Yuan-Shung V. Huang

Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data.

Background:Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of pediatric cancer in the United States. Despite cooperative group therapeutic trials, there remains a paucity of large cohort data on which to conduct epidemiology and comparative effectiveness research studies. Research Design:We designed a 3-step process utilizing International Classification of Diseases-9 Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure data contained in the Pediatric Health Information System administrative database to establish a cohort of children with de novo ALL. This process was validated by chart review at 1 of the pediatric centers. Results:An ALL cohort of 8733 patients was identified with a sensitivity of 88% [95% confidence interval (CI), 83%–92%] and a positive predictive value of 93% (95% CI, 89%–96%). The 30-day all cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI, 0.63%–1.01%), which was significantly different than the case fatality rate of 1.40% (95% CI, 1.23%–1.60%) when ICD-9 codes alone were used. Conclusions:This is the first report of assembly and validation of a cohort of de novo ALL patients from a database representative of free-standing children’s hospitals across the United States. Our data demonstrate that the use of ICD-9 codes alone to establish cohorts will lead to substantial patient misclassification and result in biased outcome estimates. Systematic methods beyond the use of just ICD-9 codes must be used before analysis to establish accurate cohorts of patients with malignancy. A similar approach should be followed when establishing future cohorts from administrative data.

Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric oncology patients

Dexrazoxane may reduce anthracycline‐associated cardiotoxicity in pediatric cancer patients. However, concerns of secondary acute myeloid leukemia (AML) have led to restrictions on pediatric dexrazoxane use in Europe. Published data about dexrazoxane‐associated secondary AML are limited and conflicting. We sought to estimate the secondary AML risk in children receiving dexrazoxane after anthracycline exposure.

Dexrazoxane Use in Pediatric Patients With Acute Lymphoblastic or Myeloid Leukemia From 1999 and 2009: Analysis of a National Cohort of Patients in the Pediatric Health Information Systems Database

Acute lymphoblastic (ALL) and myeloid leukemia (AML) account for approximately 26% of pediatric cancers. Anthracyclines are widely used to treat these leukemias, but dosing is limited by cardiotoxicity. Data support the efficacy of dexrazoxane as a cardioprotectant in children; however, dexrazoxane use in children is not universally accepted due to concerns about toxicity, impact on the antitumor effect of anthracyclines, and risk of secondary malignant neoplasms (SMN).

Variation in hospital antibiotic prescribing practices for children with acute lymphoblastic leukemia

Abstract Antibiotic variation among pediatric oncology patients has not been well-described. Identification of significant variability in antibiotic use within this population would warrant evaluation of its clinical impact. We conducted a retrospective cohort study of newly diagnosed patients with pediatric acute lymophoblastic leukemia (ALL) hospitalized from 1999 to 2009 in 39 freestanding US childrens hospitals within the Pediatric Health Information System. Medication use data were obtained for the first 30 days from each patients index ALL admission date. Antibiotic exposure rates were reported as antibiotic days/1000 hospital days. Unadjusted composite broad-spectrum antibiotic exposure rates varied from 577 to 1628 antibiotic days/1000 hospital days. This wide range of antibiotic exposure was unaffected by adjustment for age, gender, race and days of severe illness (adjusted range: 532–1635 days of antibiotic therapy/1000 hospital days). Antibiotic use for children with newly diagnosed ALL varies widely across childrens hospitals and is not explained by demographics or illness severity.

Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia

Deaths during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL) account for one‐tenth of ALL‐associated mortality and half of ALL treatment‐related mortality. We sought to ascertain patient‐ and hospital‐level factors associated with induction mortality.

A Multicenter Cohort Study of Inferior Vena Cava Filter Use in Children

To describe inferior vena cava (IVC) filter use in pediatric patients admitted to U.S. childrens hospitals and to determine factors associated with prophylactic placement.

Opioid utilization among pediatric patients treated for newly diagnosed acute myeloid leukemia

