Routine Chest Radiographs in Children After Image-Guided Central Lines Offer Little Diagnostic Value.

BACKGROUND: The aim of this study was to investigate the utility of postoperative chest radiograph (CXR) after image-guided central venous line (CVL) placement in children. METHODS: A retrospective review was conducted of all tunneled CVLs placed at two pediatric institutions from 2010 to 2017. A subgroup analysis comparing a clinically driven approach to postoperative imaging against routine imaging was performed. RESULTS: During the study period, 1080 lines were placed in 915 patients. There were 892 postoperative CXRs (82.6%). An abnormality was seen on 40 radiographs (4.5%, n = 891), with 16 false-positive (1.3%) and 5 false-negative (0.6%) CXRs. The sensitivity and specificity of CXR to identify complications requiring intervention were 50.0% (95% confidence interval [95% CI], 10.0-90.0) and 95.8% (95% CI, 94.5-97.1), respectively. Positive predictive value of CXR was 7.5% (95% CI, 0-15.7) with a negative predictive value of 99.6% (95% CI, 99.2-100). A clinically driven approach to postoperative imaging was associated with 41% decrease in CXR (P < 0.001) without increased incidence of missed complications. Only three complications requiring intervention (0.3%) were suspected on postoperative CXR alone, and all of those were symptomatic before intervention. CONCLUSIONS: Routine postoperative CXR offers minimal value in identifying technical complications requiring intervention after image-guided CVL placement in asymptomatic children. We recommend abandoning this practice in favor of a clinical symptom-driven approach to postoperative imaging.

Cost-Effectiveness of Implantable Cardioverter-Defibrillators in Children with Cardiac Conditions Associated with Risk for Sudden Cardiac Death.

Children at high risk for sudden cardiac death (SCD) receive implantable cardioverter-defibrillators (ICD) for prevention, but the cost effectiveness of ICDs in children at intermediate risk is unclear. Our objective was to create a cost-effectiveness model to compare costs and outcomes in children at risk of SCD, with and without ICD. Utilizing hypertrophic cardiomyopathy as the proxy disease, a theoretical cohort of 8150 children was followed for 69 years. Model inputs were derived from the literature, with an incremental cost-effectiveness ratio (ICER) willingness-to-pay threshold of $100,000/quality-adjusted life year (QALY) used to delineate cost effectiveness. Outcomes included prevalence of severe neurological morbidity (SNM), SCD, cost, and QALYs. In children at intermediate risk of SCD (4-6% over 5 years), ICD resulted in 56 fewer cases of SNM, 2686 fewer deaths. In children at high risk (> 6% over 5 years), ICD placement resulted in 74 fewer cases of SNM and 3663 fewer deaths from cardiac causes. The costs of ICD were higher, but placement was cost effective with an ICER of $3009 per QALY in intermediate risk children, but ICD therapy was a dominant strategy in high-risk children. Sensitivity analysis demonstrated ICD placement was cost-effective until the annual probability of SCD was < 0.22%. The model was robust over a wide range of values. For children at risk of SCD, prophylactic ICD implantation is cost effective, resulting in improved outcomes and increased QALYs, despite increased costs. These findings highlight the economic benefits of ICD utilization in this population.

A Budget Impact Analysis of Gene Therapy for Sickle Cell Disease: The Medicaid Perspective.

