Racial and Ethnic Differences in Timing of Diagnosis and Clinical Services Received in Duchenne Muscular Dystrophy.

INTRODUCTION: Racial/ethnic differences in diagnostic and treatment services have been identified for a range of health conditions and outcomes. The current study aimed to analyze whether there are racial/ethnic differences in the timing of diagnostic testing and treatments for males with Duchenne muscular dystrophy (DMD). METHODS: Diagnostic and clinical data for male individuals with DMD born during 1990-2010 were analyzed from eight sites (Arizona, Colorado, Georgia, Iowa, Piedmont Region of North Carolina, Western New York, South Carolina, and Utah) of the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Seven milestones related to diagnosis/treatment experiences were selected as outcomes. Times to each milestone were estimated and compared by four racial/ethnic groups using Kaplan-Meier estimation and Cox proportional-hazards models. Times between initial evaluation or diagnostic testing and later milestones were also compared by race/ethnicity. RESULTS: We identified 682 males with definite or probable DMD of whom 61.7% were non-Hispanic white, 20.5% Hispanic, 10.6% other, and 7.2% non-Hispanic black. Seven milestone events were studied (initial evaluation, first neurology/neuromuscular visit, diagnosis, corticosteroid treatment first offered, corticosteroid treatment started, first electrocardiogram or echocardiogram, and first pulmonary function test). The first five milestone events occurred at an older age for non-Hispanic black individuals compared to non-Hispanic white individuals. Time to first offering of corticosteroids and initiation of corticosteroid therapy was later for Hispanic individuals compared to non-Hispanic white individuals. When accounting for timing of initial evaluation/diagnosis, offering of corticosteroids continued to occur later, but first pulmonary testing occurred earlier, among Hispanic individuals compared to non-Hispanic whites. No significant delays remained for non-Hispanic black individuals after accounting for later initial evaluation/diagnosis. CONCLUSION: We described racial/ethnic differences in ages at selected diagnostic and treatment milestones. The most notable differences were significant delays for five of seven milestones in non-Hispanic black individuals, which appeared to be attributable to later initial evaluation/diagnosis. Findings for Hispanic individuals were less consistent. Efforts to address barriers to early evaluation and diagnosis for non-Hispanic black children with DMD may promote more timely initiation of recommended disease monitoring and interventions.

Evaluation of effects of continued corticosteroid treatment on cardiac and pulmonary function in non-ambulatory males with Duchenne muscular dystrophy from MD STARnet.

INTRODUCTION/AIMS: Corticosteroids have been shown to improve muscle strength and delay loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD) and are considered standard of care despite significant side-effects. The objective of this study is to evaluate whether corticosteroid treatment after LOA is beneficial for cardiac or pulmonary functions among boys with DMD. METHODS: We used the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to characterize associations between corticosteroid use and onset of abnormal left ventricular (LV) function or abnormal percent predicted forced vital capacity (ppFVC) among 398 non-ambulatory boys with DMD. Kaplan-Meier curve estimation was used to compare time to onset by corticosteroid use groups; Cox proportional hazards modeling was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals. RESULTS: We found no differences in time to onset of abnormal LV function by corticosteroid use groups. We observed a longer time from LOA to first abnormal ppFVC in boys that were treated with corticosteroid ≥1 y beyond LOA compared with those with no corticosteroid use or those who stopped corticosteroid use within 1 y of LOA. DISCUSSION: Our findings show no association of corticosteroid use beyond LOA with the onset of abnormal LV function, but a significant association with a delay in onset of abnormal ppFVC. Prospective studies of corticosteroid use in boys with DMD who have lost ambulation may identify benefits and can better elucidate risks, allowing for more effective counseling of patients on continuing treatment after LOA.

Incidence of Urinary Tract Infections in Newborns with Spina Bifida-Is Antibiotic Prophylaxis Necessary?

