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Sökning: WFRF:(Jakob Franz)

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1.
  • Danchin, Nicolas, et al. (författare)
  • Use, patient selection and outcomes of P2Y12 receptor inhibitor treatment in patients with STEMI based on contemporary European registries
  • Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837. ; 2:3, s. 152-167
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. Methods and results Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registrieswere heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% inhospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-Threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). Conclusions Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-Treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.
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2.
  • Hamidouche, Zahia, et al. (författare)
  • Autocrine Fibroblast Growth Factor 18 Mediates Dexamethasone-Induced Osteogenic Differentiation of Murine Mesenchymal Stem Cells
  • 2010
  • Ingår i: Journal of Cellular Physiology. - : John Wiley and Sons Inc.. - 1097-4652. ; 46:Supplement 1, s. 122-122
  • Tidskriftsartikel (refereegranskat)abstract
    • The potential of mesenchymal stem cells (MSC) to differentiate into functional bone forming cells provides an important tool for bone regeneration. The identification of factors capable of promoting osteoblast differentiation in MSCs is therefore critical to enhance the osteogenic potential of MSCs. Using microarray analysis combined with biochemical and molecular approach, we found that FGF18, a member of the FGF family, is upregulated during osteoblast differentiation induced by dexamethasone in murine MSCs. We showed that overexpression of FGF18 by lentiviral (LV) infection, or treatment of MSCs with recombinant human (rh)FGF18 increased the expression of the osteoblast specific transcription factor Runx2, and enhanced osteoblast phenotypic marker gene expression and in vitro osteogenesis. Molecular silencing using lentiviral shRNA demonstrated that downregulation of FGFR1 or FGFR2 abrogated osteoblast gene expression induced by either LV-FGF18 or rhFGF18, indicating that FGF18 enhances osteoblast differentiation in MSCs via activation of FGFR1 or FGFR2 signaling. Biochemical and pharmacological analyses showed that the induction of phenotypic osteoblast markers by LV-FGF18 is mediated by activation of ERK1/2-MAPKs and PI3K signaling in MSCs. These results reveal that FGF18 is an essential autocrine positive regulator of the osteogenic differentiation program in murine MSCs and indicate that osteogenic differentiation induced by FGF18 in MSCs is triggered by FGFR1/FGFR2-mediated ERK1/2-MAPKs and PI3K signaling. J. Cell. Physiol. 224: 509-515, 2010. (C) 2010 Wiley-Liss, Inc.
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3.
  • Hanschmidt, Franz (författare)
  • Barriers to Alcohol Screening Among Hypertensive Patients and the Role of Stigma : Lessons for the Implementation of Screening and Brief Interventions in European Primary Care Settings
  • 2017
  • Ingår i: Alcohol and Alcoholism. - 0735-0414 .- 1464-3502. ; 52:2, s. 572-579
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims1. To quantify barriers to alcohol screening among hypertensive patients reported by primary healthcare professionals. 2. To examine whether education and screening frequency measures are associated with stigma-related barriers.MethodsA web survey was conducted among 3081 primary healthcare professionals from France, Germany, Italy, Spain and the UK. Participants were asked about perceived barriers to alcohol screening as free-text response. The replies were independently categorized by two raters. Stigma-related barriers were predicted by logistic regressions with education, knowledge on alcohol as risk factor and frequency of alcohol screening.ResultsIn France and Italy, almost half of the reported barriers were stigma-related, whereas time constraints were cited most commonly in Spain and the UK. In Germany, nearly half of respondents rated the importance of alcohol screening for hypertension as low. Perception that regular screening is inappropriate or associated with too much effort, beliefs that screening is unnecessary, and insufficient knowledge of screening tools were cited as further barriers. Professional education on alcohol use was consistently rated to be poorer than the equivalent education on hypertension, and only a minority of respondents perceived alcohol as important risk factor for hypertension. Stigma-related barriers could not be significantly predicted by education, knowledge or screening frequency in most models.ConclusionsOverall, regular alcohol screening among hypertensive patients seems to be widely accepted, but further education (Germany) and structural support (Spain, UK) could contribute to increase screening rates. In France and Italy, screening uptake could be improved by addressing stigma.Short SummaryAlcohol screening among hypertensive patients was largely accepted among general practitioners from five different European countries. Reported screening barriers varied between countries and included time constraints, stigma and underrated importance of alcohol. Results did not indicate a positive impact of education and screening frequency on perception of stigma as barrier to screening.
