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.

Gestational Diabetes Prevalence at Moderate and High Altitude.

BACKGROUND: High-altitude (HA) pregnancies have been associated with decreased glucose levels and increased insulin sensitivity versus sea level. Our objective was to determine if the prevalence of gestational diabetes mellitus (GDM) and the impact of demographic characteristics on GDM diagnosis differed at moderate altitude (MA) versus HA. METHODS: Using a retrospective cohort design, we compared women living at HA (>8250 ft) and MA (4000-7000 ft) during pregnancy. Exclusion criteria were as follows: multiple gestation, preexisting diabetes, unavailable GDM results, or relocation from a different altitude during pregnancy. GDM diagnosis was determined using Carpenter and Coustan criteria. Data were compared by t-test (continuous variables) or chi-squared tests (categorical variables). Univariate, multivariate, and stepwise regression models were used to assess the impact of various factors on GDM prevalence. RESULTS: There was no difference in GDM prevalence between altitudes in these populations; the relationship between altitude and GDM was nonsignificant in all regression analyses. At MA, maternal age, Hispanic ethnicity, body mass index (BMI), and gestational age (GA) at testing increased GDM incidence in univariate analyses. At HA, maternal age, Hispanic ethnicity, and multiparity increased GDM incidence in univariate analyses. CONCLUSION: While GDM prevalence did not differ between MA and HA, the impact of maternal demographic characteristics on GDM risk varied by altitude group. Higher BMI and greater GA at testing increased the incidence of GDM at MA, but not at HA. Multiparity had an effect at HA, but not MA. These differences may represent subtle differences in glucose metabolism at HA.

"Omics" data integration and functional analyses link Enoyl-CoA hydratase, short chain 1 to drug refractory dilated cardiomyopathy.

BACKGROUND: Large-scale "omics" datasets have not been leveraged and integrated with functional analyses to discover potential drivers of cardiomyopathy. This study addresses the knowledge gap. METHODS: We coupled RNA sequence (RNA-Seq) variant detection and transcriptome profiling with pathway analysis to model drug refractory dilated cardiomyopathy (drDCM) using the BaseSpace sequencing hub and Ingenuity Pathway Analysis. We used RNA-Seq case-control datasets (n = 6 cases, n = 4 controls), exome sequence familial DCM datasets (n = 3 Italians, n = 5 Italians, n = 5 Chinese), and controls from the HapMap project (n = 5 Caucasians, and n = 5 Asians) for disease modeling and putative mutation discovery. Variant replication datasets: n = 128 cases and n = 15 controls. Source of datasets: NCBI Sequence Read Archive. STATISTICS: Pairwise differential expression analyses to determine differentially expressed genes and t-tests to calculate p-values. We adjusted for false discovery rates and reported q-values. We used chi-square tests to assess independence among variables, the Fisher's Exact Tests and overlap p-values for the pathways and p-scores to rank network. RESULTS: Data revealed that ECHS1(enoyl-CoA hydratase, short chain 1(log2(foldchange) = 1.63329) hosts a mirtron, MIR3944 expressed in drDCM (FPKM = 5.2857) and not in controls (FPKM = 0). Has-miR3944-3p is a putative target of BAG1 (BCL2 associated athanogene 1(log2(foldchange) = 1.31978) and has-miR3944-5p of ITGAV (integrin subunit alpha V(log2(foldchange) = 1.46107) and RHOD (ras homolog family member D(log2(foldchange) = 1.28851). There is an association between ECHS1:11 V/A(rs10466126) and drDCM (p = 0.02496). The interaction (p = 2.82E-07) between ECHS1:75 T/I(rs1049951) and ECHS1:rs10466126 is associated with drDCM (p < 2.2e-16). ECHS1:rs10466126 and ECHS1:rs1049951 are in linkage disequilibrium (D' = 1). The interaction (p = 7.84E-08) between ECHS1:rs1049951 and the novel ECHS1:c.41insT variant is associated with drDCM (p < 2.2e-16). The interaction (p = 0.001096) between DBT (Dihydrolipoamide branched chain transacylase E2):384G/S(rs12021720) and ECHS1:rs10466126 is associated with drDCM (p < 2.2e-16). At the mRNA level, there is an association between ECHS1 (log2(foldchange) = 1.63329; q = 0.013927) and DBT (log2(foldchange) = 0.955072; q = 0.0368792) with drDCM. ECHS1 is involved in valine (-log (p = 3.39E00)), isoleucine degradation (p = 0.00457), fatty acid ß-oxidation (-log(p) = 2.83E00), and drug metabolism:cytochrome P450 (z-score = 2.07985196) pathways. The mitochondria (-log(p) = 8.73E00), oxidative phosphorylation (-log(p) = 5.35E00) and TCA-cycle II (-log(p) = 2.70E00) are dysfunctional. CONCLUSIONS: We introduce an integrative data strategy that considers the interplay between the DNA, mRNA, and associated pathways, which represents a possible diagnostic, prognostic, biomarker, and personalized treatment discovery approach in genomically heterogeneous diseases.

