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Siller-Matula J.M.,Medical University of Vienna | Jilma B.,Medical University of Vienna | Schror K.,Heinrich Heine University Dusseldorf | Christ G.,Kaiser Franz Joseph Hospital | Huber K.,Wilhelminenhospital
Journal of Thrombosis and Haemostasis | Year: 2010

To investigate whether proton pump inhibitors (PPIs) negatively affect clinical outcome in patients treated with clopidogrel. Systematic review and meta-analysis. Outcomes evaluated were combined major adverse cardiac events (MACE), myocardial infarction (MI), stent thrombosis, death and gastrointestinal bleeding. Studies included were randomized trials or post-hoc analyzes of randomized trials and observational studies reporting adjusted effect estimates. Twenty five studies met the selection criteria and included 159-138 patients. Administration of PPIs together with clopidogrel corresponded to a 29% increased risk of combined major cardiovascular events [risk ratio (RR)-=-1.29, 95% confidence intervals (CI)-=-1.15-1.45] and a 31% increased risk of MI (RR-=-1.31, 95%CI-=-1.12-1.53). In contrast, PPI use did not negatively influence the mortality (RR-=-1.04, 95%CI-=-0.93-1.16), whereas the risk of developing a gastrointestinal bleed under PPI treatment decreased by 50% (RR-=-0.50, 95% CI-=-0.37-0.69). The presence of significant heterogeneity might indicate that the evidence is biased, confounded or inconsistent. The sensitivity analysis, however, yielded that the direction of the effect remained unchanged irrespective of the publication type, study quality, study size or risk of developing an event. Two studies indicate that PPIs have a negative effect irrespective of clopidogrel exposure. In conclusion, concomitant PPI use might be associated with an increased risk of cardiovascular events but does not influence the risk of death. Prospective randomized trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel treated patients as the PPI-clopidogrel drug-drug interaction does not seem to be a class effect. © 2010 International Society on Thrombosis and Haemostasis.

Resl M.,Medical University of Vienna | Neuhold S.,Medical University of Vienna | Riedl M.,Medical University of Vienna | Abrahamian H.,Karl Landsteiner Institute for Nephrology and Diabetes | And 6 more authors.
European Journal of Cardiovascular Prevention and Rehabilitation | Year: 2011

NT-proBNP is an excellent predictor of adverse events in patients with diabetes mellitus. Due to an aging population it is of interest to determine whether NT-proBNP can predict cardiac events with equal precision in subgroups with different ages. 1395 outpatients with diabetes mellitus were recruited for this prospective observational study. NT-proBNP, renal function, lipid status and other demographic variables were measured at baseline. The cohort was divided into three groups: Group I (609 patients under 60 years of age), group II (634 patients ranging from 60-75) and group III (152 patients older than 75). Patients were followed during a mean observation period of 11 months, 75 patients reached the defined endpoint, which was unplanned hospitalization due to a cardiac event. Mean age was 60±30 years, mean HbA 1c was 7.6% and mean NT-proBNP was 242±437 pg/ml. In a multiple Cox regression model, age (hazard ratio (HR) 11.18, p<0.01) and the absence of a cardiac disease (HR 0.49, p<0.01) were important variables for short-term prognosis. The addition of the logarithm of NT-proBNP provided independent prognostic information (HR 1.81 p<0.01) and significantly increased the explained variance of the model (χ 2=22.93; d.f.=1; p<0.01). More importantly, the predictive power of this model was similar in different age-groups. The prognostic information of NT-proBNP was not influenced by age and this biomarker remained a reliable predictor of short-term cardiac events in patients with diabetes mellitus aged 75 years or older. © The European Society of Cardiology 2011.

Angelini C.,University of Padua | Grisold W.,Kaiser Franz Joseph Hospital | Nigro V.,Telethon Institute of Genetics and Medicine
Acta Myologica | Year: 2011

We investigated the clinical and molecular pattern of two young men affected by dysferlinopathy, that was first diagnosed as polymyositis. We show that their symptoms and clinical course although progressive were peculiar, as well as their biopsy suggesting a subsequent analysis of dysferlin protein by western blotting. Molecular analysis of dysferlin gene revealed pathogenetic mutations in both cases. In such cases a screening with Western blot followed by DNA analysis of dysferlin gene is therefore recommended. We present a diagnostic algorythm for patients with suspected myositis but presenting signs of disease progression and poor response to steroids.

