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BACKGROUND: Fluoride has been associated with IQ deficits during early brain development, but the period in which children are most sensitive is unknown. OBJECTIVE: We assessed effects of fluoride on IQ scores across prenatal and postnatal exposure windows. METHODS: We used repeated exposures from 596 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals pregnancy and birth cohort. Fluoride was measured in urine (mg/L) collected from women during pregnancy and in their children between 1.9 and 4.4 years; urinary fluoride was adjusted for specific gravity. We estimated infant fluoride exposure (mg/day) using water fluoride concentration and duration of formula-feeding over the first year of life. Intelligence was assessed at 3-4 years using the Wechsler Preschool and Primary Scale of Intelligence-III. We used generalized estimating equations to examine the associations between fluoride exposures and IQ, adjusting for covariates. We report results based on standardized exposures given their varying units of measurement. RESULTS: The association between fluoride and performance IQ (PIQ) significantly differed across prenatal, infancy, and childhood exposure windows collapsing across child sex (p = .001). The strongest association between fluoride and PIQ was during the prenatal window, B = -2.36, 95% CI: -3.63, -1.08; the association was also significant during infancy, B = -2.11, 95% CI: -3.45, -0.76, but weaker in childhood, B = -1.51, 95% CI: -2.90, -0.12. Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows (boys: p = .01; girls: p = .01); among boys, the strongest association was during the prenatal window, B = -3.01, 95% CI: -4.60, -1.42, whereas among girls, the strongest association was during infancy, B = -2.71, 95% CI: -4.59, -0.83. Full-scale IQ estimates were weaker than PIQ estimates for every window. Fluoride was not significantly associated with Verbal IQ across any exposure window. CONCLUSION: Associations between fluoride exposure and PIQ differed based on timing of exposure. The prenatal window may be critical for boys, whereas infancy may be a critical window for girls.
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Fluoruros , Efectos Tardíos de la Exposición Prenatal , Canadá , Preescolar , Femenino , Fluoruros/toxicidad , Humanos , Lactante , Inteligencia , Pruebas de Inteligencia , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location. We therefore sought to examine IA location concordance, multiplicity, and rupture status within affected twin-pairs. METHODS: The Familial Intracranial Aneurysm study was a multicenter study whose goal was to identify genetic and other risk factors for formation and rupture of IAs. The study required at least three affected family members or an affected sibling pair for inclusion. Subjects with fusiform aneurysms, an IA associated with an AVM, or a family history of conditions known to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were excluded. Twin-pairs were identified by birth date and were classified as monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to zygosity, we evaluated twin-pairs by smoking status, major arterial territory of IAs, and rupture status. Location concordance was defined as the presence of an IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar), irrespective of laterality, in both members of a twin-pair. The Fisher exact test was used for comparisons between MZ and DZ twin-pairs. RESULTS: A total of 16 affected twin-pairs were identified. Location concordance was observed in 8 of 11 MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had unknown IA locations and comprised the three instances of MZ discordance. Six of the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of 22 MZ twins. CONCLUSIONS: We found that arterial location concordance was greater in MZ than DZ twins, which suggests a genetic influence upon aneurysm location. The 16 twin-pairs in the present study are nearly the total of affected twin-pairs that have been reported in the literature to date. Further studies are needed to determine the impact of genetics in the formation and rupture of IAs.
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Aneurisma Roto/genética , Aneurisma Intracraneal/genética , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Adulto , Anciano , Femenino , Humanos , Aneurisma Intracraneal/patología , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Rotura Espontánea , Fumar , Adulto JovenRESUMEN
OBJECTIVE: The objective of this study was to determine if computerized neurocognitive testing (Immediate Post-Concussion Assessment and Cognitive Testing [ImPACT]) in the emergency department (ED) can be used as a prognostic tool to detect young athletes at risk of having protracted concussive symptoms. METHODS: This was a prospective cohort study of athletes aged 11 to 18 years who presented to an ED less than 24 hours after sustaining a sports-related concussion. ImPACT was administered in the ED, and performance was categorized as "poor" if the athlete had 3 (of 4) or greater low domain scores. Participants completed the Post-Concussion Symptom Scale (PCSS) in the ED and by phone at 1 and 2 weeks after injury. Athletes were symptomatic if their PCSS score was more than 6 in males and more than 8 in females. RESULTS: One hundred nine patients were enrolled; 60% and 36% remained symptomatic at 1 and 2 weeks after injury, respectively. "Poor" ImPACT performance was not particularly useful in predicting athletes with protracted symptoms (at 1 week: positive predictive value, 70.8%; negative predictive value, 43.5%; at 2 weeks: positive predictive value, 47.8%; negative predictive value, 68.9%). In bivariate analysis, a higher ED PCSS score was associated with protracted symptoms (at 1 week: odds ratio, 1.1 [confidence interval, 1.0-1.1]; at 2 weeks: odds ratio, 1.0 [confidence interval, 1.0-1.1]). CONCLUSIONS: Computerized neurocognitive testing in the ED has limited usefulness in predicting protracted symptoms. Total acute symptom burden may be a useful prognostic tool in the ED evaluation of concussed young athletes, yet further research is necessary.