Importance: Hundreds of gene therapies are undergoing clinical testing and are likely to be priced more than $1 million per course of treatment. The association that high prices will have with insurance coverage of gene therapy remains unclear. Gene therapy for sickle cell disease has shown early success and would be one of the first gene therapies available for a relatively large population. Objectives: To estimate the budget impact and affordability of a gene therapy for severe sickle cell disease from the perspective of US Medicaid programs with the highest prevalence of sickle cell disease while exploring the impact of an annuity payment model. Design, Setting, and Participants: A budget impact analysis was performed from January 1 to May 31, 2020, for a sickle cell disease gene therapy from the perspective of 10 state Medicaid plans with a 5-year time horizon, using state-level disease prevalence data from 2012. Disease prevalence, Medicaid enrollment, and expenditures were derived from the available literature. The eligible population was based on modified clinical trial inclusion criteria including individuals aged 13 to 45 years with severe disease. Exposures: The gene therapy was assumed to be administered to 7% of the eligible population annually and was curative (no subsequent disease-related expenditures). The gene therapy price was $1.85 million in the base case, and baseline disease-related expenditures were $42 200 per year. Main Outcomes and Measures: The main outcomes were total budget impact and budget impact per member per month in years 1 through 5. One-way sensitivity analysis was used to evaluate uncertainty of market diffusion, size of eligible population, price of therapy, and cost of routine care. Results: An estimated 5464 Medicaid enrollees would be eligible for the gene therapy nationally, with 2315 individuals in the 10 Medicaid programs of interest (16 per 100 000 enrollees). The model projected a mean 1-year budget impact of $29.96 million per state Medicaid program in the sample ($1.91 per member per month). A 5-year annuity payment reduced the short-term budget impact. Conclusions and Relevance: This study suggests that a gene therapy for severe sickle cell disease is likely to produce a considerable budget impact for many Medicaid plans while potentially offering substantial benefit to patients. Payers may need to take steps to ensure affordability and access. Gene therapy for sickle cell disease is likely to provide an early demonstration of the unique financial challenges associated with this emerging drug class.

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.

Increased Adiposity Associated With Increased Length of Stay for Infants With Bronchiolitis.

OBJECTIVES: Excess adiposity upregulates proinflammatory adipokines in infancy that have also been implicated in the pathogenesis of bronchiolitis. The association between excess adiposity and severity of disease in bronchiolitis is unclear. We sought to examine the association between adiposity and length of hospitalization and risk of PICU transfer in children with bronchiolitis. METHODS: We conducted a retrospective cohort study examining infants 24 months and younger hospitalized at an academic children's hospital with bronchiolitis, grouped by weight status (BMI z score and ponderal index). Data were extracted from the medical record, including the following relevant covariates: age, sex, race and/or ethnicity, and International Classification of Diseases, 10th Revision codes. Outcomes included length of stay (LOS) and PICU transfer. We used multiple regression to examine the association between each anthropometric measure and LOS and likelihood of PICU transfer. RESULTS: There were 765 children in the final sample, 599 without a significant comorbidity (eg, prematurity, congenital heart disease). The median LOS was 2.8 days (interquartile range 1.7-4.9 days). LOS increased with increasing ponderal index quartile (P = .001). After accounting for age and significant comorbidities, we used multivariable regression to identify a significant association between increasing ponderal index and LOS (P = .04) and no association between BMI and LOS. Logistic regression did not reveal an association between either anthropometric measure and PICU transfer. CONCLUSIONS: In this study, we identified an association between a measure of excess adiposity in infants and length of hospitalization for bronchiolitis. Further work is needed to confirm this association, examine potential mechanisms, and account for other potential confounders.

Cost-effectiveness of in-home automated external defibrillators for children with cardiac conditions associated with risk of sudden cardiac death.

BACKGROUND: Children at high risk for sudden cardiac death (SCD) (>6% over 5 years) receive an implantable cardioverter-defibrillator (ICD), but no guidelines are available for those at lower risk. For children at intermediate risk for SCD (4%-6% over 5 years), the utility and cost-effectiveness of in-home automated external defibrillators (AEDs) are unclear. OBJECTIVE: The purpose of this study was to assess the cost-effectiveness of in-home AED for children at intermediate risk for SCD. METHODS: Using hypertrophic cardiomyopathy (HCM) as the proxy disease, a theoretical cohort of 1550 ten-year-old children with HCM was followed for 69 years. Baseline annual risk of SCD was 0.8%. Outcomes were SCD, severe neurologic morbidity (SNM), cost, and quality-adjusted life-years (QALYs). Model inputs were derived from the literature, with a willingness-to-pay threshold of $100,000 per QALY. RESULTS: Among children at intermediate risk for SCD, in-home AED resulted in 31 fewer cases of SCD but 3 more cases of SNM. There were 319 QALYs gained. Although costs were higher by $28 million, the incremental cost-effectiveness ratio was $86,458, which is below the willingness-to-pay threshold. CONCLUSION: For children at intermediate risk for SCD and HCM, in-home AED is cost-effective, resulting in fewer deaths and increased QALYS for a cost below the willingness-to-pay threshold. These findings highlight the economic benefits of in-home AED use in this population.