A Double-Blind Placebo-Controlled, Randomized Trial of Divalproex Sodium for Posttraumatic Irritability Greater Than 1 Year After Mild to Moderate Traumatic Brain Injury.

OBJECTIVE: Posttraumatic irritability after traumatic brain injury (TBI) may become a chronic problem and contribute to impaired everyday function, either alone or in combination with alcohol use disorder. The authors hypothesized that divalproex sodium (VPA) would improve posttraumatic irritability and result in lessened alcohol use. METHODS: This randomized, placebo-controlled double-blind clinical trial recruited participants with an index TBI occurring 1 or more years prior to enrollment, a history of alcohol use disorder, and posttraumatic irritability corroborated by a knowledgeable informant. An 8-item subset of the Agitated Behavior Scale served as the primary outcome measure of VPA efficacy. Doses of VPA were titrated to standard serum concentrations of 50 µg/ml to 100 µg/ml. RESULTS: Forty-eight persons completed this clinical trial (VPA, N=22; placebo, N=26). At baseline, participants rated their posttraumatic irritability as less severe than did their informants (p<0.05). During the trial, informants reported significant and sustained reduction of posttraumatic irritability (p=0.03) in the study participants. Biweekly averages during drug exposure confirmed this (p<0.03, Cohen's d=0.44). Treatment efficacy was not related to measures of anxiety, posttraumatic stress disorder, sedation, or veteran versus nonveteran status. Alcohol use did not change as a result of treatment. There were no serious adverse events. CONCLUSIONS: This study demonstrated an effect of VPA on posttraumatic irritability, and VPA was well tolerated. Further definition of treatment efficacy and safety requires a large-scale multisite trial, using a randomized, double-blind placebo-controlled design.

Age-associated hippocampal volume changes in childhood arterial ischemic stroke.

PURPOSE: Recent evidence suggests that recovery from secondary neurodegeneration following arterial ischemic stroke (AIS) may be related to age at injury and site of occlusion. We conducted a study of hippocampal volume (HCV) in a cohort of pediatric patients with middle cerebral artery (MCA) territory AIS to determine whether HCV would be preserved in younger children as compared to older children. METHODS: This single-center, HIPAA-compliant retrospective study was approved by the institutional review board. The medical records of 149 children treated for AIS between 2000 and 2016 were reviewed for inclusion criteria: unilateral MCA territory AIS and availability of high-resolution T1-weighted MR imaging at both acute and chronic time periods. Manual segmentation was utilized to measure stroke-side HCV, contralateral HCV, hemispheric volumes, and stroke volume on each scan. To correct for variable brain size, HCV measurements were ratio normalized. Patients were divided into two age-at-stroke groups: younger (30 days-9 years old) and older (> 9-18 years old). Analysis was performed using Fisher's test or Student's t test. RESULTS: The MR imaging of 19 children (9 younger, 10 older) was analyzed. At follow-up, the average stroke-side HCV increased by 10.9% in the younger group and decreased by 6.3% in the older group (P = 0.010); this between-group difference remained significant even when ratio normalized (P = 0.003). The total brain volume-adjusted acute stroke size between groups was not statistically different (P = 0.649). CONCLUSIONS: In children with AIS, younger age is associated with the relative preservation of HCV, which could reflect differences in age-related plasticity.

The impact of industry and body part injured on repeat workers' compensation claims.

BACKGROUND: Few studies investigate the influence of body part injured and industry on future workers' compensation claims. METHODS: Using claims incurred from 1 January 2005 to 31 July 2015 (n = 77 494) from the largest workers' compensation insurer in Colorado, we assessed associations between worker characteristics, second claims involving any body part and the same body part. We utilized Cox proportional hazards models to approximate the probability of a second claim. RESULTS: First claims represented 74.9% (n = 58 007) and second claims 25.2% (n = 19 487) of total claims. Sex, age, industry, and body part of the first claim were associated with the probability of second claims and the body part affected. The 5-year probabilities of second claims and same body part second claims were 27.0% (95% confidence interval [CI]: 26.6%-27.5%) and 6.2% (95% CI: 5.9%-6.5%) in males and 26.5% (95% CI: 26.0%-27.0%) and 6.7% (95% CI: 6.5%-7.0%) in females. Most second claims occurred within 3 years. CONCLUSIONS: Most second claims occur within 3 years. Body part and industry-specific injury patterns suggest missed opportunities for prevention.

