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Population-based estimates of survival among individuals with Duchenne muscular dystrophy (DMD) living in the United States are lacking. It is also unclear whether the association between glucocorticoid use and all-cause mortality persists in the context of other common treatments (cardiac medication, cough-assist, bilevel positive airway pressure, and scoliosis surgery) observed to delay mortality. Among 526 individuals identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network, the estimated median survival time from birth was 23.7 years. Current glucocorticoid users had a lower hazard of mortality than non-users. Individuals who ever had scoliosis surgery had a lower hazard of mortality than individuals who did not have scoliosis surgery. Individuals who ever used cough assist had a lower hazard of mortality than individuals who never used cough assist. Non-Hispanic Black individuals had a higher hazard of mortality than non-Hispanic White individuals. No differences in hazards of mortality were observed between ever versus never use of cardiac medication and ever versus never use of bilevel positive airway pressure. The glucocorticoid observation is consistent with the 2018 Care Considerations statement that glucocorticoid use continues in the non-ambulatory phase. Our observations may inform the clinical care of individuals living with DMD.

Background Primary periodic paralyses are rare, hereditary skeletal muscle diseases characterized by episodic muscle weakness. Dichlorphenamide was effective and well tolerated in two studies, including one with adolescents. This analysis describes effects of dichlorphenamide among adolescents and adults. Methods Patients with primary periodic paralyses in a double-blind, controlled, crossover study were randomized to dichlorphenamide or placebo for nine weeks, with a nine-week or longer between-treatment washout period. Attack rate and severity-weighted attack rate during the final eight weeks of each treatment phase were calculated for adolescents and adults separately. Results Seven adolescents (10 to ≤17 years) and 66 adults were enrolled; five of seven adolescents were evaluable for efficacy and six for safety. Dichlorphenamide total daily dosing among adolescents was 50 mg (n = 1) or 100 mg (n = 5), and in adults was 105.7 mg (mean; n = 61). In adolescents, the median decrease from baseline in frequency of weekly attacks was greater with dichlorphenamide (−0.96) than with placebo (−0.57), similar to findings in adults (dichlorphenamide, −0.83; placebo, −0.24). Severity-weighted attack frequency was likewise reduced more with dichlorphenamide than with placebo in adolescents and adults. The most common adverse event with dichlorphenamide in adolescents was skin rash (two of six [33%]). In adults, numbness was the most common adverse event (26 of 54 [48%]); skin rash occurred less frequently (10 of 54 [19%]). Conclusions Dichlorphenamide was comparably effective and tolerated among a small number of adolescents as well as adults, although types of adverse events differed between groups.

Myasthenia gravis presents a risk factor for pregnancy and delivery, and can affect the newborn. In return, pregnancy can affect the course of myasthenia and worsen the disease during pregnancy requiring treatment modifications. Treatment optimization and drug safety should be addressed before conception. Delivery is complicated by prolonged labor. Newborns can develop neonatal myasthenia gravis, a treatable and transient disease. Patients should not be discouraged to become pregnant, but provided with supportive counseling, planning, and monitoring in a multidisciplinary team involving obstetrician, anesthesiologist, pediatrician, and neurologist. Pregnancy outcome is favorable in women who receive treatment and expert care.

Background In 2005, the American Academy of Pediatrics (AAP) published a policy statement on cardiovascular health supervision for Duchenne Muscular Dystrophy (DMD). Data is lacking on its effect on cardiovascular care. Methods Using the infrastructure of the Muscular Dystrophy Surveillance, Tracking and Research Network, we examined a population-based sample of individuals with DMD, focusing on cardiac testing and prescription of cardiac medication. Comparisons were made pre- (2000–2005) and post- (2006–2011) publication Results 731 cases were studied; mean age of diagnosis 3.8 years and mean duration of follow-up 9.3 years. There was a significant decrease in time from diagnosis to first electrocardiogram (ECG) and echocardiogram (ECHO) from pre- to post-publication; 1047 (95% CI: 905–1188) days to 411 (95% CI: 324–498) days for ECG (p Conclusions Since publication of the AAP statement, DMD patients are having cardiac testing sooner and cardiac medication is prescribed more often. However, the majority are not having testing with recommended frequency. Overcoming barriers to recommended cardiac care may lead to a better understanding of the natural history of cardiomyopathy in DMD and better treatment strategies.

