Facioscapulohumeral dystrophy in children: design of a prospective, observational study on natural history, predictors and clinical impact (iFocus FSHD).

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD; OMIM 158900 & 158901) is a progressive skeletal muscle dystrophy, characterized by an autosomal dominant inheritance pattern. One of the major unsolved questions in FSHD is the marked clinical heterogeneity, ranging from asymptomatic individuals to severely affected patients with an early onset. An estimated 10% of FSHD patients have an early onset (onset before 10 years of age) and are traditionally classified as infantile FSHD. This subgroup is regarded as severely affected and extra-muscular symptoms, such as hearing loss and retinopathy, are frequently described. However, information on the prevalence, natural history and clinical management of early onset FSHD is currently lacking, thereby hampering adequate patient counselling and management. Therefore, a population-based prospective cohort study on FSHD in children is highly needed. METHODS/DESIGN: This explorative study aims to recruit all children (aged 0-17 years) with a genetically confirmed diagnosis of FSHD in The Netherlands. The children will be assessed at baseline and at 2-year follow-up. The general aim of the study is the description of the clinical features and genetic characteristics of this paediatric cohort. The primary outcome is the motor function as measured by the Motor Function Measure. Secondary outcomes include quantitative and qualitative description of the clinical phenotype, muscle imaging, genotyping and prevalence estimations. The ultimate objective will be a thorough description of the natural history, predictors of disease severity and quality of life in children with FSHD. DISCUSSION: The results of this population-based study are vital for adequate patient management and clinical trial-readiness. Furthermore, this study is expected to provide additional insight in the epigenetic and environmental disease modifying factors. In addition to improve counselling, this could contribute to unravelling the aetiology of FSHD. TRIAL REGISTRATION: clinicaltrials.gov NCT02625662.

Methodological aspects of an adaptive multidirectional pattern search to optimize speech perception using three hearing-aid algorithms.

In this study we investigated the reliability and convergence characteristics of an adaptive multidirectional pattern search procedure, relative to a nonadaptive multidirectional pattern search procedure. The procedure was designed to optimize three speech-processing strategies. These comprise noise reduction, spectral enhancement, and spectral lift. The search is based on a paired-comparison paradigm, in which subjects evaluated the listening comfort of speech-in-noise fragments. The procedural and nonprocedural factors that influence the reliability and convergence of the procedure are studied using various test conditions. The test conditions combine different tests, initial settings, background noise types, and step size configurations. Seven normal hearing subjects participated in this study. The results indicate that the reliability of the optimization strategy may benefit from the use of an adaptive step size. Decreasing the step size increases accuracy, while increasing the step size can be beneficial to create clear perceptual differences in the comparisons. The reliability also depends on starting point, stop criterion, step size constraints, background noise, algorithms used, as well as the presence of drifting cues and suboptimal settings. There appears to be a trade-off between reliability and convergence, i.e., when the step size is enlarged the reliability improves, but the convergence deteriorates.