Late Reduction of Cocaine Cravings in a Randomized, Double-Blind Trial of Aripiprazole vs Perphenazine in Schizophrenia and Comorbid Cocaine Dependence.

PURPOSE: Co-occurring schizophrenia spectrum disorder and International Statistical Classification of Diseases, 10th Revision cocaine dependence present a particularly destructive constellation that is often difficult to treat. Both conditions raise dopamine transmission effects in the brain. Traditional neuroleptics block dopamine receptors, whereas aripiprazole modulates dopamine activity as an agonist/antagonist. We tested whether dopamine modulation is superior to dopamine blocking in dual-diagnosis patients. METHODS: In a randomized, double-blind, comparison design, cocaine-dependent schizophrenic subjects actively using cocaine received either aripiprazole or perphenazine in an 8-week trial. Primary outcome targeted cocaine-free urine sample proportions, whereas cocaine craving scores were a secondary variable. RESULTS: Subjects (N = 44) randomized (n = 22 per group) did not differ at baseline. The proportion of cocaine-free urine samples did not differ by medication group. Contrasting weeks 3 to 5 vs 6 to 8 revealed significant late reductions in craving with aripiprazole. On the respective 5-point subscales, craving intensity decreased by 1.53 ± 0.43 (P < 0.0005) points, craving frequency by 1.4 ± 0.40 (P > 0.0004) points, and craving duration by 1.76 ± 0.44 (P > 0.0001) points. CONCLUSIONS: A drug effect of aripiprazole on craving items appeared at week 6 of treatment, on average, and was not seen before that length of drug exposure. The data suggest that dopamine modulation reduces cocaine cravings but requires an acclimation period. To understand the mechanism of action better, a trial of depot aripiprazole may be useful. Clinically, a reduction in craving potentially offers a clearer focus for ongoing behavioral treatment. It may also offer a longer-term treatment effect with respect to the severity of relapse.

Pediatric Cortical Vein Thrombosis: Frequency and Association With Venous Infarction.

BACKGROUND AND PURPOSE: Cortical vein thrombosis (CVT) is an uncommon site of involvement in cerebral sinovenous thrombosis. Few reports have described pediatric CVT, and none has differentiated its unique attributes. This study assessed the clinical features and radiographic outcome of a cohort of children with cerebral sinovenous thrombosis, comparing those with CVT to those without CVT. METHODS: Children diagnosed with cerebral sinovenous thrombosis were retrospectively reviewed and separated into 2 groups based on the presence or absence of cortical vein involvement. RESULTS: Fifty patients met inclusion criteria, including 12 with CVT. The CVT group was more likely to present with seizure (P=0.0271), altered mental status (P=0.0271), and a family history of clotting disorder (P=0.0477). Acute imaging of the CVT group more commonly demonstrated concurrent superior sagittal sinus thrombosis (P=0.0024), parenchymal hemorrhage (P=0.0141), and restricted diffusion (P<0.0001). At follow-up, the CVT group more commonly showed headache, seizure, and focal neurological deficit (P=0.0449), and venous infarction (P=0.0007). CONCLUSIONS: In our cohort, CVT was significantly associated with seizures at presentation, hemorrhage and restricted diffusion on acute imaging, as well as neurological disability and venous infarction at follow-up. Involvement of cortical veins in cerebral sinovenous thrombosis is associated with an increased risk of infarction and adverse outcome in children.

Inter-Rater Reliability of the CASCADE Criteria: Challenges in Classifying Arteriopathies.

