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.

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.

Longitudinal Study of Bladder Continence in Patients with Spina Bifida in the National Spina Bifida Patient Registry.

PURPOSE: Achieving bladder continence in individuals with spina bifida is a lifetime management goal. We investigated bladder continence status through time and factors associated with this status in patients with spina bifida. MATERIALS AND METHODS: We used National Spina Bifida Patient Registry data collected from 2009 through 2015 and applied generalized estimating equation models to analyze factors associated with bladder continence status. RESULTS: This analysis included 5,250 participants with spina bifida in a large, multi-institutional patient registry who accounted for 12,740 annual clinic visit records during the study period. At last followup mean age was 16.6 years, 22.4% of participants had undergone bladder continence surgery, 92.6% used some form of bladder management and 45.8% reported bladder continence. In a multivariable regression model the likelihood of bladder continence was significantly greater in those who were older, were female, were nonHispanic white, had a nonmyelomeningocele diagnosis, had a lower level of lesion, had a higher mobility level and had private insurance. Continence surgery history and current management were also associated with continence independent of all other factors (adjusted OR and 95% CI 1.9, 1.7-2.1 and 3.8, 3.2-4.6, respectively). The association between bladder management and continence was stronger for those with a myelomeningocele diagnosis (adjusted OR 4.6) than with nonmyelomeningocele (adjusted OR 2.8). CONCLUSIONS: In addition to demographic, social and clinical factors, surgical intervention and bladder management are significantly and independently associated with bladder continence status in individuals with spina bifida. The association between bladder management and continence is stronger in those with myelomeningocele.

The effect of steroid treatment on weight in nonambulatory males with Duchenne muscular dystrophy.

To describe the long-term effect of steroid treatment on weight in nonambulatory males with Duchenne Muscular Dystrophy (DMD), we identified 392 males age 7-29 years with 4,512 weights collected after ambulation loss (176 steroid-naïve and 216 treated with steroids ≥6 months) from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Comparisons were made between the weight growth curves for steroid-naïve males with DMD, steroid-treated males with DMD, and the US pediatric male population. Using linear mixed-effects models adjusted for race/ethnicity and birth year, we evaluated the association between weight-for-age and steroid treatment characteristics (age at initiation, dosing interval, cumulative duration, cumulative dose, type). The weight growth curves for steroid-naïve and steroid-treated nonambulatory males with DMD were wider than the US pediatric male growth curves. Mean weight-for-age z scores were lower in both steroid-naïve (mean = -1.3) and steroid-treated (mean = -0.02) nonambulatory males with DMD, compared to the US pediatric male population. Longer treatment duration and greater cumulative dose were significantly associated with lower mean weight-for-age z scores. Providers should consider the effect of steroid treatment on weight when making postambulation treatment decisions for males with DMD.

PhenX measures for phenotyping rare genetic conditions.

INTRODUCTION: The PhenX Toolkit, an online resource of well-established measures of phenotypes and exposures, now has 16 new measures recommended for assessing rare genetic conditions. MATERIALS AND METHODS: These measures and their protocols were selected by a working group of domain experts with input from the scientific community. RESULTS: The measures, which cover life stages from birth through adulthood, include clinical scales, characterization of rare genetic conditions, bioassays, and questionnaires. Most are broadly applicable to rare genetic conditions (e.g., family history, growth charts, bone age, and body proportions). Some protocols (e.g., sweat chloride test) target specific conditions. DISCUSSION: The rare genetic condition measures complement the existing measures in the PhenX Toolkit that cover anthropometrics, demographics, mental health, and reproductive history. They are directed at research pertaining to common and complex diseases. PhenX measures are publicly available and are recommended to help standardize assessments across a range of biomedical study designs. To facilitate incorporation of measures into human subjects' research, the Toolkit offers data collection worksheets and compatible data dictionaries. CONCLUSION: Widespread use of standard PhenX measures in clinical, translational, and epidemiological research will enable more uniform cross-study comparisons and increase statistical power with the potential for enhancing scientific discovery.Genet Med advance online publication 12 January 2017.

