Adverse events among persons with TB using in-person vs. electronic directly observed therapy.

BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted.

Challenges associated with electronic and in-person directly observed therapy during a randomized trial.

BACKGROUND: Electronic directly observed therapy (eDOT) has been proposed as an alternative to traditional in-person DOT (ipDOT) for monitoring TB treatment adherence. Information about the comparative performance and implementation of eDOT is limited.METHODS: The frequency of challenges during DOT, challenge type, and effect on medication observation were documented by DOT method during a crossover, noninferiority randomized controlled trial. A logistic mixed-effects model that adjusted for the study design was used to estimate the percentage of successfully observed doses when challenges occurred.RESULTS: A total of 20,097 medication doses were scheduled for observation with either eDOT (15,405/20,097; 76.7%) or ipDOT (4,692/20,097; 23.3%) for 213 study participants. In total, one or more challenges occurred during 17.3% (2,672/15,405) of eDOT sessions and 15.6% (730/4,692) of ipDOT sessions. Among 4,374 documented challenges, 27.3% (n = 1,192) were characterized as technical, 65.9% (n = 2,881) were patient-related, and 6.9% (n = 301) were program-related. Estimated from the logistic model (n = 6,782 doses, 173 participants), the adjusted percentage of doses successfully observed during problematic sessions was 21.7% (95% CI 11.2-37.8) for eDOT and 4.2% (95% CI 1.1-14.7) for ipDOT.CONCLUSION: Compared to ipDOT, challenges were encountered in a slightly higher percentage of eDOT sessions but were more often resolved to enable successful dose observation during problematic sessions.

In-Person vs Electronic Directly Observed Therapy for Tuberculosis Treatment Adherence: A Randomized Noninferiority Trial.

Importance: Electronic directly observed therapy (DOT) is used increasingly as an alternative to in-person DOT for monitoring tuberculosis treatment. Evidence supporting its efficacy is limited. Objective: To determine whether electronic DOT can attain a level of treatment observation as favorable as in-person DOT. Design, Setting, and Participants: This was a 2-period crossover, noninferiority trial with initial randomization to electronic or in-person DOT at the time outpatient tuberculosis treatment began. The trial enrolled 216 participants with physician-suspected or bacteriologically confirmed tuberculosis from July 2017 to October 2019 in 4 clinics operated by the New York City Health Department. Data analysis was conducted between March 2020 and April 2021. Interventions: Participants were asked to complete 20 medication doses using 1 DOT method, then switched methods for another 20 doses. With in-person therapy, participants chose clinic or community-based DOT; with electronic DOT, participants chose live video-conferencing or recorded videos. Main Outcomes and Measures: Difference between the percentage of medication doses participants were observed to completely ingest with in-person DOT and with electronic DOT. Noninferiority was demonstrated if the upper 95% confidence limit of the difference was 10% or less. We estimated the percentage of completed doses using a logistic mixed effects model, run in 4 modes: modified intention-to-treat, per-protocol, per-protocol with 85% or more of doses conforming to the randomization assignment, and empirical. Confidence intervals were estimated by bootstrapping (with 1000 replicates). Results: There were 173 participants in each crossover period (median age, 40 years [range, 16-86 years]; 140 [66%] men; 80 [37%] Asian and Pacific Islander, 43 [20%] Black, and 71 [33%] Hispanic individuals) evaluated with the model in the modified intention-to-treat analytic mode. The percentage of completed doses with in-person DOT was 87.2% (95% CI, 84.6%-89.9%) vs 89.8% (95% CI, 87.5%-92.1%) with electronic DOT. The percentage difference was -2.6% (95% CI, -4.8% to -0.3%), consistent with a conclusion of noninferiority. The 3 other analytic modes yielded equivalent conclusions, with percentage differences ranging from -4.9% to -1.9%. Conclusions and Relevance: In this trial, the percentage of completed doses under electronic DOT was noninferior to that under in-person DOT. This trial provides evidence supporting the efficacy of this digital adherence technology, and for the inclusion of electronic DOT in the standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT03266003.

