Joyce Oleszek

Patterns of growth in ambulatory males with Duchenne muscular dystrophy.

OBJECTIVE To provide weight-for-age, height-for-age, and body mass index-for-age growth reference standards for ambulatory, steroid-naïve males, ages 2-12 years, with Duchenne muscular dystrophy (DMD) and to compare these growth curves to the 2000 Centers for Disease Control and Prevention growth charts for boys, which serve as references of physical size and growth for the general male pediatric population in the US. STUDY DESIGN Through a multi-state population-based surveillance of individuals with muscular dystrophy, a total of 1877 weight and 1544 height measurements ascertained during 1985-2010 from 513 males with DMD were obtained retrospectively from medical record review. Cases were classified as DMD if loss of ambulation occurred before the 12th birthday or, if younger than 12 years and still ambulating, the earliest symptoms of dystrophinopathy occurred before the 6th birthday. Each growth chart was constructed using 5 percentiles: 10th, 25th, 50th, 75th, and 90th. Smoothing procedures were applied in 2 stages to the irregular plots of the empirical percentile values. RESULTS A set of growth curves, derived from a large cohort of male youth with DMD, are presented. These curves demonstrate that DMD males are shorter and tend to the extremes of weight and body mass index compared with the general male pediatric population in the US. CONCLUSION Charts representing the pattern of growth in ambulatory, steroid-naïve males with DMD can facilitate monitoring of growth and early detection of unusual growth patterns. Use of these growth standards also will assist in monitoring responses to corticosteroid treatment.

Trends With Corticosteroid Use in Males With Duchenne Muscular Dystrophy Born 1982-2001

This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black males used steroids less frequently and delayed initiation compared to white males. Compared to males without a Duchenne muscular dystrophy family history, males with known family history were half as likely to use steroids. Duration of steroid use increased over time and age at initiation decreased. Racial/ethnic disparities exist for steroid use and should be addressed to improve outcome and quality of life for boys with Duchenne muscular dystrophy.

Arteriopathy, D-Dimer, and Risk of Poor Neurologic Outcome in Childhood-Onset Arterial Ischemic Stroke

OBJECTIVE To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS). STUDY DESIGN Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Childrens Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. RESULTS Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02). CONCLUSION Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.

Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy

Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.

Neurobehavioral Concerns among Males with Dystrophinopathy Using Population-Based Surveillance Data from the Muscular Dystrophy Surveillance, Tracking, and Research Network

Objective: To describe the occurrence of selected neurobehavioral concerns among males with a dystrophinopathy and to explore the associations with corticosteroid or supportive device use. Methods: Medical record abstraction of neurobehavioral concerns was conducted for 857 affected males from 765 families, born since 1982 and followed through 2011, and enrolled in the population-based Muscular Dystrophy Surveillance, Tracking, and Research Network. Cumulative probabilities for attention-deficit hyperactivity disorder (ADHD), behavior problems, and depressed mood were calculated from Kaplan-Meier estimates for the subsample of oldest affected males (n = 765). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for corticosteroid and supportive device use were estimated from Cox regression models with time-dependent covariates. Results: Of the 857 affected males, 375 (44%) had at least 1 of the 3 selected neurobehavioral concerns; a similar percentage (45%) was found among the 765 oldest affected males. The estimated cumulative probabilities among these oldest affected males were 23% for ADHD, 43% for behavior problems, and 51% for depressed mood. Corticosteroid (HR = 2.35, 95% CI = 1.75–3.16) and mobility device (HR = 1.53, 95% CI = 1.06–2.21) use were associated with behavior problems. Use of a mobility device (HR = 3.53, 95% CI = 2.13–5.85), but not corticosteroids, was associated with depressed mood. ADHD was not significantly associated with corticosteroid or mobility device use. Respiratory assist device use was not examined due to low numbers of users before onset of neurobehavioral concerns. Conclusion: Selected neurobehavioral concerns were common among males with a dystrophinopathy. Reported associations highlight the importance of increased monitoring of neurobehavioral concerns as interventions are implemented and disease progresses.

Perceived quality of life among caregivers of children with a childhood-onset dystrophinopathy: a double ABCX model of caregiver stressors and perceived resources

BackgroundDuchenne and Becker muscular dystrophies, collectively referred to as dystrophinopathies, are recessive X-linked disorders characterized by progressive muscle weakness and ultimately cardiac and respiratory failure. Immediate family members are often primary caregivers of individuals with a dystrophinopathy.MethodsWe explored the impact of this role by inviting primary caregivers (n = 209) of males diagnosed with childhood-onset dystrophinopathy who were identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to complete a mailed questionnaire measuring perceived social support and stress, spirituality, and family quality of life (FQoL). Bivariate and multivariate analyses examined associations between study variables using the Double ABCX model as an analytic framework.ResultsHigher stressor pile-up was associated with lower perceived social support (r = -0.29, p < .001), availability of supportive family (r = -0.30, p < .001) or non-family (r = -0.19, p < .01) relationships, and higher perceived stress (r = 0.33, p < .001); but not with spirituality (r = -0.14, p > 0.05). FQoL was positively associated with all support measures (correlations ranged from: 0.25 to 0.58, p-values 0.01–0.001) and negatively associated with perceived stress and control (r = -0.49, p < .001). The association between stressor pile-up and FQoL was completely mediated through global perceived social support, supportive family relationships, and perceived stress and control; supportive non-family relationships did not remain statistically significant after controlling for other mediators.ConclusionsFindings suggest caregiver adaptation to a dystrophinopathy diagnosis can be optimized by increased perceived control, supporting family resources, and creation of a healthy family identity. Our findings will help identify areas for family intervention and guide clinicians in identifying resources that minimize stress and maximize family adaptation.

