Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Association of the social disorganization index with time to first septic shock event in children with acute myeloid leukemia.

BACKGROUND: Pediatric acute myeloid leukemia (AML) chemotherapy increases the risk of life-threatening complications, including septic shock (SS). An area-based measure of social determinants of health, the social disorganization index (SDI), was hypothesized to be associated with SS and SS-associated death (SS-death). METHODS: Children treated for de novo AML on two Children's Oncology Group trials at institutions contributing to the Pediatric Health Information System (PHIS) database were included. The SDI was calculated via residential zip code data from the US Census Bureau. SS was identified via PHIS resource utilization codes. SS-death was defined as death within 2 weeks of an antecedent SS event. Patients were followed from 7 days after the start of chemotherapy until the first of end of front-line therapy, death, relapse, or removal from study. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) comparing time to first SS by SDI group. RESULTS: The assembled cohort included 700 patients, with 207 (29.6%) sustaining at least one SS event. There were 233 (33%) in the SDI-5 group (highest disorganization). Adjusted time to incident SS did not statistically significantly differ by SDI (reference, SDI-1; SDI-2: HR, 0.84 [95% confidence interval (CI), 0.51-1.41]; SDI-3: HR, 0.70 [95% CI, 0.42-1.16]; SDI-4: HR, 0.97 [95% CI, 0.61-1.53]; SDI-5: HR, 0.72 [95% CI, 0.45-1.14]). Nine patients (4.4%) with SS experienced SS-death; seven of these patients (78%) were in SDI-4 or SDI-5. CONCLUSIONS: In a large, nationally representative cohort of trial-enrolled pediatric patients with AML, there was no significant association between the SDI and time to SS.

Comparative Costs of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot.

BACKGROUND: Recent data have demonstrated that overall mortality and adverse events are not significantly different for primary repair (PR) and staged repair (SR) approaches to management of neonates with symptomatic tetralogy of Fallot (sTOF). Cost data can be used to compare the relative value (cost for similar outcomes) of these approaches and are a potentially more sensitive measure of morbidity. OBJECTIVES: This study sought to compare the economic costs associated with PR and SR in neonates with sTOF. METHODS: Data from a multicenter retrospective cohort study of neonates with sTOF were merged with administrative data to compare total costs and cost per day alive over the first 18 months of life in a propensity score-adjusted analysis. A secondary analysis evaluated differences in department-level costs. RESULTS: In total, 324 subjects from 6 centers from January 2011 to November 2017 were studied (40% PR). The 18-month cumulative mortality (P = 0.18), procedural complications (P = 0.10), hospital complications (P = 0.94), and reinterventions (P = 0.22) did not differ between PR and SR. Total 18-month costs for PR (median $179,494 [IQR: $121,760-$310,721]) were less than for SR (median: $222,799 [IQR: $167,581-$327,113]) (P < 0.001). Cost per day alive (P = 0.005) and department-level costs were also all lower for PR. In propensity score-adjusted analyses, PR was associated with lower total cost (cost ratio: 0.73; P < 0.001) and lower department-level costs. CONCLUSIONS: In this multicenter study of neonates with sTOF, PR was associated with lower costs. Given similar overall mortality between treatment strategies, this finding suggests that PR provides superior value.

Mortality, Resource Utilization, and Inpatient Costs Vary Among Pediatric Heart Transplant Indications: A Merged Data Set Analysis From the United Network for Organ Sharing and Pediatric Health Information Systems Databases.

BACKGROUND: Merging United Network for Organ Sharing (UNOS) and Pediatric Health Information Systems databases has enabled a more granular analysis of pediatric heart transplant outcomes and resource utilization. We evaluated whether transplant indication at time of transplantation was associated with mortality, resource utilization, and inpatient costs during the first year after transplantation. METHODS AND RESULTS: We analyzed transplant outcomes and resource utilization from 2004 to 2015. Patients were categorized as congenital (CHD), myocarditis, or cardiomyopathy based on UNOS-defined primary indication. CHD complexity subgroup analyses (single-ventricle, complex, and simple biventricular CHD) were also performed. Of 2251 transplants (49% CHD, 5% myocarditis, 46% cardiomyopathy), CHD recipients were younger (2 [IQR 0-10], 6 [IQR 0-12], and 7 [IQR 1-14] years, respectively; P < .001) and less likely to have a ventricular assist device (VAD) at transplantation (3%, 27%, and 13%, respectively; P < .001). Patients with single-ventricle CHD had the longest time on the waitlist and were least likely to receive a VAD before transplantation. After adjusting for patient-level factors, transplant recipients with single-ventricle CHD had the greatest mortality during transplantation admission and within 1 year (odds ratio [OR] 11.8 [95% confidence interval (CI) 5.9-23.6] and OR 6.0 [95% CI 3.6-10.2], respectively, vs cardiomyopathy). Mortality was similar between patients with myocarditis and cardiomyopathy. Post-transplantation length of stay (LOS) was longer in transplant recipients with CHD than myocarditis or cardiomyopathy (25 [interquartile range [IQR] 15-45] vs 21 [IQR 12-35] vs 16 [IQR 12-25] days; P < .001), related in part to longer duration of intensive care unit-level care (ICU LOS 8 [IQR 4-20] vs 6 [IQR 4-13] vs 5 [IQR 3-8] days; P < .001). Similarly, patients with CHD had higher median post-transplantation costs than myocarditis or cardiomyopathy ($415K [IQR $201K-503K] vs $354K [IQR $179K-390K] vs $284K [IQR $145K-319K]; P < .001) that persisted after adjusting for patient-level factors (adjusted cost ratio 1.4 [95% CI 1.4-1.5], CHD vs cardiomyopathy) and was primarily driven by longer LOS. More than 50% were readmitted during the first year after transplantation, although readmission rates were similar across transplant indications (P = .42). CONCLUSIONS: Children with CHD, particularly single-ventricle patients, require substantially greater hospital resource utilization and have significantly worse outcomes during the first year after heart transplantation compared with other indications. Further work is aimed at identifying modifiable pre-transplantation risk factors, such as pre-transplantation conditioning with VAD support and cardiac rehabilitation, to improve post-transplantation outcomes and reduce resource utilization in this complex population.

Cost comparison by treatment arm and center-level variations in cost and inpatient days on the phase III high-risk B acute lymphoblastic leukemia trial AALL0232.

The Children's Oncology Group (COG) develops and implements multi-institutional clinical trials with the primary goal of assessing the efficacy and safety profile of treatment regimens for various pediatric cancers. However, the monetary costs of treatment regimens are not measured. AALL0232 was a COG randomized phase III trial for children with acute lymphoblastic leukemia that found that dexamethasone (DEX) was a more effective glucocorticoid than prednisone (PRED) in patients younger than 10 years, but PRED was equally effective and less toxic in older patients. In addition, high-dose methotrexate (HD-MTX) led to better survival than escalating doses of methotrexate (C-MTX). Cost data from the Pediatric Health Information System database were merged with clinical data from the COG AALL0232 trial. Total and component costs were compared between treatment arms and across hospitals. Inpatient costs were higher in the HD-MTX and DEX arms when compared to the C-MTX and PRED arms at the end of therapy. There was no difference in cost between these arms at last follow-up. Considerable variation in total costs existed across centers to deliver the same therapy that was driven by differences in inpatient days and pharmacy costs. The more effective regimens were found to be more expensive during therapy but were ultimately cost-neutral in longer term follow-up. The variations in cost across centers suggest an opportunity to standardize resource utilization for patients receiving similar therapies, which could translate into reduced healthcare expenditures.