Pre-exposure Prophylaxis (PrEP) Awareness and Prescribing Behaviors Among Primary Care Providers: DocStyles Survey, 2016-2020, United States.

Few studies have assessed providers' intent of prescribing PrEP in the future. We analyzed cross-sectional web-based surveys to estimate trends from 2016 to 2020 in PrEP awareness and prescribing behaviors in the United States among primary care providers. Multivariable logistic regression was used to estimate prevalence of PrEP awareness, prescribing behaviors, and likelihood of prescribing PrEP in the next 12 months. The adjusted prevalence for PrEP awareness was significantly higher in 2019 (93.7%, 95% CI 91.9%, 95.2%) compared to 2018 (88.1%, 95% CI 85.5%, 90.3%). The adjusted prevalence for prescribing PrEP was significantly higher in 2019 (16.4%, 95% CI 13.6%, 19.6%) and 2020 (15.6%, 95% CI 13.0%, 18.7%) compared to 2018 (12.2%, 95% CI 10.0%, 14.7%). Practicing in the West and regularly screening for HIV were associated with higher PrEP awareness and provision. Studies should examine factors associated with PrEP provision for groups with increased risk for HIV.

Chemical analysis of snus products from the United States and northern Europe.

INTRODUCTION: Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers. METHODS: Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured. RESULTS: Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol. CONCLUSION: Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.

Evaluation of Tobacco Smoke and Diet as Sources of Exposure to Two Heterocyclic Aromatic Amines for the U.S. Population: NHANES 2013-2014.

BACKGROUND: Heterocyclic aromatic amines (HAA) are a group of hazardous substances produced during combustion of tobacco or high-temperature cooking of meats. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is a major carcinogenic HAA in tobacco smoke. METHODS: Urinary AαC, used as a marker of AαC exposure, was analyzed on spot urine samples from adult participants of the 2013-2014 cycle of the National Health and Nutrition Examination Survey (N = 1,792). AαC was measured using isotope-dilution liquid chromatography-tandem mass spectrometry. Exclusive combusted tobacco smokers were differentiated from nonusers of tobacco products through both self-report and serum cotinine data. RESULTS: Among exclusive smokers, sample-weighted median urinary AαC was 40 times higher than nonusers. Sample-weighted regression models showed that urinary AαC increased significantly with serum cotinine among both exclusive tobacco users and nonusers with secondhand smoke exposure. Among nonusers, eating beef cooked at high temperature was associated with a significant increase in urinary AαC, whereas consuming vegetables was associated with decreased AαC. In addition, smoking one-half pack of cigarettes per day was associated with a significant increase of 23.6 pg AαC/mL calculated at geometric mean of AαC, controlling for potential confounders. In comparison, increase in AαC attributable to consuming the 99th percentile of beef cooked at high temperature was 0.99 pg AαC/mL. CONCLUSIONS: Both exclusive smokers and nonusers of tobacco in the general U.S. population are exposed to AαC from tobacco smoke, with additional, lesser contributions from certain dietary components. IMPACT: AαC is an important biomarker that is associated with tobacco smoke exposure.

Cumulative ROC curves for discriminating three or more ordinal outcomes with cutpoints on a shared continuous measurement scale.

Cumulative receiver operator characteristic (ROC) curve analysis extends classic ROC curve analysis to discriminate three or more ordinal outcome levels on a shared continuous scale. The procedure combines cumulative logit regression with a cumulative extension to the ROC curve and performs as expected with ternary (three-level) ordinal outcomes under a variety of simulated conditions (unbalanced data, proportional and non-proportional odds, areas under the ROC curve [AUCs] from 0.70 to 0.95). Simulations also compared several criteria for selecting cutpoints to discriminate outcome levels: the Youden Index, Matthews Correlation Coefficient, Total Accuracy, and Markedness. Total Accuracy demonstrated the least absolute percent-bias. Cutpoints computed from maximum likelihood regression parameters demonstrated bias that was often negligible. The procedure was also applied to publicly available data related to computer imaging and biomarker exposure science, yielding good to excellent AUCs, as well as cutpoints with sensitivities and specificities of commensurate quality. Implementation of cumulative ROC curve analysis and extension to more than three outcome levels are straightforward. The author's programs for ternary ordinal outcomes are publicly available.

