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.

Weight Status of Children Participating in the National Spina Bifida Patient Registry.

OBJECTIVES: Describe the distribution of weight status categories and determine factors associated with overweight and obesity (OW/OB) in children and adolescents with spina bifida (SB) using the National Spina Bifida Patient Registry. METHODS: Demographic, anthropometric, and clinical data collected from 2009 through 2018 was used to describe the prevalence of OW/OB. The generalized estimating equation model (GEE) identified factors associated with OW/OB among individuals with SB. RESULTS: Participants (n = 7215) were aged 2 to 19 years (mean = 11.1; standard error, 0.06) and 51.4% female. The majority were non-Hispanic white (57.2%) followed by Hispanic or Latino (25.1%) and non-Hispanic Black (7.5%). The myelomeningocele (MMC) subgroup accounted for 76.3%. Most (60.2%) were community ambulators. The overall percentage of OW/OB was 45.2%, with 49.2% of MMC and 32.0% of nonmyelomeningocele OW/OB. Following the Centers for Disease Control Obesity Severity Classification System, 19.7% of MMC were in class 1, 6.6% in class 2, and 3.5% in class 3. Univariate analysis of MMC participants demonstrated demographic (age, sex, race/ethnicity, and clinic region) and clinical variables (functional level of lesion, ambulation, and number of shunt surgeries) were associated with OW/OB. The GEE model showed that OW/OB was independently, and significantly, associated with age, sex, race/ethnicity, lesion levels, and geographic location of the clinics. CONCLUSIONS: The demographic and clinical factors associated with OW/OB in children and adolescents with SB further our understanding of factors contributing to the higher prevalence of OW/OB in this population and may inform OW/OB prevention and treatment strategies.

Association between age of starting clean intermittent catheterization and current urinary continence in individuals with myelomeningocele.

INTRODUCTION: Patients with myelomeningocele often use clean intermittent catheterization (CIC) for renal preservation and to promote urinary continence. While starting CIC at an early age is associated with better renal outcomes, the impact of age of CIC initiation on continence outcomes has not been examined. OBJECTIVE: To examine whether earlier CIC initiation is associated with higher likelihood of current urinary continence for patients with myelomeningocele. STUDY DESIGN: Data of patients aged ≥5 years at last visit were obtained from 35 spina bifida clinics participating in the National Spina Bifida Patient Registry from 2013 to 2018. Sociodemographic characteristics, disease characteristics, and current bladder management strategies were collected. Via univariate and multiple logistic regression models, the latter conducted controlling for all variables associated with current continent status, associations between continence and sociodemographic factors, condition characteristics, and age CIC began (<3 years of age, 3-5 years, 6-11 years, ≥12 years) were analyzed. RESULTS: Data from 3510 individuals were included (mean age at last visit = 17.0 years, range 5.0-88.7). The sample was evenly distributed by sex (52% female); most individuals were non-Hispanic White (62.6%). The majority of patients (55.2%) started CIC before age 3 years. Continence varied markedly across those who never started CIC (0.6% of patients were continent) and those who started at any age (range 35.3-38.5%). Among those who started CIC, the magnitude of the association was not proportional to age CIC was started. Compared with those who started CIC at age 12 or older, estimated adjusted odds ratio of being continent ranged from 1.04 (6-11 years, 95% CI, 0.72-1.52) to 1.25 (<3 years, 95% CI, 0.89-1.76). DISCUSSION: Although CIC may be positively associated with achieving urinary continence in individuals with myelomeningocele, we could not demonstrate that younger age at CIC initiation increased the likelihood of achieving this goal. Limitations include lack of data on reason for starting CIC, urodynamic data, and the observational nature of data collection. CONCLUSIONS: Further study is needed addressing limitations of the current investigation to determine if urinary continence outcomes are influenced by the age of starting CIC among patients with myelomeningocele.

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.

Epidemiology of Pediatric Hypertrophic Cardiomyopathy in a 10-Year Medicaid Cohort.

The epidemiologic data for pediatric hypertrophic cardiomyopathy (HCM) needs to be periodically updated as diagnostic techniques and management strategies improve. Herein, the incidence, prevalence, and mortality rates of pediatric HCM in a population-based treatment system are described. Patients aged ≤ 17 years and diagnosed with HCM on service visits over a 10-year period in one state Medicaid database (2007-2016) were analyzed. The cohort included 137 unique patients; 64.2% were male; 40.9% were African American; 42.3% were first diagnosed ≤ 24 months. The accrued 10-year prevalence rate for pediatric HCM was 1.2/1,000,000 and the annual incidence rate (CY 2010) was 1.3/100,000. Cardiac-related mortality was 2.9% in those who died cohort (N = 10); 70.0% of those who died were ≤ 13 months of age. Arrhythmia was diagnosed in 30.7% of the cohort, heart failure in 12.4%, and low birth weight in 8.8%. Inborn errors of metabolism were diagnosed in 8.0% of the cohort; malformation syndromes in 13.1%, and neuromuscular disorders in 2.9%; therefore, 75.9% were classified as idiopathic HCM. Our findings are somewhat higher than extant study estimates but update and augment them in representing a Southeast US statewide service system.