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Traumatismos en Atletas/diagnóstico , Conmoción Encefálica/diagnóstico , Diagnóstico por Computador/métodos , Servicio de Urgencia en Hospital , Pruebas Neuropsicológicas , Síndrome Posconmocional/diagnóstico , Adolescente , Atletas , Traumatismos en Atletas/psicología , Conmoción Encefálica/psicología , Niño , Estudios de Cohortes , Computadores , Femenino , Humanos , Masculino , Síndrome Posconmocional/psicología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Recuperación de la Función , EstudiantesRESUMEN
BACKGROUND AND PURPOSE: Our objective was to study nationwide utilization trends of computed tomographic (CT) angiogram (CTA) and CT perfusion (CTP) in acute ischemic stroke and particularly in the context of use of reperfusion therapies. METHODS: We reviewed the Premier Perspective Database for ischemic stroke-related hospitalizations of adult patients during a 5-year period, 2006 to 2010. Use of multimodal CT-based imaging and reperfusion therapies was determined through the procedure and billing codes. Logistic regression was used to identify predictors of utilization of imaging studies and reperfusion treatments. RESULTS: An increasing proportion of ischemic strokes received CTA each year: 3.8% in 2006, 5.6% in 2007, 6.5% in 2008, 7.5% in 2009, and 9.1% in 2010 (P<0.0001). The proportion of acute strokes that were imaged with CTP imaging also increased each year: 0.05% in 2006, 0.05% in 2007, 0.9% in 2008, 2.2% in 2009, and 2.9% in 2010 (P<0.0001). Reperfusion treatment was more common among those who were imaged with CTA (13.0%) and CTP (17.6%) compared with those with CT head alone (4.0%; P<0.0001). Specifically, higher rates of recombinant tissue-type plasminogen activator were observed in CTA (10.2%) and CTP (11.4%) compared with those with CT head alone (3.8%; P<0.0001). Similarly, higher rates of mechanical embolectomy were observed in CTA (2.8%) and CTP (6.3%) compared with those with CT head alone (0.2%; P<0.0001). CONCLUSIONS: There was a marked increase in the rate of CTA and CTP studies in setting of acute ischemic stroke from 2006 to 2010, and both modalities were associated with increased reperfusion therapy use.
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Isquemia Encefálica/diagnóstico por imagen , Angiografía Cerebral/estadística & datos numéricos , Imagen de Perfusión/estadística & datos numéricos , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Enfermedad Aguda , Anciano , Isquemia Encefálica/tratamiento farmacológico , Bases de Datos Factuales , Femenino , Fibrinolíticos/uso terapéutico , Hospitales Rurales/estadística & datos numéricos , Hospitales de Enseñanza/estadística & datos numéricos , Hospitales Urbanos/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Estados UnidosRESUMEN
BACKGROUND AND PURPOSE: Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. METHODS: We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family's proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. RESULTS: There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04-2.27]; P=0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22-3.22]; P=0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05-8.24], P=0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34-2.46]; P<0.001). CONCLUSIONS: In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.
