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Hannesdottir L.,Innsbruck Medical University | Tymoszuk P.,Innsbruck Medical University | Parajuli N.,Innsbruck Medical University | Wasmer M.-H.,Innsbruck Medical University | And 12 more authors.
European Journal of Immunology | Year: 2013

The dual erbB1/2 tyrosine kinase inhibitor lapatinib as well as the anthracycline doxorubicin are both used in the therapy of HER2-positive breast cancer. Using MMTV-neu mice as an animal model for HER2-positive breast cancer, we observed enhanced tumor infiltration by IFN-γ-secreting T cells after treatment with doxorubicin and/or lapatinib. Antibody depletion experiments revealed a contribution of CD8+ but not CD4+ T cells to the antitumor effect of these drugs. Doxorubicin treatment additionally decreased the content of immunosuppressive tumor-associated macrophages (TAMs) in the tumor bed. In contrast, Stat1-deficient mice were resistant to tumor growth inhibition by lapatinib and/or doxorubicin and exhibited impaired T-cell activation and reduced T-cell infiltration of the tumor in response to drug treatment. Furthermore, Stat1-deficiency resulted in reduced expression of the T-cell chemotactic factors CXCL9, CXCL10, and CXCL11 in the tumor epithelium. The inhibition of TAM infiltration of the tumor by doxorubicin and the immunosuppressive function of TAMs were found to be Stat1 independent. Taken together, the results point to an important contribution toward enhancing T-cell and IFN-γ-based immunity by lapatinib as well as doxorubicin and emphasize the role of Stat1 in building an effective antitumor immune response. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Nuijten M.J.C.,Ars Accessus Medica | Aultman R.,Roche Holding AG | Carpeo J.D.C.,Hospital Universitario La Paz | Vergnengre A.,Hpital du Cluzeau | And 3 more authors.
Current Medical Research and Opinion | Year: 2011

Objective: There are two new treatment options available for the treatment of adenocarcinoma histology non-small cell lung cancer (NSCLC) which offer improved benefit in terms of progression-free (PFS) and overall survival (OS) over chemotherapy. Both bevacizumab and pemetrexed when combined with chemotherapy significantly increase PFS and OS in patients with advanced NSCLC versus chemotherapy alone. The aim of this analysis was to compare the efficacy for patients with non-squamous adenocarcinoma NSCLC treated with bevacizumab, carboplatin and paclitaxel (BCP) to pemetrexed and cisplatin (PC) by using indirect comparison (ITC) methodology. Experimental design: In the absence of head-to-head trials, ITC was performed on patients with adenocarcinoma histology non-squamous NSCLC to compare the relative benefit of first-line therapies BCP vs. PC by hazard ratios (HR). Subsequently, these HRs were used in a decision-analytic Markov model with a lifelong time horizon to extrapolate the long-term effectiveness of the two treatments. Results: ITC estimated HRs for the primary endpoints in the bevacizumab study E4599 showed that BCP treatment in non-squamous adenocarcinoma NSCLC patients resulted in a BCP HR of 0.82 versus PC. The long-term predictions from the Markov model yielded a mean survival of 1.48 years (95% CI 1.34, 1.62 years) (or 17.7 months) for BCP compared with 1.29 years (95% CI 1.16, 1.42 years) (or 15.4 months) for PC. Conclusions: Based on our decision analysis, triplet BCP targeted therapy in patients with advanced non-squamous adenocarcinoma NSCLC compared with doublet PC chemotherapy results in improved expected values for overall long-term survival. Therefore, from the efficacy perspective, bevacizumab in combination with platinum-based chemotherapy can be considered as the targeted therapy of choice for patients with advanced non-squamous adenocarcinoma NSCLC. © 2011 Informa UK Ltd. Source


Luce B.R.,United Biosource Corporation | Luce B.R.,University of Washington | Drummond M.F.,University of York | Dubois R.W.,National Pharmaceutical Council | And 6 more authors.
Journal of Comparative Effectiveness Research | Year: 2012

