism spectrum disorder (ASD) has increased 10-fold in the past 40 years, and disparities have been noted by race/ethnicity and socioeconomic status, prompting concern about diagnostic accuracy. Provider perceptions of ASD diagnostic accuracy are not known. We conducted a survey of providers who diagnose ASD assessing how nonclinical factors might affect ASD diagnostic rates. METHODS: The mixed-mode survey was sent to the members of the Society of Developmental and Behavioral Pediatrics with clinical interest in ASD (n = 400). Respondents used a Likert-type scale to address how often they and their colleagues overdiagnosed or underdiagnosed ASD. They were also asked how families grouped by race/ethnicity, education, socioeconomic status, and urbanicity perceived an ASD diagnosis. RESULTS: Sixty-three percent of providers completed the survey. Eight point seven percent of providers self-reported that they overdiagnose ASD at least sometimes. However, 58% of providers reported that local colleagues overdiagnose ASD at least sometimes. Seven point eight percent of providers self-reported underdiagnosing ASD at least sometimes and cited parents not wanting a diagnosis as one of the most common reasons they may underdiagnose. Providers reported that non-white and rural families were more likely to think that ASD diagnosis was "a bad thing" than "a good thing" than white and urban and suburban families, respectively. CONCLUSION: Providers report moderate rates of ASD misdiagnosis and perceive differences in diagnostic preferences according to family characteristics. The study results may help explain the trends and disparities in ASD diagnosis.

Vancomycin Dosing in Children With Overweight or Obesity: A Systematic Review and Meta-analysis.

CONTEXT: Vancomycin is a medication with potential for significant harm with both overdosing and underdosing. Obesity may affect vancomycin pharmacokinetics and is increasingly common among children. OBJECTIVE: We aimed to determine if children with overweight or obesity have increased vancomycin trough concentrations with total body weight (TBW) dosing compared with children with normal weight. DATA SOURCES: We conducted a search of Medline and Medline In-Process & Other Non-Indexed Citations from 1952 (the year vancomycin was discovered) to November 2017. STUDY SELECTION: Search terms included vancomycin, body weight, and body composition terms and were limited to children. Studies were reviewed and screened by ≥2 reviewers. DATA EXTRACTION: The primary outcome was vancomycin level. Data were extracted by 2 reviewers. We performed quality assessment using the Newcastle-Ottawa quality assessment scale. RESULTS: We identified 271 records. After abstract and full-text screening, we identified 7 studies for full review. Six of the 7 studies used a matched case-control design, although there was significant variation in study methodology. Four of the 7 studies were included in a meta-analysis, which revealed a small but significant difference in vancomycin trough levels between children with normal weight and children with overweight or obesity when dosed by using TBW (N = 521; mean difference 2.2 U [95% confidence interval: 1.0-3.4]). CONCLUSIONS: High-quality data to guide vancomycin dosing in children with obesity are lacking. More studies evaluating dosing strategies in children with obesity are warranted because using TBW to dose vancomycin may lead to higher vancomycin concentrations and potential toxicity.