The Cost Effectiveness of Lisdexamfetamine Dimesylate for the Treatment of Binge Eating Disorder in the USA

BACKGROUND: Lisdexamfetamine dimesylate (LDX) demonstrated efficacy in terms of reduced binge eating days per week in adults with binge eating disorder (BED) in two randomized clinical trials (RCTs). OBJECTIVE: The objective of this study was to evaluate the cost effectiveness of LDX versus no pharmacotherapy (NPT) in adults with BED from a USA healthcare payer’s perspective. STUDY DESIGN AND METHODS: A decision-analytic Markov cohort model was developed using 1-week cycles and a 52-week time horizon. Markov health states were defined based upon the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria of BED. Model parameter estimates were obtained from RCTs, a survey, and literature. The primary outcome was incremental cost-effectiveness ratio (ICER). The analysis assumed a 12-week course of treatment, based upon RCTs’ treatment duration. One-way deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. RESULTS: Patients on LDX therapy gained 0.006 quality-adjusted life years (QALY) compared to patients on the NPT arm, while the average total cost was US$175 higher for LDX therapy. The estimated ICER for LDX compared with NPT was US$27,618 per QALY, which was shown to be cost effective given a willingness-to-pay threshold of US$50,000. CONCLUSIONS: Treatment of BED with LDX showed increase in QALYs at an acceptable cost and is considered to be cost effective at the commonly used willingness-to-pay threshold in the USA. Based on the available evidence, the current model focused on short-term benefits only. There is a need to generate additional scientific evidence supporting long-term benefits of LDX therapy for BED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40261-016-0381-3) contains supplementary material, which is available to authorized users

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets

During neurogenesis, neural stem/progenitor cells (NPCs) undergo an irreversible fate transition to become neurons. The Notch pathway is important for this process, and repression of Notch-dependent Hes genes is essential for triggering differentiation. However, Notch signaling often remains active throughout neuronal differentiation, implying a change in the transcriptional responsiveness to Notch during the neurogenic transition. We identified Bcl6, an oncogene, as encoding a proneurogenic factor that is required for proper neurogenesis of the mouse cerebral cortex. BCL6 promoted the neurogenic conversion by switching the composition of Notch-dependent transcriptional complexes at the Hes5 promoter. BCL6 triggered exclusion of the co-activator Mastermind-like 1 and recruitment of the NAD+-dependent deacetylase Sirt1, which was required for BCL6-dependent neurogenesis. The resulting epigenetic silencing of Hes5 led to neuronal differentiation despite active Notch signaling. Our findings suggest a role for BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect other aspects of physiology and disease.SCOPUS: ar.jinfo:eu-repo/semantics/publishe