Increased long-term health risks attributable to select volatile organic compounds in residential indoor air in southeast Louisiana.

Volatile organic compounds (VOCs) represent a broad class of chemicals, many of which can be found in indoor air including residential indoor air. VOCs derive from a variety of sources including cleaning products, cooking practices, fragrances and fresheners, hobbies and at-home work behaviors. This study examined residential indoor air in homes (n = 99) in southeast Louisiana using passive organic vapor monitors and gas chromatography/mass spectrometry to determine if select VOCs were present, at what concentrations, and if those posed any potential long-term health risks.

Development and validation of a Level A in-vitro in-vivo correlation for tofacitinib modified-release tablets using extrudable core system osmotic delivery technology.

Purpose: To determine if a validated Level A in-vitro in-vivo correlation (IVIVC) could be achieved with the extrudable core system (ECS) osmotic tablet platform. Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis.

Methods: Fast-, medium-, and slow-release modified-release formulations of 11 mg tofacitinib ECS tablets, and one formulation of 22 mg tofacitinib ECS tablet, were manufactured.

Modified- versus immediate-release tofacitinib in Japanese rheumatoid arthritis patients: a randomized, phase III, non-inferiority study.

Objective: Tofacitinib is an oral Janus kinase inhibitor for treatment of RA. We compared tofacitinib modified-release (MR) 11 mg once daily (QD) with tofacitinib immediate-release (IR) 5 mg twice daily (BID) in Japanese patients with RA and inadequate response to MTX.

Methods: Phase III, randomized, double-blind, double-dummy, 12-week study.

Impact of transient truck and train traffic on ambient air and noise levels in underserved communities.

Traffic-related air and noise pollution on or near major roadways have been examined but these pollutants have not been extensively investigated away from major roadways in residential communities, especially in the United States. To evaluate the impact of trucks and trains passing nearby on air and noise pollution in residential areas during non-rush hours, we simultaneously measured concentrations of size-resolved airborne particulate matter (PM) and sound pressure levels as A-weighted equivalent (dBA) with frequencies in three underserved communities adjacent to industrial facilities in Houston, TX. We found that median concentrations for PM (particle size ≤ 1 μm) and PM (particle size ≤ 10 μm) were highest when trucks passed by at sampling locations, followed by periods when trains passed by.

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study.

Background: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA.

Methods: This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015.

In Vitro and In Vivo Investigation of Potential for Complex CYP3A Interaction for PF-00251802 (Dagrocorat), a Novel Dissociated Agonist of the Glucocorticoid Receptor.

The dissociated agonists of the glucocorticoid receptor are a novel class of agents in clinical development for rheumatoid arthritis. PF-04171327 (fosdagrocorat) is a phosphate ester prodrug of PF-00251802 (dagrocorat), a selective high-affinity partial agonist of the glucocorticoid receptor, which is further metabolized to PF-04015475. This study evaluated the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of PF-00251802 and PF-04015475 in vitro and used model-based prediction approaches to estimate clinical impact.

Evaluation of VOC concentrations in indoor and outdoor microenvironments at near-road schools.

A 14-week air quality study, characterizing the indoor and outdoor concentrations of 18 VOCs at four El Paso, Texas elementary schools, was conducted in Spring 2010. Three schools were in an area of high traffic density and the fourth school, considered as a background school, was situated in an area affected minimally by stationary and mobile sources of air pollution. Passive samplers were deployed for monitoring and analyzed by GC/MS.

Improved disease activity with fosdagrocorat (PF-04171327), a partial agonist of the glucocorticoid receptor, in patients with rheumatoid arthritis: a Phase 2 randomized study.

Aim: To assess efficacy and safety of fosdagrocorat (PF-04171327), a potential dissociated agonist of the glucocorticoid receptor, in rheumatoid arthritis (RA) patients.

Methods: This multicenter, double-blind, parallel-group, active- and placebo-controlled Phase 2 study (NCT00938587) randomized 86 patients (1 : 1 : 1 : 1) to receive fosdagrocorat 10 mg, fosdagrocorat 25 mg, prednisone 5 mg or placebo, all with stable background methotrexate therapy. The primary outcome was change from baseline in Disease Activity Score of 28 joints (DAS28-4[C-reactive protein (CRP)]) after 2 weeks of treatment.

