Burden of illness of trigeminal neuralgia among patients managed in a specialist center in England.

BACKGROUND: Trigeminal neuralgia (TN) causes severe episodic, unilateral facial pain and is initially treated with antiepileptic medications. For patients not responding or intolerant to medications, surgery is an option. METHODS: In order to expand understanding of the pain-related burden of illness associated with TN, a cross-sectional survey was conducted of patients at a specialist center that utilizes a multidisciplinary care pathway. Participants provided information regarding their pain experience and treatment history, and completed several patient-reported outcome (PRO) measures. RESULTS: Of 129 respondents, 69/128 (54%; 1 missing) reported no pain in the past 4 weeks. However, 84 (65%) respondents were on medications, including 49 (38%) on monotherapy and 35 (27%) on polytherapy. A proportion of patients had discontinued at least one medication in the past, mostly due to lack of efficacy (n = 62, 48%) and side effects (n = 51, 40%). A total of 52 (40%) patients had undergone surgery, of whom 30 had microvascular decompression (MVD). Although surgery, especially MVD, provided satisfactory pain control in many patients, 29% of post-surgical patients reported complications, 19% had pain worsen or stay the same, 48% were still taking pain medications for TN, and 33% reported new and different facial pain. CONCLUSIONS: In most PRO measures, respondents with current pain interference had poorer scores than those without pain interference. In the Patient Global Impression of Change, 79% expressed improvement since beginning of treatment at this clinic. These results indicate that while the multidisciplinary approach can substantially alleviate the impact of TN, there remains an unmet medical need for additional treatment options.

Contribution of particle-size-fractionated airborne lead to blood lead during the National Health and Nutrition Examination Survey, 1999-2008.

The objective of this work is to examine associations between blood lead (PbB) and air lead (PbA) in particulate matter measured at different size cuts by use of PbB concentrations from the National Health and Nutrition Examination Survey and PbA concentrations from the U.S. Environmental Protection Agency for 1999-2008. Three size fractions of particle-bound PbA (TSP, PM10, and PM2.5) data with different averaging times (current and past 90-day average) were utilized. A multilevel linear mixed effect model was used to characterize the PbB-PbA relationship. At 0.15 µg/m(3), a unit decrease in PbA in PM10 was significantly associated with a decrease in PbB of 0.3-2.2 µg/dL across age groups and averaging times. For PbA in PM2.5 and TSP, slopes were generally positive but not significant. PbB levels were more sensitive to the change in PbA concentrations for children (1-5 and 6-11 years) and older adults (≥ 60 years) than teenagers (12-19 years) and adults (20-59 years). For the years following the phase-out of Pb in gasoline and a resulting upward shift in the PbA particle size distribution, PbA in PM10 was a statistically significant predictor of PbB. The results also suggest that age could affect the PbB-PbA association, with children having higher sensitivity than adults.

Associations between prenatal exposure to air pollution, small for gestational age, and term low birthweight in a state-wide birth cohort.

A range of health effects, including adverse pregnancy outcomes, have been associated with exposure to ambient concentrations of particulate matter (PM) and ozone (O3). The objective of this study was to determine whether maternal exposure to fine particulate matter (PM2.5) and O3 during pregnancy is associated with the risk of term low birthweight and small for gestational age infants in both single and co-pollutant models. Term low birthweight and small for gestational age were determined using all birth certificates from North Carolina from 2003 to 2005. Ambient air concentrations of PM2.5 and O3 were predicted using a hierarchical Bayesian model of air pollution that combined modeled air pollution estimates from the EPA׳s Community Multi-Scale Air Quality (CMAQ) model with air monitor data measured by the EPA׳s Air Quality System. Binomial regression, adjusted for multiple potential confounders, was performed. In adjusted single-pollutant models for the third trimester, O3 concentration was positively associated with small for gestational age and term low birthweight births [risk ratios for an interquartile range increase in O3: 1.16 (95% CI 1.11, 1.22) for small for gestational age and 2.03 (95% CI 1.80, 2.30) for term low birthweight]; however, inverse or null associations were observed for PM2.5 [risk ratios for an interquartile range increase in PM2.5: 0.97 (95% CI 0.95, 0.99) for small for gestational age and 1.01 (95% CI 0.97, 1.06) for term low birthweight]. Findings were similar in co-pollutant models and linear models of birthweight. These results suggest that O3 concentrations in both urban and rural areas may be associated with an increased risk of term low birthweight and small for gestational age births.

Early prenatal exposure to air pollution and its associations with birth defects in a state-wide birth cohort from North Carolina.

