Institute for Clinical Research and Statistics

Köln, Germany

Institute for Clinical Research and Statistics

Köln, Germany

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Mauss S.,Center for and Hepatogastroenterology | Boker K.,Center for Hepatology | Buggisch P.,Ifi Institute for Interdisciplinary Medicine | Christensen S.,The Interdisciplinary Center | And 4 more authors.
Zeitschrift fur Gastroenterologie | Year: 2015

Background and Aims: The efficacy and safety of peginterferon alfa-2a (PEG-IFN) plus ribavirin (RBV) and either boceprevir (BOC) or telaprevir (TVR), and physician adherence to treatment algorithms were evaluated in patients included in an ongoing non-interventional study (PAN) enrolling adults with chronic hepatitis C virus (HCV) infection managed in German office-based practices. Methods: The analysis included HCV genotype 1-infected, treatment-naïve and treatment-experienced patients treated with BOC or TVR. Demographic, treatment history, virological response, safety, and patient management data were collected. Results: Of a total 1087 patients, 58.1 achieved sustained virological responses (SVR). Response rates were higher in treatment-naïve (BOC 55%; TVR 63.4%) and prior relapse patients (BOC 63.2%; TVR 74.5%) versus previous null-responders (BOC 14.3%; TVR 25%). The most commonly reported adverse event overall was fatigue (60.6%); 45.8 patients experienced hemoglobin <10g/dL. Patients with cirrhosis had lower rates of SVR versus those without (42.9 vs. 60.7%, respectively), and had a higher incidence of serious adverse events (SAEs) (16.7 vs. 8.6%, respectively) and treatment discontinuation (44.6 vs. 25.2%, respectively). According to recommended response-guided treatment algorithms, about 70 of patients were managed appropriately, 11/10 (BOC/TVR) received unnecessarily extended therapy, and 19/7 (BOC/TVR) received inappropriately shortened therapy. Conclusions: The efficacy and safety of BOC- and TVR-based triple therapy in this large, real-world cohort were largely comparable to that reported in pivotal clinical trials, although SVR rates were lower overall. Recommended futility or treatment extension rules were violated in a substantial proportion of patients with potential implications for response, adverse events and costs. © Georg Thieme Verlag KG Stuttgart.


Hofmann W.P.,Practice of Gastroenterology | Mauss S.,Center for and Hepatogastroenterology | Lutz T.,Infektiologikum | Schober A.,Practice of Hepatology | And 7 more authors.
PLoS ONE | Year: 2015

Background and Aims: Individualization of treatment with peginterferon alfa and ribavirin in patients with chronic hepatitis C showed benefit in controlled trials and was implemented in treatment guidelines to increase response rates and to reduce side effects and costs. However, it is unknown whether individualization was adopted in routine daily practice and whether it translated into improved outcomes. Methods: From a large noninterventional cohort study, clinical and virologic response data of 10,262 HCV patients who received peginterferon alfa-2a and ribavirin between 2003-2007 and 2008-2011 were analyzed. To account for treatment individualization, a matched-pair analysis (2,997 matched pairs) was performed. Variation in treatment duration and dosing of ribavirin were analyzed as indicators for individualization. Results: Sustained virological response (SVR) rates were similar between 2003-2007 and 2008-2011 (62.0% vs. 63.7%). Patients with comorbidities were more abundant in the later period, (44.3% vs. 57.1%). The subsequent matched-pair analysis demonstrated higher SVR rates in the 2008-2011 period (64.3%) than in the 2003-2007 period (61.2%, p=0.008). More patients received abbreviated or extended treatment regimens in the later than the earlier period as an indicator of treatment individualization. To the same end, ribavirin doses were higher in the later period (12.6 versus 11.6 mg/kg/day). Factors independently associated with SVR included HCV genotype, low baseline viral load, younger age, route of infection, absence of concomitant diseases, lower APRI score, normal gamma-GT, higher ribavirin doses, no substitution for drug abuse, treatment duration, and treatment in the 2008-2011 period. Conclusions: Treatment individualization with peginterferon alfa and ribavirin was implemented in daily routine between 2003-2007 and 2008-2011, SVR rates improved in the same period. These findings may be most relevant in resource-limited settings. © 2015 Hofmann et al.


