Most patients hospitalized at tertiary care pediatric institutions receive at least 1 medication outside the terms of the Food and Drug Administration product license. Substantial variation in the frequency of off-label use was observed across diagnostic categories and drug classes. Despite the frequent off-label use of drugs, using an administrative database, we cannot determine which of these treatments are unsafe or ineffective and which treatments result in substantial benefit to the patient.

OBJECTIVES Early transition from intravenous to oral antimicrobial therapy for acute osteomyelitis in children has been suggested as a safe and effective alternative to traditional prolonged intravenous therapy via central venous catheter, but no studies have directly compared these two treatment modalities. We sought to compare the effectiveness of early transition from intravenous to oral antimicrobial therapy vs. prolonged intravenous antimicrobial therapy for the treatment of children with acute osteomyelitis. METHODS We conducted a retrospective cohort study of children ages 2 months to 17 years diagnosed with acute osteomyelitis between 2000 and 2005 at 29 free-standing children’s hospitals in the United States to confirm the extent of variation in use of early transition to oral therapy. We used a propensity scores to adjust for potential differences between children treated with prolonged intravenous therapy, and logistic regression to model the association of outcome (treatment failure rates within 6 months of diagnosis and difference in the mode of therapy within hospitals and across hospitals. RESULTS Of the 1969 children who met inclusion criteria, 1021 received prolonged intravenous therapy and 948 received oral therapy. Use of prolonged intravenous therapy varied significantly across hospitals (10% to 95%, P<0.001). The treatment failure rate was 5% (54 of 1021) in the prolonged intravenous therapy group and 4% (38 of 948) in the oral therapy group. There was no significant association between treatment failure and the mode of antimicrobial therapy (adjusted odds ratio=0.77, 95% confidence interval=0.49 to 1.22). Thirty-five children (3.4%) in the prolonged intravenous therapy group were readmitted for a catheter-associated complication. CONCLUSIONS Treatment of acute osteomyelitis with early transition to oral therapy is not associated with a higher risk of treatment failures and avoids the risks of prolonged intravenous therapy through central venous catheters.

Purpose National Cancer Institute (NCI)-funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children’s Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, estimate treatment-associated resource utilization and costs, and to address important clinical epidemiology questions. Methods COG and PHIS data on patients enrolled on a Phase III COG trial for de novo acute myeloid leukemia (AML) at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data. Results Of 416 patients enrolled on the Phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti-infective exposures were tabulated and standardized costs were described. Conclusions These data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set, and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to NCI Common Toxicity Criteria for monitoring toxicity, perform comparative effectiveness studies, and estimate the costs associated with protocol therapy.

Evidence-based care guidelines can successfully influence utilization and clinical outcome.

From this administrative database analysis, there is no evidence that steroids are associated with improved outcome in critically ill infants and children with sepsis. Although steroids may be given preferentially to more severely ill children, their use was associated with increased mortality. Clinicians should maintain equipoise on this topic pending prospective randomized clinical trials.