Introduction Cardiomyopathy is a common cause of morbidity and death in patients with Duchenne muscular dystrophy (DMD). Methods A cross-sectional analysis of clinical data from a multi-institutional, international CINRG DMD Natural History Study of 340 DMD patients aged 2 to 28 years. Cardiomyopathy was defined as shortening fraction (SF) <28% or ejection fraction (EF) <55%. Results 231 participants reported a prior clinical echocardiogram study, and 174 had data for SF or EF. The prevalence of cardiomyopathy was 27% (47/174), and it was significantly associated with age and clinical stage. The association of cardiomyopathy with age and clinical stage was not changed by glucocorticoid use as a covariate (P>0.68). In patients with cardiomyopathy, 57 % (27/47) reported not taking any cardiac medications. Cardiac medications were used in 12% (15/127) of patients without cardiomyopathy. Discussion Echocardiograms were underutilized, and cardiomyopathy was undertreated in this DMD natural history cohort.

This work examined acceptability of cancer genetic counseling models of service delivery among Maine residents at risk for hereditary cancer susceptibility disorders. Pre-counseling, participants ranked characteristics reflecting models of care from most to least important including: mode-of-communication (in-person versus telegenetics), provider level of training (genetic specialty versus some training/experience), delivery format (one-on-one versus group counseling), and location (local versus tertiary service requiring travel). Associations between models of care characteristic rankings and patient characteristics, including rural residence, perceived cancer risk, and perceived risk for a hereditary cancer risk susceptibility disorder were examined. A total of 149/300 (49.7% response rate) individuals from 11/16 Maine counties responded; 30.8% were from rural counties; 92.2% indicated that an important/the most important model of care characteristic is provider professional qualifications. Among other characteristics, 65.1% ranked one-on-one counseling as important/the most important. In-person and local counseling were ranked the two least important characteristics (51.8% and 52.1% important/the most important, respectively). Responses did not vary by patient characteristics with the exception of greater acceptance of group counseling among those at perceived high personal cancer risk. Cancer telegenetic services hold promise for access to expert providers in a one-on-one format for rurally remote clients.

Early clinical trials of therapies to treat Duchenne muscular dystrophy (DMD), a fatal genetic X-linked pediatric disease, have been designed based on the limited understanding of natural disease progression and variability in clinical measures over different stages of the continuum of the disease. The objective was to inform the design of DMD clinical trials by developing a disease progression modelbased clinical trial simulation (CTS) platform based on measures commonly used in DMD trials. Data were integrated from past studies through the Duchenne Regulatory Science Consortium founded by the Critical Path Institute (15 clinical trials and studies, 1505 subjects, 27,252 observations). Using a nonlinear mixedeffects modeling approach, longitudinal dynamics of five measures were modeled (NorthStar Ambulatory Assessment, forced vital capacity, and the velocities of the following three timed functional tests: time to stand from supine, time to climb 4 stairs, and 10 meter walk-run time). The models were validated on external data sets and captured longitudinal changes in the five measures well, including both early disease when function improves as a result of growth and development and the decline in function in later stages. The models can be used in the CTS platform to perform trial simulations to optimize the selection of inclusion/ exclusion criteria, selection of measures, and other trial parameters. The data sets and models have been reviewed by the US Food and Drug Administration and the European Medicines Agency; have been accepted into the Fit-for-Purpose and Qualification for Novel Methodologies pathways, respectively; and will be submitted for potential endorsement by both agencies.

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