von Navid Farassat ; Daniel Böhringer ; Sebastian Küchlin ; Fanni E. Molnár ; Anne Schwietering ; Dorina Seger ; Martin J. Hug ; Anja-Birte Knöbel ; Sabine Schneider-Fuchs ; Gabriele Ihorst ; Bettina Kathrin Wabbels ; Christina Beisse ; Focke Ziemssen ; Frank Schüttauf ; Andrea Martina Hedergott ; Theresia Ring-Mangold ; Claudia Schuart ; Armin Wolf ; Stefanie Schmickler ; Julia Biermann ; Philipp Eberwein ; Karsten Hufendiek ; Anja Eckstein ; Gabriele Gusek-Schneider ; Michael Peter Schittkowski ; Thomas Lischka ; Wolf A. Lagrèze
Clinical trials; Medical ophthalmology; OPHTHALMOLOGY; Paediatric ophthalmology
Introduction Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. - Methods and analysis AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of −1 D to −6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. - Ethics and dissemination AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. - Trial registration number NCT03865160.
BMJ open London : BMJ Publishing Group, 2011 13(2023), 4, Artikel-ID e068822, Seite 1-11 Online-Ressource
von Meike von Wulffen ; Veronika Luehrmann ; Stefanie Robeck ; Antonella Russo ; Lena Fischer-Riepe ; Martijn van den Bosch ; Petrus L. van Lent ; Karin Loser ; Dmitry I. Gabrilovich ; Sven Hermann ; Johannes Roth ; Thomas Vogl
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.
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium’s possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10−12, R2 = 1.9%) and continuous (P = 6.4 × 10−9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10−4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
Schmidt-Ohlemann, Matthias Fachbeiträge zum Rehabilitations- und Teilhaberecht 2021 1. Auflage Heidelberg : Deutsche Vereinigung für Rehabilitation e.V. (DVfR), 2022 (2022), Seite 777-782 813 Seiten
Schmidt-Ohlemann, Matthias Fachbeiträge zum Rehabilitations- und Teilhaberecht 2021 1. Auflage Heidelberg : Deutsche Vereinigung für Rehabilitation e.V. (DVfR), 2022 (2022), Seite 772-776 813 Seiten
Schmidt-Ohlemann, Matthias Fachbeiträge zum Rehabilitations- und Teilhaberecht 2021 1. Auflage Heidelberg : Deutsche Vereinigung für Rehabilitation e.V. (DVfR), 2022 (2022), Seite 783-788 813 Seiten
Zentrifugalkräfte in Europa und im sozialen Rechtsstaat 1. Auflage Baden-Baden : Nomos Verlagsgesellschaft, 2022 (2022), Seite 353-376 1 Online-Ressource (444 Seiten)
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