Individuals with Duchenne muscular dystrophy (DMD) often exhibit delayed motor and cognitive development, including delayed onset of ambulation. Data on age when loss of independent ambulation occurs are well established for DMD; however, age at onset of walking has not been well described. We hypothesize that an effective medication given in early infancy would advance the age when walking is achieved so that it is closer to age-matched norms, and that this discrete event could serve as the primary outcome measure in a clinical trial. This study examined three data sets, Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet); Dutch Natural History Survey (DNHS); and Parent Project Muscular Dystrophy (PPMD). The distribution of onset of ambulation in DMD (mean ± SD) and median age, in months, at the onset of ambulation was 17.3 (±5.5) and 16.0 in MD STARnet, 21.8 (±7.1) and 20.0 in DNHS, and 16.1 (±4.4) and 15 in PPMD. Age of ambulation in these data sets were all significantly later (P < 0.001) than the corresponding age for typically developing boys, 12.1 (±1.8). A hypothetical clinical trial study design and power analyses are presented based on these data.

Purpose: To determine whether sociodemographic factors are associated with delays at specific steps in the diagnostic process of Duchenne and Becker muscular dystrophy. Methods: We examined abstracted medical records for 540 males from population-based surveillance sites in Arizona, Colorado, Georgia, Iowa, and western New York. We used linear regressions to model the association of three sociodemographic characteristics with age at initial medical evaluation, first creatine kinase measurement, and earliest DNA analysis while controlling for changes in the diagnostic process over time. The analytical dataset included 375 males with information on family history of Duchenne and Becker muscular dystrophy, neighborhood poverty levels, and race/ethnicity. Results: Black and Hispanic race/ethnicity predicted older ages at initial evaluation, creatine kinase measurement, and DNA testing (P < 0.05). A positive family history of Duchenne and Becker muscular dystrophy predicted younger ages at initial evaluation, creatine kinase measurement and DNA testing (P < 0.001). Higher neighborhood poverty was associated with earlier ages of evaluation (P < 0.05). Conclusions: Racial and ethnic disparities in the diagnostic process for Duchenne and Becker muscular dystrophy are evident even after adjustment for family history of Duchenne and Becker muscular dystrophy and changes in the diagnostic process over time. Black and Hispanic children are initially evaluated at older ages than white children, and the gap widens at later steps in the diagnostic process.

In preparation for a clinical trial to investigate the effectiveness of drug treatment in infants with Duchenne MD, a clinically meaningful primary outcome measure needs to be established. Our hypothesis is that infants with DMD have delayed age to walking independently, have an innate desire to walk as soon as the motor system permits this task, and that an effective drug for DMD would reduce the age when independent ambulation is reached. As such, age of independent ambulation is a discrete dichotomous event that may serve as an effective primary outcome measure in a clinical trial. The age when ambulation is first achieved was studied in 2 DMD population samples: US CDC MD STARnet (Dataset 1, 1982-present, n = 449) and a more historical Dutch natural history survey (Dataset 2, 1961–1982, n = 473) and compared to the WHO reference set in normal boys (mean ± SD [months, m], where walking was achieved at 12.1 ± 1.8 m, 99% by 17.6 m. The data were not normally distributed, possibly due to recall bias and rounding error. Age of ambulation in Dataset 1 was 17.0 ± 5 m and median age was 16.0 m, IQR 13.0, 18.0 with 96% walking by 24 months. In dataset 2, the mean age of ambulation was 21.8 ± 7.1 m and median age of was 20.0 m, IQR 18.0, 24.0 with 81% walking by 24 m. Based upon Data Set 1 there is a delay in walking among DMD boys of mean 4.9 m. A clinical trial design, with 1:1 randomization, power of 90% and alpha of 0.05, for a drug that shortens age at ambulation by 2 months, to a mean delay of 2.9 months, would require 86 boys in each arm if the SD is 4 and 23 boys in each arm if the SD is 2. Prospective data is necessary to obtain more secure data, especially for the mean/median and degree of variance. This information may be useful in preparation for newborn screening in DMD and having a clinical trial design that would capture a reliable clinically meaningful outcome measure independent of patient effort or evaluator bias.

