von Jochen Maximilian Schmitt ; Thomas Bierbaum ; Max Geraedts ; Holger Gothe ; Martin Härter ; Falk Hoffmann ; Peter Ihle ; Ursula Kramer ; Monika Klinkhammer-Schalke ; Silke Kuske ; Stefanie March ; Jens-Peter Reese ; Olaf Schoffer ; Enno Swart ; Horst Christian Vollmar ; Felix Walther ; Wolfgang Hoffmann
von Christof Veit ; Thomas Bierbaum ; Simone Wesselmann ; Stephanie Stock ; Claus-Dieter Heidecke ; Christian Apfelbacher ; Stefan Rolf Benz ; Karsten Dreinhöfer ; Michael Hauptmann ; Falk Hoffmann ; Wolfgang Hoffmann ; Thomas Kaiser ; Monika Klinkhammer-Schalke ; Michael Koller ; Tanja Kostuj ; Olaf Ortmann ; Jochen Maximilian Schmitt ; Holger J. Schünemann ; Max Geraedts
von Damián Leonardo Arévalo Martínez ; Amir Haroon ; Hermann Werner Bange ; Ercan Erkul ; Marion Jegen ; Nils Moosdorf ; Jens Schneider von Deimling ; Christian Berndt ; Michael Ernst Böttcher ; Jasper Hoffmann ; Volker Liebetrau ; Ulf Mallast ; Gudrun Massmann ; Aaron Micallef ; Holly A. Michael ; Hendrik Paasche ; Wolfgang Rabbel ; Isaac Santos ; Jan Scholten ; Katrin Schwalenberg ; Beata Szymczycha ; Ariel Tremayne Thomas ; Joonas J. Virtasalo ; Hannelore Waska ; Bradley A. Weymer
Online veröffentlicht: 8. März 2023 ; Gesehen am 17.09.2024
Artificial Intelligence; Cardiovascular disease; Data and biomaterial collection; German Centre for Cardiovascular Research; Medical Ethics; Research platform; Standardisation
The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.
Clinical research in cardiology Berlin : Springer, 2006 112(2023), 7, Seite 923-941 Online-Ressource
von Kim M. Thalwitzer ; Jan Henje Driedger ; Julie Xian ; Afshin Saffari ; Pia Zacher ; Bigna K. Bölsterli ; Sarah McKeown Ruggiero ; Katie Rose Sullivan ; Alexandre N. Datta ; Christoph Kellinghaus ; Jürgen Althaus ; Adelheid Wiemer-Kruel ; Andreas van Baalen ; Armin Pampel ; Michael Alber ; Hilde M. H. Braakman ; Otfried Martin Debus ; Jonas Denecke ; Elke Hobbiebrunken ; Ina Breitweg ; Danielle Diehl ; Hans Christian Eitel ; Janina Gburek-Augustat ; Martin Preisel ; Jan-Ulrich Schlump ; Mirjam Laufs ; Dilbar Mammadova ; Carsten Wurst ; Christine Prager ; Christa Löhr-Nilles ; Peter Martin ; Sven Garbade ; Konrad Platzer ; Ira Benkel-Herrenbrueck ; Kerstin Egler ; Walid Fazeli ; Johannes R. Lemke ; Eva Runkel ; Barbara Klein ; Tobias Linden ; Julian Schröter ; Heike Steffeck ; Bastian Thies ; Florian von Deimling ; Sabine Illsinger ; Ingo Borggräfe ; Georg Classen ; Dagmar Wieczorek ; Georgia Ramantani ; Stefan Kölker ; Georg F. Hoffmann ; Markus Ries ; Ingo Helbig ; Steffen Syrbe
BACKGROUND AND OBJECTIVES: Pathogenic variants in STXBP1 are among the major genetic causes of neurodevelopmental disorders. Despite the increasing number of individuals diagnosed without a history of epilepsy, little is known about the natural history and developmental trajectories in this subgroup and endpoints for future therapeutic studies are limited to seizure control. - METHODS: We performed a cross-sectional retrospective study using standardized questionnaires for clinicians and caregivers of individuals with STXBP1-related disorders capturing medical histories, genetic findings, and developmental outcomes. Motor and language function were assessed using Gross Motor Function Classification System scores (GMFCS) and a speech impairment score and were compared within and across clinically defined subgroups. - RESULTS: We collected data of 71 individuals with STXBP1-related disorders, including 44 previously unreported individuals. Median age at inclusion was 5.3 years (IQR = 3.5-9.3) with the oldest individual aged 43.8 years. Epilepsy was absent in 18/71 (25%) of individuals. The range of developmental outcomes was broad, including two individuals presenting with close to age-appropriate motor development. 29/61 (48%) individuals were able to walk unassisted and 24/69 (35%) were able to speak single words. Individuals without epilepsy presented with a similar onset and spectrum of phenotypic features but had lower GMFCS scores (median 3 vs. 4, p < 0.01) than individuals with epilepsy. Individuals with epileptic spasms were less likely to walk unassisted than individuals with other seizure types (6% vs. 58%, p < 0.01). Individuals with early epilepsy onset had higher speech impairment scores (p = 0.02) than individuals with later epilepsy onset. - DISCUSSION: We expand the spectrum of STXBP1-related disorders and provide clinical features and developmental trajectories in individuals with and without a history of epilepsy. Individuals with epilepsy, in particular epileptic spasms, and neonatal or early-onset, presented with less favorable motor and language functional outcomes compared to individuals without epilepsy. These findings identify children at risk for severe disease and can serve as comparator for future interventional studies in STXBP1-related disorders.