Characteristics and survival of patients with end stage renal disease and spina bifida in the United States renal data system.

PURPOSE: We describe the characteristics, treatments and survival of patients with spina bifida in whom end stage renal disease developed from 2004 through 2008 in the United States Renal Data System. MATERIALS AND METHODS: We used ICD-9-CM code 741.* to identify individuals with spina bifida using hospital inpatient data from 1977 to 2010, and physician and facility claims from 2004 to 2008. We constructed a 5:1 comparison group of patients with end stage renal disease without spina bifida matched by age at first end stage renal disease service, gender and race/ethnicity. We assessed the risk of mortality and of renal transplantation while on dialysis using multivariate cause specific proportional hazards survival analysis. We also compared survival after the first renal transplant from the first end stage renal disease service to August 2011. RESULTS: We identified 439 patients with end stage renal disease and spina bifida in whom end stage renal disease developed at an average younger age than in patients without spina bifida (41 vs 62 years, p <0.001) and in whom urological issues were the most common primary cause of end stage renal disease. Compared to patients with end stage renal disease without spina bifida those who had spina bifida showed a similar mortality hazard on dialysis and after transplantation. However, patients with end stage renal disease without spina bifida were more likely to undergo renal transplantation than patients with spina bifida (HR 1.51, 95% CI 1.13-2.03). Hospitalizations related to urinary tract infections were positively associated with the risk of death on dialysis in patients with end stage renal disease and spina bifida (HR 1.42, 95% CI 1.33-1.53). CONCLUSIONS: Spina bifida was not associated with increased mortality in patients with end stage renal disease on dialysis or after renal transplantation. Proper urological and bladder management is imperative in patients with spina bifida, particularly in adults.

Age-Specific Probability of 4 Major Health Outcomes in Children with Spina Bifida.

OBJECTIVE: This study aimed to estimate the age-specific probability of 4 health outcomes in a large registry of individuals with spina bifida (SB). METHODS: The association between age and 4 health outcomes was examined in individuals with myelomeningocele (MMC, n = 5627) and non-myelomeningocele (NMMC, n = 1442) from the National Spina Bifida Patient Registry. Sixteen age categories were created, 1 for each year between the ages of 5 and 19 years and 1 for those aged 20 years or older. Generalized linear models were used to calculate the adjusted probability and 95% prediction intervals of each outcome for each age category, adjusting for sex and race/ethnicity. RESULTS: For the MMC and NMMC groups, the adjusted coefficients for the correlation between age and the probability of each outcome were -0.933 and -0.657 for bladder incontinence, -0.922 and -0.773 for bowel incontinence, 0.942 and 0.382 for skin breakdown, and 0.809 and 0.619 for lack of ambulation, respectively. CONCLUSION: In individuals with SB, age is inversely associated with the probability of bladder and bowel incontinence and directly associated with the probability of skin breakdown and lack of ambulation. The estimated age-specific probabilities of each outcome can help SB clinicians estimate the expected proportion of patients with the outcome at specific ages and explain the probability of the occurrence of these outcomes to patients and their families.

Barriers in identification and referral to genetic counseling for familial cancer risk: the perspective of genetic service providers.

The purpose of this study was to obtain genetic counselors' perspectives about the identification of appropriate patients and barriers to referral of high-risk patients for cancer genetic counseling services. Genetic service providers from eight integrated health systems were surveyed. Data analysis included descriptive statistics. Twenty-eight of 40 potential participants responded (70%). Referrals for familial cancer risk assessment overwhelmingly came from providers (89%); only 10% were self-referrals. Use of guidelines to assist providers with referral was reported by 46% of the respondents. Genetic service providers perceived patient barriers to seeking genetic counseling after referral included: risk evaluation viewed as a non-priority (72%), concerns about impact on insurability (52%), distance to appointments (48%), lack of insurance (44%), lack of patient/provider knowledge about the value of genetic counseling (36%), discouragement by family members (28%), and fear (20%). The best approaches suggested by respondents to increase appropriate referrals were attending meetings and giving presentations to oncologists, surgeons, primary care and gynecologists. The genetic service providers reported several barriers to the referral and use of genetic counseling. This finding is consistent with current literature from the providers' perspective. Our survey adds the genetic service providers' perspective and identifies areas of opportunity for further research and intervention as few of the perceived barriers are being addressed through current educational efforts.