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Familia , Predisposición Genética a la Enfermedad/genética , Aneurisma Intracraneal/genética , Aneurisma Intracraneal/patología , Carácter Cuantitativo Heredable , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
OBJECTIVES: To examine mortality patterns and dose-response relations between ionising radiation and mortality outcomes of a priori interest in 6409 uranium workers employed for at least 30 days (1951-1985), and followed through 2004. METHODS: Cohort mortality was evaluated through standardised mortality ratios (SMR). Linear excess relative risk (ERR) regression models examined associations between cause-specific mortality and exposures to internal ionising radiation from uranium deposition, external gamma and x-ray radiation, and radon decay products, while adjusting for non-radiologic covariates. RESULTS: Person-years at risk totalled 236 568 (mean follow-up 37 years), and 43% of the cohort had died. All-cause mortality was below expectation only in salaried workers. Cancer mortality was significantly elevated in hourly males, primarily from excess lung cancer (SMR=1.25, 95% CI 1.09 to 1.42). Cancer mortality in salaried males was near expectation, but lymphohaematopoietic malignancies were significantly elevated (SMR=1.52, 95% CI 1.06 to 2.12). A positive dose-response relation was observed for intestinal cancer, with a significant elevation in the highest internal organ dose category and a significant dose-response with organ dose from internal uranium deposition (ERR=1.5 per 100 µGy, 95% CI 0.12 to 4.1). CONCLUSIONS: A healthy worker effect was observed only in salaried workers. Hourly workers had excess cancer mortality compared with the US population, although there was little evidence of a dose-response trend for any cancer evaluated except intestinal cancer. The association between non-malignant respiratory disease and radiation dose observed in previous studies was not apparent, possibly due to improved exposure assessment, different outcome groupings, and extended follow-up.
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Industrias , Neoplasias Inducidas por Radiación/mortalidad , Enfermedades Profesionales/mortalidad , Exposición Profesional/efectos adversos , Radiación Ionizante , Adulto , Causas de Muerte , Estudios de Cohortes , Relación Dosis-Respuesta en la Radiación , Femenino , Efecto del Trabajador Sano , Humanos , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Modelos de Riesgos Proporcionales , Distribución por Sexo , Uranio , Adulto JovenRESUMEN
BACKGROUND: Routine renovation of older housing is a risk factor for childhood lead poisoning, but the contribution to children's blood lead levels is poorly defined for children with lower exposure levels. METHODS: We examined a prospective cohort of 276 children followed from 6 to 24 months of age. We conducted surveys of renovation activities and residential lead hazards and obtained blood lead level (B-Pb) every six months. We analyzed B-Pb in a repeated measures design using a mixed effects linear model. RESULTS: Parent reported interior renovation ranged from 11 to 25% of housing units at the four, 6-month periods. In multivariable analysis, children whose housing underwent interior renovation had a 12% higher mean B-Pb by two years of age compared with children whose housing units were not renovated (p < 0.01). The time between renovation and the child blood lead sample was associated with higher B-Pb (p-value for trend <0.01); compared to children in non-renovated housing, children whose housing units underwent renovation in the prior month had a 17% higher mean B-Pb at two years of age, whereas children whose housing renovation occurred in the prior 2-6 months had an 8% higher mean B-Pb. We also found an association between higher paint lead loading, measured using an X-ray fluorescence (XRF) based paint lead index, and child B-Pb (p = 0.02); for every 10 mg/cm2 increase in paint lead loading index there was a 7.5% higher mean childhood B-Pb. CONCLUSIONS: In an analysis of data collected before the recent changes to Environmental Protection Agency's Lead, Renovation, Repair and Painting Rule, routine interior housing renovation was associated with a modest increase in children's B-Pb. These results are important for the provision of clinical advice, for housing and public health professionals, and for policymakers.
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Exposición a Riesgos Ambientales , Intoxicación por Plomo/epidemiología , Plomo/sangre , Pintura/análisis , Estudios de Cohortes , Monitoreo del Ambiente , Vivienda , Humanos , Lactante , Intoxicación por Plomo/etiología , New York/epidemiología , Estudios Prospectivos , Espectrometría por Rayos X , Espectrofotometría AtómicaRESUMEN
The information for the present discussion on the uncertainties associated with estimation of radiation risks and probability of disease causation was assembled for the recently published NCRP Report No. 171 on this topic. This memorandum provides a timely overview of the topic, given that quantitative uncertainty analysis is the state of the art in health risk assessment and given its potential importance to developments in radiation protection. Over the past decade the increasing volume of epidemiology data and the supporting radiobiology findings have aided in the reduction of uncertainty in the risk estimates derived. However, it is equally apparent that there remain significant uncertainties related to dose assessment, low dose and low dose-rate extrapolation approaches (e.g. the selection of an appropriate dose and dose-rate effectiveness factor), the biological effectiveness where considerations of the health effects of high-LET and lower-energy low-LET radiations are required and the transfer of risks from a population for which health effects data are available to one for which such data are not available. The impact of radiation on human health has focused in recent years on cancer, although there has been a decided increase in the data for noncancer effects together with more reliable estimates of the risk following radiation exposure, even at relatively low doses (notably for cataracts and cardiovascular disease). New approaches for the estimation of hereditary risk have been developed with the use of human data whenever feasible, although the current estimates of heritable radiation effects still are based on mouse data because of an absence of effects in human studies. Uncertainties associated with estimation of these different types of health effects are discussed in a qualitative and semi-quantitative manner as appropriate. The way forward would seem to require additional epidemiological studies, especially studies of low dose and low dose-rate occupational and perhaps environmental exposures and for exposures to x rays and high-LET radiations used in medicine. The development of models for more reliably combining the epidemiology data with experimental laboratory animal and cellular data can enhance the overall risk assessment approach by providing biologically refined data to strengthen the estimation of effects at low doses as opposed to the sole use of mathematical models of epidemiological data that are primarily driven by medium/high doses. NASA's approach to radiation protection for astronauts, although a unique occupational group, indicates the possible applicability of estimates of risk and their uncertainty in a broader context for developing recommendations on: (1) dose limits for occupational exposure and exposure of members of the public; (2) criteria to limit exposures of workers and members of the public to radon and its short-lived decay products; and (3) the dosimetric quantity (effective dose) used in radiation protection.
