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Mischak H.,University of Glasgow | Ioannidis J.P.,University of Ioannina | Ioannidis J.P.,Stanford University | Argiles A.,RD Nephrologie | And 35 more authors.
European Journal of Clinical Investigation | Year: 2012

While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation. Source

Haibel H.,Charite CBF | Sieper J.,Charite CBF
Clinical and Experimental Rheumatology | Year: 2010

The disease modifying antirheumatic drug (DMARD) methotrexate (MTX) is widely used and well accepted for the treatment of patients with rheumatoid arthritis (RA). In ankylosing spondylitis (AS), the use of MTX is not recommended for the axial manifestations and may have some efficacy in the peripheral involvement. For this disease there is a lack of clinical trials, and most of the trials did not show efficacy on the axial symptoms of the disease. Furthermore, there is no evidence that MTX increases the effects or prevents the side effects of TNF-blockers if given in combination. In this paper the available data of MTX in AS will be discussed. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2010. Source

Salzwedel A.,Charite CBF | Salzwedel A.,Rehabilitation Center for Internal Medicine | Salzwedel A.,University of Potsdam | Wegscheider K.,University of Hamburg | And 7 more authors.
Aging Clinical and Experimental Research | Year: 2015

Methods: The impact of baseline characteristics on the success of CR, measured by MOC, was analysed using a mixed model for 1,220 older patients (70.9 ± 7.0 years, 78.3 % men) who enrolled in 12 CR clinics. A multitude of potentially influential baseline patient characteristics was considered including sociodemographic variables, comorbidity, duration of hospital stay, exercise capacity, cardiovascular risk factors, emotional status, and laboratory and echocardiographic data.Background: Cardiac rehabilitation (CR) seeks to simultaneously improve several outcome parameters related to patient risk factors, exercise capacity and subjective health. A single score, the multiple outcome criterion (MOC), comprised of alterations in 13 outcome variables was used to measure the overall success of CR in an older population. As this success depends on the older patient’s characteristics at the time of admission to CR, we attempted to determine the most important influences.Results: Overall, CR was successful, as indicated by the mean value of the MOC (0.6 ± 0.45; min −1.0, max 2.0; positive values denoting improvement, negative ones deterioration). Examples of association with negative MOC values included smoking (MOC −0.15, p < 0.001), female gender (MOC −0.07, p = 0.049), and a longer hospital stay (MOC −0.03, p = 0.03). An example of association with positive MOC value was depression score (MOC 0.06, p = 0.003). Further associations included maximal exercise capacity, blood pressure, heart rate and the rehabilitation centre attended.Conclusion: Our results emphasize the necessity to take into consideration baseline characteristics when evaluating the success of CR and setting treatment targets for older patients. © 2014, Springer International Publishing Switzerland. Source

Schuster R.,Charite Campus Benjamin Franklin | Bechrakis N.E.,Innsbruck Medical University | Stroux A.,Institute of Medical Informatics Biometry and Clinical Epidemiology | Busse A.,Charite Campus Benjamin Franklin | And 4 more authors.
Oncology | Year: 2011

Objective: Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as a marker for systemic disease and to determine their prognostic relevance. Methods: Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics. Results: CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 groups with distinct prognosis. Conclusion: CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma, including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for progression-free and overall survival. Characterization of CTC could improve the understanding of their biology. © 2011 S. Karger AG, Basel. Source

Schrijvers E.M.C.,Erasmus Medical Center | Schurmann B.,University of Bonn | Koudstaal P.J.,Erasmus Medical Center | Van Den Bussche H.,University of Hamburg | And 19 more authors.
Stroke | Year: 2012

Background and Purpose-: Most studies investigating the genetics of dementia have focused on Alzheimer disease, but little is known about the genetics of vascular dementia. The aim of our study was to identify new loci associated with vascular dementia. Methods-: We performed a genome-wide association study in the Rotterdam Study, a large prospective population-based cohort study in the Netherlands. We sought to replicate genome-wide significant loci in 2 independent replication samples. Results-: In the discovery analysis of 5700 dementia-free individuals, 67 patients developed incident vascular dementia over a mean follow-up time of 9.3±3.2 years. We showed genome-wide significance for rs12007229, which is located on the X chromosome near the androgen receptor gene (OR, 3.7; 95% CI, 2.3-5.8, per copy of the minor allele; P=1.3×10-8). This association was further confirmed in 2 independent populations (probability value of combined replication samples=0.024). Conclusions-: Our study shows a novel genetic locus for vascular dementia on the X chromosome. Further replication of this finding is required. © 2011 American Heart Association, Inc. Source

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