Sample records for adverse outcome pathways

  1. Adverse outcome pathways: a concise introduction for toxicologists

    PubMed Central

    Vergauwen, Lucia; Hengstler, Jan G.; Angrish, Michelle; Whelan, Maurice

    2018-01-01

    Adverse outcome pathways are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use adverse outcome pathways, have been published in the last few years. The present paper provides a synopsis of the main principles related to the adverse outcome pathway framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology. PMID:28660287

  2. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  3. Putative adverse outcome pathways relevant to neurotoxicity

    PubMed Central

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  4. Adverse Outcome Pathway (AOP) Network Development for ...

    EPA Pesticide Factsheets

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk research. According to the Organization for Economic Co-operation and Development guidelines, AOPs are pathways with one MIE anchored to an adverse outcome (AO) by key events (KEs) and key event relationships (KERs). However, this approach does not always capture the cumulative impacts of multiple MIEs on the AO. For example, hepatic lipid flux due to chemical-induced toxicity initiates from multiple ligand-activated receptors and signaling pathways that cascade across biology to converge upon a common fatty liver (FL, also known as steatosis) outcome. To capture this complexity, a top-down strategy was used to develop a FL AOP network (AOPnet). Literature was queried based on the terms steatosis, fatty liver, cirrhosis, and hepatocellular carcinoma. Search results were analyzed for physiological and pathophysiological organ level, cellular and molecular processes, as well as pathway intermediates, to identify potential KEs and MIEs that are key for hepatic lipid metabolism, maintenance, and dysregulation. The analysis identified four apical KE nodes (hepatic fatty acid uptake, de novo fatty acid and lipid synthesis, fatty acid oxidation, and lipid efflux) juxtaposed to the FL AO. The apic

  5. Computational Approaches for Identifying Adverse Outcome Pathways

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) provide a framework for organizing toxicity information to improve predictions of the potential adverse impact of environment stressors on humans or wildlife populations, but these benefits are currently limited by the small number of AOPs currentl...

  6. Adverse Outcome Pathway Network Analyses: Techniques and benchmarking the AOPwiki

    EPA Science Inventory

    Abstract: As the community of toxicological researchers, risk assessors, and risk managers adopt the adverse outcome pathway (AOP) paradigm for organizing toxicological knowledge, the number and diversity of adverse outcome pathways and AOP networks are continuing to grow. This ...

  7. Developing and applying the adverse outcome pathway ...

    EPA Pesticide Factsheets

    To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis to predict effects for structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed.A variety of cellular and molecular processes are known to be critical to normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of principles of the description and assessment of MOA and AOPs, examples of adverse out

  8. Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity

    EPA Science Inventory

    Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity The adverse outcome pathway (AOP) for embryonic vascular disruption1 leading to a range of adverse prenatal outcomes was recently entered into the AOP wiki and accepted as par...

  9. Adverse Outcome Pathways – Tailoring Development to Support Use

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

  10. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  11. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  12. .Network analytics for adverse outcome pathways

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) organize toxicological knowledge from the molecular level up to the population level, providing evidence-based causal linkages at each step. The AOPWiki serves as a repository of AOPs. With the international adoption of the AOP framework, the AOPw...

  13. The adverse outcome pathway knowledge base

    EPA Science Inventory

    The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

  14. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  15. An “ADME Module” in the Adverse Outcome Pathway Knowledgebase

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP fra...

  16. Adverse Outcome Pathways: From Research to Regulation - Scientific Workshop Report

    EPA Science Inventory

    An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify...

  17. Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology

    EPA Science Inventory

    A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course p...

  18. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  19. Adverse Outcome Pathways: From Research to Regulation ...

    EPA Pesticide Factsheets

    An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop co-sponsored by NICEATM and PCRM considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop. This manuscript provides a

  20. Applying Aggregate Exposure Pathway and Adverse Outcome ...

    EPA Pesticide Factsheets

    Hazard assessment for nanomaterials often involves applying in vitro dose-response data to estimate potential health risks that arise from exposure to products that contain nanomaterials. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biological mechanisms that lead to apical adverse health outcomes in living organisms. The Adverse Outcome Pathway (AOP) framework addresses this uncertainty by acting as a scaffold onto which in vitro toxicity testing and other data can be arranged to aid in the interpretation of these results in terms of biologically-relevant responses, as an AOP connects an upstream molecular initiating event (MIE) to a downstream adverse outcome. In addition to hazard assessment, risk estimation also requires reconciling in vitro concentrations sufficient to produce bioactivity with in vivo concentrations that can trigger a MIE at the relevant biological target. Such target site exposures (TSEs) can be estimated by integrating pharmacokinetic considerations with environmental and exposure factors. Environmental and exposure data have been historically scattered in various resources, such as monitoring data for air pollutants or exposure models for specific chemicals. The Aggregate Exposure Pathway (AEP) framework is introduced to organize existing knowledge concerning biologically, chemically, and physically plausible, as well as empirically supported, links between the i

  1. Accelerating Adverse Outcome Pathway (AOP) development via computationally predicted AOP networks

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  2. THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK ...

    EPA Pesticide Factsheets

    An Adverse Outcome Pathway (AOP) represents the organization of current and newly acquired knowledge of biological pathways. These pathways contain a series of nodes (Key Events, KEs) that when sufficiently altered influence the next node on the pathway, beginning from an Molecular Initiating Event (MIE), through intermediate KEs, ending in an Adverse Outcome (AO) which may be used as a basis for decision making. A KE is a measurable biological change, and is linked with other KEs via Key Event Relationships (KERs). A given KE may be involved in several AOPs, leading to a plausible network of biological changes that are involved in an organism’s response to an external stressor. When describing an AOP, five guiding principles have been proposed [1]: 1) an AOP is not specific to a single external stressor, 2) AOPs are modular, with KEs and KERs that can be used in several AOPs, 3) a single AOP is the unit of development, 4) most biological responses will be the result of networks of AOPs, and 5) AOPs will be modified as more biological knowledge becomes available. The collaborative development of AOPs is recommended to be performed using the AOP-Wiki (https://aopwiki.org), which is an effort between the European Commission – DG Joint Research Centre (JRC) and U.S. Environmental Protection Agency (EPA). The Wiki is one part of a larger OECD-sponsored AOP Knowledgebase effort, which is a repository for all AOPs developed as part of the Organization for Economic

  3. Informatics approaches in the Biological Characterization of Adverse Outcome Pathways

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) are a conceptual framework to characterize toxicity pathways by a series of mechanistic steps from a molecular initiating event to population outcomes. This framework helps to direct risk assessment research, for example by aiding in computational ...

  4. A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics

    EPA Science Inventory

    A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). ...

  5. Developing and applying adverse outcome pathways: What you need to know

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are a conceptual framework for organizing existing information concerning the predictive linkages between the initiation or early progression of a biological perturbation in an organism and the adverse outcome(s) of regulatory relevance (e.g., impa...

  6. Application of Adverse Outcome Pathways (AOPs) in Human ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

  7. Application of adverse outcome pathways (AOPs) in human ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

  8. Accelerating Adverse Outcome Pathway (AOP) development ...

    EPA Pesticide Factsheets

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. However, the conventional process for assembly of these AOPs is time and resource intensive, and has been a rate limiting step for AOP use and development. Therefore computational approaches to accelerate the process need to be developed. We previously developed a method for generating computationally predicted AOPs (cpAOPs) by association mining and integration of data from publicly available databases. In this work, a cpAOP network of ~21,000 associations was established between 105 phenotypes from TG-GATEs rat liver data from different time points (including microarray, pathological effects and clinical chemistry data), 994 REACTOME pathways, 688 High-throughput assays from ToxCast and 194 chemicals. A second network of 128,536 associations was generated by connecting 255 biological target genes from ToxCast to 4,980 diseases from CTD using either HT screening activity from ToxCast for 286 chemicals or CTD gene expression changes in response to 2,330 chemicals. Both networks were separately evaluated through manual extraction of disease-specific cpAOPs and comparison with expert curation of the relevant literature. By employing data integration strategies that involve the weighting of n

  9. Adverse outcome pathway (AOP) development II: Best practices

    EPA Science Inventory

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including high throughput in vitro, high content omics and imaging, and biomarkers, in risk-based decision-making....

  10. Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are designed to describe linkages of key events (KEs) within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event (MIE). Risk assessors have traditionally relied ...

  11. Accelerating Adverse Outcome Pathway Development via Systems Approaches

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  12. Adverse outcome pathways (AOPs) to enhance EDC ...

    EPA Pesticide Factsheets

    Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway (AOP) framework, which organizes information concerning measureable changes that link initial biological interactions with a chemical to adverse effects that are meaningful to risk assessment and management, can aid this process. This presentation outlines the ways in which the AOP framework has already been employed to support EDSP and how it may further enhance endocrine disruptor assessments in the future. Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway

  13. Integrating toxicogenomics data into cancer adverse outcome pathways

    EPA Science Inventory

    Integrating toxicogenomics data into adverse outcome pathways for cancer.J. Christopher CortonNHEERL/ORD, EPA, Research Triangle Park, NCAs the toxicology field continues to move towards a new paradigm in toxicity testing and safety assessment, there is the expectation that model...

  14. An Integrative data mining approach to identifying Adverse Outcome Pathway (AOP) Signatures

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or populatio...

  15. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources

    EPA Science Inventory

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledg...

  16. Application of the adverse outcome pathway framework - advances and challenges

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework, while not new in concept, has gained attention in recent years as a set of organizing principles and tools that can help facilitate greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making. Reg...

  17. 20170312 - Adverse Outcome Pathway (AOP) framework for ...

    EPA Pesticide Factsheets

    Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

  18. Adverse Outcome Pathway (AOP) framework for embryonic ...

    EPA Pesticide Factsheets

    Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

  19. Adverse outcome pathway (AOP) development and evaluation ...

    EPA Pesticide Factsheets

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar w

  20. Theoretical Framework to Extend Adverse Outcome Pathways to Include Pharmacokinetic Considerations

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) have generated intense interest for their utility in linking known population outcomes to a molecular initiating event (MIE) that can be quantified using in vitro methods. While there are tens of thousands of chemicals in commercial use, biology h...

  1. Adverse outcome pathway (AOP) development: Guiding principles and best practices

    EPA Science Inventory

    Adverse outcome pathways (AOPs) represent a conceptual framework that can support greater application of mechanistic data in regulatory decision-making. However, in order for the scientific community to collectively address the daunting challenge of describing relevant toxicologi...

  2. Frameworks for organizing exposure and toxicity data - the Aggregate Exposure Pathway (AEP) and the Adverse Outcome Pathway (AOP)

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework organizes existing knowledge regarding a series of biological events, starting with a molecular initiating event (MIE) and ending at an adverse outcome. The AOP framework provides a biological context to interpret in vitro toxicity dat...

  3. Setting the stage to advance the adverse outcome pathway (AOP) framework through horizon scanning

    EPA Science Inventory

    Recognizing the international interest surrounding the adverse outcome pathway framework, which captures existing information describing causal linkages between a molecular initiating event through levels of biological organization to an adverse outcome of regulatory significance...

  4. Adverse Outcome Pathways – Organizing Toxicological ...

    EPA Pesticide Factsheets

    The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a natural framework for connecting high throughput toxicity testing (HTT) results to potential impacts on humans and wildlife populations. An AOP consists of two main components that describe the biological mechanisms driving toxicity. Key events represent biological processes essential for causing the adverse outcome that are also measurable experimentally. Key event relationships capture the biological processes connecting the key events. Evidence documented for each KER based on measurements of the KEs can provide the confidence needed for extrapolating HTT from early key events to overt toxicity represented by later key events based on the AOP. The IPCS mode of action (MOA) framework incorporates information required for making a chemical-specific toxicity determination. Given the close relationship between the AOP and MOA frameworks, it is possible to assemble an MOA by incorporating HTT results, chemical properties including absorption, distribution, metabolism, and excretion (ADME), and an AOP describing the biological basis of toxicity thereby streamlining the process. While current applications focus on the assessment of risk for environmental chemicals,

  5. Use of Putative Adverse Outcome Pathways for Chemical Hazard Identification

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework provides a knowledge infrastructure for evaluating health effects of environmental chemicals. In this work we are examining proof-of-concept issues in the development and prospective application of AOPs in chemical safety. Key outputs i...

  6. Conceptualizing adverse outcome pathways for ...

    EPA Pesticide Factsheets

    Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions (e.g., reproduction). This study utilized newly generated high content (transcriptomic and metabolomic) empirical data in combination with existing high throughput (ACTOR, epa.gov) toxicity data to facilitate development of adverse outcome pathways (AOPs) for molecular initiating event (MIE) of COX inhibition. We examined effects of a waterborne, 96h exposure to three COX inhibitors (indomethacin (IN; 100 µg/L), ibuprofen (IB; 200 µg/L) and celecoxib (CX; 20 µg/L) on the liver metabolome and ovarian gene expression (using oligonucleotide microarray 4 x15K platform) in sexually mature fathead minnows (n=8). Differentially expressed genes were identified (t-test, p < 0.01), and functional analyses performed to determine enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (p < 0.05). Principal component analysis indicated that liver metabolomics profiles of IN, IB and CX were not significantly different from control or one another. When compared to control, exposure to IB and CX resulted in differential expression of comparable numbers of genes (IB = 433, CX= 545). In contrast, 2558 genes were differentially expressed in IN-treated fish. KEGG pathway analyses show that IN had extensive effects on oocyte meios

  7. Establishing Adverse Outcome Pathways of Thyroid Hormone Disruption in an Amphibian Model

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) provides a framework for understanding the relevance of toxicology data in ecotoxicological hazard assessments. The AOP concept can be applied to many toxicological pathways including thyroid hormone disruption. Thyroid hormones play a critical r...

  8. Developing confidence in adverse outcome pathway-based ...

    EPA Pesticide Factsheets

    An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17β-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 concentrations, and significant increases in

  9. Developing confidence in adverse outcome pathway-based ...

    EPA Pesticide Factsheets

    An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD (https://aopwiki.org/wiki/index.php/Aop:25). An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17â-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 c

  10. Practical approaches to adverse outcome pathway (AOP) ...

    EPA Pesticide Factsheets

    Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and depend largely on the intended use or motivation for development. Four ecological AOP case studies, which were developed for different purposes, are described herein. In each situation, creation of the AOP began in a manner determined by the initial motivation for its creation, and expanded either to include additional components of the pathway, or to address the domains of applicability in terms of chemical initiators, susceptible species, life stages, etc. From these case studies, some general strategies can be gleaned which a developer may find useful for supporting an existing AOP or creating a new one. Several web-based tools which can aid in AOP assembly, as well as evaluation of weight of evidence for scientific robustness of AOP components are highlighted. The need for AOP development and greater population of AOPs in the online knowledgebase has been widely recognized (e.g., OECD Project 1.29, Knapen et al 2015, Escher et al 2016; Groh et al 2015), but currently there are few AOP developers. To promote broader development of AOPs, and the inclusion of potential developers across various types of institutes and fields of study, this manuscript outlines strategies for initiating

  11. AOP-DB Frontend: A user interface for the Adverse Outcome Pathways Database.

    EPA Science Inventory

    The EPA Adverse Outcome Pathway Database (AOP-DB) is a database resource that aggregates association relationships between AOPs, genes, chemicals, diseases, pathways, species orthology information, ontologies. The AOP-DB frontend is a simple yet powerful AOP-DB user interface in...

  12. AOP-DB Frontend: A user interface for the Adverse Outcome Pathways Database

    EPA Science Inventory

    The EPA Adverse Outcome Pathway Database (AOP-DB) is a database resource that aggregates association relationships between AOPs, genes, chemicals, diseases, pathways, species orthology information, ontologies. The AOP-DB frontend is a simple yet powerful user interface in the for...

  13. The adverse outcome pathway: A multifaceted framework supporting 21st century toxicology

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework serves as a knowledge assembly, interpretation, and communication tool designed to support the translation of pathway-specific mechanistic data into responses relevant to assessing and managing risks of chemicals to human health and the...

  14. Proteomics for Adverse Outcome Pathway Discovery using Human Kidney Cells?

    EPA Science Inventory

    An Adverse Outcome Pathway (AOP) is a conceptual framework that applies molecular-based data for use in risk assessment and regulatory decision support. AOP development is based on effects data of chemicals on biological processes (i.e., molecular initiating events, key intermedi...

  15. Ionotropic GABA receptor antagonism-induced adverse outcome pathways for potential neurotoxicity biomarkers.

    PubMed

    Gong, Ping; Hong, Huixiao; Perkins, Edward J

    2015-01-01

    Antagonism of ionotropic GABA receptors (iGABARs) can occur at three distinct types of receptor binding sites causing chemically induced epileptic seizures. Here we review three adverse outcome pathways, each characterized by a specific molecular initiating event where an antagonist competitively binds to active sites, negatively modulates allosteric sites or noncompetitively blocks ion channel on the iGABAR. This leads to decreased chloride conductance, followed by depolarization of affected neurons, epilepsy-related death and ultimately decreased population. Supporting evidence for causal linkages from the molecular to population levels is presented and differential sensitivity to iGABAR antagonists in different GABA receptors and organisms discussed. Adverse outcome pathways are poised to become important tools for linking mechanism-based biomarkers to regulated outcomes in next-generation risk assessment.

  16. Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

  17. Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

    PubMed Central

    Bal-Price, Anna; Lein, Pamela J.; Keil, Kimberly P.; Sethi, Sunjay; Shafer, Timothy; Barenys, Marta; Fritsche, Ellen; Sachana, Magdalini; Meek, M.E. (Bette)

    2016-01-01

    The Adverse Outcome Pathway (AOP) concept has recently been proposed to support a paradigm shift in regulatory toxicology testing and risk assessment. This concept is similar to the Mode of Action (MOA), in that it describes a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis for predicting effects of structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed. A variety of cellular and molecular processes are known to be critical for normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of the principles of MOA and AOPs, examples of potential or putative adverse outcome pathways specific for developmental or adult neurotoxicity are summarized and aspects of their assessment considered. Their possible application in developing mechanistically informed Integrated Approaches to Testing and Assessment (IATA) is also discussed. PMID:27212452

  18. Quantitative Adverse Outcome Pathways and Their ...

    EPA Pesticide Factsheets

    A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course predictions that can support regulatory decision-making. Herein we describe several facets of qAOPs, including (a) motivation for development, (b) technical considerations, (c) evaluation of confidence, and (d) potential applications. The qAOP used as an illustrative example for these points describes the linkage between inhibition of cytochrome P450 19A aromatase (the MIE) and population-level decreases in the fathead minnow (FHM; Pimephales promelas). The qAOP consists of three linked computational models for the following: (a) the hypothalamic-pitutitary-gonadal axis in female FHMs, where aromatase inhibition decreases the conversion of testosterone to 17β-estradiol (E2), thereby reducing E2-dependent vitellogenin (VTG; egg yolk protein precursor) synthesis, (b) VTG-dependent egg development and spawning (fecundity), and (c) fecundity-dependent population trajectory. While development of the example qAOP was based on experiments with FHMs exposed to the aromatase inhibitor fadrozole, we also show how a toxic equivalence (TEQ) calculation allows use of the qAOP to predict effects of another, untested aromatase inhibitor, iprodione. While qAOP development can be resource-intensive, the quan

  19. Overview of an internationally-harmonized program for adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are critical frameworks for organizing knowledge concerning the scientifically-credible predictive linkages between toxicological observations made at molecular and cellular levels (e.g., via molecular screening assays, biomarker responses, or chem...

  20. Development of Quantitative Adverse Outcome Pathways Using Health-Protective Assumptions to Fill Data Gaps

    EPA Science Inventory

    In an adverse outcome pathway (AOP), the target site dose participates in a molecular initiating event (MIE), which in turn triggers a sequence of key events leading to an adverse outcome (AO). Quantitative AOPs (QAOP) are needed if AOP characterization is to address risk as well...

  1. The future trajectory of adverse outcome pathways: a commentary.

    PubMed

    Sewell, Fiona; Gellatly, Nichola; Beaumont, Maria; Burden, Natalie; Currie, Richard; de Haan, Lolke; Hutchinson, Thomas H; Jacobs, Miriam; Mahony, Catherine; Malcomber, Ian; Mehta, Jyotigna; Whale, Graham; Kimber, Ian

    2018-04-01

    The advent of adverse outcome pathways (AOPs) has provided a new lexicon for description of mechanistic toxicology, and a renewed enthusiasm for exploring modes of action resulting in adverse health and environmental effects. In addition, AOPs have been used successfully as a framework for the design and development of non-animal approaches to toxicity testing. Although the value of AOPs is widely recognised, there remain challenges and opportunities associated with their use in practise. The purpose of this article is to consider specifically how the future trajectory of AOPs may provide a basis for addressing some of those challenges and opportunities.

  2. An Integrative Data Mining Approach to Identify Adverse Outcome Pathway Signatures

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) provide a formal framework for describing the mechanisms underlying the toxicity of chemicals in our environment. This process improves our ability to incorporate high-throughput toxicity testing (HTT) results and biomarker information on early key...

  3. Adverse Outcome Pathways – Organizing Toxicological Information to Improve Decision Making

    EPA Science Inventory

    The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP)...

  4. PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework proceeds from a general (e.g., not chemical specific) molecular mode of action, designated as a MIE, through stepwise changes in biological status, defined as key events (KEs), to a final AO that can be used in risk assessment. Because aromatase-inhibiting pharmaceuticals are widely used to treat breast cancer patients, we explored the unintended consequences that might occur in fish exposed to these chemicals through wastewater discharge into the aquatic environment. Unlike mammals, fish have two isoforms of aromatase, one that predominates in the ovary (cyp19a1a) and a second (cyp19a1b) that prevails in the brain. Aromatase activity in fish brain can be 100 to 1000 times that in mammals and is associated with reproduction. We have developed a putative AOP for inhibition of brain aromatase in fish leading to reproductive dysfunction based on review of relevant literature and reproductive experiments with the marine fish cunner (Tautogolabrus adspersus) exposed to aromatase-inhibiting pharmaceuticals in the laboratory. The first KE in this AOP is a decrease in brain aromatase activity due to exposure to an aromatase inhibitor. KEs then progress through subsequent steps including decreas

  5. PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON OF BRAIN AROMATASE IN FISH LEADING TO REPRODUCTIVE IMPAIRMENT

    EPA Science Inventory

    The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework p...

  6. Exposure and Dosimetry Considerations for Adverse Outcome Pathways (AOPs) (NIH-AOP)

    EPA Science Inventory

    Risk is a function of both of hazard and exposure. Toxicokinetic (TK) models can determine whether chemical exposures produce potentially hazardous tissue concentrations. Whether or not the initial molecular event (MIE) in an Adverse Outcome Pathway (AOP) occurs depends on both e...

  7. Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly used to integrate data based on traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in computable terms. Herein, we present a comprehens...

  8. Experimental Approaches to Systematic Discovery and Development of Reproductive Adverse Outcome Pathways in Fish

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks that portray causal and predictive linkages between key events at multiple scales of biological organization that connect molecular initiating events and early cellular perturbations (e.g., initiation of toxicity pathways)...

  9. Use of the adverse outcome pathway framework to represent cross-species consequences of specific pathway perturbations

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework has been developed as a means for assembling scientifically defensible descriptions of how particular molecular perturbations, termed molecular initiating events (MIEs), can evoke a set of predictable responses at different levels of bi...

  10. Development & Use of Adverse Outcome Pathways for 21st Century Decision Support

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  11. Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

  12. Advancing the adverse outcome pathway framework - An international horizon scanning approach (presentation)

    EPA Science Inventory

    In preparation for a Society of Environmental Toxicology and Chemistry Pellston Workshop titled “Advancing the Adverse Outcome Pathway (AOP) Concept: An International Horizon Scanning Approach,” a horizon scanning effort was undertaken to gather input from the global ...

  13. AOP-DB: A database resource for the exploration of Adverse Outcome Pathways through integrated association networks.

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability t...

  14. An “ADME Module” in the Adverse Outcome Pathway ...

    EPA Pesticide Factsheets

    The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP framework is designed to be chemical agnostic, it is widely recognized that considering chemicals’ absorption, distribution, metabolism, and excretion (ADME) behaviors is critical in applying the AOP framework in chemical-specific risk assessment. Currently, information being generated as part of the Organisation for Economic Co-operation and Development (OECD) AOP Development Programme is being consolidated into an AOP Knowledgebase (http://aopwiki.org). To enhance the use of this Knowledgebase in risk assessment, an ADME Module has been developed to contain the ADME information needed to connect MIEs and other key events in an AOP for specific chemicals. The conceptual structure of this module characterizes the potential of a chemical to reach the target MIE based on either its structure-based features or relative rates of ADME. The key features of this module include (1) a framework for connecting biology-based AOP to biochemical-based ADME and chemical/human activity-based exposure pathways; (2) links to qualitative tools (e.g., structure-based cheminformatic model) that screen for chemicals that could potentially reach the target MIE; (3) links to quantitative tools (e.g., dose-r

  15. Differentiating pathway-specific from nonspecific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

    EPA Science Inventory

    The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential ...

  16. Studying Biology to Understand Risk: Dosimetry Models and Quantitative Adverse Outcome Pathways

    EPA Science Inventory

    Confidence in the quantitative prediction of risk is increased when the prediction is based to as great an extent as possible on the relevant biological factors that constitute the pathway from exposure to adverse outcome. With the first examples now over 40 years old, physiologi...

  17. The adverse outcome pathway for skin sensitisation: Moving closer to replacing animal testing.

    PubMed

    Schultz, Terry W; Dimitrova, Gergana; Dimitrov, Sabcho; Mekenyan, Ovanes G

    2016-10-01

    This article outlines the work of the Organisation for Economic Co-operation and Development (OECD) that led to being jointly awarded the 2015 Lush Black Box Prize. The award-winning work centred on the development of 'The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins'. This Adverse Outcome Pathway (AOP) has provided the mechanistic basis for the integration of skin sensitisation-related information. Recent developments in integrated approaches to testing and assessment, based on the AOP, are summarised. The impact of the AOP on regulatory policy and on the Three Rs are discussed. An overview of the next generation of the skin sensitisation AOP module in the OECD QSAR Toolbox, based on more-recent work at the Laboratory of Mathematical Chemistry, is also presented. 2016 FRAME.

  18. THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK: A FRAMEWORK FOR ORGANIZING BIOLOGICAL KNOWLEDGE LEADING TO HEALTH RISKS.

    EPA Science Inventory

    An Adverse Outcome Pathway (AOP) represents the organization of current and newly acquired knowledge of biological pathways. These pathways contain a series of nodes (Key Events, KEs) that when sufficiently altered influence the next node on the pathway, beginning from an Molecul...

  19. Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

  20. Differentiating pathway-specific from non-specific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

    EPA Science Inventory

    The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with pote...

  1. Use of an Adverse Outcome Pathway for Hepatic Steatosis to Build Chemical Groups

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework systematically documents the mechanisms underlying effects of chemicals starting with the initial interaction of chemicals with the biological system, i.e. the molecular initiating event (MIE). Chemical activity in assays designed to mo...

  2. The adverse outcome pathway concept: a pragmatic tool in toxicology.

    PubMed

    Vinken, Mathieu

    2013-10-04

    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Development of a Novel Quantitative Adverse Outcome Pathway Predictive Model for Lung Cancer

    EPA Science Inventory

    Traditional methods for carcinogenicity testing are resource-intensive, retrospective, and time consuming. An increasing testing burden has generated interest in the adverse outcome pathway (AOP) concept as a tool to evaluate chemical safety in a more efficient, rapid and effecti...

  4. Use of Adverse Outcome Pathways to Inform Decisions on Chemical Innovation, Regulation & Stewardship

    EPA Science Inventory

    An invited group of scientists participated in a SETAC Pellston WorkshopTM, “Advancing the Adverse Outcome Pathway (AOP) Concept – An International Horizon Scanning Approach,” in April 2017. The workshop addressed key challenges or limitations of AOP constructs...

  5. Constructing Adverse Outcome Pathways: a Demonstration of an Ontology-based Semantics Mapping Approach

    EPA Science Inventory

    Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating ...

  6. Defining Adverse Outcome Pathways for Effects of the Fungicide Propiconazole of Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are used to describe the linkage of chemical interactions in terms of molecular initiating events to whole organism responses suitable for risk assessment. This study was conducted to develop AOPs for the model fungicide propiconazole relative to r...

  7. Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and dep...

  8. Accelerating Adverse Outcome Pathway Development Using ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledgebase, however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally-predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of twenty-first century toxicity testing strategies. This review article describes how effective knowledge management and automated approaches to AOP development can enhance and accelerate the development and use of AOPs. As the principles documented in this review are put into practice, we anticipate that the quality and quantity of AOPs available will increase substantially. This, in turn, will aid in the interpretation of ToxCast and other high-throughput tox

  9. Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

  10. Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

    EPA Science Inventory

    To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecula...

  11. Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  12. Application of adverse outcome pathways (AOPs) in human health and ecotoxicology capturing divergent consequences of conserved molecular initiating events via AOP networks

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

  13. Using Adverse Outcome Pathways to Build Chemical Groups: A Case Study for Hepatic Steatosis

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework systematically documents the mechanisms underlying effects of chemicals. Ideally, the AOP traces the mechanism to the initial interaction of chemicals with the biological system. Thus, AOPs should help inform chemical grouping by identi...

  14. Can Erythrocytes Transmit Oxidative Stress Beyond the Lungs? An Adverse Outcome Pathway for the Cardiovascular Effects of Air Pollution.

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are systems biology roadmaps with potential utility in xenobiotic exposure risk assessment. AOPs connect molecular initiating events (MIEs) to population-level adverse outcomes (AOs) via cellular, organ, and organism key events (KE) and KE relatio...

  15. Linking mechanistic data to endpoints of regulatory concern using the adverse outcome pathway framework.

    EPA Science Inventory

    In order to increase the uptake and use of high throughput screening data in environmental risk assessment, it is important to establish scientifically credible links between measures of biological pathway perturbation and apical adverse outcomes in humans and wildlife. The adver...

  16. Adverse outcome pathway networks II: Network analytics.

    PubMed

    Villeneuve, Daniel L; Angrish, Michelle M; Fortin, Marie C; Katsiadaki, Ioanna; Leonard, Marc; Margiotta-Casaluci, Luigi; Munn, Sharon; O'Brien, Jason M; Pollesch, Nathan L; Smith, L Cody; Zhang, Xiaowei; Knapen, Dries

    2018-06-01

    Toxicological responses to stressors are more complex than the simple one-biological-perturbation to one-adverse-outcome model portrayed by individual adverse outcome pathways (AOPs). Consequently, the AOP framework was designed to facilitate de facto development of AOP networks that can aid in the understanding and prediction of pleiotropic and interactive effects more common to environmentally realistic, complex exposure scenarios. The present study introduces nascent concepts related to the qualitative analysis of AOP networks. First, graph theory-based approaches for identifying important topological features are illustrated using 2 example AOP networks derived from existing AOP descriptions. Second, considerations for identifying the most significant path(s) through an AOP network from either a biological or risk assessment perspective are described. Finally, approaches for identifying interactions among AOPs that may result in additive, synergistic, or antagonistic responses (or previously undefined emergent patterns of response) are introduced. Along with a companion article (part I), these concepts set the stage for the development of tools and case studies that will facilitate more rigorous analysis of AOP networks, and the utility of AOP network-based predictions, for use in research and regulatory decision-making. The present study addresses one of the major themes identified through a Society of Environmental Toxicology and Chemistry Horizon Scanning effort focused on advancing the AOP framework. Environ Toxicol Chem 2018;37:1734-1748. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the

  17. Tiered Approaches to Incorporate the Adverse Outcome Pathway Framework into Chemical-Specific Risk-Based Decision Making

    EPA Science Inventory

    The concept of Adverse Outcome Pathways (AOPs) arose as a means of addressing the challenges associated with establishing relationships between high-throughout (HT) in vitro dose response data and in vivo biological outcomes. However, AOP development has also been met with challe...

  18. Application of Adverse Outcome Pathways (AOPs) in Human Health and Ecotoxicology Capturing Divergent Consequences of Conserved Molecular Initiating Events via AOP Networks (Presentation)

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

  19. Integrating Aggregate Exposure Pathway (AEP) and Adverse ...

    EPA Pesticide Factsheets

    High throughput toxicity testing (HTT) holds the promise of providing data for tens of thousands of chemicals that currently have no data due to the cost and time required for animal testing. Interpretation of these results require information linking the perturbations seen in vitro with adverse outcomes in vivo and requires knowledge of how estimated exposure to the chemicals compare to the in vitro concentrations that show an effect. This abstract discusses how Adverse Outcome Pathways (AOPs) can be used to link HTT with adverse outcomes of regulatory significance and how Aggregate Exposure Pathways (AEPs) can connect concentrations of environment stressors at a source with an expected target site concentration designed to provide exposure estimates that are comparable to concentrations identified in HTT. Presentation at the ICCA-LRI and JRC Workshop: Fit-For-Purpose Exposure Assessment For Risk-Based Decision Making

  20. A conceptual framework to advance exposure science research and complement the Adverse Outcome Pathway framework

    EPA Science Inventory

    A tremendous amount of data on environmental stressors has been accumulated in exposure science, epidemiology, and toxicology, yet most of these data reside in different silos. The Adverse Outcome Pathway (AOP) framework was developed as an organizing principle for toxicological ...

  1. Computationally predicted Adverse Outcome Pathway networks for liver-related diseases using publicly available data sources: Case studies and lessons learned

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework summarizes key information about mechanistic events leading to an adverse health or ecological outcome. In recent years computationally predicted AOPs (cpAOP) making use of publicly available data have been proposed as a means of accele...

  2. A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment

    EPA Science Inventory

    Cumulative risk assessment (CRA) methods, which evaluate the risk of multiple adverse outcomes (AOs) from multiple chemicals, promote the use of a conceptual site model (CSM) to integrate risk from relevant stressors. The Adverse Outcome Pathway (AOP) framework can inform these r...

  3. A catalog of putative adverse outcome pathways (AOPs) that ...

    EPA Pesticide Factsheets

    A number of putative AOPs for several distinct MIEs of thyroid disruption have been formulated for amphibian metamorphosis and fish swim bladder inflation. These have been entered into the AOP knowledgebase on the OECD WIKI. The EDSP has been actively advancing high-throughput screening for chemical activity toward estrogen, androgen and thyroid targets. However, it has been recently identified that coverage for thyroid-related targets is lagging behind estrogen and androgen assay coverage. As thyroid-related medium-high throughput assays are actively being developed for inclusion in the ToxCast chemical screening program, a parallel effort is underway to characterize putative adverse outcome pathways (AOPs) specific to these thyroid-related targets. This effort is intended to provide biological and ecological context that will enhance the utility of ToxCast high throughput screening data for hazard identification.

  4. Building an Adverse Outcome Pathway Framework through HTS Data and Literature Mining Integration (FutureToxII)

    EPA Science Inventory

    Interpreting EPA’s ToxCast in vitro assay data in the context of Adverse Outcome Pathway (AOP) development is a significant challenge. While chemical activation in these assays may shed light on the molecular initiating event, the downstream effect of these activities at higher ...

  5. Adverse Outcome Pathways can drive non-animal approaches for safety assessment

    PubMed Central

    Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

    2015-01-01

    Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. This article explores how the development and application of Adverse Outcome Pathways (AOPs) could benefit the science and practice of chemical safety assessment, with a particular focus on how their use in practice could reduce reliance on traditional animal toxicity tests. This includes discussion of the key areas where current and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792

  6. Intimate Partner Violence, PTSD, and Adverse Health Outcomes

    ERIC Educational Resources Information Center

    Dutton, Mary Ann; Green, Bonnie L.; Kaltman, Stacey I.; Roesch, Darren M.; Zeffiro, Thomas A.; Krause, Elizabeth D.

    2006-01-01

    The high prevalence of adverse health outcomes related to intimate partner violence (IPV) is well documented. Yet we know little about the pathways that lead to adverse health outcomes. Research concerning the psychological, biological, neurological, behavioral, and physiological alterations following exposure to IPV--many of which are associated…

  7. A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

    EPA Science Inventory

    Background: Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowled...

  8. A three-tiered approach for linking pharmacokinetic considerations to the adverse outcome pathway framework for chemical-specific risk assessment

    EPA Science Inventory

    The power of the adverse outcome pathway (AOP) framework arises from its utilization of pathway-based data to describe the initial interaction of a chemical with a molecular target (molecular initiating event; (MIE), followed by a progression through a series of key events that l...

  9. How adverse outcome pathways can aid the development and ...

    EPA Pesticide Factsheets

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. The present manuscript reports on expert opinion and case studies that came out of a European Commission, Joint Research Centre-sponsored work

  10. Advancing the Adverse Outcome Pathway Framework - an ...

    EPA Pesticide Factsheets

    The ability of scientists to conduct whole organism toxicity tests to understand chemical safety has been significantly outpaced by the rapid synthesis of new chemicals. Therefore, to increase efficiencies in chemical risk assessment, scientists are turning to mechanistic-based studies, making greater use of in vitro and in silico methods, to screen for potential environmental and human health hazards. A framework that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP). A number of international activities have focused on AOP development and plausible applications to regulatory decision-making. These interactions have prompted dialog between research scientists and regulatory communities to consider how best to use the AOP framework in risk assessment. While expert-facilitated discussions have been instrumental in moving the science of AOPs forward, it was recognized that a survey of the broader scientific community would aid in identifying shortcomings and guiding future initiatives for the AOP framework. To that end, a ?‘Horizon Scanning’ exercise was conducted to solicit questions from the global scientific and regulatory communities concerning the challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision making. The m

  11. Discovering and annotating fish early life-stage (FELS) adverse outcome pathways: Putting the research strategy into practice

    EPA Science Inventory

    In May 2012, a HESI-sponsored expert workshop yielded a proposed research strategy for systematically discovering, characterizing, and annotating fish early life-stage (FELS) adverse outcome pathways (AOPs) as well as prioritizing AOP development in light of current restrictions ...

  12. Using adverse outcome pathway analysis to guide development of high-throughput screening assays for thyroid-disruptors

    EPA Science Inventory

    Using Adverse Outcome Pathway Analysis to Guide Development of High-Throughput Screening Assays for Thyroid-Disruptors Katie B. Paul1,2, Joan M. Hedge2, Daniel M. Rotroff4, Kevin M. Crofton4, Michael W. Hornung3, Steven O. Simmons2 1Oak Ridge Institute for Science Education Post...

  13. Weight of evidence evaluation of adverse outcome pathways converging at impaired vitellogenin synthesis leading to reproductive impairment

    EPA Science Inventory

    Adverse outcome pathways (AOPs) provide a framework that supports greater use of mechanistic data measured at lower levels of biological organization as a basis for regulatory decision-making. However, it is recognized that different types of regulatory applications and decisions...

  14. Constructing Adverse Outcome Pathways: a Demonstration of ...

    EPA Pesticide Factsheets

    Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating events (MIEs) of chemicals to their downstream phenotypes of a greater regulatory relevance. A number of ongoing public phenomics (high throughput phenotyping) efforts have been generating abundant phenotypic data annotated with ontology terms. These phenotypes can be analyzed semantically and linked to MIEs of interest, all in the context of a knowledge base integrated from a variety of ontologies for various species and knowledge domains. In such analyses, two phenotypic profiles (PPs; anchored by genes or diseases) each characterized by multiple ontology terms are compared for their semantic similarities within a common ontology graph, but across boundaries of species and knowledge domains. Taking advantage of publicly available ontologies and software tool kits, we have implemented an OS-Mapping (Ontology-based Semantics Mapping) approach as a Java application, and constructed a network of 19383 PPs as nodes with edges weighed by their pairwise semantic similarity scores. Individual PPs were assembled from public phenomics data. Out of possible 1.87×108 pairwise connections among these nodes, about 71% of them have similarity scores between 0.2 and the maximum possible of 1.0.

  15. Merging Adverse Outcome Pathway (AOP) and Mode of Action (MOA) Frameworks: Assembling Knowledge for Use in Risk Assessment

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  16. Increasing scientific confidence in adverse outcome pathways: Application of tailored Bradford-Hill considerations for evaluating weight of evidence

    EPA Science Inventory

    Systematic consideration of scientific support is a critical element in developing and, ultimately, using adverse outcome pathways (AOPs) for various regulatory applications. Though weight of evidence (WoE) analysis has been proposed as a basis for assessment of the maturity and...

  17. Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction

    EPA Science Inventory

    An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD (https://aopwiki.org/wiki/index.php/Aop:25). An intended application of t...

  18. Use of 2D chemical structure and bioactivity profiles to generate chemical categories within an Adverse Outcome Pathway network

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework has emerged to capitalise on the vast quantity of mechanistic data generated by alternative techniques, as well as advances in systems biology, cheminformatics, and bioinformatics. AOPs provide a scaffold onto which mechanistic data can...

  19. Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction (Poster)

    EPA Science Inventory

    An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of me...

  20. Advancing the adverse outcome pathway framework and its ...

    EPA Pesticide Factsheets

    Regulatory agencies worldwide are confronted with the challenging task of assessing the risks of thousands of chemicals to protect both human health and the environment. Traditional toxicity testing largely relies on apical endpoints from whole animal studies, which, in addition to ethical concerns, is costly and time prohibitive. As a result, the utility of mechanism-based in silico, in vitro, and in vivo approaches to support chemical safety evaluations have increasingly been explored. An approach that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP) framework. A number of international workshops and expert meetings have been held over the past years focusing on the AOP framework and its applications to chemical risk assessment. Although, these interactions have illustrated the necessity of expert guidance in moving the science of AOPs and their applications forward, there is also the recognition that a broader survey of the scientific community could be useful in guiding future initiatives in the AOP arena. To that end, a Horizon Scanning exercise was conducted to solicit questions from the global scientific community concerning the challenges or limitations that must be addressed in order to realize the full potential of the AOP framework in research and regulatory decision making. Over a 4 month ques

  1. Defining and Modeling Known Adverse Outcome Pathways: Domoic Acid and Neuronal Signaling as a Case Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Watanabe, Karen H.; Andersen, Melvin E.; Basu, Nil

    2011-01-01

    An adverse outcome pathway (AOP) is a sequence of key events from a molecular-level initiating event and an ensuing cascade of steps to an adverse outcome with population level significance. To implement a predictive strategy for ecotoxicology, the multiscale nature of an AOP requires computational models to link salient processes (e.g., in chemical uptake, toxicokinetics, toxicodynamics, and population dynamics). A case study with domoic acid was used to demonstrate strategies and enable generic recommendations for developing computational models in an effort to move toward a toxicity testing paradigm focused on toxicity pathway perturbations applicable to ecological risk assessment. Domoic acid,more » an algal toxin with adverse effects on both wildlife and humans, is a potent agonist for kainate receptors (ionotropic glutamate receptors whose activation leads to the influx of Na+ and Ca2+). Increased Ca2+ concentrations result in neuronal excitotoxicity and cell death primarily in the hippocampus, which produces seizures, impairs learning and memory, and alters behavior in some species. Altered neuronal Ca2+ is a key process in domoic acid toxicity which can be evaluated in vitro. Further, results of these assays would be amenable to mechanistic modeling for identifying domoic acid concentrations and Ca2+ perturbations that are normal, adaptive, or clearly toxic. In vitro assays with outputs amenable to measurement in exposed populations can link in vitro to in vivo conditions, and toxicokinetic information will aid in linking in vitro results to the individual organism. Development of an AOP required an iterative process with three important outcomes: (1) a critically reviewed, stressor-specific AOP; (2) identification of key processes suitable for evaluation with in vitro assays; and (3) strategies for model development.« less

  2. Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

    PubMed Central

    Sørhus, Elin; Incardona, John P; Furmanek, Tomasz; Goetz, Giles W; Scholz, Nathaniel L; Meier, Sonnich; Edvardsen, Rolf B; Jentoft, Sissel

    2017-01-01

    Crude oil spills are a worldwide ocean conservation threat. Fish are particularly vulnerable to the oiling of spawning habitats, and crude oil causes severe abnormalities in embryos and larvae. However, the underlying mechanisms for these developmental defects are not well understood. Here, we explore the transcriptional basis for four discrete crude oil injury phenotypes in the early life stages of the commercially important Atlantic haddock (Melanogrammus aeglefinus). These include defects in (1) cardiac form and function, (2) craniofacial development, (3) ionoregulation and fluid balance, and (4) cholesterol synthesis and homeostasis. Our findings suggest a key role for intracellular calcium cycling and excitation-transcription coupling in the dysregulation of heart and jaw morphogenesis. Moreover, the disruption of ionoregulatory pathways sheds new light on buoyancy control in marine fish embryos. Overall, our chemical-genetic approach identifies initiating events for distinct adverse outcome pathways and novel roles for individual genes in fundamental developmental processes. DOI: http://dx.doi.org/10.7554/eLife.20707.001 PMID:28117666

  3. Adverse outcome pathway and risks of anticoagulant rodenticides to predatory wildlife

    USGS Publications Warehouse

    Rattner, Barnett A.; Lazarus, Rebecca S.; Elliott, John E.; Shore, Richard F.; van den Brink, Nico

    2014-01-01

    Despite a long history of successful use, routine application of some anticoagulant rodenticides (ARs) may be at a crossroad due to new regulatory guidelines intended to mitigate risk. An adverse outcome pathway for ARs was developed to identify information gaps and end points to assess the effectiveness of regulations. This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. Risk assessments have led to restrictions affecting use of some second-generation ARs (SGARs) in North America. While the European regulatory community highlighted significant or unacceptable risk of ARs to nontarget wildlife, use of SGARs in most EU member states remains authorized due to public health concerns and the absence of safe alternatives. For purposes of conservation and restoration of island habitats, SGARs remain a mainstay for eradication of invasive species. There are significant data gaps related to exposure pathways, comparative species sensitivity, consequences of sublethal effects, potential hazards of greater AR residues in genetically resistant prey, effects of low-level exposure to multiple rodenticides, and quantitative data on the magnitude of nontarget wildlife mortality.

  4. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

    Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

    2015-01-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  5. Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

    PubMed

    Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

    2014-12-01

    Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. High-throughput assessment of oxidative respiration in fish embryos: Advancing adverse outcome pathways for mitochondrial dysfunction.

    PubMed

    Souders, Christopher L; Liang, Xuefang; Wang, Xiaohong; Ector, Naomi; Zhao, Yuan H; Martyniuk, Christopher J

    2018-06-01

    into mitochondrial bioenergetics. We present an adverse outcome pathway framework that incorporates endpoints related to mitochondrial bioenergetics. High throughput bioenergetics assays conducted using whole embryos are expected to support adverse outcome pathways for mitochondrial dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Application of Adverse Outcome Pathways to U.S. EPA’s Endocrine Disruptor Screening Program

    PubMed Central

    Noyes, Pamela D.; Casey, Warren M.; Dix, David J.

    2017-01-01

    Background: The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. Objectives: This review describes the EDSP’s use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Results: Pathway frameworks can facilitate a weight of evidence determination of a chemical’s potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. Conclusions: A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304 PMID:28934726

  8. Conceptual model for assessing criteria air pollutants in a multipollutant context: A modified adverse outcome pathway approach.

    PubMed

    Buckley, Barbara; Farraj, Aimen

    2015-09-01

    Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is difficult since components are present in different combinations and concentrations in ambient air. Recent mechanistic studies have limited utility because of the inability to link measured changes to adverse outcomes that are relevant to risk assessment. New approaches are needed to address this challenge. The purpose of this manuscript is to describe a conceptual model, based on the adverse outcome pathway approach, which connects initiating events at the cellular and molecular level to population-wide impacts. This may facilitate hazard assessment of air pollution mixtures. In the case reports presented here, airway hyperresponsiveness and endothelial dysfunction are measurable endpoints that serve to integrate the effects of individual criteria air pollutants found in inhaled mixtures. This approach incorporates information from experimental and observational studies into a sequential series of higher order effects. The proposed model has the potential to facilitate multipollutant risk assessment by providing a framework that can be used to converge the effects of air pollutants in light of common underlying mechanisms. This approach may provide a ready-to-use tool to facilitate evaluation of health effects resulting from exposure to air pollution mixtures. Published by Elsevier Ireland Ltd.

  9. Differentiating Pathway-Specific From Nonspecific Effects in High-Throughput Toxicity Data: A Foundation for Prioritizing Adverse Outcome Pathway Development.

    PubMed

    Fay, Kellie A; Villeneuve, Daniel L; Swintek, Joe; Edwards, Stephen W; Nelms, Mark D; Blackwell, Brett R; Ankley, Gerald T

    2018-06-01

    The U.S. Environmental Protection Agency's ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential apical effects relevant to risk assessors. Thus, efforts are underway to develop AOPs relevant to pathway-specific perturbations detected in ToxCast assays. Previous work identified a "cytotoxic burst" (CTB) phenomenon wherein large numbers of the ToxCast assays begin to respond at or near test chemical concentrations that elicit cytotoxicity, and a statistical approach to defining the bounds of the CTB was developed. To focus AOP development on the molecular targets corresponding to ToxCast assays indicating pathway-specific effects, we conducted a meta-analysis to identify which assays most frequently respond at concentrations below the CTB. A preliminary list of potentially important, target-specific assays was determined by ranking assays by the fraction of chemical hits below the CTB compared with the number of chemicals tested. Additional priority assays were identified using a diagnostic-odds-ratio approach which gives greater ranking to assays with high specificity but low responsivity. Combined, the two prioritization methods identified several novel targets (e.g., peripheral benzodiazepine and progesterone receptors) to prioritize for AOP development, and affirmed the importance of a number of existing AOPs aligned with ToxCast targets (e.g., thyroperoxidase, estrogen receptor, aromatase). The prioritization approaches did not appear to be influenced by inter-assay differences in chemical bioavailability. Furthermore, the outcomes were robust based on a variety of different parameters used to define the CTB.

  10. A workflow to investigate exposure and pharmacokinetic influences on high-throughput in vitro chemical screening based on adverse outcome pathways, OpenTox USA 2015 Poster

    EPA Science Inventory

    Adverse outcome pathways (AOP) link known population outcomes to a molecular initiating event (MIE) that can be quantified using high-throughput in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires consideration of exposure and absorption,...

  11. Adverse Outcome Pathways for Regulatory Applications: Examination of Four Case Studies With Different Degrees of Completeness and Scientific Confidence.

