A Zink

German Rheumatism Research Centre, Berlín, Berlin, Germany

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Publications (154)560.09 Total impact

  • A Strangfeld, A Zink
    Deutsche medizinische Wochenschrift (1946). 09/2014; 139(37):1817-20.
  • Zeitschrift fur Rheumatologie. 08/2014;
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    ABSTRACT: Our initiative aimed to produce recommendations on post-randomised controlled trial (RCT) trial extension studies (TES) reporting using European League Against Rheumatism (EULAR) standard operating procedures in order to achieve more meaningful output and standardisation of reports. We formed a task force of 22 participants comprising RCT experts, clinical epidemiologists and patient representatives. A two-stage Delphi survey was conducted to discuss the domains of evaluation of a TES and definitions. A '0-10' agreement scale assessed each domain and definition. The resulting set of recommendations was further refined and a final vote taken for task force acceptance. Seven key domains and individual components were evaluated and led to agreed recommendations including definition of a TES (100% agreement), minimal data necessary (100% agreement), method of data analysis (agreement mean (SD) scores ranging between 7.9 (0.84) and 9.0 (2.16)) and reporting of results as well as ethical issues. Key recommendations included reporting of absolute numbers at each stage from the RCT to TES with reasons given for drop-out at each stage, and inclusion of a flowchart detailing change in numbers at each stage and focus (mean (SD) agreement 9.9 (0.36)). A final vote accepted the set of recommendations. This EULAR task force provides recommendations for implementation in future TES to ensure a standardised approach to reporting. Use of this document should provide the rheumatology community with a more accurate and meaningful output from future TES, enabling better understanding and more confident application in clinical practice towards improving patient outcomes.
    Annals of the rheumatic diseases 05/2014; · 8.11 Impact Factor
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    ABSTRACT: This meta-analysis investigates the efficacy of tumour necrosis factor α (TNFα) blockers versus placebo for the treatment of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). A systematic literature search was conducted independently by two reviewers. Double-blind randomised controlled trials (RCTs) investigating the efficacy of adalimumab, certolizumab, etanercept, golimumab or infliximab in approved dosages in comparison with placebo were included. The use of concomitant non-steroidal antirheumatic drugs was allowed. The outcome parameters were improvement in disease activity and function measured by the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI) and ASAS40 response. The effect sizes of the changes in BASDAI/BASFI between TNFα blocker and placebo comparator groups were calculated. Mixed effect models were applied separately for RCTs with AS and nr-axSpA patients and differences between those groups were evaluated in a joint model. 20 studies with data from 3096 patients were included in the analysis: 15 studies with AS patients, four with nr-axSpA patients and one with both. For AS patients, TNFα blockers showed better efficacy than placebo for BASDAI (effect size 1.00), BASFI (effect size 0.67) and ASAS40 response (OR 4.7). For nr-axSpA patients, the differences were smaller (effect sizes 0.73, 0.57; OR 3.6). However, after adjustment for the year of publication as a proxy for disease severity, no differences in the effect sizes between the AS and nr-axSpA trials were observed. Compared with placebo, TNFα blockers improve disease activity and functional capacity clinically meaningful for both AS and nr-axSpA patients.
    Annals of the rheumatic diseases 04/2014; · 8.11 Impact Factor
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    ABSTRACT: Objectives: To compare the approved treatment of rheumatoid arthritis using rituximab + methotrexate (RTX+MTX) versus the off-label treatment variants of RTX in monotherapy or RTX in combination with leflunomide (RTX+LEF).Methods: We included RTX-naive patients enrolled in the German biologics register RABBIT between 2007 and 2012 (N=907) who started treatment with RTX. Three treatment regimens RTX+MTX, RTX+LEF and RTX monotherapy were analyzed regarding therapy discontinuation, drop-out, RTX re-treatment and concomitant glucocorticoid therapy. Effectiveness was evaluated with linear mixed models.Results: Baseline patient characteristics were similar across treatment regimens except for a poorer functional status and more comorbidities in RTX monotherapy. Average doses of glucocorticoids were lower in RTX+LEF compared to the two other groups. The frequency and timing of RTX re-treatment (p>0.62) as well as the improvement in DAS28 over time (p>0.15) were similar in all treatment regimens. Within the first 12 months of treatment the DAS28 decreased by 1.5 units, between month 12 and 36 by further 0.4 units equally in all groups. Nevertheless, therapy discontinuation and drop-out were significantly increased on RTX monotherapy (HR 1.7 [1.2;2.3]), additionally when patients were rheumatoid factor (RF) negative (HR 1.5 [1.0;2.1]).Conclusion:In patients who continue therapy, RTX+LEF, RTX monotherapy and RTX+MTX seem to be equally effective. However, given the lower adherence rates on monotherapy, this treatment option is not sufficient for all patients. Since many patients are intolerant to MTX, more licensed RTX treatment options are needed. © 2014 American College of Rheumatology.