Systemic absorption of nicotine following acute secondhand exposure to electronic cigarette aerosol in a realistic social setting.

Evidence suggests exposure of nicotine-containing e-cigarette aerosol to nonusers leads to systemic absorption of nicotine. However, no studies have examined acute secondhand exposures that occur in public settings. Here, we measured the serum, saliva and urine of nonusers pre- and post-exposure to nicotine via e-cigarette aerosol. Secondarily, we recorded factors affecting the exposure. Six nonusers of nicotine-containing products were exposed to secondhand aerosol from ad libitum e-cigarette use by three e-cigarette users for 2 h during two separate sessions (disposables, tank-style). Pre-exposure (baseline) and post-exposure peak levels (Cmax) of cotinine were measured in nonusers' serum, saliva, and urine over a 6-hour follow-up, plus a saliva sample the following morning. We also measured solution consumption, nicotine concentration, and pH, along with use behavior. Baseline cotinine levels were higher than typical for the US population (median serum session one = 0.089 ng/ml; session two = 0.052 ng/ml). Systemic absorption of nicotine occurred in nonusers with baselines indicative of no/low tobacco exposure, but not in nonusers with elevated baselines. Median changes in cotinine for disposable exposure were 0.007 ng/ml serum, 0.033 ng/ml saliva, and 0.316 ng/mg creatinine in urine. For tank-style exposure they were 0.041 ng/ml serum, 0.060 ng/ml saliva, and 0.948 ng/mg creatinine in urine. Finally, we measured substantial differences in solution nicotine concentrations, pH, use behavior and consumption. Our data show that although exposures may vary considerably, nonusers can systemically absorb nicotine following acute exposure to secondhand e-cigarette aerosol. This can particularly affect sensitive subpopulations, such as children and women of reproductive age.

Crotonaldehyde exposure in U.S. tobacco smokers and nonsmokers: NHANES 2005-2006 and 2011-2012.

INTRODUCTION: Crotonaldehyde is an α,ß-unsaturated carbonyl compound that is a potent eye, respiratory, and skin irritant. Crotonaldehyde is a major constituent of tobacco smoke and its exposure can be quantified using its urinary metabolite N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMM). A large-scale biomonitoring study is needed to determine HPMM levels, as a measure of crotonaldehyde exposure, in the general U.S. MATERIALS AND METHODS: Urine samples were obtained as part of the National Health and Nutrition Examination Survey 2005-2006 and 2011-2012 from participants who were at least six-years-old (N = 4692). Samples were analyzed for HPMM using ultra performance liquid chromatography - tandem mass spectrometry. Exclusive tobacco smokers were distinguished from non- tobacco users through a combination of self-reporting and serum cotinine data. RESULTS: Detection rate of HPMM among eligible samples was 99.9%. Sample-weighted, median urinary HPMM levels for smokers and non-users were 1.61 and 0.313 mg/g creatinine, respectively. Multivariable regression analysis among smokers showed that HPMM was positively associated with serum cotinine, after controlling for survey year, urinary creatinine, age, sex, race, poverty level, body mass index, pre-exam fasting time, and food intake. Other significant predictors of urinary HPMM include sex (female > male), age (children > non-user adults), race (non-Hispanic Blacks < non-Hispanic Whites). CONCLUSIONS: This study characterizes U.S. population exposure to crotonaldehyde and confirms that tobacco smoke is a major exposure source. Urinary HPMM levels were significantly higher among exclusive combusted tobacco users compared to non-users, and serum cotinine and cigarettes per day were significant predictors of increased urinary HPMM. This study also found that sex, age, ethnicity, pre-exam fasting time, and fruit consumption are related to urinary HPMM levels.