Comparison of trace elements in size-fractionated particles in two communities with contrasting socioeconomic status in Houston, TX.

Levels of ambient air pollutants, including particulate matter (PM), are often higher in low-socioeconomic status (SES) communities than in high-SES communities. Houston is the fourth largest city in the USA and is home to a large petrochemical industry, an active port, and congested roadways, which represent significant emission sources of air pollution in the region. To compare levels of air pollution between a low-SES and a high-SES community, we simultaneously collected a 7-day integrated size-fractionated PM between June 2013 and November 2013.

Feasibility of using low-cost portable particle monitors for measurement of fine and coarse particulate matter in urban ambient air.

Unlabelled: Exposure to ambient particulate matter (PM) is known as a significant risk factor for mortality and morbidity due to cardiorespiratory causes. Owing to increased interest in assessing personal and community exposures to PM, we evaluated the feasibility of employing a low-cost portable direct-reading instrument for measurement of ambient air PM exposure. A Dylos DC 1700 PM sensor was collocated with a Grimm 11-R in an urban residential area of Houston Texas.

Source proximity and meteorological effects on residential outdoor VOCs in urban areas: Results from the Houston and Los Angeles RIOPA studies.

Concentrations of volatile organic compounds (VOCs) measured outside homes in Houston, TX and Los Angeles, CA were characterized by the effects of source proximity and meteorological factors. Benzene, toluene, ethylbenzene, m,p-xylene, o-xylene (BTEX), methyl tert butyl ether (MTBE), tetrachloroethylene (perchloroethylene, PCE), and carbon tetrachloride (CCl) were examined. Multiple stepwise regression analysis converged the best-fit models with predictors from meteorological conditions and the proximity to specific point, area, and mobile sources on the residential outdoor VOC concentrations.

Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers.

Association of short-term increases in ambient air pollution and timing of initial asthma diagnosis among Medicaid-enrolled children in a metropolitan area.

Objective: We investigated associations of short-term changes in ambient ozone (O3), fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations and the timing of new-onset asthma, using a large, high-risk population in an area with historically high ozone levels.

Methods: The study population included 18,289 incident asthma cases identified among Medicaid-enrolled children in Harris County Texas between 2005-2007, using Medicaid Analytic Extract enrollment and claims files.

Association Between Ambient Levels of Polycyclic Aromatic Hydrocarbons and Small for Gestational Age Hispanic Infants Born Along the United States-Mexico Border.

Few studies have examined associations between polycyclic aromatic hydrocarbons (PAHs) and birth outcomes, and no studies have been conducted in El Paso County Texas, along the United States-Mexico border. Infants born from 2005-2007 to Hispanic mothers with a birth weight less than the 10th percentile for gestational age and sex were classified as small for gestational age (SGA). PAH exposures were estimated for the entire period of gestation and for each trimester of pregnancy using ambient air monitoring data from 2004-2007.

Effects of Air Pollution on Asthma Hospitalization Rates in Different Age Groups in Metropolitan Cities of Korea.

Many studies have shown associations between air pollution and asthma admissions in Korea, but have not reported whether these effects differ by age classification. The purpose of this study was to determine whether air pollution effects on asthmatic hospital admissions are different by three age groups (years): children (less than 15), adults (15-64; reference group), and the elderly (over 65). Daily time-series data from seven metropolitan cities in South Korea were analyzed in two stages.

Evaluating the effects of maternal exposure to benzene, toluene, ethyl benzene, and xylene on oral clefts among offspring in Texas: 1999-2008.

Background: There is evidence from previous studies that maternal occupational exposure to hazardous air pollutants (HAPs) is positively associated with oral clefts; however, studies evaluating the association between residential exposure to these toxicants and oral clefts are lacking. Therefore, our goal was to conduct a case-control study examining the association between estimated maternal residential exposure to benzene, toluene, ethyl benzene, and xylene (BTEX) and the risk of oral clefts among offspring.

Methods: Data on 6045 nonsyndromic isolated oral cleft cases (3915 cleft lip with or without cleft palate [CL ± P] and 2130 nonsyndromic isolated cleft palate [CP] cases) delivered between 1999 and 2008 were obtained from the Texas Birth Defects Registry.

Determination of dopamine D₂ receptor occupancy by lurasidone using positron emission tomography in healthy male subjects.