PURPOSE: Urinary tract infections commonly occur in patients with spina bifida and pose a risk of renal scarring. Routine antibiotic prophylaxis has been utilized in newborns with spina bifida to prevent urinary tract infections. We hypothesized that prophylaxis can safely be withheld in newborns with spina bifida until clinical assessment allows for risk stratification. MATERIALS AND METHODS: Newborns with myelomeningocele at 9 institutions were prospectively enrolled in the UMPIRE study and managed by a standardized protocol with a strict definition of urinary tract infection. Patient data were collected regarding details of reported urinary tract infection, baseline renal ultrasound findings, vesicoureteral reflux, use of clean intermittent catheterization and circumcision status in boys. Risk ratios and corresponding 95% confidence intervals were calculated using log-binomial models. RESULTS: From February 2015 through August 2019 data were available on 299 newborns (50.5% male). During the first 4 months of life, 48 newborns (16.1%) were treated for urinary tract infection with 23 (7.7%) having positive cultures; however, only 12 (4.0%) met the strict definition of urinary tract infection. Infants with grade 3-4 hydronephrosis had an increased risk of urinary tract infection compared to infants with no hydronephrosis (RR=10.1; 95% CI=2.8, 36.3). Infants on clean intermittent catheterization also had an increased risk of urinary tract infection (RR=3.3; 95% CI=1.0, 10.5). CONCLUSIONS: The incidence of a culture positive, symptomatic urinary tract infection among newborns with spina bifida in the first 4 months of life was low. Patients with high grades of hydronephrosis or those on clean intermittent catheterization had a significantly greater incidence of urinary tract infection. Our findings suggest that routine antibiotic prophylaxis may not be necessary for most newborns with spina bifida.

Duchenne and Becker Muscular Dystrophies' Prevalence in MD STARnet Surveillance Sites: An Examination of Racial and Ethnic Differences.

INTRODUCTION: Previous studies indicated variability in the prevalence of Duchenne and Becker muscular dystrophies (DBMD) by racial/ethnic groups. The Centers for Disease Control and Prevention's (CDC) Muscular Dystrophy Surveillance, Tracking, and Research network (MD STARnet) conducts muscular dystrophy surveillance in multiple geographic areas of the USA and continues to enroll new cases. This provides an opportunity to continue investigating differences in DBMD prevalence by race and ethnicity and to compare the impact of using varying approaches for estimating prevalence. OBJECTIVE: To estimate overall and race/ethnicity-specific prevalence of DBMD among males aged 5-9 years and compare the performance of three prevalence estimation methods. METHODS: The overall and race/ethnicity-specific 5-year period prevalence rates were estimated with MD STARnet data using three methods. Method 1 used the median of 5-year prevalence, and methods 2 and 3 calculated prevalence directly with different birth cohorts. To compare prevalence between racial/ethnic groups, Poisson modeling was used to estimate prevalence ratios (PRs) with non-Hispanic (NH) whites as the referent group. Comparison between methods was also conducted. RESULTS: In the final population-based sample of 1,164 DBMD males, the overall 5-year prevalence for DBMD among 5-9 years of age ranged from 1.92 to 2.48 per 10,000 males, 0.74-1.26 for NH blacks, 1.78-2.26 for NH whites, 2.24-4.02 for Hispanics, and 0.61-1.83 for NH American Indian or Alaska Native and Asian or Native Hawaiian or Pacific Islander (AIAN/API). The PRs for NH blacks/NH whites, Hispanics/NH whites, and NH AIAN/API/NH whites were 0.46 (95% CI: 0.36-0.59), 1.37 (1.17-1.61), and 0.61 (0.40-0.93), respectively. CONCLUSIONS: In males aged 5-9 years, compared to the prevalence of DBMD in NH whites, prevalence in NH blacks and NH AIAN/API was lower and higher in Hispanics. All methods produced similar prevalence estimates; however, method 1 produced narrower confidence intervals and method 2 produced fewer zero prevalence estimates than the other two methods.

Labor market participation and productivity costs for female caregivers of minor male children with Duchenne and Becker muscular dystrophies.