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4.
  • Karras, Dimitrios, et al. (författare)
  • Effectiveness of Teriparatide in Postmenopausal Women with Osteoporosis and Glucocorticoid Use : 3-Year Results from the EFOS Study
  • 2012
  • Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:3, s. 600-609
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To describe clinical fracture rates, back pain, and health-related quality of life (HROOL) in postmenopausal women with osteoporosis who are receiving glucocorticoids (GC), during a 36-month study of teriparatide treatment for up to 18 months, with an additional 18-month followup period when patients were receiving other osteoporosis medications. Methods. A prospective, multinational, observational study. Data for clinical fractures, back pain (by visual analog scale; VAS) and HRQOL (by EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month segments and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed. Results. Of 1581 enrolled women with followup data, 294 (18.6%) had antecedents of GC use. Of these, 49 (16.7%) patients sustained a total of 69 fractures during the 36-month study period. Adjusted odds of fracture were significantly decreased during the last year of followup compared with the first 6 months of teriparatide treatment: an 81% decrease in the 24 to < 30-month period (p < 0.05), and an 89% decrease in the 30 to < 36-month period (p < 0.05). There were significant reductions in back pain and improvements in HRQOL in both groups of GC users and nonusers. Conclusion. Postmenopausal women with severe osteoporosis receiving GC, who were treated with teriparatide for up to 18 months, showed a reduced incidence of clinical fractures during the third year while receiving sequential osteoporosis treatments compared with the first 6 months, together with reduced back pain and improved HRQOL. Our results should be interpreted in the context of an uncontrolled observational study in a routine clinical setting.
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5.
  • Langdahl, Bente L., et al. (författare)
  • Reduction in fracture rate and back pain and increased quality of life in postmenopausal women treated with teriparatide : 18-month data from the European Forsteo Observational Study (EFOS)
  • 2009
  • Ingår i: Calcified Tissue International. - 0171-967X .- 1432-0827. ; 85:6, s. 484-493
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and health-related quality of life (HRQoL, EQ-5D) were assessed. Spontaneous reports of adverse events were collected. All 1,648 enrolled women were teriparatide treatment-naive, 91.0% of them had previously received other anti-osteoporosis drugs, and 72.8% completed the 18-month study. A total of 168 incident clinical fractures were sustained by 138 (8.8%) women (821 fractures/10,000 patient-years). A 47% decrease in the odds of fracture in the last 6-month period compared to the first 6-month period was observed (P < 0.005). Mean back pain VAS was reduced by 25.8 mm at end point (P < 0.001). Mean change from baseline in EQ-VAS was 13 mm by 18 months. The largest improvements were reported in the EQ-5D subdomains of usual activities and pain/discomfort. There were 365 adverse events spontaneously reported, of which 48.0% were considered related to teriparatide; adverse events were the reason for discontinuation for 79 (5.8%) patients. In conclusion, postmenopausal women with severe osteoporosis who were prescribed teriparatide in standard clinical practice had a significant reduction in the incidence of fragility fractures and a reduction in back pain over an 18-month treatment period. This was associated with a clinically significant improvement in HRQoL. Safety was consistent with current prescribing information. These results should be interpreted in the context of the open-label, noncontrolled design of the study.
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6.
