TY - CHAP A1 - Démaris, Alise A1 - Grišić, Ana-Marija A1 - Huisinga, Wilhelm A1 - Walter, Reinisch A1 - Kloft, Charlotte T1 - Evaluation of dosing strategies of anti-TNF alpha monoclonal antibodies using pharmacokinetic modelling and simulation T2 - Journal of Crohn's and Colitis N2 - Background: Anti-TNFα monoclonal antibodies (mAbs) are a well-established treatment for patients with Crohn’s disease (CD). However, subtherapeutic concentrations of mAbs have been related to a loss of response during the first year of therapy1. Therefore, an appropriate dosing strategy is crucial to prevent the underexposure of mAbs for those patients. The aim of our study was to assess the impact of different dosing strategies (fixed dose or body size descriptor adapted) on drug exposure and the target concentration attainment for two different anti-TNFα mAbs: infliximab (IFX, body weight (BW)-based dosing) and certolizumab pegol (CZP, fixed dosing). For this purpose, a comprehensive pharmacokinetic (PK) simulation study was performed. Methods: A virtual population of 1000 clinically representative CD patients was generated based on the distribution of CD patient characteristics from an in-house clinical database (n = 116). Seven dosing regimens were investigated: fixed dose and per BW, lean BW (LBW), body surface area, height, body mass index and fat-free mass. The individual body size-adjusted doses were calculated from patient generated body size descriptor values. Then, using published PK models for IFX and CZP in CD patients2,3, for each patient, 1000 concentration–time profiles were simulated to consider the typical profile of a specific patient as well as the range of possible individual profiles due to unexplained PK variability across patients. For each dosing strategy, the variability in maximum and minimum mAb concentrations (Cmax and Cmin, respectively), area under the concentration-time curve (AUC) and the per cent of patients reaching target concentration were assessed during maintenance therapy. Results: For IFX and CZP, Cmin showed the highest variability between patients (CV ≈110% and CV ≈80%, respectively) with a similar extent across all dosing strategies. For IFX, the per cent of patients reaching the target (Cmin = 5 µg/ml) was similar across all dosing strategies (~15%). For CZP, the per cent of patients reaching the target average concentration of 17 µg/ml ranged substantially (52–71%), being the highest for LBW-adjusted dosing. Conclusion: By using a PK simulation approach, different dosing regimen of IFX and CZP revealed the highest variability for Cmin, the most commonly used PK parameter guiding treatment decisions, independent upon dosing regimen. Our results demonstrate similar target attainment with fixed dosing of IFX compared with currently recommended BW-based dosing. For CZP, the current fixed dosing strategy leads to comparable percentage of patients reaching target as the best performing body size-adjusted dosing (66% vs. 71%, respectively). KW - linical databases KW - crohn's disease KW - regimen KW - monoclonal antibodies KW - body surface area KW - infliximab KW - fat-free mass KW - certolizumab pegol KW - body mass index procedure Y1 - 2020 U6 - https://doi.org/10.1093/ecco-jcc/jjz203.201 SN - 1873-9946 SN - 1876-4479 VL - 14 IS - Supp. 1 SP - S171 EP - S172 PB - Oxford Univ. Press CY - Oxford ER - TY - CHAP A1 - Rungrottheera, Wannarut A1 - Chang, Der-Chen A1 - Schulze, Bert-Wolfgang T1 - The edge calculus of singularity order >3 T2 - Journal of nonlinear and convex analysis : an international journal N2 - We study Mellin pseudo-differential algebras on singular straight cones and manifolds with singularity of order >= 3. Those are necessary to express parametrices of elliptic differential operators with a corresponding