BACKGROUND: Few studies have examined the potential relationship between air pollution and birth defects. The objective of this study was to investigate whether maternal exposure to particulate matter (PM2.5 ) and ozone (O3 ) during pregnancy is associated with birth defects among women living throughout North Carolina. METHODS: Information on maternal and infant characteristics was obtained from North Carolina birth certificates and health service data (2003-2005) and linked with information on birth defects from the North Carolina Birth Defects Monitoring Program. The 24-hr PM2.5 and O3 concentrations were estimated using a hierarchical Bayesian model of air pollution generated by combining modeled air pollution predictions from the U.S. Environmental Protection Agency's Community Multi-Scale Air Quality model with air monitor data from the Environmental Protection Agency's Air Quality System. Maternal residence was geocoded and assigned pollutant concentrations averaged over weeks 3 to 8 of gestation. Binomial regression was performed and adjusted for potential confounders. RESULTS: No association was observed between either PM2.5 or O3 concentrations and most birth defects. Positive effect estimates were observed between air pollution and microtia/anotia and lower limb deficiency defects, but the 95% confidence intervals were wide and included the null. CONCLUSION: Overall, this study suggested a possible relationship between air pollution concentration during early pregnancy and certain birth defects (e.g., microtia/anotia, lower limb deficiency defects), although this study did not have the power to detect such an association. The risk for most birth defects does not appear to be affected by ambient air pollution.

The effects of exposure to particulate matter and neighbourhood deprivation on gestational hypertension.

Gestational hypertension, pre-eclampsia and eclampsia are conditions that affect the health of both mothers and infants during and after pregnancy. Recent research indicates the importance of considering environmental, social and individual contributors to poor pregnancy outcomes. Our research examined particulate matter (PM) concentrations as one measure of environmental exposure and neighbourhood quality as one measure of the social environment. We used these measures, as well as maternal characteristics, to predict the risk of gestational hypertension (including pre-eclampsia and eclampsia). North Carolina Detailed Birth Record data for 2000-2003 were obtained and geocoded for all singleton births. Levels of PM(10) and PM(2.5) were determined using air quality data from the US Environmental Protection Agency. Information on a woman's residential neighbourhood was determined from 2000 Census data. Modified Poisson regression models clustered by tract were used to examine the associations between PM levels, neighbourhood deprivation and maternal characteristics with gestational hypertension. Analysis was restricted to women residing within 20 km of a PM monitor. Both PM(10) and PM(2.5) were associated with gestational hypertension; the risk ratios for an interquartile range (IQR) increase in exposure were 1.07 [95% confidence interval (CI) 1.04, 1.11] for PM(10) (IQR: 3.92 µg/m(3)) and 1.11 [95% CI 1.08, 1.15] for PM(2.5) (IQR: 2.24 µg/m(3)). Living in a neighbourhood with increased levels of deprivation was also associated with gestational hypertension. Any smoking during pregnancy, younger age and higher level of education were inversely associated with risk of gestational hypertension. Compared with non-Hispanic White women, non-Hispanic Black women were at higher risk of gestational hypertension, whereas Hispanic women were at lower risk. Increased levels of PM and neighbourhood deprivation, as well as certain individual characteristics, were associated with higher risk of gestational hypertension.

Prevalence of ten LRRK2 variants in Parkinson's disease: A comprehensive review.

INTRODUCTION: Variants in the leucine-rich repeat kinase 2 gene (LRRK2) are risk factors for Parkinson's disease (PD), but their prevalence varies geographically, reflecting the locations of founder events and dispersion of founders' descendants. METHODS: A comprehensive literature review was conducted to identify studies providing prevalence estimates for any of ten variants in LRRK2 (G2019S, R1441C, R1441G, R1441H, I2020T, N1437H, Y1699C, S1761R, G2385R, R1628P) among individuals with PD globally. We calculated crude country-specific variant prevalence estimates and, when possible, adjusted estimates for ethno-racial composition. For clinic-based studies, probands were used over other familial cases, whereas for population-based studies, all PD cases were used. RESULTS: The analysis included 161 articles from 52 countries yielding 581 prevalence estimates across the ten variants. G2019S was the most common variant, exceeding 1.0% in 26 of 51 countries with estimates. The other variants were far less common. G2385R and R1628P were observed almost exclusively in East Asian countries, where they were found in ∼5-10% of cases. All prevalence estimates adjusted for ethno-racial composition were lower than their unadjusted counterparts, although data permitting this adjustment was only available for six countries. CONCLUSIONS: Except for G2019S, the LRRK2 variants covered in this review were uncommon in most countries studied. However, there were countries with higher prevalence for some variants, reflecting the uneven geographic distribution of LRRK2 variants. The fact that ethno-racial group‒adjusted estimates were lower than crude estimates suggests that estimates derived largely from clinic-based studies may overstate the true prevalence of some LRRK2 variants in PD.