INTRODUCTION/AIMS: Duchenne and Becker muscular dystrophies (DBMD) are X-linked neuromuscular disorders characterized by progressive muscle weakness, leading to decreased mobility and multisystem complications. We estimate productivity costs attributable to time spent by a parent caring for a male child under the age of 18 y with DBMD, with particular focus on female caregivers of boys with Duchenne muscular dystrophy (DMD) who have already lost ambulation. METHODS: Primary caregivers of males with DBMD in the Muscular Dystrophy Surveillance and Research Tracking Network (MD STARnet) were surveyed during 2011-2012 on family quality of life measures, including labor market outcomes. Of 211 respondents, 96 female caregivers of boys with DBMD were matched on state, year of survey, respondent's age, child's age, and number of minor children with controls constructed from Current Population Survey extracts. Regression analysis was used to estimate labor market outcomes and productivity costs. RESULTS: Caregivers of boys with DBMD worked 296 h less per year on average than caregivers of unaffected children, translating to a $8816 earnings loss in 2020 U.S. dollars. Caregivers of boys with DMD with ≥4 y of ambulation loss had a predicted loss in annualized earnings of $23,995, whereas caregivers of boys with DBMD of the same ages who remained ambulatory had no loss of earnings. DISCUSSION: Female caregivers of non-ambulatory boys with DMD face additional household budget constraints through income loss. Failure to include informal care costs in economic studies could understate the societal cost-effectiveness of strategies for managing DMD that might prolong ambulation.

Association of genetic mutations and loss of ambulation in childhood-onset dystrophinopathy.

BACKGROUND: Quantifying associations between genetic mutations and loss of ambulation (LoA) among males diagnosed with childhood-onset dystrophinopathy is important for understanding variation in disease progression and may be useful in clinical trial design. METHODS: Genetic and clinical data from the Muscular Dystrophy Surveillance, Tracking, and Research Network for 358 males born and diagnosed from 1982 to 2011 were analyzed. LoA was defined as the age at which independent ambulation ceased. Genetic mutations were defined by overall type (deletion/duplication/point mutation) and among deletions, those amenable to exon-skipping therapy (exons 8, 20, 44-46, 51-53) and another group. Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Mutation type did not predict time to LoA. Controlling for corticosteroids, Exons 8 (HR = 0.22; 95% CI = 0.08, 0.63) and 44 (HR = 0.30; 95% CI = 0.12, 0.78) were associated with delayed LoA compared to other exon deletions. CONCLUSIONS: Delayed LoA in males with mutations amenable to exon-skipping therapy is consistent with previous studies. These findings suggest that clinical trials including exon 8 and 44 skippable males should consider mutation information prior to randomization.

Baseline Urinary Tract Imaging in Infants Enrolled in the UMPIRE Protocol for Children with Spina Bifida.

PURPOSE: The lifetime risk of renal damage in children with spina bifida is high but only limited baseline imaging data are available for this population. We evaluated a large prospective cohort of infants with spina bifida to define their baseline imaging characteristics. MATERIALS AND METHODS: The UMPIRE Protocol for Young Children with Spina Bifida is an iterative quality improvement protocol that follows a cohort of newborns at 9 United States centers. Using descriptive statistics, we report the initial baseline imaging characteristics, specifically regarding renal bladder ultrasound, cystogram and dimercaptosuccinic acid nuclear medicine scan. RESULTS: Data on 193 infants from 2015 to 2018 were analyzed. Renal-bladder ultrasound was normal in 55.9% of infants, while 40.4% had Society for Fetal Urology grade 1 to 2 hydronephrosis in at least 1 kidney, 3.7% had grade 3 to 4 hydronephrosis in either kidney and 21.8% had grade 1 or higher bilateral hydronephrosis. There was no vesicoureteral reflux in 84.6% of infants. A third of enrolled infants underwent dimercaptosuccinic acid nuclear medicine renal scan, of whom 92.4% had no renal defects and 93.9% had a difference in differential function of less than 15%. CONCLUSIONS: The majority of infants born with spina bifida have normal baseline imaging characteristics and normal urinary tract anatomy at birth. This proactive protocol offers careful scheduled surveillance of the urinary tract with the goal of lifelong maintenance of normal renal function and healthy genitourinary development.

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

BACKGROUND: Duchenne 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. METHODS: We 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. RESULTS: Higher 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. CONCLUSIONS: Findings 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.

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida.

PURPOSE: Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. MATERIALS AND METHODS: In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. RESULTS: An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. CONCLUSIONS: The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements.

Selected clinical and demographic factors and all-cause mortality among individuals with Duchenne muscular dystrophy in the Muscular Dystrophy Surveillance, Tracking, and Research Network.

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.