Antithrombin Population Pharmacokinetics in Pediatric Ventricular Assist Device Patients.

OBJECTIVES: Describe the pharmacokinetics of antithrombin in pediatric patients undergoing ventricular assist device therapy and provide dosing recommendations for antithrombin in this population. DESIGN: A retrospective population pharmacokinetic study was designed. SETTING: Large tertiary care children\u27s hospital Subject inclusion criteria consisted of less than 19 years old. PATIENTS: Subjects less than 19 years old undergoing therapy with a HeartWare ventricular assist device (HeartWare, Framingham, MA) or Berlin EXCOR ventricular assist device (Berlin GmbH, Berlin, Germany), who received a dose of antithrombin with a postdose antithrombin activity level from January 1, 2011, to June 30, 2017. INTERVENTIONS: Population pharmacokinetic analysis and simulation using NONMEM v.7.4 (Icon, PLC, Dublin, Ireland). MEASUREMENTS AND MAIN RESULTS: A total of 41 patients met study criteria (median age, 5.8 years [interquartile range, 1.6-9.9 yr]), and 53.7% underwent therapy with the pulsatile Berlin EXCOR pediatric ventricular assist device (Berlin Heart GmbH, Berlin, Germany). All patients received unfractionated heparin continuous infusion at a mean ± SD dose of 29 ± 14 U/kg/hr. A total of 181 antithrombin doses (44.1 ± 24.6 U/kg/dose) were included, and baseline antithrombin activity levels were 77 ± 12 U/dL. Antithrombin activity levels were drawn a median 19.9 hours (interquartile range, 8.8-41.6 hr) after antithrombin dose. A one-compartment proportional error model best fit the data, with allometric scaling of fat-free mass providing a better model fit than actual body weight. Unfractionated heparin and baseline antithrombin were identified as significant covariates. A 50 U/kg dose of antithrombin had a simulated half-life 13.2 ± 6.6 hours. CONCLUSIONS: Antithrombin should be dosed on fat-free mass in pediatric ventricular assist device patients. Unfractionated heparin dose and baseline antithrombin activity level should be considered when dosing antithrombin in pediatric ventricular assist device patients

Neighborhood and Social Environmental Influences on Child Chronic Disease Prevalence

We investigate how distinct residential environments uniquely influence chronic child disease. Aggregating over 200,000 pediatric geocoded medical records to the census tract of residence and linking them to neighborhood-level measures, we use multiple data analysis techniques to assess how heterogeneous exposures of social and environmental neighborhood conditions influence an index of child chronic disease (CCD) prevalence for the neighborhood. We find there is a graded relationship between degree of overall neighborhood disadvantage and children’s chronic disease such that the highest neighborhood CCD scores reside in communities with the highest concentrated disadvantage. Finally, results show that higher levels of neighborhood concentrated disadvantage and air pollution exposure associate with higher risks of having at least one chronic condition for children after also considering their individual- and family-level characteristics. Overall, our analysis serves as a comprehensive start for future researchers interested in assessing which neighborhood factors matter most for child chronic health conditions

Child Obesity and the Interaction of Family and Neighborhood Socioeconomic Context

The literature on neighborhoods and child obesity links contextual conditions to risk, assuming that if place matters, it matters in a similar way for everyone in those places. We explore the extent to which distinctive neighborhood types give rise to social patterning that produces variation in the odds of child obesity. We leverage geocoded electronic medical records for a diverse sample of over 135,000 children aged 2 to 12 and latent profile modeling to characterize places into distinctive neighborhood contexts. Multilevel models with cross-level interactions between neighborhood type and family socioeconomic standing (SES) reveal that children with different SES, but living in the same neighborhoods, have different odds of obesity. Specifically, we find lower-SES children benefit, but to a lesser degree, from neighborhood advantages and higher-SES children are negatively influenced, to a larger degree, by neighborhood disadvantages. The resulting narrowing of the gap in obesity by neighborhood disadvantage helps clarify how place matters for children’s odds of obesity and suggests that efforts to improve access to community advantages as well as efforts to address community disadvantages are important to curbing obesity and improving the health of all children

Comprehensive Neighborhood Portraits and Child Asthma Disparities Introduction

Objectives Previous research has established links between child, family, and neighborhood disadvantages and child asthma. We add to this literature by first characterizing neighborhoods in Houston, TX by demographic, economic, and air quality characteristics to establish differences in pediatric asthma diagnoses across neighborhoods. Second, we identify the relative risk of social, economic, and environmental risk factors for child asthma diagnoses. Methods We geocoded and linked electronic pediatric medical records to neighborhood-level social and economic indicators. Using latent profile modeling techniques, we identified Advantaged, Middle-class, and Disadvantaged neighborhoods. We then used a modified version of the Blinder-Oaxaca regression decomposition method to examine differences in asthma diagnoses across children in these different neighborhoods. Results Both compositional (the characteristics of the children and the ambient air quality in the neighborhood) and associational (the relationship between child and air quality characteristics and asthma) differences within the distinctive neighborhood contexts influence asthma outcomes. For example, unequal exposure to PM2.5 and O3 among children in Disadvantaged and Middle-class neighborhoods contribute to asthma diagnosis disparities within these contexts. For children in Disadvantaged and Advantaged neighborhoods, associational differences between racial/ethnic and socioeconomic characteristics and asthma diagnoses explain a significant proportion of the gap. Conclusions for Practice Our results provide evidence that differential exposure to pollution and protective factors associated with non-Hispanic White children and children from affluent families contribute to asthma disparities between neighborhoods. Future researchers should consider social and racial inequalities as more proximate drivers, not merely as associated, with asthma disparities in children

Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients

ObjectivesThis study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation.BackgroundViral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival.MethodsBetween June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17).ResultsViral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06).ConclusionsViral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation

Neighborhoods Matter; but for Whom? Heterogeneity of Neighborhood Disadvantage on Child Obesity by Sex

Although evidence suggests that neighborhood context, particularly socioeconomic context, influences child obesity, little is known about how these neighborhood factors may be heterogeneous rather than monolithic. Using a novel dataset comprised of the electronic medical records for over 250,000 children aged 2–17 nested within 992 neighborhoods in the greater Houston area, we assessed whether neighborhoods influenced the obesity of children differently based on sex. Results indicated that neighborhood disadvantage, assessed using a comprehensive, multidimensional, latent profile analysis-generated measure, had a strong, positive association with the odds of obesity for both boys and girls. Interactions revealed that the relationship between disadvantage and obesity was stronger for girls, relative to boys. Our findings demonstrated the complex dynamics underlying the influence of residential neighborhood context on obesity for specific subgroups of children