Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Numerische Modellierung von Dualphasenstählen bei Herstellung, Verarbeitung und im Bauteil. Teil 1: Mikrostrukturbasierte Simulation vom Warmband bis zum Umformen

Der Einsatz von numerischen Modellen zur Optimierung des Herstellungsprozesses und der Betriebstauglichkeit ist in der Blechumformung mittlerweile ein etabliertes Vorgehen, wobei die Simulationen in der Regel jedoch nur einen Prozessschritt berücksichtigen. Eine darüber hinaus gehende Betrachtung der gesamten Prozesskette bietet weitreichende Vorteile. Damit besteht die Möglichkeit, im Rechner Variationen des Herstellungsprozesses vorzunehmen, und deren Einfluss auf die Werkstoffeigenschaften des Halbzeugs und auf das fertige Bauteil abzuschätzen. Der Aufwand für zeitintensive und teure Versuchsserien könnte auf diese Weise reduziert werden. Weiterhin bietet die Prozesskettensimulation die Möglichkeit, globale oder auch lokale Änderungen der Werkstoffeigenschaften infolge des vorherigen Prozessschrittes in der aktuellen Simulation zu berücksichtigen, und somit eine genauere Vorhersage der Bauteileigenschaften zu treffen. Im Rahmen eines vom BMBF geförderten Projektes wird eine durchgängige Simulationsstrategie für die Prozesskette eines Dualphasenstahls DP800 vom Warmband über das Umformen bis hin zum Crash entwickelt. Vorgestellt wird die Strategie zur Realisierung der Prozesskette, sowie aktuelle Projektergebnisse für die Prozessschritte Kaltwalzen, Glühen und Umformen vorgestellt. Die beschriebene Vorgehensweise stellt einen vielversprechenden Lösungsansatz für die durchgängige Simulation der hier betrachteten Prozesskette dar. Mit dem gewählten Ansatz ist es möglich, unterschiedliche numerische Modellierungsansätze auf verschiedenen Größenskalen in die Prozesskettensimulation einzubinden. Es ist zu erwarten, dass damit ein besserer Einblick in die mechanischen Wechselwirkungen zwischen den einzelnen Prozessschritten erreicht werden kann. Die daraus resultierenden Erkenntnisse können für eine weitere Optimierung einzelner Prozessschritte genutzt werden. Für die Stahlherstellung bietet dies eine Möglichkeit, Zeit und Kosten bei der Entwicklung und Markteinführung neuer Stähle im Automobilbereich einzusparen

Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS).

OBJECTIVES: To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. METHODS: This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10-13 and 16-19). RESULTS: At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3-41.1%; > or =50% responder rate was 40.9-44.2%; and seizure freedom rate was 15.0-15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). CONCLUSIONS: Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated

Zum Stand der virtuellen Werkstoffentwicklung: Vom Halbzeug zum Crash

Due to environmental aspects in automotive industry weight reduction of body parts is one of the main challenges. Increase of safety and comfort requirements accompanied by decrease of weight leads to the necessity of complex construction and application of innovative steel in car part production. The implementation of innovative steel grades is delayed in market introduction due to difficulties in production and processing of these steels. To overcome this problem, Salzgitter Mannesmann Research GmbH, Daimler AG, Kirchhoff automotive GmbH, DYNAmore GmbH, Fraunhofer-Institute for Mechanics of Materials IWM and Max-Planck Institute for Iron Research GmbH started a joint research project which is founded by the German Federal Ministry of Education in 2006. The goal of this project ist the acceleration of the development and market introduction of new steel grades. Within this project, a simulation strategy for modelling the process chain of dual phase steels from hot rolled strip to the behaviour of components under crash conditions was developed. These tools permit on the mechanical properties on macroscopic level and to transfer the relevant data from step to step along th whole process chain. Different length scales are applied for an adequate data structure of each simulation model. For example, numerical homogenization of the microstructure properties to provide a macroscopic material description is carried out by a so-called "Virtual lab". The developed process chain simulation, allows steel manufacturers a fast and purposeful modification of the process parameters and thus of material properties. Consequently, application of the process chain simulation enables an enormous time and cost reduction during the introduction of new steels automotive market

Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)

Objectives - To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods - This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10-13 and 16-19). Results - At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3-41.1%; >= 50% responder rate was 40.9-44.2%; and seizure freedom rate was 15.0-15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions - Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated