A Risk-Adjusted Model for Ovarian Cancer Care and Disparities in Access to High-Performing Hospitals.

ObjectiveTo validate the observed/expected ratio for adherence to ovarian cancer treatment guidelines as a risk-adjusted measure of hospital quality care, and to identify patient characteristics associated with disparities in access to high-performing hospitals.MethodsThis was a retrospective population-based study of stage I-IV invasive epithelial ovarian cancer reported to the California Cancer Registry between 1996 and 2014. A fit logistic regression model, which was risk-adjusted for patient and disease characteristics, was used to calculate the observed/expected ratio for each hospital, stratified by hospital annual case volume. A Cox proportional hazards model was used for survival analyses, and a multivariable logistic regression model was used to identify independent predictors of access to high-performing hospitals.ResultsThe study population included 30,051 patients who were treated at 426 hospitals: low observed/expected ratio (n=304) 23.5% of cases; intermediate observed/expected ratio (n=92) 57.8% of cases; and high observed/expected ratio (n=30) 18.7% of cases. Hospitals with high observed/expected ratios were significantly more likely to deliver guideline-adherent care (53.3%), compared with hospitals with intermediate (37.8%) and low (27.5%) observed/expected ratios (P<.001). Median disease-specific survival time ranged from 73.0 months for hospitals with high observed/expected ratios to 48.1 months for hospitals with low observed/expected ratios (P<.001). Treatment at a hospital with a high observed/expected ratio was an independent predictor of superior survival compared with hospitals with intermediate (hazard ratio [HR] 1.06, 95% CI 1.01-1.11, P<.05) and low (HR 1.10, 95% CI 1.04-1.16, P<.001) observed/expected ratios. Being of Hispanic ethnicity (odds ratio [OR] 0.85, 95% CI 0.78-0.93, P<.001, compared with white), having Medicare insurance (OR 0.74, 95% CI 0.68-0.81 P<.001, compared with managed care), having a Charlson Comorbidity Index score of 2 or greater (OR 0.91, 95% CI 0.83-0.99, P<.05), and being of lower socioeconomic status (lowest quintile OR 0.41, 95% CI 0.36-0.46, P<.001, compared with highest quintile) were independent negative predictors of access to a hospital with a high observed/expected ratio.ConclusionOvarian cancer care at a hospital with a high observed/expected ratio is an independent predictor of improved survival. Barriers to high-performing hospitals disproportionately affect patients according to sociodemographic characteristics. Triage of patients with suspected ovarian cancer according to a performance-based observed/expected ratio hospital classification is a potential mechanism for expanded access to expert care

Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Congenital Anomalies: A Retrospective Cohort Study

BACKGROUND: Prior animal and human studies of prenatal exposure to solvents including tetrachloroethylene (PCE) have shown increases in the risk of certain congenital anomalies among exposed offspring. OBJECTIVES: This retrospective cohort study examined whether PCE contamination of public drinking water supplies in Massachusetts influenced the occurrence of congenital anomalies among children whose mothers were exposed around the time of conception. METHODS: The study included 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. Mothers completed a self-administered questionnaire to gather information on all of their prior births, including the presence of anomalies, residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. RESULTS: Children whose mothers had high exposure levels around the time of conception had an increased risk of congenital anomalies. The adjusted odds ratio of all anomalies combined among children with prenatal exposure in the uppermost quartile was 1.5 (95% CI: 0.9, 2.5). No meaningful increases in the risk were seen for lower exposure levels. Increases were also observed in the risk of neural tube defects (OR: 3.5, 95% CI: 0.8, 14.0) and oral clefts (OR 3.2, 95% CI: 0.7, 15.0) among offspring with any prenatal exposure. CONCLUSION: The results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who are identified by independent records.National Institute of Environmental Health (5 P42 ES007381); National Institutes of Healt

Brief Report: Diminishing Geographic Variability in Autism Spectrum Disorders Over Time?

We investigated differences in the geographic distribution of autism spectrum disorders (ASD) over time in central North Carolina with data from the Autism and Developmental Disabilities Monitoring (ADDM) Network. Using generalized additive models and geographic information systems we produced maps of ASD risk in 2002–2004 and 2006–2008. Overall the risk of ASD increased 52.9% from 2002–2004 to 2006–2008. However, the magnitude of change in risk was not uniform across the study area; while some areas experienced dramatic increases in ASD risk (>400%), others experienced slight decreases. Generally, areas with the lowest risk in 2002–2004 experienced the greatest increases over time. Education and outreach efforts in North Carolina expanded during this period, possibly contributing to the observed leveling of risk over time

The spatial distribution of known predictors of autism spectrum disorders impacts geographic variability in prevalence in central North Carolina

Abstract Background The causes of autism spectrum disorders (ASD) remain largely unknown and widely debated; however, evidence increasingly points to the importance of environmental exposures. A growing number of studies use geographic variability in ASD prevalence or exposure patterns to investigate the association between environmental factors and ASD. However, differences in the geographic distribution of established risk and predictive factors for ASD, such as maternal education or age, can interfere with investigations of ASD etiology. We evaluated geographic variability in the prevalence of ASD in central North Carolina and the impact of spatial confounding by known risk and predictive factors. Methods Children meeting a standardized case definition for ASD at 8 years of age were identified through records-based surveillance for 8 counties biennially from 2002 to 2008 (n=532). Vital records were used to identify the underlying cohort (15% random sample of children born in the same years as children with an ASD, n=11,034), and to obtain birth addresses. We used generalized additive models (GAMs) to estimate the prevalence of ASD across the region by smoothing latitude and longitude. GAMs, unlike methods used in previous spatial analyses of ASD, allow for extensive adjustment of individual-level risk factors (e.g. maternal age and education) when evaluating spatial variability of disease prevalence. Results Unadjusted maps revealed geographic variation in surveillance-recognized ASD. Children born in certain regions of the study area were up to 1.27 times as likely to be recognized as having ASD compared to children born in the study area as a whole (prevalence ratio (PR) range across the study area 0.57-1.27; global P=0.003). However, geographic gradients of ASD prevalence were attenuated after adjusting for spatial confounders (adjusted PR range 0.72-1.12 across the study area; global P=0.052). Conclusions In these data, spatial variation of ASD in central NC can be explained largely by factors impacting diagnosis, such as maternal education, emphasizing the importance of adjusting for differences in the geographic distribution of known individual-level predictors in spatial analyses of ASD. These results underscore the critical importance of accounting for such factors in studies of environmental exposures that vary across regions

Derivation Of Functional Human Astrocytes From Cerebral Organoids

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells. The cellular isolation of cerebral organoids yielded cells that were morphologically and functionally like astrocytes. Immunolabelling and proteomic assays revealed that human organoid-derived astrocytes express the main astrocytic molecular markers, including glutamate transporters, specific enzymes and cytoskeletal proteins. We found that organoid-derived astrocytes strongly supported neuronal survival and neurite outgrowth and responded to ATP through transient calcium wave elevations, which are hallmarks of astrocyte physiology. Additionally, these astrocytes presented similar functional pathways to those isolated from adult human cortex by surgical procedures. This is the first study to provide proteomic and functional analyses of astrocytes isolated from human cerebral organoids. The isolation of these astrocytes holds great potential for the investigation of developmental and evolutionary features of the human brain and provides a useful approach to drug screening and neurodegenerative disease modelling.7Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de JaneiroFAPERJConselho Nacional para o Desenvolvimento Cientifico e TecnologicoCNPqCoordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorCAPESFundacao de Amparo a Pesquisa do Estado de Sao PauloFAPESP [13/08711-3, 14/10068-4, 14/21035-0, 16/07332-7]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Cluster detection methods applied to the Upper Cape Cod cancer data

BACKGROUND: A variety of statistical methods have been suggested to assess the degree and/or the location of spatial clustering of disease cases. However, there is relatively little in the literature devoted to comparison and critique of different methods. Most of the available comparative studies rely on simulated data rather than real data sets. METHODS: We have chosen three methods currently used for examining spatial disease patterns: the M-statistic of Bonetti and Pagano; the Generalized Additive Model (GAM) method as applied by Webster; and Kulldorff's spatial scan statistic. We apply these statistics to analyze breast cancer data from the Upper Cape Cancer Incidence Study using three different latency assumptions. RESULTS: The three different latency assumptions produced three different spatial patterns of cases and controls. For 20 year latency, all three methods generally concur. However, for 15 year latency and no latency assumptions, the methods produce different results when testing for global clustering. CONCLUSION: The comparative analyses of real data sets by different statistical methods provides insight into directions for further research. We suggest a research program designed around examining real data sets to guide focused investigation of relevant features using simulated data, for the purpose of understanding how to interpret statistical methods applied to epidemiological data with a spatial component

Long-term Neurotoxic Effects of Early-life Exposure to Tetrachloroethylene-contaminated Drinking Water

Background: Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distributionpipes. Objectives: A retrospective cohort study (the Cape Cod Health Study) was undertaken to examine possible health consequences of early-life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the effects of prenatal and childhood exposure on neurologic outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiologic research in this unique setting. Methods: Participants were identified by cross-matching birth certificates and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (n = 1689), neuropsychological tests (n = 63), vision examinations (n = 63), and magnetic resonance imaging (n = 42). Early-life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among individuals with prenatal and early childhood PCE exposure to unexposed individuals while considering the effect of confounding variables. Findings: The study found evidence that early-life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical nature of the exposure assessments. Conclusions: The Cape Cod Health Study demonstrates how scientists can take advantage of unique “natural experiments” to learn about the health effects of environmental pollution. This body of work has improved our understanding of the long-term health effects of early-life exposure to this common environmental contaminant and will help risk assessors and policymakers ensure that drinking water supplies in the United States are safe for vulnerable populations

Relationship of perfluorooctanoic acid exposure to pregnancy outcome based on birth records in the mid-Ohio Valley.

BACKGROUND: Perfluorooctanoic acid (PFOA) is a potential cause of adverse pregnancy outcomes, but previous studies have been limited by low exposures and small study size. OBJECTIVES: Using birth certificate information, we examined the relation between estimated PFOA exposure and birth outcomes in an area of West Virginia and Ohio whose drinking water was contaminated by a chemical plant. METHODS: Births in the study area from 1990 through 2004 were examined to generate case groups of stillbirth (n = 106), pregnancy-induced hypertension (n = 224), preterm birth (n = 3,613), term low birth weight (n = 918), term small-for-gestational-age (SGA) (n = 353), and a continuous measure of birth weight among a sample of term births (n = 4,534). A 10% sample of term births ≥ 2,500 g were selected as a source of controls (n = 3,616). Historical estimates of serum PFOA were derived from a previously developed fate and transport model. In a second study, we examined 4,547 area births linked to a survey with residential history data. RESULTS: In the analysis based only on birth records, we found no consistent evidence of an association between estimated PFOA exposure and stillbirth, pregnancy-induced hypertension, preterm birth, or indices of fetal growth. In the analysis of birth records linked to the survey, PFOA was unrelated to pregnancy-induced hypertension or preterm birth but showed some suggestion of an association with early preterm birth. Measures of growth restriction showed weak and inconsistent associations with PFOA. CONCLUSIONS: Based on the analysis using the health survey, these results provide little support for an effect of PFOA exposure on most pregnancy outcomes, except for early preterm birth and possibly fetal growth restriction