Rationale: A positron emission tomography (PET) study of dopamine D₂ receptor occupancy was conducted to support a rational dose selection for clinical efficacy studies with lurasidone, an atypical antipsychotic that was approved for the treatment of schizophrenia by the FDA in late 2010.

Objectives: To determine the dopamine D₂ receptor occupancy of lurasidone in the ventral striatum, putamen and caudate nucleus, and to characterize the relationship between lurasidone serum concentration and D₂ receptor occupancy.

Methods: A single oral dose of lurasidone (10, 20, 40, 60, or 80 mg) was administered sequentially to healthy male subjects (n = 4 in each cohort).

Associations between urban air pollution and pediatric asthma control in El Paso, Texas.

Exposure to traffic-related pollutants poses a serious health threat to residents of major urban centers around the world. In El Paso, Texas, this problem is exacerbated by the region's arid weather, frequent temperature inversions, heavy border traffic, and an aged, poorly maintained vehicle fleet. The impact of exposure to traffic pollution, particularly on children with asthma, is poorly understood.

Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate.

Objective: To evaluate efficacy and safety of CE-224,535, a selective P2X(7) receptor antagonist, versus placebo, in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX).

Methods: In our phase IIA study (ClinicalTrials.gov no.

Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial.

Introduction: The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).

Methods: This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks.

Cancer risk disparities between hispanic and non-hispanic white populations: the role of exposure to indoor air pollution.

Background: Hispanics are the fastest growing minority group in the United States; however, minimal information is available on their cancer risks from exposures to hazardous air pollutants (HAPs) and how these risks compare to risks to non-Hispanic whites.

Methods: We estimated the personal exposure and cancer risk of Hispanic and white adults who participated in the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study. We evaluated 12 of the sampled volatile organic compounds and carbonyls and identified the HAPs of most concern and their possible sources.

Post-Hurricane Katrina passive sampling of ambient volatile organic compounds in the greater New Orleans area.

On August 29, 2005, Hurricane Katrina made landfall near New Orleans, Louisiana, a major metroplex with petroleum industries. In response to the potential impact of the storm on air quality and to assess the exposures to toxic air pollutants of public health concern, the United States Environmental Protection Agency conducted passive monitoring of air toxics for three months, starting in late October 2005 through early February 2006, at up to 18 sites in the New Orleans area affected by Hurricane Katrina. The overall results of the passive ambient monitoring are summarized with the concentrations for the twenty-nine observed volatile organic chemicals, which include benzene, toluene, ethylbenzene, and xylenes, and the measured concentrations are compared with available health-based screening levels.

Demographic, residential, and behavioral determinants of elevated exposures to benzene, toluene, ethylbenzene, and xylenes among the U.S. population: results from 1999-2000 NHANES.

Volatile organic compounds (VOC) represent a broad spectrum of compounds and there is growing concern that VOC exposures, in addition to increasing risks for cancer, may be implicated in exacerbating asthma and other adverse respiratory effects. Yet little is known about exposures in the U.S.

Evaluation of the use of diffusive air samplers for determining temporal and spatial variation of volatile organic compounds in the ambient air of urban communities.

The Houston-Galveston metropolitan area has a relatively high density of point and mobile sources of air toxics, and determining and understanding the relationship between emissions and ambient air concentrations of air toxics is important for evaluating potential impacts on public health and formulating effective regulatory policies to control this impact, both in this region and elsewhere. However, conventional ambient air monitoring approaches are limited with regard to expense, siting limitations, and representative sampling necessary for adequate exposure assessment. The overall goal of this multiphase study is to evaluate the use of simple passive air samplers to determine temporal and spatial variability of the ambient air concentrations of selected volatile organic compounds (VOCs) in urban areas.

Relationships of Indoor, Outdoor, and Personal Air (RIOPA): part II. Analyses of concentrations of particulate matter species.

During the study Relationships of Indoor, Outdoor, and Personal Air (RIOPA*), 48-hour integrated indoor, outdoor, and personal air samples were collected between summer 1999 and spring 2001 in three different areas of the United States: Elizabeth NJ, Houston TX, and Los Angeles County CA. Air samples suitable for analyzing particulate matter 2.5 microm or smaller in aerodynamic diameter (PM2.