  • Lettino, Maddalena, et al. (författare)
  • Diabetic patients with acute coronary syndromes in contemporary European registries : Characteristics and outcomes
  • Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837. ; 3:4, s. 198-213
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Among patients with acute coronary syndromes (ACS), those with diabetes mellitus (DM) are at particularly high risk of recurrent cardiovascular events and premature death. We aimed to provide a descriptive overview of unadjusted analyses of patient characteristics, ACS management, and outcomes up to 1 year after hospital admission for an ACS/index-ACS event, in patients with DM in contemporary registries in Europe. Methods and results A total of 10 registries provided data in a systematic manner on ACS patients with DM (total n =28 899), and without DM (total n= 97 505). In the DM population, the proportion of patients with ST-Segment Elevation Myocardial Infarction (STEMI) ranged from 22.1% to 64.6% (other patients had non-ST-Segment Elevation Myocardial Infarction (NSTEMI-ACS) or unstable angina). All-cause mortality in the registries ranged from 1.4% to 9.4% in-hospital; 2.8% to 7.9% at 30 days post-discharge; 5.1% to 10.7% at 180 days post-discharge; and 3.3% to 10.5% at 1 year post-discharge. Major bleeding events were reported in up to 3.8% of patients while in hospital (8 registries); up to 1.3% at 30 days (data from two registries only), and 2.0% at 1 year (one registry only). Registries differed substantially in terms of study setting, site, patient selection, definition and schedule of endpoints, and use of various P2Y12 inhibitors. In most, but not all, registries, event rates in DM patients were higher than in patients without DM. Pooled risk ratios comparing cohorts with DM vs. no DM were in-hospital significantly higher in DM for all-cause death (1.66; 95% CI 1.42-1.94), for cardiovascular death (2.33; 1.78 - 3.03), and for major bleeding (1.35; 1.21-1.52). Conclusion These registry data from real-life clinical practice confirm a high risk for recurrent events among DM patients with ACS, with great variation across the different registries.
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7.
  • Ljunggren, Östen, et al. (författare)
  • Effective osteoporosis treatment with teriparatide is associated with enhanced quality of life in postmenopausal women with osteoporosis : the European Forsteo Observational Study
  • 2013
  • Ingår i: BMC Musculoskeletal Disorders. - 1471-2474 .- 1471-2474. ; 14, s. 251-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To describe changes in health-related quality of life (HRQoL) of postmenopausal women with osteoporosis treated with teriparatide for up to 18 months and followed-up for a further 18 months, and to assess the influence of recent prior and incident fractures. Methods: The European Forsteo Observational Study (EFOS) is an observational, prospective, multinational study measuring HRQoL using the EQ-5D. The primary objective was to assess changes in HRQoL during 36 months in the whole study population. A secondary post-hoc analysis examined fracture impact on HRQoL in four subgroups classified based on recent prior fracture 12 months before baseline and incident clinical fractures during the study. Changes from baseline were analysed using a repeated measures model. Results: Of the 1581 patients, 48.4% had a recent prior fracture and 15.6% of these patients had an incident fracture during follow-up. 10.9% of the 816 patients with no recent prior fracture had an incident fracture. Baseline mean EQ-VAS scores were similar across the subgroups. In the total study cohort (n = 1581), HRQoL (EQ-VAS and EQ-5D index scores) improved significantly from baseline to 18 months and this improvement was maintained over the 18-month post-teriparatide period. Improvements were seen across all five EQ-5D domains during teriparatide treatment that were maintained after teriparatide was discontinued. Subjects with incident clinical fractures had significantly less improvement in EQ-VAS than those without incident fractures. Recent prior fracture did not influence the change in EQ-VAS during treatment. Conclusions: EFOS is the first longitudinal study in women with severe postmenopausal osteoporosis in the real world setting to show a substantial improvement in HRQoL during teriparatide treatment that was sustained during subsequent treatment with other medications. The increase in HRQoL was lower in the subgroups with incident fracture but was not influenced by recent prior fracture. The results should be interpreted in the context of the design of an observational study.
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8.
  • Rajzbaum, Gerald, et al. (författare)
  • Characterization of patients in the European Forsteo Observational Study (EFOS) : postmenopausal women entering teriparatide treatment in a community setting
  • 2008
  • Ingår i: Current Medical Research and Opinion. - 0300-7995 .- 1473-4877. ; 24:2, s. 377-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The European Forsteo* Observational Study (EFOS) study was primarily designed to assess fracture incidence, degree of pain, health-related quality of life (HRQoL) and compliance in women prescribed teriparatide in a community setting. This report describes the design of the study and characteristics of the patients at entry. Methods: At entry, 1645 postmenopausal women with a diagnosis of osteoporosis and about to initiate teriparatide treatment were enrolled in eight European countries. Baseline data were collected on demographic characteristics, medical and osteoporosis history, disease status, prior use of medications and HRQoL. Results: The mean (standard deviation [SD]) age of patients was 71.5 (8.4) years, lumbar spine bone mineral density (BMD) Tscore was –3.3 (1.2), the mean number of previous fractures reported after 40 years of age was 2.9 (2.0), 70% had two or more vertebral deformities and 91.7% were pre-treated with bisphosphonates. HRQoL, evaluated by the health state value (HSV) (median: 0.59, Q1; Q3: 0.08; 0.71) and visual analogue scale (VAS) (median 50.0, Q1; Q3: 35.0; 69.0) status of the European quality of life questionnaire (EQ5D) was poor. Extreme problems were reported by 31% of patients for the pain/discomfort dimension, mobility was limited in 69% and anxiety/depression was reported by 57% of patients. Chronic or intermittent back pain was reported by 91% of patients, which occurred every day or almost every day within the last month in 66% of patients. Conclusions: The post-menopausal women prescribed teriparatide were severely osteoporotic, with a high fracture risk and poor HRQoL, despite previous therapy for osteoporosis. Moderate to severe back pain was very common.
