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Support for this research was provided by Regeneron Pharmaceuticals, Tarrytown, New York, and Sanofi US, Bridgewater, New Jersey. Menzin and Lin are employees of Boston Health Economics, which received consulting fees from Sanofi. Friedman is a consultant to Boston Health Economics. Lin, Friedman, and Menzin have received research support from Sanofi US. Sung, Mallya, Panaccio, and Koren are employees of Sanofi US and also have ownership interest in Sanofi US. Sanchez is an employee of and has ownership interest in Regeneron Pharmaceuticals. Neumann has served on advisory boards for Merck & Co, Takeda Pharmaceutical Company, Genentech, Novartis, Bayer AG, UCB, Sanofi US, Robert Wood Johnson Foundation, and Cubist and serves as consultant for Boston Health Economics, Forrest, P urdue, and Smith and Nephew. This research has been presented in part at the International Society for Pharmacoeconomics and Outcomes Research, 20th Annual International Meeting, May 16-20, 2015, Philadelphia, Pennsylvania. All authors contributed to the study design, protocol development, and results interpretation. Lin and Menzin were responsible for conducting the study analyses. All authors were involved in manuscript development and approved the submitted version.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.

BackgroundTo investigate the association between metabolic syndrome, including its factors, and gallstone disease (GSD) in a Taiwanese population.MethodsWe conducted a cross-sectional study during 2011 ~ 2012. A total of 12050 subjects who completed a questionnaire and underwent physical examination, laboratory tests and abdominal ultrasonography formed the study population.ResultsThe prevalences of metabolic syndrome and gallstone disease were 24.09% and 6.16%. In an age- and sex-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease (OR = 1.61; P < 0.0001). Age, abdominal obesity, and lower high-density lipoprotein cholesterol were associated with gallstone disease after adjusting for other factors. Females had a higher odds ratio than males in waist circumference for GSD, whereas males had a lower odds ratio than females in HDL-C for GSD.ConclusionsThe present study suggests that metabolic syndrome is related to gallstone disease. Waist circumference and high-density lipoprotein cholesterol are all associated with GSD. Men and women may possibly have different priorities and strategies to reduce the burden of GSD.

BackgroundLimited data exist on the economic implications of stroke among patients with atrial fibrillation (AF). This study assesses the impact of AF on healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS), or transient ischemic attack (TIA).Methods and ResultsA retrospective analysis of MarketScan claims data (2005‐2011) for AF patients ≥18 years old with ≥1 inpatient claim for stroke, or ≥1 ED or inpatient claim for TIA as identified by ICD‐9‐CM codes who had ≥12 months continuous enrollment prior to initial stroke. Initial event‐ and stroke‐related costs 12 months post‐index were compared among patients with AF and without AF. Adjusted costs were estimated, controlling for demographics, comorbidities, anticoagulant use, and baseline resource use. Data from 23 807 AF patients and 136 649 patients without AF were analyzed. Unadjusted mean cost of the index event was $20 933 for IS, $59 054 for HS, $8616 for TIA hospitalization, and $3395 for TIA ED visit. After controlling for potential confounders, adjusted mean incremental costs (index plus 12‐month post‐index) for AF patients were higher than those for non‐AF patients by: $4726, $7824, and $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and $1700 for TIA (identified by ED) (all P<0.01). In multivariate regression analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in total stroke‐related costs.ConclusionStroke‐related care for IS, HS, and TIA is costly, especially among individuals with AF. Reducing the risk of AF‐related stroke is important from both clinical and economic standpoints.

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The association between the hepatitis C virus (HCV) infection and the risk of myocardial infarction (MI) and stroke has been previously investigated. However, the association between the HCV infection and the risk of venous thromboembolism (VTE) has not been extensively discussed.Using the Longitudinal Health Insurance Database 2000 (LHID2000), we selected 3686 patients with newly diagnosed HCV infection. We randomly selected 14,744 people with no HCV or hepatitis B virus (HBV) infection as comparison group and frequency matched them with patients with HCV infection according to their age, sex, and index year. The incidence density rates and hazard ratios (HRs) of deep vein thrombosis (DVT) and pulmonary embolism (PE) were calculated until the end of 2011.The mean follow-up duration of 5.14 years for the HCV cohort and 5.61 years for the non-HCV cohort, the overall incidence density rates of DVT were 7.92 and 3.51 per 10,000 person-years in the non-HCV group, and the HCV groups, respectively (crude HR = 2.25; 95% confidence interval [CI] = 1.21–4.21). After adjusted for age, sex, and comorbidities, the risk of DVT remained significantly higher in the HCV group than in the non-HCV group (adjusted HR = 1.96; 95% CI = 1.03–3.73). The overall incidence density rates of PE in the HCV and non-HCV groups were not significantly different (crude HR = 2.20; 95% CI = 0.94–5.14).HCV infection is associated with the risk of DVT in a long-term follow-up period.

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