Risk factors for falls among boys under 18 years with muscular dystrophy.

PURPOSE: Studies have shown that children with muscular dystrophy are at increased risk for falls, however there is insufficient information about what predicts the first and subsequent events. The purpose of this study was to describe the experience of injury with emphasis on identifying risk factors for fall-related injuries. METHODS: We studied 269 boys with muscular dystrophy describing their injury experience and identifying risk and protective factors associated with 281 non-simultaneous injuries and 127 falls that resulted in Emergency Department visits and/or inpatient hospitalization during the period 1998-2014. We used a Cox model to estimate the predictors of an initial fall and a zero-inflated Poisson model to identify the predictors for the number of falls. RESULTS: Falls accounted for the greatest number of injury occurrences; The most frequent injury type was contusion. The factors that were protective for falls were steroid use, wheelchair use, or having a heart condition. Baseline age was negatively associated with the risk of having any fall, but not significantly related to subsequent falls. CONCLUSION: Wheelchair use and heart conditions associated with reduced risk of falls likely reflects decreased mobility. Clinicians should help families identify factors associated with falls among those who remain ambulatory.

Differences in Length of Stay and Costs Between Comparable Hospitalizations of Patients With Spina Bifida With or Without Pressure Injuries.

OBJECTIVE: To estimate differences in the length of stay and costs for comparable hospitalizations of patients with spina bifida (SB) with and without pressure injuries. DESIGN: Retrospective, cross-sectional, observational study. SETTING: Nationwide Inpatient Sample from years 2010-2014. PARTICIPANTS: Hospitalizations of patients with SB (N=7776). Hospitalizations among patients with SB and pressure injuries (n=3888) were matched to hospitalizations among patients with SB but without pressure injuries (n=3888). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Differences in length of stay and total costs between the 2 groups. RESULTS: After successful matching, multivariate modeling of costs and length of stay on matched sample showed that hospitalizations with pressure injuries had an increased 1.2 inpatient days and excess average costs of $1182 in 2014 dollars. CONCLUSIONS: The estimated average cost of hospitalization increased by 10%, and the estimated average length of stay increased by 24% in the presence of pressure injuries among hospitalized patients with SB, compared with their peers without these injuries. These results highlight the substantial morbidity associated with pressure injuries, which are potentially preventable before or during hospitalizations among persons with SB.

Gender difference in clinical conditions among hospitalized adults with myotonic dystrophy.

INTRODUCTION: In this study we examined gender differences in adult hospitalizations with myotonic dystrophy (DM). METHODS: From the Nationwide Inpatient Sample (NIS) 2010-2014, we identified 1,891 adult hospitalizations with a DM diagnosis and constructed a comparison group of hospitalizations without DM using propensity score matching. We calculated relative risk by gender for 44 clinical diagnoses that each accounted for at least 5% of DM hospitalizations. RESULTS: Hospitalizations with DM were longer (4.8 vs. 4.1 days, P < 0.0001) and more costly ($13,241 vs. $11,458, P < 0.0001) than those without DM. More than half (25 of 44) of the conditions co-occurring with DM hospitalizations did not differ in their relative risks by gender. For those that differed by gender, only 5 were specific to DM, compared with hospitalizations without DM. DISCUSSION: Our findings highlight the importance of comprehensive and coordinated care for DM rather than gender-oriented care in the inpatient setting. Muscle Nerve 59:348-353, 2019.

Population-based treated prevalence, risk factors, and outcomes of bicuspid aortic valve in a pediatric Medicaid cohort.