Improvements in ability to detect undiagnosed diabetes by using information on family history among adults in the United States.

Family history is an independent risk factor for diabetes, but it is not clear how much adding family history to other known risk factors would improve detection of undiagnosed diabetes in a population. Using the National Health and Nutrition Examination Survey for 1999-2004, the authors compared logistic regression models with established risk factors (model 1) with a model (model 2) that also included familial risk of diabetes (average, moderate, and high). Adjusted odds ratios for undiagnosed diabetes, using average familial risk as referent, were 1.7 (95% confidence interval (CI): 1.2, 2.5) and 3.8 (95% CI: 2.2, 6.3) for those with moderate and high familial risk, respectively. Model 2 was superior to model 1 in detecting undiagnosed diabetes, as reflected by several significant improvements, including weighted C statistics of 0.826 versus 0.842 (bootstrap P = 0.001) and integrated discrimination improvement of 0.012 (95% CI: 0.004, 0.030). With a risk threshold of 7.3% (sensitivity of 40% based on model 1), adding family history would identify an additional 620,000 (95% CI: 221,100, 1,020,000) cases without a significant change in false-positive fraction. Study findings suggest that adding family history of diabetes can provide significant improvements in detecting undiagnosed diabetes in the US population. Further research is needed to validate the authors' findings.

Family history in public health practice: a genomic tool for disease prevention and health promotion.

Family history is a risk factor for many chronic diseases, including cancer, cardiovascular disease, and diabetes. Professional guidelines usually include family history to assess health risk, initiate interventions, and motivate behavioral changes. The advantages of family history over other genomic tools include a lower cost, greater acceptability, and a reflection of shared genetic and environmental factors. However, the utility of family history in public health has been poorly explored. To establish family history as a public health tool, it needs to be evaluated within the ACCE framework (analytical validity; clinical validity; clinical utility; and ethical, legal, and social issues). Currently, private and public organizations are developing tools to collect standardized family histories of many diseases. Their goal is to create family history tools that have decision support capabilities and are compatible with electronic health records. These advances will help realize the potential of family history as a public health tool.

Application of support vector machine modeling for prediction of common diseases: the case of diabetes and pre-diabetes.

BACKGROUND: We present a potentially useful alternative approach based on support vector machine (SVM) techniques to classify persons with and without common diseases. We illustrate the method to detect persons with diabetes and pre-diabetes in a cross-sectional representative sample of the U.S. population. METHODS: We used data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) to develop and validate SVM models for two classification schemes: Classification Scheme I (diagnosed or undiagnosed diabetes vs. pre-diabetes or no diabetes) and Classification Scheme II (undiagnosed diabetes or pre-diabetes vs. no diabetes). The SVM models were used to select sets of variables that would yield the best classification of individuals into these diabetes categories. RESULTS: For Classification Scheme I, the set of diabetes-related variables with the best classification performance included family history, age, race and ethnicity, weight, height, waist circumference, body mass index (BMI), and hypertension. For Classification Scheme II, two additional variables--sex and physical activity--were included. The discriminative abilities of the SVM models for Classification Schemes I and II, according to the area under the receiver operating characteristic (ROC) curve, were 83.5% and 73.2%, respectively. The web-based tool-Diabetes Classifier was developed to demonstrate a user-friendly application that allows for individual or group assessment with a configurable, user-defined threshold. CONCLUSIONS: Support vector machine modeling is a promising classification approach for detecting persons with common diseases such as diabetes and pre-diabetes in the population. This approach should be further explored in other complex diseases using common variables.

A historical overview of the United States-Mexico Border Diabetes Prevention and Control Project.