Do otolaryngology residency applicants relocate for training?

OBJECTIVES/HYPOTHESIS: To determine whether there is an association between the geographic location of an applicant's undergraduate school, medical school, and residency program among matched otolaryngology residency applicants. STUDY DESIGN: Observational. METHODS: Otolaryngology residency program applications to our institution from 2009 to 2013 were analyzed. The geographic location of each applicant's undergraduate education and medical education were collected. Online public records were queried to determine the residency program location of matched applicants. Applicants who did not match or who attended medical school outside the United States were excluded. Metro area, state, and region were determined according to US Census Bureau definitions. RESULTS: From 2009 to 2013, 1,089 (78%) of 1,405 applicants who matched into otolaryngology residency applied to our institution. The number of subjects who attended medical school and residency in the same geographic region was 241 (22%) for metropolitan area, 305 (28%) for state, and 436 (40%) for region. There was no difference in geographic location retention by gender or couples match status of the subject. United States Medical Licensing Exam step 1 scores correlated with an increased likelihood of subjects staying within the same geographic region (P = .03). CONCLUSIONS: Most otolaryngology applicants leave their previous geographic area to attend residency. Based on these data, the authors recommend against giving weight to geography as a factor when inviting applicants to interview. LEVEL OF EVIDENCE: NA.

Factors predicting weight-bearing asymmetry 1month after unilateral total knee arthroplasty: a cross-sectional study.

UNLABELLED: Factors predicting weight-bearing asymmetry (WBA) after unilateral total knee arthroplasty (TKA) are not known. However, identifying modifiable and non-modifiable predictors of WBA is needed to optimize rehabilitation, especially since WBA is negatively correlated to poor functional performance. The purpose of this study was to identify factors predictive of WBA during sit-stand transitions for people 1month following unilateral TKA. METHODS: Fifty-nine people were tested preoperatively and 1month following unilateral TKA for WBA using average vertical ground reaction force under each foot during the Five Times Sit-to-Stand Test. Candidate variables tested in the regression analysis represented physical impairments (strength, muscle activation, pain, and motion), demographics, anthropometrics, and movement compensations. RESULTS: WBA, measured as the ratio of surgical/non-surgical limb vertical ground reaction force, was 0.69 (0.18) (mean (SD)) 1month after TKA. Regression analysis identified preoperative WBA (ß=0.40), quadriceps strength ratio (ß=0.31), and hamstrings strength ratio (ß=0.19) as factors predictive of WBA 1month after TKA (R(2)=0.30). CONCLUSION: Greater amounts of WBA 1month after TKA are predicted by modifiable factors including habitual movement pattern and asymmetry in quadriceps and hamstrings strength.

The role of ethnicity and culture on functional status in children with spina bifida.

PURPOSE: Spina bifida is a common cause of pediatric disability and more prevalent in the Hispanic population. Significant health disparities exist in minority populations. Culturally adapted health interventions have been attempted in conditions such as pediatric asthma with improvement. This study aims to explore the influence of ethnicity and culture with regards to functional status and care satisfaction. METHODS: Study participants were recruited from the Children's Hospital Colorado Spinal Defects Clinic. Demographics and past medical and surgical history were obtained via chart review. A questionnaire assessed ethnicity, acculturation, self-care, mobility, bowel and bladder function, and care satisfaction. RESULTS: A total of 70 subjects with spina bifida were included in the statistical analysis. There was no difference in PEDI self-care and mobility scores between ethnicities. The Hispanic group had higher urinary incontinence rates, higher percentage with bladder accidents, and lower satisfaction with bladder management. Regarding bowel function, the Hispanic group had lower satisfaction rates and a trend towards lower bowel continence. CONCLUSIONS: Further work is needed to understand the social and cultural differences between Hispanic and Non-Hispanic children and their families that impact bowel and bladder continence and care satisfaction. Once identified, culturally sensitive interventions may be implemented that can alleviate these apparent health disparities.

