Impact of computerized prescriber order entry on the incidence of adverse drug events in pediatric inpatients.

OBJECTIVES: This study was conducted to determine the impact of a computerized physician order entry system with substantial decision support on the incidence and types of adverse drug events in hospitalized children. METHODS: A prospective methodology was used for the collection of adverse drug events and potential adverse drug events from all patients admitted to the pediatric intensive care and general pediatric units over a 6-month period. Data from a previous adverse drug event study of the same patient care units before computerized physician order entry implementation were used for comparison purposes. RESULTS: Data for 1197 admissions before the introduction of computerized physician order entry were compared with 1210 admissions collected after computerized physician order entry implementation. After computerized physician order entry implementation, it was observed that the number of preventable adverse drug events (46 vs 26) and potential adverse drug events (94 vs 35) was reduced. Reductions in overall errors, dispensing errors, and drug-choice errors were associated with computerized physician order entry. There were reductions in significant events, as well as those events rated as serious or life threatening, after the implementation of computerized physician order entry. Some types of adverse drug events continued to persist, specifically underdosing of analgesics. There were no differences in length of stay or patient disposition between preventable adverse drug events and potential adverse drug events in either study period. CONCLUSIONS: This study demonstrated that a computerized physician order entry system with substantive decision support was associated with a reduction in both adverse drug events and potential adverse drug events in the inpatient pediatric population. Additional system refinements will be necessary to affect remaining adverse drug events. Preventable events did not predict excess length of stay and instead may represent a sign, rather than a cause, of more complicated illness.

Modulation of T-cell costimulation as immunotherapy or immunochemotherapy in experimental visceral leishmaniasis.

CD40 ligand (CD40L)-deficient C57BL/6 mice failed to control intracellular Leishmania donovani visceral infection, indicating that acquired resistance involves CD40-CD40L signaling and costimulation. Conversely, in wild-type C57BL/6 and BALB/c mice with established visceral infection, injection of agonist anti-CD40 monoclonal antibody (MAb) induced killing of approximately 60% of parasites within liver macrophages, stimulated gamma interferon (IFN-gamma) secretion, and enhanced mononuclear cell recruitment and tissue granuloma formation. Comparable parasite killing was also induced by MAb blockade (inhibition) of cytotoxic T lymphocyte antigen-4 (CTLA-4) which downregulates separate CD28-B7 T-cell costimulation. Optimal killing triggered by both anti-CD40 and anti-CTLA-4 required endogenous IFN-gamma and involved interleukin 12. CD40L(-/-) mice also failed to respond to antileishmanial chemotherapy (antimony), while in normal animals, anti-CD40 and anti-CTLA-4 synergistically enhanced antimony-associated killing. CD40L-CD40 signaling regulates outcome and response to treatment of experimental visceral leishmaniasis, and MAb targeting of T-cell costimulatory pathways (CD40L-CD40 and CD28-B7) yields macrophage activation and immunotherapeutic and immunochemotherapeutic activity.

Incidence and impact of adverse drug events in pediatric inpatients.

OBJECTIVES: To determine the incidence and causes of adverse drug events (ADEs) and potential ADEs in hospitalized children, and to examine the consequences of these events. DESIGN: Prospective review of medical records and staff interviews were performed. The ADEs were defined as injuries from medications or lack of an intended medication, and potential ADEs, as errors with the potential to result in injury. SETTING: A general pediatric unit and a pediatric intensive care unit in a metropolitan medical center. PATIENTS: A total of 1197 consecutive patient admissions were studied from September 15, 2000, to May 10, 2001. The admissions represented a total of 922 patients and 10,164 patient-days. RESULTS: The ADEs (6/100 admissions, 7.5/1000 patient-days) and potential ADEs (8/100 admissions, 9.3/1000 patient-days) were common in hospitalized children. Demographic variables associated with the occurrence of these events were the length of hospital stay, case-mix index, and amount of medication exposure. After adjusting for length of stay, medication exposure continued to have a significant influence on ADEs and potential ADEs. For ADEs, 18 (24%) were judged to be serious or life threatening. Most ADEs were not associated with major or permanent disability. Patients with both ADEs and potential ADEs were less likely to be routinely discharged and more likely to be discharged with home health care or to another institution, suggesting that patient disposition was not related to the adverse event. CONCLUSIONS: Both ADEs and potential ADEs are common among hospitalized children with greater disease burden and medication exposure. These findings suggest that these events were a consequence, rather than a cause, of more severe illness.