    PubMed

    Perkins, Edward J; Antczak, Philipp; Burgoon, Lyle; Falciani, Francesco; Garcia-Reyero, Natàlia; Gutsell, Steve; Hodges, Geoff; Kienzler, Aude; Knapen, Dries; McBride, Mary; Willett, Catherine

    2015-11-01

    Adverse outcome pathways (AOPs) offer a pathway-based toxicological framework to support hazard assessment and regulatory decision-making. However, little has been discussed about the scientific confidence needed, or how complete a pathway should be, before use in a specific regulatory application. Here we review four case studies to explore the degree of scientific confidence and extent of completeness (in terms of causal events) that is required for an AOP to be useful for a specific purpose in a regulatory application: (i) Membrane disruption (Narcosis) leading to respiratory failure (low confidence), (ii) Hepatocellular proliferation leading to cancer (partial pathway, moderate confidence), (iii) Covalent binding to proteins leading to skin sensitization (high confidence), and (iv) Aromatase inhibition leading to reproductive dysfunction in fish (high confidence). Partially complete AOPs with unknown molecular initiating events, such as 'Hepatocellular proliferation leading to cancer', were found to be valuable. We demonstrate that scientific confidence in these pathways can be increased though the use of unconventional information (eg, computational identification of potential initiators). AOPs at all levels of confidence can contribute to specific uses. A significant statistical or quantitative relationship between events and/or the adverse outcome relationships is a common characteristic of AOPs, both incomplete and complete, that have specific regulatory uses. For AOPs to be useful in a regulatory context they must be at least as useful as the tools that regulators currently possess, or the techniques currently employed by regulators. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

  12. Adapting biomarker technologies to adverse outcome pathways (AOPs) research: current thoughts on using in vivo discovery for developing in vitro target methods

    EPA Science Inventory

    Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, the...

  13. An integrative data mining approach to identifying adverse outcome pathway signatures.

    PubMed

    Oki, Noffisat O; Edwards, Stephen W

    2016-03-28

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP network with the AHR gene, an interesting subnetwork including glaucoma was identified. While substantial literature exists to support the potential for AHR ligands to elicit glaucoma, it was not explicitly captured in the public annotation information in CTD. The subnetwork from this analysis suggests a cpAOP that includes changes in CYP1B1 expression, which has been previously established in the literature as a primary cause of glaucoma. These case studies highlight the value in integrating multiple data

  14. Role of the Varroa mite in honeybee (Apis mellifera) colony loss: A case study for adverse outcome pathway development with a nonchemical stressor

    EPA Science Inventory

    Significant honeybee colony losses have been reported across North America and Europe in recent years. A number of factors, both chemical and nonchemical, have been associated with such losses. Adverse outcome pathways (AOPs) provide a conceptual framework to describe and evalu...

  15. Linking Adverse Outcome Pathways to Dynamic Energy Budgets: A Conceptual Model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Murphy, Cheryl; Nisbet, Roger; Antczak, Philipp

    Ecological risk assessment quantifies the likelihood of undesirable impacts of stressors, primarily at high levels of biological organization. Data used to inform ecological risk assessments come primarily from tests on individual organisms or from suborganismal studies, indicating a disconnect between primary data and protection goals. We know how to relate individual responses to population dynamics using individual-based models, and there are emerging ideas on how to make connections to ecosystem services. However, there is no established methodology to connect effects seen at higher levels of biological organization with suborganismal dynamics, despite progress made in identifying Adverse Outcome Pathways (AOPs) thatmore » link molecular initiating events to ecologically relevant key events. This chapter is a product of a working group at the National Center for Mathematical and Biological Synthesis (NIMBioS) that assessed the feasibility of using dynamic energy budget (DEB) models of individual organisms as a “pivot” connecting suborganismal processes to higher level ecological processes. AOP models quantify explicit molecular, cellular or organ-level processes, but do not offer a route to linking sub-organismal damage to adverse effects on individual growth, reproduction, and survival, which can be propagated to the population level through individual-based models. DEB models describe these processes, but use abstract variables with undetermined connections to suborganismal biology. We propose linking DEB and quantitative AOP models by interpreting AOP key events as measures of damage-inducing processes in a DEB model. Here, we present a conceptual model for linking AOPs to DEB models and review existing modeling tools available for both AOP and DEB.« less

  16. Probe molecules (PrM) approach in adverse outcome pathway (AOP) based high throughput screening (HTS): in vivo discovery for developing in vitro target methods

    EPA Science Inventory

    Efficient and accurate adverse outcome pathway (AOP) based high-throughput screening (HTS) methods use a systems biology based approach to computationally model in vitro cellular and molecular data for rapid chemical prioritization; however, not all HTS assays are grounded by rel...

  17. Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant.

    PubMed

    Leem, Jong-Han; Chung, Kyu Hyuck

    2016-01-01

    According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs' victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.

  18. Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant

    PubMed Central

    2017-01-01

    According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD. PMID:28111421

  19. Utilizing ToxCast Data and Lifestage Physiologically-Based Pharmacokinetic (PBPK) models to Drive Adverse Outcome Pathways (AOPs)-Based Margin of Exposures (ABME) to Chemicals.

    EPA Science Inventory

    Utilizing ToxCast Data and Lifestage Physiologically-Based Pharmacokinetic (PBPK) models to Drive Adverse Outcome Pathways (AOPs)-Based Margin of Exposures (ABME) to Chemicals. Hisham A. El-Masri1, Nicole C. Klienstreur2, Linda Adams1, Tamara Tal1, Stephanie Padilla1, Kristin I...

  20. Using adaptive processes and adverse outcome pathways to develop meaningful, robust, and actionable environmental monitoring programs.

    PubMed

    Arciszewski, Tim J; Munkittrick, Kelly R; Scrimgeour, Garry J; Dubé, Monique G; Wrona, Fred J; Hazewinkel, Rod R

    2017-09-01

    The primary goals of environmental monitoring are to indicate whether unexpected changes related to development are occurring in the physical, chemical, and biological attributes of ecosystems and to inform meaningful management intervention. Although achieving these objectives is conceptually simple, varying scientific and social challenges often result in their breakdown. Conceptualizing, designing, and operating programs that better delineate monitoring, management, and risk assessment processes supported by hypothesis-driven approaches, strong inference, and adverse outcome pathways can overcome many of the challenges. Generally, a robust monitoring program is characterized by hypothesis-driven questions associated with potential adverse outcomes and feedback loops informed by data. Specifically, key and basic features are predictions of future observations (triggers) and mechanisms to respond to success or failure of those predictions (tiers). The adaptive processes accelerate or decelerate the effort to highlight and overcome ignorance while preventing the potentially unnecessary escalation of unguided monitoring and management. The deployment of the mutually reinforcing components can allow for more meaningful and actionable monitoring programs that better associate activities with consequences. Integr Environ Assess Manag 2017;13:877-891. © 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

  1. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

  2. Psychoneuroimmunology in Pregnancy: Immune Pathways Linking Stress with Maternal Health, Adverse Birth Outcomes, and Fetal Development

    PubMed Central

    Christian, Lisa M.

    2011-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development. PMID:21787802

  3. Weight-of-evidence evaluation of an adverse outcome ...

    EPA Pesticide Factsheets

    Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

  4. Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  5. EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

    EPA Science Inventory

    Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

  6. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

    NASA Astrophysics Data System (ADS)

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P.

    2016-02-01

    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals.

  7. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment.more » Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.« less

  8. AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity

    EPA Science Inventory

    Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. ...

  9. Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes

    PubMed Central

    Smith, Laura E.; Prendergast, Andrew J.; Turner, Paul C.; Humphrey, Jean H.; Stoltzfus, Rebecca J.

    2017-01-01

    Pregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight. PMID:28500823

  10. Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes.

    PubMed

    Smith, Laura E; Prendergast, Andrew J; Turner, Paul C; Humphrey, Jean H; Stoltzfus, Rebecca J

    2017-04-01

    AbstractPregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight.

  11. Derivation and evaluation of putative adverse outcome ...

    EPA Pesticide Factsheets

    Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions including reproduction. High content (transcriptomic) empirical data and publicly available high throughput toxicity data (actor.epa.gov) were utilized to develop putative adverse outcome pathways (AOPs) for molecular initiating event (MIE) of COX inhibition. Effects of a waterborne, 96h exposure to indomethacin (IN; 100 µg/L), ibuprofen (IB; 200 µg/L) and celecoxib (CX; 20 µg/L) on liver metabolome and ovarian gene expression (using oligonucleotide microarrays) in sexually mature fathead minnows (n=8) were examined. Metabolomic profiles of IN, IB and CX were not significantly different from control or one another. Exposure to IB and CX resulted in differential expression of comparable numbers of genes (IB = 433, CX= 545). In contrast, 2558 genes were differentially expressed in IN-treated fish. Functional analyses (canonical pathway and gene set enrichment) indicated extensive effects of IN on prostaglandin synthesis pathway, oocyte meiosis and several other processes consistent with physiological roles of prostaglandins. Transcriptomic data was congruent with apical endpoint data - IN reduced plasma prostaglandin F2 alpha concentrations, and ovarian COX activity, whereas IB and CX did not. Putative AOPs pathways for

  12. Adverse Outcome Pathway for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptors During Development

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  13. Quantitative Adverse Outcome Pathway for Neurodevelopmental Effects of Thyroid Peroxidase-Induced Thyroid Hormone Synthesis Inhibition

    EPA Science Inventory

    Adequate levels of thyroid hormones (TH) are needed for proper brain development and deficiencies lead to adverse neurological outcomes in humans and in animal models. Environmental chemicals have been shown to disrupt TH levels, yet the relationship between developmental exposur...

  14. Stress and resource pathways connecting early socioeconomic adversity to young adults' physical health risk.

    PubMed

    Wickrama, Kandauda K A S; Lee, Tae Kyoung; O'Neal, Catherine Walker; Kwon, Josephine A

    2015-05-01

    Although research has established the impact of early stress, including stressful life contexts, and early resources, such as educational attainment, on various adolescent health outcomes, previous research has not adequately investigated "integrative models" incorporating both stress and resource mediational pathways to explain how early socioeconomic adversity impacts physical health outcomes, particularly in early life stages. Data on early childhood/adolescent stress and socioeconomic resources as well as biomarkers indicating physical health status in young adulthood were collected from 11,798 respondents (54 % female) over a 13-year period from youth participating in the National Study of Adolescent Health (Add Health). Physical health risk in young adulthood was measured using a composite index of nine regulatory biomarkers of cardiovascular and metabolic systems. Heterogeneity in stress and socioeconomic resource pathways was assessed using latent class analysis to identify clusters, or classes, of stress and socioeconomic resource trajectories. The influence of early socioeconomic adversity on young adults' physical health risk, as measured by biomarkers, was estimated, and the role of stress and socioeconomic resource trajectory classes as linking mechanisms was assessed. There was evidence for the influence of early socioeconomic adversity on young adults' physical health risk directly and indirectly through stress and socioeconomic resource trajectory classes over the early life course. These findings suggest that health models should be broadened to incorporate both stress and resource experiences simultaneously. Furthermore, these findings have prevention and intervention implications, including the importance of early socioeconomic adversity and key intervention points for "turning" the trajectories of at-risk youth.

  15. The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment

    PubMed Central

    Brockmeier, Erica K.; Hodges, Geoff; Hutchinson, Thomas H.; Butler, Emma; Hecker, Markus; Tollefsen, Knut Erik; Garcia-Reyero, Natalia; Kille, Peter; Becker, Dörthe; Chipman, Kevin; Colbourne, John; Collette, Timothy W.; Cossins, Andrew; Cronin, Mark; Graystock, Peter; Gutsell, Steve; Knapen, Dries; Katsiadaki, Ioanna; Lange, Anke; Marshall, Stuart; Owen, Stewart F.; Perkins, Edward J.; Plaistow, Stewart; Schroeder, Anthony; Taylor, Daisy; Viant, Mark; Ankley, Gerald; Falciani, Francesco

    2017-01-01

    Abstract In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework. PMID:28525648

  16. Childhood and Adolescent Adversity and Cardiometabolic Outcomes: A Scientific Statement From the American Heart Association.

    PubMed

    Suglia, Shakira F; Koenen, Karestan C; Boynton-Jarrett, Renée; Chan, Paul S; Clark, Cari J; Danese, Andrea; Faith, Myles S; Goldstein, Benjamin I; Hayman, Laura L; Isasi, Carmen R; Pratt, Charlotte A; Slopen, Natalie; Sumner, Jennifer A; Turer, Aslan; Turer, Christy B; Zachariah, Justin P

    2018-01-30

    Adverse experiences in childhood and adolescence, defined as subjectively perceived threats to the safety or security of the child's bodily integrity, family, or social structures, are known to be associated with cardiometabolic outcomes over the life course into adulthood. This American Heart Association scientific statement reviews the scientific literature on the influence of childhood adversity on cardiometabolic outcomes that constitute the greatest public health burden in the United States, including obesity, hypertension, type 2 diabetes mellitus, and cardiovascular disease. This statement also conceptually outlines pathways linking adversity to cardiometabolic health, identifies evidence gaps, and provides suggestions for future research to inform practice and policy. We note that, despite a lack of objective agreement on what subjectively qualifies as exposure to childhood adversity and a dearth of prospective studies, substantial evidence documents an association between childhood adversity and cardiometabolic outcomes across the life course. Future studies that focus on mechanisms, resiliency, and vulnerability factors would further strengthen the evidence and provide much-needed information on targets for effective interventions. Given that childhood adversities affect cardiometabolic health and multiple health domains across the life course, interventions that ameliorate these initial upstream exposures may be more appropriate than interventions remediating downstream cardiovascular disease risk factor effects later in life. © 2017 American Heart Association, Inc.

  17. Application of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks to advance cumulative risk assessment by integrating human health and ecological endpoints

    EPA Science Inventory

    Evaluating risk of adverse outcomes from chemical exposure is essential for understanding the impacts of environmental contaminants. While human health outcomes are of primary concern and are often the focus of risk assessments, important non-human species are also exposed to co...

  18. Gastroschisis: antenatal sonographic predictors of adverse neonatal outcome.

    PubMed

    Page, Rachael; Ferraro, Zachary Michael; Moretti, Felipe; Fung, Karen Fung Kee

    2014-01-01

    The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis. A quasi-systematic review was conducted in PubMed and Ovid using the key terms "gastroschisis," "predictors," "outcome," and "ultrasound." A total of 18 papers were included. The most common sonographic predictors were intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR), and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were consistently found to be statistically insignificant with respect to predicting adverse outcome including abdominal circumference, stomach herniation and dilatation, and extra-abdominal bowel dilatation (EABD). Gastroschisis is associated with several comorbidities, yet there is much discrepancy in the literature regarding which specific ultrasound markers best predict adverse neonatal outcomes. Future research should include prospective trials with larger sample sizes and use well-defined and consistent definitions of the adverse outcomes investigated with consideration given to IABD.

  19. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology.

    PubMed

    Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M E Bette; Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M; Whelan, Maurice

    2017-02-01

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24-25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

  20. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

    PubMed Central

    Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J.; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M. E. (Bette); Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M.; Whelan, Maurice

    2017-01-01

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24–25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. PMID:27994170

  1. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology.

    PubMed

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    To elucidate the effects of chemicals on populations of different species in the environment, efficient testing and modeling approaches are needed that consider multiple stressors and allow reliable extrapolation of responses across species. An adverse outcome pathway (AOP) is a concept that provides a framework for organizing knowledge about the progression of toxicity events across scales of biological organization that lead to adverse outcomes relevant for risk assessment. In this paper, we focus on exploring how the AOP concept can be used to guide research aimed at improving both our understanding of chronic toxicity, including delayed toxicity as well as epigenetic and transgenerational effects of chemicals, and our ability to predict adverse outcomes. A better understanding of the influence of subtle toxicity on individual and population fitness would support a broader integration of sublethal endpoints into risk assessment frameworks. Detailed mechanistic knowledge would facilitate the development of alternative testing methods as well as help prioritize higher tier toxicity testing. We argue that targeted development of AOPs supports both of these aspects by promoting the elucidation of molecular mechanisms and their contribution to relevant toxicity outcomes across biological scales. We further discuss information requirements and challenges in application of AOPs for chemical- and site-specific risk assessment and for extrapolation across species. We provide recommendations for potential extension of the AOP framework to incorporate information on exposure, toxicokinetics and situation-specific ecological contexts, and discuss common interfaces that can be employed to couple AOPs with computational modeling approaches and with evolutionary life history theory. The extended AOP framework can serve as a venue for integration of knowledge derived from various sources, including empirical data as well as molecular, quantitative and evolutionary-based models

  2. 1991 Gulf War exposures and adverse birth outcomes.

    PubMed

    Arnetz, Bengt; Drutchas, Alexis; Sokol, Robert; Kruger, Michael; Jamil, Hikmet

    2013-01-01

    We studied 1991 Gulf War (GW)-related environmental exposures and adverse birth outcomes in Iraqis. A random cross-sectional sample of 307 Iraqi families that immigrated to the United States responded to a structured interview covering socioeconomics, lifestyle, environmental exposures, and birth outcome. Data per each family was collected either from the man or the woman in the respective family. The respondents were divided into those that resided in Iraq during and following the GW (post-GW, n=185) and those that had left before (pre-GW, n=122). The primary outcome was lifetime prevalence of adverse birth outcomes, ie, congenital anomalies, stillbirth, low birth weight, and preterm delivery and its relationship to GW exposures. Mean number of adverse birth outcomes increased from 3.43 (SD=2.11) in the pre-GW to 4.63 (SD=2.63) in the post-GW group (P<.001). Mean chemical (Ch) and nonchemical (NCh) environmental exposure scores increased from pre-GW scores of 0.38 units (SD=1.76) and 0.43 (SD=1.86), respectively, to post-GW scores of 5.65 units (SD=6.23) and 7.26 (SD=5.67), P<.001 between groups for both exposures. There was a significant dose-response relationship between Ch environmental exposure (P=.001), but not NCh exposure, and number of adverse birth outcomes. Exposure to burning oil pits and mustard gas increased the risks for specific adverse birth outcomes by 2 to 4 times. Results indicate that Gulf War Ch, but not NCh exposures are related to adverse birth outcomes. Pregnancies in women with a history of war exposures might benefit from more intensive observation.

  3. The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment.

    PubMed

    Brockmeier, Erica K; Hodges, Geoff; Hutchinson, Thomas H; Butler, Emma; Hecker, Markus; Tollefsen, Knut Erik; Garcia-Reyero, Natalia; Kille, Peter; Becker, Dörthe; Chipman, Kevin; Colbourne, John; Collette, Timothy W; Cossins, Andrew; Cronin, Mark; Graystock, Peter; Gutsell, Steve; Knapen, Dries; Katsiadaki, Ioanna; Lange, Anke; Marshall, Stuart; Owen, Stewart F; Perkins, Edward J; Plaistow, Stewart; Schroeder, Anthony; Taylor, Daisy; Viant, Mark; Ankley, Gerald; Falciani, Francesco

    2017-08-01

    In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.

  4. Adverse outcome pathways linked to population models as a methodology for investigating effects of chemical stressors

    EPA Science Inventory

    In addressing the complexity and toxicity of chemical contaminants in Great Lakes ecosystems, we describe an approach to link chemically induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. Analysis of population impac...

  5. Interaction of Adverse Disease Related Pathways in Hypertrophic Cardiomyopathy.

    PubMed

    Rowin, Ethan J; Maron, Martin S; Chan, Raymond H; Hausvater, Anais; Wang, Wendy; Rastegar, Hassan; Maron, Barry J

    2017-12-15

    Hypertrophic cardiomyopathy (HC) has been characterized as a generally progressive genetic heart disease, creating an ominous perspective for patients and managing cardiologists. We explored the HC disease burden and interaction of adverse clinical pathways to clarify patient expectations over long time periods in the contemporary therapeutic era. We studied 1,000 consecutive HC patients (52 ± 17 years) at Tufts Medical Center, followed 9.3 ± 8 years from diagnosis, employing a novel disease pathway model: 46% experienced a benign course free of adverse pathways, but 42% of patients progressed along 1 major pathway, most commonly refractory heart failure to New York Heart Association class III or IV requiring surgical myectomy (or alcohol ablation) or heart transplant; repetitive or permanent atrial fibrillation; and least commonly arrhythmic sudden death events. Eleven percent experienced 2 of these therapeutic end points at different times in their clinical course, most frequently the combination of advanced heart failure and atrial fibrillation, whereas only 1% incurred all 3 pathways. Freedom of progression from 1 to 2 disease pathways, or from 2 to 3 was 80% and 93% at 5 years, respectively. Annual HC-related mortality did not differ according to the number of pathways: 1 (0.8%), 2 (0.8%), or 3 (2.4%) (p = 0.56), and 93% of patients were in New York Heart Association classes I or II at follow-up. In conclusion, it is uncommon for HC patients to experience multiple adverse (but treatable) disease pathways, underscoring the principle that HC is not a uniformly progressive disease. These observations provide a measure of clarity and/or reassurance to patients regarding the true long-term disease burden of HC. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Physiologically-based Pharmacokinetic(PBPK) Models Application to Screen Environmental Hazards Related to Adverse Outcome Pathways(AOPs)

    EPA Science Inventory

    PBPK models are useful in estimating exposure levels based on in vitro to in vivo extrapolation (IVIVE) calculations. Linkage of large sets of chemically screened vitro signature effects to in vivo adverse outcomes using IVIVE is central to the concepts of toxicology in the 21st ...

  7. Cross-species integration of human health and ecological endpoints into risk assessment using the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks

    EPA Science Inventory

    Exposure to environmental contaminants can influence both human health and ecological endpoints. Chemical risk assessments combine exposure and toxicity data to estimate the likelihood of adverse outcomes for these endpoints, but are rarely conducted in a manner that integrates ...

  8. Significant Adverse Events and Outcomes After Medical Abortion

    PubMed Central

    Cleland, Kelly; Creinin, Mitchell D.; Nucatola, Deborah; Nshom, Montsine; Trussell, James

    2013-01-01

    Objective To analyze rates of significant adverse events and outcomes in women having a medical abortion at Planned Parenthood health centers in 2009 and 2010, and to identify changes in the rates of adverse events and outcomes between the 2 years. Methods In this database review we analyzed data from Planned Parenthood affiliates that provided medical abortion in 2009 and 2010, almost exclusively using an evidence-based buccal misoprostol regimen. We evaluated the incidence of six clinically significant adverse events (hospital admission, blood transfusion, emergency room treatment, intravenous antibiotics administration, infection, and death) and two significant outcomes (ongoing pregnancy and ectopic pregnancy diagnosed after medical abortion treatment was initiated). We calculated an overall rate as well as rates for each event and identified changes between the 2 years. Results Amongst 233,805 medical abortions provided in 2009 and 2010, significant adverse events or outcomes were reported in 1,530 cases (0.65%). There was no statistically significant difference in overall rates between years. The most common significant outcome was ongoing intrauterine pregnancy (0.50%); significant adverse events occurred in 0.16% of cases. One patient death occurred due to an undiagnosed ectopic pregnancy. Only rates for emergency room treatment and blood transfusion differed by year, and were slightly higher in 2010. Conclusion Review of this large dataset reinforces the safety of the evidence-based medical abortion regimen. PMID:23262942

  9. Pathways from Adolescent Deliberate Self-Poisoning to Early Adult Outcomes: A Six-Year Follow-Up

    ERIC Educational Resources Information Center

    Aglan, Azza; Kerfoot, Michael; Pickles, Andrew

    2008-01-01

    Background: Prospective studies show that the adult outcomes of adolescents who deliberately harm themselves are marked by high rates of adversity and psychiatric disorders. The goal of this study was to identify pathways linking childhood risk factors to early adult outcomes of suicidal adolescents. Methods: A clinical sample of 158 adolescents…

  10. Pathways between childhood/adolescent adversity, adolescent socioeconomic status, and long-term cardiovascular disease risk in young adulthood.

    PubMed

    Doom, Jenalee R; Mason, Susan M; Suglia, Shakira F; Clark, Cari Jo

    2017-09-01

    The current study investigated mediators between childhood/adolescent adversities (e.g., dating violence, maltreatment, homelessness, and parental death), low socioeconomic status (SES) during adolescence, and cardiovascular disease (CVD) risk in young adulthood. The purpose of these analyses was to understand whether SES during adolescence and childhood/adolescent adversities affect CVD risk through similar pathways, including maternal relationship quality, health behaviors, financial stress, medical/dental care, educational attainment, sleep problems, and depressive symptoms. Using the National Longitudinal Study of Adolescent to Adult Health (N = 14,493), which has followed US adolescents (Wave 1; M = 15.9 years) through early adulthood (Wave 4; M = 28.9 years), associations were examined between childhood/adolescent adversity and SES to 30-year CVD risk in young adulthood. The outcome was a Framingham-based prediction model of CVD risk that included age, sex, body mass index, smoking, systolic blood pressure, diabetes, and antihypertensive medication use at Wave 4. Path analysis was used to examine paths through the adolescent maternal relationship to young adult mediators of CVD risk. Childhood/adolescent adversity significantly predicted greater adult CVD risk through the following pathways: maternal relationship, health behaviors, financial stress, lack of medical/dental care, and educational attainment; but not through depressive symptoms or sleep problems. Lower SES during adolescence significantly predicted greater adult CVD risk through the following pathways: health behaviors, financial stress, lack of medical/dental care, and educational attainment, but not maternal relationship, depressive symptoms, or sleep problems. Childhood/adolescent adversities and SES affected CVD risk in young adulthood through both similar and unique pathways that may inform interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Modeling life course pathways from adverse childhood experiences to adult mental health.

    PubMed

    Jones, Tiffany M; Nurius, Paula; Song, Chiho; Fleming, Christopher M

    2018-06-01

    Although the association between adverse childhood experiences (ACEs) and adult mental health is becoming well established, less is known about the complex and multiple pathways through which ACEs exert their influence. Growing evidence suggests that adversity early in life conveys not only early impacts, but also augments risk of stress-related life course cascades that continue to undermine health. The present study aims to test pathways of stress proliferation and stress embodiment processes linking ACEs to mental health impairment in adulthood. Data are from the 2011 Behavioral Risk Factor Surveillance Survey, a representative sample of Washington State adults ages 18 and over (N = 14,001). Structural equation modeling allowed for testing of direct and indirect effects from ACEs though low income status, experiences of adversity in adulthood, and social support. The model demonstrated that adult low income, social support and adult adversity are in fact conduits through which ACEs exert their influence on mental health impairment in adulthood. Significant indirect pathways through these variables supported hypotheses that the effect of ACEs is carried through these variables. This is among the first models that demonstrates multiple stress-related life course pathways through which early life adversity compromises adult mental health. Discussion elaborates multiple service system opportunities for intervention in early and later life to interrupt direct and indirect pathways of ACE effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Adverse Outcome Pathway (AOP) for a Mutagenic Mode of ...

    EPA Pesticide Factsheets

    AOPs provide a framework to describe a sequence of measureable key events (KEs), beginning with a molecular initiating event (MIE), followed by a series of identified KEs linked to one another by KE Relationships (KERs), all anchored by a specific adverse outcome (AO). Each KE/KER is supported by data and evaluated against criteria to assess biological plausibility, weight/strength of evidence, specificity, and confidence. AOPs offer an approach to using toxicological data and predictive modeling to actualize use of mode-of-action (MOA) for such purposes as read-across, integrated approaches to testing & assessment, and risk assessment. Different applications will depend partly on the scientific confidence underpinning each KE/KER and the overall AOP. An OECD program encourages development of AOPs, with a wiki that allows for public review & comment to foster collaborations and broaden understanding & application of AOPs. Developing an AOP for a mutagenic MOA for cancer as a case study in the OECD program lays a path towards determination of such an MOA and its use in chemical assessment programs. Aflatoxin B1 (AFB1), with ubiquitous exposure and a rich database, was selected for this case study. AFB1 has been determined to induce HCC via a DNA-reactive MOA in many species, including humans. The sequential KEs identified for AFB1 are as follows: pre-MIE: Hepatic metabolic activation; MIE: Formation of a pro-mutagenic DNA adduct (N7-AFB1-guanine or AFB1-FAPy); KE

  13. Conceptual Model for Assessing Criteria Air Pollutants in a Multipollutant Context: A Modified Adverse Outcome Pathway Approach

    EPA Science Inventory

    Background: Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is d...

  14. Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework

    EPA Science Inventory

    Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures an...

  15. Integrative data mining of high-throughput in vitro screens, in vivo data, and disease information to identify Adverse Outcome Pathway (AOP) signatures:ToxCast high-throughput screening data and Comparative Toxicogenomics Database (CTD) as a case study.

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework provides a systematic way to describe linkages between molecular and cellular processes and organism or population level effects. The current AOP assembly methods however, are inefficient. Our goal is to generate computationally-pr...

  16. Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes.

    PubMed

    Labib, Sarah; Williams, Andrew; Yauk, Carole L; Nikota, Jake K; Wallin, Håkan; Vogel, Ulla; Halappanavar, Sabina

    2016-03-15

    A diverse class of engineered nanomaterials (ENMs) exhibiting a wide array of physical-chemical properties that are associated with toxicological effects in experimental animals is in commercial use. However, an integrated framework for human health risk assessment (HHRA) of ENMs has yet to be established. Rodent 2-year cancer bioassays, clinical chemistry, and histopathological endpoints are still considered the 'gold standard' for detecting substance-induced toxicity in animal models. However, the use of data derived from alternative toxicological tools, such as genome-wide expression profiling and in vitro high-throughput assays, are gaining acceptance by the regulatory community for hazard identification and for understanding the underlying mode-of-action. Here, we conducted a case study to evaluate the application of global gene expression data in deriving pathway-based points of departure (PODs) for multi-walled carbon nanotube (MWCNT)-induced lung fibrosis, a non-cancer endpoint of regulatory importance. Gene expression profiles from the lungs of mice exposed to three individual MWCNTs with different physical-chemical properties were used within the framework of an adverse outcome pathway (AOP) for lung fibrosis to identify key biological events linking MWCNT exposure to lung fibrosis. Significantly perturbed pathways were categorized along the key events described in the AOP. Benchmark doses (BMDs) were calculated for each perturbed pathway and were used to derive transcriptional BMDs for each MWCNT. Similar biological pathways were perturbed by the different MWCNT types across the doses and post-exposure time points studied. The pathway BMD values showed a time-dependent trend, with lower BMDs for pathways perturbed at the earlier post-exposure time points (24 h, 3d). The transcriptional BMDs were compared to the apical BMDs derived by the National Institute for Occupational Safety and Health (NIOSH) using alveolar septal thickness and fibrotic lesions

  17. Adapting biomarker technologies to adverse outcome ...

    EPA Pesticide Factsheets

    Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, there are now new technologies being considered derived from the broad field of breath research, especially in applications of gas-phase analysis and instrumentation. The ultimate goal is to discover disease progressions in human or animal systems, identify them at the molecular or cellular level, and then choose analytes that can distinctly define the presence of a particular path (Ankley et al. 2010, Villeneuve et al. 2014). Once such in vivo pathways are identified, then in vitro assays can be developed for streamlined testing of chemical effects without additional human or animal based studies (Pleil et al. 2012). Recent work has focused on discovery analysis in breath, or other biological media, wherein as many as possible compounds are cataloged and then linked to their biochemical source as exogenous (external), endogenous (internal) or from the microbiome (Pleil et al. 2013a, de Lacy Costello 2014, Pleil et al. 2013b, Trefz et al. 2013, Pleil et al. 2014). Such research lays the groundwork for identifying compounds from systems biology that might be relevant for developing AOPs for in vitro research. The National Exposure Research Laboratory’s (NERL’s) Human Exposure and Atm

  18. Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease.

    PubMed

    Kuhlman, Kate Ryan; Chiang, Jessica J; Horn, Sarah; Bower, Julienne E

    2017-09-01

    Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Smoking and Adverse Maternal and Child Health Outcomes in Brazil

    PubMed Central

    2013-01-01

    Introduction: Numerous studies from high-income countries document the causal relationship between cigarette smoking during pregnancy and adverse maternal and child health (MCH) outcomes. Less research has been conducted in low and middle income countries, but a burgeoning literature can be found for Brazil. Methods: We review Brazilian studies of the prevalence of maternal smoking, the relative risk of smoking-attributable adverse MCH outcomes, and present new estimates for these outcomes, using the attributable fraction method. Results: We found that Brazilian studies of the relative risks of smoking-attributable adverse MCH outcomes were broadly consistent with previous reviews. Based on a comparison of maternal smoking over time, smoking during pregnancy has declined by about 50% over the last 20 years in Brazil. For 2008, we estimate that 5,352 cases of spontaneous abortion, 10,929 cases of preterm birth, 20,717 cases of low birth weight, and 29 cases of sudden infant death syndrome are attributable to maternal smoking. Between 1989 and 2008, the percent of smoking-attributable adverse MCH outcomes in Brazil was at least halved. Conclusions: The results show that over a 20-year period, during which Brazil implemented numerous effective tobacco control measures, the country experienced a dramatic decrease in both maternal smoking prevalence and smoking-attributable adverse MCH outcomes. Countries that implement effective tobacco control measures can expect to reduce both maternal smoking and adverse MCH outcomes, thereby improving the public health. PMID:23873977

  20. Authentic leadership and nurse-assessed adverse patient outcomes.

    PubMed

    Wong, Carol A; Giallonardo, Lisa M

    2013-07-01

    Our purpose was to test a model examining relationships among authentic leadership, nurses' trust in their manager, areas of work life and nurse-assessed adverse patient outcomes. Although several work environment factors have been cited as critical to patient outcomes, studies linking nursing leadership styles with patient outcomes are limited suggesting the need for additional research to investigate the mechanisms by which leadership may influence patient outcomes. Secondary analysis of data collected in a cross-sectional survey of 280 (48% response rate) registered nurses working in acute care hospitals in Ontario was conducted using structural equation modelling. The final model fit the data acceptably (χ(2) = 1.30, df = 2, P = 0.52, IFI = 0.99, CFI = 1.00, RMSEA = 0.00). Authentic leadership was significantly associated with decreased adverse patient outcomes through trust in the manager and areas of work life. The findings suggest that nurses who see their managers as demonstrating high levels of authentic leadership report increased trust, greater congruence in the areas of work life and lower frequencies of adverse patient outcomes. Managers who emphasize transparency, balanced processing, self-awareness and high ethical standards in their interactions with nurses may contribute to safer work environments for patients and nurses. © 2013 John Wiley & Sons Ltd.

  1. Presentations: Adverse Outcome Pathways for Abnormal Phenotypes

    EPA Science Inventory

    Birth defects affect many infants and the etiology for most are unknown. Although environmental factors are known to influence pregnancy outcome, thousands of chemicals, present in the environment, are untested for developmental toxicity potential. Application of computational p...

  2. Adverse psychological outcomes following colposcopy and related procedures: a systematic review.

    PubMed

    O'Connor, M; Gallagher, P; Waller, J; Martin, C M; O'Leary, J J; Sharp, L

    2016-01-01

    Although colposcopy is the leading follow-up option for women with abnormal cervical cytology, little is known about its psychological consequences. We performed a systematic review to examine: (1) what, if any, are the adverse psychological outcomes following colposcopy and related procedures; (2) what are the predictors of adverse psychological outcomes post-colposcopy; and (3) what happens to these outcomes over time. Five electronic databases (PubMed, PsychINFO, CINAHL, Web of Science, Scopus) were searched for studies published in English between January 1986 and February 2014. Eligible studies assessed psychological wellbeing at one or more time-points post-colposcopy. Two reviewers independently screened titles and abstracts. Full texts of potentially eligible papers were reviewed. Data were abstracted from, and a quality appraisal performed of, eligible papers. Twenty-three papers reporting 16 studies were eligible. Colposcopy and related procedures can lead to adverse psychological outcomes, particularly anxiety. Ten studies investigated predictors of adverse psychological outcomes; management type and treatment had no impact on this. Seven studies investigated temporal trends in psychological outcomes post-colposcopy; findings were mixed, especially in relation to anxiety and distress. Studies were methodologically heterogeneous. Follow-up investigations and procedures for abnormal cervical cytology can cause adverse psychological outcomes among women. However, little is known about the predictors of these outcomes or how long they persist. There is a need for a more standardised approach to the examination of the psychological impact of colposcopy, especially longer-term outcomes. Follow-up investigations for abnormal cervical cytology can cause adverse psychological outcome among women. © 2015 Royal College of Obstetricians and Gynaecologists.

  3. Adverse pregnancy outcomes following syphilis treatment in pregnancy in the UK.

    PubMed

    Wallace, Harriet E; Isitt, Catherine E; Broomhall, Harriet M; Perry, Alison E; Wilson, Janet D

    2016-10-01

    Syphilis infection in pregnancy is known to cause a number of severe adverse pregnancy outcomes, including second-trimester miscarriage, stillbirth, very pre-term delivery and neonatal death, in addition to congenital syphilis. A retrospective review of women with positive syphilis serology and a pregnancy outcome between 2005 and 2012 in Leeds, UK, was performed. In all, 57 cases of positive syphilis serology in pregnancy were identified: 24 with untreated syphilis treated in the current pregnancy (Group 1); seven with reported but unconfirmed prior treatment who were retreated (Group 2); and 26 adequately treated prior to pregnancy (Group 3). The rate of severe adverse pregnancy outcomes in Group 1 at 21% was significantly higher than the 0% outcome of Group 3 (p = 0.02). The severe adverse pregnancy outcomes were two second-trimester miscarriages, two pre-term births at 25 and 28 weeks and one stillbirth at 32 weeks. There were no cases of term congenital syphilis or term neonatal death, but we observed high rates of other adverse pregnancy outcomes despite treatment during pregnancy. Rapid referral for treatment is needed before 18 weeks in order to minimise adverse pregnancy outcomes. © The Author(s) 2016.

  4. Advancing adverse outcome pathways for integrated toxicology and regulatory applications

    EPA Science Inventory

    Recent regulatory efforts in many countries have focused on a toxicological pathway-based vision for human health assessments relying on in vitro systems and predictive models to generate the toxicological data needed to evaluate chemical hazard. A pathway-based vision is equally...

  5. Systematic review of pediatric health outcomes associated with childhood adversity.

    PubMed

    Oh, Debora Lee; Jerman, Petra; Silvério Marques, Sara; Koita, Kadiatou; Purewal Boparai, Sukhdip Kaur; Burke Harris, Nadine; Bucci, Monica

    2018-02-23

    Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity. PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers. After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion. Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better

  6. Adverse Outcome Pathway (AOP) for a Mutagenic Mode of Action for Cancer: AFB1 and Hepatocellular Carcinoma (HCC)

    EPA Science Inventory

    AOPs provide a framework to describe a sequence of measureable key events (KEs), beginning with a molecular initiating event (MIE), followed by a series of identified KEs linked to one another by KE Relationships (KERs), all anchored by a specific adverse outcome (AO). Each KE/KE...

  7. Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

    PubMed

    Tolcher, Mary Catherine; Torbenson, Vanessa E; Weaver, Amy L; McGree, Michaela E; El-Nashar, Sherif A; Nesbitt, Katharine M; Gostout, Bobbie S; Famuyide, Abimbola O

    2016-03-01

    The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43

  8. Adverse outcome pathways (AOPs): A framework to support predictive toxicology

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  9. Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

    PubMed Central

    Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C.; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M.; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L. A.; van der Ven, Leo T. M.

    2016-01-01

    Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes. PMID:27827847

  10. Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

    PubMed

    Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; van der Ven, Leo T M

    2016-11-02

    Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S -adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

  11. [Severe Adverse Pregnancy Outcomes in Placenta Previa and Prior Cesarean Delivery].

    PubMed

    Zhou, Mi; Chen, Meng; Zhang, Li; He, Guo-Lin; He, Lei; Wei, Qiang; Li, Tao; Liu, Xing-Hui

    2017-09-01

    To investigate the severe adverse pregnancy outcomes in pregnancies with placenta previa and prior cesarean delivery and its risk factors. This retrospective casecontrol study reviewed all pregnancies with placenta previa and prior cesarean delivery delivered by repeat cesarean section in our institution between January 2005 and June 2015,and investigated the incidence of severe adverse pregnancy outcome. A composite of severe adverse pregnancy outcomes (including transfusion of 10 units or more red blood cells,maternal ICU admission,unanticipated injuries,repeat operation,hysterectomy,and maternal death) and other maternal and neonatal outcomes were described. Univariate and multivariable logistic regression analysis were used to quantify the effects of risk factors on severe adverse pregnancy outcomes. There were 478 women with placenta previa and prior cesarean delivery in our hospital over the last decade. The average age of them was 32.5±4.8 years old,most women were beyond 30 years old,the average gravidity and parity were 4 and 1,131 cases (27.4%) had severe adverse pregnancy outcomes. Transfusion of 10 units or more red blood cells happened in 75 cases (15.7%,75/478); 44 cases (9.2%,44/478) necessitated maternal ICU admission; unanticipated bladder injury occurred in 11 cases,but non ureter or bowel injury happened; All 4 repeat operations were due to delayed hemorrhage after conservative management during cesarean delivery,and an emergent hysterectomy was performed for all of the 4 cases. Hysterectomy (107 cases,22.4%) was the most common severe adverse pregnancy outcome. Among all 311 morbidly adherent placenta cases finally confirmed by pathological or surgical findings or both,only 172 (55.3%) were suspected before delivery. Multivariable logistic regression analysis showed that the risk of severe adverse pregnancy outcomes was significantly increased by pernicious placenta previa (i.e. anterior placenta overlying the prior cesarean scar),suspicion of

  12. Factors associated with adverse clinical outcomes among obstetric trainees

    PubMed Central

    Aiken PhD, Catherine E.; Aiken, Abigail; Park, Hannah; Brockelsby, Jeremy C.; Prentice, Andrew

    2016-01-01

    Objective To determine whether UK obstetric trainees transitioning from directly to indirectly-supervised practice have a higher likelihood of adverse patient outcomes from operative deliveries compared to other indirectly supervised trainees and to examine whether performing more procedures under direct supervision is associated with fewer adverse outcomes in initial indirect practice. Methods We examined all deliveries (13,861) conducted by obstetricians at a single centre over 5 years (2008-2013). Mixed-effects logistic regression models were used to compare estimated blood loss, maternal trauma, umbilical arterial pH, delayed neonatal respiration, failed instrumental delivery, and critical incidents for trainees in their first indirectly-supervised year with trainees in all other years of indirect practice. Outcomes for trainees in their first indirectly-supervised 3 months were compared to their outcomes for the remainder of the year. Linear regression was used to examine the relationship between number of procedures performed under direct supervision and initial outcomes under indirect supervision. Results Trainees in their first indirectly-supervised year had a higher likelihood of >2 litres estimated blood loss at any delivery (OR 1.32;CI(1.01-1.64) p<0.05) and of failed instrumental delivery (OR 2.33;CI(1.37-3.29) p<0.05) compared with other indirectly-supervised trainees. Other measured outcomes showed no significant differences. Within the first three months of indirect supervision, the likelihood of operative vaginal deliveries with >1litre estimated blood loss (OR 2.54;CI(1.88-3.20) p<0.05) was higher compared to the remainder of the first year. Performing more deliveries under direct supervision prior to beginning indirectly-supervised training was associated with decreased risk of >1litre estimated blood loss (p<0.05). Conclusions Obstetric trainees in their first year of indirectly-supervised practice have a higher likelihood of immediate adverse

  13. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  14. Residential Proximity to Environmental Hazards and Adverse Health Outcomes

    PubMed Central

    Maantay, Juliana A.; Chakraborty, Jayajit

    2011-01-01

    How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses. PMID:22028451

  15. Adverse pregnancy outcomes in women with nausea and vomiting of pregnancy.

    PubMed

    Temming, Lorene; Franco, Albert; Istwan, Niki; Rhea, Debbie; Desch, Cheryl; Stanziano, Gary; Joy, Saju

    2014-01-01

    To examine the influence of nausea and vomiting of pregnancy (NVP) on pregnancy outcomes. Outcomes were compared for primigravidas with a current singleton gestation enrolled at <20 weeks' gestation in a maternity risk screening and education program (n = 81 486). Patient-reported maternal characteristics and pregnancy outcomes were compared for women with and without NVP and within the NVP group for those with and without poor weight gain. 6.4% of women reported NVP as a pregnancy complication. Women reporting NVP were more likely to be younger, obese, single and smoke. They had higher rates of preterm delivery, pregnancy-induced hypertension and low birth weight <2500 g. Almost one-quarter of women with NVP had lower than recommended weight gain. Poor weight gain was associated with a higher incidence of adverse outcomes. Obesity, tobacco use and poor pregnancy weight gain independently increased the odds of an adverse outcome. NVP and subsequent poor weight gain may be associated with adverse pregnancy outcomes.

  16. Paternal education and adverse birth outcomes in Canada.

    PubMed

    Shapiro, Gabriel D; Bushnik, Tracey; Sheppard, Amanda J; Kramer, Michael S; Kaufman, Jay S; Yang, Seungmi

    2017-01-01

    Research on predictors of adverse birth outcomes has focused on maternal characteristics. Much less is known about the role of paternal factors. Paternal education is an important socioeconomic marker that may predict birth outcomes over and above maternal socioeconomic indicators. Using data from the 2006 Canadian Birth-Census Cohort, we estimated the associations between paternal education and preterm birth, small-for-gestational-age (SGA) birth, stillbirth and infant mortality in Canada, controlling for maternal characteristics. Binomial regression was used to estimate risk ratios and risk differences for adverse birth outcomes associated with paternal education, after controlling for maternal education, age, marital status, parity, ethnicity and nativity. A total of 131 285 singleton births were included in the present study. Comparing the lowest to the highest paternal education category, adjusted risk ratios (95% CIs) were 1.22 (1.10 to 1.35) for preterm birth, 1.13 (1.03 to 1.23) for SGA birth, 1.92 (1.28 to 2.86) for stillbirth and 1.67 (1.01 to 2.75) for infant mortality. Consistent patterns of associations were observed for absolute risk differences. Our study suggests that low paternal education increases the risk of adverse birth outcomes, and especially of fetal and infant mortality, independently from maternal characteristics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Trends in adverse maternal outcomes during childbirth: a population-based study of severe maternal morbidity.

    PubMed

    Roberts, Christine L; Ford, Jane B; Algert, Charles S; Bell, Jane C; Simpson, Judy M; Morris, Jonathan M

    2009-02-25

    Maternal mortality is too rare in high income countries to be used as a marker of the quality of maternity care. Consequently severe maternal morbidity has been suggested as a better indicator. Using the maternal morbidity outcome indicator (MMOI) developed and validated for use in routinely collected population health data, we aimed to determine trends in severe adverse maternal outcomes during the birth admission and in particular to examine the contribution of postpartum haemorrhage (PPH). We applied the MMOI to the linked birth-hospital discharge records for all women who gave birth in New South Wales, Australia from 1999 to 2004 and determined rates of severe adverse maternal outcomes. We used frequency distributions and contingency table analyses to examine the association between adverse outcomes and maternal, pregnancy and birth characteristics, among all women and among only those with PPH. Using logistic regression, we modelled the effects of these characteristics on adverse maternal outcomes. The impact of adverse outcomes on duration of hospital admission was also examined. Of 500,603 women with linked birth and hospital records, 6242 (12.5 per 1,000) suffered an adverse outcome, including 22 who died. The rate of adverse maternal outcomes increased from 11.5 in 1999 to 13.8 per 1000 deliveries in 2004, an annual increase of 3.8% (95%CI 2.3-5.3%). This increase occurred almost entirely among women with a PPH. Changes in pregnancy and birth factors during the study period did not account for increases in adverse outcomes either overall, or among the subgroup of women with PPH. Among women with severe adverse outcomes there was a 12% decrease in hospital days over the study period, whereas women with no severe adverse outcome occupied 23% fewer hospital days in 2004 than in 1999. Severe adverse maternal outcomes associated with childbirth have increased in Australia and the increase was entirely among women who experienced a PPH. Reducing or stabilising

  18. Area-level risk factors for adverse birth outcomes: trends in urban and rural settings.

    PubMed

    Kent, Shia T; McClure, Leslie A; Zaitchik, Ben F; Gohlke, Julia M

    2013-06-10

    Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban-rural status. Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991-2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse birth outcomes elsewhere may not be reaching

  19. Area-level risk factors for adverse birth outcomes: trends in urban and rural settings

    PubMed Central

    2013-01-01

    Background Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban–rural status. Methods Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Results Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991–2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Conclusions Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse

  20. Adverse effects of microplastics and oxidative stress-induced MAPK/Nrf2 pathway-mediated defense mechanisms in the marine copepod Paracyclopina nana

    PubMed Central

    Jeong, Chang-Bum; Kang, Hye-Min; Lee, Min-Chul; Kim, Duck-Hyun; Han, Jeonghoon; Hwang, Dae-Sik; Souissi, Sami; Lee, Su-Jae; Shin, Kyung-Hoon; Park, Heum Gi; Lee, Jae-Seong

    2017-01-01

    Microplastic pollution causes a major concern in the marine environment due to their worldwide distribution, persistence, and adverse effects of these pollutants in the marine ecosystem. Despite its global presence, there is still a lack of information on the effect of microplastics on marine organisms at the molecular level. Herein we demonstrated ingestion and egestion of nano- (0.05 μm) and micro-sized (0.5 and 6 μm) polystyrene microbeads in the marine copepod Paracyclopina nana, and examined molecular responses to exposure to microbeads with in vivo endpoints such as growth rate and fecundity. Also, we proposed an adverse outcome pathway for microplastic exposure that covers molecular and individual levels. This study provides the first insight into the mode of action in terms of microplastic-induced oxidative stress and related signaling pathways in P. nana. PMID:28117374

  1. Adverse effects of microplastics and oxidative stress-induced MAPK/Nrf2 pathway-mediated defense mechanisms in the marine copepod Paracyclopina nana

    NASA Astrophysics Data System (ADS)

    Jeong, Chang-Bum; Kang, Hye-Min; Lee, Min-Chul; Kim, Duck-Hyun; Han, Jeonghoon; Hwang, Dae-Sik; Souissi, Sami; Lee, Su-Jae; Shin, Kyung-Hoon; Park, Heum Gi; Lee, Jae-Seong

    2017-01-01

    Microplastic pollution causes a major concern in the marine environment due to their worldwide distribution, persistence, and adverse effects of these pollutants in the marine ecosystem. Despite its global presence, there is still a lack of information on the effect of microplastics on marine organisms at the molecular level. Herein we demonstrated ingestion and egestion of nano- (0.05 μm) and micro-sized (0.5 and 6 μm) polystyrene microbeads in the marine copepod Paracyclopina nana, and examined molecular responses to exposure to microbeads with in vivo endpoints such as growth rate and fecundity. Also, we proposed an adverse outcome pathway for microplastic exposure that covers molecular and individual levels. This study provides the first insight into the mode of action in terms of microplastic-induced oxidative stress and related signaling pathways in P. nana.

  2. Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus

    PubMed Central

    Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

    2016-01-01

    Abstract Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

  3. Adverse outcome pathways

    EPA Science Inventory

    The Systems Toxicology Unit of the European Commission Joint Research Centre (JRC) is strongly committed to development and uptake of AOPs. In coordination with the OECD, the JRC and EPA have collaborated closely in the development of training and outreach materials related to th...

  4. Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian Women with Preeclampsia.

    PubMed

    March, Melissa I; Geahchan, Carl; Wenger, Julia; Raghuraman, Nandini; Berg, Anders; Haddow, Hamish; Mckeon, Bri Ann; Narcisse, Rulx; David, Jean Louis; Scott, Jennifer; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2015-01-01

    Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE. We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions. Among patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome. PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

  5. Pathways from childhood abuse and other adversities to adult health risks: The role of adult socioeconomic conditions.

    PubMed

    Font, Sarah A; Maguire-Jack, Kathryn

    2016-01-01

    Adverse childhood experiences (ACEs), including child abuse, have been linked with poor health outcomes in adulthood. The mechanisms that explain these relations are less understood. This study assesses whether associations of ACEs and health risks are mediated by adult socioeconomic conditions, and whether these pathways are different for maltreatment than for other types of adversities. Using the Behavioral Risk Factor Surveillance System 2012 survey (N=29,229), we employ structural equation modeling to (1) estimate associations of the number and type of ACEs with five health risks-depression, obesity, tobacco use, binge drinking, and self-reported sub-optimal health; and (2) assess whether adult socioeconomic conditions-marriage, divorce and separation, educational attainment, income and insurance status-mediate those associations. Findings suggest both direct and indirect associations between ACEs and health risks. At high numbers of ACEs, 15-20% of the association between number of ACEs and adult health risks was attributable to socioeconomic conditions. Associations of three ACEs (exposure to domestic violence, parental divorce, and residing with a person who was incarcerated) with health risks were nearly entirely explained by socioeconomic conditions in adulthood. However, child physical, emotional, and sexual abuse were significantly associated with several adult health risks, beyond the effects of other adversities, and socioeconomic conditions explained only a small portion of these associations. These findings suggest that the pathways to poor adult health differ by types of ACEs, and that childhood abuse is more likely than other adversities to have a direct impact. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The long reach of early adversity: Parenting, stress, and neural pathways to antisocial behavior in adulthood.

    PubMed

    Gard, Arianna M; Waller, Rebecca; Shaw, Daniel S; Forbes, Erika E; Hariri, Ahmad R; Hyde, Luke W

    2017-10-01

    Early life adversities including harsh parenting, maternal depression, neighborhood deprivation, and low family economic resources are more prevalent in low-income urban environments and are potent predictors of psychopathology, including, for boys, antisocial behavior (AB). However, little research has examined how these stressful experiences alter later neural function. Moreover, identifying genetic markers of greater susceptibility to adversity is critical to understanding biopsychosocial pathways from early adversity to later psychopathology. Within a sample of 310 low-income boys followed from age 1.5 to 20, multimethod assessments of adversities were examined at age 2 and age 12. At age 20, amygdala reactivity to emotional facial expressions was assessed using fMRI, and symptoms of Antisocial Personality Disorder were assessed via structured clinical interview. Genetic variability in cortisol signaling ( CRHR1 ) was examined as a moderator of pathways to amygdala reactivity. Observed parenting and neighborhood deprivation at age 2 each uniquely predicted amygdala reactivity to emotional faces at age 20 over and above other adversities measured at multiple developmental periods. Harsher parenting and greater neighborhood deprivation in toddlerhood predicted clinically-significant symptoms of AB via less amygdala reactivity to fearful facial expressions and this pathway was moderated by genetic variation in CRHR1 . These results elucidate a pathway linking early adversity to less amygdala reactivity to social signals of interpersonal distress 18 years later, which in turn increased risk for serious AB. Moreover, these findings suggest a genetic marker of youth more susceptible to adversity.

  7. A critical pathway for patients with acute chest pain and low risk for short-term adverse cardiac events: role of outpatient stress testing.

    PubMed

    Meyer, Mary C; Mooney, Robert P; Sekera, Anna K

    2006-05-01

    We evaluate the safety and feasibility of a critical care pathway protocol in which patients with acute chest pain who are low risk for coronary artery disease and short-term adverse cardiac outcomes receive outpatient stress testing within 72 hours of an emergency department (ED) visit. We performed an observational study of an ED-based chest pain critical pathway in an urban, community hospital in 979 consecutive patients. Patients enrolled in the protocol were observed in the ED before receiving 72-hour outpatient stress testing. The pathway was primarily analyzed for rates of death or myocardial infarction in the 6 months after ED discharge and outpatient stress testing. Secondary outcome measures included need for coronary intervention at initial stress testing and within 6 months after discharge, subsequent ED visits for chest pain, and subsequent hospitalization. Of 871 stress-tested patients aged 40 years or older, who had low risk for coronary artery disease and short-term adverse cardiac events, and had 6-month follow-up, 18 (2%) required coronary intervention, 1 (0.1%) had a myocardial infarction within 1 month, 2 (0.2%) had a myocardial infarction within 6 months, 6 (0.7%) had normal stress test results after discharge but required cardiac catheterization within 6 months, and 5 (0.6%) returned to the ED within 6 months for ongoing chest pain. Hospital admission rates decreased significantly from 31.2% to 26.1% after initiation of the protocol (P<.001). For patients with chest pain and low risk for short-term cardiac events, outpatient stress testing is feasible, safe, and associated with decreased hospital admission rates. With an evidence-based protocol, physicians efficiently identify patients at low risk for clinically significant coronary artery disease and short-term adverse cardiac outcomes.

  8. Early Elevations of the Complement Activation Fragment C3a and Adverse Pregnancy Outcomes

    PubMed Central

    Lynch, Anne M.; Gibbs, Ronald S.; Murphy, James R.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

    2016-01-01

    OBJECTIVE To estimate whether elevations of complement C3a early in pregnancy are predictive of the subsequent development of adverse pregnancy outcomes. METHODS A plasma sample was obtained from each enrolled pregnant woman before 20 weeks of gestation. The cohort (n=1,002) was evaluated for the development of adverse pregnancy outcomes defined as hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of gestation), premature rupture of the membranes, pregnancy loss (during the embryonic and fetal period), intrauterine growth restriction, and the composite outcome of any adverse outcome. RESULTS One or more adverse pregnancy outcomes occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early pregnancy were significantly (P=<.001) higher among women with one or more adverse outcomes (858±435) compared with women with an uncomplicated pregnancy (741±407). Adjusted for parity and prepregnancy body mass index, women with levels of C3a in the upper quartile in early pregnancy were three times more likely to have an adverse outcome later in pregnancy compared with women in the lowest quartile (95% confidence interval, 1.8–4.8; P<.001). The link between early elevated C3a levels and adverse pregnancy outcomes was driven primarily by individual significant (P<.05) associations of C3a with hypertensive diseases of pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION Elevated C3a as early as the first trimester of pregnancy is an independent predictive factor for adverse pregnancy outcomes, suggesting that complement-related inflammatory events in pregnancy contribute to the subsequent development of poor outcomes at later stages of pregnancy. PMID:21173647

  9. INVESTIGATING ALTERNATIVES TO THE FISH EARLY-LIFE STAGE TEST: A STRATEGY FOR DISCOVERING AND ANNOTATING ADVERSE OUTCOME PATHWAYS FOR EARLY FISH DEVELOPMENT

    PubMed Central

    Villeneuve, Daniel; Volz, David C; Embry, Michelle R; Ankley, Gerald T; Belanger, Scott E; Léonard, Marc; Schirmer, Kristin; Tanguay, Robert; Truong, Lisa; Wehmas, Leah

    2014-01-01

    The fish early-life stage (FELS) test (Organisation for Economic Co-operation and Development [OECD] test guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an ongoing effort to develop efficient and cost-effective alternatives to the FELS test, there is a need to identify and describe potential adverse outcome pathways (AOPs) relevant to FELS toxicity. To support this endeavor, the authors outline and illustrate an overall strategy for the discovery and annotation of FELS AOPs. Key events represented by major developmental landmarks were organized into a preliminary conceptual model of fish development. Using swim bladder inflation as an example, a weight-of-evidence–based approach was used to support linkage of key molecular initiating events to adverse phenotypic outcomes and reduced young-of-year survival. Based on an iterative approach, the feasibility of using key events as the foundation for expanding a network of plausible linkages and AOP knowledge was explored and, in the process, important knowledge gaps were identified. Given the scope and scale of the task, prioritization of AOP development was recommended and key research objectives were defined relative to factors such as current animal-use restrictions in the European Union and increased demands for fish toxicity data in chemical management programs globally. The example and strategy described are intended to guide collective efforts to define FELS-related AOPs and develop resource-efficient predictive assays that address the toxicological domain of the OECD 210 test. Environ Toxicol Chem 2014;33:158–169. © 2013 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any

  10. The influence of the built environment on adverse birth outcomes.

    PubMed

    Woods, N; Gilliland, J; Seabrook, J A

    2017-01-01

    Adverse birth outcomes are associated with neonatal morbidity and mortality, and higher risk for coronary heart disease, non-insulin-dependent diabetes and hypertension in adulthood. Although there has been considerable research investigating the association between maternal and environmental factors on adverse birth outcomes, one risk factor, not fully understood, is the influence of the built environment. A search of MEDLINE, Scopus, and Cochrane was conducted to find articles assessing the influence of the built environment on preterm birth (PTB), low birth weight (LBW), and small-for-gestational-age (SGA). In total, 41 studies met our inclusion criteria, and were organized into nine categories: Roadways, Greenness, Power Plants, Gas Stations/Wells, Waste Management, Power Lines, Neighborhood Conditions, Food Environment, and Industry. The most common built environmental variable was roads/traffic, encompassing 17/41 (41%) of the articles reviewed, of which 12/17 (71%) found a significant small to moderate association between high traffic exposure and adverse birth outcomes.

  11. Adverse effects of anticancer agents that target the VEGF pathway.

    PubMed

    Chen, Helen X; Cleck, Jessica N

    2009-08-01

    Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an important part of standard therapy in multiple cancer indications. With expanded clinical experience with this class of agents has come the increasing recognition of the diverse adverse effects related to disturbance of VEGF-dependent physiological functions and homeostasis in the cardiovascular and renal systems, as well as wound healing and tissue repair. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences, particularly in high-risk patients and in certain clinical settings. This Review examines the toxicity profiles of anti-VEGF antibodies and small-molecule inhibitors. The potential mechanisms of the adverse effects, risk factors, and the implications for selection of patients and management are discussed.

  12. Social capital and adverse treatment outcomes of tuberculosis: a case-control study.

    PubMed

    Deshmukh, P R; Mundra, A; Dawale, A

    2017-08-01

    'Social capital' refers to social norms, relationships, networks and values that affect the functioning and development of society. Social capital influences health positively, but its role in the treatment outcomes of tuberculosis (TB) is not known. To study the role of social capital in determining adverse TB treatment outcomes. Of 516 patients registered under the Revised National Tuberculosis Control Programme in 2014 in Wardha Tuberculosis Unit, Wardha, India, we included 88 patients with adverse treatment outcomes as cases and 187 controls from among those without adverse outcomes. Multiple logistic regression was used to compare standardised Z-scores. A greater proportion of controls than cases belonged to higher quartiles of social capital and its domains than cases, and the mean standardised Z-score was also consistently higher among controls than cases. Respectively 47% and 15% of cases and controls were in the poorest quartile of social capital, whereas respectively 10% and 33% of cases and controls were in the richest quartile. Each unit increase in Z-score of overall social capital reduced the odds of adverse treatment outcomes by 63.1%. Appropriate interventions for building social capital for TB patients and linking them with the programme would improve programme performance.

  13. Adverse outcome pathways (AOPs): A framework to support predictive toxicology (presentation)

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  14. Embryonic vascular disruption adverse outcomes: Linking high-throughput signaling signatures with functional consequences.

    PubMed

    Ellis-Hutchings, Robert G; Settivari, Raja S; McCoy, Alene T; Kleinstreuer, Nicole; Franzosa, Jill; Knudsen, Thomas B; Carney, Edward W

    2017-04-13

    Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High-throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences.

    PubMed

    Ellis-Hutchings, Robert G; Settivari, Raja S; McCoy, Alene T; Kleinstreuer, Nicole; Franzosa, Jill; Knudsen, Thomas B; Carney, Edward W

    2017-06-01

    Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. A thick placenta: a predictor of adverse pregnancy outcomes.

    PubMed

    Miwa, Ichiro; Sase, Masakatsu; Torii, Mayumi; Sanai, Hiromi; Nakamura, Yasuhiko; Ueda, Kazuyuki

    2014-01-01

    The aim of this study is to evaluate the efficacy of an ultrasonographic measurement of placental thickness and the correlation of a thick placenta with adverse perinatal outcome. Placental thickness was measured in single gravidas, 16 to 40 weeks of gestation, between 2005 and 2009. Placentas were considered to be thick if their measured thickness were above the 95th percentile for gestational age. The incidence of thick placentas was 4.3% (138/3,183). Perinatal morbidity and neonatal conditions were worse in cases with thick placenta rather than without thick placenta. Ultrasonographic measurement of placental thickness is a simple method to estimate placental size. Thick placenta may be a useful predictor of adverse pregnancy outcomes.

  17. Applicability of a high-throughput shotgun plasma protein screening approach in understanding maternal biological pathways relevant to infant birth weight outcome.

    PubMed

    Kumarathasan, P; Vincent, R; Das, D; Mohottalage, S; Blais, E; Blank, K; Karthikeyan, S; Vuong, N Q; Arbuckle, T E; Fraser, W D

    2014-04-04

    There are reports linking maternal nutritional status, smoking and environmental chemical exposures to adverse pregnancy outcomes. However, biological bases for association between some of these factors and birth outcomes are yet to be established. The objective of this preliminary work is to test the capability of a new high-throughput shotgun plasma proteomic screening in identifying maternal changes relevant to pregnancy outcome. A subset of third trimester plasma samples (N=12) associated with normal and low-birth weight infants were fractionated, tryptic-digested and analyzed for global proteomic changes using a MALDI-TOF-TOF-MS methodology. Mass spectral data were mined for candidate biomarkers using bioinformatic and statistical tools. Maternal plasma profiles of cytokines (e.g. IL8, TNF-α), chemokines (e.g. MCP-1) and cardiovascular endpoints (e.g. ET-1, MMP-9) were analyzed by a targeted approach using multiplex protein array and HPLC-Fluorescence methods. Target and global plasma proteomic markers were used to identify protein interaction networks and maternal biological pathways relevant to low infant birth weight. Our results exhibited the potential to discriminate specific maternal physiologies relevant to risk of adverse birth outcomes. This proteomic approach can be valuable in understanding the impacts of maternal factors such as environmental contaminant exposures and nutrition on birth outcomes in future work. We demonstrate here the fitness of mass spectrometry-based shot-gun proteomics for surveillance of biological changes in mothers, and for adverse pathway analysis in combination with target biomarker information. This approach has potential for enabling early detection of mothers at risk for low infant birth weight and preterm birth, and thus early intervention for mitigation and prevention of adverse pregnancy outcomes. This article is part of a Special Issue entitled: Can Proteomics Fill the Gap Between Genomics and Phenotypes? Copyright

  18. Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study.

    PubMed

    Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

    2017-08-15

    Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Retrospective cohort study. Primary care practices affiliated with 2 academic medical centers. Patients with a presumed adverse reaction to a statin between 2000 and 2011. Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College

  19. The Associations Between Air Pollution and Adverse Pregnancy Outcomes in China.

    PubMed

    Tan, Yafei; Yang, Rong; Zhao, Jinzhu; Cao, Zhongqiang; Chen, Yawen; Zhang, Bin

    2017-01-01

    Research on the potential impact of air pollution on the human's health has increased rapidly in recent years. Several studies have suggested that exposure to air pollutants during period of pregnancy which is a crucial time point of mother-fetus development may have long-term and serious impact on adverse pregnancy outcomes. There is lack of review to evaluate the existed epidemiologic evidence on the associations between air pollutants and adverse pregnancy outcomes in China, so we conducted a review to explore the current epidemiological evidence on the effects of air pollutants to pregnancy outcomes and possible mechanisms during the pregnancy process. We used keywords to systematically search all the English and Chinese literatures on studies that were conducted in China. Exposure to air pollutants during pregnancy had shown there were harmful effects for different birth outcomes: preterm birth, low birth weight, stillbirth, birth defects, infertility, and macrosomia fetus. Results on the effects of air pollutants on adverse pregnancy outcomes are small and inconsistent because they vary in their design and methodology. The existed available evidence is compatible with either a small negative effect of air pollutants on pregnancy outcomes or with no effect; therefore, further studies are needed to confirm and quantify the possible associations and potential biologic mechanisms between air pollutants and pregnancy outcomes.

  20. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome.

    PubMed

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-07-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome.

  1. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome

    PubMed Central

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-01-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  2. Elevated risk of adverse obstetric outcomes in pregnant women with depression.

    PubMed

    Kim, Deborah R; Sockol, Laura E; Sammel, Mary D; Kelly, Caroline; Moseley, Marian; Epperson, C Neill

    2013-12-01

    In this study, we evaluated the association between prenatal depression symptoms adverse birth outcomes in African-American women. We conducted a retrospective cohort study of 261 pregnant African-American women who were screened with the Edinburgh Postnatal Depression Scale (EPDS) at their initial prenatal visit. Medical records were reviewed to assess pregnancy and neonatal outcomes, specifically preeclampsia, preterm birth, intrauterine growth retardation, and low birth weight. Using multivariable logistic regression models, an EPDS score ≥10 was associated with increased risk for preeclampsia, preterm birth, and low birth weight. An EPDS score ≥10 was associated with increased risk for intrauterine growth retardation, but after controlling for behavioral risk factors, this association was no longer significant. Patients who screen positive for depression symptoms during pregnancy are at increased risk for multiple adverse birth outcomes. In a positive, patient-rated depression screening at the initial obstetrics visit, depression is associated with increased risk for multiple adverse birth outcomes. Given the retrospective study design and small sample size, these findings should be confirmed in a prospective cohort study.

  3. Integrated Approaches to Testing and Assessment: OECD Activities on the Development and Use of Adverse Outcome Pathways and Case Studies.

    PubMed

    Sakuratani, Yuki; Horie, Masashi; Leinala, Eeva

    2018-01-09

    The Organisation for Economic Co-operation and Development (OECD) works with member countries and other stakeholders to improve and harmonize chemical assessment methods. In 2012, the OECD Adverse Outcome Pathways (AOPs) Development Programme started. The Programme has published six AOPs thus far and more than 60 AOPs are under various stages of development under the Programme. This article reviews recent OECD activities on the use of AOPs in developing Integrated Approaches to Testing and Assessments (IATAs). The guidance document for the use of AOPs in developing IATA, published in 2016, provides a framework for developing and using IATA and describes how IATA can be based on an AOP. The guidance document on the reporting of defined approaches to be used within IATA, also published in 2016, provides a set of principles for reporting defined approaches to testing and assessment to facilitate their evaluation. In the guidance documents, the AOP concept plays an important role for building IATA approaches in a science-based and transparent way. In 2015, the IATA Case Studies Project was launched to increase experience with the use of IATA and novel hazard methodologies by developing case studies, which constitute examples of predictions that are fit-for-regulatory use. This activity highlights the importance of international collaboration for harmonizing and improving chemical safety assessment methods. © 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  4. Chemical-agnostic hazard prediction: statistical inference of in vitro toxicity pathways from proteomics responses to chemical mixtures

    EPA Science Inventory

    Toxicity pathways have been defined as normal cellular pathways that, when sufficiently perturbed as a consequence of chemical exposure, lead to an adverse outcome. If an exposure alters one or more normal biological pathways to an extent that leads to an adverse toxicity outcome...

  5. Pregnancy loss history at first parity and selected adverse pregnancy outcomes.

    PubMed

    Ahrens, Katherine A; Rossen, Lauren M; Branum, Amy M

    2016-07-01

    To evaluate the association between pregnancy loss history and adverse pregnancy outcomes. Pregnancy history was captured during a computer-assisted personal interview for 21,277 women surveyed in the National Survey of Family Growth (1995-2013). History of pregnancy loss (<20 weeks) at first parity was categorized in three ways: number of losses, maximum gestational age of loss(es), and recency of last pregnancy loss. We estimated risk ratios for a composite measure of selected adverse pregnancy outcomes (preterm, stillbirth, or low birthweight) at first parity and in any future pregnancy, separately, using predicted margins from adjusted logistic regression models. At first parity, compared with having no loss, having 3+ previous pregnancy losses (adjusted risk ratio (aRR) = 1.66 [95% CI = 1.13, 2.43]), a maximum gestational age of loss(es) at ≥10 weeks (aRR = 1.28 [1.04, 1.56]) or having experienced a loss 24+ months ago (aRR = 1.36 [1.10, 1.68]) were associated with increased risks of adverse pregnancy outcomes. For future pregnancies, only having a history of 3+ previous pregnancy losses at first parity was associated with increased risks (aRR = 1.97 [1.08, 3.60]). Number, gestational age, and recency of pregnancy loss at first parity were associated with adverse pregnancy outcomes in U.S. women. Published by Elsevier Inc.

  6. Adverse Perinatal Outcomes among Immigrant Women from Ethiopia in Israel.

    PubMed

    Calderon-Margalit, Ronit; Sherman, Dan; Manor, Orly; Kurzweil, Yaffa

    2015-06-01

    Immigration from Ethiopia to Israel started about 30 years ago. We aimed to compare birth outcomes between Israeli women of Ethiopian origin and Israeli-born, non-Ethiopian women. We hypothesized a higher frequency of adverse birth outcomes among Ethiopian women and a trend of improvement among those who were raised in Israel since early childhood. This is a descriptive study, comparing birth outcomes of Ethiopian (n = 1,319) and non-Ethiopian women (n = 27,307) who gave birth in a medical center in Central Israel in 2002 to 2009. Ethiopian women were further categorized by age at immigration. Logistic regressions were constructed to compare the incidence of adverse birth outcomes between Ethiopian and non-Ethiopian women, controlling for potential confounders. Ethiopian women had about twice the incidence of very and extremely preterm births, compared with non-Ethiopians. Ethiopian women had twice the odds for neonates who were either small for gestational age or had low 5-minute Apgar scores. Ethiopian women had about threefold increased risk of stillbirths (OR 2.9 [95% CI 1.87-4.49]). No trend of improvement was noted for women who were raised in Israel from early childhood. Ethiopian women are at increased risk of adverse birth outcomes. Future research is needed to investigate the underlying causes for the increased risks and lack of improvement among those who were raised in Israel that will lead to effective interventions. © 2015 Wiley Periodicals, Inc.

  7. Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

    PubMed

    Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

    2018-02-01

    Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

  8. Dental neglect and adverse birth outcomes: a validation and observational study.

    PubMed

    Acharya, S; Pentapati, K C; Bhat, P V

    2013-05-01

    The objectives of this study were to validate the Indian translation of the Dental Neglect Scale (DNS) among a sample of parturient Indian women and to investigate dental neglect as a possible risk indicator in adverse birth outcomes. Three hundred and sixteen parturient women were administered the DNS and the Modified Dental Beliefs Scale (MDBS) and were also clinically examined for oral health status. Information regarding socio-economic status, weeks of gestation and birth weight was also collected. A gestation period of less than 37 weeks was considered as preterm and a birth weight of less than 2500 gm as 'low birth weight'. The Indian version of the DNS was found to be reliable (Cronbach's Alpha = 0.72) and valid for assessing dental neglect among the women. Factor analysis of the DNS revealed a two-factor structure accounting for 56% variance. Dental neglect was higher among those with poorer oral health status, lower socio-economic and educational status. Multinomial logistic regression showed high dental neglect and negative dental beliefs and not poor oral health, as significant risk indicators for occurrence of adverse birth outcomes. The finding of an association of adverse birth outcomes with dental neglect and beliefs, but not with poor oral health could be due to the influence of other more important general factors which had a direct bearing on birth outcomes. There is a need for further research to assess the role of behavioural factors like dental neglect as risk indicators for adverse birth outcomes. © 2012 John Wiley & Sons A/S.

  9. Two pathways through adversity: Predicting well-being and housing outcomes among homeless service users.

    PubMed

    Walter, Zoe C; Jetten, Jolanda; Dingle, Genevieve A; Parsell, Cameron; Johnstone, Melissa

    2016-06-01

    People who experience homelessness face many challenges and disadvantages that negatively impact health and well-being and form barriers to achieving stable housing. Further, people who are homeless often have limited social connections and support. Building on previous research that has shown the beneficial effect of group identification on health and well-being, the current study explores the relationship between two social identity processes - multiple group memberships and service identification - and well-being and positive housing outcomes. Measures were collected from 76 participants while they were residing in a homeless accommodation service (T1) and again 2-4 weeks after leaving the service (or 3 months after T1 if participants had not left the service). Mediation analyses revealed that multiple group memberships and service identification at T1 independently predicted well-being at T2 indirectly, via social support. Further, both social identity processes also indirectly predicted housing outcomes via social support. The implications of these findings are twofold. First, while belonging to multiple social groups may provide a pathway to gaining social support and well-being, group belonging may not necessarily be beneficial to achieve stable housing. Second, fostering identification with homeless services may be particularly important as a source of support that contributes to well-being. © 2015 The British Psychological Society.

  10. Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy.

    PubMed

    Sachs, Adam; Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

    2017-05-01

    Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9 points). Approximately 5% of women experience adverse obstetrical outcomes after appendectomy

  11. Maternal psychological distress during pregnancy does not increase the risk for adverse birth outcomes.

    PubMed

    Staneva, Aleksandra A; Morawska, Alina; Bogossian, Fiona; Wittkowski, Anja

    2018-01-01

    Maternal psychological distress during pregnancy is a potential risk factor for various birth complications. This study aimed to explore psychological factors associated with adverse birth outcomes. Symptoms of psychological distress, individual characteristics, and medical complications were assessed at two time points antenatally in 285 women from Australia and New Zealand; birth outcomes were assessed postpartum, between January 2014 and September 2015. Hierarchical multiple regression analyses were conducted to examine the relation of psychological distress to adverse birth outcomes. Medical complications during pregnancy, such as serious infections, placental problems and preeclampsia, and antenatal cannabis use, were the factors most strongly associated with adverse birth outcomes, accounting for 22 percent of the total variance (p < .001). Symptoms of depression and/or anxiety, low social support, and low sense of coherence were not associated with birth complications. In unadjusted analyses, self-reported diagnosis of anxiety disorder during pregnancy and an orientation toward a Regulator mothering style were associated with adverse birth outcomes; however, after controlling for medical complications, these were no longer associated. Our study results indicate that antenatal depressive and/or anxiety symptoms were not independently associated with adverse birth outcomes, a reassuring finding for women who are already psychologically vulnerable during pregnancy.

  12. Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking

    PubMed Central

    Cornelius, Marie D.; De Genna, Natacha M.; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L.

    2016-01-01

    We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n = 917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

  13. Chemical exposure and infant leukaemia: development of an adverse outcome pathway (AOP) for aetiology and risk assessment research.

    PubMed

    Pelkonen, Olavi; Terron, Andrea; Hernandez, Antonio F; Menendez, Pablo; Bennekou, Susanne Hougaard

    2017-08-01

    Infant leukaemia (<1 year old) is a rare disease of an in utero origin at an early phase of foetal development. Rearrangements of the mixed-lineage leukaemia (MLL) gene producing abnormal fusion proteins are the most frequent genetic/molecular findings in infant B cell-acute lymphoblastic leukaemia. In small epidemiological studies, mother/foetus exposures to some chemicals including pesticides have been associated with infant leukaemia; however, the strength of evidence and power of these studies are weak at best. Experimental in vitro or in vivo models do not sufficiently recapitulate the human disease and regulatory toxicology studies are unlikely to capture this kind of hazard. Here, we develop an adverse outcome pathway (AOP) based substantially on an analogous disease-secondary acute leukaemia caused by the topoisomerase II (topo II) poison etoposide-and on cellular and animal models. The hallmark of the AOP is the formation of MLL gene rearrangements via topo II poisoning, leading to fusion genes and ultimately acute leukaemia by global (epi)genetic dysregulation. The AOP condenses molecular, pathological, regulatory and clinical knowledge in a pragmatic, transparent and weight of evidence-based framework. This facilitates the interpretation and integration of epidemiological studies in the process of risk assessment by defining the biologically plausible causative mechanism(s). The AOP identified important gaps in the knowledge relevant to aetiology and risk assessment, including the specific embryonic target cell during the short and spatially restricted period of susceptibility, and the role of (epi)genetic features modifying the initiation and progression of the disease. Furthermore, the suggested AOP informs on a potential Integrated Approach to Testing and Assessment to address the risk caused by environmental chemicals in the future.

  14. Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

    PubMed Central

    Goetzl, Laura

    2010-01-01

    Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

  15. Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy

    PubMed Central

    Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

    2017-01-01

    Importance Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. Objectives To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. Design, Setting, and Participants A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. Main Outcomes and Measures A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Results Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9

  16. Racial Discrimination and Adverse Birth Outcomes: An Integrative Review.

    PubMed

    Alhusen, Jeanne L; Bower, Kelly M; Epstein, Elizabeth; Sharps, Phyllis

    2016-11-01

    This article presents an integrative review of the literature examining the relationship between racial discrimination and adverse birth outcomes. Searches for research studies published from 2009 to 2015 were conducted using PubMed, CINAHL, Scopus, PsycINFO, Web of Science, and Embase. Articles were assessed for potential inclusion using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 framework. Fifteen studies met criteria for review. The majority of the studies found a significant relationship between racial discrimination and low birth weight, preterm birth, and small for gestational age. Each of the studies that examined more proximal variables related to birth outcomes such as entry into prenatal care, employment opportunities, neighborhood characteristics, or inflammatory markers found significant associations between the specific variables examined and racial discrimination. Participants in qualitative studies discussed experiences of institutional racism with regard to several components of prenatal care including access and quality of care. Racial discrimination is a significant risk factor for adverse birth outcomes. To best understand the mechanisms by which racial discrimination impacts birth outcomes, and to inform the development of effective interventions that eliminate its harmful effects on health, longitudinal research that incorporates comprehensive measures of racial discrimination is needed. Health care providers must fully acknowledge and address the psychosocial factors that impact health outcomes in minority racial/ethnic women. © 2016 by the American College of Nurse-Midwives.

  17. Racial Discrimination and Adverse Birth Outcomes: An Integrative Review

    PubMed Central

    Alhusen, Jeanne L.; Bower, Kelly; Epstein, Elizabeth; Sharps, Phyllis

    2016-01-01

    Introduction This article presents an integrative review of the literature examining the relationship between racial discrimination and adverse birth outcomes. Methods Searches for research studies published from 2009 to 2015 were conducted using PubMed, CINAHL, Scopus, PsycINFO, Web of Science, and Embase. Articles were assessed for potential inclusion using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 framework. Results Fifteen studies met criteria for review. The majority of the studies found a significant relationship between racial discrimination and low birth weight, preterm birth, and small for gestational age. Each of the studies that examined more proximal variables related to birth outcomes such as entry into prenatal care, employment opportunities, neighborhood characteristics, or inflammatory markers found significant associations between the specific variables examined and racial discrimination. Participants in qualitative studies discussed experiences of institutional racism with regard to several components of prenatal care including access and quality of care. Discussion Racial discrimination is a significant risk factor for adverse birth outcomes. To best understand the mechanisms by which racial discrimination impacts birth outcomes, and to inform the development of effective interventions that eliminate its harmful effects on health, longitudinal research that incorporates comprehensive measures of racial discrimination is needed. Health care providers must fully acknowledge and address the psychosocial factors that impact health outcomes in minority racial/ethnic women. PMID:27737504

  18. [Chorionicity and adverse perinatal outcome].

    PubMed

    Ferreira, Isabel; Laureano, Carla; Branco, Miguel; Nordeste, Ana; Fonseca, Margarida; Pinheiro, Adelaide; Silva, Maria Isabel; Almeida, Maria Céu

    2005-01-01

    Considering the highest rate of morbidity and mortality in diamniotic monochorionic twins, the authors evaluated and compared the adverse obstetric and perinatal outcome in twin pregnancies according to chorionicity. A retrospective study was conducted in all twin deliveries that occurred in the Obstetric Unit of Maternidade Bissaya-Barreto, for a period of tree years (from the 1st of January 1999 until the 31st of December 2001). From de 140 diamniotic twin pregnancies studied, we considered two groups according to the chorionicity: monochorionic and dichorionic. We compared multiple parameters as, epidemiologic data, adverse obstetric outcome, gestacional delivery age, type of delivery and the morbidity, the mortality and the follow-up of the newborn. The statistic tests used were the X2 and the t student. From the 140 twin pregnancies included in the study, 66% (92 cases) presented dichorionic placentation and 34% (48 cases) were monochorionic. In the group of monochorionic pregnancies, we observed highly difference related to pathology of amniotic fluid (14.5% vs 2.2%), discordant fetal growth (41.6% vs 22.8%) and rate of preterm delivery (66.6% vs 32.6%). Related to the newborn we verified that they had a lower average birth weight (1988g vs 2295g), a highly rate of weight discordancy (23% vs 15.3%), intraventricular haemorrhage (2.2% vs 0%) and IUGR (6.6% vs 1.6%), statistically significant in the monochorionic group. Also the perinatal mortality rate was significantly higher in the monochorionic pregnancies (93.7 per thousand vs 21.7 per thousand). The high rate of morbidity and mortality related to the monochorionic twin pregnancies, implies the need of a correct identification of the type of chorionicity and also a high standard of prenatal surveillance in prenatal specialised health centers.

  19. p38 Mitogen Activated Protein Kinase (MAPK): A New Therapeutic Target for Reducing the Risk of Adverse Pregnancy Outcomes

    PubMed Central

    Menon, Ramkumar; Papaconstantinou, John

    2016-01-01

    Introduction Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert Opinion This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation and its functional effects. PMID:27459026

  20. Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

    PubMed Central

    Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

    2014-01-01

    Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

  1. ADVERSE PREGNANCY OUTCOMES ASSOCIATED WITH MATERNAL ENALAPRIL ANTIHYPERTENSIVE TREATMENT

    EPA Science Inventory

    Enalapril, one of several antihypertensive drugs that act as angiotensin-converting enzyme (ACE) inhibitors, is often used for treatment of hypertension in women of reproductive age. Adverse birth outcomes following the use of ACE inhibitors, including enalapril, during pregnanc...

  2. Predicting adverse neonatal outcomes in fetuses with abdominal wall defects using prenatal risk factors.

    PubMed

    Nicholas, Sara S; Stamilio, David M; Dicke, Jeffery M; Gray, Diana L; Macones, George A; Odibo, Anthony O

    2009-10-01

    The aim of this study was to determine whether prenatal variables can predict adverse neonatal outcomes in fetuses with abdominal wall defects. A retrospective cohort study that used ultrasound and neonatal records for all cases of gastroschisis and omphalocele seen over a 16-year period. Cases with adverse neonatal outcomes were compared with noncases for multiple candidate predictive factors. Univariable and multivariable statistical methods were used to develop the prediction models, and effectiveness was evaluated using the area under the receiver operating characteristic curve. Of 80 fetuses with gastroschisis, 29 (36%) had the composite adverse outcome, compared with 15 of 33 (47%) live neonates with omphalocele. Intrauterine growth restriction was the only significant variable in gastroschisis, whereas exteriorized liver was the only predictor in omphalocele. The areas under the curve for the prediction models with gastroschisis and omphalocele are 0.67 and 0.74, respectively. Intrauterine growth restriction and exteriorization of the liver are significant predictors of adverse neonatal outcome with gastroschisis and omphalocele.

  3. Does early second-trimester sonography predict adverse perinatal outcomes in monochorionic diamniotic twin pregnancies?

    PubMed

    Allaf, M Baraa; Campbell, Winston A; Vintzileos, Anthony M; Haeri, Sina; Javadian, Pouya; Shamshirsaz, Amir A; Ogburn, Paul; Figueroa, Reinaldo; Wax, Joseph; Markenson, Glenn; Chavez, Martin R; Ravangard, Samadh F; Ruano, Rodrigo; Sangi-Haghpeykar, Haleh; Salmanian, Bahram; Meyer, Marjorie; Johnson, Jeffery; Ozhand, Ali; Davis, Sarah; Borgida, Adam; Belfort, Michael A; Shamshirsaz, Alireza A

    2014-09-01

    To determine whether intertwin discordant abdominal circumference, femur length, head circumference, and estimated fetal weight sonographic measurements in early second-trimester monochorionic diamniotic twins predict adverse obstetric and neonatal outcomes. We conducted a multicenter retrospective cohort study involving 9 regional perinatal centers in the United States. We examined the records of all monochorionic diamniotic twin pregnancies with two live fetuses at the 16- to 18-week sonographic examination who had serial follow-up sonography until delivery. The intertwin discordance in abdominal circumference, femur length, head circumference, and estimated fetal weight was calculated as the difference between the two fetuses, expressed as a percentage of the larger using the 16- to 18-week sonographic measurements. An adverse composite obstetric outcome was defined as the occurrence of 1 or more of the following in either fetus: intrauterine growth restriction, twin-twin transfusion syndrome, intrauterine fetal death, abnormal growth discordance (≥20% difference), and very preterm birth at or before 28 weeks. An adverse composite neonatal outcome was defined as the occurrence of 1 or more of the following: respiratory distress syndrome, any stage of intraventricular hemorrhage, 5-minute Apgar score less than 7, necrotizing enterocolitis, culture-proven early-onset sepsis, and neonatal death. Receiver operating characteristic and logistic regression-with-generalized estimating equation analyses were constructed. Among the 177 monochorionic diamniotic twin pregnancies analyzed, intertwin abdominal circumference and estimated fetal weight discordances were only predictive of adverse composite obstetric outcomes (areas under the curve, 79% and 80%, respectively). Receiver operating characteristic curves showed that intertwin discordances in abdominal circumference, femur length, head circumference, and estimated fetal weight were not acceptable predictors of twin

  4. [Adverse pregnancy outcomes after Assisted Reproduction Technology in women with endometriosis].

    PubMed

    Carassou-Maillan, A; Pouly, J-L; Mulliez, A; Dejou-Bouillet, L; Gremeau, A-S; Brugnon, F; Janny, L; Canis, M

    2014-04-01

    While association between endometriosis and infertility is well established, there are few studies about the impact of endometriosis on adverse pregnancy outcomes. The aim of this study was to determine the effect of endometriosis on obstetric outcomes and whether the severity of the disease had an influence on these. We performed a retrospective study to investigate the obstetric outcomes of a population of 1204 subfertile women, including 258 with endometriosis, who obtained, thanks to assisted reproduction technology, a singleton pregnancy evolving beyond embryonic stage. Two analyzes were performed. The first compared women with endometriosis to women with other causes of infertility. The second observed adverse pregnancy outcomes according to AFS-R stages of endometriosis. The overall rate of live birth children was 95.8%. In case of endometriosis, there was a significant increase of the incidence of preterm delivery, especially before 32 weeks amenorrhea (6.2% vs 3.1% in the group "without endometriosis", P = 0.03), antenatal bleeding (5.3% vs 2.2%, P = 0.01) and placenta previa (4.9% vs 0.9%, P < 0.0001). The incidence of gestational diabetes was significantly decreased (0.4% vs 2.7%, P = 0.04). There was no correlation between endometriosis and cesarean section or preeclampsia, or between the AFS-R stage and adverse pregnancy outcomes. Endometriosis is a factor of obstetrical risk, independently of the infertility it causes. The AFS-R score does not seem to be representative of obstetric outcomes beyond first trimester of pregnancy for women with endometriosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.

    PubMed

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    PubMed

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  7. Association of maternal periodontal health with adverse pregnancy outcome.

    PubMed

    Kumar, Ashok; Basra, Minu; Begum, Nargis; Rani, Vigya; Prasad, Sudha; Lamba, Arundeep Kaur; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

    2013-01-01

    The present study aims to determine the association of periodontal disease (identified early in pregnancy) and adverse pregnancy outcomes in a North Indian population.   A total of 340 primigravida women, aged 20-35 years with single live pregnancy were recruited at 14-20 weeks period of gestation from the antenatal clinic. These women had undergone periodontal examination at time of recruitment. The pregnancy outcomes were recorded. Out of 340 primigravida women, 147 (43.23%) women had gingivitis and 61 (17.94%) women had periodontitis. Periodontitis was found to be significantly associated with pre-eclampsia, intrauterine growth restriction, preterm delivery, and low birthweight with odds ratios (95% confidence interval) of 7.48 (2.72-22.42), 3.35 (1.20-9.55), 2.72 (1.30-5.68) and 3.03 (1.53-5.97), respectively. The study shows a significant association between periodontitis (but not with gingivitis) and adverse pregnancy outcomes. Maternal periodontitis is associated with an increased risk of pre-eclampsia, intrauterine growth restriction, preterm delivery and low birthweight infants. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  8. Maternal language and adverse birth outcomes in a statewide analysis.

    PubMed

    Sentell, Tetine; Chang, Ann; Ahn, Hyeong Jun; Miyamura, Jill

    2016-01-01

    Limited English proficiency is associated with disparities across diverse health outcomes. However, evidence regarding adverse birth outcomes across languages is limited, particularly among U.S. Asian and Pacific Islander populations. The study goal was to consider the relationship of maternal language to birth outcomes using statewide hospitalization data. Detailed discharge data from Hawaii childbirth hospitalizations from 2012 (n = 11,419) were compared by maternal language (English language or not) for adverse outcomes using descriptive and multivariable log-binomial regression models, controlling for race/ethnicity, age group, and payer. Ten percent of mothers spoke a language other than English; 93% of these spoke an Asian or Pacific Islander language. In multivariable models, compared to English speakers, non-English speakers had significantly higher risk (adjusted relative risk [ARR]: 2.02; 95% confidence interval [CI]: 1.34-3.04) of obstetric trauma in vaginal deliveries without instrumentation. Some significant variation was seen by language for other birth outcomes, including an increased rate of primary Caesarean sections and vaginal births after Caesarean, among non-English speakers. Non-English speakers had approximately two times higher risk of having an obstetric trauma during a vaginal birth when other factors, including race/ethnicity, were controlled. Non-English speakers also had higher rates of potentially high-risk deliveries.

  9. The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory.

    PubMed

    Levens, Sara M; Armstrong, Laura Marie; Orejuela-Dávila, Ana I; Alverio, Tabitha

    2017-09-01

    Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity.

  10. The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study.

    PubMed

    Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Ko, Chih-Hung

    2008-05-01

    Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome.

  11. Cytomegalovirus seroprevalence in pregnant women and association with adverse pregnancy/neonatal outcomes in Jiangsu Province, China.

    PubMed

    Zhang, Shu; Hu, Lingqing; Chen, Jie; Xu, Biyun; Zhou, Yi-Hua; Hu, Yali

    2014-01-01

    In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China. In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15-20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes. The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01-6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes. In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes.

  12. Cytomegalovirus Seroprevalence in Pregnant Women and Association with Adverse Pregnancy/Neonatal Outcomes in Jiangsu Province, China

    PubMed Central

    Chen, Jie; Xu, Biyun; Zhou, Yi-Hua; Hu, Yali

    2014-01-01

    Background In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China. Methods In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15–20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes. Results The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01–6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes. Conclusions In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes. PMID:25211647

  13. Pathways Post-Participation Outcomes: Preliminary Findings. Carnegie Math Pathways Research Brief

    ERIC Educational Resources Information Center

    Norman, Jon

    2017-01-01

    The Carnegie Foundation for the Advancement of Teaching's Math Pathways seek to improve outcomes for community college students who take remedial math courses. The Pathways include two comprehensive instructional systems--Statway® and Quantaway® and are described in this report. They are designed to support students to achieve the necessary math…

  14. Revealing pathways from payments for ecosystem services to socioeconomic outcomes

    PubMed Central

    Zhang, Jindong

    2018-01-01

    Payments for ecosystem services (PES) programs have been widely implemented as a promising tool to conserve ecosystems while facilitating socioeconomic development. However, the underlying pathways (or processes) through which PES programs affect socioeconomic outcomes remain elusive, and existing literature provides little guidance to quantify them. By integrating linkages among PES programs, livelihood activities, and socioeconomic outcomes, we develop a framework to reveal pathways from PES programs to socioeconomic outcomes. We empirically demonstrate the framework’s operationalization and uncover the pathways that lead to unexpected negative effects of two important PES programs on participating households’ income. With improved understanding of the pathways (for example, the programs decreased income through reducing crop production), we provide recommendations to enhance the PES programs’ outcomes in our demonstration site and beyond. Our study highlights the finding that elucidating the pathways from PES programs to their outcomes can help identify specific strategies to achieve ecosystem conservation and socioeconomic development simultaneously. PMID:29750187

  15. Adverse Pregnancy Outcomes Among Women with Prior Spontaneous or Induced Abortions

    PubMed Central

    Makhlouf, Michel A; Clifton, Rebecca G.; Roberts, James M.; Myatt, Leslie; Hauth, John C.; Leveno, Kenneth J.; Varner, Michael W.; Thorp, John M.; Mercer, Brian M.; Peaceman, Alan M.; Ramin, Susan M.; Iams, Jay D.; Sciscione, Anthony; Tolosa, Jorge E.; Sorokin, Yoram

    2014-01-01

    OBJECTIVE To determine whether prior spontaneous (SAB) or induced (IAB) abortions, or the inter-pregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared to primigravid participants. RESULTS Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (OR 1.5; 95% CI 1.1–2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (OR 2.6, 95% CI 1.7–4.0), preterm PROM (OR 2.9, 95% CI 1.6–5.3) and perinatal death (OR 2.8, 95% CI 1.5–5.3). Women with one previous IAB had higher rates of spontaneous preterm birth (OR 1.4, 95% CI 1.0–1.9) and preterm PROM (OR 2.0, 95% CI 1.4–3.0). An inter-pregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. PMID:24347257

  16. Frequency, Risk Factors, and Adverse Fetomaternal Outcomes of Placenta Previa in Northern Tanzania

    PubMed Central

    Senkoro, Elizabeth Eliet; Mwanamsangu, Amasha H.; Chuwa, Fransisca Seraphin; Msuya, Sia Emmanuel; Mnali, Oresta Peter

    2017-01-01

    Background and Objective. Placenta previa (PP) is a potential risk factor for obstetric hemorrhage, which is a major cause of fetomaternal morbidity and mortality in developing countries. This study aimed to determine frequency, risk factors, and adverse fetomaternal outcomes of placenta previa in Northern Tanzania. Methodology. A retrospective cohort study was conducted using maternally-linked data from Kilimanjaro Christian Medical Centre birth registry spanning 2000 to 2015. All women who gave birth to singleton infants were studied. Adjusted odds ratios (ORs) with 95% confidence intervals for risk factors and adverse fetomaternal outcomes associated with PP were estimated in multivariable logistic regression models. Result. A total of 47,686 singleton deliveries were analyzed. Of these, the frequency of PP was 0.6%. Notable significant risk factors for PP included gynecological diseases, alcohol consumption during pregnancy, malpresentation, and gravidity ≥5. Adverse maternal outcomes were postpartum haemorrhage, antepartum haemorrhage, and Caesarean delivery. PP increased odds of fetal Malpresentation and early neonatal death. Conclusion. The prevalence of PP was comparable to that found in past research. Multiple independent risk factors were identified. PP was found to have associations with several adverse fetomaternal outcomes. Early identification of women at risk of PP may help clinicians prevent such complications. PMID:28321338

  17. Urinary tract infection and adverse outcome of pregnancy.

    PubMed

    Dimetry, Shaira R; El-Tokhy, Hanan M; Abdo, Nagla M; Ebrahim, Moustafa A; Eissa, Mohammed

    2007-01-01

    Urinary tract infections (UTIs) during pregnancy are among the commonest health problems world wide, specially in developing countries, including Egypt. It has several adverse outcomes not only on the mother but also on the fetus as well.. The aim of this study is to determine the incidence of UTIs during pregnancy, study the main risk factors associated with such infections and find the impact of these infections on some pregnancy outcomes namely the gestational age and birth weight. A follow-up study on 249 pregnant women attending the ante natal care clinic at Zagazig university hospital. They were recruited over a period from 1st of September to 30th of or November, 2005. The outcome could be recorded for 201 of them. Data were collected through a pretested questionnaire, repeated urine analyses and recording of outcome of pregnancy. The study revealed that the incidence of UTIs during pregnancy was 31.3%. The commonest organisms were Klebsiella and E-coli. Several socio-demographic characteristics were found significantly associated with UTIs, age being 30 years and more, illiterates and low educational level, low socio-economic level and those with unsatisfactory personal hygiene and those using underwear clothes other than cotton. Significant associations with UTIs were also found in multigravidae 4th and more, those having more than one child and those who previously suffered UTIs. The only predicting variable with UTIs was low socio-economic level. The study revealed that the probability of delivering premature infants and low birth weights was significantly higher among those who experienced UTIs during pregnancy. Multivariate analysis revealed that UTI was one of the main contributors to pre-mature deliveries. Urinary tract infections with pregnancy still constitute a big problem with high incidence. It has a great impact on pregnancy outcome mainly pre-mature labor. So, the study recommends health education about personal hygiene, repeated urine

  18. Early Imaging and Adverse Neurodevelopmental Outcome in Asphyxiated Newborns Treated With Hypothermia.

    PubMed

    Al Amrani, Fatema; Kwan, Saskia; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

    2017-08-01

    Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years. Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome. Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter. Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

    PubMed Central

    Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

    2013-01-01

    Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

  20. Predictors of Adverse Cosmetic Outcome in the RAPID Trial: An Exploratory Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peterson, David; Truong, Pauline T.; Parpia, Sameer

    Purpose: To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. Methods and Materials: Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assessmore » the association of risk factors for these outcomes among all patients and those treated with APBI only. Results: Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. Conclusion: In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high

  1. Prenatal Depression and Adverse Birth Outcomes: An Updated Systematic Review

    PubMed Central

    Accortt, Eynav Elgavish; Cheadle, Alyssa C. D.; Schetter, Christine Dunkel

    2015-01-01

    Complications related to preterm birth (PTB) and low birth weight (LBW) are leading causes of infant morbidity and mortality. Prenatal depression is a hypothesized psychosocial risk factor for both birth outcomes. The purpose of this systematic review was to examine evidence published between 1977 and 2013 on prenatal depression and risks of these primary adverse birth outcomes. A systematic search of the PUBMED and PsycINFO databases was conducted to identify studies testing the associations between prenatal depressive symptoms, or diagnoses of depression, and risk of PTB or LBW. We systematically selected 50 published reports on PTB and length of gestation, and 33 reports on LBW and BW. Results were reviewed by two independent reviewers and we evaluated the quality of the evidence with an established systematic review method, the Newcastle Ottawa Scale. We then undertook a narrative synthesis of the results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Less than a quarter of 50 published reports found that prenatal depression was significantly associated with PTB or gestational age. In contrast, slightly more than half of the 33 reports found that prenatal depression was associated with LBW or BW. When weighing methodological features, we determined that the effects of prenatal depression on LBW are more consistent than effects on length of gestation or PTB. Although the evidence may not be strong enough to support routine depression screening for risk of adverse outcomes, screening to enable detection and timely treatment to reduce risk of postpartum depression is warranted. Further rigorous research on prenatal depression and adverse birth outcomes is needed. PMID:25452215

  2. Maternal Language and Adverse Birth Outcomes in a Statewide Analysis

    PubMed Central

    Sentell, Tetine; Chang, Ann; Jun Ahn, Hyeong; Miyamura, Jill

    2016-01-01

    Background Limited English proficiency is associated with disparities across diverse health outcomes. However, evidence regarding adverse birth outcomes across languages is limited, particularly among US Asian and Pacific Islander populations. The study goal was to consider the relationship of maternal language to birth outcomes using statewide hospitalization data. Methods Detailed discharge data from Hawai‘i childbirth hospitalizations from 2012 (n=11,419) were compared by maternal language (English language or not) for adverse outcomes using descriptive and multivariable log-binomial regression models, controlling for race/ethnicity, age group, and payer. Results Ten percent of mothers spoke a language other than English; 93% of these spoke an Asian or Pacific Islander language. In multivariable models, compared to English speakers non-English speakers had significantly higher risk (adjusted relative risk [ARR]: 2.02; 95% Confidence Interval [CI]: 1.34–3.04) of obstetric trauma in vaginal deliveries without instrumentation. Some significant variation was seen by language for other birth outcomes, including an increased rate of primary Caesarean sections and vaginal births after Caesarean among non-English speakers. Conclusions Non-English speakers had approximately two times higher risk of having an obstetric trauma during a vaginal birth when other factors, including race/ethnicity, were controlled. Non-English speakers also had higher rates of potentially high-risk deliveries. PMID:26361937

  3. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    PubMed Central

    Leung, Maxwell C.K.; Phuong, Jimmy; Baker, Nancy C.; Sipes, Nisha S.; Klinefelter, Gary R.; Martin, Matthew T.; McLaurin, Keith W.; Setzer, R. Woodrow; Darney, Sally Perreault; Judson, Richard S.; Knudsen, Thomas B.

    2015-01-01

    Background: Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies. Objective: In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system. Methods: We used U.S. EPA’s animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features. Results: A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network. Conclusion: Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s. Citation: Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male

  4. Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

    PubMed

    Makhlouf, Michel A; Clifton, Rebecca G; Roberts, James M; Myatt, Leslie; Hauth, John C; Leveno, Kenneth J; Varner, Michael W; Thorp, John M; Mercer, Brian M; Peaceman, Alan M; Ramin, Susan M; Iams, Jay D; Sciscione, Anthony; Tolosa, Jorge E; Sorokin, Yoram

    2014-10-01

    The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Magnitude of income-related disparities in adverse perinatal outcomes.

    PubMed

    Shankardass, Ketan; O'Campo, Patricia; Dodds, Linda; Fahey, John; Joseph, Ks; Morinis, Julia; Allen, Victoria M

    2014-03-04

    To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases.

  6. Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus: A Retrospective Cohort Study.

    PubMed

    Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

    2016-01-01

    Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach.

  7. Adverse pregnancy outcomes in women with systemic lupus erythematosus from a multiethnic US cohort: LUMINA (LVI) [corrected].

    PubMed

    Andrade, R; Sanchez, M L; Alarcón, G S; Fessler, B J; Fernández, M; Bertoli, A M; Apte, M; Vilá, L M; Arango, A M; Reveille, J D

    2008-01-01

    To study the factors associated with an adverse pregnancy outcome in women with systemic lupus erythematosus (SLE). SLE women from LUMINA of Hispanic, African American and Caucasian ethnicity were studied. Adverse pregnancy outcome was a miscarriage or abortion (<20 weeks), a stillbirth (> or = 20) and/or a moderate to severe preterm-baby (<34 weeks); good outcome was either a mild preterm-baby (> or = 34 weeks) or a full-term baby [C-section or vaginal delivery (38-42 weeks)]. Pregnancies occurring after SLE diagnosis (TD) were included; pregnancy outcome was the unit of analyses. The relationship between selected variables and pregnancy outcomes was examined by univariable and multivariable analyses. Adverse outcomes occurred in 63.7% of 102 pregnancies. In the univariable analyses, Texan Hispanic and African American ethnicities, fewer years of education, higher number of ACR criteria, renal involvement, glucocorticoid exposure and the maximum dose of glucocorticoids used prior to the pregnancy outcome were associated with an adverse pregnancy outcome. Renal involvement was independently associated with an adverse pregnancy outcome [Odds ratio (OR)=5.219 (95% Confidence Interval (CI) 1.416-19.239, p=0.0131] as were the maximum dose of glucocorticoids used prior to the pregnancy outcome (OR=1.028; CI:1.002-1.054; p=0.0315) and fewer years of education (OR=1.204; CI:1.006-1.472; p=0.0437). Ethnicity was not retained in the multivariable model. Renal involvement, the maximum dose of glucocorticoids used prior to pregnancy and fewer years of education were associated with adverse pregnancy outcomes. These data have implications for the management of women with lupus planning to become pregnant.

  8. Associations of neighborhood-level racial residential segregation with adverse pregnancy outcomes.

    PubMed

    Salow, Arturo D; Pool, Lindsay R; Grobman, William A; Kershaw, Kiarri N

    2018-03-01

    Previous analyses utilizing birth certificate data have shown environmental factors such as racial residential segregation may contribute to disparities in adverse pregnancy outcomes. However, birth certificate data are ill equipped to reliably differentiate among small for gestational age, spontaneous preterm birth, and medically indicated preterm birth. We sought to utilize data from electronic medical records to determine whether residential segregation among Black women is associated with an increased risk of adverse pregnancy outcomes. The study population was composed of 4770 non-Hispanic Black women who delivered during the years 2009 through 2013 at a single urban medical center. Addresses were geocoded at the level of census tract, and this tract was used to determine the degree of residential segregation for an individual's neighborhood. Residential segregation was measured using the Gi* statistic, a z-score that measures the extent to which the neighborhood racial composition deviates from the composition of the larger surrounding area. The Gi* statistic z-scores were categorized as follows: low (z < 0), medium (z = 0-1.96), and high (z > 1.96). Adverse pregnancy outcomes included overall preterm birth, spontaneous preterm birth, medically indicated preterm birth, and small for gestational age. Hierarchical logistic regression models accounting for clustering by census tract and repeated births among mothers were used to estimate odds ratios of adverse pregnancy outcomes associated with segregation. In high segregation areas, the prevalence of overall preterm birth was significantly higher than that in low segregation areas (15.5% vs 10.7%, respectively; P < .001). Likewise, the prevalence of spontaneous preterm birth and medically indicated preterm birth were higher in high (9.5% and 6.0%) vs low (6.2% and 4.6%) segregation neighborhoods (P < .001 and P = .046, respectively). The associations of high segregation with overall preterm birth (odds

  9. The Association between Rural-Urban Continuum, Maternal Education and Adverse Birth Outcomes in Quebec, Canada

    ERIC Educational Resources Information Center

    Auger, Nathalie; Authier, Marie-Andree; Martinez, Jerome; Daniel, Mark

    2009-01-01

    Context: Rural relative to urban area and low socioeconomic status (SES) are associated with adverse birth outcomes. Whether a graded association of increasing magnitude is present across the urban-rural continuum, accounting for SES, is unclear. We examined the association between rural-urban continuum, SES and adverse birth outcomes. Methods:…

  10. The Association Between Learning Climate and Adverse Obstetrical Outcomes in 16 Nontertiary Obstetrics-Gynecology Departments in the Netherlands.

    PubMed

    Smirnova, Alina; Ravelli, Anita C J; Stalmeijer, Renée E; Arah, Onyebuchi A; Heineman, Maas Jan; van der Vleuten, Cees P M; van der Post, Joris A M; Lombarts, Kiki M J M H

    2017-12-01

    To investigate the association between learning climate and adverse perinatal and maternal outcomes in obstetrics-gynecology departments. The authors analyzed 23,629 births and 103 learning climate evaluations from 16 nontertiary obstetrics-gynecology departments in the Netherlands in 2013. Multilevel logistic regressions were used to calculate the odds of adverse perinatal and maternal outcomes, by learning climate score tertile, adjusting for maternal and department characteristics. Adverse perinatal outcomes included fetal or early neonatal mortality, five-minute Apgar score < 7, or neonatal intensive care unit admission for ≥ 24 hours. Adverse maternal outcomes included postpartum hemorrhage and/or transfusion, death, uterine rupture, or third- or fourth-degree perineal laceration. Bias analyses were conducted to quantify the sensitivity of the results to uncontrolled confounding and selection bias. Learning climate scores were significantly associated with increased odds of adverse perinatal outcomes (aOR 2.06, 95% CI 1.14-3.72). Compared with the lowest tertile, departments in the middle tertile had 46% greater odds of adverse perinatal outcomes (aOR 1.46, 95% CI 1.09-1.94); departments in the highest tertile had 69% greater odds (aOR 1.69, 95% CI 1.24-2.30). Learning climate was not associated with adverse maternal outcomes (middle vs. lowest tertile: OR 1.04, 95% CI 0.93-1.16; highest vs. lowest tertile: OR 0.98, 95% CI 0.88-1.10). Learning climate was associated with significantly increased odds of adverse perinatal, but not maternal, outcomes. Research in similar clinical contexts is needed to replicate these findings and explore potential mechanisms behind these associations.

  11. Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

    PubMed

    Thomas, Jeremy; Hanby, Andrew; Pinder, Sarah E; Ball, Graham; Lawrence, Gill; Maxwell, Anthony; Wallis, Matthew; Evans, Andrew; Dobson, Hilary; Clements, Karen; Thompson, Alastair

    2014-07-01

    The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Adverse perinatal outcomes in borderline amniotic fluid index.

    PubMed

    Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

    2016-11-01

    Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10 th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10 th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI.

  13. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis

    PubMed Central

    Kamb, Mary L; Newman, Lori M; Mark, Jennifer; Broutet, Nathalie; Hawkes, Sarah J

    2013-01-01

    Abstract Objective To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. Methods PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Findings Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0–74.1]; I2 = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8–17.2]; I2 = 95.9%; P < 0.001). Conclusion Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women. PMID:23476094

  14. Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.

    PubMed

    Yaron, Yuval; Heifetz, Sigal; Ochshorn, Yifat; Lehavi, Ofer; Orr-Urtreger, Avi

    2002-09-01

    Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome. Copyright 2002 John Wiley & Sons, Ltd.

  15. Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection.

    PubMed

    Agra, Isabela Karine Rodrigues; Amorim Filho, Antonio Gomes; Lin, Lawrence Hsu; Biancolin, Sckarlet Ernandes; Francisco, Rossana Pulcineli Vieira; Brizot, Maria de Lourdes

    2017-11-01

    Objective  To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods  This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered non-recovery and categorized as an adverse outcome. Results  The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the non-recovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion  We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

  16. Magnitude of income-related disparities in adverse perinatal outcomes

    PubMed Central

    2014-01-01

    Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. Results The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. Conclusions This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases. PMID:24589212

  17. Meningitis With a Negative Cerebrospinal Fluid Gram Stain in Adults: Risk Classification for an Adverse Clinical Outcome

    PubMed Central

    Khoury, Nabil T.; Hossain, Md Monir; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

    2012-01-01

    Objective To derive and validate a risk score for an adverse clinical outcome in adults with meningitis and a negative cerebrospinal fluid (CSF) Gram stain. Patients and Methods We conducted a retrospective study of 567 adults from Houston, Texas, with meningitis evaluated between January 1, 2005, and January 1, 2010. The patients were divided into derivation (N=292) and validation (N=275) cohorts. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Of the 567 patients, 62 (11%) had an adverse clinical outcome. A predictive model was created using 3 baseline variables that were independently associated with an adverse clinical outcome (P<.05): age greater than 60 years, abnormal findings on neurologic examination (altered mental status, focal neurologic deficits, or seizures), and CSF glucose level of less than 2.4975 mmol/L (to convert CSF glucose to mmol/L, multiply by 0.05551). The model classified patients into 2 categories of risk for an adverse clinical outcome—derivation sample: low risk, 0.6% and high risk, 32.8%; P<.001; and validation sample: low risk, 0.5% and high risk, 21.1%; P<.001. Conclusion Adults with meningitis and a negative CSF Gram stain can be accurately stratified for the risk of an adverse clinical outcome using clinical variables available at presentation. PMID:23218086

  18. [Maternal hemoglobin in Peru: regional differences and its association with adverse perinatal outcomes].

    PubMed

    Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos

    2011-01-01

    To evaluate hemoglobin (Hb) levels in pregnant women from different geographical regions from Peru; to establish anemia and erythrocytocis rates and to establish the role of Hb on adverse perinatal outcomes using the Perinatal Information System (PIS) database of Peruvian Ministry of Health. Data were obtained from 379,816 births of 43 maternity care units between 2000 and 2010. Anemia and erythrocytocis rates were determined in each geographical region as well as rates of adverse perinatal outcomes. To analyze data the STATA program (versión 10.0,Texas, USA) was used. The results were considered significant at p<0.01. Mild anemia rate was higher in the coast (25.8%) and low forest (26.2%). Moderate/severe anemia rate in low forest was 2.6% and at the coast was 1.0%. In the highland, the highest rate of moderate/severe anemia was in the southern highlands (0.6%). The highest rate of erythrocytocis was found in the central highland (23.7%), 11.9% in the southern highland and 9.5% in the north highland. Severe anemia and erythrocytocis were associated with adverse perinatal outcomes. There are differences by Peruvian geographical region in anemia rates. In the central highlands were found the highest rates of erythrocytocis due to hypoxia effect in the high altitudes; however in the southern highlands, erythrocytocis was lower. Severe anemia and erythrocytosis were associated with increased adverse perinatal outcomes.

  19. Risk factors for adverse outcomes in older adults with blunt chest trauma: A systematic review.

    PubMed

    Sawa, Jake; Green, Robert S; Thoma, Brent; Erdogan, Mete; Davis, Philip J

    2017-08-11

    The objective of this study was to systematically review the published literature for risk factors associated with adverse outcomes in older adults sustaining blunt chest trauma. EMBASE and MEDLINE were searched from inception until March 2017 for prognostic factors associated with adverse outcomes in older adults sustaining blunt chest trauma using a pre-specified search strategy. References were independently screened for inclusion by two reviewers. Study quality was assessed using the Quality in Prognostic Studies tool. Where appropriate, descriptive statistics were used to evaluate study characteristics and predictors of adverse outcomes. Thirteen cohort studies representing 79,313 patients satisfied our selection criteria. Overall, 26 prognostic factors were examined across studies and were reported for morbidity (8 studies), length of stay (7 studies), mortality (6 studies), and loss of independence (1 study). No studies examined patient quality of life or emergency department recidivism. Prognostic factors associated with morbidity and mortality included age, number of rib fractures, and injury severity score. Although age and rib fractures were found to be associated with adverse outcomes in more than 3 studies, meta-analysis was not performed due to heterogeneity amongst included studies in how these variables were measured. While blunt chest wall trauma in older adults is relatively common, the literature on prognostic factors for adverse outcomes in this patient population remains inadequate due to a paucity of high quality studies and lack of consistent reporting standards.

  20. Is polypharmacy an independent risk factor for adverse outcomes after an emergency department visit?

    PubMed

    Salvi, Fabio; Rossi, Lorena; Lattanzio, Fabrizia; Cherubini, Antonio

    2017-03-01

    This study aimed at verifying the role of polypharmacy as an independent risk factor for adverse health outcomes in older emergency department (ED) patients. This was a large (n = 2057) sample of older ED patients (≥65 years) participating in an observational cohort study. Polypharmacy and excessive polypharmacy were defined as having 6-9 drug prescriptions and 10 or more drug prescriptions in the last 3 months, respectively. The total number of medication prescriptions was also available. Outcome measures were in-hospital mortality; 30-day ED return; ED revisit, hospital admission, and mortality at 6 months. Logistic and Cox regression models as well as receiver operating characteristic curves using the Youden index and the area under the curve were calculated. Polypharmacy and excessive polypharmacy were present in 624 (30.3 %) and 367 (17.8 %) subjects, respectively. The mean number of prescriptions in the last 3 months was 5.7 (range 0-25) drugs. Polypharmacy and, particularly, excessive polypharmacy were constantly and independently associated with worse outcomes. A cut-off of 6 had the highest value of the Youden Index in predicting the majority of the adverse outcomes considered. Polypharmacy and excessive polypharmacy are independent risk factors for adverse health outcomes after an ED visit. Further studies are needed to clarify whether drug related issues (such as non-compliance, inappropriate or suboptimal prescribing, adverse drug reactions, and drug-drug or drug-disease interactions) or underlying multimorbidity and disease severity, as well as clinical complexity and frailty, are responsible for the negative outcomes associated with polypharmacy.

  1. Role of adverse outcome pathways in developing computational models for regulatory toxicology

    EPA Science Inventory

    Regulatory toxicology for both human health and the environment increasingly is moving from a sole reliance on direct observation of apical toxicity outcomes in whole organism toxicity tests, to predictive approaches in which unacceptable outcomes and risk are inferred from mecha...

  2. Further evidence for periodontal disease as a risk indicator for adverse pregnancy outcomes.

    PubMed

    Turton, Mervyn; Africa, Charlene W J

    2017-06-01

    Although there is increasing evidence to suggest an association between periodontal disease and adverse pregnancy outcomes, the issue remains controversial. This study tested the hypothesis that periodontal disease is a risk indicator for preterm delivery of low-birthweight infants. The study sample comprised 443 pregnant women with a mean (± standard deviation) age of 24.13 (±5.30) years. At first visit, maternal oral health status was assessed by the measurement of probing pocket depth and clinical attachment loss, and periodontal status was graded as absent, mild, moderate or severe. An association was sought between pregnancy outcomes and maternal periodontal status. While controlling for other factors, significant associations were found between pregnancy outcomes and maternal periodontal index scores. This study provides further evidence that periodontal disease is a risk indicator for adverse pregnancy outcomes. © 2016 FDI World Dental Federation.

  3. A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes.

    PubMed

    Milton, Abul H; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A; Mitchell, Kane

    2017-05-23

    Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low-moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations.

  4. A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes

    PubMed Central

    Milton, Abul H.; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A.; Mitchell, Kane

    2017-01-01

    Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low–moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations. PMID:28545256

  5. Adverse Experiences in Early Childhood and Kindergarten Outcomes.

    PubMed

    Jimenez, Manuel E; Wade, Roy; Lin, Yong; Morrow, Lesley M; Reichman, Nancy E

    2016-02-01

    To examine associations between adverse childhood experiences (ACEs) in early childhood and teacher-reported academic and behavioral problems in kindergarten. We conducted a secondary analysis of data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort. Subjects with primary caregiver-reported information on ACE exposures ascertained at 5 years and teacher-reported outcomes at the end of the child's kindergarten year were included. Outcomes included teacher ratings of academic skills, emergent literacy skills, and behavior. We included 8 ACE exposures on the basis of the original Centers for Disease Control and Prevention Kaiser study and created an ACE score by summing individual adversities. We examined the associations between teacher-reported academic and behavioral outcomes and ACE scores by using logistic regression. In the study sample, 1007 children were included. Fifty-five percent had experienced 1 ACE and 12% had experienced ≥ 3. Adjusting for potential confounders, experiencing ≥ 3 ACEs was associated with below-average language and literacy skills (adjusted odds ratio [AORs]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and math skills (AOR: 1.8, 95% CI: 1.1-2.9), poor emergent literacy skills, attention problems (AOR: 3.5, 95% CI: 1.8-6.5), social problems (AOR: 2.7, 95% CI: 1.4-5.0), and aggression (AOR: 2.3, 95% CI: 1.2-4.6). In this study of urban children, experiencing ACEs in early childhood was associated with below-average, teacher-reported academic and literacy skills and behavior problems in kindergarten. These findings underscore the importance of integrated approaches that promote optimal development among vulnerable children. Copyright © 2016 by the American Academy of Pediatrics.

  6. Women's health: periodontitis and its relation to hormonal changes, adverse pregnancy outcomes and osteoporosis.

    PubMed

    Krejci, Charlene B; Bissada, Nabil F

    2012-01-01

    To examine the literature with respect to periodontitis and issues specific to women's health, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. The literature was evaluated to review reported associations between periodontitis and genderspecific issues, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. Collectively, the literature provided a large body of evidence that supports various associations between periodontitis and hormonal changes, adverse pregnancy outcomes and osteoporosis; however, certain shortcomings were noted with respect to biases involving definitions, sample sizes and confounding variables. Specific cause and effect relationships could not be delineated at this time and neither could definitive treatment interventions. Future research must include randomised controlled trials with consistent definitions, adequate controls and sufficiently large sample sizes in order to clarify specific associations, identify cause and effect relationships, define treatment options and determine treatment interventions which will lessen the untoward effects on the at-risk populations.

  7. Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

    PubMed

    van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

    2009-01-01

    BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care.

  8. Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes.

    PubMed

    Adachi, Kristina; Klausner, Jeffrey D; Xu, Jiahong; Ank, Bonnie; Bristow, Claire C; Morgado, Mariza G; Watts, D Heather; Weir, Fred; Persing, David; Mofenson, Lynne M; Veloso, Valdilea G; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J; Grinsztejn, Beatriz; Bastos, Francisco I; Siberry, George; Nielsen-Saines, Karin

    2016-08-01

    Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03-1.76). STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.

  9. Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

    PubMed Central

    Adachi, Kristina; Klausner, Jeffrey D.; Xu, Jiahong; Ank, Bonnie; Bristow, Claire C.; Morgado, Mariza G.; Watts, D. Heather; Weir, Fred; Persing, David; Mofenson, Lynne M.; Veloso, Valdilea G.; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J.; Grinsztejn, Beatriz; Bastos, Francisco I.; Siberry, George; Nielsen-Saines, Karin

    2016-01-01

    BACKGROUND Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. METHODOLOGY Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. RESULTS Of 1373 maternal urines, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG, and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery, death) were noted in infants of women with CT and NG (23/35, 65.7%) compared to NG (16/28, 57.1%), CT (84/214, 39.3%), and no STI (405/1096, 37%, p=0.001). Death (11.4% vs. 3%, p=0.02), low birth weight (42.9% vs. 16.9%, p=0.001), and preterm delivery (28.6% vs. 10.2%, p=0.008) were higher among infants of CT and NG co-infected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV-infected after controlling for maternal syphilis (OR 3.5, 95% CI 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (OR 1.35, 95% CI 1.03-1.76). CONCLUSION STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants. PMID:27164464

  10. Cardiovascular recovery from psychological and physiological challenge and risk for adverse cardiovascular outcomes and all-cause mortality

    PubMed Central

    Panaite, Vanessa; Salomon, Kristen; Jin, Alvin; Rottenberg, Jonathan

    2015-01-01

    Objective Exaggerated cardiovascular (CV) reactivity to laboratory challenge has been shown to predict future CV morbidity and mortality. CV recovery, has been less studied, and has yielded inconsistent findings, possibly due to presence of moderators. Reviews on the relationship between CV recovery and CV outcomes have been limited to cross-sectional studies and have not considered methodological factors. We performed a comprehensive meta-analytic review of the prospective literature investigating CV recovery to physical and psychological challenge and adverse cardiovascular outcomes. Methods We searched PsycINFO and PubMed for prospective studies investigating the relationship between CV recovery and adverse CV outcomes. Studies were coded for variables of interest and for effect sizes (ES). We conducted a random effects weighted meta-analysis. Moderators were examined with ANOVA-analog and meta-regression analyses. Results Thirty seven studies met inclusion criteria (N=125386). Impaired recovery from challenge predicted adverse cardiovascular outcomes (summary effect, r = .17, p < .001). Physical challenge was associated with larger predictive effects than psychological challenge. Moderator analyses revealed that recovery measured at 1 minute post-exercise, passive recovery, use of mortality as an outcome measure, and older sample age were associated with larger effects. Conclusions Poor recovery from laboratory challenges predicts adverse CV outcomes, with recovery from exercise serving as a particularly strong predictor of CV outcomes. The overall ES for recovery and CV outcomes is similar to that observed for CV reactivity and suggests that the study of recovery may have incremental value for understanding adverse CV outcomes. PMID:25829236

  11. Partner Disengagement from Pregnancy and Adverse Maternal and Infant Outcomes.

    PubMed

    Urquia, Marcelo L; Pulver, Ariel; Heaman, Maureen I; Ray, Joel G; Daoud, Nihaya; O'Campo, Patricia

    2017-03-01

    To assess whether partner disengagement from pregnancy is associated with adverse maternal and infant outcomes. We analyzed data from the 2006-2007 Canadian Maternity Experiences Survey, comprising a cross-sectional representative sample of 6,421 childbearing women. Multiple logistic regression assessed the association between adverse outcomes and three indicators of partner disengagement: (1) partner did not want the pregnancy, (2) partner argued more than usual in the year prior to the baby's birth, and (3) partner was absent at the delivery. Of all respondents, 3.8% had partners who did not want the pregnancy, 16.1% argued more than usual with their partner in the past year, and 7.6% had partners who were absent at the delivery. Women whose partner did not want the pregnancy were more likely to report intimate partner violence (IPV) (adjusted odds ratio [AOR] 3.55; 95% confidence interval [95% CI] 2.36-5.14), elevated depressive symptoms in the extended postpartum period (AOR 2.56, 95% CI 1.70-3.83), and nonroutine child healthcare visits after birth (AOR 1.54, 95% CI 1.13-2.11). Women whose partner argued more in the past year had higher odds of IPV (AOR 4.82, 95% CI 3.69-6.30), elevated depressive symptoms in the extended postpartum period (AOR 3.63; 95% CI 2.84-4.64), and nonroutine child healthcare visits (AOR 1.49, 95% CI 1.26-1.77), after adjustment for potential confounders. Partner disengagement is common and is associated with adverse maternal and infant outcomes. Affected women may benefit from special assistance during pregnancy and after delivery.

  12. Anti-prothrombin antibodies are associated with adverse pregnancy outcome.

    PubMed

    Marozio, Luca; Curti, Antonella; Botta, Giovanni; Canuto, Emilie M; Salton, Loredana; Tavella, Anna Maria; Benedetto, Chiara

    2011-11-01

    Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti-β(2) glycoprotein-1 antibodies are at high risk of late pregnancy complications, such as severe pre-eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid-binding plasma proteins, including also anti-prothrombin (anti-PT), anti-protein S (anti-PS), and anti-protein C (anti-PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. Anti-PT, anti-PS, and anti-PC antibodies were evaluated in 163 patients with previous severe pre-eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. The prevalence of anti-PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52-26.38). The highest prevalence was observed in subjects with fetal death. Anti-PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL. © 2011 John Wiley & Sons A/S.

  13. Adverse health outcomes in women exposed in utero to diethylstilbestrol.

    PubMed

    Hoover, Robert N; Hyer, Marianne; Pfeiffer, Ruth M; Adam, Ervin; Bond, Brian; Cheville, Andrea L; Colton, Theodore; Hartge, Patricia; Hatch, Elizabeth E; Herbst, Arthur L; Karlan, Beth Y; Kaufman, Raymond; Noller, Kenneth L; Palmer, Julie R; Robboy, Stanley J; Saal, Robert C; Strohsnitter, William; Titus-Ernstoff, Linda; Troisi, Rebecca

    2011-10-06

    Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood. We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes

  14. Patient-Reported Disease Activity and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

    PubMed

    Harris, Nathaniel; Eudy, Amanda; Clowse, Megan

    2018-06-15

    While increased rheumatic disease activity during pregnancy has been associated with adverse pregnancy outcomes, this activity is typically assessed by the physician. Little is known, however, about the association between patient-reported measures of disease activity and pregnancy outcomes. Univariate and multivariable regression models were used to assess the relationship between patient and physician-reported measures of disease activity and adverse pregnancy outcomes in 225 patients with lupus or rheumatoid arthritis (RA) enrolled in a prospective registry at a single academic center from 2008-2016. In women with RA, patient-reported disease activity is associated with preterm birth (OR 5.9 (1.5-23.9)), and gestational age (beta -1.5 weeks (-2.6, -0.4 weeks)). The physician assessment of disease activity also predicted preterm (OR 2.1 (1.2-3.5)), small for gestational age births (OR 1.8 (1.03-3.1), and gestational age in weeks (beta -0.6 weeks (-0.9, -0.02 weeks)). On the other hand, SLE patient-reported disease activity measures, including the HAQ, pain or global health measures, are not associated with adverse pregnancy outcomes. However, physician measures of SLE disease activity are associated with preterm birth (OR 2.9 (1.-6.3)), cesarean delivery (OR 2.3 (1.0-5.3)), and preeclampsia (OR 2.8 (1.3-6.3)). The results do not appear to be driven by lupus nephritis or antiphospholipid syndrome. For women with RA, patient-reported measures of disease activity may be useful adjuncts to physician-reported measures in identifying pregnancies at greater risk. In contrast, in SLE, no patient-reported measures were associated with adverse outcomes while physician measures of disease activity helped predict several adverse pregnancy outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Placental maternal vascular malperfusion and adverse pregnancy outcomes in gestational diabetes mellitus.

    PubMed

    Scifres, Christina M; Parks, W Tony; Feghali, Maisa; Caritis, Steve N; Catov, Janet M

    2017-01-01

    Maternal vascular malperfusion (MVM) lesions represent hypoxic-ischemic damage to the placenta, and they are associated with adverse pregnancy outcomes. Women with gestational diabetes (GDM) are at increased risk for pregnancy complications, so we set out to characterize the prevalence and clinical correlates of MVM lesions in this cohort. This was a retrospective cohort study of 1187/1374 (86.4%) women with GDM delivered between 2009 and 2012 who had placental pathology available. Placental lesions of all types were tabulated and grouped into constructs of related entities. MVM lesions specifically included villous infarcts, decidual vasculopathy, increased syncytial knots, perivillous fibrin, and fibrin deposition. We compared maternal characteristics between women with and without MVM lesions, and we also assessed the impact of these lesions on birth weight, preterm birth, and pre-eclampsia using multivariable logistic regression analysis. MVM lesions were the most common placental lesion type in women with GDM (n = 362, 30.5%). Excess gestational weight gain was independently associated with MVM lesions (aOR 1.42, 95% CI 1.06-1.91, p = 0.02) after adjusting for maternal characteristics. MVM lesions were associated with lower birth weight (-90.3 g, 95% CI -148.0 to -32.7, p = 0.002), as well as a 2-fold increased risk for delivery of a small for gestational age infant (10.8 vs 5.9%, p = 0.01) in overweight and obese women. MVM lesions were also associated with increased risk for preterm birth <34 weeks (adjusted OR 2.36, 95% CI 1.31-4.23, p = 0.004) and hypertensive disorders of pregnancy (HDP; adjusted OR 1.58, 95% CI 1.13-2.22, p = 0.02). Placental maternal vascular malperfusion lesions may be one pathway linking excess gestational weight gain to adverse pregnancy outcomes in women with GDM, and future studies are needed to identify metabolic factors that may explain this association. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Classification of individual well-being scores for the determination of adverse health and productivity outcomes in employee populations.

    PubMed

    Shi, Yuyan; Sears, Lindsay E; Coberley, Carter R; Pope, James E

    2013-04-01

    Adverse health and productivity outcomes have imposed a considerable economic burden on employers. To facilitate optimal worksite intervention designs tailored to differing employee risk levels, the authors established cutoff points for an Individual Well-Being Score (IWBS) based on a global measure of well-being. Cross-sectional associations between IWBS and adverse health and productivity outcomes, including high health care cost, emergency room visits, short-term disability days, absenteeism, presenteeism, low job performance ratings, and low intentions to stay with the employer, were studied in a sample of 11,702 employees from a large employer. Receiver operating characteristics curves were evaluated to detect a single optimal cutoff value of IWBS for predicting 2 or more adverse outcomes. More granular segmentation was achieved by computing relative risks of each adverse outcome from logistic regressions accounting for sociodemographic characteristics. Results showed strong and significant nonlinear associations between IWBS and health and productivity outcomes. An IWBS of 75 was found to be the optimal single cutoff point to discriminate 2 or more adverse outcomes. Logistic regression models found abrupt reductions of relative risk also clustered at IWBS cutoffs of 53, 66, and 88, in addition to 75, which segmented employees into high, high-medium, medium, low-medium, and low risk groups. To determine validity and generalizability, cutoff values were applied in a smaller employee population (N=1853) and confirmed significant differences between risk groups across health and productivity outcomes. The reported segmentation of IWBS into discrete cohorts based on risk of adverse health and productivity outcomes should facilitate well-being comparisons and worksite interventions.

  17. Future Directions in Childhood Adversity and Youth Psychopathology.

    PubMed

    McLaughlin, Katie A

    2016-01-01

    Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology-and whether those mechanisms are general or specific to particular kinds of adversity-remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children's development.

  18. Surgical Adverse Events, Risk Management, and Malpractice Outcome: Morbidity and Mortality Review Is Not Enough

    PubMed Central

    Morris, John A.; Carrillo, Ysela; Jenkins, Judith M.; Smith, Philip W.; Bledsoe, Sandy; Pichert, James; White, Andrew

    2003-01-01

    Objective To review all admissions (age > 13) to three surgical patient care centers at a single academic medical center between January 1, 1995, and December 6, 1999, for significant surgical adverse events. Summary Background Data Little data exist on the interrelationships between surgical adverse events, risk management, malpractice claims, and resulting indemnity payments to plaintiffs. The authors hypothesized that examination of this process would identify performance improvement opportunities overlooked by standard medical peer review; the risk of litigation would be constant across the three homogeneous patient care centers; and the risk management process would exceed the performance improvement process. Methods Data collected included patient demographics (age, gender, and employment status), hospital financials (hospital charges, costs, and financial class), and outcome. Outcome categories were medical (disability: <1 month, 1–6 months, permanent/death), legal (no legal action, settlement, summary judgment), financial (indemnity payments, legal fees, write-offs), and cause and effect analysis. Cause and effect analysis attempts to identify system failures contributing to adverse outcomes. This was determined by two independent analysts using the 17 Harvard criteria and subdividing these into subsystem causative factors. Results The study group consisted of 130 patients with surgical adverse events resulting in total liabilities of $8.2 million. The incidence of adverse events per 1,000 admissions across the three patient care centers was similar, but indemnity payments per 1,000 admissions varied (cardiothoracic = $30, women’s health = $90, trauma = $520). Patient demographics were not predictive of high-risk subgroups for adverse events or litigation. In terms of medical outcome, 51 patients had permanent disability or death, accounting for 98% of the indemnity payments. In terms of legal outcome, 103 patients received no indemnity payments, 15

  19. Early Childhood Adversity and Pregnancy Outcomes

    PubMed Central

    Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

    2016-01-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  20. National cohort study of absolute risk and age-specific incidence of multiple adverse outcomes between adolescence and early middle age.

    PubMed

    Mok, Pearl L H; Antonsen, Sussie; Pedersen, Carsten Bøcker; Appleby, Louis; Shaw, Jenny; Webb, Roger T

    2015-09-19

    . Approximately 1 in 50 males and 1 in 120 females who are alive on their 15th birthday will die by age 40. By examining the same cohort at risk, we compared risks for multiple outcomes without differential inter-cohort biases. These epidemiological profiles will inform further research into the pathways leading to these adverse events and future preventive strategies.

  1. Future Directions in Childhood Adversity and Youth Psychopathology

    PubMed Central

    McLaughlin, Katie A.

    2016-01-01

    Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology—and whether those mechanisms are general or specific to particular kinds of adversity—remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children’s development. PMID:26849071

  2. Acculturation and Adverse Birth Outcomes in a Predominantly Puerto Rican Population.

    PubMed

    Barcelona de Mendoza, Veronica; Harville, Emily; Theall, Katherine; Buekens, Pierre; Chasan-Taber, Lisa

    2016-06-01

    Introduction Latinas in the United States on average have poorer birth outcomes than Whites, yet considerable heterogeneity exists within Latinas. Puerto Ricans have some of the highest rates of adverse outcomes and are understudied. The goal of this study was to determine if acculturation was associated with adverse birth outcomes in a predominantly Puerto Rican population. Methods We conducted a secondary analysis of Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011. A convenience sample of pregnant Latina women were recruited from a tertiary care hospital in Massachusetts. Acculturation was measured in early pregnancy; directly via the Psychological Acculturation Scale, and via proxies of language preference and generation in the United States. Birth outcomes (gestational age and birthweight) were abstracted from medical records (n = 1362). Results After adjustment, psychological acculturation, language preference, and generation was not associated with odds of preterm birth. However, every unit increase in psychological acculturation score was associated with an increase in gestational age of 0.22 weeks (SE = 0.1, p = 0.04) among all births. Women who preferred to speak Spanish (β = -0.39, SE = 0.2, p = 0.02) and who were first generation in the US (β = -0.33, SE = 0.1, p = 0.02) had significantly lower gestational ages than women who preferred English or who were later generation, respectively. Similarly, women who were first generation had babies who weighed 76.11 g less (SE = 35.2, p = 0.03) than women who were later generation. Discussion We observed a small, but statistically significant adverse impact of low acculturation on gestational age and birthweight in this predominantly Puerto Rican population.

  3. Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

    PubMed

    Ibrahim, Z M; Sayed Ahmed, W A; El-Hamid, S A; Hagras, A M

    2015-01-01

    To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

  4. Incidence and Predictors of Long-Term Adverse Outcomes in Patients with Rheumatic Mitral Stenosis in Sinus Rhythm.

    PubMed

    Nachom, Patsadee; Ratanasit, Nithima

    2016-04-01

    Rheumatic fever and rheumatic heart disease remain important health problems in developing countries. Mitral stenosis (MS) is the most common form of rheumatic heart disease. The aim of this study was to investigate incidence and echocardiographic predictors of long-term adverse outcomes in patients with rheumatic mitral stenosis in sinus rhythm. We retrospectively reviewed medical records of patients diagnosed with isolated rheumatic MS of any severity at Siriraj Hospital between 1996 and 2013. Demographic data, echocardiographic data, and long-term adverse outcomes were collected. Long-term adverse outcomes included all-cause mortality, hospitalization due to heart failure, new-onset atrial fibrillation, and/or embolic stroke during follow-up. One hundred eighty five patients (aged 41.9 ± 13.2 years, 81.1% female) were included during the median follow-up period of 12.6 years (95% CI: 11.2-14.0). MS was classified as mild, moderate, and severe in 8.6%, 2 7.6%, and 63.8% of patients, respectively. Average mitral valve score was 8.25 ± 1.5. Most patients (61.6%) underwent percutaneous balloon mitral valvulotomy. Incidence of long-term adverse outcome was 43.2% (95% CI: 36.0-50.7%) and included mortality in two patients (1.1%, 95% CI: 0.13-3.9%), hospitalization due to heart failure in 20 patients (10.8%, 95% CI: 6.7-16.2%), new-onset atrial fibrillation in 71 patients (38.4%, 95% CI: 31.3-45.8%), and embolic stroke in 14 patients (7.6%, 95% CI: 4.2-12.4%). Echocardiographic parameters associated with long-term adverse outcomes were left atrial dimension greater than 50 mm (HR 2.61, 95% CI: 1.08-6.30; p = 0.03) and left ventricular end-systolic dimension less than 28 mm (HR 3.06, 95% CI: 1.25-7.49; p = 0.01). Long-term adverse outcomes are common in patients with rheumatic MS in sinus rhythm. Long-term adverse outcomes were found to correlate with left atrial dimension and left ventricular end-systolic dimension.

  5. Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

    PubMed

    Shih, Yu-Hsuan; Islam, Tariqul; Hore, Samar Kumar; Sarwar, Golam; Shahriar, Mohammad Hasan; Yunus, Mohammad; Graziano, Joseph H; Harjes, Judith; Baron, John A; Parvez, Faruque; Ahsan, Habibul; Argos, Maria

    2017-10-01

    Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Application of Signaling Pathway-Based Adverse Outcome Pathways and High Throughput Toxicokinetic-PBPK for Developmental Cardiac Malformations

    EPA Science Inventory

    Associating putative molecular initiating events (MIE) with downstream cell signaling pathways and modeling fetal exposure kinetics is an important challenge for integration in developmental systems toxicology. Here, we describe an integrative systems toxicology model for develop...

  7. Evaluating legacy contaminants and emerging chemicals in marine environments using adverse outcome pathways and biological effects-directed analysis.

    PubMed

    Hutchinson, Thomas H; Lyons, Brett P; Thain, John E; Law, Robin J

    2013-09-30

    important scientific, economic and health challenges. In order to meet these challenges and pursue cost-effective scientific approaches that can provide evidence necessary to support policy needs (e.g. the European Marine Strategy Framework Directive), it is widely recognised that there is a need to (i) provide marine exposure assessments for priority contaminants using a range of validated models, passive samplers and biomarkers; (ii) integrate chemical monitoring data with biological effects data across spatial and temporal scales (including quality controls); and (iii) strengthen the evidence base to understand the relationship between exposure to complex chemical mixtures, biological and ecological impacts through integrated approaches and molecular data (e.g. genomics, proteomics and metabolomics). Additionally, we support the widely held view that (iv) that rather than increasing the analytical chemistry monitoring of large number of emerging contaminants, it will be important to target analytical chemistry towards key groups of chemicals of concern using effects-directed analysis. It is also important to evaluate to what extent existing biomarkers and bioassays can address various classes of emerging chemicals using the adverse outcome pathway (AOP) approach now being developed by the Organization for Economic Cooperation and Development (OECD) with respect to human toxicology and ecotoxicology. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  8. Temporal and external validation of a prediction model for adverse outcomes among inpatients with diabetes.

    PubMed

    Adderley, N J; Mallett, S; Marshall, T; Ghosh, S; Rayman, G; Bellary, S; Coleman, J; Akiboye, F; Toulis, K A; Nirantharakumar, K

    2018-06-01

    To temporally and externally validate our previously developed prediction model, which used data from University Hospitals Birmingham to identify inpatients with diabetes at high risk of adverse outcome (mortality or excessive length of stay), in order to demonstrate its applicability to other hospital populations within the UK. Temporal validation was performed using data from University Hospitals Birmingham and external validation was performed using data from both the Heart of England NHS Foundation Trust and Ipswich Hospital. All adult inpatients with diabetes were included. Variables included in the model were age, gender, ethnicity, admission type, intensive therapy unit admission, insulin therapy, albumin, sodium, potassium, haemoglobin, C-reactive protein, estimated GFR and neutrophil count. Adverse outcome was defined as excessive length of stay or death. Model discrimination in the temporal and external validation datasets was good. In temporal validation using data from University Hospitals Birmingham, the area under the curve was 0.797 (95% CI 0.785-0.810), sensitivity was 70% (95% CI 67-72) and specificity was 75% (95% CI 74-76). In external validation using data from Heart of England NHS Foundation Trust, the area under the curve was 0.758 (95% CI 0.747-0.768), sensitivity was 73% (95% CI 71-74) and specificity was 66% (95% CI 65-67). In external validation using data from Ipswich, the area under the curve was 0.736 (95% CI 0.711-0.761), sensitivity was 63% (95% CI 59-68) and specificity was 69% (95% CI 67-72). These results were similar to those for the internally validated model derived from University Hospitals Birmingham. The prediction model to identify patients with diabetes at high risk of developing an adverse event while in hospital performed well in temporal and external validation. The externally validated prediction model is a novel tool that can be used to improve care pathways for inpatients with diabetes. Further research to assess

  9. Prenatal hazardous substance use and adverse birth outcomes

    PubMed Central

    Quesada, Odayme; Gotman, Nathan; Howell, Heather B.; Funai, Edmund F.; Rounsaville, Bruce J.; Yonkers, Kimberly A.

    2012-01-01

    Objective Assess the relative effects of a variety of illicit and licit drugs on risk for adverse birth outcomes. Methods We used data from two large prospective investigations, and a novel analytic method, recursive partitioning class analysis to identify risk factors associated with preterm birth and delivering a small for gestational age infant. Results Compared to cocaine and opiate non-users, cocaine users were 3.53 times as likely (95% Cl: 1.65–7.56; p=0.001) and opiate users 2.86 times as likely (95% Cl: 1.11–7.36; p=0.03) to deliver preterm. The odds of delivering a small for gestational age infant for women who smoked more than two cigarettes daily was 3.74, (95% Cl: 2.47–5.65; p<0.0001) compared to women who smoked two or less cigarettes daily and had one previous child. Similarly, less educated, nulliparous women who smoked two or fewer cigarettes daily were 4.12 times as likely (95% Cl: 2.04–8.34; p<0.0001) to have a small for gestational age infant. Conclusions Among our covariates, prenatal cocaine and opiate use are the predominant risk factors for preterm birth; while tobacco use was the primary risk factor predicting small for gestational age at delivery. Multi-substance use did not substantially increase risk of adverse birth outcomes over these risk factors. PMID:22489543

  10. Classification of Individual Well-Being Scores for the Determination of Adverse Health and Productivity Outcomes in Employee Populations

    PubMed Central

    Sears, Lindsay E.; Coberley, Carter R.; Pope, James E.

    2013-01-01

    Abstract Adverse health and productivity outcomes have imposed a considerable economic burden on employers. To facilitate optimal worksite intervention designs tailored to differing employee risk levels, the authors established cutoff points for an Individual Well-Being Score (IWBS) based on a global measure of well-being. Cross-sectional associations between IWBS and adverse health and productivity outcomes, including high health care cost, emergency room visits, short-term disability days, absenteeism, presenteeism, low job performance ratings, and low intentions to stay with the employer, were studied in a sample of 11,702 employees from a large employer. Receiver operating characteristics curves were evaluated to detect a single optimal cutoff value of IWBS for predicting 2 or more adverse outcomes. More granular segmentation was achieved by computing relative risks of each adverse outcome from logistic regressions accounting for sociodemographic characteristics. Results showed strong and significant nonlinear associations between IWBS and health and productivity outcomes. An IWBS of 75 was found to be the optimal single cutoff point to discriminate 2 or more adverse outcomes. Logistic regression models found abrupt reductions of relative risk also clustered at IWBS cutoffs of 53, 66, and 88, in addition to 75, which segmented employees into high, high-medium, medium, low-medium, and low risk groups. To determine validity and generalizability, cutoff values were applied in a smaller employee population (N=1853) and confirmed significant differences between risk groups across health and productivity outcomes. The reported segmentation of IWBS into discrete cohorts based on risk of adverse health and productivity outcomes should facilitate well-being comparisons and worksite interventions. (Population Health Management 2013;16:90–98) PMID:23013034

  11. Increasing Scientific Confidence in Adverse Outcome Pathways: Application of Tailored Bradford-Hill Considerations for Evaluating Weight of Evidence.

    PubMed

    Becker, Richard A; Ankley, Gerald T; Edwards, Stephen W; Kennedy, Sean W; Linkov, Igor; Meek, Bette; Sachana, Magdalini; Segner, Helmut; Van Der Burg, Bart; Villeneuve, Daniel L; Watanabe, Haruna; Barton-Maclaren, Tara S

    2015-08-01

    Systematic consideration of scientific support is a critical element in developing and, ultimately, using adverse outcome pathways (AOPs) for various regulatory applications. Though weight of evidence (WoE) analysis has been proposed as a basis for assessment of the maturity and level of confidence in an AOP, methodologies and tools are still being formalized. The Organization for Economic Co-operation and Development (OECD) Users' Handbook Supplement to the Guidance Document for Developing and Assessing AOPs (OECD 2014a; hereafter referred to as the OECD AOP Handbook) provides tailored Bradford-Hill (BH) considerations for systematic assessment of confidence in a given AOP. These considerations include (1) biological plausibility and (2) empirical support (dose-response, temporality, and incidence) for Key Event Relationships (KERs), and (3) essentiality of key events (KEs). Here, we test the application of these tailored BH considerations and the guidance outlined in the OECD AOP Handbook using a number of case examples to increase experience in more transparently documenting rationales for assigned levels of confidence to KEs and KERs, and to promote consistency in evaluation within and across AOPs. The major lessons learned from experience are documented, and taken together with the case examples, should contribute to better common understanding of the nature and form of documentation required to increase confidence in the application of AOPs for specific uses. Based on the tailored BH considerations and defining questions, a prototype quantitative model for assessing the WoE of an AOP using tools of multi-criteria decision analysis (MCDA) is described. The applicability of the approach is also demonstrated using the case example aromatase inhibition leading to reproductive dysfunction in fish. Following the acquisition of additional experience in the development and assessment of AOPs, further refinement of parameterization of the model through expert

  12. Influence of median surgeon operative duration on adverse outcomes in bariatric surgery.

    PubMed

    Reames, Bradley N; Bacal, Daniel; Krell, Robert W; Birkmeyer, John D; Birkmeyer, Nancy J O; Finks, Jonathan F

    2015-01-01

    Evidence suggests that prolonged operative time adversely affects surgical outcomes. However, whether faster surgeons have better outcomes is unclear, as a surgeon׳s speed could reflect skill and efficiency, but may alternatively reflect haste. This study evaluates whether median surgeon operative time is associated with adverse surgical outcomes after laparoscopic Roux-en-Y gastric bypass. We performed a retrospective cohort study using statewide clinical registry data from the years 2006 to 2012. Surgeons were ranked by their median operative time and grouped into terciles. Multivariable logistic regression with robust standard errors was used to evaluate the influence of median surgeon operative time on 30-day surgical outcomes, adjusting for patient and surgeon characteristics, trainee involvement, concurrent procedures, and the complex interaction between these variables. A total of 16,344 patients underwent surgery during the study period. Compared to surgeons in the fastest tercile, slow surgeons required 53 additional minutes to complete a gastric bypass procedure (median [interquartile range] 139 [133-150] versus 86 [69-91], P<.001). After adjustment for patient characteristic only, slow surgeons had significantly higher adjusted rates of any complication, prolonged length of stay, emergency department visits or readmissions, and venous thromboembolism (VTE). After further adjustment for surgeon characteristics, resident involvement, and the interaction between these variables, slow surgeons had higher rates of any complication (10.5% versus 7.1%, P=.039), prolonged length of stay (14.0% versus 4.4%, P=.002), and VTE (0.39% versus .22%, P<.001). Median surgeon operative duration is independently associated with adjusted rates of certain adverse outcomes after laparoscopic Roux-en-Y gastric bypass. Improving surgeon efficiency while operating may reduce operative time and improve the safety of bariatric surgery. Copyright © 2015 American Society for

  13. Early adverse experience and substance addiction: dopamine, oxytocin, and glucocorticoid pathways

    PubMed Central

    Kim, Sohye; Kwok, Stephanie; Mayes, Linda C.; Potenza, Marc N.; Rutherford, Helena J. V.; Strathearn, Lane

    2016-01-01

    Substance addiction may follow a chronic, relapsing course and critically undermine the physical and psychological well-being of the affected individual and the social units of which the individual is a member. Despite the public health burden associated with substance addiction, treatment options remain suboptimal, with relapses often seen. The present review synthesizes growing insights from animal and human research to shed light upon developmental and neurobiological pathways that may increase susceptibility to addiction. We examine the dopamine system, the oxytocin system, and the glucocorticoid system, as they are particularly relevant to substance addiction. Our aim is to delineate how early adverse experience may induce long-lasting alterations in each of these systems at molecular, neuroendocrine, and behavioral levels and ultimately lead to heightened vulnerability to substance addiction. We further discuss how substance addiction in adulthood may increase the risk of suboptimal caregiving for the next generation, perpetuating the intergenerational cycle of early adverse experiences and addiction. PMID:27508337

  14. Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

    PubMed

    Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

    2010-01-01

    Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal

  15. Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes

    PubMed Central

    Kundakovic, Marija; Lim, Sean; Gudsnuk, Kathryn; Champagne, Frances A.

