Between 2002 and 2007, the nonmedical use of prescription pain relievers grew from 11.0 million to 12.5 million people in the United States. Societal costs attributable to prescription opioid abuse were estimated at $55.7 billion in 2007. The purpose of this study was to comprehensively review the recent clinical and economic evaluations of prescription opioid abuse. A comprehensive literature search was conducted for studies published from 2002 to 2012. Articles were included if they were original research studies in English that reported the clinical and economic burden associated with prescription opioid abuse. A total of 23 studies (183 unique citations identified, 54 articles subjected to full text review) were included in this review and analysis. Findings from the review demonstrated that rates of opioid overdose-related deaths ranged from 5528 deaths in 2002 to 14,800 in 2008. Furthermore, overdose reportedly results in 830,652 years of potential life lost before age 65. Opioid abusers were generally more likely to utilize medical services, such as emergency department, physician outpatient visits, and inpatient hospital stays, relative to non-abusers. When compared to a matched control group (non-abusers), mean annual excess health care costs for opioid abusers with private insurance ranged from $14,054 to $20,546. Similarly, the mean annual excess health care costs for opioid abusers with Medicaid ranged from $5874 to $15,183. The issue of opioid abuse has significant clinical and economic consequences for patients, health care providers, commercial and government payers, and society as a whole.

Previous studies from our laboratory have indicated that overexpression of the epidermal growth factor receptor pathway substrate 8 (EPS8) enhances cell proliferation, migration and tumorigenicity in vivo, although the mechanisms involved remain unexplored. A microarray screen to search for potential mediators of EPS8 identified upregulation of multiple cell cycle-related targets such as the transcription factor FOXM1 and several of its reported downstream mediators, including cdc20, cyclin B1, cyclin A, aurora-B kinase and cdc25C in cells with elevated EPS8, as well as matrix metalloproteinase-9, which we reported previously to be upregulated by EPS8-dependent mechanisms. Cells engineered to overexpress FOXM1 showed increased proliferation, similar to EPS8-overexpressing cells. Conversely, targeted knockdown of FOXM1 in EPS8-overexpressing cells reduced proliferation. Cotransfection of EPS8 with a FOXM1-luciferase reporter plasmid into 293-T- or SVpgC2a-immortalized buccal keratinocytes demonstrated that EPS8 enhances FOXM1 promoter activity, whereas chromatin immunoprecipitation assays revealed elevated levels of acetylated histone H3 associated with the FOXM1 promoter in cells expressing high levels of EPS8. Treatment of EPS8-overexpressing cells with inhibitors of phosphoinositide 3-OH kinase or AKT reduced expression of FOXM1 and aurora-B kinase, a transcriptional target of FOXM1. Overexpression of EPS8 induced expression of the chemokine ligands CXCL5 and CXCL12 in a FOXM1-dependent manner, which was blocked by LY294002 or a dominant-negative form of AKT. Additionally, overexpression of FOXM1 enhanced cell migration, whereas targeted knockdown of CXCL5 or inhibition of AKT reduced migration of EPS8-expressing cells. These data suggest that EPS8 enhances cell proliferation and migration in part by deregulating FOXM1 activity and inducing CXC-chemokine expression, mediated by PI3K- and AKT-dependent mechanisms.

Background: The study provides real-world data on the impact of Huntington’s disease (HD) from the perspective of individuals with HD (IHD) and care partners (HD-CP) and contextualizes these results relative to Parkinson’s disease (PD) and the general population (GP). Methods: Cross-sectional survey of IHD and HD-CP in the US (July 2019–August 2019) conducted using the Rare Patient Voice panel. Data for individuals with Parkinson’s Disease (IPD), the general population (GP), and respective care partners (PD-CP; GP-CP) came from the 2018 US National Health and Wellness Survey. Outcomes included demographics, mental health, clinical characteristics, and health-related quality of life (HRQoL). Results: IHD had greater comorbid anxiety (IHD = 51.2%, IPD = 28.8%, GP = 2.0%), and HD-CP had greater comorbid anxiety (HD-CP = 52.5%, PD-CP = 28.6%, GP-CP = 19.6%) and depression (HD-CP = 65.0%, PD-CP = 29.9%, GP-CP = 19.6%), relative to other cohorts (p < 0.05). Respective of their GP cohorts, IHD exhibited lower HRQoL (EQ-5D: 0.66 ± 0.21 vs. 0.81 ± 0.17) and greater depression (PHQ-9: 11.59 ± 7.20 vs. 5.85 ± 6.71), whereas HD-CP exhibited greater depression only (PHQ-9: 6.84 ± 6.38 vs. 4.15 ± 5.58) (p < 0.001). No differences were observed between HD/HD-CP and PD/PD-CP cohorts on PHQ-9 or HRQoL. Conclusions: HD has a significant burden on patients and care partners, which is higher than GP. Notably, anxiety and depression were greater among HD vs. PD, despite similar HRQoL.

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No funding supported this study. The authors reported no potential conflicts of interest. Kale, Patel, and Carroll were responsible for study concept and design. Data analysis was conducted by Kale, assisted by Patel. The manuscript was written primarily by Kale, with assistance from Carroll. Some findings from this study were presented during the poster presentation at the Academy of Managed Care Pharmacy Nexus held in National Harbor, Maryland, on October 4, 2016.