Prevalence of RPGR-mutated X-linked retinitis pigmentosa among males.

BACKGROUND: X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease predominantly affecting males. MATERIALS AND METHODS: A comprehensive literature review was conducted to determine the prevalence of retinitis pigmentosa GTPase regulator (RPGR)-mutated XLRP. Identified studies were used to estimate four components among males: the prevalence of retinitis pigmentosa (RP), the proportion of RP that was X-linked, the proportion of misclassified inheritance type among RP cases, and the proportion of XLRP that was RPGR-mutated. Studies providing a direct estimate of XLRP prevalence were also included. The components' sample size-weighted averages were combined to determine an overall prevalence estimate. RESULTS: The prevalence of XLRP was estimated to be between 2.7-3.5 per 100,000 males in the US, Europe, and Australia. After correction for misclassification, the prevalence increased to 4.0-5.2 per 100,000 males. Finally, the proportion of XLRP cases due to RPGR mutations was applied, resulting in an RPGR-mutated XLRP estimate of 3.4-4.4 per 100,000 males. Studies from other countries were consistent with the results for the overall XLRP prevalence but were not included in the final calculation because of regional variations and lack of detailed information. CONCLUSIONS: These findings address an important gap in the understanding of RPGR-mutated XLRP by summarizing the global burden of this condition.

Food insecurity during pregnancy leads to stress, disordered eating, and greater postpartum weight among overweight women.

OBJECTIVE: To investigate the influence of food insecurity on women's stress, disordered eating, dietary fat intake, and weight during the postpartum period. METHODS: The association between marginal food security and food insecurity-measured during pregnancy and postpartum-and stress, disordered eating, dietary fat intake, and weight at 3 and 12 months postpartum was estimated using multivariate linear regression, controlling for demographic and socioeconomic characteristics and health behaviors. Effect modification between level of food insecurity and prepregnancy weight status was assessed, hypothesizing a stronger association would be found among women who started pregnancy with overweight or obesity. RESULTS: Food insecurity status during pregnancy was strongly associated with higher levels of stress, disordered eating, and dietary fat intake at 3 and 12 months postpartum; during the postpartum period, food insecurity was associated with these measures at 12 months postpartum. A significant interaction was found between level of food insecurity and prepregnancy weight status; food insecurity was associated with greater weight and BMI at 12 months only among women with overweight or obesity. CONCLUSIONS: In order to return to one's prepregnancy weight, women with overweight and obesity who face household food insecurity may need multipronged assistance that not only addresses having enough high-quality food, but also include stress reduction and eating behavior interventions.

An exploratory analysis of the relationship between ambient ozone and particulate matter concentrations during early pregnancy and selected birth defects in Texas.

We performed an exploratory analysis of ozone (O3) and fine particulate matter (PM2.5) concentrations during early pregnancy and multiple types of birth defects. Data on births were obtained from the Texas Birth Defects Registry (TBDR) and the National Birth Defects Prevention Study (NBDPS) in Texas. Air pollution concentrations were previously determined by combining modeled air pollution concentrations with air monitoring data. The analysis generated hypotheses for future, confirmatory studies; although many of the observed associations were null. The hypotheses are provided by an observed association between O3 and craniosynostosis and inverse associations between PM2.5 and septal and obstructive heart defects in the TBDR. Associations with PM2.5 for septal heart defects and ventricular outflow tract obstructions were null using the NBDPS. Both the TBDR and the NBPDS had inverse associations between O3 and septal heart defects. Further research to confirm the observed associations is warranted.

Cross-species coherence in effects and modes of action in support of causality determinations in the U.S. Environmental Protection Agency's Integrated Science Assessment for Lead.

The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States (U.S.) Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of relationships between Pb exposure and specific endpoints that are shared by humans, laboratory animals, and ecological receptors (i.e., hematological effects, reproductive and developmental effects, and nervous system effects). Other effects of Pb (i.e., cardiovascular, renal, and inflammatory responses) are less commonly assessed in aquatic and terrestrial wildlife limiting the application of cross-species comparisons. Determinations of causality in ISAs are guided by a framework for classifying the weight of evidence across scientific disciplines and across related effects by considering aspects such as biological plausibility and coherence. As illustrated for effects of Pb where evidence across species exists, the integration of coherent effects and common underlying modes of action can serve as a means to substantiate conclusions regarding the causal nature of the health and ecological effects of environmental toxicants.