    Arthritis Care & Research. 03/2014;
  • A Zink
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    ABSTRACT: Health services research in rheumatology investigates the healthcare needs, the quality of care and trends in healthcare for patients with musculoskeletal disorders. Using rheumatoid arthritis (RA) as an example, key results of health services research during the last 25 years are summarized. There are currently approximately 540,000 persons with RA in Germany of which some two thirds are regularly seen by rheumatologists. The data from the national database of the German collaborative arthritis centres show that patients are now seen earlier and to a greater extent. The intensity of drug treatment with synthetic or biological disease-modifying antirheumatic drugs (DMARDs) has increased continuously. At the same time, the mean disease activity (DAS28) has decreased from 4.7 to 3.3 and approximately 50 % of patients treated early achieve remission. Physician-rated disease severity has considerably improved and fewer patients suffer from erosive disease. This corresponds with improvements in functional capacity and work participation. Health services research impressively shows the advances in rheumatological care. Further improvements at the population level are limited by the low numbers of rheumatologists in outpatient care.
    Zeitschrift für Rheumatologie 02/2014; · 0.45 Impact Factor
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    ABSTRACT: To estimate the changes in direct and indirect costs induced by patients with rheumatoid arthritis (RA) in German rheumatology, between 2002 and 2011. To examine the impact of functional status on various cost domains. To compare the direct costs incurred by patients at working age (18-64 years) to patients at an age of retirement (≥65 years). We analysed data from the National Database of the German Collaborative Arthritis Centres with about 3400 patients each year. Costs were calculated using fixed prices as well as annually updated cost factors. Indirect costs were calculated using the human capital as well as the friction cost approaches. There was a considerable increase in direct costs: from €4914 to €8206 in patients aged 18-64, and from €4100 to €6221 in those aged ≥65, attributable to increasing prescription of biologic agents (18-64 years from 5.6% to 31.2%, ≥65 years from 2.8% to 19.2%). This was accompanied by decreasing inpatient treatment expenses and indirect costs due to sick leave and work disability. The total growth of cost, on average, was €2437-2981 for patients at working age, and €2121 for patients at retirement age. The increase in treatment costs for RA over the last decade was associated with lower hospitalisation rates, better functional status and a lower incidence of work disability, offsetting a large proportion of risen drug costs. Since the rise in drug costs has manifested a plateau from 2009 onwards, no relevant further increase in total costs for patients with RA treated in German rheumatology is expected.
    Annals of the rheumatic diseases 01/2014; · 8.11 Impact Factor
  • J. Wollenhaupt, A. Zink
    Zeitschrift für Rheumatologie 01/2014; 73(3). · 0.45 Impact Factor
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    ABSTRACT: To investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival. Data of the German biologics register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking. During 31 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28 > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids > 5 mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor α (TNFα) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97). Patients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.
    Annals of the rheumatic diseases 11/2013; · 8.11 Impact Factor
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    ABSTRACT: Objective. Using meta-analysis methods, this study aimed to estimate the impact of biologic agents on physical function in patients with RA.Methods. A systematic literature search was conducted independently by two investigators. Double-blind randomized controlled trials (RCTs) investigating the efficacy of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab or rituximab in approved dosages in comparison with treatment with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) and placebo were included. The outcome parameter was improvement in function measured by the standardized mean difference (SMD) of HAQ scores. The SMD is the difference of the change in HAQ between biologic and DMARD comparator groups divided by the pooled standard deviation. Mixed effect models were applied separately for RCTs with DMARD-naive patients and those with DMARD inadequate responders (IRs).Results. Thirty-five RCTs were included in the analysis, 10 with DMARD-naive patients and 25 with DMARD IRs. Overall, biologics led to a greater improvement of physical function than nbDMARDs, with an SMD of the HAQ of 0.44 (95% CI 0.38, 0.50). The improvement was greater for DMARD IRs (SMD 0.48, 95% CI 0.41, 0.56) than for DMARD-naïve patients (SMD 0.32, 95% CI 0.23, 0.41). There were no significant differences between individual biologics in both groups.Conclusion. Treatment with biologics led to a clinically relevant greater improvement in physical function than treatment with nbDMARDs. Our results suggest that the improvement found on the group level was caused by a clinically relevant improvement on the patient level in more than 50% of the patients.