PubMed | Center for and Hepatogastroenterology, Charité - Medical University of Berlin, Infektiologikum, Hoffmann-La Roche and 4 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Individualization of treatment with peginterferon alfa and ribavirin in patients with chronic hepatitis C showed benefit in controlled trials and was implemented in treatment guidelines to increase response rates and to reduce side effects and costs. However, it is unknown whether individualization was adopted in routine daily practice and whether it translated into improved outcomes.From a large noninterventional cohort study, clinical and virologic response data of 10,262 HCV patients who received peginterferon alfa-2a and ribavirin between 2003-2007 and 2008-2011 were analyzed. To account for treatment individualization, a matched-pair analysis (2,997 matched pairs) was performed. Variation in treatment duration and dosing of ribavirin were analyzed as indicators for individualization.Sustained virological response (SVR) rates were similar between 2003-2007 and 2008-2011 (62.0% vs. 63.7%). Patients with comorbidities were more abundant in the later period, (44.3% vs. 57.1%). The subsequent matched-pair analysis demonstrated higher SVR rates in the 2008-2011 period (64.3%) than in the 2003-2007 period (61.2%, p=0.008). More patients received abbreviated or extended treatment regimens in the later than the earlier period as an indicator of treatment individualization. To the same end, ribavirin doses were higher in the later period (12.6 versus 11.6 mg/kg/day). Factors independently associated with SVR included HCV genotype, low baseline viral load, younger age, route of infection, absence of concomitant diseases, lower APRI score, normal gamma-GT, higher ribavirin doses, no substitution for drug abuse, treatment duration, and treatment in the 2008-2011 period.Treatment individualization with peginterferon alfa and ribavirin was implemented in daily routine between 2003-2007 and 2008-2011, SVR rates improved in the same period. These findings may be most relevant in resource-limited settings.


Turan R.G.,University of Rostock | Bozdag-Turan I.,University of Rostock | Ortak J.,University of Rostock | Akin I.,University of Rostock | And 13 more authors.
Stem Cells and Development | Year: 2011

Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45 + and CD133/45 + CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45 + and CD133/45 + BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45 + and CD133/45 + BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45 + and CD133/45 + BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD. © Copyright 2011, Mary Ann Liebert, Inc.


Turan R.G.,University of Rostock | Bozdag-T I.,University of Rostock | Ortak J.,University of Rostock | Kische S.,University of Rostock | And 13 more authors.
Stem Cell Reviews and Reports | Year: 2011

Objectives: There is growing evidence that intracoronary autologous bone marrow cells transplantation (BMCs-Tx) in patients with chronic myocardial infarction beneficially affects postinfarction remodelling. In this randomized controlled study we analyzed the influence of intracoronary autologous freshly isolated bone marrow cells transplantation by use of point of care system on cardiac function and on the functional activity of bone marrow derived circulating progenitor cells (BM-CPCs) in patients with ischemic heart disease (IHD). Methods: 56 patients with IHD were randomized to either received freshly isolated BMC-Tx or a control group that did not receive cell therapy. The functional activity of BM-CPCs in peripheral blood (PB) was measured by migration assay and colony forming unit assay pre- and 3, 6 as well as 12 months after procedure. Global ejection fraction (EF) and infarct size area were determined by left ventriculography. Results: Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size and an increase of global EF as well as infarct wall movement velocity after 3 and 12 months follow-up compared to control group. The colony-forming capacity of BM-CPCs significantly increased 3, 6 and 12 months after cell therapy compared to pre BMCs-Tx and control group (CFU-E: p<0.001, CFU-GM: p<0.001). Likewise, we found significant increase of migratory response to stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) after cell therapy compared to pre BMCs-Tx (SDF-1: p<0.001, VEGF: p<0.001) and to control (SDF-1: p<0.001, VEGF: p<0.001). There was no significant difference of migratory- and colony forming capacity between pre- and 3, 6, 12 months after coronary angiography in control group without cell therapy. Conclusions: Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system may lead to improvement of BM-CPCs functional activity in peripheral blood, which might increase the regenerative potency in patients with IHD. © 2010 The Author(s).


Turan R.G.,University of Rostock | Bozdag-T. I.,University of Rostock | Turan C.H.,University of Rostock | Ortak J.,University of Rostock | And 16 more authors.
Journal of Cellular and Molecular Medicine | Year: 2012

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45+- and CD133/45+-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45+ and CD133/45+ BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45+: P < 0.001, CD133/45+: P < 0.001). Moreover, this significant mobilization of BMCPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45+ and CD133/45+ BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45+ and CD133/45+ BM-CPCs in PB and this might increase the regenerative potency after AMI. © 2011 Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


Goekmen Turan R.,University of Rostock | Hakan Turan C.,University of Rostock | Bozdag-Turan I.,University of Rostock | Ortak J.,University of Rostock | And 15 more authors.
Circulation Journal | Year: 2011

Background: The influence of the number of diseased coronary arteries on the mobilization of CD133/45 +bone marrow-derived circulating progenitor cells (BM-CPCs) in peripheral blood (PB) in patients with ischemic heart disease (IHD) was analyzed. Methods and Results: Mobilization of CD133/45 +BM-CPCs by flow cytometry was measured in 120 patients with coronary 1 vessel (IHD1, n=40), coronary 2 vessel (IHD2, n=40), and coronary 3 vessel disease (IHD3, n=40), and in a control group (n=40). The mobilization of CD133/45 +BM-CPCs was significantly reduced in patients with IHD compared to the control group (P<0.001). The mobilization of CD133/45 +BM-CPCs was impaired in patients with IHD3 compared to IHD1 (P<0.001) and to IHD2 (P<0.001). But there was no significant difference in mobilization of CD133/45 +BM-CPCs between the patients with IHD2 and IHD1 (P=0.35). Moreover, we found significantly reduced CD133/45 +cell mobilization in patients with a high SYNTAX-Score (SS) compared to a low SS (P<0.001) and an intermediate SS (P<0.001). In subgroup analyzes, we observed a significantly negative correlation between levels of hemoglobin A 1cand the mobilization of CD133/45 +BM-CPCs (P=0.001, r=-0.6). Conclusions: The mobilization of CD133/45 +BM-CPCs in PB is impaired in patients with IHD. This impairment might augment with increased number of diseased coronary arteries. Moreover, mobilization of CD133/45 +BM-CPCs in ischemic tissue is further impaired by diabetes in patients with IHD.


