ABSTRACT
AIMS: Our objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD). METHODS: The French dystrophinopathy database provided clinical, histochemical and molecular data of 278 DMD patients (mean longitudinal follow-up: 14.2 years). Diagnosis was based on mutation identification in the DMD gene. Three groups were defined according to the age at ambulation loss: before 8 years (group A); between 8 and 11 years (group B); between 11 and 16 years (group C). RESULTS: Motor and respiratory declines were statistically different between the three groups, as opposed to heart involvement. When acquired, running ability was lost at the mean age of 5.41 (group A), 7.11 (group B), 9.19 (group C) years; climbing stairs ability at 6.24 (group A), 7.99 (group B), 10,42 (group C) years, and ambulation at 7.10 (group A), 9.25 (group B), 12.01 (group C) years. Pulmonary growth stopped at 10.26 (group A), 12.45 (group B), 14.58 (group C) years. Then, forced vital capacity decreased at the rate of 8.83 (group A), 7.52 (group B), 6.03 (group C) percent per year. Phenotypic variability did not rely on specific mutational spectrum. CONCLUSION: Beside the most common form of DMD (group B), we provide detailed description on two extreme clinical subgroups: a severe one (group A) characterized by early severe motor and respiratory decline and a milder subgroup (group C). Compared to group B or C, four to six times fewer patients from group A are needed to detect the same decrease in disease progression in a clinical trial.
Subject(s)
Movement/physiology , Muscular Dystrophy, Duchenne/physiopathology , Respiratory Mechanics/physiology , Adolescent , Age of Onset , Cardiomyopathies/etiology , Child , Clinical Trials as Topic , DNA Mutational Analysis , Dystrophin/genetics , Female , Follow-Up Studies , France , Gait Disorders, Neurologic/etiology , Humans , Longitudinal Studies , Male , Muscular Dystrophy, Duchenne/genetics , Phenotype , Research Design , Respiratory Insufficiency/etiology , Scoliosis/etiology , Survival , Vital Capacity/physiologyABSTRACT
We examined geographic variations in the dispensing of anxiolytics and hypnotics (AX-HY) and their determinants at the canton level in southeastern France. Data were collected from the 2005 outpatient database of the Southeastern France General Health Insurance Fund, covering more than 70% of the population. We calculated the annual age-adjusted prevalence rates of subjects filling prescriptions for AX-HY at least once (to measure 'overall use') and at least six times ('chronic use'), assessed geographic variations with the extremal quotient and weighted coefficient of variation, and conducted simple and multiple linear regression analysis to study their determinants. Prevalence rates of overall and chronic AX-HY use were 15.5% and 5.9%, respectively, and varied significantly between cantons, by a factor of 3-4. The prevalence of mental illness and that of chronic illness were independently and positively associated with overall and chronic use; unemployment rates and mean family income were positively associated only with overall use. Density of general practitioners did not explain geographic variations. These results provide a basis for targeting interventions to reduce AX-HY use and promoting appropriate discontinuation. Future studies should examine trends in those geographic variations.