BACKGROUND AND PURPOSE: There are limited data about the reliability of subtype classification in childhood arterial ischemic stroke, an issue that prompted the IPSS (International Pediatric Stroke Study) to develop the CASCADE criteria (Childhood AIS Standardized Classification and Diagnostic Evaluation). Our purpose was to determine the CASCADE criteria's reliability in a population of children with stroke. METHODS: Eight raters from the IPSS reviewed neuroimaging and clinical records of 64 cases (16 cases each) randomly selected from a prospectively collected cohort of 113 children with arterial ischemic stroke and classified them using the CASCADE criteria. Clinical data abstracted included history of present illness, risk factors, and acute imaging. Agreement among raters was measured by unweighted κ statistic. RESULTS: The CASCADE criteria demonstrated a moderate inter-rater reliability, with an overall κ statistic of 0.53 (95% confidence interval [CI]=0.39-0.67). Cardioembolic and bilateral cerebral arteriopathy subtypes had much higher agreement (κ=0.84; 95% CI=0.70-0.99; and κ=0.90; 95% CI=0.71-1.00, respectively) than cases of aortic/cervical arteriopathy (κ=0.36; 95% CI=0.01-0.71), unilateral focal cerebral arteriopathy of childhood (FCA; κ=0.49; 95% CI=0.23-0.76), and small vessel arteriopathy of childhood (κ=-0.012; 95% CI=-0.04 to 0.01). CONCLUSIONS: The CASCADE criteria have moderate reliability when used by trained and experienced raters, which suggests that it can be used for classification in multicenter pediatric stroke studies. However, the moderate reliability of the arteriopathic subtypes suggests that further refinement is needed for defining subtypes. Such revisions may reduce the variability in the literature describing risk factors, recurrence, and outcomes associated with childhood arteriopathy.

Corticosteroid Treatment and Growth Patterns in Ambulatory Males with Duchenne Muscular Dystrophy.

OBJECTIVES: To evaluate growth patterns of ambulatory males with Duchenne muscular dystrophy (DMD) treated with corticosteroids compared with ambulatory, steroid-naïve males with DMD and age-matched unaffected general-population males and to test associations between growth and steroid treatment patterns among treated males. STUDY DESIGN: Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network, we identified a total of 1768 height, 2246 weight, and 1755 body mass index (BMI) measurements between age 2 and 12 years for 324 ambulatory males who were treated with corticosteroids for at least 6 months. Growth curve comparisons and linear mixed-effects modeling, adjusted for race/ethnicity and birth year, were used to evaluate growth and steroid treatment patterns (age at initiation, dosing interval, duration, cumulative dose). RESULTS: Growth curves for ambulatory males treated with corticosteroids showed significantly shorter stature, heavier weight, and greater BMI compared with ambulatory, steroid-naïve males with DMD and general-population US males. Adjusted linear mixed-effects models for ambulatory males treated with corticosteroids showed that earlier initiation, daily dosing, longer duration, and greater dosages predicted shorter stature with prednisone. Longer duration and greater dosages predicted shorter stature for deflazacort. Daily prednisone dosing predicted lighter weight, but longer duration, and greater dosages predicted heavier weight. Early initiation, less than daily dosing, longer duration, and greater doses predicted greater BMIs. Deflazacort predicted shorter stature, but lighter weight, compared with prednisone. CONCLUSION: Prolonged steroid use is significantly associated with short stature and heavier weight. Growth alterations associated with steroid treatment should be considered when making treatment decisions for males with DMD.

Rituximab versus cyclophosphamide for ANCA-associated vasculitis.

BACKGROUND: Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS: We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS: Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS: Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)

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.

Development and Validation of Crosswalks Between FIM® and SCIM III for Voluntary Musculoskeletal Movement Functions.

Background. In spinal cord injury, there are multiple databases containing information on functional recovery, but data cannot be pooled or compared due to differences in how function is measured. A crosswalk is needed to link or convert scores between instruments. Objectives. To create a crosswalk between the voluntary musculoskeletal movement items in the Functional Independence Measure (FIM®) and the Spinal Cord Independence Measure III (SCIM III) for spinal cord injury. Methods. Retrospective datasets with FIM® and SCIM III on the same people were used to develop (Swiss dataset, n = 662) and validate (US, n = 119, and Canadian datasets, n = 133) the crosswalks. Three different crosswalk methods (expert panel, equipercentile, and Rasch analysis) were employed. We used the correlation between observed scores on FIM® and SCIM III to crosswalked scores as the primary criterion to assess the strength of the crosswalk. Secondary criteria such as score distributions, Cohen's effect size, point differences, and subgroup invariance were also evaluated. Results. All three methods resulted in strong correlation coefficients, exceeding the primary criterion value of r = .866 (.897-.972). Assessment of secondary criteria suggests the equipercentile and Rasch methods produced the strongest crosswalks. Conclusions. The Rasch FIM®/SCIM III crosswalk is recommended because it is based on co-calibration of linearized measures, allowing for more sophisticated parametric analyses. The crosswalk will allow comparisons of voluntary musculoskeletal functional recovery across international databases using different functional measures, as well as different systems of care and rehabilitation approaches.