    2013-01-01

    Early life adversity can have a significant long-term impact with implications for the emergence of psychopathology. Disruption to mother-infant interactions is a form of early life adversity that may, in particular, have profound programing effects on the developing brain. However, despite converging evidence from human and animal studies, the precise mechanistic pathways underlying adversity-associated neurobehavioral changes have yet to be elucidated. One approach to the study of mechanism is exploration of epigenetic changes associated with early life experience. In the current study, we examined the effects of postnatal maternal separation (MS) in mice and assessed the behavioral, brain gene expression, and epigenetic effects of this manipulation in offspring. Importantly, we included two different mouse strains (C57BL/6J and Balb/cJ) and both male and female offspring to determine strain- and/or sex-associated differential response to MS. We found both strain-specific and sex-dependent effects of MS in early adolescent offspring on measures of open-field exploration, sucrose preference, and social behavior. Analyses of cortical and hippocampal mRNA levels of the glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf) genes revealed decreased hippocampal Bdnf expression in maternally separated C57BL/6J females and increased cortical Bdnf expression in maternally separated male and female Balb/cJ offspring. Analyses of Nr3c1and Bdnf (IV and IX) CpG methylation indicated increased hippocampal Nr3c1 methylation in maternally separated C57BL/6J males and increased hippocampal Bdnf IX methylation in male and female maternally separated Balb/c mice. Overall, though effect sizes were modest, these findings suggest a complex interaction between early life adversity, genetic background, and sex in the determination of neurobehavioral and epigenetic outcomes that may account for differential vulnerability to later-life disorder. PMID:23914177

  16. Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study

    PubMed Central

    Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu

    2017-01-01

    Objectives To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. Methods We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. Results The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23–1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. Conclusions We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age. PMID:28850585

  17. Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study.

    PubMed

    Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu; Kim, Eun-A

    2017-01-01

    To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23-1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age.

  18. OS104. Are preeclampsia and adverse obstetrical outcomes predictors for longterm cardiovascular disease?

    PubMed

    Sia, W W; Tsuyuki, R; Pertman, S; Hui, W

    2012-07-01

    Epidemiologic studies suggest that pregnancy complications such as preeclampsia, gestational diabetes, preterm delivery and low birth weight independently increase maternal risk for future development of cardiovascular disease. To further investigate whether preeclampsia, gestational diabetes, and adverse obstetrical outcomes such as placental abruption, intrauterine growth restriction and preterm delivery, are independent risk factors for longterm cardiovascular disease. This was a case-control study where 252 parous women (cases) with coronary artery disease were matched with a parous woman within 5 years of age with no known coronary artery disease (controls). Participants were recruited from the Royal Alexandra Hospital in cardiac catheterization lab recovery room in Edmonton, Canada. Women with significant angiographic coronary artery stenosis were eligible as cases and those without were eligible as controls. Participants were interviewed on their pregnancy histories and traditional cardiovascular risk factors, such as hypertension, diabetes etc. Descriptive statistics, chi-square tests and conditional regression analysis were performed. We recruited 244 cases and 246 controls. The average age was 66.3 and 65.8 respectively. Cases were more likely obese, had more pregnancies as well as traditional cardiovascular risk factors than controls. Adverse pregnancy outcomes were similar between the two groups except gestational hypertension. However, it was not statistically significant in the conditional logistic regression model. Independent risk factors for future cardiovascular diseases were: dyslipidemia (OR 12.8), hypertension (3.0), and being a current (OR 7.4) or former smoker (1.8). Adverse pregnancy outcomes In this study, adverse pregnancy outcomes were not independently associated with cardiovascular disorders. Our study was limited by recall bias, and ascertainment of diagnosis.Our study supports that dyslipidemia, hypertensiion and smoking increase

  19. Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

    PubMed

    Jones, Michael J; Neal, Christopher P; Ngu, Wee Sing; Dennison, Ashley R; Garcea, Giuseppe

    2017-08-01

    The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

  20. Treating periodontal disease for preventing adverse birth outcomes in pregnant women.

    PubMed

    Iheozor-Ejiofor, Zipporah; Middleton, Philippa; Esposito, Marco; Glenny, Anne-Marie

    2017-06-12

    Periodontal disease has been linked with a number of conditions, such as cardiovascular disease, stroke, diabetes and adverse pregnancy outcomes, all likely through systemic inflammatory pathways. It is common in women of reproductive age and gum conditions tend to worsen during pregnancy. Some evidence from observational studies suggests that periodontal intervention may reduce adverse pregnancy outcomes. There is need for a comprehensive Cochrane review of randomised trials to assess the effect of periodontal treatment on perinatal and maternal health. To assess the effects of treating periodontal disease in pregnant women in order to prevent or reduce perinatal and maternal morbidity and mortality. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 6 October 2016), Cochrane Pregnancy and Childbirth's Trials Register (to 7 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 9) in the Cochrane Library, MEDLINE Ovid (1946 to 6 October 2016), Embase Ovid (1980 to 6 October 2016), and LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 6 October 2016). ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials on 6 October 2016. We placed no restrictions on the language or date of publication when searching the electronic databases. We included all randomised controlled trials (RCTs) investigating the effects of periodontal treatment in preventing or reducing perinatal and maternal morbidity and mortality. We excluded studies where obstetric outcomes were not reported. Two review authors independently screened titles and abstracts and extracted data using a prepiloted data extraction form. Missing data were obtained by contacting authors and risk of bias was assessed using Cochrane's 'Risk of bias' tool. Where appropriate

  1. Adverse nurse outcomes: correlation to nurses' workload, staffing, and shift rotation in Kuwaiti hospitals.

    PubMed

    Al-Kandari, Fatimah; Thomas, Deepa

    2008-08-01

    This study was conducted to identify adverse outcomes to nurses in relation to their daily patient load, nursing care activities, staffing, and shift rotation. A structured questionnaire was used to collect data from medical and surgical nurses (N = 784). Skipping tea/coffee breaks (95%), feeling responsible for more patients than they could safely care for (87%), inadequate help available (86%), inadequate time to document care (80%), verbal abuse by a patient or a visitor (77%), and concern about quality of care (71%) were the major reported adverse outcomes related to short staffing, increased patient load, and increased nursing care activities.

  2. Association of assisted reproductive technology with adverse pregnancy outcomes

    PubMed Central

    Jie, Zhang; Yiling, Ding; Ling, Yu

    2015-01-01

    Background: More and more infertile patients have accepted the assisted reproductive technique (ART) therapy. Concerns have been raised over an increased risk of adverse maternal outcomes in ART populations as compared with natural conception (NC). Objective: The aim was to improve the ART in clinicial work and to reduce the incidence of pregnancy complications in ART group according to analyzing the reasons of high incidence of pregnancy complications in ART group, comparing the incidence of pregnancy complications in different controlled ovarian hyperstimulation (COH) programs and evaluating the effects of ART which attribute to adverse pregnancy outcomes. Materials and Methods: In this prospective population-based cohort study,3216 pregnant women with gestational age ≤12 weeks, regular antenatal examination,and ultrasound identification of intrauterine pregnancy were enrolled from January 2010 to June 2013. According to having ART history, the participantswere divided into two groups: ART group (contains fresh embryo transfer group or frozen-thawed embryo transfer group) and NC group. We compared the incidence of pregnancy complications between different groups and evaluated the factors which could affect the occurrence of these complications. Results: When compared to NC group, significantly increased rates of gestational diabetes mellitus (GDM) (p<0.01), preeclampsia (PE) (p<0.01) and intrahepatic cholestasis of pregnancy (ICP) (p˂0.01) were observed in ART group. There was no significant difference in the incidence of birth defect between the two groups (p=0.07). Multiple pregnancies and Gonadotropin (Gn) were risk factors in GDM, PE, and ICP. The exogenous progesterone treatment had no effect on GDM, PE or ICP. Conclusion: ART increases the risk of adverse maternal complications such as GDM, PE and ICP. The dosages of Gn should be reduced to an extent and the number of embryo implantation should be controlled. Exogenous progesterone treatment is safe

  3. Interpregnancy interval following miscarriage and adverse pregnancy outcomes: systematic review and meta-analysis.

    PubMed

    Kangatharan, Chrishny; Labram, Saffi; Bhattacharya, Sohinee

    2017-03-01

    A short interpregnancy interval (IPI) following a delivery is believed to be associated with adverse outcomes in the next pregnancy. The optimum IPI following miscarriage is controversial. Based on a single large-scale study in Latin and South America, the World Health Organization recommends delaying pregnancy for 6 months after a miscarriage to achieve optimal outcomes in the next pregnancy. Our aim was to determine if a short IPI (<6 months) following miscarriage is associated with adverse outcomes in the next pregnancy. Studies were retrieved from MEDLINE, Embase and Pubmed, with no time and language restrictions. The search strategy used a combination of Medical Subject Headings terms for miscarriage, IPI and adverse outcomes. Bibliographies of the retrieved articles were also searched by hand. All studies including women with at least one miscarriage, comparing subsequent adverse pregnancy outcomes for IPIs of less than and more than 6 months were included. Two independent reviewers screened titles and abstracts for inclusion. Characteristics of the studies were extracted and quality assessed using Critical Appraisal Skills Programme criteria. A systematic review and meta-analysis were conducted to compare short (<6 months) versus long (>6 months) IPI following miscarriage in terms of risk of further miscarriage, preterm birth, stillbirth, pre-eclampsia and low birthweight babies in the subsequent pregnancy. Review Manager 5.3 was used for conducting meta-analyses. Sixteen studies including 1 043 840 women were included in the systematic review and data from 10 of these were included in one or more meta-analyses (977 972 women). With an IPI of less than 6 months, the overall risk of further miscarriage (Risk ratio (RR) 0.82 95% CI 0.78, 0.86) and preterm delivery (RR 0.79 95% CI 0.75, 0.83) were significantly reduced. The pooled risks of stillbirth (RR 0.88 95% CI 0.76, 1.02); low birthweight (RR 1.05 95% CI 0.48, 2.29) and pre-eclampsia (RR 0.95 95% CI 0

  4. Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis.

    PubMed

    Wang, J; Moore, D; Subramanian, A; Cheng, K K; Toulis, K A; Qiu, X; Saravanan, P; Price, M J; Nirantharakumar, K

    2018-05-21

    Low and high birthweight is known to increase the risk of acute and longer-term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations. The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters. We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old. Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high-density-lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small-for-gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy. This meta-analysis suggested that the potential under-recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials. © 2018 World Obesity Federation.

  5. Frailty in community-dwelling older adults: association with adverse outcomes

    PubMed Central

    Sánchez-García, Sergio; García-Peña, Carmen; Salvà, Antoni; Sánchez-Arenas, Rosalinda; Granados-García, Víctor; Cuadros-Moreno, Juan; Velázquez-Olmedo, Laura Bárbara; Cárdenas-Bahena, Ángel

    2017-01-01

    Background The study of frailty is important to identify the additional needs of medical long-term care and prevent adverse outcomes in community dwelling older adults. This study aimed to determine the prevalence of frailty and its association with adverse outcomes in community dwelling older adults. Methods A cross-sectional study was carried out from April to September 2014. The population sample was 1,252 older adults (≥60 years) who were beneficiaries of the Mexican Institute of Social Security (IMSS) in Mexico City. Data were derived from the database of the “Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults” (COSFOMA). Operationalization of the phenotype of frailty was performed using the criteria of Fried et al (weight loss, self-report of exhaustion, low physical activity, slow gait, and weakness). Adverse outcomes studied were limitation in basic activities of daily living (ADLs), falls and admission to emergency services in the previous year, and low quality of life (WHOQOL-OLD). Results Frailty was identified in 20.6% (n=258), pre-frailty in 57.6% (n=721), and not frail in 21.8% (n=273). The association between frailty and limitations in ADL was odds ratio (OR) =2.3 (95% confidence interval [CI] 1.7–3.2) and adjusted OR =1.7 (95% CI 1.2–2.4); falls OR =1.6 (95% CI 1.2–2.1) and adjusted OR =1.4 (95% CI 1.0–1.9); admission to emergency services OR =1.9 (95% CI 1.1–3.1) and adjusted OR =1.9 (95% CI 1.1–3.4); low quality of life OR =3.4 (95% CI 2.6–4.6) and adjusted OR =2.1 (95% CI 1.5–2.9). Conclusion Approximately 2 out of 10 older adults demonstrate frailty. This is associated with limitations in ADL, falls, and admission to emergency rooms during the previous year as well as low quality of life. PMID:28721028

  6. Risk factors for adverse driving outcomes in Dutch adults with ADHD and controls.

    PubMed

    Bron, Tannetje I; Bijlenga, Denise; Breuk, Minda; Michielsen, Marieke; Beekman, Aartjan T F; Kooij, J J Sandra

    2018-02-01

    To identify risk factors for adverse driving outcomes and unsafe driving among adults with and without ADHD in a Dutch sample. In this cross-sectional study, validated self-report questionnaires were used to compare driving history and current driving behavior between 330 adults diagnosed with ADHD and 330 controls. Adults with ADHD had significantly more adverse driving outcomes when compared to controls. Having an ADHD diagnosis significantly increased the odds for having had 3 or more vehicular crashes (OR = 2.72; p = .001). Driving frequency, male gender, age, high anxiety levels, high hostility levels, and alcohol use all significantly influenced the odds for unsafe driving behavior, for having had 12 or more traffic citations, and/or for having had 3 or more vehicular crashes. Alcohol use, and high levels of anxiety and hostility are highly prevalent among adults with ADHD, and they mediate the risk for negative driving outcomes in this group. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Waste incineration and adverse birth and neonatal outcomes: a systematic review.

    PubMed

    Ashworth, Danielle C; Elliott, Paul; Toledano, Mireille B

    2014-08-01

    Public concern about potential health risks associated with incineration has prompted studies to investigate the relationship between incineration and risk of cancer, and more recently, birth outcomes. We conducted a systematic review of epidemiologic studies evaluating the relationship between waste incineration and the risk of adverse birth and neonatal outcomes. Literature searches were performed within the MEDLINE database, through PubMed and Ovid interfaces, for the search terms; incineration, birth, reproduction, neonatal, congenital anomalies and all related terms. Here we discuss and critically evaluate the findings of these studies. A comprehensive literature search yielded fourteen studies, encompassing a range of outcomes (including congenital anomalies, birth weight, twinning, stillbirths, sex ratio and infant death), exposure assessment methods and study designs. For congenital anomalies most studies reported no association with proximity to or emissions from waste incinerators and "all anomalies", but weak associations for neural tube and heart defects and stronger associations with facial clefts and urinary tract defects. There is limited evidence for an association between incineration and twinning and no evidence of an association with birth weight, stillbirths or sex ratio, but this may reflect the sparsity of studies exploring these outcomes. The current evidence-base is inconclusive and often limited by problems of exposure assessment, possible residual confounding, lack of statistical power with variability in study design and outcomes. However, we identified a number of higher quality studies reporting significant positive relationships with broad groups of congenital anomalies, warranting further investigation. Future studies should address the identified limitations in order to help improve our understanding of any potential adverse birth outcomes associated with incineration, particularly focussing on broad groups of anomalies, to inform

  8. Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California.

    PubMed

    Larsen, Ashley E; Gaines, Steven D; Deschênes, Olivier

    2017-08-29

    Virtually all agricultural communities worldwide are exposed to agricultural pesticides. Yet, the health consequences of such exposure are poorly understood, and the scientific literature remains ambiguous. Using individual birth and demographic characteristics for over 500 000 birth observations between 1997-2011 in the agriculturally dominated San Joaquin Valley, California, we statistically investigate if residential agricultural pesticide exposure during gestation, by trimester, and by toxicity influences birth weight, gestational length, or birth abnormalities. Overall, our analysis indicates that agricultural pesticide exposure increases adverse birth outcomes by 5-9%, but only among the population exposed to very high quantities of pesticides (e.g., top 5th percentile, i.e., ~4200 kg applied over gestation). Thus, policies and interventions targeting the extreme right tail of the pesticide distribution near human habitation could largely eliminate the adverse birth outcomes associated with agricultural pesticide exposure documented in this study.The health consequences of exposure to pesticides are uncertain and subject to much debate. Here, the effect of exposure during pregnancy is investigated in an agriculturally dominated residential area, showing that an increase in adverse birth outcomes is observed with very high levels of pesticide exposure.

  9. Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data.

    PubMed

    Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

    2013-01-01

    The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage. Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment

  10. Prostate cancer outcomes in France: treatments, adverse effects and two-year mortality

    PubMed Central

    2014-01-01

    Background This very large population-based study investigated outcomes after a diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and adverse effects. Methods Among the 11 million men aged 40 years and over covered by the general national health insurance scheme, those with newly managed PCa in 2009 were followed for two years based on data from the national health insurance information system (SNIIRAM). Patients were identified using hospitalisation diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects of PCa treatments were identified by using hospital diagnoses, specific procedures and drug refunds. Results The age-standardised two-year all-cause mortality rate among the 43,460 men included in the study was 8.4%, twice that of all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had undergone prostatectomy, 36% had been treated by hormone therapy, 29% by radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of treatment-related adverse effects varied according to age and type of treatment. Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were treated for erectile dysfunction and 24% were treated for urinary disorders. The frequency of treatment for these disorders decreased during the second year compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders: 9% vs 20%). The frequencies of these treatments among men treated by external beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and 69 years with treated PCa, 46% received treatments for erectile dysfunction and 22% for urinary disorders. For controls without PCa but treated surgically for benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively. Conclusions We report high survival rates two years after a diagnosis of PCa, but a high frequency of PCa treatment-related adverse effects. These frequencies remain

  11. Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies.

    PubMed

    Jaques, Alice M; Amor, David J; Baker, H W Gordon; Healy, David L; Ukoumunne, Obioha C; Breheny, Sue; Garrett, Claire; Halliday, Jane L

    2010-12-01

    To determine whether adverse perinatal outcomes are increased in subfertile women. Cohort study. Two tertiary assisted reproductive technologies (ART) centers; Victorian births register. Records of women who registered with the clinics (1991-2000), but did not have an infant using ART, were linked to the birth register (1991-2004) to identify singleton non-ART births within 5 years of registration (N = 2171). Controls, matched by maternal age and year of infant's birth, were selected randomly from birth records (N = 4363). None. Adverse obstetric and perinatal outcomes. After adjusting for confounders, compared with controls, subfertile women had increased odds of hypertension or preeclampsia (adjusted odds ratio [OR] 1.29, 1.02-1.61), antepartum hemorrhage (adjusted OR 1.41, 1.05-1.89), perinatal death (adjusted OR 2.19, 1.10-4.36), low birth weight (adjusted OR 1.44, 1.11-1.85), preterm birth <37 weeks (adjusted OR 1.32, 1.05-1.67) or <31 weeks (adjusted OR 2.37, 1.35-4.13), and cesarean delivery (adjusted OR 1.56, 1.37-1.77). There was weak evidence for increased birth defects (adjusted OR 1.30, 0.98-1.72) and gestational diabetes (adjusted OR 1.25, 0.96-1.63). No increased risk was found for prelabor rupture of membranes, small for gestational age, or postpartum hemorrhage. Subfertile women with singleton births are at increased risk of several adverse outcomes. These risks should be considered during their antenatal care and when analyzing adverse effects of ART. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes.

    PubMed

    Lowe, Lynn P; Metzger, Boyd E; Dyer, Alan R; Lowe, Julia; McCance, David R; Lappin, Terence R J; Trimble, Elisabeth R; Coustan, Donald R; Hadden, David R; Hod, Moshe; Oats, Jeremy J N; Persson, Bengt

    2012-03-01

    To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 24-32 weeks' gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women.

  13. Prediction of adverse pregnancy outcome in monochorionic- diamniotic twin pregnancies complicated by selective fetal growth restriction.

    PubMed

    Monaghan, Caitriona; Kalafat, Erkan; Binder, Julia; Thilaganathan, Baskaran; Khalil, Asma

    2018-04-28

    To identify key factors implicated in adverse perinatal outcome in monochorionic twin pregnancies complicated by selective fetal growth restriction. This is a retrospective cohort study conducted in a single tertiary referral centre included all monochorionic diamniotic (MCDA) twin pregnancies complicated by selective fetal growth restriction (sFGR). The presence of co-existing twin to twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow (EDF) in the UA of the smaller twin. DV pulsatility indices were converted to z-scores and estimated fetal weight (EFW) values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome. Adverse perinatal outcome was defined according to survival and included both intra-uterine fetal demise and neonatal death of the FGR twin. We analysed 104 pregnancies complicated by sFGR. Sixty-six (63.5%) were diagnosed with type I and 38 (36.5%) with type II at initial presentation. Pregnancies complicated by type II sFGR were diagnosed (median GA 19.6 weeks' vs 21.5 weeks, p=0.012) and delivered (median GA 30.4 weeks' vs 32.57 weeks; p=0.055) earlier and are associated with increased risk of adverse perinatal outcomes (intrauterine demise of the smaller twin 19.7% vs 10.6%, p=0.001), when compared to type I sFGR. Twin pregnancies complicated by sFGR, whether type I or II, resulting in intrauterine demise have a significantly earlier onset of diagnosis (p<0.001), earlier GA at delivery (p<0.05), higher DV pulsatility index (p<0.05), and lower birth weight (BW) centile of the smaller twin (p<0.01) when compared to pregnancies resulting in livebirth. Co-existing TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with

  14. Identification of Putative Cardiovascular System Developmental Toxicants using a Classification Model based on Signaling Pathway-Adverse Outcome Pathways

    EPA Science Inventory

    An important challenge for an integrative approach to developmental systems toxicology is associating putative molecular initiating events (MIEs), cell signaling pathways, cell function and modeled fetal exposure kinetics. We have developed a chemical classification model based o...

  15. Biomarkers for Adverse Pregnancy Outcomes in Rheumatic Diseases.

    PubMed

    Soh, May Ching; Nelson-Piercy, Catherine

    2017-05-01

    Pregnancy is a delicate balance of angiogenic factors. Adverse pregnancy outcomes in the form of placental insufficiency occur when antiangiogenic factors predominate, which manifests as maternal-placental syndrome (MPS). Women with rheumatic disease are at increased risk of MPS. Endothelial damage from circulating antiangiogenic factors and other inflammatory molecules in combination with preexisting maternal vascular risk factors is the likely underlying pathophysiological process for MPS. It is likely that these changes persist, and additional "insults" from ongoing inflammation, medications, and disease damage contribute to the development of accelerated cardiovascular disease seen in young women with rheumatic disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands.

    PubMed

    Ravelli, A C J; Jager, K J; de Groot, M H; Erwich, J J H M; Rijninks-van Driel, G C; Tromp, M; Eskes, M; Abu-Hanna, A; Mol, B W J

    2011-03-01

    To study the effect of travel time, at the start or during labour, from home to hospital on mortality and adverse outcomes in pregnant women at term in primary and secondary care. Population-based cohort study from 2000 up to and including 2006. The Netherlands Perinatal Registry. A total of 751,926 singleton term hospital births. We assessed the impact of travel time by car, calculated from the postal code of the woman's residence to the 99 maternity units, on neonatal outcome. Logistic regression modelling with adjustments for gestational age, maternal age, parity, ethnicity, socio-economic status, urbanisation, tertiary care centres and volume of the hospital was used. Mortality (intrapartum, and early and late neonatal mortality) and adverse neonatal outcomes (mortality, Apgar <4 and/or admission to a neonatal intensive care unit). The mortality was 1.5 per 1000 births, and adverse outcomes occurred in 6.0 per 1000 births. There was a positive relationship between longer travel time (≥20 minutes) and total mortality (OR 1.17, 95% CI 1.002-1.36), neonatal mortality within 24 hours (OR 1.51, 95% CI 1.13-2.02) and with adverse outcomes (OR 1.27, 95% CI 1.17-1.38). In addition to travel time, both delivery at 37 weeks of gestation (OR 2.23, 95% CI 1.81-2.73) or 41 weeks of gestation (OR 1.52, 95% CI 1.29-1.80) increased the risk of mortality. A travel time from home to hospital of 20 minutes or more by car is associated with an increased risk of mortality and adverse outcomes in women at term in the Netherlands. These findings should be considered in plans for the centralisation of obstetric care. © 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.

  17. Fetal sex modifies effects of prenatal stress exposure and adverse birth outcomes.

    PubMed

    Wainstock, Tamar; Shoham-Vardi, Ilana; Glasser, Saralee; Anteby, Eyal; Lerner-Geva, Liat

    2015-01-01

    Prenatal maternal stress is associated with pregnancy complications, poor fetal development and poor birth outcomes. Fetal sex has also been shown to affect the course of pregnancy and its outcomes. The aim of this study was to evaluate whether fetal sex modifies the association between continuous exposure to life-threatening rocket attack alarms and adverse pregnancy outcomes. A retrospective cohort study was conducted in which the exposed group was comprised of 1846 women exposed to rocket-attack alarms before and during pregnancy. The unexposed group, with similar sociodemographic characteristics, delivered during the same period of time at the same medical center, but resided out of rocket-attack range. Multivariable models for each gender separately, controlling for possible confounders, evaluated the risk associated with exposure for preterm births (PTB), low birthweight (LBW), small for gestational age and small head circumference (HC). In both univariable and multivariable analyses exposure status was a significant risk factor in female fetuses only: PTB (adj. OR = 1.43; 1.04-1.96), LBW (adj. OR = 1.41; 1.02-1.95) and HC < 31 cm (adj. OR = 1.78; 1.11-2.88). In addition, regarding all adverse outcomes, the male-to-female ratio was higher in the exposed group than in the unexposed group. The findings support the hypothesis that male and female fetuses respond differentially to chronic maternal stress.

  18. Intersections of poverty, race/ethnicity, and sex: Alcohol consumption and adverse outcomes in the United States

    PubMed Central

    Glass, Joseph E.; Rathouz, Paul J.; Gattis, Maurice; Joo, Young Sun; Nelson, Jennifer C.; Williams, Emily C.

    2017-01-01

    We examine whether intersectionality theory—which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic —can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the U.S. Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption. PMID:28349171

  19. Intersections of poverty, race/ethnicity, and sex: alcohol consumption and adverse outcomes in the United States.

    PubMed

    Glass, Joseph E; Rathouz, Paul J; Gattis, Maurice; Joo, Young Sun; Nelson, Jennifer C; Williams, Emily C

    2017-05-01

    We examine whether intersectionality theory-which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic-can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the US Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption.

  20. Industrial PM2.5 cause pulmonary adverse effect through RhoA/ROCK pathway.

    PubMed

    Yan, Junyan; Lai, Chia-Hsiang; Lung, Shih-Chun Candice; Chen, Chongjun; Wang, Wen-Cheng; Huang, Pin-I; Lin, Chia-Hua

    2017-12-01

    According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM 2.5 ) is associated with adverse health effects, the major action mechanisms of different compositions of PM 2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM 2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM 2.5 , including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM 2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM 2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM 2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM 2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM 2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM 2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM 2.5 . Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Testing and testing positive: childhood adversities and later life HIV status among Kenyan women and their partners.

    PubMed

    Goodman, Michael L; Raimer-Goodman, Lauren; Chen, Catherine X; Grouls, Astrid; Gitari, Stanley; Keiser, Philip H

    2017-12-01

    Adverse childhood experiences are a critical feature of lifelong health. No research assesses whether childhood adversities predict HIV-testing behaviors, and little research analyzes childhood adversities and later life HIV status in sub-Saharan Africa. We use regression models with cross-sectional data from a representative sample (n = 1974) to analyze whether adverse childhood experiences, separately or as cumulative exposures, predict reports of later life HIV testing and testing HIV+ among semi-rural Kenyan women and their partners. No significant correlation was observed between thirteen cumulative childhood adversities and reporting prior HIV testing for respondent or partner. Separately, childhood sexual abuse and emotional neglect predicted lower odds of reporting having previously been tested for HIV. Witnessing household violence during one's childhood predicted significantly higher odds of reporting HIV+. Sexual abuse predicted higher odds of reporting a partner tested HIV+. Preventing sexual abuse and household violence may improve HIV testing and test outcomes among Kenyan women. More research is required to understand pathways between adverse childhood experiences and partner selection within Kenya and sub-Saharan Africa, and data presented here suggest understanding pathways may help improve HIV outcomes. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Allostatic load: A theoretical model for understanding the relationship between maternal posttraumatic stress disorder and adverse birth outcomes.

    PubMed

    Li, Yang; Rosemberg, Marie-Anne Sanon; Seng, Julia S

    2018-07-01

    Adverse birth outcomes such as preterm birth and low birth weight are significant public health concerns and contribute to neonatal morbidity and mortality. Studies have increasingly been exploring the predictive effects of maternal posttraumatic stress disorder (PTSD) on adverse birth outcomes. However, the biological mechanisms by which maternal PTSD affects birth outcomes are not well understood. Allostatic load refers to the cumulative dysregulations of the multiple physiological systems as a response to multiple social-ecological levels of chronic stress. Allostatic load has been well documented in relation to both chronic stress and adverse health outcomes in non-pregnant populations. However, the mediating role of allostatic load is less understood when it comes to maternal PTSD and adverse birth outcomes. To propose a theoretical model that depicts how allostatic load could mediate the impact of maternal PTSD on birth outcomes. We followed the procedures for theory synthesis approach described by Walker and Avant (2011), including specifying focal concepts, identifying related factors and relationships, and constructing an integrated representation. We first present a theoretical overview of the allostatic load theory and the other 4 relevant theoretical models. Then we provide a brief narrative review of literature that empirically supports the propositions of the integrated model. Finally, we describe our theoretical model. The theoretical model synthesized has the potential to advance perinatal research by delineating multiple biomarkers to be used in future. After it is well validated, it could be utilized as the theoretical basis for health care professionals to identify high-risk women by evaluating their experiences of psychosocial and traumatic stress and to develop and evaluate service delivery and clinical interventions that might modify maternal perceptions or experiences of stress and eliminate their impacts on adverse birth outcomes. Copyright

  3. Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins.

    PubMed

    van Bilsen, Jolanda H M; Sienkiewicz-Szłapka, Edyta; Lozano-Ojalvo, Daniel; Willemsen, Linette E M; Antunes, Celia M; Molina, Elena; Smit, Joost J; Wróblewska, Barbara; Wichers, Harry J; Knol, Edward F; Ladics, Gregory S; Pieters, Raymond H H; Denery-Papini, Sandra; Vissers, Yvonne M; Bavaro, Simona L; Larré, Colette; Verhoeckx, Kitty C M; Roggen, Erwin L

    2017-01-01

    The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www

  4. Childhood adversity and social functioning in psychosis: Exploring clinical and cognitive mediators.

    PubMed

    Palmier-Claus, Jasper; Berry, Katherine; Darrell-Berry, Hannah; Emsley, Richard; Parker, Sophie; Drake, Richard; Bucci, Sandra

    2016-04-30

    Childhood adversity may increase risk of impaired social functioning across the continuum of psychosis. However, the pathways by which adversity dictates functional outcome remain underexplored. This study investigated the association between childhood adversity and social functioning, and the clinical and cognitive mediators of this relationship. Fifty-four clinical (20 chronic, 20 first episode, 14 at ultra-high risk) and 120 non-clinical participants completed standardised questionnaires, semi-structured interviews and tests of theory of mind ability. The authors used multiple group structural equation modelling to fit mediation models allowing for differential relationships between the clinical and non-clinical samples. When examining each pathway separately, depression, paranoia and anxious attachment mediated the effect of childhood adversity on social functioning. In a combined model, depression was the only significant mediating variable with greater adversity predicting lower mood across groups. Childhood adversity did not significantly predict theory of mind ability in any of the models. This is the first study to indicate that childhood adversity acts on social functioning by increasing levels of depression, suggesting a common mechanism across the spectrum of psychosis. Clinical interventions should target low mood in order to improve social functioning at all stages of psychotic disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Adverse obstetric outcomes during delivery hospitalizations complicated by suicidal behavior among US pregnant women.

    PubMed

    Zhong, Qiu-Yue; Gelaye, Bizu; Smoller, Jordan W; Avillach, Paul; Cai, Tianxi; Williams, Michelle A

    2018-01-01

    The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. We performed a cross-sectional analysis of delivery hospitalizations from 2007-2012 National (Nationwide) Inpatient Sample. From the same hospitalization record, International Classification of Diseases codes were used to identify suicidal behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were obtained using logistic regression. Of the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal behavior. Women with suicidal behavior were at a heightened risk for outcomes including antepartum hemorrhage (aOR = 2.34; 95% CI: 1.47-3.74), placental abruption (aOR = 2.07; 95% CI: 1.17-3.66), postpartum hemorrhage (aOR = 2.33; 95% CI: 1.61-3.37), premature delivery (aOR = 3.08; 95% CI: 2.43-3.90), stillbirth (aOR = 10.73; 95% CI: 7.41-15.56), poor fetal growth (aOR = 1.70; 95% CI: 1.10-2.62), and fetal anomalies (aOR = 3.72; 95% CI: 2.57-5.40). No significant association was observed for maternal suicidal behavior with cesarean delivery, induction of labor, premature rupture of membranes, excessive fetal growth, and fetal distress. The mean length of stay was longer for women with suicidal behavior. During delivery hospitalization, women with suicidal behavior are at increased risk for many adverse obstetric outcomes, highlighting the importance of screening for and providing appropriate clinical care for women with suicidal behavior during pregnancy.

  6. Multiple Pathways Linking Racism to Health Outcomes

    PubMed Central

    Harrell, Camara Jules P.; Burford, Tanisha I.; Cage, Brandi N.; Nelson, Travette McNair; Shearon, Sheronda; Thompson, Adrian; Green, Steven

    2012-01-01

    This commentary discusses advances in the conceptual understanding of racism and selected research findings in the social neurosciences. The traditional stress and coping model holds that racism constitutes a source of aversive experiences that, when perceived by the individual, eventually lead to poor health outcomes. Current evidence points to additional psychophysiological pathways linking facets of racist environments with physiological reactions that contribute to disease. The alternative pathways emphasize prenatal experiences, subcortical emotional neural circuits, conscious and preconscious emotion regulation, perseverative cognitions, and negative affective states stemming from racist cognitive schemata. Recognition of these pathways challenges change agents to use an array of cognitive and self-controlling interventions in mitigating racism’s impact. Additionally, it charges policy makers to develop strategies that eliminate deep-seated structural aspects of racism in society. PMID:22518195

  7. Four trace elements in pregnant women and their relationships with adverse pregnancy outcomes.

    PubMed

    Shen, P-J; Gong, B; Xu, F-Y; Luo, Y

    2015-12-01

    Lack of trace elements during pregnancy is detrimental to maternal and fetal health. Our aim is to study the changes in trace element levels in Chinese pregnant women and their association with adverse pregnancy outcomes. 1568 cases of Chinese pregnant women in remote areas were collected for a prospective cohort study. Serum copper, zinc, calcium and iron levels were measured at pre-pregnancy, 1st trimester (7w-12w), 2nd trimester (24w-28w) and 3rd trimester (35w-40w). (1) Serum copper levels was significantly higher after pregnancy than before, calcium and iron levels decreased, but zinc levels did not change significantly. (2) Copper and zinc deficiency in pregnant women was not a common finding, but lack of iron and calcium was frequently encountered; iron deficiency was especially common in the 3rd trimester (42.27%). (3) Serum zinc and iron levels in patients who either had a miscarriage or a preterm delivery were significantly lower than in the control group (p < 0.05). In patients with premature rupture of membranes, serum zinc levels were significantly lower (p < 0.05). In patients with intrauterine growth restriction (IUGR), serum copper, zinc, calcium and iron were significantly lower (p < 0.05). Trace elements is closely associated with fetal growth and development during pregnancy. Deficiency can lead to adverse pregnancy outcomes. Therefore, we should have a reasonable diet, replenish trace elements, therefore reducing the occurrence of adverse pregnancy outcomes.

  8. VIOLENT CRIME EXPOSURE CLASSIFICATION AND ADVERSE BIRTH OUTCOMES: A GEOGRAPHICALLY-DEFINED COHORT STUDY

    EPA Science Inventory

    Background

    Area-level socioeconomic disparities have long been associated with adverse pregnancy outcomes. Crime is an important element of the neighborhood environment inadequately investigated in the public health literature. Using geocoded linked birth, crime and cens...

  9. Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data

    PubMed Central

    Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

    2013-01-01

    Background The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of pregnant women to be tested for syphilis and ≥90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Methods and Findings Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was “probable active,” and for testing and treatment coverage. Conclusions Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that

  10. Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows

    EPA Science Inventory

    Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

  11. Differentiating high priority pathway-based toxicity from non-specific effects in high throughput toxicity data: A foundation for prioritizing AOP development.

    EPA Science Inventory

    The ToxCast chemical screening approach enables the rapid assessment of large numbers of chemicals for biological effects, primarily at the molecular level. Adverse outcome pathways (AOPs) offer a means to link biomolecular effects with potential adverse outcomes at the level of...

  12. Adverse perinatal outcomes associated with moderate or severe maternal anaemia based on parity in Finland during 2006-10.

    PubMed

    Räisänen, Sari; Kancherla, Vijaya; Gissler, Mika; Kramer, Michael R; Heinonen, Seppo

    2014-09-01

    Anaemia during pregnancy is an important public health problem. We investigated whether the association between maternal anaemia during pregnancy and adverse perinatal outcomes differed between nulliparous and multiparous women. A retrospective population-based cohort study was conducted using data on all singleton births (n = 290 662) recorded in the Finnish Medical Birth Register during 2006-10. Maternal anaemia was defined as a maternal haemoglobin level of <100 g/L). Adverse perinatal outcomes that were examined included preterm delivery (<37 weeks), small-for-gestational age (SGA, <2 standard deviation), admission to neonatal intensive care, stillbirth, early neonatal death, and major congenital anomalies. An association between anaemia and adverse outcomes was assessed by logistic regression analysis. The prevalence of anaemia during pregnancy was 2.5% among nulliparous women and 2.3% among multiparous women. Among nulliparous women, anaemia was not associated with adverse perinatal outcomes. Among multiparous women, anaemia was associated with preterm delivery (adjusted odds ratio [aOR] 1.32, [95% CI 1.14, 1.53]), SGA (aOR 1.27, [95% CI 1.04, 1.55]), and admission to neonatal intensive care (aOR 1.23, [95% CI 1.10, 1.38]); there was a trend towards increased odds of major congenital anomalies (aOR 1.15, [95% CI 0.99, 1.34]). These data underscore that maternal anaemia is associated with several adverse perinatal outcomes. This association was, however, confined to multiparous women. Future research should explore in detail the timing of anaemia in these associations. © 2014 John Wiley & Sons Ltd.

  13. Preventable health and cost burden of adverse birth outcomes associated with pregestational diabetes in the United States.

    PubMed

    Peterson, Cora; Grosse, Scott D; Li, Rui; Sharma, Andrea J; Razzaghi, Hilda; Herman, William H; Gilboa, Suzanne M

    2015-01-01

    Preconception care for women with diabetes can reduce the occurrence of adverse birth outcomes. We aimed to estimate the preconception care (PCC)-preventable health and cost burden of adverse birth outcomes associated with diagnosed and undiagnosed pregestational diabetes mellitus (PGDM) in the United States. Among women of reproductive age (15-44 years), we estimated age- and race/ethnicity-specific prevalence of diagnosed and undiagnosed diabetes. We applied age and race/ethnicity-specific pregnancy rates, estimates of the risk reduction from PCC for 3 adverse birth outcomes (preterm birth, major birth defects, and perinatal mortality), and lifetime medical and lost productivity costs for children with those outcomes. Using a probabilistic model, we estimated the reduction in adverse birth outcomes and costs associated with universal PCC compared with no PCC among women with PGDM. We did not assess maternal outcomes and associated costs. We estimated 2.2% of US births are to women with PGDM. Among women with diagnosed diabetes, universal PCC might avert 8397 (90% prediction interval [PI], 5252-11,449) preterm deliveries, 3725 (90% PI, 3259-4126) birth defects, and 1872 (90% PI, 1239-2415) perinatal deaths annually. Associated discounted lifetime costs averted for the affected cohort of children could be as high as $4.3 billion (90% PI, 3.4-5.1 billion) (2012 US dollars). PCC among women with undiagnosed diabetes could yield an additional $1.2 billion (90% PI, 951 million-1.4 billion) in averted cost. Results suggest a substantial health and cost burden associated with PGDM that could be prevented by universal PCC, which might offset the cost of providing such care. Published by Elsevier Inc.

  14. Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

    PubMed

    Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah

    2012-01-01

    Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. Prospective cohort. HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%. In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. Clinicaltrials.gov NCT00993031.

  15. Malaria infection, poor nutrition and indoor air pollution mediate socioeconomic differences in adverse pregnancy outcomes in Cape Coast, Ghana.

    PubMed

    Amegah, Adeladza K; Damptey, Obed K; Sarpong, Gideon A; Duah, Emmanuel; Vervoorn, David J; Jaakkola, Jouni J K

    2013-01-01

    The epidemiological evidence linking socioeconomic deprivation with adverse pregnancy outcomes has been conflicting mainly due to poor measurement of socioeconomic status (SES). Studies have also failed to evaluate the plausible pathways through which socioeconomic disadvantage impacts on pregnancy outcomes. We investigated the importance of maternal SES as determinant of birth weight and gestational duration in an urban area and evaluated main causal pathways for the influence of SES. A population-based cross-sectional study was conducted among 559 mothers accessing postnatal services at the four main health facilities in Cape Coast, Ghana in 2011. Information on socioeconomic characteristics of the mothers was collected in a structured questionnaire. In multivariate linear regression adjusting for maternal age, parity and gender of newborn, low SES resulted in 292 g (95% CI: 440-145) reduction in birth weight. Important SES-related determinants were neighborhood poverty (221 g; 95% CI: 355-87), low education (187 g; 95% CI: 355-20), studentship during pregnancy (291 g; 95% CI: 506-76) and low income (147 g; 95% CI: 277-17). In causal pathway analysis, malaria infection (6-20%), poor nutrition (2-51%) and indoor air pollution (10-62%) mediated substantial proportions of the observed effects of socioeconomic deprivation on birth weight. Generalized linear models adjusting for confounders indicated a 218% (RR: 3.18; 95% CI: 1.41-7.21) risk increase of LBW and 83% (RR: 1.83; 95% CI: 1.31-2.56) of PTB among low income mothers. Low and middle SES was associated with 357% (RR: 4.57; 95% CI: 1.67-12.49) and 278% (RR: 3.78; 95% CI: 1.39-10.27) increased risk of LBW respectively. Malaria infection, poor nutrition and indoor air pollution respectively mediated 10-21%, 16-44% and 31-52% of the observed effects of socioeconomic disadvantage on LBW risk. We provide evidence of the effects of socioeconomic deprivation, substantially mediated by malaria infection, poor nutrition

  16. Systematic review of adverse outcomes of external cephalic version and persisting breech presentation at term.

    PubMed

    Nassar, Natasha; Roberts, Christine L; Barratt, Alexandra; Bell, Jane C; Olive, Emily C; Peat, Brian

    2006-03-01

    The aim of this study was to determine the frequency of adverse maternal and fetal outcomes of both external cephalic version (ECV) and persisting breech presentation at term. We conducted a systematic review of the literature using Medline, Embase and All Evidence Based Medicine (EBM) Reviews databases. Data were extracted from studies that compared women who had an ECV from 36 weeks' gestation with a similar control group of women enrolled at the same gestational age, eligible for, but who did not have an ECV. Eleven studies with a total of 2503 women were included. Adverse outcomes related to ECV were rarely reported and in most studies there was no evidence that relevant outcomes were ascertained among similar women who did not have an ECV. There was no increased risk of antepartum fetal death associated with ECV, but numbers were small. There were no reported cases of uterine rupture, placental abruption, prelabour rupture of membranes or cord prolapse, but these outcomes were not examined among controls. Onset of labour within 24 h and nuchal cord was non-significantly higher among women who had an ECV compared with those with a persisting breech. Despite limited reporting and small numbers, the results of our review suggest that adverse maternal and fetal outcomes of both ECV and persisting breech presentation are rare. Only with improved reporting and collection of safety data on ECV and persisting breech presentation can we provide high-quality information to assist informed decision making by pregnant women with a breech presentation at term.

  17. Adverse Childhood Experiences and Young Adult Health Outcomes among Youth Aging Out of Foster Care.

    PubMed

    Rebbe, Rebecca; Nurius, Paula S; Courtney, Mark E; Ahrens, Kym R

    2018-04-27

    Former youth in foster care (YFC) are at greater risk of chronic health conditions than their peers. Although research in general population samples has demonstrated a dose-response relationship between adverse childhood experiences (ACEs) and adult health outcomes, few studies have conducted similar analyses in highly stress-exposed populations such as YFC. This paper uses person-centered latent class analysis (LCA) methods to examine the relationship between different profiles of ACE exposures and divergent health trajectories amongst this high-risk population. Data are from longitudinal research that followed transition-age YFC from age 17-26 (N =732). Using three subgroups previously identified by their ACEs histories, Complex, Environmental, and Lower Adversity groups, we applied group mean statistics to test for differences between the groups for physical and sexual health outcomes in young adulthood. In contrast to prior research demonstrating that the Environmental group was at the highest risk of criminal behavior outcomes, for most of the physical and sexual health risk outcomes evaluated in this paper, the Complex Adversity group had the highest risk. This study demonstrates that there are subgroups of YFC which each have a distinct profile of risk in young adulthood, with the Complex group being at highest risk of the physical and sexual health risk outcomes evaluated. Findings strongly suggest the need for targeted strategies to promote screening for ACEs and chronic health conditions, linkage to adult healthcare, and continuity of care for adolescents and young adults in foster care to offset these trajectories. Copyright © 2018. Published by Elsevier Inc.

  18. Adverse obstetric outcomes during delivery hospitalizations complicated by suicidal behavior among US pregnant women

    PubMed Central

    Gelaye, Bizu; Smoller, Jordan W.; Avillach, Paul; Cai, Tianxi; Williams, Michelle A.

    2018-01-01

    Objective The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. Methods We performed a cross-sectional analysis of delivery hospitalizations from 2007–2012 National (Nationwide) Inpatient Sample. From the same hospitalization record, International Classification of Diseases codes were used to identify suicidal behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were obtained using logistic regression. Results Of the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal behavior. Women with suicidal behavior were at a heightened risk for outcomes including antepartum hemorrhage (aOR = 2.34; 95% CI: 1.47–3.74), placental abruption (aOR = 2.07; 95% CI: 1.17–3.66), postpartum hemorrhage (aOR = 2.33; 95% CI: 1.61–3.37), premature delivery (aOR = 3.08; 95% CI: 2.43–3.90), stillbirth (aOR = 10.73; 95% CI: 7.41–15.56), poor fetal growth (aOR = 1.70; 95% CI: 1.10–2.62), and fetal anomalies (aOR = 3.72; 95% CI: 2.57–5.40). No significant association was observed for maternal suicidal behavior with cesarean delivery, induction of labor, premature rupture of membranes, excessive fetal growth, and fetal distress. The mean length of stay was longer for women with suicidal behavior. Conclusion During delivery hospitalization, women with suicidal behavior are at increased risk for many adverse obstetric outcomes, highlighting the importance of screening for and providing appropriate clinical care for women with suicidal behavior during pregnancy. PMID:29447245

  19. Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows (poster)

    EPA Science Inventory

    Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

  20. Cigarette smoking and adverse health outcomes among adults receiving federal housing assistance☆

    PubMed Central

    Helms, Veronica E.; King, Brian A.; Ashley, Peter J.

    2017-01-01

    Cigarette smoking is higher among low-income adults and individuals who reside in federally assisted housing are particularly susceptible to the adverse effects of smoking and secondhand smoke exposure. This study assessed smoking-related behaviors and health outcomes among U.S. adults who received federal housing assistance during 2006–2012. National Health Interview Survey data linked with administrative data from the U.S. Department of Housing and Urban Development were analyzed; 5218 HUD-assisted adults were assessed. Demographic characteristics associated with smoking, including frequency and consumption, were assessed among adult cigarette smokers. Fourteen adverse health outcomes were examined among cigarette smoking and nonsmoking adults. One-third (33.6%) of HUD-assisted adults were current cigarette smokers. Smoking prevalence was highest among adults aged 25–44 (42.5%), non-Hispanic whites (39.5%), and adults who resided in households with children (37.5%). Half attempted to quit in the past year; 82.1% were daily smokers; and, 35.8% of daily smokers reported smoking 20+ cigarettes a day. Multivariable analyses revealed that compared to nonsmokers, cigarette smokers had increased likelihood of reporting fair or poor health (95% CI: 1.04–1.52), chronic obstructive pulmonary disease (CI: 1.87–3.06), disability (CI: 1.25–1.83), asthma (CI: 1.02–1.55), serious psychological distress (CI: 1.39–2.52), >1 emergency room visit in the past year (CI: 1.09–1.56), and ≥10 work loss days in the past year (CI: 1.15–3.06). Adults who receive housing assistance represent an at-risk population for adverse health outcomes associated with smoking and secondhand smoke. Housing assistance programs provide a valuable platform for the implementation of evidence-based tobacco prevention and control measures, including smokefree policies. PMID:28192095

  1. Cellulitis in Obesity: Adverse Outcomes Affected by Increases in Body Mass Index.

    PubMed

    Theofiles, Meghan; Maxson, Julie; Herges, Lori; Marcelin, Alberto; Angstman, Kurt B

    2015-10-01

    Cellulitis in obese patients is associated with increased rates of treatment failure compared to those with normal body mass index (BMI); however, patients have not been extensively studied in the outpatient environment or stratified based on range of obesity and associated risk factors. This study looked at antibiotic dosing and treatment failure in the obese population from the primary care perspective and accounts for BMI range, weight, comorbid diabetes, and tobacco use. This study was a retrospective chart review of 637 adult primary care patients designed to evaluate rates of treatment failure of outpatient cellulitis among patients of varying BMI. Treatment failure was defined as (a) hospital admission for intravenous antibiotics, (b) prolonged antibiotic course, or (c) requiring a different antibiotic after initial course. Adverse outcomes were not statistically significant between normal BMI and those with BMI ≥40 kg/m(2). A subset of patients with a BMI ≥50 kg/m(2) was noted to have approximately twice the rate of adverse outcomes as the normal BMI group. While controlling for age, gender, race, diagnosis of diabetes mellitus, and tobacco use, a BMI of ≥50 kg/m(2) and a weight ≥120 kg was associated with adverse outcomes with an odds ratio of 2.440 (95% CI, 1.260-4.724; P = .008) and 2.246 (95% CI, 1.154-4.369; P = .017), respectively. Patients with cellulitis weighing >120kg or with a BMI ≥50 kg/m(2) were at greatest risk for treatment failure in the outpatient setting, even when controlling for comorbid diabetes and tobacco use. As morbid obesity continues to become more prevalent, it becomes imperative that primary care physicians have better antibiotic dosing guidelines to account for the physiologic effects of obesity to minimize the risk of increased morbidity, health care costs, and antibiotic resistance. © The Author(s) 2015.

