11 research outputs found
Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score
Background: The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families. The aim of this study was to assess effects of ETI on GI symptoms using the CFAbd-Score.
Methods: Gastrointestinal symptoms were prospectively assessed in pwCF using the CFAbd-Score before and up to 26 weeks during therapy. The CFAbd-Score was also administered to a healthy control (HC) group. The one-sided questionnaire includes 28 items grouped in five domains. Data analysis included calculation of scores with a weighting tool, developed according to FDA recommendations.
Results: A total of 107 pwCF attended in four CF centres in Germany and four centres in the UK completed the CFAbd-Score on at least two occasions. Results were compared to those obtained from the questionnaire of 45 HCs. Despite differences in demographics, age and proportion of pancreatic insufficiency between German and UK patients, analyses based on linear mixed-effects models at week 24 of ETI therapy revealed that estimated marginal means (EMMs) of total CFAbd-Scores significantly reduced (mean ± SE: 14.9 ± 1.2â10.6 ± 1.4; p < 0.01). Also EMMs of all five domains significantly declined (âpainâ 16.3 ± 1.6â10.2 ± 2.3, âGERDâ 15.8 ± 1.8â8.2 ± 1.9, âdisorders of bowel movementâ 20.9 ± 1.5â16.0 ± 1.7, âdisorders of appetiteâ 7.9 ± 1.1â2.6 ± 1.1 and âquality of life impairmentâ 10.1 ± 1.92â3.9 ± 1.9). However, during 24 weeks, CF participantsâ symptoms mostly still did not reach the reference levels of HCs.
Discussion: Using the CFAbd-Score, the first PROM specifically developed for assessment of CF-related abdominal symptoms, we demonstrate comprehensive improvements in GI symptoms after initiation of the highly effective modulator therapy ETI
The Localization Transition of the Two-Dimensional Lorentz Model
We investigate the dynamics of a single tracer particle performing Brownian
motion in a two-dimensional course of randomly distributed hard obstacles. At a
certain critical obstacle density, the motion of the tracer becomes anomalous
over many decades in time, which is rationalized in terms of an underlying
percolation transition of the void space. In the vicinity of this critical
density the dynamics follows the anomalous one up to a crossover time scale
where the motion becomes either diffusive or localized. We analyze the scaling
behavior of the time-dependent diffusion coefficient D(t) including corrections
to scaling. Away from the critical density, D(t) exhibits universal
hydrodynamic long-time tails both in the diffusive as well as in the localized
phase.Comment: 13 pages, 7 figures