cornerdegenerate behavior, and we obtain regularity in weighted spaces. KW - Pseudo-differential algebras KW - symbols KW - singular manifolds KW - Mellin KW - operator calculus Y1 - 2020 SN - 1345-4773 SN - 1880-5221 VL - 21 IS - 2 SP - 387 EP - 401 PB - Yokohama Publishers CY - Yokohama ER - TY - CHAP ED - Kortenkamp, Ulrich ED - Kuzle, Ana T1 - Beiträge zum Mathematikunterricht 2017 BT - Vorträge auf der 51. Tagung für Didaktik der Mathematik vom 27.02.2017 bis 02.03.2017 in Potsdam Y1 - 2018 UR - http://www.wtm-verlag.de/beitraege-zum-mathematikunterricht/ SN - 978-3-95987-072-6 SN - 978-3-95987-089-4 PB - WTM-Verlag CY - Münster ER - TY - CHAP A1 - Kiy, Alexander A1 - Strickroth, Sven ED - Ullrich, Casten ED - Wessner, Martin T1 - Potentiale aufzeigen und Synergien nutzen BT - Audience Response Systeme als ein Anwendungsgebiet hochschulübergreifender Kooperationen T2 - Workshopband der 15. e-Learning Fachtagung Informatik (DeLFI) N2 - Audience Response Systems (ARS) are an enhancement to teaching in higher education with the aim to strengthen participant activation and the involvement of students directly in lectures. There is a wide range of different solutions available. However, these solutions either rely on personal devices of students (so-called software clicker) or require the purchase of mostly commercial hardware solutions. Here, the presented Hands.UP approach tries to bridge these two complementary concepts. Based on a cost and effort estimation of selected ARS, the necessity of inter-university cooperation with regard to adequate further development and the use of ARS in teaching are motivated. N2 - Audience Response Systeme (ARS) stellen eine Ergänzung der Hochschullehre dar, um die Teilnehmeraktivierung zu stärken und die Studierenden unmittelbar in das Vorlesungsgeschehen einzubinden. Es existiert eine Fülle an Lösungen, die entweder ohne dedizierte Hardware auskommen (sogenannte Software-Clicker) oder die Anschaffung meist kommerzieller Hardware- Lösungen voraussetzen. An dieser Stelle versucht Hands. UP eine integrative Brücke zu schlagen. Auf Grundlage einer Kosten- und Aufwandsschätzung ausgewählter ARS-Lösungen soll die Notwendigkeit hochschulübergreifender Kooperationen hinsichtlich einer adäquate Weiterentwicklung und des Einsatzes von ARS in der Lehre motiviert werden. KW - Audience Response System KW - Classroom Response System KW - Personal Response System KW - Clicker KW - COCOMO Y1 - 2017 PB - Kollen CY - Bonn ER - TY - CHAP A1 - Steenholdt, Casper A1 - Edlund, Helena A1 - Ainsworth, Mark A. A1 - Brynskov, Jorn A1 - Thomsen, Ole Ostergaard A1 - Huisinga, Wilhelm A1 - Kloft, Charlotte T1 - Relationship between measures of infliximab exposure and clinical outcome of infliximab intensification at therapeutic failure in Crohn's disease T2 - JOURNAL OF CROHNS & COLITIS Y1 - 2015 SN - 1873-9946 SN - 1876-4479 VL - 9 SP - S330 EP - S330 PB - Oxford Univ. Press CY - Oxford ER - TY - CHAP A1 - Andersson, H. A1 - Keunecke, A. A1 - Eser, A. A1 - Huisinga, Wilhelm A1 - Reinisch, W. A1 - Kloft, Charlotte T1 - Pharmacokinetic considerations for optimising dosing regimens of a potsdam univ infliximab in patients with Crohn's disease T2 - JOURNAL OF CROHNS & COLITIS Y1 - 2014 U6 - https://doi.org/10.1016/S1873-9946(14)60086-6 SN - 1873-9946 SN - 1876-4479 VL - 8 SP - S44 EP - S44 PB - Oxford Univ. Press CY - Oxford ER - TY - CHAP A1 - Hafer, Jörg A1 - Kiy, Alexander ED - Buchem, Ilona ED - Graham, Attwell ED - Tur, Gemma T1 - The university-wide introduction of an ePortfolio system as transdisciplinary task BT - Results of an implementation process and perspectives on an optimized process model T2 - Proceedings of the PLE Conference 2013: Learning and Diversity in the Cities of the Future Y1 - 2013 SP - 363 EP - 373 PB - Logos CY - Berlin ER -