Diabetes is a serious public health problem in the border region between the United States of America and Mexico, reflecting and by some measures surpassing the extent of national diabetes burden of each country. The U.S.-Mexico Border Diabetes Prevention and Control Project, a two-phase prevalence study on type 2 diabetes and its risk factors, was conceived and developed by culturally diverse groups of people representing more than 100 government agencies and nongovernmental organizations; health care providers; and residents of 10 U.S. and Mexican border states, using a participatory approach, to address this disproportionate incidence of diabetes. This report describes the project's history, conceptualization, participatory approach, implementation, accomplishments, and challenges, and recommends a series of steps for carrying out other binational participatory projects based on lessons learned.

The association between family history of asthma and the prevalence of asthma among US adults: National Health and Nutrition Examination Survey, 1999-2004.

PURPOSE: To assess the overall prevalence of asthma and the association between family history of asthma and the prevalence of asthma among US adults. METHODS: We analyzed National Health and Nutrition Examination Survey data from 1999 to 2004 for 15,008 respondents aged 20 years or older with no history of emphysema. We divided respondents into three familial risk groups (high, moderate, and average) on the basis of the number and closeness of relatives, that they reported as having asthma and then assessed the asthma prevalence in each. We also assessed associations between asthma prevalence and age, sex, race/ethnicity, income, body mass index, smoking status, household smoking exposure, and physical activity. RESULTS: By our definitions, 2.3% of respondents were at high, 13.0% at moderate, and 84.7% at average familial risk for asthma. The crude prevalence of self-reported lifetime asthma was 11.5% (95% confidence interval [CI]: 10.7-12.3%) among all respondents, and 37.6% (95% CI: 30.4-45.4%), 20.4% (95% CI: 18.2-22.7%), and 9.4% (95% CI: 8.7-10.2%) among those at high, moderate, and average familial risk, respectively. Among all risk factors we looked at, family history had the strongest association with lifetime asthma prevalence, and the association remained significant after adjustments for other risk factors. Compared with average familial risk, the adjusted odds ratios for lifetime asthma were 2.4 (95% CI: 2.0 -2.8) for moderate and 4.8 (95% CI: 3.5-6.7) for high familial risk. CONCLUSION: Our findings showed that a family history of asthma is an important risk factor for asthma and that familial risk assessments can help identify people at highest risk for developing asthma. Additional research is needed to assess how health care professionals can use family history information in the early detection and management of asthma.

Does frank diabetes in first-degree relatives of a pregnant woman affect the likelihood of her developing gestational diabetes mellitus or nongestational diabetes?

OBJECTIVE: We sought to examine the associations between patterns of family histories of diabetes and a history of gestational diabetes mellitus (hGDM). STUDY DESIGN: Parous women participating in the National Health and Nutrition Examination Survey III (n=4566) were classified as having hGDM only, diagnosed diabetes, or neither. Family history of diabetes was categorized as: maternal only, paternal only, biparental, and sibling only. The covariate-adjusted prevalence and odds of having hGDM were estimated. RESULTS: Compared to women without a family history of diabetes, women with a maternal (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.2-7.3), paternal (OR, 3.3; 95% CI, 1.1-10.2), or sibling (OR, 7.1; 95% CI, 1.6-30.9) history of diabetes had greater odds of hGDM, after adjustment for age and race/ethnicity. CONCLUSION: Women with a sibling history of diabetes were more likely to have hGDM than women with other family history patterns.

A Review of MD STAR net'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 STAR net) in 2002 in the United States. From 2002 to 2012, MD STAR net 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 STAR net peer-reviewed publications. MD STAR net 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.

Preventive care services and health behaviors in children with fragile X syndrome.