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Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/prevención & control , Radiación Ionizante , Salud Radiológica , Animales , Animales de Laboratorio , Relación Dosis-Respuesta en la Radiación , Exposición a Riesgos Ambientales , Humanos , Exposición Profesional , Fotones , Dosis de Radiación , Protección Radiológica , Radón , Medición de Riesgo , Incertidumbre , Estados Unidos , United States National Aeronautics and Space Administration/normasRESUMEN
BACKGROUND: Exposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. OBJECTIVE: To quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex. METHODS: We measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics. RESULTS: Geometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10-2.50), 4.97 (3.20-6.20) and 1.09 (0.67-1.60) µg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p < .01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = -2.80, 95% CI: -4.92, -0.68; PFOS: B = -2.64, 95% CI: -4.77, -0.52; PFHxS: B = -2.92, 95% CI: -4.72, -1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = -3.16, 95% CI: -4.90, -1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: -0.99, 2.26). No significant associations were found for EF in either males or females. CONCLUSIONS: Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific.
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Contaminantes Ambientales , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Masculino , Embarazo , Femenino , Humanos , Niño , Preescolar , Contaminantes Ambientales/toxicidad , Canadá , Fluorocarburos/toxicidadRESUMEN
BACKGROUND: Genomewide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought to confirm previously reported loci, to identify novel risk factors, and to evaluate the contribution of these factors to familial and sporadic IA. METHOD: We utilized 2 complementary samples, one recruited on the basis of a dense family history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other without regard to family history (discovery sample 2: 1095 IA cases and 1286 controls). Imputation was used to generate a common set of single nucleotide polymorphisms (SNP) across samples, and a logistic regression model was used to test for association in each sample. Results from each sample were then combined in a metaanalysis. RESULTS: There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach genomewide significance. However, the metaanalysis yielded genomewide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P=3.6×10(-8)) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P=8.7×10(-5)). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype. CONCLUSIONS: In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA).
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Predisposición Genética a la Enfermedad/genética , Aneurisma Intracraneal/genética , ARN Largo no Codificante/genética , Factores de Transcripción SOXF/genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Fumar/efectos adversosRESUMEN
OBJECTIVES: Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. METHODS: A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. RESULTS: Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. CONCLUSIONS: These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 µg/m(3) Cd.
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Arsénico/toxicidad , Cadmio/toxicidad , Carcinógenos Ambientales/toxicidad , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/mortalidad , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Adulto , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/mortalidad , Análisis de Regresión , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Objective: Fluoride exposure >1.5 mg/L from water has been associated with adverse pregnancy and birth outcomes. Little is known, however, about the effect of fluoride at levels consistent with water fluoridation (i.e., 0.7 mg/L) on pregnancy and birth outcomes. We examined the relationship between maternal fluoride exposure, fertility, and birth outcomes in a Canadian pregnancy cohort living in areas where municipal drinking water fluoride concentrations ranged from 0.04 to 0.87 mg/L. Methods: Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, we estimated fluoride exposure during pregnancy using three different metrics: (1) maternal urinary fluoride concentrations standardized for specific gravity (MUFSG) and averaged across all three trimesters (N = 1566), (2) water fluoride concentration (N = 1370), and (3) fluoride intake based on self-reported consumption of water, coffee, and tea, adjusted for body weight (N = 1192). Data on fertility, birth weight, gestational age, preterm birth, and small-for-gestational age (SGA) were assessed. We used multiple linear regression to examine associations between fluoride exposure, birth weight and gestational age, and logistic regression to examine associations with fertility, preterm birth, and SGA, adjusted for relevant covariates. Results: Median (IQR) MUFSG was 0.50 (0.33-0.76) mg/L, median water fluoride was 0.52 (0.17-0.64) mg/L, and median fluoride intake was 0.008 (0.003-0.013) mg/kg/day. MUFSG, water fluoride concentrations, and fluoride intake were not significantly associated with fertility, birth weight, gestational age, preterm birth, or SGA. Fetal sex did not modify any of the associations. Conclusion: Fluoride exposure during pregnancy was not associated with fertility or birth outcomes in this Canadian cohort.