Siller-Matula J.M.,Medical University of Vienna | Huber K.,Cardiology and Emergency Medicine | Christ G.,Kaiser Franz Joseph Hospital | Schror K.,Heinrich Heine University Dusseldorf | And 3 more authors.
Heart | Year: 2011

Context: Enhanced platelet inhibition by clopidogrel decreases the risk of ischemic events but carries a risk for a concomitant increase in bleeding. Objectives: To compare the efficacy and safety of two clopidogrel loading regimens (300mg vs. 600mg) in patients undergoing percutaneous coronary intervention (PCI) at one month after start of therapy. Data sources: A systematic literature search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases using predefined search terms for relevant articles in any language. Study selection and data extraction: Randomised controlled trials and non-randomised studies reporting adjusted effect estimates were included. Summary estimates of the risks ratios (RRs) with therapy were calculated using a random-effect model. Outcomes evaluated were combined major adverse cardiovascular events (MACE) and major bleedings. Results: Seven studies met the inclusion criteria and included 25,383 patients. A 600mg clopidogrel loading was associated with a 34% relative risk reduction of MACE (RR=0.66; 95% confidence intervals CI=0.52-0.84; p<0.001). Sub-analysis revealed a 47% risk reduction of MACE in randomised trials (RR=0.53; 95% CI=0.32-0.88; p=0.01) and a 31% relative risk reduction in non-randomised trials (RR=0.69; 95%CI=0.54-0.90; p=0.005) in patients receiving 600mg loading with clopidogrel. In patients suffering from acute coronary syndrome, 600mg clopidogrel loading was associated with a 24% relative risk reduction in MACE (RR=0.76; 95%CI=0.60-0.95; p=0.02). Importantly, the 600mg clopidogrel loading dose was not associated with an increased risk of major bleedings (RR=0.91; 95% CI=0.73-1.15; p=0.44). Conclusions: This meta-analysis demonstrates that intensified clopidogrel loading with 600mg reduces the rate of major cardiovascular events without increase in major bleeding compared to 300mg in patients undergoing PCI during one month follow-up.

Koekkoek J.A.F.,VU University Amsterdam | Koekkoek J.A.F.,Medical Center Haaglanden | Dirven L.,VU University Amsterdam | Reijneveld J.C.,VU University Amsterdam | And 16 more authors.
Journal of Neuro-Oncology | Year: 2014

Exploring cross-national differences is useful to evaluate whether different patterns of end of life (EOL) care meet patient’s specific needs. This study aimed to (1) compare EOL care processes for high-grade glioma (HGG) patients in three European countries, (2) explore differences in perceived quality of care (QOC), and (3) identify aspects of good QOC in the EOL phase. We analyzed 207 questionnaires from relatives of deceased HGG patients, using a similar retrospective study design in three countries [The Netherlands (n = 83), Austria (n = 72) and the UK (n = 52)], and examined four subthemes: (1) organization of EOL care, (2) treatment preferences, (3) experiences with EOL care, (4) perceived QOC. Three months before death 75 % of patients were at home. In all countries, on average, 50 % were transferred to a hospital at least once and received effective symptom treatment during the last 3 months. In The Netherlands, Austria and UK, respectively, patients most often died at home (60 %), in a hospital (41 %) or hospice (41 %) (p < 0.001). Advance directives were present in 46 % of Dutch, 36 % of British and 6 % of Austrian patients (p < 0.001). Fifty-three percent of patients experienced good QOC, irrespective of country. Dying at the preferred place, satisfaction with information provided and effective symptom treatment were independently associated with good QOC. There are various cross-national differences in organization and experiences with EOL care for HGG, but patient’s perceived QOC is similar in the three countries. As symptom treatment was considered effective in only half of HGG patients, and independently predicted good QOC, this particularly needs further improvement in all countries. © Springer Science+Business Media New York 2014.

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