Time Course of C-Reactive Protein and Procalcitonin Levels During the Treatment of Acute Bacterial Skin Infections.

In a pilot study of 22 patients with an acute bacterial skin infection, serum levels of C-reactive protein and procalcitonin tended to be elevated at presentation and declined within 3-5 days of treatment. Further study of a biomarker-guided treatment strategy to reduce antibiotic overuse in skin infections is warranted.

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.

Unadjusted point of care creatinine results overestimate acute kidney injury incidence during field testing in Guatemala.

OBJECTIVE: Acute kidney injury (AKI) occurs at high rates among agricultural workers (12-33%) in tropical environments. Because of the remote locations affected, traditional laboratory services are often unavailable. In this study we compare point of care (POC) creatinine values to standardized laboratory values, and examine the effect of POC testing on the interpretation of AKI rates under tropical field conditions. METHODS: Blood samples were collected from 104 sugarcane workers from two time points in January 2018 as a derivation cohort, and from 105 workers from February to April 2017 as a validation cohort. Finger stick and venipuncture samples were drawn at the end of a worker's shift to measure creatinine. Laboratory samples were tested in Guatemala City, Guatemala, in duplicate using the Jaffe Generation 2 method. An adjustment factor to improve agreement with serum creatinine was statistically derived and validated, and then used to determine impact on observed rates of acute kidney injury based on across shift changes in creatinine. RESULTS: POC creatinine and serum creatinine measures showed that POC consistently overestimated the creatinine by an average of 22% (95% CI: 19.8%, 24.7%) and the disagreement appeared greater at higher values of serum creatinine. An adjustment factor of 0.7775 was applied, which led to significantly greater agreement between the two measures. Rates of AKI in the two combined groups fell from 72% before adjustment to 57% afterwards. CONCLUSIONS: POC testing under tropical field conditions routinely overestimates creatinine compared to laboratory testing, which leads to overestimation of rates of acute kidney injury. The application of an adjustment factor significantly improved the accuracy of the POC value.

Reoccurring Injury, Chronic Health Conditions, and Behavioral Health: Gender Differences in the Causes of Workers' Compensation Claims.

OBJECTIVE: The aim of this study was o examine how work and nonwork health-related factors contribute to workers' compensation (WC) claims by gender. METHODS: Workers (N = 16,926) were enrolled in the Pinnacol Assurance Health Risk Management study, a multiyear, longitudinal research program assessing small and medium-sized enterprises in Colorado. Hypotheses were tested using gender-stratified logistic regression models. RESULTS: For both women and men, having incurred a prior WC claim increased the odds of a future claim. The combination of incurring a prior claim and having metabolic health conditions resulted in lower odds of a future claim. Behavioral health risk factors increased the odds of having a claim more so among women than among men. CONCLUSION: This study provides data to support multifactorial injury theories, and the need for injury prevention efforts that consider workplace conditions as well as worker health.

The impact of heat and impaired kidney function on productivity of Guatemalan sugarcane workers.

BACKGROUND: Climate change has implications for human health and productivity. Models suggest that heat extremes affect worker health, reduce labor capacity, and commodity supply. Chronic health conditions are on the rise internationally. However there is a paucity of direct empirical evidence relating increasing temperatures to both agricultural worker health and productivity. METHODS AND FINDINGS: We evaluated the relationship between temperature exposure, kidney function, and two measures of productivity-tons of commodity produced and job attrition, of 4,095 Guatemalan sugarcane cutters over a 6-month harvest. We used distributed lag non-linear models to evaluate associations between wet bulb globe temperature (WBGT) and productivity of workers with normal or impaired kidney function. The cumulative effect of exposure to a max WBGT of 34°C was 1.16 tons (95% CI: -2.87, 0.54) less sugarcane cut over the next five days by workers with impaired kidney function, compared to exposure to 29°C. Impaired kidney function was associated with premature workforce attrition. Workers starting the harvest season with impaired kidney function were more than twice as likely to leave employment (HR: 2.92, 95% CI: 1.88, 4.32). CONCLUSIONS: Heat extremes may be associated with loss of agricultural worker productivity and employment, especially among those with impaired kidney function. Agricultural workers who develop health conditions, such as kidney disease, are particularly vulnerable in the face of climate change and increasing heat extremes. The resultant loss of employment and productivity has significant implications for global commodity supplies.