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In animal studies, the combination of in utero fluoride exposure and low iodine has greater negative effects on offspring learning and memory than either alone, but this has not been studied in children. We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys' and girls' intelligence. We used data from 366 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals Study. We corrected trimester-specific MUF and MUIC for creatinine, and averaged them to yield our exposure variables (MUFCRE, mg/g; MUICCRE, µg/g). We assessed children's full-scale intelligence (FSIQ) at 3 to 4 years. Using multiple linear regression, we estimated a three-way interaction between MUFCRE, MUICCRE, and child sex on FSIQ, controlling for covariates. The MUICCRE by MUFCRE interaction was significant for boys (p = 0.042), but not girls (p = 0.190). For boys whose mothers had low iodine, a 0.5 mg/g increase in MUFCRE was associated with a 4.65-point lower FSIQ score (95% CI: -7.67, -1.62). For boys whose mothers had adequate iodine, a 0.5 mg/g increase in MUFCRE was associated with a 2.95-point lower FSIQ score (95% CI: -4.77, -1.13). These results suggest adequate iodine intake during pregnancy may minimize fluoride's neurotoxicity in boys.
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Yodo , Efectos Tardíos de la Exposición Prenatal , Femenino , Fluoruros/efectos adversos , Humanos , Inteligencia , Pruebas de Inteligencia , Yodo/efectos adversos , Madres , EmbarazoRESUMEN
BACKGROUND AND PURPOSE: Recombinant tissue-type plasminogen activator (rtPA) is the only approved therapy for acute ischemic stroke (AIS). In 2004, 1.8% to 2.1% of AIS patients in the United States received rtPA. Given incentives from regulatory agencies and payors to increase rtPA use, we hypothesized that rtPA use in the United States would increase from 2005 to 2009. METHODS: AIS cases were defined by exclusion of hemorrhagic stroke and transient ischemic attack International Classification of Diseases 9th revision codes (430, 431, 432, and 435) from diagnosis-related groups 14, 15, 524, and 559 discharges. Patients receiving thrombolytics were identified using International Classification of Diseases 9th revision code 99.10 (Medicare Provider and Analysis Review and Premier databases) and pharmacy billing records (Premier). Change over time and differences between databases were tested using negative binomial regression. RESULTS: Within Medicare Provider and Analysis Review, thrombolytic use increased from 1.1% in 2005 to 3.4% in 2009 (P<0.001 for trend). Within Premier, thrombolytic use increased from 1.4% in 2005 to 3.7% in 2009 for all cases (P<0.001). Analysis of pharmacy billing records in Premier for 50-mg or 100-mg doses of rtPA showed that 3.4% of AIS cases were treated in 2009. Inclusion of patients with transient ischemic attack or hemorrhagic stroke International Classification of Diseases 9th revision codes who received any thrombolytic as "ischemic stroke patients receiving rtPA" changed the rate of thrombolysis to 5.2%. CONCLUSIONS: In 2009, 3.4% to 5.2% of AIS patients in the United States received thrombolytics, approximately double the rate of treatment in 2005. Rapid recognition and transport and quick treatment in the emergency department remain goals for further improving treatment rates.