  2. Metabolic Profiles Predict Adverse Events Following Coronary Artery Bypass Grafting

    PubMed Central

    Shah, Asad A.; Craig, Damian M.; Sebek, Jacqueline K.; Haynes, Carol; Stevens, Robert C.; Muehlbauer, Michael J.; Granger, Christopher B.; Hauser, Elizabeth R.; Newby, L. Kristin; Newgard, Christopher B.; Kraus, William E.; Hughes, G. Chad; Shah, Svati H.

    2012-01-01

    Objectives Clinical models incompletely predict outcomes following coronary artery bypass grafting. Novel molecular technologies may identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. Methods The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected prior to surgery. Principal-components analysis and Cox proportional hazards regression modeling were used to assess the relation between metabolite factor levels and a composite outcome of post-coronary artery bypass grafting myocardial infarction, need for percutaneous coronary intervention, repeat coronary artery bypass grafting, or death. Results Over a mean follow-up of 4.3 ± 2.4 years, 126 subjects (26.4%) suffered an adverse event. Three principal-components analysis-derived factors were significantly associated with adverse outcome in univariable analysis: short-chain dicarboxylacylcarnitines (factor 2, P=0.001); ketone-related metabolites (factor 5, P=0.02); and short-chain acylcarnitines (factor 6, P=0.004). These three factors remained independently predictive of adverse outcome after multivariable adjustment: factor 2 (adjusted hazard ratio 1.23; 95% confidence interval [1.10-1.38]; P<0.001), factor 5 (1.17 [1.01-1.37], P=0.04), and factor 6 (1.14 [1.02-1.27], P=0.03). Conclusions Metabolic profiles are independently associated with adverse outcomes following coronary artery bypass grafting. These profiles may represent novel biomarkers of risk that augment existing tools for risk stratification of coronary artery bypass grafting patients and may elucidate novel biochemical pathways that mediate risk. PMID:22306227

  3. The household food insecurity gradient and potential reductions in adverse population mental health outcomes in Canadian adults.

    PubMed

    Jessiman-Perreault, Geneviève; McIntyre, Lynn

    2017-12-01

    Household food insecurity is related to poor mental health. This study examines whether the level of household food insecurity is associated with a gradient in the risk of reporting six adverse mental health outcomes. This study further quantifies the mental health impact if severe food insecurity, the extreme of the risk continuum, were eliminated in Canada. Using a pooled sample of the Canadian Community Health Survey (N = 302,683), we examined the relationship between level of food insecurity, in adults 18-64 years, and reporting six adverse mental health outcomes. We conducted a probit analysis adjusted for multi-variable models, to calculate the reduction in the odds of reporting mental health outcomes that might accrue from the elimination of severe food insecurity. Controlling for various demographic and socioeconomic covariates, a food insecurity gradient was found in six mental health outcomes. We calculated that a decrease between 8.1% and 16.0% in the reporting of these mental health outcomes would accrue if those who are currently severely food insecure became food secure, after controlling for covariates. Household food insecurity has a pervasive graded negative effect on a variety of mental health outcomes, in which significantly higher levels of food insecurity are associated with a higher risk of adverse mental health outcomes. Reduction of food insecurity, particularly at the severe level, is a public health concern and a modifiable structural determinant of health worthy of macro-level policy intervention.

  4. Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

    PubMed

    Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

    2017-03-01

    Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1

  5. Clinical Presentation and Outcome of Patients With Optic Pathway Glioma.

    PubMed

    Robert-Boire, Viviane; Rosca, Lorena; Samson, Yvan; Ospina, Luis H; Perreault, Sébastien

    2017-10-01

    Optic pathway gliomas (OPGs) occur sporadically or in patients with neurofibromatosis type 1 (NF1). The purpose of this study was to evaluate the clinical presentation at diagnosis and at progression of patients with OPGs. We conducted a chart review of patients with OPGs diagnosed in a single center over a period of 15 years. Demographic data including age, sex, NF1 status, clinical presentation, and outcome were collected. Of the 40 patients who were identified, 23 had sporadic tumors (57.5%) and 17 had NF1-related tumors (42.5%). Among the children with NF1, there was a significant overrepresentation of girls (82.3%) (P = 0.02), while among the children without NF1, there were slightly more boys (56.5%) than girls (43.5%). The presence of nystagmus was strongly associated with sporadic optic pathway gliomas. Poor visual outcome was related to tumor affecting both optic pathways, hydrocephalus at diagnosis, and optic nerve atrophy. Of the 40 patients, five died of OPG complications (12.5%) and all had sporadic tumors. Our cohort is one of the largest with OPGs and a detailed description of the clinical presentation both at diagnosis and at progression. We observed a significant difference between sporadic and NF1 optic pathway gliomas in terms of demographics, clinical presentation, and outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Linking mode of action of the model respiratory and photosynthesis uncoupler 3,5-dichlorophenol to adverse outcomes in Lemna minor.

    PubMed

    Xie, Li; Gomes, Tânia; Solhaug, Knut Asbjørn; Song, You; Tollefsen, Knut Erik

    2018-04-01

    Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers. The results demonstrated that 3,5-DCP caused concentration-dependent effects in chloroplasts and mitochondria. Uncoupling of oxidative phosphorylation (OXPHOS), reduction in chlorophyll (Chlorophyll a and b) content, reproduction rate and frond size were the most sensitive endpoints, followed by formation of reactive oxygen species (ROS), lipid peroxidation (LPO), reduction of carotenoid content and impairment of photosynthesis efficiency. Suppression of photosystem II (PSII) efficiency, electron transport rate (ETR), chlorophyll (a and b) contents and oxidative phosphorylation (OXPHOS) were closely correlated while ROS production and LPO were negative correlated with ETR, carotenoid content and growth parameters. A network of conceptual Adverse Outcome Pathways (AOPs) was developed to decipher the causal relationships between molecular, cellular, and apical adverse effects occurring in L. minor to form a basis for future studies with similar compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Maternal Snoring May Predict Adverse Pregnancy Outcomes: A Cohort Study in China.

    PubMed

    Ge, Xing; Tao, Fangbiao; Huang, Kun; Mao, Leijing; Huang, Sanhuan; Niu, Ying; Hao, Jiahu; Sun, Yanli; Rutayisire, Erigene

    2016-01-01

    To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes. Pregnant women were consecutively recruited in their first trimester. Habitual snoring was screened by using a questionnaire in the 1st and 3rd trimester, respectively. According to the time of snoring, participants were divided into pregnancy onset snorers, chronic snorers and non-snorers. Logistic regressions were performed to examine the associations between snoring and pregnancy outcomes. Of 3 079 pregnant women, 16.6% were habitual snorers, with 11.7% were pregnancy onset snorers and 4.9% were chronic snorers. After adjusting for potential confounders, chronic snorers were independently associated with gestational diabetes mellitus (GDM) (RR 1.66, 95%CI 1.09-2.53). Both pregnancy onset and chronic snorers were independently associated with placental adhesion (RR 1.96, 95%CI 1.17-3.27, and RR 2.33, 95%CI 1.22-4.46, respectively). Pregnancy onset snorers were at higher risk of caesarean delivery (RR 1.37, 95%CI 1.09-1.73) and having macrosomia (RR 1.54, 95%CI 1.05-2.27) and large for gestational age (LGA) (RR 1.71, 95%CI 1.31-2.24) infants. In addition, being overweight or obese before pregnancy plays an important role in mediating snoring and adverse pregnancy outcomes. Maternal snoring may increase the risk of adverse pregnancy outcomes, and being overweight or obese before pregnancy with snoring is remarkable for researchers. Further studies are still needed to confirm our results.

  8. Maternal Snoring May Predict Adverse Pregnancy Outcomes: A Cohort Study in China

    PubMed Central

    Ge, Xing; Tao, Fangbiao

    2016-01-01

    Objective To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes. Methods Pregnant women were consecutively recruited in their first trimester. Habitual snoring was screened by using a questionnaire in the 1st and 3rd trimester, respectively. According to the time of snoring, participants were divided into pregnancy onset snorers, chronic snorers and non-snorers. Logistic regressions were performed to examine the associations between snoring and pregnancy outcomes. Results Of 3 079 pregnant women, 16.6% were habitual snorers, with 11.7% were pregnancy onset snorers and 4.9% were chronic snorers. After adjusting for potential confounders, chronic snorers were independently associated with gestational diabetes mellitus (GDM) (RR 1.66, 95%CI 1.09–2.53). Both pregnancy onset and chronic snorers were independently associated with placental adhesion (RR 1.96, 95%CI 1.17–3.27, and RR 2.33, 95%CI 1.22–4.46, respectively). Pregnancy onset snorers were at higher risk of caesarean delivery (RR 1.37, 95%CI 1.09–1.73) and having macrosomia (RR 1.54, 95%CI 1.05–2.27) and large for gestational age (LGA) (RR 1.71, 95%CI 1.31–2.24) infants. In addition, being overweight or obese before pregnancy plays an important role in mediating snoring and adverse pregnancy outcomes. Conclusions Maternal snoring may increase the risk of adverse pregnancy outcomes, and being overweight or obese before pregnancy with snoring is remarkable for researchers. Further studies are still needed to confirm our results. PMID:26871434

  9. Intrahospital transfers and adverse patient outcomes: An analysis of administrative health data.

    PubMed

    Blay, Nicole; Roche, Michael; Duffield, Christine; Xu, Xiaoyue

    2017-12-01

    To determine whether there was an association between intra-hospital transfers and adverse outcomes. Transfers between clinical units and between beds on the same unit are routine aspects of an episode of care in acute hospitals. The rate of these transfers per episode has increased in response to high occupancy levels, a decline in bed numbers, and increased demand for hospital services. The impact of the number of transfers between both wards and beds on patient outcomes is not widely explored. Retrospective cross sectional design using hospital administrative data. Data were extracted from existing hospital administrative datasets for one large metropolitan hospital for the financial year 2008-09 in Australia (n = 14,133). Descriptive analyses and logistic regression models were developed for each of 3 selected patient outcomes. Nearly one-tenth of patients (9.2%) experienced a fall with injury, 3.8% of surgical patients a wound infection and 0.1% a complication from medication errors. For each bed or ward transfer, the odds of falls and wound infections increased. Medication errors were not associated with either bed or ward moves. Hospitals should minimise the number of bed and ward transfers per episode of care in order to reduce the likelihood of adverse patient outcomes. Current bed management policies and practices should be evaluated and further refined to address this need. Additional strategies include improving coordination and communication during and after transfer. Nurses must consider the potential cost of intrahospital transfers on patients, length of stay and bed availability. © 2017 John Wiley & Sons Ltd.

  10. Maternal Nutritional Status Predicts Adverse Birth Outcomes among HIV-Infected Rural Ugandan Women Receiving Combination Antiretroviral Therapy

    PubMed Central

    Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah

    2012-01-01

    Objective Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. Design Prospective cohort. Methods HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. Results Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%. Conclusions In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. Trial Registration Clinicaltrials.gov NCT00993031 PMID:22879899

  11. Television viewing associated with adverse dietary outcomes in children ages 2-6.

    PubMed

    Ford, C; Ward, D; White, M

    2012-12-01

    The aim of this paper was to systematically review the evidence for the association between television viewing and diet in children ages 2-6. Data sources included PubMed, PsycINFO, EMBASE, ERIC, SportDISCUS, Sociological Abstracts, Web of Science and hand searches of reference lists of relevant articles. Twelve studies were reviewed in which the relationship between television viewing and diet was assessed in children between the ages of 2 and 6. All but one study reported significant relationship between television viewing time and adverse dietary outcomes. Parent-reported television viewing time was used to assay child television viewing in all included studies. Food frequency survey was the most frequent method of dietary assessment, and parent served as proxies for children in all studies. Lower fruit and/or vegetable intake was the most frequently reported dietary outcome, followed by increased energy intake with increased television viewing. The majority of studies reported adverse dietary outcomes with as little as 1 h of daily television exposure. While these results are consistent with recommendations from child health advocates to limit television viewing in young children, they also suggest that further efforts to limit television viewing in young children may be needed to aid in obesity prevention. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

  12. Risk-adjusted models for adverse obstetric outcomes and variation in risk-adjusted outcomes across hospitals.

    PubMed

    Bailit, Jennifer L; Grobman, William A; Rice, Madeline Murguia; Spong, Catherine Y; Wapner, Ronald J; Varner, Michael W; Thorp, John M; Leveno, Kenneth J; Caritis, Steve N; Shubert, Phillip J; Tita, Alan T; Saade, George; Sorokin, Yoram; Rouse, Dwight J; Blackwell, Sean C; Tolosa, Jorge E; Van Dorsten, J Peter

    2013-11-01

    Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take preexisting patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for 5 obstetric outcomes and assess hospital performance across these outcomes. We studied a cohort of 115,502 women and their neonates born in 25 hospitals in the United States from March 2008 through February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed. Venous thromboembolism occurred too infrequently (0.03%; 95% confidence interval [CI], 0.02-0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage, 2.29%; 95% CI, 2.20-2.38, peripartum infection, 5.06%; 95% CI, 4.93-5.19, severe perineal laceration at spontaneous vaginal delivery, 2.16%; 95% CI, 2.06-2.27, neonatal composite, 2.73%; 95% CI, 2.63-2.84). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital-adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration. Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance. Copyright © 2013 Mosby, Inc. All rights reserved.

  13. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

  14. The Association Between Adverse Child Health, Psychological, Educational and Social Outcomes, and Nondependent Parental Substance: A Rapid Evidence Assessment.

    PubMed

    McGovern, Ruth; Gilvarry, Eilish; Addison, Michelle; Alderson, Hayley; Geijer-Simpson, Emma; Lingam, Raghu; Smart, Debbie; Kaner, Eileen

    2018-01-01

    Between 5% and 30% of children in high-income countries live with a substance misusing parent, the majority of which is below dependent levels. However, little is understood about the impact of nondependent parental substance misuse upon children. We searched the international literature using rigorous systematic methods to identify studies examining parental substance misuse and adverse outcomes in children. The inclusion criteria were cross-sectional, longitudinal, case-control, and cohort studies; of children aged 0-18 years whose parents are high-risk substance misusers; reporting on their health, psychological, substance use, educational, and social outcomes. We identified 36 papers (from 33 unique studies), most of which were assessed as being of medium to high methodological quality ( N= 28). Parental nondependent substance misuse was found to be associated with adversity in children, with strong evidence of an association with externalizing difficulties ( N = 7 papers, all finding an association) and substance use ( N = 23 papers, all finding an association) in adolescents and some evidence of adverse health outcomes in early childhood ( N = 6/8 papers finding an association). There is less evidence of an association between parental substance misuse and adverse educational and social outcomes. The body of evidence was largest for parental alcohol misuse, with research examining the impact of parental illicit drug use being limited. Methodological limitations restrict our ability to make causal inference. Nonetheless, the prevalence of adverse outcomes in children whose parents are nondependent substance misusers highlights the need for practitioners to intervene with this population before a parent has developed substance dependency.

  15. Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis

    PubMed Central

    Derricott, Hayley; Jones, Rebecca L.; Heazell, Alexander E. P.

    2017-01-01

    Background Advanced maternal age (AMA; ≥35 years) is an increasing trend and is reported to be associated with various pregnancy complications. Objective To determine the risk of stillbirth and other adverse pregnancy outcomes in women of AMA. Search strategy Embase, Medline (Ovid), Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LILACS and conference proceedings were searched from ≥2000. Selection criteria Cohort and case-control studies reporting data on one or more co-primary outcomes (stillbirth or fetal growth restriction (FGR)) and/or secondary outcomes in mothers ≥35 years and <35 years. Data collection and analysis The effect of age on pregnancy outcome was investigated by random effects meta-analysis and meta-regression. Stillbirth rates were correlated to rates of maternal diabetes, obesity, hypertension and use of assisted reproductive therapies (ART). Main results Out of 1940 identified titles; 63 cohort studies and 12 case-control studies were included in the meta-analysis. AMA increased the risk of stillbirth (OR 1.75, 95%CI 1.62 to 1.89) with a population attributable risk of 4.7%. Similar trends were seen for risks of FGR, neonatal death, NICU unit admission restriction and GDM. The relationship between AMA and stillbirth was not related to maternal morbidity or ART. Conclusions Stillbirth risk increases with increasing maternal age. This is not wholly explained by maternal co-morbidities and use of ART. We propose that placental dysfunction may mediate adverse pregnancy outcome in AMA. Further prospective studies are needed to directly test this hypothesis. PMID:29040334

  16. Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Malaria and Sexually Transmitted and Reproductive Tract Infections.

    PubMed

    Chico, R Matthew; Chaponda, Enesia Banda; Ariti, Cono; Chandramohan, Daniel

    2017-04-15

    We conducted a prospective cohort study in Zambia among pregnant women who received intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP). We calculated the odds ratios (ORs) of adverse birth outcomes by IPTp-SP exposure, 0-1 dose (n = 126) vs ≥2 doses (n = 590) and ≥2 doses (n = 310) vs ≥3 doses (n = 280) in 7 categories of malaria infection and sexually transmitted and reproductive tract infections (STIs/RTIs). We found no significant differences in baseline prevalence of infection across IPTp-SP exposure groups. However, among women given 2 doses compared to 0-1 dose, the odds of any adverse birth outcome were reduced 45% (OR, 0.55; 95% confidence interval [CI], 0.36, 0.86) and 13% further with ≥3 doses (OR, 0.43; 95% CI, 0.27, 0.68). Two or more doses compared to 0-1 dose reduced preterm delivery by 58% (OR, 0.42; 95% CI, 0.27, 0.67) and 21% further with ≥3 doses (OR, 0.21; 95% CI, 0.13, 0.35). Women with malaria at enrollment who received ≥2 doses vs 0-1 had 76% lower odds of any adverse birth outcome (OR, 0.24; 95% 0.09, 0.66), and Neisseria gonorrhoeae and/or Chlamydia trachomatis had 92% lower odds of any adverse birth outcome (OR, 0.08; 95% CI, 0.01, 0.64). Women with neither a malaria infection nor STIs/RTIs who received ≥2 doses had 73% fewer adverse birth outcomes (OR, 0.27; 95% CI, 0.11, 0.68). IPTp-SP appears to protect against malaria, STIs/RTIs, and other unspecified causes of adverse birth outcome. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. The relationship between residential proximity to extremely low frequency power transmission lines and adverse birth outcomes.

    PubMed

    Auger, Nathalie; Joseph, Dominique; Goneau, Marc; Daniel, Mark

    2011-01-01

    Occupational exposure to electromagnetic fields has been linked to adverse birth outcomes. This study evaluated whether maternal residential proximity to power transmission lines was associated with adverse birth outcomes. Live singleton births in the Montréal and Québec census metropolitan areas from 1990 to 2004 were extracted from the Québec birth file (N=707,215). Proximity was defined as residing within 400 m of a transmission line. Generalised estimating equations were used to evaluate associations between residential proximity to transmission lines and preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA) birth and infant sex, accounting for maternal age, education, marital status, ethnicity, parity, period of birth, and neighbourhood median household income. There was no association between residential proximity to transmission lines and PTB, LBW and infant sex in unadjusted and adjusted models. A lower likelihood of SGA birth was present for some distance categories (eg, adjusted OR 0.88, 95% CI 0.81 to 0.95 for 50-75 m relative to ≥400 m). Residential proximity to transmission lines is not associated with adverse births outcomes.

  18. The role of Mycoplasma and Ureaplasma in adverse pregnancy outcomes.

    PubMed

    Murtha, Amy P; Edwards, James M

    2014-12-01

    Genital mycoplasmas are frequently found in the vaginal flora across socioeconomic and ethnic groups and have been demonstrated to be involved in adverse perinatal outcomes. Both Mycoplasma and Ureaplasma spp cause inflammation potentially leading to spontaneous preterm birth and PPROM as well as postdelivery infectious complications and neonatal infections. Herein we have provided an overview of the existing literature and supportive evidence for genital mycoplasma's role in perinatal complications. Future research will need to focus on clearly delineating the species, allowing for discrimination of their effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Adverse Neurodevelopmental Outcomes.

    PubMed

    Mainigi, Monica; Rosenzweig, Jason M; Lei, Jun; Mensah, Virginia; Thomaier, Lauren; Talbot, C Conover; Olalere, Devvora; Ord, Teri; Rozzah, Rayyan; Johnston, Michael V; Burd, Irina

    2016-06-01

    While live births resulting from assisted reproductive technology (ART) exceed 1% of total births annually, the effect of ART on fetal development is not well understood. Data have demonstrated that IVF leads to alterations in DNA methylation and gene expression in the placenta that may have long-term effects on health and disease. Studies have linked adverse neurodevelopmental outcomes to ART, although human studies are inconclusive. In order to isolate the peri-implantation environment and its effects on brain development, we utilized a mouse model with and without superovulation and examined the effect of adult behavior as well as adult cortical neuronal density. Adult offspring of superovulated dams showed increased anxiety-like behavior compared to offspring of naturally mated dams (P < .05). There was no difference in memory and learning tests between the 2 groups. The adult brains from offspring of superovulated recipients had fewer neurons per field compared to naturally mated control offspring (P < .05). In order to examine potential pathways leading to these changes, we measured messenger RNA and microRNA (miRNA) expression in fetal brains at E18.5. Microarray analysis found that miRNAs miR-122, miR-144, and miR-211, involved in regulation of neuronal migration and differentiation, were downregulated in brains of offspring exposed to a superovulated environment(P < .05). There was also altered expression of genes involved in neuronal development. These results suggest that the peri-implantation environment can affect neurodevelopment and can lead to behavioral changes in adulthood. Human studies with long-term follow-up of children from ART are necessary to further investigate the influence of ART on the offspring. © The Author(s) 2015.

  20. Inflammatory bowel disease: risk factors for adverse pregnancy outcome and the impact of maternal weight gain.

    PubMed

    Oron, Galia; Yogev, Yariv; Shcolnick, Smadar; Shkolnik, Smadar; Hod, Moshe; Fraser, Gerald; Wiznitzer, Arnon; Melamed, Nir

    2012-11-01

    To identify risk factors for adverse pregnancy outcome in women with inflammatory bowel disease (IBD) and to assess the effect of maternal pre-pregnancy weight and weight gain during pregnancy on pregnancy outcome. A retrospective, matched control study of all gravid women with IBD treated in a single tertiary center. Data were compared with healthy controls matched to by age, parity and pre-pregnancy BMI in a 3:1 ratio. Overall, 300 women were enrolled, 75 women in the study group (28 with ulcerative colitis and 47 with Crohn's disease) and 225 in the control group. The rates of preterm delivery and small for gestational age were higher in the study group (13.3 vs. 5.3% p = 0.02 and 6.7 vs. 0.9%, p = 0.004). The rate of cesarean section (36 vs. 19.1%; p = 0.002), NICU admission (10.7 vs. 4.0%, p = 0.03) and low 5-Min Apgar (4.0 vs. 0.4%, p = 0.02) were increased in the study group. Disease activity within 3 months of conception [OR 8.4 (1.3-16.3)] and maternal weight gain of less than 12 kg. [OR 3.6 (1.1-12.2)] were associated with adverse pregnancy outcome. Active disease at conception and inappropriate weight gain during pregnancy are associated with increased adverse pregnancy outcome in patients with IBD.

  1. Weight of evidence evaluation of a network of adverse ...

    EPA Pesticide Factsheets

    Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating many high nutrient crops, such as fruits, vegetables, and nuts. Both chemical and non-chemical stressors have been implicated as possible contributors to colony failure, however, the potential role(s) of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptors (nAChRs) in the central nervous system to eliminate target pest insects. However, mounting evidence indicates that these neonicotinoids also may adversely affect beneficial pollinators, such as the honey bee, via impairments on learning and memory, and ultimately foraging success. The specific mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. The objective of this review was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between activation of the physiological target site, the nAChR, and colony level consequences. Development of AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect norm

  2. B-type natriuretic peptide and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the Folic Acid for Vascular Outcome Reduction in...

  3. Physical Performance Characteristics of Assisted Living Residents and Risk for Adverse Health Outcomes

    ERIC Educational Resources Information Center

    Giuliani, Carol A.; Gruber-Baldini, Ann L.; Park, Nan S.; Schrodt, Lori A.; Rokoske, Franzi; Sloane, Philip D.; Zimmerman, Sheryl

    2008-01-01

    Purpose: Researchers know little about the physical performance ability of residential care/assisted living (RC/AL) residents and its relationship to adverse outcomes such as fracture, nursing home placement, functional decline, and death. The purposes of this article are to (a) describe the functional characteristics of RC/AL residents, (b)…

  4. Prognostic accuracy of cerebroplacental ratio and middle cerebral artery Doppler for adverse perinatal outcome: systematic review and meta‐analysis

    PubMed Central

    De Boer, M. A.; Heymans, M. W.; Schoonmade, L. J.; Bossuyt, P. M. M.; Mol, B. W. J.; De Groot, C. J. M.; Bax, C. J.

    2018-01-01

    ABSTRACT Objective Doppler ultrasonographic assessment of the cerebroplacental ratio (CPR) and middle cerebral artery (MCA) is widely used as an adjunct to umbilical artery (UA) Doppler to identify fetuses at risk of adverse perinatal outcome. However, reported estimates of its accuracy vary considerably. The aim of this study was to review systematically the prognostic accuracies of CPR and MCA Doppler in predicting adverse perinatal outcome, and to compare these with UA Doppler, in order to identify whether CPR and MCA Doppler evaluation are of added value to UA Doppler. Methods PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, from inception to June 2016, for studies on the prognostic accuracy of UA Doppler compared with CPR and/or MCA Doppler in the prediction of adverse perinatal outcome in women with a singleton pregnancy of any risk profile. Risk of bias and concerns about applicability were assessed using the QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies‐2) tool. Meta‐analysis was performed for multiple adverse perinatal outcomes. Using hierarchal summary receiver–operating characteristics meta‐regression models, the prognostic accuracy of CPR vs MCA Doppler was compared indirectly, and CPR and MCA Doppler vs UA Doppler compared directly. Results The search identified 4693 articles, of which 128 studies (involving 47 748 women) were included. Risk of bias or suboptimal reporting was detected in 120/128 studies (94%) and substantial heterogeneity was found, which limited subgroup analyses for fetal growth and gestational age. A large variation was observed in reported sensitivities and specificities, and in thresholds used. CPR outperformed UA Doppler in the prediction of composite adverse outcome (as defined in the included studies) (P < 0.001) and emergency delivery for fetal distress (P = 0.003), but was comparable to UA Doppler for the other outcomes. MCA Doppler performed significantly worse

  5. Adverse Outcome Pathways in Ecotoxicology Research

    EPA Science Inventory

    Just as for chemical risk assessments for human health, ecotoxicology risk assessments face the daunting challenge posed by the large number of chemicals currently in use that could potentially impact the environment. In addition, the limited amount of toxicological data on many ...

  6. Self-Reported Benefits and Adverse Outcomes of Hot Yoga Participation.

    PubMed

    Mace, Casey; Eggleston, Brandon

    2016-01-01

    There is little to no scientific data about the health benefits or risks to participating in hot yoga, in particular distinguishing it from the practice of non-hot yoga. This study aims to provide some preliminary evidence about the risks and benefits of participating in hot yoga. Future studies will be able to build off the findings herein. This study utilized online survey software (Qualtrics) and recruited participants through convenience sampling (n = 157) by targeting yoga websites and online forums. As there is currently no known questionnaire that has been developed to assess the risks and benefits of hot yoga participation, an exploratory measure was designed to gain more detailed responses from participants. Descriptive epidemiological analyses we re conducted. Participants of hot yoga had a number of pre-existing health conditions. Both benefits and adverse outcomes were reported. The most frequently reported health benefits of hot yoga in this sample included increased flexibility (63%), improved mood (58%), increased fitness (43%), and improved stamina (42%). Just over half of the participants reported some sort of adverse event during a hot yoga session (n = 82). The most commonly reported adverse events included dizziness (60%), feeling light headed (61%), nausea (35%), and dehydration (34%), amongst others. Further study on the risks and benefits of hot yoga participation is required.

  7. Self-Reported Benefits and Adverse Outcomes of Hot Yoga Participation.

    PubMed

    Mace, Casey; Eggleston, Brandon

    2016-08-15

    There is little to no scientific data about the health benefits or risks to participating in hot yoga, in particular distinguishing it from the practice of non-hot yoga. This study aims to provide some preliminary evidence about the risks and benefits of participating in hot yoga. Future studies will be able to build off the findings herein. This study utilized online survey software (Qualtrics) and recruited participants through convenience sampling (n = 157) by targeting yoga websites and online forums. As there is currently no known questionnaire that has been developed to assess the risks and benefits of hot yoga participation, an exploratory measure was designed to gain more detailed responses from participants. Descriptive epidemiological analyses we re conducted. Participants of hot yoga had a number of pre-existing health conditions. Both benefits and adverse outcomes were reported. The most frequently reported health benefits of hot yoga in this sample included increased flexibility (63%), improved mood (58%), increased fitness (43%), and improved stamina (42%). Just over half of the participants reported some sort of adverse event during a hot yoga session (n = 82). The most commonly reported adverse events included dizziness (60%), feeling light headed (61%), nausea (35%), and dehydration (34%), amongst others. Further study on the risks and benefits of hot yoga participation is required.

  8. Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

    ERIC Educational Resources Information Center

    Conradt, Elisabeth; Abar, Beau; Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2014-01-01

    Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn…

  9. Prevalence, risk factors and associated adverse pregnancy outcomes of anaemia in Chinese pregnant women: a multicentre retrospective study.

    PubMed

    Lin, Li; Wei, Yumei; Zhu, Weiwei; Wang, Chen; Su, Rina; Feng, Hui; Yang, Huixia

    2018-04-23

    Anaemia in pregnant women is a public health problem, especially in developing countries. The aim of this study was to assess the prevalence and related risk factors of anaemia during pregnancy in a large multicentre retrospective study (n = 44,002) and to determine the adverse pregnancy outcomes in women with or without anaemia. The study is a secondary data analysis of a retrospective study named "Gestational diabetes mellitus Prevalence Survey (GPS) study in China". Structured questionnaires were used to collect socio-demographic characteristics, haemoglobin levels and pregnancy outcomes from all the participants. Anaemia in pregnancy is defined as haemoglobin < 110 g/L. We used SPSS software to assess the predictors of anaemia and associated adverse pregnancy outcomes. The overall prevalence of anaemia was 23.5%. Maternal anaemia was significantly associated with maternal age ≥ 35 years (AOR = 1.386), family per capita monthly income< 1000 CNY (AOR = 1.671), rural residence (AOR = 1.308) and pre-pregnancy BMI < 18.5 kg/m 2 (AOR = 1.237). Adverse pregnancy outcomes, including GDM, polyhydramnios, preterm birth, low birth weight (< 2500 g), neonatal complications and NICU admission, increased significantly (P < 0.001) in those with anaemia than those without. The results indicated that anaemia continues to be a severe health problem among pregnant women in China. Anaemia is associated with adverse pregnancy outcomes. Pregnant women should receive routine antenatal care and be given selective iron supplementation when appropriate.

  10. Do adult men with untreated hypospadias have adverse outcomes? A pilot study using a social media advertised survey

    PubMed Central

    Schlomer, Bruce; Breyer, Benjamin; Copp, Hillary; Baskin, Laurence; DiSandro, Michael

    2014-01-01

    Objective Hypospadias is usually treated in childhood. Therefore, the natural history of untreated mild hypospadias is unknown. We hypothesized that men with untreated hypospadias, especially mild, do not have adverse outcomes. Materials Facebook was used to advertise an electronic survey to men older than 18 years. Men with untreated hypospadias identified themselves and indicated the severity of hypospadias with a series of questions. Outcomes included: Sexual Health Inventory for Men (SHIM), penile curvature and difficulty with intercourse, International Prostate Symptom Score (IPSS), Penile Perception Score (PPS), psychosexual milestones, paternity, infertility, sitting to urinate, and the CDC HRQOL-4 module. Results 736 men completed self-anatomy questions and 52 (7.1%) self-identified with untreated hypospadias. Untreated hypospadias participants reported worse SHIM (p < 0.001) and IPSS scores (p = 0.05), more ventral penile curvature (p = 0.003) and resulting difficulty with intercourse (p < 0.001), worse satisfaction with meatus (p = 0.011) and penile curvature (p = 0.048), and more sitting to urinate (p = 0.07). When stratified by mild and severe hypospadias, severe hypospadias was associated with more adverse outcomes than mild hypospadias. Conclusion Men with untreated hypospadias reported worse outcomes compared with non-hypospadiac men. Mild untreated hypospadias had fewer adverse outcomes than severe hypospadias. Research is needed to determine if treatment of childhood hypospadias improves outcomes in adults, especially for mild hypospadias. PMID:24613143

  11. Anemia: An Independent Predictor Of Adverse Outcomes In Older Patients With Atrial Fibrillation.

    PubMed

    Ali, Ali N; Athavale, Nandkishor V; Abdelhafiz, Ahmed H

    2016-01-01

    Both anemia and atrial fibrillation are common in older people and their prevalence is age dependent which increases as population ages. Anemia, especially acute onset, predisposes to new onset atrial fibrillation which is likely to be mediated through inducing heart failure first and this predisposition seems to be potentiated by the presence of renal impairment. Anemia adds to the comorbidity burden of patients with atrial fibrillation and independently increases the risks of adverse outcomes such as increased hospitalization, mortality, bleeding and thromboembolic events. Early detection and correction of anemia in patients with atrial fibrillation may have a positive impact on reducing these adverse events.

  12. Adverse birth outcomes associated with Zika virus exposure during pregnancy in São José do Rio Preto, Brazil.

    PubMed

    Nogueira, M L; Nery Júnior, N R R; Estofolete, C F; Bernardes Terzian, A C; Guimarães, G F; Zini, N; Alves da Silva, R; Dutra Silva, G C; Junqueira Franco, L C; Rahal, P; Bittar, C; Carneiro, B; Vasconcelos, P F C; Freitas Henriques, D; Barbosa, D M U; Lopes Rombola, P; de Grande, L; Negri Reis, A F; Palomares, S A; Wakai Catelan, M; Cruz, L E A A; Necchi, S H; Mendonça, R C V; Penha Dos Santos, I N; Alavarse Caron, S B; Costa, F; Bozza, F A; Soares de Souza, A; Brandão de Mattos, C C; de Mattos, L C; Vasilakis, N; Oliani, A H; Vaz Oliani, D C M; Ko, A I

    2018-06-01

    We aimed to report the first 54 cases of pregnant women infected by Zika virus (ZIKV) and their virologic and clinical outcomes, as well as their newborns' outcomes, in 2016, after the emergence of ZIKV in dengue-endemic areas of São Paulo, Brazil. This descriptive study was performed from February to October 2016 on 54 quantitative real-time PCR ZIKV-positive pregnant women identified by the public health authority of São José do Rio Preto, São Paulo, Brazil. The women were followed and had clinical and epidemiologic data collected before and after birth. Adverse outcomes in newborns were analysed and reported. Urine or blood samples from newborns were collected to identify ZIKV infection by reverse transcription PCR (RT-PCR). A total of 216 acute Zika-suspected pregnant women were identified, and 54 had the diagnosis confirmed by RT-PCR. None of the 54 women miscarried. Among the 54 newborns, 15 exhibited adverse outcomes at birth. The highest number of ZIKV infections occurred during the second and third trimesters. No cases of microcephaly were reported, though a broad clinical spectrum of outcomes, including lenticulostriate vasculopathy, subependymal cysts, and auditory and ophthalmologic disorders, were identified. ZIKV RNA was detected in 18 of 51 newborns tested and in eight of 15 newborns with adverse outcomes. Although other studies have associated many newborn outcomes to ZIKV infection during pregnancy, these same adverse outcomes were rare or nonexistent in this study. The clinical presentation the newborns we studied was mild compared to other reports, suggesting that there is significant heterogeneity in congenital Zika infection. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. Coronary atherosclerosis and adverse outcomes in patients with recent-onset atrial fibrillation and troponin rise.

    PubMed

    Conti, Alberto; Angeli, Elena; Scorpiniti, Margherita; Alesi, Andrea; Trausi, Federica; Lazzeretti, Delia; Padeletti, Luigi; Gensini, Gian Franco

    2015-10-01

    The relationship between troponin and atrial fibrillation (AF) without acute coronary syndrome is still unclear. We sought to investigate the presence of coronary atherosclerosis and adverse outcomes in patients with AF. Consecutive patients with recent-onset AF and without severe comorbidities were enrolled between 2004 and 2013. Patients with a troponin rise or with adverse outcomes were considered for coronary angiography and revascularization when "critical" stenosis (≥70%) was recognized. Propensity score matching was performed to adjust for baseline characteristics; after matching, no differences existed between the groups of patients with or without troponin rise. The primary end point was the composite of acute coronary syndrome, revascularization, and cardiac death at 1- and 12-month follow-ups. Of 3627 patients enrolled, 3541 completed the study; 202 (6%) showed troponin rise; and 91 (3%), an adverse outcome. In the entire cohort, on multivariate analysis, the odds ratio for the occurrence of the primary end point of troponin rise was 14 (95% confidence interval [CI], 10-23; P<.001), and that of known coronary artery disease was 3 (CI, 2-5; P=.001). In the matching cohort, the odds ratio of troponin rise was 10 (CI, 4-22; P<.001), and that of TIMI score greater than 2 was 4 (CI, 2-9; P≤.001). In the entire cohort, patients with or without troponin rise achieved the primary end point in 38 (19%) and 43 (1%) patients, respectively (P<.001). Stroke occurred in 4 (2%) and 20 (1%), respectively (P=.018). Critical stenosis and revascularization account for 23 (12%) and 15 (1%), respectively (P<.001). In the matching cohort, results were confirmed, but incidence of stroke was comparable. Patients with recent-onset AF and troponin rise showed higher prevalence of coronary atherosclerosis and adverse cardiac events. Stroke per se did not succeed in justifying the high morbidity. Thus, beyond stroke, coronary atherosclerosis might have a pivotal role in poor

  14. Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study, Peru

    PubMed Central

    Wingfield, Tom; Boccia, Delia; Tovar, Marco; Gavino, Arquímedes; Zevallos, Karine; Montoya, Rosario; Lönnroth, Knut; Evans, Carlton A.

    2014-01-01

    Background Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs. Methods and Findings From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1

  15. Defining catastrophic costs and comparing their importance for adverse tuberculosis outcome with multi-drug resistance: a prospective cohort study, Peru.

    PubMed

    Wingfield, Tom; Boccia, Delia; Tovar, Marco; Gavino, Arquímedes; Zevallos, Karine; Montoya, Rosario; Lönnroth, Knut; Evans, Carlton A

    2014-07-01

    Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed "catastrophic" but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs. From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2-4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%-43%) in the least-poor houses versus 48% (95% CI = 36%-50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%-61%] versus 38% [95% CI = 34%-41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7-15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3-3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00-1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95% CI = 1.1-2.6], p = 0.01). The

  16. Does the thyroid-stimulating hormone measured concurrently with first trimester biochemical screening tests predict adverse pregnancy outcomes occurring after 20 weeks gestation?

    PubMed

    Ong, Gregory S Y; Hadlow, Narelle C; Brown, Suzanne J; Lim, Ee Mun; Walsh, John P

    2014-12-01

    Maternal hypothyroidism in early pregnancy is associated with adverse outcomes, but not consistently across studies. First trimester screening for chromosomal anomalies is routine in many centers and provides an opportunity to test thyroid function. To determine if thyroid function tests performed with first trimester screening predicts adverse pregnancy outcomes. A cohort study of 2411 women in Western Australia with singleton pregnancies attending first trimester screening between 9 and 14 weeks gestation. We evaluated the association between TSH, free T4, free T3, thyroid antibodies, free beta human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein A (PAPP-A) with a composite of adverse pregnancy events as the primary outcome. Secondary outcomes included placenta previa, placental abruption, pre-eclampsia, pregnancy loss after 20 weeks gestation, threatened preterm labor, preterm birth, small size for gestational age, neonatal death, and birth defects. TSH exceeded the 97.5th percentile for the first trimester (2.15 mU/L) in 133 (5.5%) women, including 22 (1%) with TSH above the nonpregnant reference range (4 mU/L) and 5 (0.2%) above 10 mU/L. Adverse outcomes occurred in 327 women (15%). TSH and free T4 did not differ significantly between women with or without adverse pregnancy events. On the multivariate analysis, neither maternal TSH >2.15 mU/L nor TSH as a continuous variable predicted primary or secondary outcomes. Testing maternal TSH as part of first trimester screening does not predict adverse pregnancy outcomes. This may be because in the community setting, mainly mild abnormalities in thyroid function are detected.

  17. Effect of interpregnancy interval on adverse pregnancy outcomes in northern Tanzania: a registry-based retrospective cohort study.

    PubMed

    Mahande, Michael J; Obure, Joseph

    2016-06-07

    Both short and long interpregnancy intervals have been associated with an increased risk of adverse pregnancy outcomes. There is limited information about the impact of interpregnancy interval on pregnancy (IPI) outcomes in Tanzania. The objective of this study was to assess the effect of IPI on adverse pregnancy outcomes. We performed a retrospective cohort study using maternally-linked data from Kilimanjaro Christian Medical Centre (KCMC) birth registry. A total of 17,030 singlet births from women who delivered singleton infant at KCMC from 2000 to 2010 were studied. Women with multi-fetal gestations and those who were referred from rural areas for various medical reasons were excluded. Outcome variables were preterm birth, low birth weight infants and perinatal death. A multiple logistic regression was used to assess the association between IPI and pregnancy outcomes. The median IPI was 36 months. Compared with IPIs of 24-36 months (referent group), short interpregnancy intervals (<24 months) was associated with preterm delivery (OR 1 · 52; 95 % CI 1.31-1.74); low birth weight (OR 1 · 61; 95 % CI 1 · 34-1.72) and perinatal death, (OR 1 · 63; 95 % CI 1.22-1.91). The IPI of 37-59 months or longer were also associated with higher risks of preterm birth and low birth weight, but not with perinatal death. Our study confirmed that both short and long IPI are independent risk factors for adverse pregnancy outcomes. These finding emphasize the importance of providing support for family planning programs which will support optimal IPI and improve pregnancy outcomes.

  18. Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles across the Lifespan

    PubMed Central

    Zilioli, Samuele; Slatcher, Richard B.; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

    2016-01-01

    Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here we tested whether childhood adversity was associated with diurnal cortisol parameters, and whether this link was partially explained by self-esteem. In both adults and children, childhood adversity was associated with lower levels of cortisol at awakening and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Lastly, those youth who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared to those youth whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the lifespan. PMID:27481911

  19. Potential roles of omics data in the use of adverse outcome pathways for environmental risk assessment

    EPA Science Inventory

    The current approach to assessing adverse effects of chemicals in the environment is largely based on a battery of in-vivo study methods and a limited number of accepted in-silico approaches. For most substances the pool of data from which to predict ecosystem effects is limited ...

  20. Aggregate Exposure Pathways in Support of Risk Assessment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tan, Yu-Mei; Leonard, Jeremy A.; Edwards, Stephen

    Over time, risk assessment has shifted from establishing relationships between exposure to a single chemical and a resulting adverse health outcome, to evaluation of multiple chemicals and disease outcomes simultaneously. As a result, there is an increasing need to better understand the complex mechanisms that influence risk of chemical and non-chemical stressors, beginning at their source and ending at a biological endpoint relevant to human or ecosystem health risk assessment. Just as the Adverse Outcome Pathway (AOP) framework has emerged as a means of providing insight into mechanism-based toxicity, the exposure science community has seen the recent introduction of themore » Aggregate Exposure Pathway (AEP) framework. AEPs aid in making exposure data applicable to the FAIR (i.e., findable, accessible, interoperable, and reusable) principle, especially by (1) organizing continuous flow of disjointed exposure information;(2) identifying data gaps, to focus resources on acquiring the most relevant data; (3) optimizing use and repurposing of existing exposure data; and (4) facilitating interoperability among predictive models. Herein, we discuss integration of the AOP and AEP frameworks and how such integration can improve confidence in both traditional and cumulative risk assessment approaches.« less

  1. Aggregate Exposure Pathways in Support of Risk Assessment

    DOE PAGES

    Tan, Yu-Mei; Leonard, Jeremy A.; Edwards, Stephen; ...

    2018-03-29

    Over time, risk assessment has shifted from establishing relationships between exposure to a single chemical and a resulting adverse health outcome, to evaluation of multiple chemicals and disease outcomes simultaneously. As a result, there is an increasing need to better understand the complex mechanisms that influence risk of chemical and non-chemical stressors, beginning at their source and ending at a biological endpoint relevant to human or ecosystem health risk assessment. Just as the Adverse Outcome Pathway (AOP) framework has emerged as a means of providing insight into mechanism-based toxicity, the exposure science community has seen the recent introduction of themore » Aggregate Exposure Pathway (AEP) framework. AEPs aid in making exposure data applicable to the FAIR (i.e., findable, accessible, interoperable, and reusable) principle, especially by (1) organizing continuous flow of disjointed exposure information;(2) identifying data gaps, to focus resources on acquiring the most relevant data; (3) optimizing use and repurposing of existing exposure data; and (4) facilitating interoperability among predictive models. Herein, we discuss integration of the AOP and AEP frameworks and how such integration can improve confidence in both traditional and cumulative risk assessment approaches.« less

  2. Adverse fetal outcome in road accidents: Injury mechanism study and injury criteria development in a pregnant woman finite element model.

    PubMed

    Auriault, F; Thollon, L; Pérès, J; Behr, M

    2016-12-01

    This study documents the development of adverse fetal outcome predictors dedicated to the analysis of road accidents involving pregnant women. To do so, a pre-existing whole body finite element model representative of a 50th percentile 26 weeks pregnant woman was used. A total of 8 accident scenarios were simulated with the model positioned on a sled. Each of these scenarios was associated to a risk of adverse fetal outcome based on results from real car crash investigations involving pregnant women from the literature. The use of airbags and accidents involving unbelted occupants were not considered in this study. Several adverse fetal outcome potential predictors were then evaluated with regard to their correlation to this risk of fetal injuries. Three predictors appeared strongly correlated to the risk of adverse fetal outcome: (1) the intra uterine pressure at the placenta fetal side area (r=0.92), (2) the fetal head acceleration (HIC) (r=0.99) and (3) area of utero-placental interface over a strain threshold (r=0.90). Finally, sensitivity analysis against slight variations of the simulation parameters was performed and assess robustness of these criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Terbutaline pump maintenance therapy after threatened preterm labour for reducing adverse neonatal outcomes.

    PubMed

    Chawanpaiboon, Saifon; Laopaiboon, Malinee; Lumbiganon, Pisake; Sangkomkamhang, Ussanee S; Dowswell, Therese

    2014-03-23

    After successful inhibition of threatened preterm labour women are at high risk of recurrent preterm labour. Terbutaline pump maintenance therapy has been used to reduce adverse neonatal outcomes. This review replaces an earlier Cochrane review, published in 2002, which is no longer being updated by the team. To determine the effectiveness of terbutaline pump maintenance therapy after threatened preterm labour in reducing adverse neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014) and reference lists of retrieved studies. Randomised controlled trials comparing terbutaline pump therapy with alternative therapy, placebo, or no therapy after arrest of threatened preterm labour. Two review authors independently assessed the studies for inclusion and then extracted data as eligible for inclusion in qualitative and quantitative synthesis (meta-analysis). Four studies were included with a total of 234 women randomised. The overall methodological quality of the included studies was mixed; two studies provided very little information on study methods, there was high sample attrition in one study and in three studies the risk of performance bias was high. We found no strong evidence that terbutaline maintenance therapy offered any advantages over saline placebo or oral terbutaline maintenance therapy in reducing adverse neonatal outcomes by prolonging pregnancy among women with arrested preterm labour. The mean difference (MD) for gestational age at birth was -0.14 weeks (95% confidence interval (CI) -1.66 to 1.38) for terbutaline pump therapy compared with saline placebo pump for two trials combined. One trial reported a risk ratio (RR) of 1.17 (95% CI 0.79 to 1.73) for preterm birth (less than 37 completed weeks) and a RR of 0.97 (95% CI 0.51 to 1.84) of very preterm birth (less than 34 completed weeks) for terbutaline pump compared with saline placebo pump. We found no evidence that terbutaline pump therapy was

  4. Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis.

    PubMed

    Farrar, Diane; Simmonds, Mark; Bryant, Maria; Sheldon, Trevor A; Tuffnell, Derek; Golder, Su; Dunne, Fidelma; Lawlor, Debbie A

    2016-09-13

     To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified.  Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials.  Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts.  Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.  Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools.  25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1

  5. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework.

    PubMed

    Teeguarden, Justin G; Tan, Yu-Mei; Edwards, Stephen W; Leonard, Jeremy A; Anderson, Kim A; Corley, Richard A; Kile, Molly L; Simonich, Staci M; Stone, David; Tanguay, Robert L; Waters, Katrina M; Harper, Stacey L; Williams, David E

    2016-05-03

    Driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the "systems approaches" used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.

  6. Risk predictors for adverse outcome in pediatric febrile neutropenia: Single center experience from a low and middle-income country.

    PubMed

    Prasad, M; Chinnaswamy, G; Arora, B; Vora, T; Hawaldar, R; Banavali, S

    2014-01-01

    Risk stratification of patients with febrile neutropenia (FN) into those at "High Risk" and "Low Risk" of developing complications helps in making decisions regarding optimal treatment, such as whether to treat with oral or intravenous antibiotics, whether to treat as inpatient or outpatient and how long to treat. Risk predictors obtained from Western studies on pediatric FN are unlikely to be relevant to low middle-income country (LMICs). Our study aimed to identify clinical and laboratory parameters predictive of poor outcomes in children with chemotherapy-induced FN in a LMIC. Two hundred and fifty consecutive episodes of chemotherapy-induced FN in pediatric (<15 years) patients were analyzed prospectively. Adverse outcomes were defined as per SPOG 2003 FN study as serious medical complications (SMC) due to infection, microbiologically defined infection, and radiologically defined pneumonia (RDP). Variables found to be significant for adverse outcome (P < 0.05) on univariate analysis were selected for multivariate analysis. Five factors that were found to independently predict adverse outcome were (a) previously documented infection in the past 6 months, (b) presence of significant focus of infection, (c) absolute phagocyte count <100/mm3, (d) peak temperature more than 39°C in this episode of FN, and (e) fever lasting more than 5 days during this episode of FN. Identifying the risk factors for adverse outcome in pediatric FN, which are objective and applicable across LMICs would contribute in developing guidelines for the management of FN in a resource-limited setting.