Surveillance of Nicotine and pH in Cigarette and Cigar Filler.

OBJECTIVE: We examined differences between nicotine concentrations and pH in cigarette and cigar tobacco filler. METHODS: Nicotine and pH levels for 50 cigarette and 75 cigar brands were measured. Non-mentholated and mentholated cigarette products were included in the analysis along with several cigar types as identified by the manufacturer: large cigars, pipe tobacco cigars, cigarillos, mini cigarillos, and little cigars. RESULTS: There were significant differences found between pH and nicotine for cigarette and cigar tobacco products. Mean nicotine concentrations in cigarettes (19.2 mg/g) and large cigars (15.4 mg/g) were higher than the other cigars types, especially the pipe tobacco cigars (8.79 mg/g). The mean pH for cigarettes was pH 5.46. Large cigars had the highest mean pH value (pH 6.10) and pipe tobacco cigars had the lowest (pH 5.05). CONCLUSIONS: Although cigarettes are the most common combustible tobacco product used worldwide, cigar use remains popular. Our research provides a means to investigate the possibility of distinguishing the 2 tobacco product types and offers information on nicotine and pH across a wide range of cigarette and cigar varieties that may be beneficial to help establish tobacco policies and regulations across product types.

Evaluation of Multiple Blood Matrices for Assessment of Human Exposure to Nerve Agents.

Biomedical samples may be used to determine human exposure to nerve agents through the analysis of specific biomarkers. Samples received may include serum, plasma, whole blood, lysed blood and, due to the toxicity of these compounds, postmortem blood. To quantitate metabolites resulting from exposure to sarin (GB), soman (GD), cyclosarin (GF), VX and VR, these blood matrices were evaluated individually for precision, accuracy, sensitivity and specificity. Accuracies for these metabolites ranged from 100 to 113% with coefficients of variation ranging from 2.31 to 13.5% across a reportable range of 1-100 ng/mL meeting FDA recommended guidelines for bioanalytical methods in all five matrices. Limits of detection were calculated to be 0.09-0.043 ng/mL, and no interferences were detected in unexposed matrix samples. The use of serum calibrators was also determined to be a suitable alternative to matrix-matched calibrators. Finally, to provide a comparative value between whole blood and plasma, the ratio of the five nerve agent metabolites measured in whole blood versus plasma was determined. Analysis of individual whole blood samples (n = 40), fortified with nerve agent metabolites across the reportable range, resulted in average nerve agent metabolite blood to plasma ratios ranging from 0.53 to 0.56. This study demonstrates the accurate and precise quantitation of nerve agent metabolites in serum, plasma, whole blood, lysed blood and postmortem blood. It also provides a comparative value between whole blood and plasma samples, which can assist epidemiologists and physicians with interpretation of test results from blood specimens obtained under variable conditions.

Acrolein Exposure in U.S. Tobacco Smokers and Non-Tobacco Users: NHANES 2005-2006.