Bozdag-Turan I.,University of Rostock | Turan R.G.,University of Rostock | Turan C.H.,University of Rostock | Ludovicy S.,University of Rostock | And 14 more authors.
Cardiovascular Diabetology | Year: 2011

Background: Bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with coronary heart disease are impaired with respect to number and mobilization. However, it is unknown whether the mobilization of BM-CPCs depends on the number of diseased coronary arteries. Therefore, in our study, we analysed the correlation between the diseased coronary arteries and the frequency of CD34/45+ BM-CPCs in peripheral blood (PB) in patients with ischemic heart disease (IHD).Methods: The frequency of CD34/45+BM-CPCs was measured by flow cytometry in 120 patients with coronary 1 vessel (IHD1, n = 40), coronary 2 vessel (IHD2, n = 40), coronary 3 vessel disease (IHD3, n = 40) and in a control group of healthy subjects (n = 40). There was no significant difference of the total number of cardiovascular risk factors between IHD groups, beside diabetes mellitus (DM), which was significantly higher in IHD3 group compared to IHD2 and IHD1 groups.Results: The frequency of CD34/45+BM-CPCs was significantly reduced in patients with IHD compared to the control group (CD34/45+; p < 0.001). The frequency of BM-CPCs was impaired in patients with IHD3 compared to IHD1 (CD34/45+; p < 0.001) and to IHD2 (CD34/45+; p = 0.001). But there was no significant difference in frequency of BM-CPCs between the patients with IHD2 and IHD1 (CD34/45+; p = 0.28). In a subgroup we observed a significant negative correlation between levels of hemoglobin AIc (HbAIc) and the frequency of BM-CPCs (CD34/45+; p < 0.001, r = -0.8).Conclusions: The frequency of CD34/45+BM-CPCs in PB is impaired in patients with IHD. This impairment may augment with an increased number of diseased coronary arteries. Moreover, the frequency of CD34/45+BM-CPCs in ischemic tissue is further impaired by diabetes in patients with IHD. © 2011 Bozdag-Turan et al; licensee BioMed Central Ltd.


Bozdag-Turan I.,University of Rostock | Goekmen Turan R.,University of Rostock | Ludovicy S.,University of Rostock | Akin I.,University of Rostock | And 13 more authors.
BMC Research Notes | Year: 2012

Background: Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. In this study we analyzed whether intracoronary autologous freshly isolated BMCs-Tx have beneficial effects on cardiac function in patients with ischemic heart disease (IHD). Results: In this prospective nonrandomized study we treated 12 patients with IHD by freshly isolated BMCs-Tx by use of point of care system and compared them with a representative 12 control group without cell therapy. Global ejection fraction (EF) and infarct size area were determined by left ventriculography. Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size (p<0.001) and an increase of global EF (p=0.003) as well as infarct wall movement velocity (p<0.001) after 6months follow-up compared to control group. In control group there were no significant differences of global EF, infarct size and infarct wall movement velocity between baseline and 6months after coronary angiography. Furthermore, we found significant decrease in New York Heart Association (NYHA) as well as significant decrease of B-type natriuretic peptide (BNP) level 6months after intracoronary cell therapy (p<0.001), whereas there were no significant differences in control group 6months after coronary angiography. Conclusions: These results demonstrate that intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system is safe and may lead to improvement of cardiac function in patients with IHD. Trial registration. Registration number: ISRCTN54510226. © 2012 Bozdag-Turan et al.; licensee BioMed Central Ltd.


Turan R.G.,University of Rostock | Bozdag-Turan I.,University of Rostock | Ortak J.,University of Rostock | Akin I.,University of Rostock | And 10 more authors.
Circulation Journal | Year: 2011

Background: We analyzed in the present study the influence of intracoronary autologous freshly isolated bone marrow cells transplantation (BMCs-Tx) on cardiac function in patients with acute myocardial infarction (AMI). Methods and Results: The 32 patients with AMI were enrolled in this prospective nonrandomized study to either freshly isolated BMC-Tx or to a control group without cell therapy. Global left ventricular ejection fraction (LVEF) and the size of infarct area were determined by left ventriculography. We observed in patients with autologous freshly isolated BMCs-Tx at 6 months follow up a significant reduction of infarct size as compared to control group. Moreover, we found a significant increase of LVEF as well as infarct wall movement velocity at 6 months follow up in cell therapy group as compared to control group. In the control group there was no significant difference of LVEF, infarct size and infarct wall movement velocity between baseline and 6 months after AMI. Conclusions: These results demonstrate for the first time that intracoronary transplantation of autologous freshly isolated BMCs by use of a point of care system is safe, and may lead to improvement of cardiac function in patients with AMI.

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