  7. Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

    PubMed Central

    Fong, Tamara G.; Jones, Richard N.; Marcantonio, Edward R.; Tommet, Douglas; Gross, Alden L.; Habtemariam, Daniel; Schmitt, Eva; Yap, Liang; Inouye, Sharon K.

    2012-01-01

    Background Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). Objective To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. Design Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimer’s Disease Research Center (MADRC) patient registry. Setting Community-based. Participants 771 persons aged 65 years or older with a clinical diagnosis of AD. Measurements Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). Results Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. Limitations Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. Conclusion Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may

  8. Echocardiographic predictors of adverse outcomes after continuous left ventricular assist device implantation.

    PubMed

    Topilsky, Yan; Oh, Jae K; Shah, Dipesh K; Boilson, Barry A; Schirger, John A; Kushwaha, Sudhir S; Pereira, Naveen L; Park, Soon J

    2011-03-01

    The purpose of the study was to identify echocardiographic predictors of adverse outcome in patients implanted with continuous-flow left ventricular assist devices (LVAD). Continuous flow LVAD have become part of the standard of care for the treatment of advanced heart failure. However, knowledge of echocardiographic predictors of outcome after LVAD are lacking. Overall, 83 patients received continuous-flow LVAD (HeartMate II, Thoratec Corporation, Pleasanton, California) from February 2007 to June 2010. The LVAD database, containing various echocardiographic parameters, was examined to analyze their influence on in-hospital mortality, a compound cardiac event (in-hospital mortality or acute right ventricular [RV] dysfunction), and long-term mortality. Eight patients died before discharge (operative mortality 9.6%), and another 15 patients were considered to have acute RV dysfunction immediately after surgery. Patients with relatively small left ventricular end-diastolic diameters (<63 mm) had significantly higher risk for in-hospital mortality (odds ratio [OR]: 0.9; 95% confidence interval [CI]: 0.83 to 0.99; p = 0.04) or occurrence of the compound cardiac event (OR: 0.89; 95% CI: 0.84 to 0.95; p < 0.001). The most significant predictor of outcome was the decreased timing interval between the onset and the cessation of tricuspid regurgitation flow corrected for heart rate (TRDc), a surrogate for early systolic equalization of RV and right atrial pressure. Short TRDc predicted in-hospital mortality (OR: 0.85; 95% CI: 0.74 to 0.97; p = 0.01) and the compound cardiac event (OR: 0.83; 95% CI: 0.74 to 0.91; p < 0.0001). Multivariate analysis based on a logistic regression model demonstrated that the accuracy of predicting the 30-day compound adverse outcome was improved with the addition of echocardiographic variables when added to the commonly used hemodynamic or clinical scores. TRDc predicted long-term survival, with adjusted risk ratios of 0.89 for death from any

  9. Applying adverse outcome pathways and species sensitivity-weighted distribution to predicted-no-effect concentration derivation and quantitative ecological risk assessment for bisphenol A and 4-nonylphenol in aquatic environments: A case study on Tianjin City, China.

    PubMed

    Wang, Ying; Na, Guangshui; Zong, Humin; Ma, Xindong; Yang, Xianhai; Mu, Jingli; Wang, Lijun; Lin, Zhongsheng; Zhang, Zhifeng; Wang, Juying; Zhao, Jinsong

    2018-02-01

    Adverse outcome pathways (AOPs) are a novel concept that effectively considers the toxic modes of action and guides the ecological risk assessment of chemicals. To better use toxicity data including biochemical or molecular responses and mechanistic data, we further developed a species sensitivity-weighted distribution (SSWD) method for bisphenol A and 4-nonylphenol. Their aquatic predicted-no-effect concentrations (PNECs) were derived using the log-normal statistical extrapolation method. We calculated aquatic PNECs of bisphenol A and 4-nonylphenol with values of 4.01 and 0.721 µg/L, respectively. The ecological risk of each chemical in different aquatic environments near Tianjin, China, a coastal municipality along the Bohai Sea, was characterized by hazard quotient and probabilistic risk quotient assessment techniques. Hazard quotients of 7.02 and 5.99 at 2 municipal sewage sites using all of the endpoints were observed for 4-nonylphenol, which indicated high ecological risks posed by 4-nonylphenol to aquatic organisms, especially endocrine-disrupting effects. Moreover, a high ecological risk of 4-nonylphenol was indicated based on the probabilistic risk quotient method. The present results show that combining the SSWD method and the AOP concept could better protect aquatic organisms from adverse effects such as endocrine disruption and could decrease uncertainty in ecological risk assessment. Environ Toxicol Chem 2018;37:551-562. © 2017 SETAC. © 2017 SETAC.

  10. Analyzing risks of adverse pregnancy outcomes.

    PubMed

    Kramer, Michael S; Zhang, Xun; Platt, Robert W

    2014-02-01

    Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

  11. Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer: Evaluation of Outcomes in the Regione Emilia-Romagna, Italy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Showalter, Timothy N., E-mail: tns3b@virginia.edu; Hegarty, Sarah E.; Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania

    Purpose: Although the likelihood of radiation-related adverse events influences treatment decisions regarding radiation therapy after prostatectomy for eligible patients, the data available to inform decisions are limited. This study was designed to evaluate the genitourinary, gastrointestinal, and sexual adverse events associated with postprostatectomy radiation therapy and to assess the influence of radiation timing on the risk of adverse events. Methods: The Regione Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried to identify a cohort of men who received radical prostatectomy for prostate cancer during 2003 to 2009, including patients who received postprostatectomy radiation therapy. Patients with prior radiation therapymore » were excluded. Outcome measures were genitourinary, gastrointestinal, and sexual adverse events after prostatectomy. Rates of adverse events were compared between the cohorts who did and did not receive postoperative radiation therapy. Multivariable Cox proportional hazards models were developed for each class of adverse events, including models with radiation therapy as a time-varying covariate. Results: A total of 9876 men were included in the analyses: 2176 (22%) who received radiation therapy and 7700 (78%) treated with prostatectomy alone. In multivariable Cox proportional hazards models, the additional exposure to radiation therapy after prostatectomy was associated with increased rates of gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27; P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001) but not urinary incontinence events or erectile dysfunction. The addition of the time from prostatectomy to radiation therapy interaction term was not significant for any of the adverse event outcomes (P>.1 for all outcomes). Conclusion: Radiation therapy after prostatectomy is associated with an increase in gastrointestinal and genitourinary adverse events

  12. Do adult men with untreated hypospadias have adverse outcomes? A pilot study using a social media advertised survey.

    PubMed

    Schlomer, Bruce; Breyer, Benjamin; Copp, Hillary; Baskin, Laurence; DiSandro, Michael

    2014-08-01

    Hypospadias is usually treated in childhood. Therefore, the natural history of untreated mild hypospadias is unknown. We hypothesized that men with untreated hypospadias, especially mild, do not have adverse outcomes. Facebook was used to advertise an electronic survey to men older than 18 years. Men with untreated hypospadias identified themselves and indicated the severity of hypospadias with a series of questions. Outcomes included: Sexual Health Inventory for Men (SHIM), penile curvature and difficulty with intercourse, International Prostate Symptom Score (IPSS), Penile Perception Score (PPS), psychosexual milestones, paternity, infertility, sitting to urinate, and the CDC HRQOL-4 module. 736 men completed self-anatomy questions and 52 (7.1%) self-identified with untreated hypospadias. Untreated hypospadias participants reported worse SHIM (p < 0.001) and IPSS scores (p = 0.05), more ventral penile curvature (p = 0.003) and resulting difficulty with intercourse (p < 0.001), worse satisfaction with meatus (p = 0.011) and penile curvature (p = 0.048), and more sitting to urinate (p = 0.07). When stratified by mild and severe hypospadias, severe hypospadias was associated with more adverse outcomes than mild hypospadias. Men with untreated hypospadias reported worse outcomes compared with non-hypospadiac men. Mild untreated hypospadias had fewer adverse outcomes than severe hypospadias. Research is needed to determine if treatment of childhood hypospadias improves outcomes in adults, especially for mild hypospadias. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  13. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

    PubMed Central

    Teeguarden, Justin. G.; Tan, Yu-Mei; Edwards, Stephen W.; Leonard, Jeremy A.; Anderson, Kim A.; Corley, Richard A.; Harding, Anna K; Kile, Molly L.; Simonich, Staci M; Stone, David; Tanguay, Robert L.; Waters, Katrina M.; Harper, Stacey L.; Williams, David E.

    2016-01-01

    Synopsis Driven by major scientific advances in analytical methods, biomonitoring, computational tools, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the Aggregate Exposure Pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the Adverse Outcome Pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more efficient integration of exposure assessment and hazard identification. Together, the two pathways form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making. PMID:26759916

  14. Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk of adverse outcomes, a population-based study

    PubMed Central

    Kessler, Jörg

    2018-01-01

    Objectives To determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length. Design Population based registry study. Setting Medical Birth Registry of Norway 1999–2013. Population All singleton births (gestational age>22weeks<45 weeks) (n = 856 300). Methods Descriptive statistics and odds ratios of risk factors for extreme cord length and adverse outcomes based on logistic regression adjusted for confounders. Main outcome measures Short or long cord (<10th or >90th percentile), cord knot and entanglement, adverse pregnancy outcomes including perinatal and intrauterine death. Results Increasing parity, maternal height and body mass index, and diabetes were associated with increased risk of a long cord. Large placental and birth weight, and fetal male sex were factors for a long cord, which again was associated with a doubled risk of intrauterine and perinatal death, and increased risk of adverse neonatal outcome. Anomalous cord insertion, female sex, and a small placenta were associated with a short cord, which was associated with increased risk of fetal malformations, placental complications, caesarean delivery, non-cephalic presentation, perinatal and intrauterine death. At term, cord knot was associated with a quadrupled risk of perinatal death. The combination of a cord knot and entanglement had a more than additive effect to the association to perinatal death. There was a more than doubled risk of recurrence of a long or short cord, knot and entanglement in a subsequent pregnancy of the same woman. Conclusion Cord length is influenced both by maternal and fetal factors, and there is increased risk of recurrence. Extreme cord length, entanglement and cord knot are associated with increased risk of adverse

  15. Illicit drug use and adverse birth outcomes: is it drugs or context?

    PubMed

    Schempf, Ashley H; Strobino, Donna M

    2008-11-01

    Prenatal drug use is commonly associated with adverse birth outcomes, yet no studies have controlled for a comprehensive set of associated social, psychosocial, behavioral, and biomedical risk factors. We examined the degree to which adverse birth outcomes associated with drug use are due to the drugs versus surrounding factors. Data are from a clinical sample of low-income women who delivered at Johns Hopkins Hospital between 1995 and 1996 (n = 808). Use of marijuana, cocaine, and opiates was determined by self-report, medical record, and urine toxicology screens at delivery. Information on various social, psychosocial, behavioral, and biomedical risk factors was gathered from a postpartum interview or the medical record. Multivariable regression models of birth outcomes (continuous birth weight and low birth weight ([LBW] < 2,500 g)) were used to assess the effect of drug use independent of associated factors. In unadjusted results, all types of drug use were related to birth weight decrements and increased odds of LBW. However, only the effect of cocaine on continuous birth weight remained significant after adjusting for all associated factors (-142 g, p = 0.05). No drug was significantly related to LBW in fully adjusted models. About 70% of the unadjusted effect of cocaine use on continuous birth weight was explained by surrounding psychosocial and behavioral factors, particularly smoking and stress. Most of the unadjusted effects of opiate use were explained by smoking and lack of early prenatal care. Thus, prevention efforts that aim to improve newborn health must also address the surrounding context in which drug use frequently occurs.

  16. Early Dialysis and Adverse Outcomes After Hurricane Sandy.

    PubMed

    Lurie, Nicole; Finne, Kristen; Worrall, Chris; Jauregui, Maria; Thaweethai, Tanayott; Margolis, Gregg; Kelman, Jeffrey

    2015-09-01

    Hemodialysis patients have historically experienced diminished access to care and increased adverse outcomes after natural disasters. Although "early dialysis" in advance of a storm is promoted as a best practice, evidence for its effectiveness as a protective measure is lacking. Building on prior work, we examined the relationship between the receipt of dialysis ahead of schedule before the storm (also known as early dialysis) and adverse outcomes of patients with end-stage renal disease in the areas most affected by Hurricane Sandy. Retrospective cohort analysis, using claims data from the Centers for Medicare & Medicaid Services Datalink Project. Patients receiving long-term hemodialysis in New York City and the state of New Jersey, the areas most affected by Hurricane Sandy. Receipt of early dialysis compared to their usual treatment pattern in the week prior to the storm. Emergency department (ED) visits, hospitalizations, and 30-day mortality following the storm. Of 13,836 study patients, 8,256 (60%) received early dialysis. In unadjusted logistic regression models, patients who received early dialysis were found to have lower odds of ED visits (OR, 0.75; 95% CI, 0.63-0.89; P=0.001) and hospitalizations (OR, 0.77; 95% CI, 0.65-0.92; P=0.004) in the week of the storm and similar odds of 30-day mortality (OR, 0.80; 95% CI, 0.58-1.09; P=0.2). In adjusted multivariable logistic regression models, receipt of early dialysis was associated with lower odds of ED visits (OR, 0.80; 95% CI, 0.67-0.96; P=0.01) and hospitalizations (OR, 0.79; 95% CI, 0.66-0.94; P=0.01) in the week of the storm and 30-day mortality (OR, 0.72; 95% CI, 0.52-0.997; P=0.048). Inability to determine which patients were offered early dialysis and declined and whether important unmeasured patient characteristics are associated with receipt of early dialysis. Patients who received early dialysis had significantly lower odds of having an ED visit and hospitalization in the week of the storm and of

  17. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    PubMed Central

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

  18. Adverse effects of perinatal nicotine exposure on reproductive outcomes.

    PubMed

    Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

    2015-12-01

    Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

  19. Gestational Weight Gain: Association with Adverse Pregnancy Outcomes.

    PubMed

    Hannaford, Karen E; Tuuli, Methodius G; Odibo, Linda; Macones, George A; Odibo, Anthony O

    2017-01-01

    Background  It is unclear how adherence to the Institute of Medicine's (IOM) guidelines for weight gain affects pregnancy outcomes. Objective  We investigated how weight gain outside the IOM's recommendations affects the risks of adverse pregnancy outcomes. Study Design  We performed a secondary analysis of a prospective cohort study including singleton, nonanomalous fetuses. The risks of small for gestational age (SGA), macrosomia, preeclampsia, cesarean delivery, gestational diabetes, or preterm birth were calculated for patients who gained weight below or above the IOM's recommendations based on body mass index category. A time-to-event analysis was performed to account for gestational age at delivery. A Cox proportional model was fit to estimate hazard ratios accounting for possible confounders. Results  Women who gained weight below recommendations were 2.5 times more likely to deliver SGA and twice as likely to deliver preterm. Normal-weight patients who gained below recommendations were 2.5 times more likely to deliver SGA and twice as likely to deliver preterm. Obese patients who gained inadequate weight were 2.5 times more likely to deliver SGA. Conclusion  Among normal-weight patients, adhering to IOM recommendations may prevent growth abnormalities and preterm delivery. Among obese patients, a minimum weight gain requirement may prevent SGA infants. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. How do Singapore patients view post-anaesthesia adverse outcomes? A single-centre willingness-to-pay study.

    PubMed

    Look, Xinqi; Mok, May Un Sam; Tay, Yan Sheng; Abdullah, Hairil Rizal

    2018-05-01

    Knowing how patients value the quality of anaesthesia helps anaesthesiologists to customise their service. However, generalising findings from Western population-based willingness-to-pay studies across different cultures and societies might result in the oversight of some contextualised perspectives of the anaesthesia experience. This study aimed to capture the Singapore perspective of undesired post-anaesthesia outcomes. 132 patients recruited in a pre-anaesthetic evaluation clinic were given questionnaires describing ten possible post-anaesthetic outcomes. Outcomes were ranked for undesirability and assigned relative value through the hypothetical proportioning of SGD 100 to avoid their occurrence. Data was analysed with reference to patients' background and anaesthetic history. A response rate of 69.1% (n = 132/191) was achieved. Outcomes from the most to least undesirable were pain; vomiting; nausea; shivering; orodental trauma; sore throat; abrasions; somnolence; and thirst. Relative values allocated, in descending order, were pain; vomiting; nausea; orodental trauma; abrasions; sore throat; shivering; somnolence; and thirst. Similar to previous studies in Western populations, pain, vomiting and nausea were the top three adverse outcomes that Singapore patients wished to avoid. However, discrepancies with Western patients were seen in spending attitudes, possibly accounted for by differences in healthcare socioeconomics. This study provided a better understanding of Singapore patients' perspectives on post-anaesthesia adverse outcomes and could help to improve treatment strategy and resource management. Copyright: © Singapore Medical Association.

  1. How do Singapore patients view post-anaesthesia adverse outcomes? A single-centre willingness-to-pay study

    PubMed Central

    Look, Xinqi; Mok, May Un Sam; Tay, Yan Sheng; Abdullah, Hairil Rizal

    2018-01-01

    INTRODUCTION Knowing how patients value the quality of anaesthesia helps anaesthesiologists to customise their service. However, generalising findings from Western population-based willingness-to-pay studies across different cultures and societies might result in the oversight of some contextualised perspectives of the anaesthesia experience. This study aimed to capture the Singapore perspective of undesired post-anaesthesia outcomes. METHODS 132 patients recruited in a pre-anaesthetic evaluation clinic were given questionnaires describing ten possible post-anaesthetic outcomes. Outcomes were ranked for undesirability and assigned relative value through the hypothetical proportioning of SGD 100 to avoid their occurrence. Data was analysed with reference to patients’ background and anaesthetic history. RESULTS A response rate of 69.1% (n = 132/191) was achieved. Outcomes from the most to least undesirable were pain; vomiting; nausea; shivering; orodental trauma; sore throat; abrasions; somnolence; and thirst. Relative values allocated, in descending order, were pain; vomiting; nausea; orodental trauma; abrasions; sore throat; shivering; somnolence; and thirst. CONCLUSION Similar to previous studies in Western populations, pain, vomiting and nausea were the top three adverse outcomes that Singapore patients wished to avoid. However, discrepancies with Western patients were seen in spending attitudes, possibly accounted for by differences in healthcare socioeconomics. This study provided a better understanding of Singapore patients’ perspectives on post-anaesthesia adverse outcomes and could help to improve treatment strategy and resource management. PMID:28805235

  2. Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

    PubMed

    Zilioli, Samuele; Slatcher, Richard B; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

    2016-09-01

    Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here, we tested whether childhood adversity was associated with diurnal cortisol parameters and whether this link was partially explained by self-esteem. In both adults and youths, childhood adversity was associated with lower levels of cortisol at awakening, and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Finally, youths who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared with youths whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the life span. © The Author(s) 2016.

  3. Factors Associated with Timing and Adverse Outcomes in Patients with Biliary Atresia Undergoing Kasai Hepatoportoenterostomy.

    PubMed

    Townsend, Michael Ross; Jaber, Adeeb; Abi Nader, Hanina; Eid, Shaker M; Schwarz, Kathleen

    2018-05-14

    To assess factors associated with timing of hepatoportoenterostomy (HPE) and adverse perioperative outcomes in patients with biliary atresia in the US. We examined hospitalizations in infants aged <1 year using the National Inpatient Sample database for 2000-2011. We identified cases using the International Classification of Diseases, Ninth Revision, Clinical Modification codes for biliary atresia and HPE. Multivariable logistic regression models were used to examine association between select factors and age at HPE, as well as adverse perioperative outcomes. Our analysis of 1243 biliary atresia hospitalizations showed that only 37.7% of patients had HPE in the first 60 days of life. Patients who underwent HPE after 60 days of age were uninsured, were more likely to be black (aOR, 4.22; 95% CI, 1.49-11.95), less likely to be admitted at a teaching hospital (aOR, 0.27; 95% CI 0.10-0.79), and less likely to have a concomitant congenital malformation (aOR, 0.49; 95% CI 0.25-0.98). Patients with delayed age at HPE incurred significantly higher hospital costs ($57 914 vs $34 074; P = .026). Delayed age at HPE and weekend admission were independently associated with increased odds of adverse perioperative outcome (aOR, 1.09; 95% CI, 1.01-3.02 and 3.98; 95% CI, 1.67-9.46, respectively). Current outcomes in patients with biliary atresia in the United States are suboptimal and result in higher costs. The specific factors associated with delayed care are further evidence that universal health care and screening are needed for all infants, along with systematic referral of potential patients with biliary atresia to specialized health centers. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Association between adverse pregnancy outcome and imbalance in angiogenic regulators and oxidative stress biomarkers in gestational hypertension and preeclampsia.

    PubMed

    Turpin, Cornelius A; Sakyi, Samuel A; Owiredu, William K B A; Ephraim, Richard K D; Anto, Enoch O

    2015-08-25

    Gestational hypertension (GH) and Preeclampsia, (PE) are the most complicated amongst hypertensive disorders of pregnancy. The mechanism that links hypertension in pregnancy to adverse maternal outcomes is not fully understood though some relate this to endothelial dysfunction originating from an imbalanced angiogenic regulators and oxidative stress biomarkers. This study assessed the correlation between angiogenic regulators and oxidative stress biomarker levels with adverse pregnancy outcomes among GH and PE participants. A cohort of pregnant women who received antenatal care at the Obstetrics and Gynaecology department of the Komfo Anokye Teaching Hospital (KATH) were followed. During their antenatal visits, 100 developed PE and 70 developed GE, of these, 50 PE and 50 GH gave informed consent. Their blood samples were taken at time of diagnosis and 48 h post-partum. 50 other aged-matched women who did not develop neither GH nor PE were selected as controls. Placental growth factor (PLGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and 8-epi-prostaglandin F2alpha (8-epi-PGF2α) levels were estimated by ELISA and total antioxidant capacity (T-AOC) was measured spectrophotometrically. Graphpad Prism was used for data analysis. Median levels of sFlt-1, 8-epi-PGF2α and sFlt-1/PLGF were elevated among participants with PE co-existing with intrauterine fetal death (IUFD), placental abruptio, placental previa, HELLP syndrome and intrauterine growth restriction (IUGR) compared to PE without adverse outcomes (p = 0.041, p = 0.005, p = 0.0002). Levels of PLGF, T-AOC and PLGF/sFlt-1 were significantly reduced among participants with PE co-existing with IUFD, placental abruptio, placental previa, HELLP syndrome and IUGR compared to PE without adverse outcomes (p = 0.0013, p = 0.006, p < 0.0001). A significant negative correlation of IUGR (p = 0.0030; p < 0.0001), placental abruptio (p < 0.0001; p < 0.0001), IUFD (p < 0.0001; p

  5. An elevated gap between admission and A1C-derived average glucose levels is associated with adverse outcomes in diabetic patients with pyogenic liver abscess.

    PubMed

    Liao, Wen-I; Sheu, Wayne Huey-Herng; Chang, Wei-Chou; Hsu, Chin-Wang; Chen, Yu-Long; Tsai, Shih-Hung

    2013-01-01

    To assess whether chronic glycemic control and stress-induced hyperglycemia, determined by the gap between admission glucose levels and A1C-derived average glucose (ADAG) levels adversely affects outcomes in diabetic patients with pyogenic liver abscess (PLA). Clinical, laboratory, and multi-detector computed tomography (MDCT) findings of 329 PLA patients (2004-2010) were retrospectively reviewed. HbA1C levels were used to determine long-term glycemic control status, which were then converted to estimated average glucose values. For the gap between admission glucose levels and ADAG levels, we used receiver operating characteristic (ROC) curve to determine the optimal cut-off values predicting adverse outcomes. Univariate and multivariate logistic regressions were used to identify predictors of adverse outcomes. Diabetic PLA patients with poorer glycemic control had significantly higher Klebsiella pneumoniae (KP) infection rates, lower albumin levels, and longer hospital stays than those with suboptimal and good glycemic control. The ROC curve showed that a glycemic gap of 72 mg/dL was the optimal cut-off value for predicting adverse outcomes and showed a 22.3% relative increase in adverse outcomes compared with a glycemic gap<72 mg/dL. Multivariate analysis revealed that an elevated glycemic gap≥72 mg/dL was important predictor of adverse outcomes. A glycemic gap≥72 mg/dL, rather than admission hyperglycemia or chronic glycemic control, was significantly correlated with adverse outcomes in diabetic PLA patients. Poorer chronic glycemic control in diabetic PLA patients is associated with high incidence of KP infection, hypoalbuminemia and longer hospital stay.

  6. Dependence in prestroke mobility predicts adverse outcomes among patients with acute ischemic stroke.

    PubMed

    Dallas, Mary I; Rone-Adams, Shari; Echternach, John L; Brass, Lawrence M; Bravata, Dawn M

    2008-08-01

    Stroke survivors are commonly dependent in activities of daily living; however, the relation between prestroke mobility impairment and poststroke outcomes is poorly understood. The primary objective of this study was to evaluate the association between prestroke mobility impairment and 4 poststroke outcomes. The secondary objective was to evaluate the association between prestroke mobility impairment and a plan for physical therapy. This was a secondary analysis of the National Stroke Project data, a retrospective cohort of Medicare beneficiaries who were hospitalized with an acute ischemic stroke (1998 to 2001). Logistic-regression modeling was used to examine the adjusted association between prestroke mobility impairment with patient outcomes and a plan for physical therapy. Among the 67,445 patients hospitalized with an ischemic stroke, 6% were dependent in prestroke mobility. Prestroke mobility dependence was independently associated with an increased odds of poststroke mobility impairment (odds ratio [OR]=9.9; 95% CI, 9.0 to 10.8); in-hospital mortality (OR=2.4; 95% CI, 2.2 to 2.7); discharge to a skilled nursing facility (OR=3.5; 95% CI, 3.2 to 3.8); and the combination of in-hospital death or discharge to a skilled nursing facility (OR=3.5; 95% CI, 3.3 to 3.8). Prestroke mobility dependence was independently associated with a decreased odds of having a plan for physical therapy (OR=0.79; 95% CI, 0.73 to 0.85). These data, obtained from a large, geographically diverse cohort from the United States, demonstrate a strong association between dependence in prestroke mobility and adverse outcomes among elderly stroke patients. Clinicians should screen patients for prestroke mobility impairment to identify patients at greatest risk for adverse events.

  7. Impact of a critical pathway on postoperative length of stay and outcomes after infrainguinal bypass.

    PubMed

    Stanley, A C; Barry, M; Scott, T E; LaMorte, W W; Woodson, J; Menzoian, J O

    1998-06-01

    To determine the effect of a critical pathway on postoperative length of stay and outcomes after infrainguinal bypass. A critical pathway for care of patients after infrainguinal bypass was introduced in December 1995 to coordinate postoperative care at our institution. We compared care of 67 consecutively treated patients before institution of the pathway with care of 69 consecutively treated patients with the critical pathway in place. Data collection was done by means of chart review. Univariate analyses were used to identify differences between prepathway and postpathway patients and to identify factors influencing postoperative length of stay. Multivariate analysis was used to identify factors that influenced length of stay and to examine the effect of use of the pathway after adjusting for other factors. Patients on the pathway were similar to prepathway controls with respect to comorbid illnesses, vascular risk factors, indications for surgical treatment, type of conduit, and type of operation. Factors associated with longer postoperative stays included distal anastomoses to tibial rather than popliteal vessels (p = 0.02), preexisting cardiac disease (p = 0.005), postoperative complications (p = 0.0003), lower preoperative hematocrit (p = 0.01), and elevated preoperative creatinine level (p = 0.006). Overall, pathway patients had somewhat shorter postoperative lengths of stay (median value 7 days; range 2 to 29 days) than prepathway patients (median value 6 days; range 2 to 35; p = 0.01), and the two groups had similar frequencies of postoperative complications, readmission, and 6-month mortality. However, patients on the pathway were more likely to be discharged to an intermediate-care facility rather than directly home. After 12 patients with extraordinarily prolonged postoperative stays were excluded, multivariate analysis indicated that pathway patients had significantly shorter postoperative stays (p = 0.001). However, the difference was not significant

  8. Functional and cognitive impairment, social environment, frailty and adverse health outcomes in older patients with head and neck cancer, a systematic review.

    PubMed

    van Deudekom, Floor J; Schimberg, Anouk S; Kallenberg, Marije H; Slingerland, Marije; van der Velden, Lily-Ann; Mooijaart, Simon P

    2017-01-01

    Older head and neck cancer patients are at increased risk for adverse health outcomes, but little is known about which geriatric assessment associates with poor outcome. The aim is to study the association of functional or cognitive impairment, social environment and frailty with adverse health outcomes in patients with head and neck cancer. Four libraries were searched for studies reporting on an association of functional or cognitive impairment, social environment and frailty with adverse outcomes in head and neck cancer patients. Of 4158 identified citations, 31 articles were included. The mean age was ⩾60years in twelve studies (39%). Geriatric conditions were prevalent: between 40 and 50% of the included participants were functional impaired, around 50% had depressive symptoms, and around 40% did not have a partner. Functional impairment was assessed in 18 studies, two studies reported on a cognitive test, eight studies examined mood and social status was depicted by 14 studies. None of the included studies addressed frailty or objectively measured physical capacity such as hand grip strength, gait speed or balance tests. In 64% of the reported associations, a decline in functional or cognitive impairment, mood or social environment was associated with adverse outcomes. Functional and cognitive impairment, depressive symptoms and social isolation are highly prevalent in head and neck cancer patients and associate with high risk of adverse health outcomes. In the future, these measurements may guide decision-making and customize treatments, but more research is needed to further improve and firmly establish clinical usability. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. The Effect of Linked Learning Certified Pathways on Selected Student Outcomes

    ERIC Educational Resources Information Center

    Fitzgerald, Robert; Ottem, Randolph; Hufford, Justine

    2016-01-01

    This report examines outcomes for grade-12 students in academic years (AY) 2010-11, 2011-12, and 2012-13 who were enrolled in a Linked Learning certified pathway (LLCP) in California. Outcomes include student engagement in learning, measured by high school attendance and discipline events, as well as college readiness and postsecondary enrollment.…

  10. Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies.

    PubMed

    Hung, Szu-Chun; Lai, Yi-Shin; Kuo, Ko-Lin; Tarng, Der-Cherng

    2015-05-05

    Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume overload and adverse outcomes in CKD is not fully understood. A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end-stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high-salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor-α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes. Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  11. Serum uric acid level predicts adverse outcomes after myocardial revascularization or cardiac valve surgery.

    PubMed

    Lazzeroni, Davide; Bini, Matteo; Camaiora, Umberto; Castiglioni, Paolo; Moderato, Luca; Bosi, Davide; Geroldi, Simone; Ugolotti, Pietro T; Brambilla, Lorenzo; Brambilla, Valerio; Coruzzi, Paolo

    2018-01-01

    Background High levels of serum uric acid have been associated with adverse outcomes in cardiovascular diseases such as myocardial infarction and heart failure. The aim of the current study was to evaluate the prognostic role of serum uric acid levels in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. Design We performed an observational prospective cohort study. Methods The study included 1440 patients with available serum uric acid levels, prospectively followed for 50 ± 17 months. Mean age was 67 ± 11 years; 781 patients (54%) underwent myocardial revascularization, 474 (33%) cardiac valve surgery and 185 (13%) valve-plus-coronary artery by-pass graft surgery. The primary endpoints were overall and cardiovascular mortality while secondary end-points were combined major adverse cardiac and cerebrovascular events. Results Serum uric acid level mean values were 286 ± 95 µmol/l and elevated serum uric acid levels (≥360 µmol/l or 6 mg/dl) were found in 275 patients (19%). Overall mortality (hazard ratio = 2.1; 95% confidence interval: 1.5-3.0; p < 0.001), cardiovascular mortality (hazard ratio = 2.0; 95% confidence interval: 1.2-3.2; p = 0.004) and major adverse cardiac and cerebrovascular events rate (hazard ratio = 1.5; 95% confidence interval: 1.0-2.0; p = 0.019) were significantly higher in patients with elevated serum uric acid levels, even after adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate, atrial fibrillation and medical therapy. Moreover, strong positive correlations between serum uric acid level and probability of overall mortality ( p < 0.001), cardiovascular mortality ( p < 0.001) and major adverse cardiac and cerebrovascular events ( p = 0.003) were found. Conclusions Serum uric acid levels predict mortality and adverse cardiovascular outcome in patients undergoing myocardial revascularization

  12. USE OF CASE REPORTS IN ASSESSING ADVERSE OUTCOMES OF HUMAN PRENATAL DRUG EXPOSURES: AN APPROACH

    EPA Science Inventory

    The use of case reports for assessing the developmental consequences of prenatal drug exposure is limited by the inability to determine the incidence of adverse outcomes and by the high likelihood for bias. Yet, because it is impossible to conduct clinical trials for the assessme...

  13. Unsatisfactory Glucose Management and Adverse Pregnancy Outcomes of Gestational Diabetes Mellitus in the Real World of Clinical Practice: A Retrospective Study.

    PubMed

    Feng, Ru; Liu, Lu; Zhang, Yuan-Yuan; Yuan, Zhong-Shang; Gao, Ling; Zuo, Chang-Ting

    2018-05-05

    Facing the increasing prevalence of gestational diabetes mellitus (GDM), this study aimed to evaluate the management of GDM and its association with adverse pregnancy outcomes. The data of 996 inpatients with GDM who terminated pregnancies in our hospital from January 2011 to December 2015 were collected. Treatments during pregnancy and the last hospital admission before delivery were analyzed. Pregnancy outcomes of the GDM patients were compared with 996 nondiabetic subjects matched by delivery year and gestational age. The association between fasting plasma glucose (FPG) and adverse pregnancy outcomes was examined by logistic regression analyses. The average prevalence of GDM over the 5 years was 4.4% (1330/30,191). Within the GDM patients, 42.8% (426/996) received dietary intervention, whereas 19.1% (190/996) received insulin treatment. Adverse outcomes were more likely to occur in patients with unsatisfactory control of blood glucose such as respiratory distress syndrome (RDS, χ 2 = 13.373, P < 0.01). Elevated FPG was identified as an independent risk factor for premature birth (odds ratio [OR] = 1.460, P < 0.001), neonatal care unit admission (OR = 1.284, P < 0.001), RDS (OR = 1.322, P = 0.001), and stillbirth (OR = 1.427, P < 0.001). Management of GDM in the real world of clinical practice was unsatisfactory, which might have contributed to adverse pregnancy outcomes.

  14. Completing the link between exposure science and toxicology for improved environmental health decision making: The aggregate exposure pathway framework

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Teeguarden, Justin G.; Tan, Yu -Mei; Edwards, Stephen W.

    Here, driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences.more » Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.« less

  15. Completing the link between exposure science and toxicology for improved environmental health decision making: The aggregate exposure pathway framework

    DOE PAGES

    Teeguarden, Justin G.; Tan, Yu -Mei; Edwards, Stephen W.; ...

    2016-01-13

    Here, driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences.more » Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.« less

  16. Parental depression and child outcomes – is marital conflict the missing link?

    PubMed Central

    Hanington, L; Heron, J; Stein, A; Ramchandani, P

    2012-01-01

    Background Both maternal and paternal depression during the perinatal period are associated with adverse effects on child outcomes. Attention has started to focus on the mechanisms mediating these relationships. Marital conflict may play a role in this context. Methods In a large cohort study, the Avon Longitudinal Study of Parents and Children (n= 14 541 pregnancies), we aimed to (i) investigate the relative influences of parental postnatal depression and marital conflict on child outcomes and to attempt to determine the pathway(s) of risk; (ii) investigate the impact of two types of antenatal stress (parental depression and marital conflict) on child outcomes; and (iii) determine the relative contributions of antenatal and postnatal risk. Parents completed the Edinburgh Postnatal Depression Scale and a marital conflict scale during the second trimester and at 8 months postnatally. Child outcomes were assessed at 42 months using the Rutter revised pre-school scales. Results Marital conflict partially mediated the relationship between postnatal depression in both mothers and fathers and child outcomes, and acted as an independent risk for adverse outcomes. Parental depression (maternal and paternal) and marital conflict in the antenatal period were both associated with adverse effects which persisted even when postnatal stresses were taken into account. Conclusions These findings, if replicated, suggest that screening and intervention programmes targeted at parental depression and marital problems should be considered antenatally, as well as postnatally. PMID:21771000

  17. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    EPA Science Inventory

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  18. Adverse effects of MWCNTs on life parameters, antioxidant systems, and activation of MAPK signaling pathways in the copepod Paracyclopina nana.

    PubMed

    Kim, Duck-Hyun; Puthumana, Jayesh; Kang, Hye-Min; Lee, Min-Chul; Jeong, Chang-Bum; Han, Jeonghoon; Hwang, Dae-Sik; Kim, Il-Chan; Lee, Jin Wuk; Lee, Jae-Seong

    2016-10-01

    Engineered multi-walled carbon nanotubes (MWCNTs) have received widespread applications in a broad variety of commercial products due to low production cost. Despite their significant commercial applications, CNTs are being discharged to aquatic ecosystem, leading a threat to aquatic life. Thus, we investigated the adverse effect of CNTs on the marine copepod Paracyclopina nana. Additional to the study on the uptake of CNTs and acute toxicity, adverse effects on life parameters (e.g. growth, fecundity, and size) were analyzed in response to various concentrations of CNTs. Also, as a measurement of cellular damage, oxidative stress-related markers were examined in a time-dependent manner. Moreover, activation of redox-sensitive mitogen-activated protein kinase (MAPK) signaling pathways along with the phosphorylation pattern of extracellular signal-regulated kinase (ERK), p38, and c-Jun-N-terminal kinases (JNK) were analyzed to obtain a better understanding of molecular mechanism of oxidative stress-induced toxicity in the copepod P. nana. As a result, significant inhibition on life parameters and evoked antioxidant systems were observed without ROS induction. In addition, CNTs activated MAPK signaling pathway via ERK, suggesting that phosphorylated ERK (p-ERK)-mediated adverse effects are the primary cause of in vitro and in vivo endpoints in response to CNTs exposure. Moreover, ROS-independent activation of MAPK signaling pathway was observed. These findings will provide a better understanding of the mode of action of CNTs on the copepod P. nana at cellular and molecular level and insight on possible ecotoxicological implications in the marine environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

    PubMed Central

    2012-01-01

    Background Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention. Methods Using a collection of reviews identified previously, 166 references including a meta-analysis were selected for review. At least one of the primary outcomes in each review was an adverse or unintended event. The nature of the intervention, source of funding, number of individual meta-analyses performed, number of primary studies included in the review, and use of meta-analytic methods were all recorded. Specific areas of interest relating to the methods used included the choice of outcome metric, methods of dealing with sparse events, heterogeneity, publication bias and use of individual patient data. Results The 166 included reviews were published between 1994 and 2006. Interventions included drugs and surgery among other interventions. Many of the references being reviewed included multiple meta-analyses with 44.6% (74/166) including more than ten. Randomised trials only were included in 42.2% of meta-analyses (70/166), observational studies only in 33.7% (56/166) and a mix of observational studies and trials in 15.7% (26/166). Sparse data, in the form of zero events in one or both arms where the outcome was a count of events, was found in 64 reviews of two-arm studies, of which 41 (64.1%) had zero events in both arms. Conclusions Meta-analyses of adverse events data are common and useful in terms of increasing the power to

  20. Ongoing pregnancies in patients with unexplained recurrent pregnancy loss: adverse obstetric outcomes.

    PubMed

    Cozzolino, Mauro; Rizzello, Francesca; Riviello, Chiara; Romanelli, Chiara; Coccia Elisabetta, Maria

    2018-05-25

    To investigate the incidence of adverse pregnancy outcomes in couples with an unexplained Recurrent Pregnancy Loss (RPL) history, a retrospective cohort study was conducted between 2014 and 2015. The study group (A) included couples with an unexplained RPL, and the control group (B) was composed of couples who attended the Low-Risk Antenatal Unit during the same period. On the other hand, 53 couples were included in the study group (A) and on the other hand, 65 in the control group (B). Women with previous unexplained recurrent pregnancies loss had a significantly increased risk of gestational diabetes with 12 cases (22.6%) in the study group and 3 cases (4.6%) in the control (OR: 6.048; 95% CI: 1.607-22.762; p = 0.007). A slight increase in the risk of preterm delivery and hepatic cholestasis was observed in the study group (6 cases, 11.3%, in study group and 1 case, 1.5% in the controls (OR: 8.170; 95% CI: 0.951-70.158; p = 0.0555). Women with a history of RPL delivered more frequently by caesarean section (OR: 3.252; 95% CI: 1.460-7.241; p = 0.0039). Women with a history of RPL were at an increased risk for adverse pregnancy outcomes, mainly gestational diabetes. Therefore, a closer surveillance during the antenatal period is recommended in this group of patients.

  1. Teen Pregnancy: Are Pregnancies following an Elective Termination Associated with Increased Risk for Adverse Perinatal Outcomes?

    PubMed

    van Veen, Teelkien R; Haeri, Sina; Baker, Arthur M

    2015-12-01

    The authors sought to determine whether pregnancies in adolescents following an abortion of pregnancy is associated with an elevated risk for adverse perinatal outcomes. In a cohort study of all adolescent (younger than 18 years) deliveries over a 4-year period at 1 institution, we compared nulliparous women with a history of a prior abortion (cases) to those without a spontaneous loss or abortion of pregnancy (referent) for adverse perinatal outcomes, including preterm birth and fetal growth restriction. Of the 654 included nulliparous adolescent deliveries, 102 (16%) had an abortion before the index pregnancy. Compared with the referent group, adolescents with a history of a abortion were older (17.8 ± 0.8 vs 16.7 ± 1.2 years, P = .0001), enrolled earlier for prenatal care (14.4 ± 5.6 vs 17.2 ± 7.6 weeks, P = .0004), along with a higher incidence of African American race (95% vs 88%, P = .05). The groups did not differ with respect to other maternal demographics. Perinatal outcomes, including spontaneous preterm birth, abnormal placentation, birth weight, and gestational age at delivery, did not differ between the 2 groups. Compared with adolescent women who had just delivered and did not have a prior abortion, women who had just delivered and had a previous abortion were more likely to be older at the age of their first pregnancy and more likely to initiate early prenatal care. Thus, having a prior abortion may improve the health of a pregnancy though adverse outcomes do not differ between the 2 groups. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  2. Surgical adverse outcome reporting as part of routine clinical care.

    PubMed

    Kievit, J; Krukerink, M; Marang-van de Mheen, P J

    2010-12-01

    In The Netherlands, health professionals have created a doctor-driven standardised system to report and analyse adverse outcomes (AO). The aim is to improve healthcare by learning from past experiences. The key elements of this system are (1) an unequivocal definition of an adverse outcome, (2) appropriate contextual information and (3) a three-dimensional hierarchical classification system. First, to assess whether routine doctor-driven AO reporting is feasible. Second, to investigate how doctors can learn from AO reporting and analysis to improve the quality of care. Feasibility was assessed by how well doctors reported AO in the surgical department of a Dutch university hospital over a period of 9 years. AO incidence was analysed per patient subgroup and over time, in a time-trend analysis of three equal 3-year periods. AO were analysed case by case and statistically, to learn lessons from past events. In 19,907 surgical admissions, 9189 AOs were reported: one or more AO in 18.2% of admissions. On average, 55 lessons were learnt each year (in 4.3% of AO). More AO were reported in P3 than P1 (OR 1.39 (1.23-1.57)). Although minor AO increased, fatal AO decreased over time (OR 0.59 (0.45-0.77)). Doctor-driven AO reporting is shown to be feasible. Lessons can be learnt from case-by-case analyses of individual AO, as well as by statistical analysis of AO groups and subgroups (illustrated by time-trend analysis), thus contributing to the improvement of the quality of care. Moreover, by standardising AO reporting, data can be compared across departments or hospitals, to generate (confidential) mirror information for professionals cooperating in a peer-review setting.

  3. Surgical adverse outcome reporting as part of routine clinical care

    PubMed Central

    Krukerink, M; Marang-van de Mheen, P J

    2010-01-01

    Background In The Netherlands, health professionals have created a doctor-driven standardised system to report and analyse adverse outcomes (AO). The aim is to improve healthcare by learning from past experiences. The key elements of this system are (1) an unequivocal definition of an adverse outcome, (2) appropriate contextual information and (3) a three-dimensional hierarchical classification system. Objectives First, to assess whether routine doctor-driven AO reporting is feasible. Second, to investigate how doctors can learn from AO reporting and analysis to improve the quality of care. Methods Feasibility was assessed by how well doctors reported AO in the surgical department of a Dutch university hospital over a period of 9 years. AO incidence was analysed per patient subgroup and over time, in a time-trend analysis of three equal 3-year periods. AO were analysed case by case and statistically, to learn lessons from past events. Results In 19 907 surgical admissions, 9189 AOs were reported: one or more AO in 18.2% of admissions. On average, 55 lessons were learnt each year (in 4.3% of AO). More AO were reported in P3 than P1 (OR 1.39 (1.23–1.57)). Although minor AO increased, fatal AO decreased over time (OR 0.59 (0.45–0.77)). Conclusions Doctor-driven AO reporting is shown to be feasible. Lessons can be learnt from case-by-case analyses of individual AO, as well as by statistical analysis of AO groups and subgroups (illustrated by time-trend analysis), thus contributing to the improvement of the quality of care. Moreover, by standardising AO reporting, data can be compared across departments or hospitals, to generate (confidential) mirror information for professionals cooperating in a peer-review setting. PMID:20430928

  4. Gender differences in the pathway from adverse life events to adolescent emotional and behavioural problems via negative cognitive errors.

    PubMed

    Flouri, Eirini; Panourgia, Constantina

    2011-06-01

    The aim of this study was to test for gender differences in how negative cognitive errors (overgeneralizing, catastrophizing, selective abstraction, and personalizing) mediate the association between adverse life events and adolescents' emotional and behavioural problems (measured with the Strengths and Difficulties Questionnaire). The sample consisted of 202 boys and 227 girls (aged 11-15 years) from three state secondary schools in disadvantaged areas in one county in the South East of England. Control variables were age, ethnicity, special educational needs, exclusion history, family structure, family socio-economic disadvantage, and verbal cognitive ability. Adverse life events were measured with Tiet et al.'s (1998) Adverse Life Events Scale. For both genders, we assumed a pathway from adverse life events to emotional and behavioural problems via cognitive errors. We found no gender differences in life adversity, cognitive errors, total difficulties, peer problems, or hyperactivity. In both boys and girls, even after adjustment for controls, cognitive errors were related to total difficulties and emotional symptoms, and life adversity was related to total difficulties and conduct problems. The life adversity/conduct problems association was not explained by negative cognitive errors in either gender. However, we found gender differences in how adversity and cognitive errors produced hyperactivity and internalizing problems. In particular, life adversity was not related, after adjustment for controls, to hyperactivity in girls and to peer problems and emotional symptoms in boys. Cognitive errors fully mediated the effect of life adversity on hyperactivity in boys and on peer and emotional problems in girls.

  5. Associations Between Residential Proximity to Power Plants and Adverse Birth Outcomes

    PubMed Central

    Ha, Sandie; Hu, Hui; Roth, Jeffrey; Kan, Haidong; Xu, Xiaohui

    2015-01-01

    Few studies have assessed the associations between residential proximity to power plants and adverse birth outcomes including preterm delivery (PTD), very preterm delivery (VPTD), and term low birth weight (LBW). We geocoded 423,719 singleton Florida births born from 2004 to 2005 and all active power plants and determined residential proximity to the nearest power plant for each birth. Prenatal exposure to particulate matter less than 2.5 µm in diameter for women living near different types of power plants was also determined by using National Environmental Public Health Tracking Network data. Logistic regression models were used to test the hypothesized associations. Women who lived closer to coal and solid waste power plants were exposed to higher levels of particulate matter less than 2.5 µm in diameter compared with other types. We observed a 1.8% (95% confidence interval (CI): 1.3, 2.3) increased odds for PTD, 2.2% (95% CI: 1.0, 3.4) for VPTD, and 1.1% (95% CI: 0.2, 2.0) for term LBW for each 5 km closer to any power plant. When stratifying by different fuel type, we found that only solid waste had an association with term LBW, whereas oil, gas, and solid waste all had an association with PTD and VPTD. Results were consistent when exposure was categorized by number of power plants. Our study found evidence of increasing odds of adverse birth outcomes among infants born to pregnant women living closer to power plants. More research is warranted to better understand the causal relationship. PMID:26121989

  6. The effect of customization and use of a fetal growth standard on the association between birthweight percentile and adverse perinatal outcome.

    PubMed

    Sovio, Ulla; Smith, Gordon C S

    2018-02-01

    It has been proposed that correction of offspring weight percentiles (customization) might improve the prediction of adverse pregnancy outcome; however, the approach is not accepted universally. A complication in the interpretation of the data is that the main method for calculation of customized percentiles uses a fetal growth standard, and multiple analyses have compared the results with birthweight-based standards. First, we aimed to determine whether women who deliver small-for-gestational-age infants using a customized standard differed from other women. Second, we aimed to compare the association between birthweight percentile and adverse outcome using 3 different methods for percentile calculation: (1) a noncustomized actual birthweight standard, (2) a noncustomized fetal growth standard, and (3) a fully customized fetal growth standard. We analyzed data from the Pregnancy Outcome Prediction study, a prospective cohort study of nulliparous women who delivered in Cambridge, UK, between 2008 and 2013. We used a composite adverse outcome, namely, perinatal morbidity or preeclampsia. Receiver operating characteristic curve analysis was used to compare the 3 methods of calculating birthweight percentiles in relation to the composite adverse outcome. We confirmed previous observations that delivering an infant who was small for gestational age (<10th percentile) with the use of a fully customized fetal growth standard but who was appropriate for gestational age with the use of a noncustomized actual birthweight standard was associated with higher rates of adverse outcomes. However, we also observed that the mothers of these infants were 3-4 times more likely to be obese and to deliver preterm. When we compared the risk of adverse outcome from logistic regression models that were fitted to the birthweight percentiles that were derived by each of the 3 predefined methods, the areas under the receiver operating characteristic curves were similar for all 3 methods: 0

  7. The Relationship between Body Mass Index in Pregnancy and Adverse Maternal, Perinatal, and Neonatal Outcomes in Rural India and Pakistan.