BACKGROUND: Acrolein is a highly reactive α,ß unsaturated aldehyde and respiratory irritant. Acrolein is formed during combustion (e.g., burning tobacco or biomass), during high-temperature cooking of foods, and in vivo as a product of oxidative stress and polyamine metabolism. No biomonitoring reference data have been reported to characterize acrolein exposure for the U.S. OBJECTIVES: Our goals were to a) evaluate two acrolein metabolites in urine--N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA) and N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA)--as biomarkers of exposure to acrolein for the U.S. population by age, sex, race, and smoking status; and b) assess tobacco smoke as a predictor of acrolein exposure. METHODS: We analyzed urine from National Health and Nutrition Examination Survey (NHANES 2005-2006) participants ≥ 12 years old (n = 2,866) for 3HPMA and CEMA using ultra-high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC/ESI-MSMS). Sample-weighted linear regression models stratified for non-tobacco users versus tobacco smokers (as defined by serum cotinine and self-report) characterized the association of urinary 3HPMA and CEMA with tobacco smoke exposure, adjusting for urinary creatinine, sex, age, and race/ethnicity. RESULTS: 3HPMA and CEMA levels were higher among tobacco smokers (cigarettes, cigars, and pipe users) than among non-tobacco users. The median 3HPMA levels for tobacco smokers and non-tobacco users were 1,089 and 219 µg/g creatinine, respectively. Similarly, median CEMA levels were 203 µg/g creatinine for tobacco smokers and 78.8 µg/g creatinine for non-tobacco users. Regression analysis showed that serum cotinine was a significant positive predictor (p < 0.0001) of both 3HPMA and CEMA among tobacco smokers. CONCLUSIONS: Tobacco smoke was a significant predictor of acrolein exposure in the U.S. population.

Dietary sources of methylated arsenic species in urine of the United States population, NHANES 2003-2010.

BACKGROUND: Arsenic is an ubiquitous element linked to carcinogenicity, neurotoxicity, as well as adverse respiratory, gastrointestinal, hepatic, and dermal health effects. OBJECTIVE: Identify dietary sources of speciated arsenic: monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). METHODS: Age-stratified, sample-weighted regression of NHANES (National Health and Nutrition Examination Survey) 2003-2010 data (∼8,300 participants ≥6 years old) characterized the association between urinary arsenic species and the additional mass consumed of USDA-standardized food groups (24-hour dietary recall data), controlling for potential confounders. RESULTS: For all arsenic species, the rank-order of age strata for median urinary molar concentration was children 6-11 years > adults 20-84 years > adolescents 12-19 years, and for all age strata, the rank-order was DMA > MMA. Median urinary molar concentrations of methylated arsenic species ranged from 0.56 to 3.52 µmol/mol creatinine. Statistically significant increases in urinary arsenic species were associated with increased consumption of: fish (DMA); fruits (DMA, MMA); grain products (DMA, MMA); legumes, nuts, seeds (DMA); meat, poultry (DMA); rice (DMA, MMA); rice cakes/crackers (DMA, MMA); and sugars, sweets, beverages (MMA). And, for adults, rice beverage/milk (DMA, MMA). In addition, based on US (United States) median and 90th percentile consumption rates of each food group, exposure from the following food groups was highlighted: fish; fruits; grain products; legumes, nuts, seeds; meat, poultry; and sugars, sweets, beverages. CONCLUSIONS: In a nationally representative sample of the US civilian, noninstitutionalized population, fish (adults), rice (children), and rice cakes/crackers (adolescents) had the largest associations with urinary DMA. For MMA, rice beverage/milk (adults) and rice cakes/crackers (children, adolescents) had the largest associations.

Acrolein and asthma attack prevalence in a representative sample of the United States adult population 2000-2009.

BACKGROUND: Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment) and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. OBJECTIVES: Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. METHODS: NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old) in the NHIS (National Health Interview Survey) 2000-2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. RESULTS: In the highest quintile of outdoor acrolein exposure (0.05-0.46 µg/m3), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI]  = 1.08 [0.98∶1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29]) in a model limited to never smokers (n = 153,820). CONCLUSIONS: Chronic exposure to outdoor acrolein of 0.05-0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population.

Profiling cholinesterase adduction: a high-throughput prioritization method for organophosphate exposure samples.

