Duration of corticosteroid use in chronic obstructive pulmonary disease exacerbations: improving prescribing practices on clinical teaching units with peer-to-peer teaching.

INTRODUCTION: The most recent Global Initiative for Chronic Obstructive Lung Disease consensus recommends a 5-day course of corticosteroid (CS) therapy for acute chronic obstructive pulmonary disease exacerbations (ACOPDE). As inappropriate use of CS therapy is associated with adverse events, we implemented a peer-to-peer education intervention to improve adherence to guidelines for patients with ACOPDE admitted to a medical clinical teaching unit at a tertiary care university centre. METHODS: Our study was a before-after design study with a concurrent control of a 15 min peer-to-peer educational intervention targeting medical residents at the beginning of a 4-week rotation for 12 consecutive months. Another medical teaching unit within the same university network, but at a different site, served as a concurrent control. The primary outcome was the proportion of patients who received appropriate duration of CS therapy (5 days) for ACOPDE during the intervention period as compared with the 12-month preintervention period at the intervention and control hospitals. RESULTS: Following the intervention, there was an increase in the proportion of patients receiving appropriate duration of CS therapy (34.2% to 51.3%, p=0.02) at the intervention hospital and no significant difference at the control hospital (22.8% to 34.1%, p=0.15). This effect was maintained at the intervention hospital 3 months postintervention period. CONCLUSION: A short peer-to-peer educational intervention targeting medical residents on a clinical teaching unit improved adherence to appropriate duration of CS therapy for ACOPDE.

In vitro degradation of hexanitrohexaazaisowurtzitane (CL-20) by cytosolic enzymes of Japanese quail and the rabbit.

Hexanitrohexaazaisowurtzitane (CL-20) is a polycyclic nitramine explosive and propellant, currently being considered as a potential replacement for existing cyclic nitramine explosives. Earlier studies have provided evidence suggestive of adverse liver effects in adult Coturnix spp. exposed to CL-20, yet analysis of tissue samples (plasma, liver, brain, heart, or spleen) indicated that CL-20 was not detectable in these treated animals. The present study was conducted to identify and purify the enzymes capable of CL-20 biotransformation. Results indicate that the hepatic biotransformation of CL-20 in vitro was inhibited by ethacrynic acid (93%) and by the glutathione (GSH) analogue S-octylglutathione (80%), suggesting the involvement of glutathione-S-transferase (GST). Partially purified cytosolic alpha- and mu-type GST (requiring presence of GSH as a cofactor) from quail and rabbit liver was capable of CL-20 biotransformation. The degradation of CL-20 (0.30 +/- 0.05 and 0.40 +/- 0.02 nmol/min/mg protein for quail and rabbit, respectively) was accompanied with the formation of nitrite and consumption of GSH. Using liquid chromatography/mass spectrometry, we detected two intermediates, that is, open-ring, monodenitrated GSH-conjugated CL-20 biotransformation product with the same deprotonated molecular mass ion at 699 Da, suggesting isomeric forms of the intermediate metabolites. Identity of the conjugated metabolites was confirmed by using ring-labeled [15N]CL-20 and the nitro group-labeled [15NO2]CL-20. These data suggest that the in vitro biotransformation of CL-20 by GST under the conditions tested may be a key initial step in the in vivo degradation of CL-20 in the quail and resulted in the formation of more biologically reactive intermediates than the parent compound. These data will aid in our understanding of the biotransformation processes of CL-20 in vivo.