Purpose A cohort of pediatric patients with AML treated at hospitals contributing to the Pediatric Health Information System was used to evaluate differences in opioid utilization by sex, age, race, and insurance. Methods Billing data were used to compute the prevalence of opioid exposure and to quantify rates of utilization among those exposed to opioids as days of use per 1000 inpatient days. Multivariable regressions were used to compare opioid prevalence, and rates of utilization among those exposed. Results On average across courses, 95.2% of patients were exposed to analgesics, 84.7% were exposed to non-opioid analgesics and 77.7% were exposed to opioids. The proportion of opioid-exposed patients increased with age, but did not differ by gender, race, or insurance status. Analyses limited to patients exposed to opioids revealed modest differences in days of opioid use among female patients (adjusted rate ratio (aRR) = 1.19, 95% CI: 1.11, 1.28), patients <1 year (aRR = 1.37, 95% CI: 1.21, 1.55) or ≥10 years of age (aRR = 1.63, 95% CI: 1.46, 1.82), whereas Asian patients received fewer days of opioids compared with white patients (aRR = 0.76, 95% CI: 0.61, 0.95). There was moderate hospital-level variability in both the prevalence of opioid utilization overall and preference for specific opioid medications. There was greater inconsistency in practice concerning choices for supplemental and alternative opioids than in first-line opioid utilization. Conclusion Additional work is needed to discern whether observed differences in opioid utilization by age and race reflect a difference in treatment or a difference in the experience of pain. Future studies should also explore the factors which guide decisions on opioid selections in an attempt to explain the variability across institutions.

Burden of Influenza-Related Hospitalizations and Attributable Mortality in Pediatric Acute Lymphoblastic Leukemia

BACKGROUND Influenza can be severe in patients with underlying malignancy; however, the rate of influenza hospitalizations and attributable mortality in children with cancer is unknown. METHODS We performed a retrospective cohort study among 10 698 children with new-onset acute lymphoblastic leukemia (ALL) from 41 US childrens hospitals between January 1999 and September 2011. Influenza-related hospitalizations were identified using ICD-9 discharge diagnosis codes, excluding hospitalizations during low-prevalence influenza periods. Follow-up was censored at the earliest of 5 events: end of study period, expected end of chemotherapy, last known hospitalization, hematopoietic stem cell transplant, or death. Data were collected on hospitalization characteristics and resource utilization. Hospitalization rates were calculated using season-adjusted person-time. Crude attributable in-hospital mortality was calculated using baseline mortality for noninfluenza hospitalizations during the same period. Subgroup analysis was performed by time from ALL diagnosis and by age category. RESULTS The rate of influenza-related hospitalizations was 618.3 per 100 000 person-months. Rates were similar by time from ALL diagnosis and across age categories. Overall attributable in-hospital mortality was 1.0% (95% confidence interval [CI], 0.3%-2.3%) and was highest for children <6 months from diagnosis (1.6%; 95% CI, 0.4%-4.5%) and children <2 years of age (6.7%; 95% CI, 1.3%-22.7%). Total length of stay, days of broad-spectrum antibiotic exposure, and duration of intensive care were significantly greater for influenza-related hospitalizations compared with noninfluenza hospitalizations. CONCLUSIONS The burden of influenza-related hospitalizations in children with ALL is high and associated with significantly increased resource utilization and attributable mortality.

Zoonotic infections in pediatric patients with acute leukemia

Few studies have described the impact of zoonotic diseases in children with leukemia. This study aimed to describe the frequency of and associated demographic factors for zoonotic diseases in pediatric acute leukemia patients. Descriptive and comparative statistics relative to age, sex, and patient region were performed on an assembled 11‐year retrospective cohort of acute leukemia patients. Of 10,197 patients, 88 patients (0.86%) were found to have a zoonotic infection. Gastrointestinal diseases were the most commonly (86.4%) identified zoonotic illnesses. Although rare, zoonotic diseases do occur in children with leukemia and frequency varies by age, region, and gender. Pediatr Blood Cancer 2013;60:E160–E162.

Successful merging of data from the United Network for Organ Sharing and the Pediatric Health Information System databases

Data routinely collected through United Network for Organ Sharing (UNOS) lack the detailed information on medical resource utilization and treatment costs required to accomplish for center‐level comparisons of quality of care and cost for pediatric heart transplantation. We aimed to overcome this limitation by merging UNOS with the Pediatric Health Information System (PHIS) database, an administrative database containing inpatient, emergency department, ambulatory surgery, and observation unit information from over 40 not‐for‐profit, tertiary care pediatric hospitals. Utilizing a probabilistic match based on center, date of birth, recipient gender, and transplant date within ±2 days, more than 90% of eligible UNOS patients (N = 2264) were successfully merged to their corresponding PHIS records. Thirty‐day and 1‐year mortality rates observed for the merged cohort (3.2% and 9.0%, respectively) were compared with those previously reported for pediatric heart transplants, as were the significant predictors of increased mortality. These results demonstrate that the established UNOS‐PHIS cohort will provide a valid platform for subsequent research aimed at identifying center‐level differences that could be exploited to optimize quality of care while minimizing cost across institutions.