BACKGROUND: We investigated the treated prevalence of bicuspid aortic valve in a pediatric population with congenital heart disease and its incident complications. MATERIALS AND METHODS: A 15-year retrospective data set was analyzed. Selection criteria included age ≤17 years, enrollees in the South Carolina State Medicaid program and diagnosed as having bicuspid aortic valve on one or more service visits. RESULTS: The 15-year-treated prevalence of predominantly isolated bicuspid aortic valve was 2% (20/1000) of pediatric congenital heart disease cases, with a non-African American: African-American ratio of 3.5:1, and a male:female ratio of 1.6:1. Aortic stenosis (28.0%), ventricular septal defect (20.6%), and coarctation of the aorta (20.6%) were the most prevalent coexisting congenital heart lesions. Of the 378 bicuspid aortic valve cases examined, 10.3% received aortic valve repair/replacement, which was significantly more likely to be performed in children with diagnosed aortic stenosis (adjusted odds ratio = 12.90; 95% confidence interval = 5.66-29.44). Cohort outcomes over the study period indicated that 9.5% had diagnosed heart failure, but <1% had diagnosed supraventricular tachycardia, infective endocarditis, aneurysm, dissection, or death. CONCLUSIONS: The majority of isolated bicuspid aortic valve cases without aortic stenosis did not require surgical intervention. Outcomes for cases requiring repair/replacement were relatively benign.

Risk Factors for Heart Failure and Its Costs Among Children with Complex Congenital Heart Disease in a Medicaid Cohort.

Little research attention has been paid to the occurrence of heart failure (HF) in children with complex congenital heart diseases (CHDs). Herein, we describe the prevalence, risk factors, and costs associated with HF in complex CHD. Patients aged ≤17 years and diagnosed with a complex CHD on multiple service visits over a 15-year period in the SC Medicaid dataset (1996-2010) were tracked and analyzed. The cohort included 2999 unduplicated patients; 51.0% were male; 34.4% were African American. HF was diagnosed in 7.6%. Single ventricle lesions, genetic syndromes, and ventricular arrhythmia were significantly associated with an increased likelihood of being diagnosed with HF, controlling for development of comorbid pulmonary hypertension. Patients with HF received significantly more subspecialty care, more surgeries, more hospitalizations, more total days of inpatient care, and more emergency department care than those without HF. Patients with significantly higher total care costs paid by Medicaid had HF, more cardiac surgeries, and more specialized mechanical or other support procedures, controlling for diagnosed single ventricle CHD, a genetic syndrome, and number of non-cardiac surgeries. Complex CHD patients with HF incur significantly higher care costs but require multifaceted, intensive supports for management of incident complications and comorbid conditions.

Factors Associated With Musculoskeletal Injuries in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Musculoskeletal injuries may be associated with attention-deficit/hyperactivity disorder (ADHD) symptom severity, comorbid psychiatric or medical conditions, and the prescribed psychostimulant. METHODS: A population-based, retrospective cohort design was employed using South Carolina's Medicaid claims data set covering outpatient and inpatient medical services and medication prescriptions over an 11-year period (January 1, 1996, through December 31, 2006) for patients ≤ 17 years of age with ≥ 2 visits for ICD-9-CM diagnostic codes for ADHD. A cohort of 7,725 cases was identified and analyzed using logistic regression to compare risk factors for those who sustained focal musculoskeletal injuries and those who did not. RESULTS: The risk of sustaining sprains, arthropathy and connective tissue disorders, or muscle and joint disorders was significantly related to being diagnosed with comorbid hypertension (adjusted odds ratios [aORs] = 1.60, 2.09, and 1.46, respectively) and a substance use disorder (aORs = 1.58, 1.38, and 1.28). Having a substance use disorder was also related to incident fractures and dorso/spinal injuries (aORs = 1.42 and 1.21). Diagnosed hypertension was related to incident concussions (aOR = 2.00), a diagnosed thyroid disorder was related to an increased risk of sprain and concussion (aORs = 1.44 and 2.05), a diagnosed anxiety disorder was related to an increased risk of dorso/spinal disorders (aOR = 1.71), and diagnosed diabetes was related to incident bone and cartilage disorders (aOR = 1.61). CONCLUSIONS: Comorbid hypertension, substance use disorders, and thyroid disorders deserve increased clinical surveillance in children and adolescents with ADHD because they may be associated with an increased risk of more than one musculoskeletal injury.

The use of a physiologically-based extraction test to assess relationships between bioaccessible metals in urban soil and neurodevelopmental conditions in children.