A high-throughput prioritization method was developed for use with a validated confirmatory method detecting organophosphorus nerve agent exposure by immunomagnetic separation high-performance liquid chromatography tandem mass spectrometry. A ballistic gradient was incorporated into this analytical method to profile unadducted butyrylcholinesterase (BChE) in clinical samples. With Zhang et al.'s Z' factor of 0.88 ± 0.01 (SD) of control analytes and Z factor of 0.25 ± 0.06 (SD) of serum samples, the assay is rated an "excellent assay" for the synthetic peptide controls used and a "double assay" when used to prioritize clinical samples. Hits, defined as samples containing BChE Ser-198 adducts or no BChE present, were analyzed in a confirmatory method for identification and quantitation of the BChE adduct, if present. The ability to prioritize samples by highest exposure for confirmatory analysis is of particular importance in an exposure to cholinesterase inhibitors such as organophosphorus nerve agents, in which a large number of clinical samples may be collected. In an initial blind screen, 67 of 70 samples were accurately identified, giving an assay accuracy of 96%, and it yielded no false-negatives. The method is the first to provide a high-throughput prioritization assay for profiling adduction of Ser-198 BChE in clinical samples.

Urinary perchlorate as a measure of dietary and drinking water exposure in a representative sample of the United States population 2001-2008.

Perchlorate (ClO(4)(-)) is ubiquitous in the environment and inhibits the thyroid's uptake of iodide. Food and tap water are likely sources of environmental exposure to perchlorate. The aim of this study was to identify significant dietary sources of perchlorate using perchlorate measured in urine as an exposure indicator. Sample-weighted, age-stratified linear regression models of National Health and Nutrition Examination Survey (NHANES) 2001-2008 data (n=16,955 participants) characterized the association between urinary perchlorate and the mass consumed in USDA food groups, controlling for urinary creatinine and other potential confounders. Separate models of NHANES 2005-2006 data (n=2841) evaluated the association between urinary perchlorate and perchlorate consumed via residential tap water. Consumption of milk products was associated with statistically significant contributions to urinary perchlorate across all age strata: 2.93 ng ClO(4)(-)/ml per kg consumed for children (6-11 years-old (YO)); 1.54 ng ClO(4)(-)/ml per kg for adolescents (12-19 YO); and 0.69 ng ClO(4)(-)/ml per kg for adults (20-84 YO). Vegetables were a significant contributor for adolescents and adults, whereas fruits and eggs contributed significantly only for adults. Dark-green leafy vegetables contributed the most among all age strata: 30.83 ng ClO(4)(-)/ml per kg for adults. Fats, oils, and salad dressings were significant contributors only for children. Three food groups were negatively associated with urinary perchlorate: grain products for children; sugars, sweets, and beverages for adolescents; and home tap water for adults. In a separate model, however, perchlorate consumed via home tap water contributed significantly to adult urinary perchlorate: 2.11E-4 ng ClO(4)(-)/ml per ng perchlorate in tap water consumed. In a nationally representative sample of the United States 6-84 YO, diet and tap water contributed significantly to urinary perchlorate, with diet contributing substantially more than tap water.

The longitudinal dependence of black carbon concentration on traffic volume in an urban environment.

The purpose of this study was to evaluate the effect of traffic volume on ambient black carbon (BC) concentration in an inner-city neighborhood "hot spot" while accounting for modifying effects of weather and time. Continuous monitoring was conducted for 12 months at the Baltimore Traffic Study site surrounded by major urban streets that together carry over 150,000 vehicles per day. Outdoor BC concentration was measured with an Aethalometer; vehicles were counted pneumatically on two nearby streets. Meteorological data were also obtained. Missing data were imputed and all data were normalized to a 5-min observational interval (n = 105,120). Time-series modeling accounted for autoregressively (AR) correlated errors. This study found that outdoor BC was positively correlated at a statistically significant level with neighborhood-level vehicle counts, which contributed at a rate of 66 +/- 10 (SE) ng/m3 per 100 vehicles every 5 min. Winds from the SW-S-SE quarter were associated with the greatest increases in BC (376-612 ng/m3). These winds would have entrained BC from Baltimore's densely trafficked central business district, as well as a nearby interstate highway. The strong influence of wind direction implicates atmospheric transport processes in determining BC exposure. Dew point, mixing height, wind speed, season, and workday were also statistically significant predictors. Background exposure to BC was estimated to be 905 ng/m3. The optimal, statistically significant representation of BC's autocorrelation was AR([1:6]) x 288 x 2016, where the short-term AR factor (lags 1-6) indicated that BC concentrations are correlated for up to 30 min, and the AR factors for lags 288 and 2016 indicate longer-term autocorrelations at diurnal and weekly cycles, respectively. It was concluded that local exposure to BC from mobile sources is substantially modified by meteorological and temporal conditions, including atmospheric transport processes. BC concentration also demonstrates statistically significant autocorrelation at several time scales.