The Impact of Worksite Wellness Programs by Size of Business: A 3-Year Longitudinal Study of Participation, Health Benefits, Absenteeism, and Presenteeism.

Objective: Worksite wellness programs (WWP) may positively impact employee health, medical expenditures, absenteeism, and presenteeism. However, there has been little research to assess the benefits of WWP in small businesses. The purpose of this study is to prospectively evaluate changes in health, absenteeism, and presenteeism for employees who participated in a WWP. Methods: We conducted an observational, 3-year cohort study of 5766 employees from 314 businesses of differing sizes. We followed two cohorts of employees, who completed at least two annual health risk assessments (HRA) between May 2010 and December 2014. Changes from baseline to the first and second follow-up periods were assessed for chronic and non-chronic health conditions, absenteeism, and presenteeism. Results: Small business employees were more likely to participate in the WWP than were employees from large businesses. Changes in chronic and non-chronic health conditions varied by size of business, with small business employees showing improvements in stress, overall health, depression, smoking status, vegetable and fruit consumption, and physical activity, and in their perceptions of job health culture. In contrast, large business employees experienced improvements in stress, vegetable consumption, and alcohol use. No changes in absenteeism or presenteeism were observed. Conclusions: Small businesses achieve higher employee participation rates and more health improvements when compared to employees from large employers. Findings suggest that small businesses may gain the most from a WWP.

"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.

Risk Factors for Declines in Kidney Function in Sugarcane Workers in Guatemala.

OBJECTIVES: To characterize kidney function of sugarcane workers in Guatemala over the 6-month harvest and identify risk factors associated with changes in kidney function. METHODS: Demographic and biological data were collected for 330 sugarcane cutters at the beginning and end of the harvest. Multivariable regression analyses were used to assess factors related to kidney function. RESULTS: A decline in kidney function across the harvest was observed in 36% of the participants. Risk factors associated with this decline included working at a particular plantation mill, local area workers compared with highland workers, and current smokers. CONCLUSION: Results showed both occupational and behavioral factors play significant roles in declines in kidney function. These results underline the need for a comprehensive approach to the epidemic as well as further investigation of risk factors to guide research and interventions.

Small business Total Worker Health: A conceptual and methodological approach to facilitating organizational change.

Nearly half of Americans are employed by small businesses, and future projections suggest that the number of those employed by small businesses will rise. Despite this, there is relatively little small business intervention research on the integration of health protection and health promotion, known as Total Worker Health® (TWH). We first discuss the importance of studying small businesses in TWH research and practice. Second, we describe an example of a small business TWH intervention, Health Links™ plus TWH owner/senior manager leadership training, that we are evaluating via the Small+Safe+Well (SSWell) study. Key features of the intervention and the SSWell study include attention to multi-level influences on worker health, safety and well-being; organizational change; and dissemination and implementation science strategies via the RE-AIM model. We offer several considerations for future small business TWH research and practice both in terms of the small business context as well as intervention development and evaluation. Our goal is to provide TWH researchers and practitioners with a framework and an example of how to approach small business TWH interventions. Ultimately, through the SSWell study, we aim to provide small businesses with strong evidence to support the use of TWH strategies that are practical, effective and sustainable.

Serious psychological distress among parenting and nonparenting adults.

OBJECTIVES: We compared the prevalence of serious psychological distress among parenting adults with the prevalence among nonparenting adults and the sociodemographic correlates of serious psychological distress between these 2 populations. METHODS: We drew data from 14240 parenting adults and 19224 nonparenting adults who responded to the 2002 National Survey on Drug Use and Health. We used logistic regression procedures in our analysis. RESULTS: An estimated 8.9% of parenting adults had serious psychological distress in the prior year compared with 12.0% of nonparenting adults of similar age. In both groups, the adjusted odds of having serious psychological distress were higher among adults who were women, younger (between the ages of 18 and 44 years), low income, or receiving Medicaid. We found some differences in the correlates of serious psychological distress between parenting adults and nonparenting adults. The odds of having serious psychological distress were lower among parenting adults after we controlled for demographic characteristics. CONCLUSIONS: Serious psychological distress is fairly prevalent among parenting adults, and high-risk sociodemographic groups of parenting adults should be targeted to ensure access to coordination of services.