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9.
  • Walsh, J. Bernard, et al. (författare)
  • Effectiveness of Teriparatide in Women Over 75 Years of Age with Severe Osteoporosis : 36-Month Results from the European Forsteo Observational Study (EFOS)
  • 2012
  • Ingår i: Calcified Tissue International. - 0171-967X .- 1432-0827. ; 90:5, s. 373-383
  • Tidskriftsartikel (refereegranskat)abstract
    • This predefined analysis of the European Forsteo Observational Study (EFOS) aimed to describe clinical fracture incidence, back pain, and health-related quality of life (HRQoL) during 18 months of teriparatide treatment and 18 months post-teriparatide in the subgroup of 589 postmenopausal women with osteoporosis aged a parts per thousand yen75 years. Data on clinical fractures, back pain (visual analogue scale, VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. A repeated-measures model analyzed changes from baseline in back pain VAS and EQ-VAS. During the 36-month observation period, 87 (14.8 %) women aged a parts per thousand yen75 years sustained a total of 111 new fractures: 37 (33.3 %) vertebral fractures and 74 (66.7 %) nonvertebral fractures. Adjusted odds of fracture was decreased by 80 % in the 30 to < 36-month interval compared with the first 6-month interval (P < 0.009). Although the older subgroup had higher back pain scores and poorer HRQoL at baseline than the younger subgroup, both age groups showed significant reductions in back pain and improvements in HRQoL postbaseline. In conclusion, women aged a parts per thousand yen75 years with severe postmenopausal osteoporosis treated with teriparatide in normal clinical practice showed a reduced clinical fracture incidence by 30 months compared with baseline. An improvement in HRQoL and, possibly, an early and significant reduction in back pain were also observed, which lasted for at least 18 months after teriparatide discontinuation when patients were taking other osteoporosis medication. The results should be interpreted in the context of an uncontrolled observational study.
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10.
  • Zeymer, Uwe, et al. (författare)
  • P2Y12 receptor inhibitors in patients with non-STelevation acute coronary syndrome in the real world : Use, patient selection, and outcomes from contemporary European registries
  • Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837. ; 2:4, s. 229-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Non-ST-elevation acute coronary syndrome (NSTE-ACS) is present in about 60-70% of patients admitted with acute coronary syndromes in clinical practice. This study provides a 'real-life' overview of NSTE-ACS patient characteristics, dual antiplatelet therapy clinical practice, and outcomes at both the time of discharge from hospital and up to 1-year post-discharge. Methods and results A total of 10 registries (documenting 84 054 NSTE-ACS patients) provided data in a systematic manner on patient characteristics and outcomes for NSTE-ACS in general, and 6 of these (with 52 173 NSTE-ACS patients) also provided more specific data according to P2Y12 receptor inhibitor used. Unadjusted analyses were performed at the study level, and no formal meta-Analysis was performed due to large heterogeneity between studies in the settings, patient characteristics, and outcome definitions. All-cause death rates across registries ranged from 0.76 to 4.79% in-hospital, from 1.61 to 6.65% at 30 days, from 3.66 to 7.16% at 180 days, and from 3.14 to 9.73% at 1 year. Major bleeding events were reported in up to 2.77% of patients while in hospital (in seven registries), up to 1.08% at 30 days (data from one registry only), and 2.06% at 1 year (one registry). Conclusions There were substantial differences in the use of and patient selection for clopidogrel, prasugrel, and ticagrelor, which were associated with differences in short-And long-Term ischaemic and bleeding events. In future registries, data collection should be performed in a more standardized way with respect to endpoints, definitions, and time points.
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