Effect measure modification of blood lead-air lead slope factors.

There is abundant literature finding that susceptibility factors, including race and ethnicity, age, and housing, directly influence blood lead levels. No study has explored how susceptibility factors influence the blood lead-air lead relationship nationally. The objective is to evaluate whether susceptibility factors act as effect measure modifiers on the blood lead-air lead relationship. Participant level blood lead data from the 1999 to 2008 National Health and Nutrition Examination Survey were merged with air lead data from the US Environmental Protection Agency. Linear mixed effects models were run with and without an air lead interaction term for age group, sex, housing age, or race/ethnicity to determine whether these factors are effect measure modifiers for all ages combined and for five age brackets. Age group and race/ethnicity were determined to be effect measure modifiers in the all-age model and for some age groups. Being a child (1-5, 6-11, and 12-19 years) or of Mexican-American ethnicity increased the effect estimate. Living in older housing (built before 1950) decreased the effect estimate for all models except for the 1-5-year group, where older housing was an effect measure modifier. These results are consistent with the peer-reviewed literature of time-activity patterns, ventilation, and toxicokinetics.

Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study.

OBJECTIVE: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. METHODS: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. RESULTS: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. CONCLUSIONS: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed.

Evaluating potential response-modifying factors for associations between ozone and health outcomes: a weight-of-evidence approach.

BACKGROUND: Epidemiologic and experimental studies have reported a variety of health effects in response to ozone (O3) exposure, and some have indicated that certain populations may be at increased or decreased risk of O3-related health effects. OBJECTIVES: We sought to identify potential response-modifying factors to determine whether specific groups of the population or life stages are at increased or decreased risk of O3-related health effects using a weight-of-evidence approach. METHODS: Epidemiologic, experimental, and exposure science studies of potential factors that may modify the relationship between O3 and health effects were identified in U.S. Environmental Protection Agency's 2013 Integrated Science Assessment for Ozone and Related Photochemical Oxidants. Scientific evidence from studies that examined factors that may influence risk were integrated across disciplines to evaluate consistency, coherence, and biological plausibility of effects. The factors identified were then classified using a weight-of-evidence approach to conclude whether a specific factor modified the response of a population or life stage, resulting in an increased or decreased risk of O3-related health effects. DISCUSSION: We found "adequate" evidence that populations with certain genotypes, preexisting asthma, or reduced intake of certain nutrients, as well as different life stages or outdoor workers, are at increased risk of O3-related health effects. In addition, we identified other factors (i.e., sex, socioeconomic status, and obesity) for which there was "suggestive" evidence that they may increase the risk of O3-related health effects. CONCLUSIONS: Using a weight-of-evidence approach, we identified a diverse group of factors that should be considered when characterizing the overall risk of health effects associated with exposures to ambient O3.

The influence of declining air lead levels on blood lead-air lead slope factors in children.

BACKGROUND: It is difficult to discern the proportion of blood lead (PbB) attributable to ambient air lead (PbA), given the multitude of lead (Pb) sources and pathways of exposure. The PbB-PbA relationship has previously been evaluated across populations. This relationship was a central consideration in the 2008 review of the Pb national ambient air quality standards. OBJECTIVES: The objectives of this study were to evaluate the relationship between PbB and PbA concentrations among children nationwide for recent years and to compare the relationship with those obtained from other studies in the literature. METHODS: We merged participant-level data for PbB from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 9908 (1999-2008) with PbA data from the U.S. Environmental Protection Agency. We applied mixed-effects models, and we computed slope factor, d[PbB]/d[PbA] or the change in PbB per unit change in PbA, from the model results to assess the relationship between PbB and PbA. RESULTS: Comparing the NHANES regression results with those from the literature shows that slope factor increased with decreasing PbA among children 0-11 years of age. CONCLUSION: These findings suggest that a larger relative public health benefit may be derived among children from decreases in PbA at low PbA exposures. Simultaneous declines in Pb from other sources, changes in PbA sampling uncertainties over time largely related to changes in the size distribution of Pb-bearing particulate matter, and limitations regarding sampling size and exposure error may contribute to the variability in slope factor observed across peer-reviewed studies.

