Discussion
NSAA, DMD, pain, Chronic progressive neuromuscular diseases, loss of ambulation
DISEASE PROGRESSION, DISEASE
Chronic progressive neuromuscular diseases such as DMD frequently cause reduced ambulatory function and mobility and are known to give rise to diminished HRQoL, and resultant utility values, over time [In the current study, a strong correlation was observed between NSAA scores and TFTs (10MWR and RFF grades, in addition to 6MWT distance), supporting the value of the NSAA as a measure of motor performance. Other studies have found similar associations between NSAA score and TFTs [Results of the current study showed moderate positive correlations between NSAA score and particular HUI attributes, including HUI3 ambulation, HUI2 mobility, and HUI2 self-care attributes. This finding speaks to criterion validity, as the degree and direction of correlation was expected given that the NSAA and the specified HUI attributes measure similar underlying target concepts.However, the correlation between baseline NSAA and HUI scores, and in changes in these scores over time, was weak. There are several potential hypotheses to explain this. First, the relationship between ambulatory function or mobility, motor performance, overall health status, and HRQoL is not straightforward. For example, individuals may report improved HRQoL after the occurrence of functional loss accompanying major disease milestones in DMD (such as loss of ambulation) due to adaptation where patients accommodate to their changed functional status [The study findings support that changes in NSAA score alone are not necessarily a sole predictor of change in HUI utility and vice versa. The HUI documents health status using a multi-attribute health status classification system, including aspects of ambulatory, physical, cognitive, and sensory function; social and emotional health; and attributes such as ability to complete self-care activities and presence of pain [The HUI by design is a generic, multidimensional health status assessment instrument, and such instruments are not always sufficient for measuring disease-specific impacts in a given population [Potential limitations of this study include the use of a relatively small sample size, which limits the statistical power of the analysis. The generalizability of the study may be limited by the fact that the demographic characteristics (e.g., patients were exon 51/53 skip-amenable) were not representative of the wider population of those with DMD; although those who are exon 51/53 skip amenable represent one of the larger mutation subgroups with DMD, their phenotype may be more severe than some others in terms of time to loss of ambulation [The results of these analyses highlight that DMD is a multifaceted disease and although functional impairment occurs early in the disease progression, motor performance alone does not fully explain changes in HRQoL in ambulatory individuals with DMD. While NSAA score is correlated with the ambulatory- and mobility-related components of the HUI, it is not strongly correlated with overall HUI utility, suggesting that additional important drivers of utility exist. It is also important to acknowledge that although some domains of the HUI have an appreciable association with the NSAA, overall the two instruments measure different, yet meaningful concepts. It is important to recognize the role of HRQoL and utility, as well as function, in assessing the patient experience in ambulatory children with DMD.
