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Soota K.,Unity Health System | Maliakkal B.,University of Rochester
World Journal of Gastroenterology | Year: 2014

Hepatitis C virus (HCV) is not usually cleared by our immune system, leading to the development of chronic hepatitis C infection. Chronic HCV induces the production of various cytokines, predominantly by Kupffer cells (KCs), and creates a pro-inflammatory state in the liver. The chronic dysregulated production of interferon (IFN) and other cytokines by KCs also promotes innate immune tolerance. Ribavirin (RBV) monotherapy has been shown to decrease inflammation in liver of patients with chronic hepatitis C. Sustained virological response (SVR) is significantly higher when IFN is combined with RBV in chronic HCV (cHCV) infection. However, the mechanism of their synergy remains unclear. Previous theories have attempted to explain the anti-HCV effect based on direct action of RBV alone on the virus or on the immune system; however, these theories have serious shortcomings. We propose that hemolysis, which universally occurs with RBV therapy and which is considered a limiting side effect, is precisely the mechanism by which the anti-HCV effect is exerted. Passive hemolysis results in anti-inflammatory/antiviral actions within the liver that disrupt the innate immune tolerance, leading to the synergy of RBV with IFN-α. Ribavirin-induced hemolysis floods the hepatocytes and KCs with heme, which is metabolized and detoxified by heme oxygenase-1 (HMOX1) to carbon monoxide (CO), biliverdin and free iron (which induces ferritin). These metabolites of heme possess anti-inflammatory and antioxidant properties. Thus, HMOX1 plays an extremely important anti-oxidant, anti-inflammatory and cytoprotective role, particularly in KCs and hepatocytes. HMOX1 has been noted to have anti-viral effects in hepatitis C infected cell lines. Additionally, it has been shown to enhance the response to IFN-α by restoring interferon-stimulated genes (ISGs). This mechanism can be clinically corroborated by the following observations that have been found in patients undergoing RBV/IFN combination therapy for cHCV: (1) SVR rates are higher in patients who develop anemia; (2) once anemia (due to hemolysis) occurs, the SVR rate does not depend on the treatment utilized to manage anemia; and (3) ribavirin analogs, such as taribavirin and levovirin, which increase intrahepatic ribavirin levels and which produce lesser hemolysis, are inferior to ribavirin for treating cHCV. This mechanism can also explain the observed RBV synergy with direct antiviral agents. This hypothesis is testable and may lead to newer and safer medications for treating cHCV infection. © 2014 Baishideng Publishing Group Inc. Source

Rao S.V.,Duke Clinical Research Institute | Hess C.N.,Duke Clinical Research Institute | Barham B.,Duke Clinical Research Institute | Aberle L.H.,Duke Clinical Research Institute | And 17 more authors.
JACC: Cardiovascular Interventions | Year: 2014

Objectives This study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial. Background Women are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear. Methods Women undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population. Results The trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access. Conclusions In this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236) © 2014 by the American College of Cardiology Foundation. Source

Vogl S.M.,Unity Health System
CONTINUUM Lifelong Learning in Neurology | Year: 2011

Outcome management, performance improvement, evidence-based practice, and policy payment mechanisms are critical operational drivers at every level of health care delivery. It is essential that all health care providers involved in patient care have a working knowledge of health care operations, including the policies and reimbursement mechanisms that drive their particular clinical practice. Providing excellent patient care includes understanding health care policies, regulations, and outcomes that have a historical and current impact on health care delivery. Some of these factors include patient access, patient safety, and information measurement and management. Inpatient acute neurorehabilitation programs have standard outcome measures and a unique set of fiscal rules and regulations. This article discusses the most common variables and terms found in program evaluation systems for acute neurorehabilitation programs as well as some of the clinical and regulatory requirements and reimbursement and level-of-care considerations that are critical for neurorehabilitation health care practitioners. The current health care environment requires providers to understand and continually evaluate quality outcomes, patient access, and patient safety, all within the confines of an efficacy-based care delivery system. Copyright © 2011, American Academy of Neurology. All rights reserved. Source

Manchanda A.,Intermountain Valley View Heart Clinic | Aggarwal A.,Unity Health System | Aggarwal N.,Geisinger Medical Center | Soran O.,University of Pittsburgh
Cardiology Journal | Year: 2011

Despite significant advances in revascularization techniques and medical therapy, there remains a significant population of patients who continue to have intractable angina symptoms. This review aims to define the patients with refractory angina pectoris (RAP) and to present the therapeutic options currently available for this condition. RAP itself is defined and the pharmacological treatment options other than traditional medical therapies are discussed. The latest therapeutic options for this patient population are extensively reviewed. Among the multitude of pharmacological and non-invasive therapeutic options for patients with RAP, ranolazine is a new drug indicated for the treatment of chronic angina, in combination with amlodipine, beta-blockers or nitrates. Enhanced external coun-terpulsation has not only been shown to improve symptoms, but also to improve long-term ventricular function in these patients. In randomized trials, neurostimulation has been shown to be effective in reducing angina symptoms. Transmyocardial laser revascularization has emerged as an invasive treatment for RAP over the last two decades. Extracorporeal shockwave myocardial revascularization gene therapy and percutaneous in situ coronary venous arteria-lization are still under investigation. © 2011 Via Medica. Source

Tantillo M.,Unity Health System | Sanftner J.L.,Slippery Rock University
Journal of Nursing Measurement | Year: 2010

This article describes the development and psychometric testing of the Connection-Disconnection Scale (CDS), the only self-report measure designed to assess perceived mutuality experienced in close relationships by women with eating disorders. Item development was informed by relational-cultural theory and focus groups with patients and recovered individuals. Content and construct validity, test-retest reliability, and internal consistency were examined in samples of female outpatient (n = 131) and partial hospitalization (n = 85) patients. Factor analysis with promax rotation for each version of the CDS in outpatients resulted in a single-factor model explaining 77.53% of the variance for CDS-Mother, 71.86% for CDS-Father, 77.79% for CDS-Partner, and 67.67% for CDS-Friend. Cronbach's alphas ranged from .97 to.99 for both samples. Overall, the CDS demonstrated good discriminant and convergent validity with moderate to strong correlations between CDS parent forms and the Parental Attachment Questionnaire, Dyadic Adjustment Scale, and the Social Support Questionnaire. Regression equations revealed that scores on CDS parent forms were inversely related to several subscale scores on the Eating Disorders Inventory-2. The CDS is a reliable and valid measure of perceived mutuality that can enrich relational understanding of the etiology and treatment of eating disorders in women. © 2010 Springer Publishing Company. Source

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