Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy
Abstract Duchenne muscular dystrophy (DMD) is a rare X‐linked recessive disorder characterized by loss‐of‐function mutations in the gene encoding dystrophin. These mutations lead to progressive functional deterioration including muscle weakness, respiratory insufficiency, and musculoskeletal deformi...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-05-01
|
| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13126 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850086330611007488 |
|---|---|
| author | Jiexin Deng Fangli Liu Zhifen Feng Zhigang Liu |
| author_facet | Jiexin Deng Fangli Liu Zhifen Feng Zhigang Liu |
| author_sort | Jiexin Deng |
| collection | DOAJ |
| description | Abstract Duchenne muscular dystrophy (DMD) is a rare X‐linked recessive disorder characterized by loss‐of‐function mutations in the gene encoding dystrophin. These mutations lead to progressive functional deterioration including muscle weakness, respiratory insufficiency, and musculoskeletal deformities. Three‐dimensional gait analysis (3DGA) has been used as a tool to analyze gait pathology through the quantification of altered joint kinematics, kinetics, and muscle activity patterns. Among 3DGA indices, the Gait Profile Score (GPS), has been used as a sensitive overall measure to detect clinically relevant changes in gait patterns in children with DMD. To enhance our understanding of the clinical translation of 3DGA, we report here the development of a population nonlinear mixed‐effect model that jointly describes the disease progression of the 3DGA index, GPS, and the functional endpoint, North Star Ambulatory Assessment (NSAA). The final model consists of a quadratic structure for GPS progression and a linear structure for GPS‐NSAA correlation. Our model was able to capture the improvement in function in GPS and NSAA in younger subjects, as well as the decline of function in older subjects. Furthermore, the model predicted NSAA (CFB) at 1 year reasonably well for DMD subjects ≤7 years old at baseline. The model tended to slightly underpredict the decline in NSAA after 1 year for those >7 years old at baseline, but the prediction summary statistics were well maintained within the standard deviation of observed data. Quantitative models such as this may help answer clinically relevant questions to facilitate the development of novel therapies in DMD. |
| format | Article |
| id | doaj-art-836246586fc144fe8febfac9bf7efac5 |
| institution | DOAJ |
| issn | 2163-8306 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj-art-836246586fc144fe8febfac9bf7efac52025-08-20T02:43:31ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062024-05-0113589190310.1002/psp4.13126Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophyJiexin Deng0Fangli Liu1Zhifen Feng2Zhigang Liu3School of Nursing and Health Henan University Kaifeng ChinaSchool of Nursing and Health Henan University Kaifeng ChinaSchool of Nursing and Health Henan University Kaifeng ChinaDepartment of Orthopedics First Affiliated Hospital of Henan University Kaifeng ChinaAbstract Duchenne muscular dystrophy (DMD) is a rare X‐linked recessive disorder characterized by loss‐of‐function mutations in the gene encoding dystrophin. These mutations lead to progressive functional deterioration including muscle weakness, respiratory insufficiency, and musculoskeletal deformities. Three‐dimensional gait analysis (3DGA) has been used as a tool to analyze gait pathology through the quantification of altered joint kinematics, kinetics, and muscle activity patterns. Among 3DGA indices, the Gait Profile Score (GPS), has been used as a sensitive overall measure to detect clinically relevant changes in gait patterns in children with DMD. To enhance our understanding of the clinical translation of 3DGA, we report here the development of a population nonlinear mixed‐effect model that jointly describes the disease progression of the 3DGA index, GPS, and the functional endpoint, North Star Ambulatory Assessment (NSAA). The final model consists of a quadratic structure for GPS progression and a linear structure for GPS‐NSAA correlation. Our model was able to capture the improvement in function in GPS and NSAA in younger subjects, as well as the decline of function in older subjects. Furthermore, the model predicted NSAA (CFB) at 1 year reasonably well for DMD subjects ≤7 years old at baseline. The model tended to slightly underpredict the decline in NSAA after 1 year for those >7 years old at baseline, but the prediction summary statistics were well maintained within the standard deviation of observed data. Quantitative models such as this may help answer clinically relevant questions to facilitate the development of novel therapies in DMD.https://doi.org/10.1002/psp4.13126 |
| spellingShingle | Jiexin Deng Fangli Liu Zhifen Feng Zhigang Liu Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy CPT: Pharmacometrics & Systems Pharmacology |
| title | Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy |
| title_full | Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy |
| title_fullStr | Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy |
| title_full_unstemmed | Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy |
| title_short | Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy |
| title_sort | population longitudinal analysis of gait profile score and north star ambulatory assessment in children with duchenne muscular dystrophy |
| url | https://doi.org/10.1002/psp4.13126 |
| work_keys_str_mv | AT jiexindeng populationlongitudinalanalysisofgaitprofilescoreandnorthstarambulatoryassessmentinchildrenwithduchennemusculardystrophy AT fangliliu populationlongitudinalanalysisofgaitprofilescoreandnorthstarambulatoryassessmentinchildrenwithduchennemusculardystrophy AT zhifenfeng populationlongitudinalanalysisofgaitprofilescoreandnorthstarambulatoryassessmentinchildrenwithduchennemusculardystrophy AT zhigangliu populationlongitudinalanalysisofgaitprofilescoreandnorthstarambulatoryassessmentinchildrenwithduchennemusculardystrophy |