Publications

The tartrate-resistant acid phosphatase (TRAP) is present in multiple tissues, including kidney, liver, lung, spleen, and bone. Recent study of (TRAP) gene expression has provided evidence for distinct promoters within the (TRAP) gene, suggesting that the gene has alternative, tissue-preferred mRNA transcripts. Examination of endogenous (TRAP) exon 1B and 1C mRNA transcripts revealed tissue-preferred transcript abundance with increased exon 1B transcripts detected in liver and kidney and increased exon 1C transcripts detected in bone and spleen. In this investigation, we have made transgenic mice that express a marker gene driven by two candidate promoters, designated BC and C, within the (TRAP) gene. The BC and C promoters are 2.2 and 1.6 kb, respectively, measured from the translation initiation site. Evaluation of BC transgenic lines demonstrated robust expression in multiple tissues. In contrast, significant transgene expression was not detected in C transgenic lines. Evaluation of transgene mRNAs in BC transgenic lines revealed that virtually all expression was in the form of B transcripts, suggesting that the tissue-preferred pattern of endogenous (TRAP) was not replicated in the BC transgenic line. Likewise, osteoclastogenic cultures from BC, but not C, transgenic bone marrow cells expressed the transgene following receptor activator of NFkappaB ligand/macrophage colony-stimulating factor stimulation. In conclusion, when compared with the 2.2-kb BC portion of the (TRAP) promoter region, the 1.6-kb C portion does not account for significant gene expression in vivo or in vitro; production of the bone- and spleen-preferred (TRAP) C transcript must depend on regulatory elements outside of the 2.2-kb promoter. As the majority of currently investigated transcription factors that influence transcriptional regulation of osteoclast gene expression bind within the 1.6-kb C portion of the (TRAP) promoter, it is likely that transcription binding sites outside of the 2.2-kb region will have profound effects on regulation of the gene in vivo and in vitro.

We observed four cases of therapeutic failures while patients were simultaneously taking medications that contained divalent cations and oral fluoroquinolones. Patients improved after conversion to the intravenous formulation of the same antibiotics, proper spacing of the divalent cation, or conversion to a different antibiotic class. Patients prescribed oral fluoroquinolones should receive instructions on proper separations of these antibiotics with divalent cations. Health care professionals should be cognizant of these interactions and educated on their potential deleterious effect.

BACKGROUND: To explore the incidence and severity of potential interactions between prescription medications and dietary supplements.

METHODS: A survey was conducted on dietary supplement use in 458 veteran outpatients currently taking prescription medications. Self-reported dietary supplement use was cross-referenced with each patient's prescription medication list, and potential interactions were identified from several tertiary sources and medical literature searches.

RESULTS: One hundred ninety-seven patients (43%) were currently taking at least 1 dietary supplement with prescription medication(s). The most common products included vitamins and minerals, garlic, Ginkgo biloba, saw palmetto, and ginseng. Among these, 89 (45%) had a potential for drug-dietary supplement interactions of any significance. Most of these interactions (n = 84 [94%]) were not serious based on limited available evidence, giving an incidence of 6% (5/89) of potentially severe interactions among patients taking interacting drugs and dietary supplements and 3% (5/197) among patients taking coincident dietary supplements and medications.

CONCLUSIONS: Although the use of dietary supplements appears to be very common among patients who also take prescription medications, most potential drug-dietary supplement interactions found were not serious. However, literature support was sparse at best. Health care providers should continue to inquire about dietary supplement use and consider the potential for interactions, regardless of their severity.

OBJECTIVE: To assess physician satisfaction with Department of Veterans Affairs (VA) formulary policies and to examine the correlation between physician satisfaction and perceived access to formulary and nonformulary medications.

STUDY DESIGN: Cross-sectional survey with specific questions on access to formulary and nonformulary medications. Statistical analyses included assessment of associations between physician satisfaction and various measures of access.

PARTICIPANTS AND METHODS: Initial sample of 4015 staff physicians working in VA healthcare facilities. Responses were received from 1812 (49%) of the 3682 physicians in the final eligible sample population.

RESULTS: Most clinicians (72%) reported that their local formulary covered more than 90% of the medications they wanted to prescribe. Most (73%) agreed that drug restrictions were important to contain costs, and 86% agreed that it was important for VA to choose "best-value" drugs. Respondents reported an 89% approval rate for nonformulary drugs, though 31% indicated that approvals routinely took 3 or more days. We found strong associations between physician satisfaction and self-reported approval rates for nonformulary drugs (P = .001), timely approval of nonformulary requests (P < .001), and percentage of nonformulary prescriptions as a proportion of overall prescriptions at a regional level (P< .01). There was no significant correlation between physician satisfaction and number of medications added to regional formularies or with drug costs per unique patient.

CONCLUSIONS: VA physicians were generally supportive of VA formulary policies including choosing best-value drugs to control pharmaceutical expenditures. Nevertheless, access to nonformulary drugs and timely approval of requests for nonformulary medications were strong predictors of clinician satisfaction and support for cost-containment measures.

OBJECTIVES: We sought to examine the impact of direct-to-consumer advertising (DTCA) and pharmaceutical promotion to physicians on the likelihood that (1) an individual diagnosed with depression received antidepressant medication and that (2) antidepressant medication was used for the appropriate duration.

RESEARCH DESIGN AND SUBJECTS: A quasiexperimental design was used to examine treatment patterns of 30,621 depressed individuals whose insurance claims were included in the MarketScan database from 1997 through 2000. The main explanatory variables were spending on DTCA, detailing to physicians, and free samples for 6 antidepressant medications.

RESULTS: Individuals diagnosed with depression during periods when class-level antidepressant DTCA spending was highest (cumulative spending more than US 18.5 million dollars) had 32% higher relative odds of initiating medication therapy compared with those diagnosed during periods when DTCA spending was lowest (P < 0.0001). Free samples of medications dispensed to physicians had no effect on odds of initiating antidepressant use. Class-level DTCA spending on antidepressants had a small positive effect on the duration of antidepressant use, whereas DTCA spending for the specific medication taken by an individual had no effect on treatment duration. Detailing spending at the class or product level had no significant effect on duration of treatment with an antidepressant medication.

CONCLUSIONS: Our results suggest that DTCA of antidepressants was associated with an increase in the number of people diagnosed with depression who initiated medication therapy. DTCA was associated with a small increase in the number of individuals treated with antidepressants who received the appropriate duration of therapy. Promotion to physicians was not associated with either the initiation of treatment with an antidepressant or with the duration of therapy.