Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 allele, but the mechanism for these effects is unknown. Long-term potentiation (LTP) is an experimentally induced increase in synaptic efficacy that models memory. Using hippocampal slices from wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing human apoE2, E3, or E4 (apoE-TR) we found that although all strains had comparable basal synaptic transmission, LTP was significantly greater in WT and apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR. This novel system may be used to investigate the mechanisms of apoE isoform dependent modulation of susceptibility to memory impairment.

patients ($1,042 vs. $1,593, pϭ0.0034). The pharmacy costs were, however, higher in these patients, compared to SOC-initiated patients ($4,358 vs. $3,235, pϽ0.001). In addition, duloxetine-initiated patients were less likely to use any opioids (56% vs. 63%, pϽ0.05) compared with SOC patients not initiated on opioids. CONCLUSIONS: Commercially-insured CLBP patients initiating duloxetine were associated with significantly lower inpatient costs and CLBP-related outpatient costs, but higher pharmacy costs, compared to patients initiating other SOC treatments. Duloxetineinitiated patients were also less likely to use opioids in the post-index year. OBJECTIVES:The impact of on-demand (OD) treatment for bleeding episodes is rarely quantified in Italian hemophilia patients with inhibitors. This study calculated lifetime events, hospitalizations, and quality-of-life (QoL) associated with recombinant activated Factor VIIa (rFVIIa) and plasma-derived activated prothrombin complex concentrate (pd-aPCC). This study also compared a hypothetical improved bypassing agent (BA) with faster, more sustained bleed resolution than rFVIIa against pd-aPCC. METHODS: We developed an Italian semi-Markov cohort model to reflect treatment effect on bleeds across a lifetime horizon for 2-year old hemophilia patients with high-responding inhibitors. The model tracks patients through eight health states (pre-ITI, delayed ITI, ITI low dose, ITI high dose, tolerized, partially-tolerized, non-tolerized, death) in 3-month cycles; bleeds and treatment success are simulated within states. Published international studies informed efficacy estimates, and published utility data informed QoL parameter values. RESULTS: In analysis of rFVIIa vs pd-aPCC, fewer rFVIIa patients required Ͼ1 series of home infusions per bleed (13% vs. Ͼ40% for pd-aPCC), leading to 4% fewer hospitalizations following 2ϩ unsuccessful home treatments. QALYs, dependent on tolerization status in the basecase, are 43.13 for rFVIIa vs. 43.06 for pd-aPCC. Exploratory comparison with improved rFVIIa bleed-resolution showed reducing the rebleed rate by 15% reduces use of Ͼ1 line of therapy by 2%, decreasing hospitalization 13% compared to basecase values. If fewer infusions of the new BA are required to control a bleed per line of therapy, patients may experience QoL benefits; utility improvement of 5%-20% raises total QALYs to 43.98-46.54 for the new BA. CONCLUSIONS: rFVIIa may lower on-demand treatment resource use for inhibitor patients in Italy, and improving haemostasis of BAs would further improve patient care for this population; additional research around Italian treatment patterns for inhibitor patients as well as the impact of faster bleed resolution is warranted.

4765 Introduction: Patients with FLT3-mutated AML have poor prognoses due to shorter survival, a high incidence of relapse, and a lack of effective treatment options. Limited information is published on the burden of illness (BOI) of AML, especially for patients with FLT3-mutated disease. This study reviewed the epidemiologic, clinical, humanistic, and economic literature and estimated the burden of FLT3-mutated AML in the US. Methods: A systematic literature review was conducted in PubMed to identify clinical and economic publications on AML published in English from 2000 to 2011. Data relevant to the burden of FLT3-mutated AML were abstracted. 607 citations were identified in PubMed. 581 abstracts were screened and 35 articles were abstracted. Epidemiologic data were also sought from the Surveillance, Epidemiology and End Results (SEER) database. Areas where information was limited or not available were identified and discussed with clinicians experienced in treating AML. An Excel model was then developed to estimate the population-level BOI of AML by FLT3 status. Resource utilization estimates were obtained from the literature and expert opinion. Direct costs included procedures, hospitalizations, outpatient/office visits, other resource use (home health care, hospice, skilled nursing facility), and medications (including chemotherapy). Indirect costs included lost productivity but did not include costs associated with premature retirement or premature mortality. Results: In patients age <60 years, the literature reported FLT3 mutations in up to 30% of AML cases. Patients with FLT3-mutated AML have poorer prognoses: per the literature, median overall survival estimates of 15.2–15.5 months for FLT3-mutated AML patients <60 years of age was noted compared to 19.3–28.6 months for wild-type AML patients. Five-year survival rates for age <60 years range from 15% for high ITD-mutant levels to 31% in low ITD mutant-levels for FLT3-mutated AML patients vs. 42% for wild-type AML patients. No studies were identified containing estimates for the incidence or prevalence of FLT-3 mutated AML. The prevalence of AML in 2008 was obtained from SEER data and was estimated at 27,813 patients aged ≥20 years. Age- and gender-specific incidence and relative 5-year survival rates were obtained from SEER data. Projections for the prevalence, incidence, and mortality of FLT3-mutated AML through 2020 were calculated based on the SEER estimates, age- and gender-specific US Census population projections, and an assumption of FLT3 mutations in 23% of AML cases. In 2010, it was estimated that 725 patients aged 20–60 years were diagnosed with FLT3-mutated AML, with 572 disease-related deaths. Three studies were identified which reported information on the impact of AML on quality of life (QoL), though none described the QoL impact of FLT-3 mutated AML. One study specifically examined the <60 year old population, noting that AML patients receiving stem cell transplants had significantly worse long-term impact on QoL vs. patients receiving conventional chemotherapy. No studies quantifying the impact of AML on productivity were identified. In our analysis, the overall economic burden of FLT-3 mutated AML in the US was estimated at $244 million in 2010, including $184 million in direct costs and $60 million in indirect costs from lost productivity. Stem cell transplants accounted for 21% of direct costs, inpatient hospitalizations accounted for 44%, and medications for 4%. For AML patients <60 years, the overall cost per newly diagnosed FLT3-mutated AML patient was estimated at $114,198 vs. $105,825 for newly diagnosed FLT3-wild-type AML patients. This is likely an underestimate of the cost as the impacts of early mortality and early retirement were not included in the indirect costs. In addition, the impact of QoL was not included and this may also underestimate costs due to more frequent use of transplantation in the FLT3-mutated AML population. Conclusions: AML poses a large economic burden, both for the healthcare system and society. FLT3-mutated AML potentially represents a greater per-patient burden than FLT3 wild type AML due to shorter survival rates and use of more costly therapies such as stem cell transplants. Investigational treatments targeting the FLT3 mutation may provide an additional therapeutic option for these patients and have the potential to improve clinical outcomes. Disclosures: Sotak: Novartis: Research Funding. Marin:Novartis: Research Funding. Coombs:Novartis: Employment. Schiller:BMS: Research Funding; Celgene: Research Funding; Ambit: Research Funding; Novartis: Research Funding; Sunesis: Research Funding. Teitelbaum:Novartis: Research Funding.