Modeling time-location patterns of inner-city high school students in New York and Los Angeles using a longitudinal approach with generalized estimating equations.

The TEACH Project obtained subjects' time-location information as part of its assessment of personal exposures to air toxics for high school students in two major urban areas. This report uses a longitudinal modeling approach to characterize the association between demographic and temporal predictors and the subjects' time-location behavior for three microenvironments--indoor-home, indoor-school, and outdoors. Such a longitudinal approach has not, to the knowledge of the authors, been previously applied to time-location data. Subjects were 14- to 19-year-old, self reported non-smokers, and were recruited from high schools in New York, NY (31 subjects: nine male, 22 female) and Los Angeles, CA (31 subjects: eight male, 23 female). Subjects reported their time-location in structured 24-h diaries with 15-min intervals for three consecutive weekdays in each of winter and summer-fall seasons in New York and Los Angeles during 1999-2000. The data set contained 15,009 observations. A longitudinal logistic regression model was run for each microenvironment where the binary outcome indicated the subject's presence in a microenvironment during a 15-min period. The generalized estimating equation (GEE) technique with alternating logistic regressions was used to account for the correlation of observations within each subject. The multivariate models revealed complex time-location patterns, with subjects predominantly in the indoor-home microenvironment, but also with a clear influence of the school schedule. The models also found that a subject's presence in a particular microenvironment may be significantly positively correlated for as long as 45 min before the current observation. Demographic variables were also predictive of time-location behavior: for the indoor-home microenvironment, having an after school job (OR=0.67 [95% confidence interval: 0.54:0.85]); for indoor-school, living in New York (0.42 [0.29:0.59]); and for outdoor, being 16-year-old (0.80 [0.67:0.96]), 17-year-old (0.71 [0.54:0.92]), and having an after school job (1.29 [1.07:1.56]).

Estrogenic activity of polychlorinated biphenyls present in human tissue and the environment.

This study evaluated the estrogenicity of polychlorinated biphenyls (PCBs) present in environmental media and human tissue and assessed exposure pathways for PCB-derived estrogenic potency in air, soil, and dust from New Bedford, MA, an area with a PCB-contaminated Superfund site. Thirty-four PCB congeners were assayed for estrogenic potency using E-SCREEN, an assay based on the estrogen-dependent proliferation of MCF-7 cells in vitro. Childhood exposure to estradiol-equivalents via PCBs in environmental media was estimated byweighting previously reported New Bedford congener-specific concentrations by their relative estrogenic potency and published inhalation and soil ingestion rates. Thirteen congeners were weakly estrogenic in E-SCREEN: PCBs 17, 18, 30, 44, 49, 66, 74, 82, 99, 103, 110, 128, and 179. These PCBs were typically 6 orders of magnitude less potent than 17beta-estradiol, with proliferative potencies ranging from 0.0007% to 0.0040%. Of the environmental media assessed, air (inhalation) had the highest PCB-derived estradiol-equivalent exposure. PCB estrogenic potency information from this study provides an important resource both for preliminary estimation of routes of human exposure to xenoestrogens and for application to human health studies focused on estrogen-responsive health outcomes, such as reproductive development and related malignancies.