Comments on: Chari, R.; Burke, T.A.; White, R.H.; Fox, M.A. Integrating Susceptibility into environmental policy: an analysis of the national ambient air quality standard for lead. Int. J. Environ. Res. Public Health 2012, 9, 1077-1096.

In their recent article [1], Chari et al. call attention to the important subject of setting National Ambient Air Quality Standards (NAAQS) to provide requisite protection for public health, including the health of sensitive groups, as specified under the Clean Air Act (73 FR 66965) [2]. The authors focus on consideration of susceptibility to inform policy choices, using lead (Pb)-related neurocognitive effects and children from low socioeconomic status (SES) families in the context of alternative Pb standard levels. Our comments focus on the authors' analysis of the scientific evidence and not on policy. We agree with the authors that the health effects evidence for Pb indicates a role (or roles) for SES-related factors in influencing childhood Pb exposure and associated health effects. We disagree, however, with the authors' interpretation of the literature on SES influence on the shape of the concentration-response (C-R) relationship between children's blood Pb and IQ (e.g., steepness of the slope). We further address aspects of the scientific evidence that are important to the consideration of sensitive populations in the context of the Pb NAAQS, and how the U.S. Environmental Protection Agency (EPA) considered this evidence in setting the Pb NAAQS in 2008.

A multi-level model of blood lead as a function of air lead.

National and local declines in lead (Pb) in blood (PbB) over the past several years coincide with the decline in ambient air Pb (PbA) concentrations. The objective of this work is to evaluate how the relationship between PbB levels and PbA levels has changed following the phase out of leaded gasoline and tightened controls on industrial Pb emissions over the past 30 years among a national population sample. Participant-level data from the National Health and Nutrition Examination Survey (NHANES) were employed for two time periods (1988-1994 and 1999-2008), and the model was corrected for housing, demographic, socioeconomic, and other covariates present in NHANES. NHANES data for PbB and covariates were merged with PbA data from the U.S. Environmental Protection Agency. Linear mixed effects models (LMEs) were run to assess the relationship of PbB with PbA; sample weights were omitted, given biases encountered with the use of sample weights in LMEs. The 1988-1994 age-stratified results found that ln(PbB) was statistically significantly associated with ln(PbA) for all age groups. The consistent influence of PbA on PbB across age groups for the years 1988-1994 suggests a ubiquitous exposure unrelated to age of the sample population. The comparison of effect estimates for ln(PbA) shows a statistically significant effect estimate and ANOVA results for ln(PbB) for the 6- to 11-year and 12- to 19-year age groups during 1999-2008. The more recent finding suggests that PbA has less consistent influence on PbB compared with other factors.

Conceptualizing neighborhood space: consistency and variation of associations for neighborhood factors and pregnancy health across multiple neighborhood units.

The purpose of this research was to assess the consistency of associations between neighborhood characteristics and pregnancy-related behaviors and outcomes across four nested neighborhood boundaries using race-stratified fixed-slope random-intercept multilevel logistic models. High incivilities was associated with increased smoking, inadequate weight gain and pregnancy-induced hypertension (PIH), while walkability was associated with decreased smoking and PIH for white women across all neighborhood definitions. For African American women, high incivilities was associated with increased smoking and inadequate gestational weight gain, while more walkable neighborhoods appeared protective against smoking and inadequate weight gain in all but the smallest neighborhoods. Associations with neighborhood attributes were similar in effect size across geographies, but less precise as neighborhoods became smaller.

An ecologic analysis of county-level PM2.5 concentrations and lung cancer incidence and mortality.

Few studies have explored the relationship between PM2.5 and lung cancer incidence. Although results are mixed, some studies have demonstrated a positive relationship between PM2.5 and lung cancer mortality. Using an ecologic study design, we examined the county-level associations between PM2.5 concentrations (2002-2005) and lung cancer incidence and mortality in North Carolina (2002-2006). Positive trends were observed between PM2.5 concentrations and lung cancer incidence and mortality; however, the R2 for both were <0.10. The slopes for the relationship between PM2.5 and lung cancer incidence and mortality were 1.26 (95% CI 0.31, 2.21, p-value 0.01) and 0.73 (95% CI 0.09, 1.36, p-value 0.03) per 1 µg/m3 PM2.5, respectively. These associations were slightly strengthened with the inclusion of variables representing socioeconomic status and smoking. Although variability is high, thus reflecting the importance of tobacco smoking and other etiologic agents that influence lung cancer incidence and mortality besides PM2.5, a positive trend is observed between PM2.5 and lung cancer incidence and mortality. This suggests the possibility of an association between PM2.5 concentrations and lung cancer incidence and mortality.