Aims: To develop principles for planning and conducting comparative effectiveness research (CER). Methods: Beginning with a modified existing list of health technology assessment principles, we developed a set of CER principles using literature review, engagement of multiple experts and broad stakeholder feedback. Results & conclusion: Thirteen principles and actions to fulfill their intent are proposed. Principles include clarity of objectives, transparency, engagement of stakeholders, consideration of relevant perspectives, use of relevant comparators, and evaluation of relevant outcomes and treatment heterogeneity. Should these principles be found appropriate and useful, CER studies should be audited for adherence to them and monitored for their impact on care management, patient relevant outcomes and clinical guidelines. © 2012 Future Medicine Ltd. Source


Ammenwerth E.,UMIT University for Health Sciences, Medical Informatics and Technology | Schnell-Inderst P.,UMIT University for Health Sciences, Medical Informatics and Technology | Schnell-Inderst P.,Oncotyrol Center for Personalized Cancer Medicine | Hoerbst A.,UMIT University for Health Sciences, Medical Informatics and Technology
Journal of Medical Internet Research | Year: 2012

Background: Modern information technology is changing and provides new challenges to health care. The emergence of the Internet and the electronic health record (EHR) has brought new opportunities for patients to play a more active role in his/her care. Although in many countries patients have the right to access their clinical information, access to clinical records electronically is not common. Patient portals consist of provider-tethered applications that allow patients to electronically access health information that are documented and managed by a health care institution. Although patient portals are already being implemented, it is still unclear in which ways these technologies can influence patient care. Objective: To systematically review the available evidence on the impact of electronic patient portals on patient care. Methods: A systematic search was conducted using PubMed and other sources to identify controlled experimental or quasi-experimental studies on the impact of patient portals that were published between 1990 and 2011. A total of 1,306 references from all the publication hits were screened, and 13 papers were retrieved for full text analysis. Results: We identified 5 papers presenting 4 distinct studies. There were no statistically significant changes between intervention and control group in the 2 randomized controlled trials investigating the effect of patient portals on health outcomes. Significant changes in the patient portal group, compared to a control group, could be observed for the following parameters: quicker decrease in office visit rates and slower increase in telephone contacts; increase in number of messages sent; changes of the medication regimen; and better adherence to treatment. Conclusions: The number of available controlled studies with regard to patient portals is low. Even when patient portals are often discussed as a way to empower patients and improve quality of care, there is insufficient evidence to support this assumption. Source


Deuffic-Burban S.,University of Lille Nord de France | Deltenre P.,Service des Maladies de lAppareil Digestif et de la Nutrition | Buti M.,CIBER ISCIII | Parkes J.,University of Southampton | And 10 more authors.
Gastroenterology | Year: 2012

BACKGROUND & AIMS: The dynamics of hepatitis C virus (HCV) infection, as well as screening practices and access to therapy, vary among European countries. It is important to determine the magnitude of the effects of such differences on incidence and mortality of infection. We compared the dynamics of infection and screening and treatment practices among Belgium, France, Germany, Italy, Spain, and the United Kingdom. We also assessed the effects of treatment with pegylated interferon and additional effects of triple therapy with protease inhibitors. METHODS: We created a country-specific Markov model of HCV progression based on published epidemiologic data (on HCV prevalence, screening, genotype, alcohol consumption among patients, and treatments) and reports of competitive and hepatocellular carcinoma mortality for the 6 countries. The model was used to predict the incidence of HCV-related cirrhosis and its mortality until 2021 for each country. RESULTS: From 2002 to 2011, antiviral therapy reduced the cumulative incidence of cirrhosis by 7.1% and deaths by 3.4% overall. Reductions in incidence and mortality values ranged from 4.0% and 1.9%, respectively, in Italy to 16.3% and 9.0%, respectively, in France. From 2012 to 2021, antiviral treatment of patients with HCV genotype 1 infection that includes protease inhibitor-based triple therapy will reduce the cumulative incidence of cirrhosis by 17.7% and mortality by 9.7% overall. The smallest reduction is predicted for Italy (incidence reduced by 10.1% and mortality by 5.4%) and the highest is for France (reductions of 34.3% and 20.7%, respectively). CONCLUSIONS: Although HCV infection is treated with the same therapies in different countries, the effects of the therapies on morbidity and mortality vary significantly. In addition to common guidelines that are based on virologic response-guided therapy, there is a need for public health policies based on population-guided therapy. © 2012 AGA Institute. Source

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