    Rheumatology (Oxford, England) 08/2013; · 4.24 Impact Factor
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    ABSTRACT: OBJECTIVE: To evaluate the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score for serious infections in patients with rheumatoid arthritis (RA). METHODS: The RABBIT Risk Score for serious infections was developed in 2011 on a cohort of RA patients enrolled in the German biologics register RABBIT between 2001 and 2007. To evaluate this score, we used data from patients enrolled in RABBIT after 1 January 2009. Expected numbers of serious infections and expected numbers of patients with at least one serious infection per year were calculated by means of the RABBIT Risk Score and compared with observed numbers in the evaluation sample. RESULTS: The evaluation of the score in an independent cohort of 1522 RA patients treated with tumour necrosis factor α (TNFα) inhibitors and 1468 patients treated with non-biological disease-modifying antirheumatic drugs (DMARDs) showed excellent agreement between observed and expected rates of serious infections. For patients exposed to TNF inhibitors, expected as well as observed numbers of serious infections were 3.0 per 100 patient-years (PY). For patients on non-biological DMARDs the expected and observed numbers were 1.5/100 PY and 1.8/100 PY, respectively. The score was highly predictive in groups of patients with low as well as with high infection risk. CONCLUSIONS: The RABBIT Risk Score is a reliable instrument which determines the risk of serious infection in individual patients based on clinical and treatment information. It helps the rheumatologist to balance benefits and risks of treatment, to avoid high-risk treatment combinations and thus to make informed clinical decisions.
    Annals of the rheumatic diseases 06/2013; · 8.11 Impact Factor
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    ABSTRACT: OBJECTIVES: This study aims to assess the prevalence of comorbidities in adult JIA and the impact of comorbidity on patients' perceived health state. METHODS: Self-reported comorbidity was studied in 344 adult JIA patients who have been included in the biologic register JuMBO. The comorbidity prevalence among the patients was compared to an age- and sex-matched reference group from the population. The correlation of comorbidity with clinical and demographic parameters was analysed by linear or logistic regression models. RESULTS: Sixty two percent of the JIA patients reported at least one comorbidity. Uveitis was the most common comorbid condition (17.7%), followed by allergic rhinitis (14.5%), migraine (8.7%), and atopic dermatitis (8.7%). The prevalence of cardiovascular disorders was 9.9%, which was not higher than that in the population. However, patients with a systemic onset of JIA (soJIA) had a substantially higher rate of cardiovascular diseases of 40.6% (p=0.033). Patients with soJIA also had the highest prevalence (80.0%) and the highest mean number (1.8) of comorbidities. Patients with at least one comorbid condition suffered more often from fatigue and pain, had a lower functional capacity (p<0.001, each), and a lower physical and mental health-related quality of life than those without comorbidities (p<0.001 and p=0.017, respectively). The presence of any comorbidity and the level of disease activity were independent predictors of a lower SF-36 score. CONCLUSIONS: Our results indicate that comorbid conditions have a significant impact on the perceived health state in adult JIA. Among all JIA patients, those with systemic onset carry the highest risk for comorbidities, in particular for cardiovascular disorders.
    Clinical and experimental rheumatology 04/2013; · 2.66 Impact Factor
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    ABSTRACT: In recent years the treatment of juvenile idiopathic arthritis (JIA) has changed dramatically. Nowadays one out of three children with polyarticular JIA is treated with a biologic drug; however, knowledge about the long-term safety of biologics is still limited. Information on drug safety is collected in the JIA biologic register (BiKeR) and the follow-up register juvenile arthritis methotrexate/biologics long-term observation (JuMBO). The latter currently includes information on more than 700 young adults most of whom were treated with etanercept and prospectively followed for more than 5 years. Preliminary data on the long-term safety of etanercept for JIA are therefore available. Over an observation period of 1,800 etanercept exposure-years, events of particular interest, such as malignancies, serious infections and new onset immune-mediated diseases have been recorded which occurred at rates of 0.1, 1.1 and 0.9/100 patient-years, respectively. Overall, new safety risks were not detected during long-term etanercept exposure. Moreover, JuMBO has also provided information on the long-term outcome of JIA and initial evidence suggests that JIA outcome, especially in functional aspects has improved in the biologic era. Data from BiKeR and JuMBO contribute to the risk-benefit assessment of biologic drugs which have been implemented in the routine treatment of JIA.