Intellectual disability (ID) and cerebral palsy (CP) are serious neurodevelopment conditions and low birth weight (LBW) is correlated with both ID and CP. The actual causes and mechanisms for each of these child outcomes are not well understood. In this study, the relationship between bioaccessible metal concentrations in urban soil and these child conditions were investigated. A physiologically based extraction test (PBET) mimicking gastric and intestinal processes was applied to measure the bio-accessibility of four metals (cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb)) in urban soil, and a Bayesian Kriging method was used to estimate metal concentrations in geocoded maternal residential sites. The results showed that bioaccessible metal concentrations of Cd, Ni, and Pb in the intestinal phase were statistically significantly associated with the child outcomes. Lead and nickel were associated with ID, lead and cadmium was associated with LBW, and cadmium was associated with CP. The total concentrations and stomach concentrations were not correlated to significant effects in any of the analyses. For lead, an estimated threshold value was found that was statistically significant in predicting low birth weight. The change point test was statistically significant (p value = 0.045) at an intestine threshold level of 9.2 mg/kg (95% confidence interval 8.9-9.4, p value = 0.0016), which corresponds to 130.6 mg/kg of total Pb concentration in the soil. This is a narrow confidence interval for an important relationship.

Preventing intellectual disability during pregnancy: what are the potentially high yield targets?

OBJECTIVE: To identify risk factors among children with unknown cause intellectual disability (ID) and to estimate the population-attributable risk (PAR) associated with these factors. METHODS: This was a retrospective cohort study of maternal and child pairs born between 2004 and 2010 in South Carolina, and information was obtained from Medicaid billing records, birth certificates, and other administrative data. The data included 123,922 children and logistic generalized estimating equations (GEE) regression models were used to estimate the association of maternal risk factors and ID. We estimated models with and without birth weight as a covariate, since low birth weight is known to be a mediator of the association between some risk factors and ID in children. RESULTS: The prevalence of ID in the children was 3.85% and the associations between risk factors and ID were similar for female and male children. We found that the odds of having ID were increased if a child's mother had a diagnosis of major depression; for male children, the odds ratio (OR) was 1.34 (95% confidence interval [CI] 1.14-1.59, PAR 2.17%); and for females, the OR was 1.59 (95% CI 1.30-1.95, PAR 4.70%). The odds of having ID were also increased for children of women with bipolar disorder (males - OR 1.95, 95% CI 1.53-2.48, PAR 2.85%; females - OR 1.63, 95% CI 1.20-2.22, PAR 2.05%). CONCLUSIONS: Major maternal depression and bipolar disorder were each significantly associated with the odds of ID in children, each accounting for approximately 2-5% of the PAR, when controlling for covariates.

Skin Ulcers and Mortality Among Adolescents and Young Adults With Spina Bifida in South Carolina During 2000-2010.

The authors investigated 48 deaths (7% death rate) among 690 adolescents and young adults with spina bifida in South Carolina during 2000-2010. The authors used Medicaid and other administrative data and a retrospective cohort design that included people with spina bifida identified using ICD-9 codes. Cox regression models with time-dependent and time-invariant covariates, and Kaplan-Meier survival curves were constructed. The authors found that 21.4% of the study group had a skin ulcer during the study period and individuals with skin ulcers had significantly higher mortality than those without ulcers (P < .0001). People who had their first skin ulcer during adolescence had higher mortality than those who had the first skin ulcer during young adulthood (P = .0002; hazard ratio = 10.70, 95% confidence interval for hazard ratio: 3.01, 38.00) and those without skin ulcers, controlling for other covariates. This study showed that age at which individuals first had a skin ulcer was associated with mortality.

HPV prevalence at enrollment and baseline results from the Carolina Women's Care Study, a longitudinal study of HPV persistence in women of college age.

BACKGROUND: Cervical cancer, a rare outcome of high-risk human papillomavirus (HPV) infection, disproportionately affects African American women, who are about twice more likely than European American women to die of the disease. Most cervical HPV infections clear in about one year. However, in some women HPV persists, posing a greater risk for cervical dysplasia and cancer. The Carolina Women's Care Study (CWCS) was conducted to explore the biological, genetic, and lifestyle determinants of persistent HPV infection in college-aged European American and African American women. This paper presents the initial results of the CWCS, based upon data obtained at enrollment. METHODS: Freshman female students attending the University of South Carolina were enrolled in the CWCS and followed until graduation with biannual visits, including two Papanicolaou tests, cervical mucus collection, and a questionnaire assessing lifestyle factors. We recruited 467 women, 293 of whom completed four or more visits for a total of 2274 visits. RESULTS AND CONCLUSION: CWCS participants were 70% European American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment, 32% tested positive for any HPV. HPV16 infection was the most common (18% of infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV infections. Sixty-four percent of all HPV-positive samples contained more than one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We found differences between African American and European American women in the prevalence of HPV infection (38.1% African American, 30.7% European American) and abnormal Papanicolaou test results (9.8% African-American, 5.8% European American). While these differences did not reach statistical significance at enrollment, as the longitudinal data of this cohort are analyzed, the sample size will allow us to confirm these results and compare the natural history of HPV infection in college-aged African American and European American women.