@article{MuehlbergUmstaetterDomhanetal.2020,
  author    = {M{\"u}hlberg, Eric and Umst{\"a}tter, Florian and Domhan, Cornelius and Hertlein, Tobias and Ohlsen, Knut and Krause, Andreas and Kleist, Christian and Beijer, Barbro and Zimmermann, Stefan and Haberkorn, Uwe and Mier, Walter and Uhl, Philipp},
  title     = {Vancomycin-lipopeptide conjugates with high antimicrobial activity on vancomycin-resistant enterococci},
  series = {Pharmaceuticals},
  volume    = {13},
  journal   = {Pharmaceuticals},
  number    = {6},
  issn      = {1424-8247},
  doi       = {10.3390/ph13060110},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205879},
  year      = {2020},
  abstract  = {Multidrug-resistant bacteria represent one of the most important health care problems worldwide. While there are numerous drugs available for standard therapy, there are only a few compounds capable of serving as a last resort for severe infections. Therefore, approaches to control multidrug-resistant bacteria must be implemented. Here, a strategy of reactivating the established glycopeptide antibiotic vancomycin by structural modification with polycationic peptides and subsequent fatty acid conjugation to overcome the resistance of multidrug-resistant bacteria was followed. This study especially focuses on the structure-activity relationship, depending on the modification site and fatty acid chain length. The synthesized conjugates showed high antimicrobial potential on vancomycin-resistant enterococci. We were able to demonstrate that the antimicrobial activity of the vancomycin-lipopeptide conjugates depends on the chain length of the attached fatty acid. All conjugates showed good cytocompatibility in vitro and in vivo. Radiolabeling enabled the in vivo determination of pharmacokinetics in Wistar rats by molecular imaging and biodistribution studies. An improved biodistribution profile in comparison to unmodified vancomycin was observed. While vancomycin is rapidly excreted by the kidneys, the most potent conjugate shows a hepatobiliary excretion profile. In conclusion, these results demonstrate the potential of the structural modification of already established antibiotics to provide highly active compounds for tackling multidrug-resistant bacteria.},
  language  = {en}
}
@article{WendlerBurmesterSoerensenetal.2014,
  author    = {Wendler, J{\"o}rg and Burmester, Gerd R. and S{\"o}rensen, Helmut and Krause, Andreas and Richter, Constanze and Tony, Hans-Peter and Rubbert-Roth, Andrea and Bartz-Bazzanella, Peter and Wassenberg, Siegfried and Haug-Rost, Iris and D{\"o}rner, Thomas},
  title     = {Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS): six-year results from a prospective, multicentre, non-interventional study in 2,484 patients},
  series = {Arthritis Research \& Therapy},
  volume    = {16},
  journal   = {Arthritis Research \& Therapy},
  number    = {2},
  doi       = {10.1186/ar4521},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121184},
  pages     = {R80},
  year      = {2014},
  abstract  = {INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of rituximab (RTX) in a large cohort of patients with rheumatoid arthritis in routine care, and to monitor changes in daily practice since the introduction of RTX therapy. METHODS: This was a multicentre, prospective, non-interventional study conducted under routine practice conditions in Germany. Efficacy was evaluated using Disease Activity Score in 28 joints (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed by recording adverse drug reactions (ADRs). Physician and patient global efficacy and tolerability assessments were also evaluated. RESULTS: Overall, 2,484 patients (76.7\% female, mean age 56.4 years, mean disease duration 11.7 years) received RTX treatment (22.7\% monotherapy). The total observation period was approximately six-years (median follow-up 14.7 months). RTX treatment led to improvements in DAS28 and HAQ-DI that were sustained over multiple courses. DAS28 improvements positively correlated with higher rheumatoid factor levels up to 50 IU/ml. Response and tolerability were rated good/very good by the majority of physicians and patients. Mean treatment intervals were 10.5 and 6.8 months for the first and last 400 enrolled patients, respectively. Infections were the most frequently reported ADRs (9.1\%; 11.39/100 patient-years); approximately 1\% of patients per course discontinued therapy due to ADRs. CONCLUSIONS: Prolonged RTX treatment in routine care is associated with good efficacy and tolerability, as measured by conventional parameters and by physicians' and patients' global assessments. Rheumatoid factor status served as a distinct and quantitative biomarker of RTX responsiveness. With growing experience, physicians repeated treatments earlier in patients with less severe disease activity.},
  language  = {en}
}
@article{KleinertTonyKrauseetal.2012,
  author    = {Kleinert, Stefan and Tony, Hans-Peter and Krause, Andreas and Feuchtenberger, Martin and Wassenberg, Siegfried and Richter, Constanze and R{\"a}ther, Ekkehard and Spieler, Wolfgang and Gnann, Holger and Wittig, Bianca M.},
  title     = {Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: data from a German noninterventional observational study},
  series = {Rheumatology International},
  volume    = {32},
  journal   = {Rheumatology International},
  number    = {9},
  doi       = {10.1007/s00296-011-2033-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125118},
  pages     = {2759-2767},
  year      = {2012},
  abstract  = {The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9-3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.},
  language  = {en}
}
@article{KleinertTonyKrauseetal.2012,
  author    = {Kleinert, Stefan and Tony, Hans-Peter and Krause, Andreas and Feuchtenberger, Martin and Wassenberg, Siegfried and Richter, Constanze and R{\"o}ther, Ekkehard and Spieler, Wolfgang and Gnann, Holger and Wittig, Bianca M.},
  title     = {Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: data from a German},
  series = {Rheumatology International},
  volume    = {32},
  journal   = {Rheumatology International},
  number    = {9},
  doi       = {10.1007/s00296-011-2033-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126220},
  pages     = {2759-2767},
  year      = {2012},
  abstract  = {The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9-3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.},
  language  = {en}
}
@article{PaethPaxianSeinetal.2017,
  author    = {Paeth, Heiko and Paxian, Andreas and Sein, Dimitry V. and Jacob, Daniela and Panitz, Hans-J{\"u}rgen and Warscher, Michael and Fink, Andreas H. and Kunstmann, Harald and Breil, Marcus and Engel, Thomas and Krause, Andreas and Toedter, Julian and Ahrens, Bodo},
  title     = {Decadal and multi-year predictability of the West African monsoon and the role of dynamical downscaling},
  series = {Meteorologische Zeitschrift},
  volume    = {26},
  journal   = {Meteorologische Zeitschrift},
  number    = {4},
  doi       = {10.1127/metz/2017/0811},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172018},
  pages     = {363-377},
  year      = {2017},
  abstract  = {West African summer monsoon precipitation is characterized by distinct decadal variability. Due to its welldocumented link to oceanic boundary conditions in various ocean basins it represents a paradigm for decadal predictability. In this study, we reappraise this hypothesis for several sub-regions of sub-Saharan West Africa using the new German contribution to the coupled model intercomparison project phase 5 (CMIP5) near-term prediction system. In addition, we assume that dynamical downscaling of the global decadal predictions leads to an enhanced predictive skill because enhanced resolution improves the atmospheric response to oceanic forcing and landsurface feedbacks. Based on three regional climate models, a heterogeneous picture is drawn: none of the regional climate models outperforms the global decadal predictions or all other regional climate models in every region nor decade. However, for every test case at least one regional climate model was identified which outperforms the global predictions. The highest predictive skill is found in the western and central Sahel Zone with correlation coefficients and mean-square skill scores exceeding 0.9 and 0.8, respectively.},
  language  = {en}
}