BACKGROUND: This is the first description of preventive care services specifically received by children and young adults with fragile X syndrome (FXS). We compare these rates to those of other pediatric populations and identify care disparities within our cohort. OBJECTIVE: Describe the frequency of preventive care services and health behaviors by young people with FXS, and identify disparities in care. METHODS: We assessed four preventive care outcomes and the total number of preventive care guidelines met among individuals under 21 years from the ongoing Fragile X Online Registry with Accessible Research Database (N = 406) using data from 2012 to 2015. We used adjusted odds ratios (AORs) from multiple logistic regression models to describe associations between demographic factors and preventive care outcomes. RESULTS: Seventy-five percent of our sample met dental care guidelines, 55.4% met influenza vaccination guidelines, 92.1% met immunization guidelines, and 24.4% met physical activity (PA) guidelines. Compared to children six to 10 years, younger children were less likely to have seen a dentist as recommended (AOR: 0.26) and young adults aged 16-20 were less likely to have received immunizations (AOR: 0.14) or to have engaged in recommended PA (AOR: 0.29). Black participants (AOR: 0.25) were less likely to have received an influenza vaccination than white participants. Individuals with autism (AOR: 0.25) were less likely to have sufficient PA, while individuals with hypersensitivity were more likely to have sufficient PA (AOR: 2.37) than unaffected individuals. CONCLUSIONS: The proportion of young people with FXS that meet basic recommendations in preventive care guidelines varies according to health condition and demographic characteristics. This proportion could be increased for some groups, particularly in the cases of influenza vaccination and physical activity.

A compilation of national plans, policies and government actions for rare diseases in 23 countries.

Previous studies have focused on the comparison of specific laws among multiple countries and regions; for example, laws related to facilitating treatments with orphan drugs or laws seeking to address the multiple needs of patients with rare diseases. The purpose of this scoping review is to examine and compare published reports on national plans, polices and legislation related to all rare diseases in different countries. We also examine strategies or programs that countries may have for these diseases. Articles were obtained from journals and books published between January 1, 2000, through December 15, 2017. Reports from the grey literature (documents issued by government and private organizations) were included if they were available on the internet. The databases used were Google and Google Scholar, PubMed, and the websites of Orphanet and the National Organization for Rare Disorders (NORD). We obtained information on 23 countries. Among these countries, the way in which rare diseases were defined varied from having similar definitions to no definition. Multinational programs supported by common or similar laws are likely to have a greater impact on rare diseases than single country programs.

Changes in care coordination and health insurance in the population of US children with muscular dystrophy, 2005-2006 and 2009-2010.

INTRODUCTION: We aimed to assess changes in care coordination and health insurance coverage among US children with muscular dystrophy. METHODS: We used 2005-2006 and 2009-2010 data from the National Survey of Children with Special Health Care Needs. We examined the distribution of sociodemographic and health characteristics of children with muscular dystrophy by survey cycle. Multivariable regression was used to calculate odds of not receiving effective care coordination, not having adequate health insurance coverage, receiving no help coordinating care, and having problems obtaining referrals in each survey cycle. RESULTS: In the 2005-2006 and 2009-2010 survey cycles, there were 135 and 117 children with muscular dystrophy (representing 34,672 and 31,169 US children with muscular dystrophy), respectively. The percentage of children with muscular dystrophy who did not receive effective care coordination changed from 59.2% (95% confidence interval (CI), 45.6%-72.7%) in 2005-2006 to 53.4% (95% CI, 38.3%-68.6%) in 2009-2010. The odds of not receiving effective care coordination (adjusted odds ratio (aOR) = 0.77; 95% CI, 0.32-1.89) or having problems obtaining referrals (aOR = 0.52; 95% CI, 0.17-1.59) did not change significantly between the two periods, whereas odds of having inadequate insurance coverage decreased significantly (aOR = 0.41, 95% CI, 0.18-0.93) and odds of not receiving help coordinating care increased significantly (aOR = 4.22, 95% CI, 1.24-14.29) between the two periods. CONCLUSION: Our results suggest key health care needs for many families with children with muscular dystrophy have remained unmet for a prolonged period. Although there were significant improvements in health insurance coverage, nearly one-third of children with muscular dystrophy still had inadequate health insurance coverage in 2009-2010; it is likely that this situation has not changed much since then.