Increase in lipid-lowering treatment rates among TRICARE beneficiaries: a population-based study.

PURPOSE: To evaluate the use of lipid-lowering treatment (LLT) among patients at risk for cardiovascular disease (CVD) in the US Military Health System (MHS). METHODS: The study examined healthcare service and prescription records among beneficiaries > or =18 years for calendar years 2002, 2004, and 2006. Patients were categorized based on cardiovascular (CV) risk, with exposure to LLT defined as one or more prescriptions for lipid-lowering medication. Logistic regression models estimated odds of treatment in 2004 and 2006 relative to 2002 after adjustment for age, gender, and CV risk. RESULTS: The yearly unadjusted population prevalence of LLT increased from 9.3% in 2002 to 14.7% in 2006. Among subjects with the highest CV risk, established coronary artery disease (CAD) or peripheral vascular disease (PVD), those receiving LLT increased from 55% in 2002 to 65% in 2006 (adjusted OR = 1.50, 95% CI 1.48, 1.52, p < 0.00). Treatment rates among diabetic patients with no coded CAD or PVD showed the largest relative increase from 47% in 2002 to 66% in 2006 (adjusted OR = 2.30, 95% CI 2.26, 2.332, p < 0.00). LLT growth was lowest among those with only 1 coded CV risk factor (adjusted OR = 1.32, 95% CI 1.31, 1.34, p < 0.00). CONCLUSIONS: The MHS experienced a significant increase in LLT among patients at greatest risk for cardiovascular disease. However, treatment may still be underutilized as approximately one-third of high-risk patients did not receive lipid-lowering medication.

Formulary management in the Department of Defense.

BACKGROUND: The U.S. Department of Defense (DoD) health care benefit (TRICARE) provides 9.2 million active-duty and retired uniformed services personnel and their family members with access to a comprehensive pharmacy benefit with low out-of-pocket costs. DoD's Uniform Formulary is available worldwide at DoD's 3 pharmacy points of service (military pharmacies, contracted mail order, and community [network and non-network] pharmacies). Community pharmacies, military pharmacies, and mail order accounted for 64%, 23%, and 13%, respectively, of DoD's $6.5 billion total drug expenditures during fiscal year (FY) 2007 (October 1, 2006, through September 30, 2007). OBJECTIVE: To describe the DoD formulary management process and estimate cost savings associated with implementation of DoD's 3-tier formulary. SUMMARY: DoD implemented its 3-tier Uniform Formulary in 2005. This implementation required the development of a transparent formulary management process that (a) assesses medications for formulary status based on an evidence-based clinical evaluation and assessment of relative cost-effectiveness using pharmacoeconomic and budget impact modeling, (b) allows open and equitable price competition among pharmaceutical manufacturers based on formulary status, and (c) provides a public forum for beneficiaries and beneficiary organizations to comment on formulary changes. Through April 16, 2008, Uniform Formulary decisions had been implemented in 32 drug classes representing 53% of FY 2007 total drug expenditures. The 32 classes containing 343 drugs were reviewed at 12 quarterly meetings of the DoD Pharmacy and Therapeutics (P&T) Committee and the Beneficiary Advisory Panel, resulting in the classification of 85 drugs (24.8%) in tier 3, 92 drugs (26.8%) in tier 2, and 166 drugs (48.4%) in tier 1. Implementation of the 3-tier formulary was associated with an estimated $926 million in cost avoidance in FY 2007, primarily due to price reductions at military pharmacies and mail order, tier 3 copayments at community pharmacies and mail order, and change in product mix and pharmacy type (point of service). An additional $60 million in rebates were obtained in FY 2007 through the Voluntary Agreements for TRICARE Retail Pharmacy Refunds (UF VARR) program for prescriptions filled at community pharmacies; the UF VARR program first became available for drug classes reviewed in August 2006. The total of $986 million in cost avoidance and rebates represents an approximate 13% reduction, compared with what DoD otherwise would have paid in FY 2007 ($7.5 billion, compared with actual drug expenditures of $6.5 billion). CONCLUSION: As in most private-sector health plans, the DoD formulary management process (a) includes rigorous decision making that is informed by clinical literature evaluations and pharmacoeconomic analyses, (b) results in drug formulary changes that require considerable effort in communication with providers and beneficiaries, and (c) produces drug cost savings derived from increased price competition among drug manufacturers. Unlike private sector health plans, the DoD uses more disclosure of the results of evaluation of the evidence, solicits provider opinions before P&T committee deliberation, and provides the opportunity for beneficiaries to have input before implementation of formulary changes.

Response of human mammary epithelial cells to DNA damage induced by BPDE: involvement of novel regulatory pathways.

The responses of a line of normal human mammary epithelial cells, HME87, to treatment with the ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE) were analyzed using a directed gene expression analysis technique, RAGE. Under conditions where cell number was decreased by 50% 24 or 48 h post-treatment, flow cytometry demonstrated no establishment of a G(1)/S arrest nor induction of apoptosis; cells continued to enter S phase from G(1) for at least 24 h but were blocked at G(2)/M. Using the RAGE technique, changes in gene expression were assayed for over 1000 genes, and multiple time-point data were collected for approximately 90 genes. In accord with the cell cycle studies, expression of the p21-WAF1 gene, the major mediator of p53-dependent G(1)/S arrest, did not increase until 24 h post-treatment. The expression of other target genes for transactivation by p53 was increased at early time points, including GADD45, an effector of the G(2)/M checkpoint, and WIP1. Analyses of proteins in treated cells indicated that p53 was phosphorylated at Ser15 but not at Ser20 within 30 min of treatment, and this correlated with an increase in the total amount of p53 protein. Significant expression changes were noted in a number of transcription factor genes, including ATF3 and E2A, genes that have not been previously connected to a response to DNA damage involving bulky chemical adducts. In addition, expression of the XPC gene was induced by BPDE treatment; the XPC product is thought to be involved in recognition of DNA damage by the nucleotide excision repair system.