Katherine A. James

Prevalence of Duchenne and Becker Muscular Dystrophies in the United States

OBJECTIVE: To estimate prevalence of childhood-onset Duchenne and Becker muscular dystrophies (DBMD) in 6 sites in the United States by race/ethnicity and phenotype (Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]). METHODS: In 2002, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to conduct longitudinal, population-based surveillance and research of DBMD in the United States. Six sites conducted active, multiple-source case finding and record abstraction to identify MD STARnet cases born January 1982 to December 2011. We used cross-sectional analyses to estimate prevalence of DBMD per 10u2009000 boys, ages 5 to 9 years, for 4 quinquennia (1991–1995, 1996–2000, 2001–2005, and 2006–2010) and prevalence per 10u2009000 male individuals, ages 5 to 24 years, in 2010. Prevalence was also estimated by race/ethnicity and phenotype. RESULTS: Overall, 649 cases resided in an MD STARnet site during ≥1 quinquennia. Prevalence estimates per 10u2009000 boys, ages 5 to 9 years, were 1.93, 2.05, 2.04, and 1.51, respectively, for 1991–1995, 1996–2000, 2001–2005, and 2006–2010. Prevalence tended to be higher for Hispanic individuals than non-Hispanic white or black individuals, and higher for DMD than BMD. In 2010, prevalence of DBMD was 1.38 per 10u2009000 male individuals, ages 5 to 24 years. CONCLUSIONS: We present population-based prevalence estimates for DBMD in 6 US sites. Prevalence differed by race/ethnicity, suggesting potential cultural and socioeconomic influences in the diagnosis of DBMD. Prevalence also was higher for DMD than BMD. Continued longitudinal surveillance will permit us to examine racial/ethnic and socioeconomic differences in treatment and outcomes for MD STARnet cases.

Association between Lifetime Exposure to Inorganic Arsenic in Drinking Water and Coronary Heart Disease in Colorado Residents

Background: Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associations have been inconclusive in populations with lower levels (< 100 μg/L) of inorganic arsenic exposure. Objectives: We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD. Methods: This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD. Results: We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 μg/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 μg/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20–30 μg/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30–45 μg/L; and HR = 3, 95% CI: 1.1, 9.1 for 45–88 μg/L). Conclusions: Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population. Citation: James KA, Byers T, Hokanson JE, Meliker JR, Zerbe GO, Marshall JA. 2015. Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents. Environ Health Perspect 123:128–134;u2002http://dx.doi.org/10.1289/ehp.1307839

A case-cohort study examining lifetime exposure to inorganic arsenic in drinking water and diabetes mellitus.

BACKGROUNDnConsumption of drinking water with high levels of inorganic arsenic (over 500 μg/L) has been associated with type II diabetes mellitus (DM), but previous studies have been inconclusive about risks at lower levels (<100 μg/L). We present a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of DM.nnnMETHODSnThis case-cohort study included 141 cases of DM diagnosed between 1984 and 1998 as part of the prospective San Luis Valley Diabetes Study. A comparison sub-cohort of 488 participants was randomly sampled from 936 eligible participants who were disease free at baseline. Individual lifetime arsenic exposure estimates were determined using a methodology that incorporates the use of a structured interview to determine lifetime residence and employment history, geospatial modeling of arsenic concentrations in drinking water, and urine arsenic concentrations. A Cox proportional hazards model with known DM risk factors as time-dependent covariates was used to assess the association between lifetime exposure to inorganic arsenic in drinking water and incident DM.nnnRESULTSnOur findings show a significant association between inorganic arsenic exposure and DM risk (hazard ratio [HR]=1.27, 95%=1.01, 1.59 per 15 μg/L) while adjusting for ethnicity and time varying covariates age, body mass index and physical activity level.nnnCONCLUSIONSnExposure to low-level inorganic arsenic in drinking water is associated with increased risk for type II DM in this population based on a comprehensive lifetime exposure assessment.