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Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/estadística & datos numéricos , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Interpretación Estadística de Datos , Costos de la Atención en Salud , Humanos , Revisión de Utilización de Seguros , Medicare , Persona de Mediana Edad , Farmacia/estadística & datos numéricos , Proteínas Recombinantes/uso terapéutico , Análisis de Regresión , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: To identify the optimal measure of active and passive prenatal tobacco exposure to predict wheeze in early life. STUDY DESIGN: We conducted a birth cohort study of 398 mother-infant dyads enrolled during the second trimester of pregnancy and followed through age 2 years. We measured tobacco exposure with maternal report, serum cotinine level, and meconium cotinine level. We assessed wheeze with parent report every 6 months. We used a repeated measures logistic regression model. RESULTS: Of 367 children with respiratory data, 26% percent had parent reported active or passive prenatal maternal tobacco exposure, but cotinine was detected in 61% of mothers during pregnancy. Compared with children of mothers in the fifth percentile of tobacco exposure, children of mothers in the 95th percentile had increased odds of wheeze when exposure was measured with maternal serum cotinine level (adjusted OR, 2.6; 95% CI, 1.3-5.2; P < .006) versus meconium cotinine level (adjusted OR, 2.0; 95% CI, 1.0-4.0; P = .04) and total parent-reported exposure (adjusted OR, 1.7; 95% CI, 1.1-2.7; P = .01). CONCLUSIONS: Serum cotinine, a biomarker of tobacco exposure, was more strongly associated with wheeze than parent-reported exposure. Studies that rely on parent report of prenatal tobacco exposure may underestimate risk of wheeze.
Asunto(s)
Cotinina/análisis , Padres , Ruidos Respiratorios/etiología , Fumar/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos , Biomarcadores/análisis , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Meconio/química , Análisis Multivariante , Embarazo , Efectos Tardíos de la Exposición Prenatal , Autoinforme , Fumar/sangre , Contaminación por Humo de Tabaco/análisisRESUMEN
Recent randomized trials have shown a significant survival and functional outcome benefit with hemicraniectomy compared with medical therapy for carefully selected patients with acute ischemic stroke (AIS). Using a national hospital database, we sought to determine trends over time in rates of hemicraniectomy after AIS before and after publication of the pooled analysis of hemicraniectomy trials demonstrating the benefit of this approach. We queried the Premier database for all stroke-related admissions (denominator) using Diagnosis-Related Group codes 14, 15, and 524 and International Classification of Disease 9 codes 433, 434, and 436, and for hemicraniectomy (numerator) with Current Procedural Terminology codes 01.2, 01.24, 01.25, and 01.39 for fiscal years 2005-2008. Change over time was tested using negative binomial regression. During the study period, a total of 592,933 admissions for AIS were identified. A procedure code for hemicraniectomy was identified in 426 patients (0.072%). These patients tended to be younger, nonwhite, and male; however, 28% of these patients were over age 65. The rate of hemicraniectomy for AIS increased linearly by 21% per year during the study period (P < .001 for trend). After publication of the pooled analysis in the first quarter of 2007, the rate of hemicraniectomy did not increase further (P = .67 for rates before and after). Our data indicate that the rate of hemicraniectomy in AIS patients in the United States has increased over the past few years, but the total number of procedures remains low. Publication of the landmark study did not appear to significantly change this rate. Future studies should investigate the appropriateness of patient selection and missed opportunities for treatment.
Asunto(s)
Isquemia Encefálica/cirugía , Craniectomía Descompresiva/estadística & datos numéricos , Accidente Cerebrovascular/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/epidemiología , Isquemia Encefálica/mortalidad , Niño , Preescolar , Bases de Datos como Asunto , Craniectomía Descompresiva/efectos adversos , Craniectomía Descompresiva/mortalidad , Medicina Basada en la Evidencia , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: The purpose of this study was to replicate the previous association of single nucleotide polymorphisms (SNPs) with risk of intracranial aneurysm (IA) and to examine the relationship of smoking with these variants and the risk of IA. METHODS: White probands with an IA from families with multiple affected members were identified by 26 clinical centers located throughout North America, New Zealand, and Australia. White control subjects free of stroke and IA were selected by random digit dialing from the Greater Cincinnati population. SNPs previously associated with IA on chromosomes 2, 8, and 9 were genotyped using a TaqMan assay or were included in the Affymetrix 6.0 array that was part of a genomewide association study of 406 IA cases and 392 control subjects. Logistic regression modeling tested whether the association of replicated SNPs with IA was modulated by smoking. RESULTS: The strongest evidence of association with IA was found with the 8q SNP rs10958409 (genotypic P=9.2x10(-5); allelic P=1.3x10(-5); OR=1.86, 95% CI: 1.40 to 2.47). We also replicated the association with both SNPs on chromosome 9p, rs1333040 and rs10757278, but were not able to replicate the previously reported association of the 2 SNPs on chromosome 2q. Statistical testing showed a multiplicative relationship between the risk alleles and smoking with regard to the risk of IA. CONCLUSIONS: Our data provide complementary evidence that the variants on chromosomes 8q and 9p are associated with IA and that the risk of IA in patients with these variants is greatly increased with cigarette smoking.