ABSTRACT
Introduction: Individuals affected with ryanodine receptor isoform-1-related myopathies (RYR1-RM) commonly experience fatigability in the quadriceps, which may limit physical function and potentially diminish quality of life. Fatigability, in RYR1-RM, results from skeletal muscle injury secondary to dysfunction of the major skeletal muscle Ca++ channel. However, during fatigability testing, affected individuals did not always reach the point of local muscle fatigue as defined by a fatigue index (FATI) at 50% of peak torque. Surakka et al. compared three versions of FATI equations, which vary by the area under the force curve (AUC). By performing this comparison, they were able to determine the optimal equation in individuals with Multiple Sclerosis. Purpose: Using a similar comparison, we sought to identify the optimal FATI equation in the RYR1-RM population. Secondly, because local muscle fatigability might have an impact on independent living, this study also assessed change in local muscle fatigability over a 6-month time frame. Methods: Thirty participants were analyzed from the RYR1-RM natural history study and double-blind, placebo-controlled N-acetylcysteine (NAC) trial, NCT02362425. Twenty-seven had fatigability data, from isometric knee extension and flexion fatigability tests, available for the purpose of establishing a method for predicting FATI at 50% peak torque. For the natural history study, 30 participants were used to assess disease progression of local muscle fatigability achieved during the knee extension fatigability test, and 29 participants for the knee flexion fatigability test. Results: Surakka's equation 1, using the prediction approach, led to the smallest median error, the smallest square-root of uncorrected sum of squares, and the smallest average of the absolute value of the differences. No difference was observed in FATI at 50% peak torque between month 0 and month 6 for extension (p = 0.606) and flexion (p = 0.740). Conclusion: Surakka's equation 1, with the prediction approach, was found to be the most accurate for imputing values when fatigue was not reached during a sustained knee isometric fatigability test in RYR1-RM. Furthermore, when used to assess fatigability-based disease stability, local muscle fatigability, in this RYR1-RM population remained stable.
ABSTRACT
Background: The typical American worker spends about two-thirds of their work day standing. Prolonged standing has been found to be associated with acute and chronic adverse health outcomes. There is considerable variability among existing methods of analysis for prolonged-standing data, and therefore difficulty interpreting and comparing results across studies. Purpose: The purpose of this study is to develop a bodyweight transfer analysis method that incorporates factors of both time and amplitude of loading. This method was then applied to actual prolonged-standing data, to understand how the results of this method are impacted by time spent standing, and how the results relate to previously-reported methods of analysis for weight shifting data. Methods: Seven subjects (six male, one female) stood with each foot on one of two force plates for 6 h with a 5-min seated rest break between hours. Our new method identified two different types of events: fidgets and weight shifts. Center-of-pressure data were analyzed with the proposed method and three existing methods of analysis. Results: Subjects utilized different quantities of fidgets and weight shifts over the course of the trials. Existing methods of analysis identified a wide range in number of events, with some methods consistently identifying more events than others. These existing methods significantly differed from the proposed method. Fidgets, weight shifts, and fidgets + weight shifts, as identified using the proposed method, had significant interactions with time, while only one of the existing methods showed a significant time interaction. Conclusions: The conclusions drawn from analysis of prolonged standing center-of-pressure data can differ significantly depending on the method of analysis used. The method proposed here accounts for the different sources of discomfort and the tissue characteristics of these sources. Future work should explore the relationships between physiologic parameters and fidgets and weight shifts, so that appropriate clinical interventions can be identified.