s S305 Purpose: The need for ventricular assist devices (VADs) has been increasing over the past several years. Sensitized patients defined as those with the development of circulating antibodies most likely due to blood transfusions, pregnancy, and previous organ transplants are known to have poorer outcome after organ transplantation. Patients who undergo VAD implantation may be given blood products and therefore are reported to have a higher incidence of sensitization. It is not known whether these circulating antibodies in a VAD patient have the same immunological impact compared to sensitized non-VAD patients after heart transplant. Methods: Between 1994 and 2012 we evaluated 160 VAD and 297 non-VAD patients awaiting heart transplant. Specifically, we assessed patients who were sensitized (PRA > 10%) to assess their three year post-transplant outcomes [Actuarial survival, freedom from Cardiac Allograft Vasculopathy (CAV) and freedom from Non-Fatal Major Adverse Cardiac Events (NF-MACE, defined as: myocardial infarction, worsening congestive heart failure, percutaneous coronary intervention, ICD/pacemaker insertion, and/or stroke)]. 1 year freedom from cellular (ISHLT grade 2R, 3R) and antibody-mediated rejection (pAMR 1, 2, 3) were also assessed. Results: There were 65 sensitized VAD patients compared to 71 sensitized non-VAD patients. Sensitized VAD patients had significantly higher 1 year freedom from antibody-mediated rejection (81.5% vs. 62.0%, p = 0.01) compared to sensitized non-VAD patients (see table). Both Sensitized VAD and sensitized non-VAD patients had comparable 3-year post-transplant outcomes. Conclusion: Compared to sensitized non-VAD patients, sensitized VAD patients appear to have less pAMR after heart transplant, suggesting that their immune response is truncated after removal of the VAD after undergoing heart transplant. Further study into the mechanisms of this observed response is warranted. Sensitized VAD (n= 65) Sensitized Non-VAD (n= 71) P-Value 1-Year Freedom from Cellular Rejection (ISHLT grade 2R, 3R) 81.5% 77.5% 0.53 1-year Freedom from Antibody-Mediated Rejection (pAMR 1,2,3) 79.0% 61.0% 0.02 3-Year Actuarial Survival 81.5% 84.5% 0.62 3-Year Freedom from CAV 92.3% 97.2% 0.20 3-year Freedom from NF-MACE 93.8% 94.4% 0.91

Duchenne and Becker muscular dystrophies (DBMD) are associated with left ventricular dysfunction (LVD; ejection fraction (EF)

Improved respiratory and cardiac management along with glucocorticoid therapy have contributed to increasing survival of patients with DBMD.This has led to a growing population of adults with DBMD. The purpose of this population based study was to describe the sociodemographic profile and health related outcomes of individuals with DBMD followed in the MD STARnet. MD STARnet is a multi state population based surveillance system that collects data on all individuals with DBMD born since 1/1/1982. In addition to epidemiologic data, MD STARnet collects extensive sociodemograhic and clinical data related to natural history milestones and treatments and services received by individuals with DBMD. The cohort for this analysis was all individuals born from 1/1/1982 to 12/31/1992 and followed through 8/31/2011. Overall, 384 individuals were identified of which 32% have died [mean age 17.6 years (8.7–25.5)], and 20% were lost to follow up [mean age 15.3 (0.9–25.8)]. The remainder continue to be followed [mean age 21.5 (17–28.6)]. Most individuals were white, non-Hispanic (59%) and live with parent/s/family (98%), have post high school/college training (24%). The number of individuals and the average age (range) at which they crossed clinical milestones or required specific treatments were as follows: loss of ambulation [ N = 300, 11.7 years (6.9–24.50)], scoliosis surgery [ N = 128, 14.7 years (10.3–20.2)], night time ventilator support [ N = 158, 16.9 years (9.4–26.2)], cardiomyopathy (SF N = 188, 16.5 years (9–25.5)], PEG [ N = 58, 19.2 years (11.8–26.0)]. Forty nine percentage have been treated with corticosteroids. Our population based data support an emerging population of adults with DBMD. This sociodemographic and health related profile provides information for providers, payors and policy makers to help design the appropriate care models for the needs of adults with DBMD and their families.