    Zeitschrift für Rheumatologie 03/2013; · 0.45 Impact Factor
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    ABSTRACT: The aim of this report was to propose a definition for erosive disease in the context of inflammatory arthritis in light of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) criteria for use in clinical practice and studies. A EULAR task force was formed including 16 rheumatologists and one rheumatology fellow. The process was both evidence based and consensus based, and included, between March 2010 and April 2012, analyses of data from two cohorts, two face-to-face meetings, one online voting and one teleconference. The Leiden Early Arthritis Cohort and the French ESPOIR cohort were used for the evidence-based part. The outcome measures, which were initiation of methotrexate therapy, or any disease-modifying antirheumatic drug therapy within the first year of disease and arthritis persistency over 5 years, were studied with the aim to give the best definition of erosive disease. A decision was made to select a definition with a high specificity and focus on patients who did not otherwise fulfil the 2010 ACR/EULAR RA criteria (<6 points). By a unanimous vote the following definition was selected: erosive disease for use in the 2010 ACR/EULAR RA classification criteria is defined when an erosion (defined as a cortical break) is seen in at least three separate joints at any of the following sites: the proximal interphalangeal, the metacarpophalangeal, the wrist (counted as one joint) and the metatarsophalangeal joints on radiographs of both hands and feet. A highly specific definition for erosive disease has thus been formulated.
    Annals of the rheumatic diseases 02/2013; · 8.11 Impact Factor
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    ABSTRACT: OBJECTIVES: The aim of this study is to compare clinical features and treatment of young onset rheumatoid arthritis with late-onset rheumatoid arthritis. METHODS: Nine thousand five hundred forty-one patients with rheumatoid arthritis (RA) enrolled in the national database of the German Collaborative Arthritis Centres in 2007-2009 were stratified by age at disease onset: up to 65 years (YORA), >65 years (LORA). To enable unbiased comparisons between the two groups despite their systematic differences in age and disease duration, we performed two separate matched-pairs analyses: the impact of current age was assessed by matching YORA and LORA patients for disease duration and sex (n=1,550 pairs). To identify the influence of disease duration, a second sample matched for age and sex (n=1,158 pairs) was drawn. RESULTS: At identical age, YORA patients had higher disease activity (DAS28), worse functional capacity and were less frequently in remission when compared with LORA patients. YORA patients also suffered more frequently from RA-related co-morbidities such as cardiovascular disease, chronic renal disease and osteoporosis. Matched for disease duration, there were no differences between the two groups concerning disease severity and remission rates, global health or pain intensity. Independent of age or disease duration, YORA patients reported more sleep disorders and fatigue. LORA patients received significantly fewer synthetic or biologic DMARDs than YORA patients. CONCLUSIONS: Duration of RA, rather than age, explains differences in disease burden between YORA and LORA patients. The lower prescription rates of synthetic and in particular biologic DMARDs, despite lower remission rates, indicate a potential treatment deficit in older patients.
    Clinical and experimental rheumatology 01/2013; · 2.66 Impact Factor
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    ABSTRACT: Die Therapie der juvenilen idiopathischen Arthritis (JIA) hat sich in den letzten Jahren gravierend geändert. Mittlerweile erhält hierzulande jedes dritte Kind mit polyartikulärer JIA ein Biologikum. Die Kenntnisse zur Langzeitsicherheit der Biologika sind noch begrenzt. Informationen hierzu werden mit dem JIA-Biologikaregister BiKeR und dessen Follow-up-Register JuMBO (Juvenile Arthritis Methotrexat/Biologics long-term observation) erhoben. Letzteres umfasst derzeit über 700 junge Erwachsene. Die meisten wurden mit Etanercept behandelt und über mehr als 5 Jahre beobachtet. Erste Rückschlüsse auf die Langzeitsicherheit einer Etanercept-Therapie bei der JIA können deshalb gezogen werden. Über einen Beobachtungszeitraum von 1800 Expositionsjahren wurden Malignome, schwere Infektionen und inzidente immunvermittelte Erkrankungen mit Raten von 0,1, 1,1 bzw. 0,9/100 Patientenjahre erfasst. Neue Sicherheitsrisiken bei längerer Etanercept-Exposition wurden nicht aufgedeckt. Zusätzlich werden mit JuMBO Informationen zum Langzeitoutcome der Patienten gewonnen. Diese belegen eine Verbesserung der Langzeitprognose der JIA vor allem im funktionellen Bereich. Daten des BiKeR/JuMBO-Registers tragen zur Risiko-Nutzen-Bewertung der bei der JIA eingesetzten Biologika bei.