Environmental cadmium exposure and osteoporosis: a review

ObjectivesTo review the published literature investigating the association between cadmium exposure and osteoporosis.MethodsA review of published peer-reviewed literature based on a priori criteria was completed. Odds ratios (OR) were abstracted or estimated from observational studies to calculate a pooled OR using inverse variance weighted random effects models.ResultsThe review identified seven studies with a pooled OR of ORxa0=xa02.22 (95xa0% CI: 1.16, 4.28) [I2xa0=xa054.8xa0% (pxa0<xa00.05)] (comparing highest urine cadmium category to lowest). In women over the age of 50xa0years, the pooled OR was 1.82 (95xa0% CI: 1.63, 2.02) [I2xa0=xa073.1xa0% (pxa0<xa00.05)]. A dose response evaluation (six studies) suggested increasing odds for osteoporosis with increasing urine cadmium levels.ConclusionsThis review detected an association between cadmium exposure and the occurrence of osteoporosis in a small number of cross-sectional studies which requires confirmation in using prospective study design.

Phenotypes within sensory modulation dysfunction

Sensory modulation disorder (SMD) is a severe inability to regulate responses to everyday sensory stimulation to which most people easily adapt. It is estimated to affect 5% to 16% of the general population of children. Although heterogeneity is seen in the presentation clinically, previous research has not empirically investigated whether the clinical heterogeneity of SMD can be classified into subtypes. This study explores a cohort of 98 children identified with SMD at the Department of Pediatric Rehabilitation by a member of the occupational therapy team at The Childrens Hospital of Denver. Two subtypes of SMD were identified through cluster analysis based on data from 4 parent-report instruments. The first subtype is characterized by sensory seeking/craving, hyperactive, impulsive, externalizing (eg, delinquent, aggressive), unsocial, inadaptive, and impaired cognitive/social behavior. The second subtype is characterized by movement sensitivity, emotionally withdrawal, and low energy/weak behavior. Findings from this study present a step toward understanding and classifying the complexities of children with SMDs.

Groundwater Pesticide Levels and the Association With Parkinson Disease

It is unclear whether exposure to environmentally relevant levels of pesticides in groundwater is associated with an increased risk of Parkinson disease (PD). The purpose of this study was to examine the relationship between PD and pesticide levels in groundwater. This cross-sectional study included 332 971 Medicare beneficiaries, including 4207 prevalent cases of PD from the 2007 Colorado Medicare Beneficiary Database. Residential pesticide levels were estimated from a spatial model based on 286 well water samples with atrazine, simazine, alachlor, and metolachlor measurements. A logistic regression model with known PD risk factors was used to assess the association between residential groundwater pesticide levels and prevalent PD. We found that for every 1.0 µg/L of pesticide in groundwater, the risk of PD increases by 3% (odds ratio = 1.03; 95% confidence interval: 1.02-1.04) while adjusting for age, race/ethnicity, and gender suggesting that higher age-standardized PD prevalence ratios are associated with increasing levels of pesticides in groundwater.

Risk factors for first fractures among males with duchenne or becker muscular dystrophy

Background: Fractures are a significant concern for individuals with Duchenne/Becker muscular dystrophy with 21% to 44% of males experiencing a fracture. Factors that increase or decrease the risk for fracture have been suggested in past research, although statistical risk has not been determined. Methods: In this retrospective cohort study, we used the Muscular Dystrophy Surveillance, Tracking and Research Network cohort, a large, population-based sample to identify risk factors associated with first fractures in patients with Duchenne or Becker muscular dystrophy. Our study cohort included males with Duchenne or Becker muscular dystrophy born between 1982 and 2006 who resided in Arizona, Colorado, Georgia, Iowa, and Western New York, retrospectively identified and followed through 2010. We utilized a multivariate Cox proportional hazard model to determine hazard ratios for relevant factors associated with first fracture risk including race/ethnicity, surveillance site, ambulation status, calcium/vitamin D use and duration, bisphosphonate use and duration, and corticosteroid use and duration. Results: Of 747 cases, 249 had at least 1 fracture (33.3%). Full-time wheelchair use increased the risk of first fracture by 75% for every 3 months of use (hazard ratio=1.75, 95% confidence interval, 1.14, 2.68), but corticosteroid use, bisphosphonate use, and calcium/vitamin D use did not significantly affect risk in the final adjusted model. Conclusions: In this cohort, first fractures were common and full-time wheelchair use, but not corticosteroid use, was identified as a risk factor. The impact of prevention measures should be more thoroughly assessed. Clinical Relevance: Fractures are a significant concern for individuals with dystrophinopathies, but the contribution of various risk factors has not been consistently demonstrated.

Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater. This study included historical water samples with total arsenic concentrations from 595 unique well locations. A longitudinal analysis established temporal stability in arsenic levels in individual wells. The mean arsenic levels for a random sample of 535 wells were incorporated into five kriging models to predict groundwater arsenic concentrations at any point in time. A separate validation dataset (nxa0=xa060 wells) was used to identify the model with strongest predictability. Findings indicate that arsenic concentrations are temporally stable (rxa0=xa00.88; 95xa0% CI 0.83–0.92 for samples collected from the same well 15–25xa0years apart) and the spatial model created using ordinary kriging best predicted arsenic concentrations (ρxa0=xa00.72 between predicted and observed validation data). These findings illustrate the value of geostatistical modeling of arsenic and suggest the San Luis Valley is a good region for conducting epidemiologic studies of groundwater metals because of the ability to accurately predict variation in groundwater arsenic concentrations.

A dose-response meta-analysis of chronic arsenic exposure and incident cardiovascular disease

BackgroundnConsistent evidence at high levels of water arsenic (≥100 µg/l), and growing evidence at low-moderate levels (<100 µg/l), support a link with cardiovascular disease (CVD). The shape of the dose-response across low-moderate and high levels of arsenic in drinking water is uncertain and critical for risk assessment.nnnMethodsnWe conducted a systematic review of general population epidemiological studies of arsenic and incident clinical CVD (all CVD, coronary heart disease (CHD) and stroke) with three or more exposure categories. In a dose-response meta-analysis, we estimated the pooled association between log-transformed water arsenic (log-linear) and restricted cubic splines of log-transformed water arsenic (non-linear) and the relative risk of each CVD endpoint.nnnResultsnTwelve studies (pooled N = 408 945) conducted at high (N = 7) and low-moderate (N = 5) levels of water arsenic met inclusion criteria, and 11 studies were included in the meta-analysis. Compared with 10 µg/l, the estimated pooled relative risks [95% confidence interval (CI)] for 20 µg/l water arsenic, based on a log-linear model, were 1.09 (1.03, 1.14) (N = 2) for CVD incidence, 1.07 (1.01, 1.14) (N = 6) for CVD mortality, 1.11 (1.05, 1.17) (N = 4) for CHD incidence, 1.16 (1.07, 1.26) (N = 6) for CHD mortality, 1.08 (0.99, 1.17) (N = 2) for stroke incidence and 1.06 (0.93, 1.20) (N = 6) for stroke mortality. We found no evidence of non-linearity, although these tests had low statistical power.nnnConclusionsnAlthough limited by the small number of studies, this analysis supports quantitatively including CVD in inorganic arsenic risk assessment, and strengthens the evidence for an association between arsenic and CVD across low-moderate to high levels.

Validation of estimates of past exposure to arsenic in drinking water using historical urinary arsenic concentrations.

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Research groups have estimated historic exposure using databases and models of arsenic in drinking water supplies, along with participant residential histories. Urinary arsenic species are an established biomarker of recent exposure; we compare arsenic concentrations in historically collected urine samples with predicted estimates of arsenic exposure. Using a cohort of 462 subjects with at least one urine sample collected from 1984-1992 and an arsenic exposure estimate through drinking water at the time of the urine sample, individual exposure estimates were compared with speciated urine arsenic (UAs) concentrations using correlation and multiple regression analyses. Urine inorganic arsenic (UIAs) concentrations (trivalent arsenic, pentavalent arsenic, monomethylarsonic acid, dimethylarsonic acid) were best predicted by residential water arsenic concentrations (R2=0.3688), compared with metrics including water consumption (R2=0.2038) or water concentrations at employment locations (R2=0.2331). UIAs concentrations showed similar correlation when stratified by whether the arsenic concentration was predicted or measured. Residential water arsenic concentrations, independent of water intake or water concentrations at places of employment, best explain the variability in UIAs concentrations, suggesting historical reconstruction of arsenic exposure that accounts for space-time variability and water concentrations may serve as a proxy for exposure.