Prevalence of Polypharmacy Exposure Among Hospitalized Children in the United States Feudtner C, Dai D, Hexem KR, Luan X, Metjian TA. Prevalence of polypharmacy exposure among hospitalized children in the United States. Arch Pediatr Adolesc Med. Published online September 5, doi: /archpediatrics Copyright restrictions may apply

Introduction Background –In the hospital setting, efficacy and safety of many pediatric medications have not been well established. –Recent federal legislation has called for greater attention to safety and effectiveness of on- and off-label drug treatments for children. Study Goal –To characterize overall patterns of pediatric inpatient drug and therapeutic agent use in order to enhance efforts to prioritize and design future research studies regarding effectiveness and safety of pediatric inpatient medications. Copyright restrictions may apply

Methods Study Design –Secondary analyses of pediatric inpatient data (from patients aged <18 years) from 2 data sources (Pediatric Health Information System and Perspective Data Warehouse) that together include approximately 20% of pediatric inpatient hospitalizations in Sample – unique pediatric inpatients, responsible for hospitalizations in 52 children’s hospitals. – unique pediatric inpatients, responsible for hospitalizations in 411 general hospitals. Outcome/Analyses –Differences in exposures to pharmaceutical agents by hospital type, adjusted for patient covariates (age, sex, length of stay, surgery). Copyright restrictions may apply

Methods Limitations –Prescribed medications do not ensure that the medications were administered. –Although pro re nata (PRN) medications ordered should not be billed if not used, it is possible that some PRN medications are included but were not administered. –Drug doses were not available from the data. –Intentions and clinical purposes for which drugs were prescribed are not known with certainty. Copyright restrictions may apply

Percentage of patients exposed to major drug and therapeutic agent classes by age group and hospital type. (Only the upper portion of the figure is shown; for data regarding other agents, please see the article.) Results

Copyright restrictions may apply a Percentage of patients exposed to the named drug at any point during the hospitalization; rank ordering omits intravenous fluids, sterile water, dextrose water, heparin intravenous flushes, hyperalimentation, multivitamins, and glycerin suppository. (Only the upper portion of the table is shown; for data regarding older age groups, please see the article.) Top Generic Drug Entity Exposures by Hospital Type a Results

Copyright restrictions may apply Cumulative number of distinct drug and therapeutic agent exposures per hospitalization by length of stay, hospital type, and patient age. IQR indicates interquartile range. Results

Copyright restrictions may apply Multivariable Adjusted Rate Ratios of Cumulative Total Number of Exposures to Distinct Drugs and Therapeutic Agents for Hospitalized Pediatric Patients Results

Comment A large proportion of children are exposed to 5 or more drugs or therapeutic agents during each day of hospitalization. Differences in exposure by hospital type are largely nullified when differences in patients are taken into account. Variation among children’s hospitals and among general hospitals in drug and therapeutic agent use was substantial (see the article for details). Copyright restrictions may apply

Comment Implications for Future Research in This Area –Opportunity to apply use data in prioritization of research on safety and efficacy, especially for off-label use. –Development of new mechanisms to detect adverse events in pediatric settings. –Further research regarding possible drug-drug interactions that may place children at risk in the setting of polypharmacy. –Opportunities for comparative effectiveness research given the broad variation across institutions in the management of common clinical problems. Copyright restrictions may apply

Contact Information If you have questions, please contact the corresponding author: –Chris Feudtner, MD, PhD, MPH, CHOP North–Room 1523, The Children’s Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA Funding/Support This study was supported by Center for Education and Research on Therapeutics grant U18 HS from the Agency for Healthcare Research and Quality. Copyright restrictions may apply