Measuring patient safety in ambulatory care: potential for identifying medical group drug-drug interaction rates using claims data.

OBJECTIVE: To evaluate the feasibility of using health-plan administrative data to measure potential drug-drug interaction (DDI) rates in the ambulatory setting at the medical-group level and to assess the potential use of DDI rates in performance measurement, quality improvement, and research in patient safety. STUDY DESIGN: We combined administrative and pharmacy claims data from 2 large health plans to calculate the rates at which member users of selected chronic medications were potentially exposed to a second drug known to pose a risk of harmful interactions. METHODS: We divided 44 medication combinations with risk of adverse interactions into those with DDIs of moderate/severe clinical significance and those with DDIs of mild significance. We then calculated yearly rates of potential DDIs in continuously enrolled members aged 19 and older from 1998 through 2001. Rates were calculated for all members, overall base-medication users, and, individual medical groups responsible for their care. RESULTS: The analytic data set included 756 047 patient-years of data and 110 to 123 medical groups per year. During the 4-year interval, one or more unique potential DDIs occurred in 6.2% to 6.7% of base-drug users and 2.0% to 2.3% of all adult health-plan members per year. Medical-group mean user rates were slightly lower (5.33%-5.81%), with wide variance (SD = 2.6%-3.1%) and high stability over time. CONCLUSION: Potential DDI rates calculated from health-plan data have promise for measurement in patient medication safety. This readily available and inexpensive evaluation tool has potential for monitoring, improvement, and research purposes if further studies validate their relationship to actual adverse events.

2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo.

Slow-growing cell populations located within solid tumors are difficult to target selectively because most cells in normal tissues also have low replication rates. However, a distinguishing feature between slow-growing normal and tumor cells is the hypoxic microenvironment of the latter, which makes them extraordinarily dependent on anaerobic glycolysis for survival. Previously, we have shown that hypoxic tumor cells exhibit increased sensitivity to inhibitors of glycolysis in three distinct in vitro models. Based on these results, we predicted that combination therapy of a chemotherapeutic agent to target rapidly dividing cells and a glycolytic inhibitor to target slow-growing tumor cells would have better efficacy than either agent alone. Here, we test this strategy in vivo using the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) in combination with Adriamycin (ADR) or paclitaxel in nude mouse xenograft models of human osteosarcoma and non-small cell lung cancer. Nude mice implanted with osteosarcoma cells were divided into four groups as follows: (a) untreated controls; (b) mice treated with ADR alone; (c) mice treated with 2-DG alone; or (d) mice treated with a combination of ADR + 2-DG. Treatment began when tumors were either 50 or 300 mm(3) in volume. Starting with small or large tumors, the ADR + 2-DG combination treatment resulted in significantly slower tumor growth (and therefore longer survival) than the control, 2-DG, or ADR treatments (P < 0.0001). Similar beneficial effects of combination treatment were found with 2-DG and paclitaxel in the MV522 non-small cell lung cancer xenograft model. In summary, the treatment of tumors with both the glycolytic inhibitor 2-DG and ADR or paclitaxel results in a significant reduction in tumor growth compared with either agent alone. Overall, these results, combined with our in vitro data, provide a rationale for initiating clinical trials using glycolytic inhibitors in combination with chemotherapeutic agents to increase their therapeutic effectiveness.