Performance of 3-dimensional echocardiography in measuring left ventricular volumes and ejection fraction: a systematic review and meta-analysis.

OBJECTIVES: The primary aim of this systematic review is to objectively evaluate the test performance characteristics of three-dimensional echocardiography (3DE) in measuring left ventricular (LV) volumes and ejection fraction (EF). BACKGROUND: Despite its growing use in clinical laboratories, the accuracy of 3DE has not been studied on a large scale. It is unclear if this technology offers an advantage over traditional two-dimensional (2D) methods. METHODS: We searched for studies that compared LV volumes and EF measured by 3DE and cardiac magnetic resonance (CMR) imaging. A subset of those also compared standard 2D methods with CMR. We used meta-analyses to determine the overall bias and limits of agreement of LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF measured by 3DE and 2D echocardiography (2DE). RESULTS: Twenty-three studies (1,638 echocardiograms) were included. The pooled biases ± 2 SDs for 3DE were -19.1 ± 34.2 ml, -10.1 ± 29.7 ml, and - 0.6 ± 11.8% for EDV, ESV, and EF, respectively. Nine studies also included data from 2DE, where the pooled biases were -48.2 ± 55.9 ml, -27.7 ± 45.7 ml, and 0.1 ± 13.9% for EDV, ESV, and EF, respectively. In this subset, the difference in bias between 3DE and 2D volumes was statistically significant (p = 0.01 for both EDV and ESV). The difference in variance was statistically significant (p < 0.001) for all 3 measurements. CONCLUSIONS: Three-dimensional echocardiography underestimates volumes and has wide limits of agreement, but compared with traditional 2D methods in these carefully performed studies, 3DE is more accurate for volumes and more precise in all 3 measurements.

Predictors of personal care assistance for people with spinal cord injury.

OBJECTIVE: To assess the predictors of personal care assistance (PCA) use in people with spinal cord injury (SCI). DESIGN: Cross-sectional. SETTING: Follow-up of individuals crossing their 1st, 5th, 10th, 15th, 20th, or 25th anniversary of injury who underwent their initial rehabilitation at a Spinal Cord Injury Model Systems center. PARTICIPANTS: A total of 2154 participants (2547 records) who met the inclusion criteria for the National Spinal Cord Injury Database and had valid values for the main outcome measures. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Daily hours of paid, unpaid, and occasional PCA services. RESULTS: Differences in an interval version of the motor portion of the FIM trade mark instrument accounted for 26.3% of the variance in total PCA hours, Model Systems differences accounted for 9.3%, and no other predictor accounted for more than 2.1% of the variance. CONCLUSION: Activities of daily living functioning, as measured by the motor portion of the FIM, was the strongest predictor of PCA use among people with SCI.

Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer.

OBJECTIVES: To evaluate whether the risk of bladder cancer is greater in individuals with spinal cord injury (SCI) than in the general population and whether indwelling catheter (IDC) use is a significant independent risk factor for bladder cancer. DESIGN: Historical cohort study in which subjects with SCI were stratified according to bladder management method and followed for the development of bladder cancer. SETTING: A large rehabilitation hospital in the Spinal Cord Injury Model Systems. PARTICIPANTS: A total of 3670 patients with SCI who were evaluated for bladder cancer on at least 1 occasion by cystoscopy over a period of 1 to 47 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Bladder cancer occurring after SCI determined by diagnosis at our facility, by subject report, or by report of next of kin. RESULTS: Twenty-one cases of bladder cancer were found in the 3670 study participants. The risk of bladder cancer for subjects with SCI using IDC is 77 per 100,000 person-years, corresponding to an age- and gender-adjusted standardized morbidity ratio (SMR) of 25.4 (95% confidence interval [CI], 14.0--41.9) when compared with the general population. After controlling for age at injury, gender, level and completeness of SCI, history of bladder calculi, and smoking, those using solely IDC had a significantly greater risk of bladder cancer (relative risk [RR] = 4.9; 95% CI, 1.3--13.8) than those using nonindwelling methods. Mortality caused by bladder cancer in individuals with SCI was significantly greater than that of the US population (SMR = 70.6; 95% CI, 36.9--123.3). CONCLUSIONS: Bladder cancer risk and mortality are heightened in SCI compared with the general population. IDC is a significant independent risk factor for the increased risk of and mortality caused by bladder cancer in the SCI population.