Health Care Transition Experiences of Males with Childhood-onset Duchenne and Becker Muscular Dystrophy: Findings from the Muscular Dystrophy Surveillance Tracking and Research Network (Md Starnet) Health Care Transitions and Other Life Experiences Survey

Introduction: As the proportion of males with Duchenne muscular dystrophy (DMD) surviving into adulthood increases, more information is needed regarding their health care transition planning, an essential process for adolescents and young adults with DMD. The objective of this study was to describe the health care transition experiences of a population of males living with Duchenne or Becker muscular dystrophy (DBMD). Methods: The eligible participants, identified through the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) surveillance project, were 16–31 years old and lived in Arizona, Colorado, Georgia, Iowa, or western New York (n=258). The MD STARnet Health Care Transitions and Other Life Experiences Survey was conducted in 2013 and administered online or in a telephone interview. Sixty-five males (25%) completed the survey. Among non-ambulatory males, response differences were compared by age group. Statistical comparisons were conducted using Fisher’s exact test, or when appropriate, the Chisquare test. Results: Twenty-one percent of non-ambulatory males aged 16–18 years, 28% of non-ambulatory males aged 19–23 years, 25% of non-ambulatory males aged 24–30 years, and 18 ambulatory males had a written transition plan. Nineteen percent of non-ambulatory males aged 24–30 years had delayed or gone without needed health care in the past 12 months. Among non-ambulatory males aged 24–30 years, 75% had cardiology providers and 69% had pulmonology providers involved in their care in the past 12 months. Twentyeight percent of non-ambulatory males aged 19–23 years and 25% of non-ambulatory males aged 24–30 years reported that they did not receive health care or other services at least once because they were unable to leave their home. Non-ambulatory males aged 16–18 years (29%) were less likely to have ever discussed how to obtain or keep health insurance as they get older compared to non-ambulatory males aged 24-30 years (69%) (p <0.01). Discussion: This study identified potential barriers to the successful health care transition of males with DBMD. The results of this study may indicate a lack of targeted informational resources and education focused on supporting the transition of young men with DBMD as they age from adolescence into adulthood within the healthcare system. Future studies could determine the reasons for the potential barriers to health care and identify the optimal transition programs for males with DBMD. There are a few online resources on transition available to adolescents and young adults with special health care needs.

A Review of MD STARnet’s Research Contributions to Pediatric-Onset Dystrophinopathy in the United States; 2002-2017

Population studies of rare disorders, such as Duchenne and Becker muscular dystrophies (dystrophinopathies), are challenging due to diagnostic delay and heterogeneity in disorder milestones. To address these challenges, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) in 2002 in the United States. From 2002 to 2012, MD STARnet longitudinally tracked the prevalence, clinical, and health care outcomes of 1054 individuals born from 1982 to 2011 with pediatric-onset dystrophinopathy through medical record abstraction and survey data collection. This article summarizes 31 MD STARnet peer-reviewed publications. MD STARnet provided the first population-based prevalence estimates of childhood-onset dystrophinopathy in the United States. Additional publications provided insights into diagnostic delay, dystrophinopathy-specific growth charts, and health services use. Ongoing population-based surveillance continually improves our understanding of clinical and diagnostic outcomes of rare disorders.

Muscular Dystrophy Surveillance, Tracking, and Research Network pilot: Population-based surveillance of major muscular dystrophies at four U.S. sites, 2007-2011

BACKGROUND For 10 years, the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducted surveillance for Duchenne and Becker muscular dystrophy (DBMD). We piloted expanding surveillance to other MDs that vary in severity, onset, and sources of care. METHODS Our retrospective surveillance included individuals diagnosed with one of nine eligible MDs before or during the study period (January 2007-December 2011), one or more health encounters, and residence in one of four U.S. sites (Arizona, Colorado, Iowa, or western New York) at any time within the study period. We developed case definitions, surveillance protocols, and software applications for medical record abstraction, clinical review, and data pooling. Potential cases were identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 359.0, 359.1, and 359.21 and International Classification of Diseases, Tenth Revision (ICD-10) codes G71.0 and G71.1. Descriptive statistics were compared by MD type. Percentage of MD cases identified by each ICD-9-CM code was calculated. RESULTS Of 2,862 cases, 32.9% were myotonic, dystrophy 25.8% DBMD, 9.7% facioscapulohumeral MD, and 9.1% limb-girdle MD. Most cases were male (63.6%), non-Hispanic (59.8%), and White (80.2%). About, half of cases were genetically diagnosed in self (39.1%) or family (6.2%). About, half had a family history of MD (48.9%). The hereditary progressive MD code (359.1) was the most common code for identifying eligible cases. The myotonic code (359.21) identified 83.4% of eligible myotonic dystrophy cases (786/943). CONCLUSIONS MD STARnet is the only multisite, population-based active surveillance system available for MD in the United States. Continuing our expanded surveillance will contribute important epidemiologic and health outcome information about several MDs.

PROGRESSION OF LEFT VENTRICULAR DYSFUNCTION IN CHILDHOOD-ONSET DUCHENNE AND BECKER MUSCULAR DYSTROPHIES

Duchenne and Becker muscular dystrophies (DBMD) are associated with left ventricular dysfunction (LVD; ejection fraction (EF) <55% or qualitative dysfunction), which typically occurs during adolescence, and is a significant cause of morbidity and mortality. There are few data on progression of LVD.