    Zeitschrift für Rheumatologie 01/2013; 72(4). · 0.45 Impact Factor
  • A Zink
    Zeitschrift für Rheumatologie 12/2012; · 0.45 Impact Factor
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    ABSTRACT: RA is known to be associated with an increased risk of serious infection. Even more than 50 years ago, observational studies showed a greater than 2-fold increased risk of serious infection in RA. This was reinforced by various subsequent cohort studies. The elevated susceptibility of patients with RA can be explained by the pathobiology of the disease itself, the impact of chronic comorbid conditions, as well as sequelae of immunosuppressive treatment. It has been suggested that premature ageing of the immune system in RA contributes to weakened protection against infectious organisms. In addition, chronic comorbid conditions such as diabetes or chronic lung or kidney disease, disease-related functional disability, as well as lifestyle factors such as smoking, increase the risk in individual patients. For a long time glucocorticoids (GCs) have been used as potent immunosuppressive drugs in RA. There is evidence that they increase the risk of serious infections up to 4-fold in a dose-dependent manner. TNF-α inhibitors increase the serious infection risk up to 2-fold. They have, however, the potential to outweigh their risk when higher GC doses can be tapered down. If patients need higher dosages of GCs in addition to treatment with biologic agents, their risk of infection is substantial. This combination should be used carefully and, if possible, avoided in patients with additional risk factors such as older age or comorbid conditions.
    Rheumatology (Oxford, England) 11/2012; · 4.24 Impact Factor
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    ABSTRACT: OBJECTIVE: To compare the performance of the preliminary American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria with the 28-joint count Disease Activity Score (DAS28) remission in unselected 'real-life' patients. METHODS: Remission was calculated according to the DAS28 and to both versions of the ACR/EULAR criteria (Boolean or Simplified Disease Activity Index (SDAI)-based) for 6864 patients with rheumatoid arthritis (RA) who were enrolled in the national database of the German Collaborative Arthritis Centres between 2007 and 2009. Logistic regression analyses identified factors that were responsible for patients in DAS28 remission to miss the new criteria. In addition, the functional status of patients who fulfilled the different remission criteria was compared with that of an age- and sex-matched population sample. RESULTS: Of all patients, 28% were in DAS28, 7% in Boolean and 11% in SDAI remission. Of those in DAS28 remission, 21.0% were also in Boolean and 34% also in SDAI remission. Higher scores for pain and fatigue, the presence of degenerative spine disease, longer disease duration and male gender were significantly associated with missing the new criteria despite being in DAS28 remission. Compared with age- and sex-matched samples from the general population, patients in DAS28 remission had a similar functional ability while patients in remission according to the new criteria had better functional scores. CONCLUSIONS: Patients fulfilling the new remission criteria tend to be not only free from active RA, but also from other disabling diseases. If these criteria are applied in clinical practice to guide treatment decisions, the impact of comorbidity should be taken into account.
    Annals of the rheumatic diseases 08/2012; · 8.11 Impact Factor
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    ABSTRACT: The introduction of biologics has continuously increased the demand for biomarkers for early diagnosis and therapeutic stratification. ArthroMark, a research network funded by the Federal Ministry of Education and Research, aims to establish such biomarkers for rheumatoid arthritis and spondyloarthritides. Biobanks and previous work on genotyping, gene expression and autoreactivity profiling build the basis. Bioinformatic networks will help to harmonize the investigations and a clinical study with modern imaging techniques to characterize the functional relevance of the new biomarkers as effectively as possible. To validate the markers for diagnostic application the network aims to expand gradually.
    Zeitschrift für Rheumatologie 05/2012; 71(4):314-8. · 0.45 Impact Factor

Publication Stats

4k Citations
560.09 Total Impact Points

Institutions

  • 1997–2014
    • German Rheumatism Research Centre
      Berlín, Berlin, Germany
  • 2010–2013
    • Charité Universitätsmedizin Berlin
      • Medical Department, Division of Rheumatology and Clinical Immunology
      Berlín, Berlin, Germany
    • University of Alabama at Birmingham
      • Division of Clinical Immunology and Rheumatology
      Birmingham, AL, United States
  • 2011
    • University of Applied Sciences Fulda
      Fulda, Hesse, Germany
  • 2005–2008
    • Martin Luther University of Halle-Wittenberg
      • Institut für Rehabilitationsmedizin
      Halle, Saxony-Anhalt, Germany
    • InForMed GmbH
      Ingolstadt, Bavaria, Germany
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2002–2003
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1996
    • Deutsches Herzzentrum Berlin
      Berlín, Berlin, Germany