Early toxicology signal generation in the mouse.

The rat has been the preferred rodent toxicology species since before regulatory requirements have been in place, and there exists in the pharmaceutical industry and the regulatory agencies a significant amount of historical data for the rat. The resulting experience base with the rat makes the possibility of replacing it with the mouse for regulated toxicology studies untenable for all but the most extreme circumstances. However, toxicologists are very familiar with the mouse as a model for chronic carcinogenicity studies, and there exist multiple preclinical mouse models of disease. The authors evaluated the use of the mouse for early in vivo toxicology signal generation and prioritization of small molecule lead compounds prior to nomination of a development candidate. In five-day oral gavage studies with three test agents in the mouse, the authors were able to identify the same dose-limiting toxicities as those identified in the rat, including examples of compound-mediated hemolysis as well as microscopic lesions in the alimentary canal, kidney, and pancreas. Performing early signal generation studies in the mouse allows for earlier assessment of the safety liabilities of small molecules, requires significantly less compound, and allows evaluation of more compounds earlier in the project's life cycle.

Pain Assessment Documentation After Opioid Administration at a Community Teaching Hospital.

PURPOSE: To compare pain assessment documentation postopioid administration in hospitalized patients before and after implementing nurse education. METHODS: Patients 18 years and older were randomly selected for inclusion if they received 1 opioid dose while admitted to the hospital. Through retrospective chart review, opioid data, including date and time, were collected for each opioid administered. Pain score data, including time and date of documentation, were recorded for analysis. The primary objective of this study was to determine whether a nursing education intervention would improve documentation of pain scores within an appropriate time frame postadministration of an opioid medication. The intervention was a training presentation uploaded to the institution's intranet with an assessment. The primary outcome was measured by comparing the frequency by which nurses documented pain scores following opioid administration before and after education. RESULTS: Three hundred twenty patients (160 patients per time period) were evaluated. The percentage of pain scores recorded within the appropriate assessment time following opioid administration increased from 32.9% to 37.8% ( P = .003). The proportion of appropriate pain score documentation increased 4.9% (95% confidence interval [CI]: 1.6%-8.2%). CONCLUSION: An increase in the documentation of efficacy assessments after opioid administration was demonstrated after nursing education. Further studies should be done to identify additional strategies to increase monitoring as well as to identify a benchmark for institutions with regard to pain management monitoring.