    PubMed

    Short, Vanessa L; Geller, Stacie E; Moore, Janet L; McClure, Elizabeth M; Goudar, Shivaprasad S; Dhaded, Sangappa M; Kodkany, Bhalachandra S; Saleem, Sarah; Naqvi, Farnaz; Pasha, Omrana; Goldenberg, Robert L; Patel, Archana B; Hibberd, Patricia L; Garces, Ana L; Koso-Thomas, Marion; Miodovnik, Menachem; Wallace, Dennis D; Derman, Richard J

    2018-01-24

     The objective of this study was to describe the relationship between early pregnancy body mass index (BMI) and maternal, perinatal, and neonatal outcomes in rural India and Pakistan.  In a prospective, population-based pregnancy registry implemented in communities in Thatta, Pakistan and Nagpur and Belagavi, India, we obtained women's BMI prior to 12 weeks' gestation (categorized as underweight, normal, overweight, and obese following World Health Organization criteria). Outcomes were assessed 42 days postpartum.  The proportion of women with an adverse maternal outcome increased with increasing maternal BMI. Less than one-third of nonoverweight/nonobese women, 47.2% of overweight women, and 56.0% of obese women experienced an adverse maternal outcome. After controlling for site, maternal age and parity, risks of hypertensive disease/severe preeclampsia/eclampsia, cesarean/assisted delivery, and antibiotic use were higher among women with higher BMIs. Overweight women also had significantly higher risk of perinatal and early neonatal mortality compared with underweight/normal BMI women. Overweight women had a significantly higher perinatal mortality rate.  High BMI in early pregnancy was associated with increased risk of adverse maternal, perinatal, and neonatal outcomes in rural India and Pakistan. These findings present an opportunity to inform efforts for women to optimize weight prior to conception to improve pregnancy outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Vitamin D and adverse pregnancy outcomes: beyond bone health and growth.

    PubMed

    Brannon, Patsy M

    2012-05-01

    Concerns exist about adequacy of vitamin D in pregnant women relative to both maternal and fetal adverse health outcomes. Further contributing to these concerns is the prevalence of inadequate and deficient vitamin D status in pregnant women, which ranges from 5 to 84% globally. Although maternal vitamin D metabolism changes during pregnancy, the mechanisms underlying these changes and the role of vitamin D during development are not well understood. Observational evidence links low maternal vitamin D status with an increased risk of non-bone health outcome in the mother (pre-eclampsia, gestational diabetes, obstructed labour and infectious disease), the fetus (gestational duration) and the older offspring (developmental programming of type 1 diabetes, inflammatory and atopic disorders and schizophrenia); but the totality of the evidence is contradictory (except for maternal infectious disease and offspring inflammatory and atopic disorders), lacking causality and, thus, inconclusive. In addition, recent evidence links not only low but also high maternal vitamin D status with increased risk of small-for-gestational age and schizophrenia in the offspring. Rigorous and well-designed randomised clinical trials need to determine whether vitamin D has a causal role in non-bone health outcomes in pregnancy.

  9. Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies.

    PubMed

    de Araujo, Jessica S A; Delgado, Isabella F; Paumgartten, Francisco J R

    2016-06-06

    A study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic potential of glyphosate-based herbicides. These public concerns prompted us to conduct a systematic review of the epidemiological studies testing hypotheses of associations between glyphosate exposure and adverse pregnancy outcomes including birth defects. A systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Bireme-BVS and SCOPUS databases using different combinations of exposure and outcome terms. A case-control study on the association between pesticides and congenital malformations in areas of extensive GM soy crops in South America, and reports on the occurrence of birth defects in these regions were reviewed as well. The search found ten studies testing associations between glyphosate and birth defects, abortions, pre-term deliveries, small for gestational date births, childhood diseases or altered sex ratios. Two additional studies examined changes of time-to-pregnancy in glyphosate-exposed populations. Except for an excess of Attention Deficit Hyperactivity Disorder - ADHD (OR = 3.6, 1.3-9.6) among children born to glyphosate appliers, no significant associations between this herbicide and adverse pregnancy outcomes were described. Evidence that in South American regions of intensive GM-soy planting incidence of birth defects is high remains elusive. Current epidemiological evidence, albeit limited to a few studies using non-quantitative and indirect estimates and dichotomous analysis of exposures, does not lend support to public concerns that glyphosate-based pesticides might pose developmental risks to the unborn child. Nonetheless, owing to methodological limitations of existing analytical observational studies, and particularly to a lack of a direct measurement (urine and/or blood levels), or an indirect estimation of exposure that has proven valid, these

  10. Childhood Adversities Associated with Poor Adult Mental Health Outcomes in Older Homeless Adults: Results From the HOPE HOME Study.

    PubMed

    Lee, Chuan Mei; Mangurian, Christina; Tieu, Lina; Ponath, Claudia; Guzman, David; Kushel, Margot

    2017-02-01

    To examine whether childhood adversity is associated with depressive symptoms, suicide attempts, or psychiatric hospitalization. History of seven childhood adversities (physical neglect, verbal abuse, physical abuse, sexual abuse, parental death, parental incarceration, and child welfare system placement) was gathered through in-person interviews. Multivariate models examined associations between history of childhood adversities and moderate to severe depressive symptoms, lifetime history of suicide attempt, or lifetime history of psychiatric hospitalization. The study enrolled 350 homeless adults, aged 50 and older, in Oakland, California, using population-based sampling methods. Moderate to severe depressive symptoms were measured on a Center for Epidemiologic Studies-Depression Scale (≥22), self-reported lifetime history of suicide attempt, and self-reported lifetime history of psychiatric hospitalization. Participants with exposure to one childhood adversity had elevated odds of reporting moderate to severe depressive symptoms (adjusted odds ratio [AOR]: 2.0; 95% confidence interval [CI]: 1.1-3.7) and lifetime history of suicide attempt (AOR: 4.6; 95% CI: 1.0-21.6) when compared with those who had none; the odds of these two outcomes increased with exposure to additional childhood adversities. Participants with four or more childhood adversities had higher odds of having a lifetime history of psychiatric hospitalization (AOR: 7.1; 95% CI: 2.8-18.0); no increase with fewer adversities was found. Childhood adversities are associated with poor mental health outcomes among older homeless adults. Clinicians should collect information about childhood adversities among this high-risk population to inform risk assessment and treatment recommendations. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. A randomized clinical trial on the effects of remote intercessory prayer in the adverse outcomes of pregnancies.

    PubMed

    da Rosa, Maria Inês; Silva, Fabio Rosa; Silva, Bruno Rosa; Costa, Luciana Carvalho; Bergamo, Angela Mendes; Silva, Napoleão Chiaramonte; Medeiros, Lidia Rosi de Freitas; Battisti, Iara Denise Endruweit; Azevedo, Rafael

    2013-08-01

    The scope of this article was to investigate whether intercessory prayer (IP) influences the adverse outcomes of pregnancies. A double-blind, randomized clinical trial was conducted with 564 pregnant women attending a prenatal public health care service. The women were randomly assigned to an IP group or to a control group (n = 289 per group). They were simultaneously and randomly assigned to practice prayer off-site or not. The following parameters were evaluated: Apgar scores, type of delivery and birth weight. The mean age of the women was 25.1 years of age (± 7.4), and the average gestational age was 23.4 weeks (± 8.1). The average number of years of schooling for the women was 8.1 years (± 3.1). The women in the IP and control groups presented a similar number of adverse medical events with non-significant p. No significant differences were detected in the frequency of adverse outcomes in pregnant women who practiced IP and those in the control group.

  12. Associations between maternal serum free beta human chorionic gonadotropin (β-hCG) levels and adverse pregnancy outcomes.

    PubMed

    Sirikunalai, P; Wanapirak, C; Sirichotiyakul, S; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K; Tongsong, T

    2016-01-01

    The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low β-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

  13. Misuse of antenatal care and its association with adverse outcomes of pregnancy in a Southern rural area of Vietnam.

    PubMed

    Ngo, Thi-Thuy-Dung; Nguyen, The-Dung; Goyens, Philippe; Robert, Annie

    2018-04-01

    Researchers in Vietnam reported a high percentage of pregnant women attending ANC at least once, but an insufficient utilization of ANC services remains. The evidence demonstrating how the utilization of these services affect pregnancy outcome is not documented in Vietnam. We investigated the association between the misuse of ANC services and pregnancy outcome, and assessed other determinants associated with ANC services utilization. We conducted a prospective community-based study in Trang Bom district, Dong Nai, during 12 consecutive months. Data were collected using a structured questionnaire and medical records. Women were followed up to delivery. Misuse of ANC services, related factors and its association with adverse events were assessed using logistic regression. Out of 3301 pregnant women, 91% initiated an ANC visit within first trimester, 95% attended at least three ANC visits, but a low percentage of pregnant women underwent blood and urine tests at least once (20% and 39%, respectively). Factors significantly associated with a higher risk of adverse outcomes were lack of blood test and urine test, parity ≥ 3, ANC visits < 3, history of an adverse outcome, and having a clinical condition. Blood and urine tests were less frequently used by young women, women from ethnic minorities, women using only private facilities for ANC attendance, and women with a low number of ANC visits. Despite a high percentage of early entry into ANC and of at least three ANC visits, misuse of ANC services still exists and contributes to adverse outcomes. There is a need to increase the awareness of women on the benefits of ANC services by educating young women as well as women with several children. Health workers should be encouraged to propose suitable ANC services to pregnant women.

  14. An investigation into the relationship between region specific quality of life and adverse tuberculosis treatment outcomes in Istanbul, Turkey.

    PubMed

    Babalik, A; Kiziltas, S; Gencer, S; Kilicaslan, Z

    2014-01-01

    Istanbul has the highest incidence of tuberculosis (TB) in Turkey. It is also the largest city, with considerable differences in quality of life across its urban regions. The aim of this study is to investigate the relationship between (i) the diverse quality of life across specific urban regions, (ii) TB incidence rates, inclusive of demographic and clinical characteristics of TB patients, and (iii) adverse treatment outcomes. This retrospective study included 23,845 new TB patients (recorded in the National TB Registry between 2006 and 2010) in Istanbul. Thirty-nine urban districts of Istanbul were ranked into five groups on the basis of an urban quality of life index. Patient data were matched with these groups, and further categorized according to 'age', 'sex', 'country of birth' and 'antibiotics resistance'. Adverse treatment outcomes and TB incidence rates were extracted from official records. Logistic regression, clustered analyses, 95% CI and p values (STATA) were reported to describe the association between variables. Six per cent of total cases had 'at least one adverse treatment outcome' (default 3.8%, failure 0.5%, death 1.7% in total cases). 'An adverse treatment outcome' was found to be associated with age OR (CI 95%) (1.02 (1.01-1.03)); 'male sex' 1.65 (1.28-2.12); 'other country of birth' 4.82 (3.05-7.62); 100,000 per 'over 60' insidence goups 1.61 (1.32-1.97), the lowest quality of life index 0.65 (0.47-0.83). Patients with high tuberculosis risk factors living in high incidence regions need to be closely monitored. Patients living in lower ranking regions are more likely to have 'poor treatment outcomes'. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  15. Non-cigarette tobacco use among women and adverse pregnancy outcomes

    PubMed Central

    ENGLAND, LUCINDA J.; KIM, SHIN Y.; TOMAR, SCOTT L; RAY, CECILY S; GUPTA, PRAKASH C.; EISSENBERG, THOMAS; CNATTINGIUS, SVEN; BERNERT, JOHN T.; TITA, ALAN THEVENET N.; WINN, DEBORAH M.; DJORDJEVIC, MIRJANA V.; LAMBE, MATS; STAMILIO, DAVID; CHIPATO, TSUNGAI; TOLOSA, JORGE E.

    2017-01-01

    Although cigarette smoking remains the most prevalent form of tobacco use in girls and in women of reproductive age globally, use of non-cigarette forms of tobacco is prevalent or gaining in popularity in many parts of the world, especially in low- and middle-income countries. Sparse but growing evidence suggests that the use of some non-cigarette tobacco products during pregnancy increases the risk of adverse pregnancy outcomes. In this paper we review the literature on the prevalence of non-cigarette tobacco product use in pregnant women and in women of reproductive age in high-, middle-, and low-income countries and the evidence that maternal use of these products during pregnancy has adverse health effects. In addition, we communicate findings from an international group of perinatal and tobacco experts that was convened to establish research priorities concerning the use of non-cigarette tobacco products during pregnancy. The working group concluded that attempts to develop a public health response to non-cigarette tobacco use in women are hindered by a lack of data on the epidemiology of use in many parts of the world and by our limited understanding of the type and magnitude of the health effects of these products. We highlight research gaps and provide recommendations for a global research agenda. PMID:20225987

  16. Short-Term Adverse Outcomes After Deep Brain Stimulation Treatment in Patients with Parkinson Disease.

    PubMed

    Hu, Kejia; Moses, Ziev B; Hutter, Matthew M; Williams, Ziv

    2017-02-01

    Despite ongoing progress in our understanding of long-term outcomes after neuromodulation procedures, acute adverse outcomes shortly after deep brain stimulation (DBS) treatment have remained remarkably limited. To identify risk factors associated with acute 30-day outcomes after DBS treatment in patients with Parkinson disease (PD). We evaluated patients who underwent DBS treatment for PD from 2005 to 2014 through the American College of Surgeons National Surgical Quality Improvement Program database. We used bivariate analysis and multivariate logistic regression to identify short-term postoperative outcomes, including 30-day complication, discharge destination, and unplanned readmission. Overall, 650 patients with PD underwent DBS procedures and complications were identified in 32 patients (4.9%). Of 481 patients who had complete discharge data, 18 patients (3.7%) were discharged to a facility and 16 patients (3.3%) experienced an unplanned readmission. Patients with PD who were obese (P = 0.045), who had preoperative anemia (P = 0.008), and who experienced longer operative durations (P = 0.01) had increased odds of postoperative complications. Inpatient status (P = 0.001), dependent functional status (P < 0.001), and anemia (P = 0.043) were all associated with discharge to a facility other than home. Longer operative duration (P = 0.013), anemia (P = 0.036), and dependent functional status (P = 0.03) were significantly associated with unplanned readmission. As expected, complications increased the likelihood of unplanned readmission (P < 0.001). This study provides individualized estimates of the risks associated with short-term adverse outcomes based on patient demographics and comorbidities. These data can be used as an adjunct for short-term risk stratification of patients with PD being considered for DBS treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Low diastolic blood pressure and adverse outcomes in heart failure with preserved ejection fraction.

    PubMed

    Tsujimoto, Tetsuro; Kajio, Hiroshi

    2018-07-15

    It remains unknown whether a low diastolic blood pressure (DBP) increases the risks of cardiovascular events and death in patients with heart failure with preserved ejection fraction (HFpEF). We used data from the TOPCAT trial. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure. Hazard ratios (HRs) were analyzed for DBPs of <60, 60-69, 70-79, and ≥90 mm Hg in comparison with a DBP of 80-89 mm Hg using multivariable Cox proportional hazard models. This study included 3417 patients with HFpEF who had a controlled blood pressure. In the mean follow-up period of 3.0 years, 881 patients experienced at least one confirmed primary outcome event. Compared with patients with a DBP of 80-89 mm Hg, the adjusted HRs for primary outcome events were significantly higher in those with DBPs of <60 mm Hg (HR: 2.19 [95% confidence interval,1.72-2.78]) and 60-69 mm Hg (HR: 1.52 [1.23-1.87]). Similarly, the adjusted HRs for all-cause death, major cardiovascular events, and hospitalization for heart failure, but not stroke, were significantly higher in patients with a DBP of <70 mm Hg. A relationship between a low DBP and adverse outcomes was found in HFpEF patients with a systolic blood pressure of ≥120 mm Hg; however, a low systolic blood pressure with a DBP of ≥70 mm Hg was not associated with these event risks. A low DBP increased the risks of adverse outcomes in patients with HFpEF. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Pneumococcal pneumonia - Are the new severity scores more accurate in predicting adverse outcomes?

    PubMed

    Ribeiro, C; Ladeira, I; Gaio, A R; Brito, M C

    2013-01-01

    The site-of-care decision is one of the most important factors in the management of patients with community-acquired pneumonia. The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision. The aim of this paper was to compare the discriminatory power of four scores - the classic PSI and CURB65 ant the most recent SCAP and SMART-COP - in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support in patients admitted with pneumococcal pneumonia. A five year retrospective study of patients admitted for pneumococcal pneumonia. Patients were stratified based on admission data and assigned to low-, intermediate-, and high-risk classes for each score. Results were obtained comparing low versus non-low risk classes. We studied 142 episodes of hospitalization with 2 deaths and 10 patients needing mechanical ventilation and vasopressor support. The majority of patients were classified as low risk by all scores - we found high negative predictive values for all adverse events studied, the most negative value corresponding to the SCAP score. The more recent scores showed better accuracy for predicting ICU admission and need for ventilation or vasopressor support (mostly for the SCAP score with higher AUC values for all adverse events). The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores appear to have a higher discriminatory power in all adverse events in our study, particularly, the SCAP score. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  19. Ecdysone receptor agonism leading to lethal molting disruption in arthropods: Review and adverse outcome pathway development

    EPA Science Inventory

    Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, s...

  20. Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-analysis.

    PubMed

    Carpenter, Christopher R; Shelton, Erica; Fowler, Susan; Suffoletto, Brian; Platts-Mills, Timothy F; Rothman, Richard E; Hogan, Teresita M

    2015-01-01

    A significant proportion of geriatric patients experience suboptimal outcomes following episodes of emergency department (ED) care. Risk stratification screening instruments exist to distinguish vulnerable subsets, but their prognostic accuracy varies. This systematic review quantifies the prognostic accuracy of individual risk factors and ED-validated screening instruments to distinguish patients more or less likely to experience short-term adverse outcomes like unanticipated ED returns, hospital readmissions, functional decline, or death. A medical librarian and two emergency physicians conducted a medical literature search of PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov using numerous combinations of search terms, including emergency medical services, risk stratification, geriatric, and multiple related MeSH terms in hundreds of combinations. Two authors hand-searched relevant specialty society research abstracts. Two physicians independently reviewed all abstracts and used the revised Quality Assessment of Diagnostic Accuracy Studies instrument to assess individual study quality. When two or more qualitatively similar studies were identified, meta-analysis was conducted using Meta-DiSc software. Primary outcomes were sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for predictors of adverse outcomes at 1 to 12 months after the ED encounters. A hypothetical test-treatment threshold analysis was constructed based on the meta-analytic summary estimate of prognostic accuracy for one outcome. A total of 7,940 unique citations were identified yielding 34 studies for inclusion in this systematic review. Studies were significantly heterogeneous in terms of country, outcomes assessed, and the timing of post-ED outcome assessments. All studies occurred in ED settings and none used published clinical decision rule derivation methodology. Individual risk factors assessed included dementia, delirium, age, dependency

  1. A Multivariate Analysis of Adverse Childhood Experiences and Health Behaviors and Outcomes among College Students

    ERIC Educational Resources Information Center

    Windle, Michael; Haardörfer, Regine; Getachew, Beth; Shah, Jean; Payne, Jackie; Pillai, Dina; Berg, Carla J.

    2018-01-01

    Objective: This study investigated associations between adverse childhood experiences (ACE) prior to age 18 years and multiple health behaviors (eg, cigarette and other substance use) and outcomes (eg, obesity, depression) for a large college sample. Participants: 2,969 college students from seven universities in the state of Georgia were included…

  2. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  3. Differentiating high priority pathway-based toxicity from non ...

    EPA Pesticide Factsheets

    The ToxCast chemical screening approach enables the rapid assessment of large numbers of chemicals for biological effects, primarily at the molecular level. Adverse outcome pathways (AOPs) offer a means to link biomolecular effects with potential adverse outcomes at the level of the individual or population, thus enhancing the utility of the ToxCast effort for hazard assessment. Thus, efforts are underway to develop AOPs relevant to the pathway perturbations detected in ToxCast assays. However, activity (?‘hits’) determined for chemical-assay pairs may reflect target-specific activity relevant to a molecular initiating event of an AOP, or more generalized cell stress and cytotoxicity-mediated effects. Previous work identified a ?‘cytotoxic burst’ phenomenon wherein large numbers of assays begin to respond at or near concentrations that elicit cytotoxicity. The concentration range at which the “burst” occurs is definable, statistically. Consequently, in order to focus AOP development on the ToxCast assay targetswhich are most sensitive and relevant to pathway-specific effects, we conducted a meta-analysis to identify which assays were frequently responding at concentrations well below the cytotoxic burst. Assays were ranked by the fraction of chemical hits below the burst concentration range compared to the number of chemicals tested, resulting in a preliminary list of potentially important, target-specific assays. After eliminating cytotoxicity a

  4. Becoming a "second victim" in health care: Pathway of recovery after adverse event.

    PubMed

    Rinaldi, C; Leigheb, F; Vanhaecht, K; Donnarumma, C; Panella, M

    2016-07-01

    The healthcare worker involved in an unanticipated adverse patient event can become second victim. These workers suffer physically and psycho-socially and try to overcome the post-event emotional stress by obtaining emotional support in a variety of ways. The goal of this research was to study second victims among health care providers in Italy. This contribution contains the results of 33 interviews of nurses, physicians and other healthcare workers. After institutional approval, the semi-structured interview, composed of 25 questions, was translated from English into Italian. The audio-interviews were transcribed on paper verbatim by the interviewer. It was then verified if the interviewees experienced the six post-event stages of second victim recovery previously described within the literature. The interviewees described the post-event recovery stages described by literature but stages were not detailed in the exact succession order as the American study. All participants clearly remembered the adverse event and referred the physical and psycho-social symptoms. The psychological support obtained by second victims was described as poor and inefficient. The post-event recovery pathway is predictable but not always clearly respected as defined within this Italian sample. Future study of the second-victim phenomenon and desired supportive interventions is necessary to understand the experience and interventions to mitigate harm of future clinicians. Every day healthcare workers become second victims and, considering that human resources are the most important heritage of healthcare infrastructures, after an adverse event it is very important to execute valid interventional programs to support and train these workers. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. The Adverse Outcome Pathway: A conceptual framework to support toxicity testing in the 21st century

    EPA Science Inventory

    The field of regulatory toxicity testing is at a turning point. The U.S. National Research Council (NRC) envisioned a shift away from traditional toxicity testing and towards a focused effort to explore and understand pathways perturbed by biologically active substances or their ...

  6. Adverse cardiovascular outcomes between insulin-treated and non-insulin treated diabetic patients after percutaneous coronary intervention: a systematic review and meta-analysis.

    PubMed

    Bundhun, Pravesh Kumar; Li, Nuo; Chen, Meng-Hua

    2015-10-07

    Type 2 diabetes mellitus (DM) patients have worse adverse cardiovascular outcomes after Percutaneous Coronary Intervention (PCI). However, the adverse cardiovascular outcomes between insulin-treated and non-insulin treated DM patients have been a subject of debate. We sought to compare the short-term (<1 year) and long-term (≥1 year) cardiovascular outcomes between insulin-treated and non-insulin treated DM patients after PCI. Medline and Embase databases were searched for studies by typing 'diabetes and percutaneous coronary intervention/PCI' or 'insulin-treated and non-insulin treated diabetes mellitus and PCI'. Endpoints included adverse cardiovascular outcomes reported in these DM patients during the corresponding follow-up periods. Odd Ratio (OR) with 95% confidence interval (CI) was used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. 21 studies have been included in this meta-analysis consisting of a total of 21,759 diabetic patients (6250 insulin-treated and 15,509 non-insulin treated DM patients). Short term mortality, myocardial infarction, target lesion revascularization, major adverse cardiac effects and, stent thrombosis were significantly higher in insulin-treated diabetic patients (OR 1.69, 95% CI 1.40-2.04, p < 0.00001), (OR 1.40, 95% CI 1.16-1.70, p = 0.0005), (OR 1.37, 95% CI 1.06-1.76, p = 0.02), (OR 1.46, 95% CI 1.22-1.76, p < 0.0001) and (OR 1.66, 95% CI 1.16-2.38, p = 0.005) respectively. Long-term cardiovascular outcomes were also significantly higher in insulin-treated DM patients. Insulin treatment in these DM patients was associated with a significantly higher short and long-term adverse cardiovascular outcomes after PCI compared to those DM patients not treated by insulin therapy.

  7. Plasma Glycoproteomics Reveals Sepsis Outcomes Linked to Distinct Proteins in Common Pathways

    PubMed Central

    DeLeon-Pennell, Kristine Y.; Nguyen, Nguyen T.; de Castro Brás, Lisandra E.; Flynn, Elizabeth R.; Cannon, Presley L.; Griswold, Michael E.; Jin, Yu-Fang; Puskarich, Michael A.; Jones, Alan E.; Lindsey, Merry L.

    2015-01-01

    Objective Sepsis remains a predominant cause of mortality in the ICU, yet strategies to increase survival have proved largely unsuccessful. This study aimed to identify proteins linked to sepsis outcomes using a glycoproteomic approach to target extracellular proteins that trigger downstream pathways and direct patient outcomes. Design Plasma was obtained from the LacTATEs cohort. N-linked plasma glycopeptides were quantified by solid-phase extraction coupled with mass spectrometry. Glycopeptides were assigned to proteins using RefSeq and visualized in a heat map. Protein differences were validated by immunoblotting, and proteins were mapped for biological processes using Database for Annotation, Visualization and Integrated Discovery and for functional pathways using Kyoto Encyclopedia of Genes and Genomes databases. Setting Hospitalized care. Measurements and Main Results A total of 501 glycopeptides corresponding to 234 proteins were identified. Of these, 66 glycopeptides were unique to the survivor group and corresponded to 54 proteins, 60 were unique to the nonsurvivor group and corresponded to 43 proteins, and 375 were common responses between groups and corresponded to 137 proteins. Immunoblotting showed that nonsurvivors had increased total kininogen; decreased total cathepsin-L1, vascular cell adhesion molecule, periostin, and neutrophil gelatinase–associated lipocalin; and a two-fold decrease in glycosylated clusterin (all p < 0.05). Kyoto Encyclopedia of Genes and Genomes analysis identified six enriched pathways. Interestingly, survivors relied on the extrinsic pathway of the complement and coagulation cascade, whereas nonsurvivors relied on the intrinsic pathway. Conclusion This study identifies proteins linked to patient outcomes and provides insight into unexplored mechanisms that can be investigated for the identification of novel therapeutic targets. (Crit Care Med 2015; XX:00–00) PMID:26086942

  8. Clinical outcomes and adverse effect monitoring in allergic rhinitis.

    PubMed

    Juniper, Elizabeth F; Ståhl, Elisabeth; Doty, Richard L; Simons, F Estelle R; Allen, David B; Howarth, Peter H

    2005-03-01

    The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably

  9. The joint contribution of maternal history of early adversity and adulthood depression to socioeconomic status and potential relevance for offspring development.

    PubMed

    Bouvette-Turcot, Andrée-Anne; Unternaehrer, Eva; Gaudreau, Hélène; Lydon, John E; Steiner, Meir; Meaney, Michael J

    2017-01-01

    We examined the interactive effects of maternal childhood adversity and later adulthood depression on subsequent socioeconomic status (SES). Our community sample ranged from 230 to 243 mothers (across measures) drawn from a prospective, longitudinal cohort study. Maternal childhood adversity scores were derived using an integrated measure derived from the Childhood Trauma Questionnaire (CTQ) and the Parental Bonding Index (PBI). Maternal depression was measured in the prenatal period with the Center for Epidemiologic Studies Depression Scale (CES-D). SES measures included maternal highest level of education and family income as obtained prenatally. The analyses yielded significant interaction effects between maternal childhood adversity and prenatal depression that predicted income, prenatally. Women who reported higher levels of childhood adversity combined with higher levels of self-reported depressive symptoms were significantly more likely to live in low SES environments. Results also showed that level of education was predicted by childhood adversity independent of maternal symptoms of depression. The results suggest that SES is influenced by a life course pathway that begins in childhood and includes adversity-related mental health outcomes. Since child health and development is influenced by both maternal mental health and SES, this pathway may also contribute to the intergenerational transmission of the risk for psychopathology in the offspring. The results also emphasize the importance of studying potential precursors of low SES, a well-documented environmental risk factor for poor developmental outcomes in the offspring. Copyright © 2016. Published by Elsevier B.V.

  10. Comparison of cystatin C and creatinine to determine the incidence of composite adverse outcomes in HIV-infected individuals.

    PubMed

    Yanagisawa, Naoki; Sasaki, Shugo; Suganuma, Akihiko; Imamura, Akifumi; Ajisawa, Atsushi; Ando, Minoru

    2015-02-01

    Cystatin C is an overall biomarker of pathophysiologic abnormalities that accompany chronic kidney disease (CKD). The utility of cystatin C is not fully understood in an HIV-infected population. This prospective study investigated 661 HIV-infected individuals for 4 years to determine the incidence of adverse outcomes, including all-cause mortality, cardiovascular disease, and renal dysfunction. The risk of developing the outcomes was discriminated with a 4 color-coded classification in a 3 × 6 contingency table, that combined 3 grades of dipstick proteinuria with 6 grades of estimated glomerular filtration rate (eGFR) calculated using either serum creatinine (eGFRcr) or cystatin C (eGFRcy): green, low risk; yellow, moderately increased risk; orange, high risk; and red, very high risk. The cumulative incidence of the outcomes was assessed by the Kaplan-Meier method, and the association between color-coded risk and the time to outcome was evaluated using multivariate proportional hazards analysis. Compared with eGFRcr, the use of eGFRcy reduced the prevalence of risk ≥ orange by 0.8%. The adverse outcomes were significantly more likely to occur to the patients with baseline risk category ≥orange than those with ≤ yellow, independent of risk categories based on eGFRcr or eGFRcy. However, in multivariate analysis, risk category ≥orange with eGFRcy-based classification was significantly associated with adverse outcomes, but not the one with eGFRcr. Replacing creatinine by cystatin C in the CKD color-coded risk classification may be appropriate to discriminate HIV-infected patients at increased risk of a poor prognosis. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Life Course Pathways of Adversities Linking Adolescent Socioeconomic Circumstances and Functional Somatic Symptoms in Mid-Adulthood: A Path Analysis Study

    PubMed Central

    Jonsson, Frida; San Sebastian, Miguel; Strömsten, Lotta M. J.; Hammarström, Anne; Gustafsson, Per E.

    2016-01-01

    While research examining the health impact of early socioeconomic conditions suggests that effects may exist independently of or jointly with adult socioeconomic position, studies exploring other potential pathways are few. Following a chain of risk life course model, this prospective study seeks to examine whether pathways of occupational class as well as material and social adversities across the life course link socioeconomic disadvantage in adolescent to functional somatic symptoms in mid-adulthood. Applying path analysis, a multiple mediator model was assessed using prospective data collected during 26 years through the Northern Swedish Cohort. The sample contained 987 individuals residing in the municipality of Luleå, Sweden, who participated in questionnaire surveys at age 16, 21, 30 and 42. Socioeconomic conditions (high/low) in adolescence (age 16) were operationalized using the occupation of the parents, while occupational class in adulthood (manual/non-manual) was measured using the participant’s own occupation at age 21 and 30. The adversity measurements were constructed as separate age specific parcels at age 21 and 30. Social adversity included items pertaining to stressful life events that could potentially harm salient relationships, while material adversity was operationalized using items concerning unfavorable financial and material circumstances. Functional somatic symptoms at age 42 was a summary measure of self-reported physical symptoms, palpitation and sleeping difficulties that had occurred during the last 12 months. An association between socioeconomic conditions at age 16 and functional somatic symptoms at age 42 (r = 0.068) which was partially explained by people’s own occupational class at age 21 and then material as well as social adversity at age 30 was revealed. Rather than proposing a direct and independent health effect of the socioeconomic conditions of the family, the present study suggests that growing up in an unfavorable

  12. Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria.

    PubMed

    Monseu, Mathilde; Gand, Elise; Saulnier, Pierre-Jean; Ragot, Stéphanie; Piguel, Xavier; Zaoui, Philippe; Rigalleau, Vincent; Marechaud, Richard; Roussel, Ronan; Hadjadj, Samy; Halimi, Jean-Michel

    2015-12-01

    Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Postoperative adverse outcomes among physicians receiving major surgeries

    PubMed Central

    Yeh, Chun-Chieh; Liao, Chien-Chang; Shih, Chun-Chuan; Jeng, Long-Bin; Chen, Ta-Liang

    2016-01-01

    Abstract Outcomes after surgeries involving physicians as patients have not been researched. This study compares postoperative adverse events between physicians as surgical patients and nonhealth professional controls. Using reimbursement claims data from Taiwan's National Health Insurance Program, we conducted a matched retrospective cohort study of 7973 physicians as surgical patients and 7973 propensity score–matched nonphysician controls receiving in-hospital major surgeries between 2004 and 2010. We compared postoperative major complications, length of hospital stay, intensive care unit (ICU), medical expenditure, and 30-day mortality. Compared with nonphysician controls, physicians as surgical patients had lower adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of postoperative deep wound infection (OR 0.63, 95% CI 0.40–0.99; P < 0.05), prolonged length of stay (OR 0.68, 95% CI 0.62–0.75; P < 0.0001), ICU admission (OR 0.74, 95% CI 0.66–0.83; P < 0.0001), and increased medical expenditure (OR 0.80, 95% CI 0.73–0.88; P < 0.0001). Physicians as surgical patients were not associated with 30-day in-hospital mortality after surgery. Physicians working at medical centers (P < 0.05 for all), dentists (P < 0.05 for all), and those with fewer coexisting medical conditions (P < 0.05 for all) had lower risks for postoperative prolonged length of stay, ICU admission, and increased medical expenditure. Although our study's findings suggest that physicians as surgical patients have better outcomes after surgery, future clinical prospective studies are needed for validation. PMID:27684836

  14. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Teeguarden, Justin G.; Tan, Yu-Mei; Edwards, Stephen W.

    Driven by major scientific advances in analytical methods, biomonitoring, and computational exposure assessment, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the computationally enabled “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) conceptmore » in the toxicological sciences. The AEP framework offers an intuitive approach to successful organization of exposure science data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathway and adverse outcome pathways, completing the source to outcome continuum and setting the stage for more efficient integration of exposure science and toxicity testing information. Together these frameworks form and inform a decision making framework with the flexibility for risk-based, hazard-based or exposure-based decisions.« less

  15. Inadequate Gestational Weight Gain Predicts Adverse Pregnancy Outcomes in Mothers with Inflammatory Bowel Disease: Results from a Prospective US Pregnancy Cohort.

    PubMed

    Bengtson, May-Bente; Martin, Christopher F; Aamodt, Geir; Vatn, Morten H; Mahadevan, Uma

    2017-08-01

    Malnutrition and weight loss are common features of patients with inflammatory bowel disease (IBD). To explore the impact of inadequate gestational weight gain (GWG) on adverse outcomes among IBD mothers in the prospective US pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) cohort. The PIANO cohort comprises 559 and 363 pregnant mothers with Crohn's disease (CD) and ulcerative colitis (UC), respectively, enrolled between 2006 and 2014. The mothers were followed during and after pregnancy to ascertain medication, measurement of disease activity and complications during pregnancy and at delivery. Inadequate GWG was based on US Institute of Medicine recommendations. The associations between inadequate GWG and adverse pregnancy outcomes in maternal IBD were analyzed, adjusted for diabetes, hypertension, smoking, maternal age, education, and disease activity. Maternal CD and UC with inadequate GWG had a 2.5-fold increased risk of preterm birth (OR 2.5, CI 1.3, 4.9 and OR 2.5, CI 1.2, 5.6). Furthermore, an increased risk of intrauterine growth restriction and a trend for small for gestational age were demonstrated in CD but not in UC (OR 3.3, CI 1.1, 10.0, OR 4.5, CI 0.8, 24.3, p = 0.08). Flares increased risk of inadequate GWG (OR 1.6, CI 1.2, 2.3, p = 0.002) but did not change the associations between inadequate GWG and adverse pregnancy outcomes in our models. The US PIANO cohort demonstrated that inadequate GWG was a strong independent predictor of adverse pregnancy outcomes in IBD mothers.

  16. Adverse outcome pathway networks II: Network analytics

    EPA Science Inventory

    The US EPA is developing more cost effective and efficient ways to evaluate chemical safety using high throughput and computationally based testing strategies. An important component of this approach is the ability to translate chemical effects on fundamental biological processes...

  17. Adverse outcome pathways | Science Inventory | US EPA

    EPA Pesticide Factsheets

    The Systems Toxicology Unit of the European Commission Joint Research Centre (JRC) is strongly committed to development and uptake of AOPs. In coordination with the OECD, the JRC and EPA have collaborated closely in the development of training and outreach materials related to the development and application of AOPs. The European Food Safety Authority (EFSA) has requested that the JRC provide eight training courses, each 2 days in duration, to EFSA over a 2.5 year period. Given EPA’s expertise in the development of AOPs and the AOP-wiki, as well as EPA’s experience in training others on the AOP concepts and best practices in this rapidly moving arena, the JRC has engaged EPA expertise in this training activity, which reaches groups of 30-40 participants from regulatory authorities and academic institutes across Europe. Not Applicable

  18. Discriminative ability of commonly used indices to predict adverse outcomes after poster lumbar fusion: a comparison of demographics, ASA, the modified Charlson Comorbidity Index, and the modified Frailty Index.

    PubMed

    Ondeck, Nathaniel T; Bohl, Daniel D; Bovonratwet, Patawut; McLynn, Ryan P; Cui, Jonathan J; Shultz, Blake N; Lukasiewicz, Adam M; Grauer, Jonathan N

    2018-01-01

    As research tools, the American Society of Anesthesiologists (ASA) physical status classification system, the modified Charlson Comorbidity Index (mCCI), and the modified Frailty Index (mFI) have been associated with complications following spine procedures. However, with respect to clinical use for various adverse outcomes, no known study has compared the predictive performance of these indices specifically following posterior lumbar fusion (PLF). This study aimed to compare the discriminative ability of ASA, mCCI, and mFI, as well as demographic factors including age, body mass index, and gender for perioperative adverse outcomes following PLF. A retrospective review of prospectively collected data was performed. Patients undergoing elective PLF with or without interbody fusion were extracted from the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program (NSQIP). Perioperative adverse outcome variables assessed included the occurrence of minor adverse events, severe adverse events, infectious adverse events, any adverse event, extended length of hospital stay, and discharge to higher-level care. Patient comorbidity indices and characteristics were delineated and assessed for discriminative ability in predicting perioperative adverse outcomes using an area under the curve analysis from the receiver operating characteristics curves. In total, 16,495 patients were identified who met the inclusion criteria. The most predictive comorbidity index was ASA and demographic factor was age. Of these two factors, age had the larger discriminative ability for three out of the six adverse outcomes and ASA was the most predictive for one out of six adverse outcomes. A combination of the most predictive demographic factor and comorbidity index resulted in improvements in discriminative ability over the individual components for five of the six outcome variables. For PLF, easily obtained patient ASA and age have overall similar or better

  19. Maternal Dietary L-Arginine and Adverse Birth Outcomes in Dar es Salaam, Tanzania.

    PubMed

    Darling, Anne Marie; McDonald, Chloe R; Urassa, Willy S; Kain, Kevin C; Mwiru, Ramadhani S; Fawzi, Wafaie W

    2017-09-01

    The amino acid arginine is a physiological precursor to nitric oxide, which is a key mediator of embryonic survival, fetal growth, and pregnancy maintenance. We evaluated the association between consumption of the amino acid arginine and the rate of adverse birth outcomes using data from a double-blind, randomized, placebo-controlled micronutrient supplementation trial among pregnant women in Dar es Salaam, Tanzania (2001-2004). Dietary intakes of arginine were assessed using repeated 24-hour recalls that were administered throughout pregnancy. Participants (n = 7,591) were monitored by research midwives throughout follow-up to assess pregnancy outcomes. Cubic-restricted splines and multivariable log-Poisson regression with empirical standard errors were used to estimate the continuous and categorical associations between arginine intake and adverse birth outcomes. Compared with women within the lowest quintile of arginine intake, those within the highest quintile had 0.79 times the risk of preterm birth before 37 weeks (95% confidence interval: 0.63, 1.00; P = 0.03). The continuous associations of arginine intake with preterm birth before 37 weeks and with preterm birth before 34 weeks were characterized by an initial rapid decrease in risk with increasing intake (P for nonlinearity < 0.01). Arginine intake was not associated with fetal loss or giving birth to infants who were born small for their gestational ages. This data suggest that the association between dietary arginine intake and preterm birth warrants further investigation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Establishing a Multidisciplinary Head and Neck Clinical Pathway: An Implementation Evaluation and Audit of Dysphagia-Related Services and Outcomes.

    PubMed

    Messing, Barbara Pisano; Ward, Elizabeth C; Lazarus, Cathy; Ryniak, Keri; Kim, Melissa; Silinonte, Jessica; Gold, Dorothy; Thompson, Carol B; Pitman, Karen T; Blanco, Ray; Sobel, Ryan; Harrer, Karen; Ulmer, Karen; Neuner, Geoffrey; Patel, Kruti; Tang, Mei; Lee, Gregory

    2018-06-19

    Head and neck cancer (HNC) guidelines recommend regular multidisciplinary team (MDT) monitoring and early intervention to optimize dysphagia outcomes; however, many factors affect the ability to achieve these goals. The aims of this study were to explore the barriers/facilitators to establishing and sustaining a MDT HNC care pathway and to examine the dysphagia-related speech-language pathology (SLP) and dietetic components of the pathway. Using the Consolidated Framework for Implementation Research (CFIR), a mixed methods study design was used to evaluate an established MDT HNC pathway. Ten MDT members provided perceptions of facilitators/barriers to implementing and sustaining the pathway. Patients attending the SLP and dietetic components of the pathway who commenced treatment between 2013 and 2014 (n = 63) were audited for attendance, outcome data collected per visit, and swallowing outcomes to 24-month post-treatment. Dysphagia outcomes were compared to a published cohort who had received intensive prophylactic dysphagia management. Multiple CFIR constructs were identified as critical to implementing and sustaining the pathway. Complexity was a barrier. Patient attendance was excellent during treatment, with low rates of non-compliance (< 15%) to 24 months. Collection of clinician/patient outcome tools was good during treatment, but lower post-treatment. Dysphagia outcomes were good and comparable to prior published data. The pathway provided patients with access to regular supportive care and provided staff opportunities to provide early and ongoing dysphagia monitoring and management. However, implementing and sustaining a HNC pathway is complex, requiring significant staff resources, financial investment, and perseverance. Regular audits are necessary to monitor the quality of the pathway.

  1. The association between ambient air pollution and selected adverse pregnancy outcomes in China: A systematic review.

    PubMed

    Jacobs, Milena; Zhang, Guicheng; Chen, Shu; Mullins, Ben; Bell, Michelle; Jin, Lan; Guo, Yuming; Huxley, Rachel; Pereira, Gavin

    2017-02-01

    The association between exposure to ambient air pollution and respiratory or cardiovascular endpoints is well-established. An increasing number of studies have shown that this exposure is also associated with adverse pregnancy outcomes. However, the majority of research has been undertaken in high-income western countries, with relatively lower levels of exposure. There is now a sufficient number of studies to warrant an assessment of effects in China, a relatively higher exposure setting. We conducted a systematic review of 25 studies examining the association between ambient air pollution exposure and adverse pregnancy outcomes (lower birth weight, preterm birth, mortality, and congenital anomaly) in China, published between 1980 and 2015. The results indicated that sulphur dioxide (SO 2 ) was more consistently associated with lower birth weight and preterm birth, and that coarse particulate matter (PM 10 ) was associated with congenital anomaly, notably cardiovascular defects. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Improving outcomes following penetrating colon wounds: application of a clinical pathway.

    PubMed

    Miller, Preston R; Fabian, Timothy C; Croce, Martin A; Magnotti, Louis J; Elizabeth Pritchard, F; Minard, Gayle; Stewart, Ronald M

    2002-06-01

    During World War II, failure to treat penetrating colon injuries with diversion could result in court martial. Based on this wartime experience, colostomy for civilian colon wounds became the standard of care for the next 4 decades. Previous work from our institution demonstrated that primary repair was the optimal management for nondestructive colon wounds. Optimal management of destructive wounds requiring resection remains controversial. To address this issue, we performed a study that demonstrated risk factors (pre or intraoperative transfusion requirement of more than 6 units of packed red blood cells, significant comorbid diseases) that were associated with a suture line failure rate of 14%, and of whom 33% died. Based on these outcomes, a clinical pathway for management of destructive colon wounds was developed. The results of the implementation of this pathway are the focus of this report. Patients with penetrating colon injury were identified from the registry of a level I trauma center over a 5-year period. Records were reviewed for demographics, injury characteristics, and outcome. Patients with nondestructive injuries underwent primary repair. Patients with destructive wounds but no comorbidities or large transfusion requirement underwent resection and anastomosis, while patients with destructive wounds and significant medical illness or transfusion requirements of more than 6 units/blood received end colostomy. The current patients (CP) were compared to the previous study (PS) to determine the impact of the clinical pathway. Outcomes examined included colon related mortality and morbidity (suture line leak and abscess). Over a 5.5-year period, 231 patients had penetrating colon wounds. 209 survived more 24 hours and comprise the study population. Primary repair was performed on 153 (73%) patients, and 56 patients had destructive injuries (27%). Of these, 40 (71%) had resection and anastomosis and 16 (29%) had diversion. More destructive injuries were

  3. Fetal cerebro-placental ratio and adverse perinatal outcome: systematic review and meta-analysis of the association and diagnostic performance.

    PubMed

    Nassr, Ahmed Abobakr; Abdelmagied, Ahmed M; Shazly, Sherif A M

    2016-03-01

    The objective of this meta-analysis is to assess the value of fetal cerebro-placental Doppler ratio (CPR) in predicting adverse perinatal outcome in pregnancies with fetal growth restriction (FGR). Three databases were used: MEDLINE, EMBASE (with online Ovid interface) and SCOPUS and studies from inception to April 2015 were included. Studies that reported perinatal outcomes of fetuses at risk of FGR or sonographically diagnosed FGR that were evaluated with CPR were considered eligible. Perinatal outcomes include cesarean section (CS) for fetal distress, APGAR scores at 5 min, neonatal complications and admission to neonatal intensive care unit (NICU). Pooled data were expressed as odds ratio (OR) and confidence intervals (CI), and the summary receiver operating characteristic (SROC) curve was used to illustrate the diagnostic accuracy of CPR. Seven studies were eligible (1428 fetuses). Fetuses with abnormal CPR were at higher risk of CS for fetal distress (OR=4.49, 95% CI [1.63, 12.42]), lower APGAR scores (OR=4.01, 95% CI [2.65, 6.08]), admission to NICU (OR=9.65, 95% CI [3.02, 30.85]), and neonatal complications (OR=11.00, 95% [3.64, 15.37]) than fetuses who had normal CPR. These risks were higher among studies that included fetuses diagnosed with FGR than fetuses at risk of FGR. Abnormal CPR had higher diagnostic accuracy for adverse perinatal outcomes among "sonographically diagnosed FGR" studies than "at risk of FGR" studies. Abnormal CPR is associated with substantial risk of adverse perinatal outcomes. The test seems to be particularly useful for follow up of fetuses with sonographically diagnosed FGR.

  4. Contribution of new technologies to characterization and prediction of adverse effects.

    PubMed

    Rouquié, David; Heneweer, Marjoke; Botham, Jane; Ketelslegers, Hans; Markell, Lauren; Pfister, Thomas; Steiling, Winfried; Strauss, Volker; Hennes, Christa

    2015-02-01

    Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. In the past decades, increased consistency in the definition of adversity with chemically-induced effects in laboratory animals, as well as in the assessment of human relevance has been reached. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, in vitro approaches, toxicogenomic technologies and computational tools, are available to provide mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects observed in laboratory animals. The vision described as Tox21c (Toxicity Testing in the 21st century) aims at predicting in vivo toxicity using a bottom-up-approach, starting with understanding of MOA based on in vitro data to ultimately predict adverse effects in humans. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on in vitro data, a stepwise reduction of in vivo testing is foreseen by combining in vitro with in vivo tests. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in repeated-dose in vivo toxicity studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the toxicity pathway and adverse outcome pathway

  5. A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery.

    PubMed

    Gist, Katja M; Kaufman, Jonathan; da Cruz, Eduardo M; Friesen, Robert H; Crumback, Sheri L; Linders, Megan; Edelstein, Charles; Altmann, Christopher; Palmer, Claire; Jalal, Diana; Faubel, Sarah

    2016-04-01

    Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. Prospective single center observational study. Pediatric cardiac ICU. Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012). None. A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay. In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in

  6. Activation of the Serotonin Pathway is Associated with Poor Outcome in COPD Exacerbation: Results of a Long-Term Cohort Study.

    PubMed

    Meier, Marc A; Ottiger, Manuel; Vögeli, Alaadin; Steuer, Christian; Bernasconi, Luca; Thomann, Robert; Christ-Crain, Mirjam; Henzen, Christoph; Hoess, Claus; Zimmerli, Werner; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

    2017-06-01

    Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine. An increase of its activity is associated with severity in patients with pneumonia. In chronic obstructive pulmonary disease (COPD) patients, an elevation of serotonin has been reported. Experimental models showed that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of serotonin. We investigated the prognostic ability of tryptophan, serotonin, kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term outcomes in patients with a COPD exacerbation. We measured tryptophan, serotonin, and kynurenine on admission plasma samples in patients with a COPD exacerbation from a previous trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). IDO and TPH were calculated as ratios of kynurenine over tryptophan, and serotonin over tryptophan, respectively. We studied their association with parameters measured in clinical routine at emergency department admission representing inflammation (C-reactive protein [CRP]), infection (procalcitonin [PCT]), oxygenation (SpO 2 ), as well as patients' clinical outcome, confirmed by structured phone interviews. Mortality in the 149 included patients was 53.7% within six years of follow-up. While IDO activity showed strong positive correlations, tryptophan was negatively correlated with CRP and PCT. For 30-day adverse outcome defined as death and/or intensive care unit (ICU) admission, a multivariate regression analysis adjusted for age and comorbidities found strong associations for IDO activity (adjusted odds ratios of 31.4 (95%CI 1.1-857), p = 0.041) and TPH (adjusted odds ratios 27.0 (95%CI 2.2-327), p = 0.010). TPH also showed a significant association with mortality at 18 months, (hazard ratio 2.61 (95%CI 1.2-5.8), p = 0.020). In hospitalized patients with a COPD exacerbation, higher IDO and TPH activities independently predicted adverse short-term outcomes and TPH levels were also

  7. Periodontal disease and adverse birth outcomes: a study from Pakistan.

    PubMed

    Mobeen, N; Jehan, I; Banday, N; Moore, J; McClure, E M; Pasha, O; Wright, L L; Goldenberg, R L

    2008-05-01

    Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the relationship between periodontal disease and birth outcomes in a community setting in Pakistan. This was a prospective cohort study. Enrollment occurred at 20-26 weeks of gestation. A study dentist performed the periodontal examination to assess probing depth, clinical attachment level, gingival index, and plaque index. Outcomes included stillbirth, neonatal death, perinatal death, < 32 weeks preterm birth, 32-36 weeks preterm birth, and low birthweight and are presented for increasing periodontal disease severity by quartiles. Dental examinations and outcome data were completed for 1152 women: 81% of the women were multiparous, with a mean age of 27 years; 33% of the women had no education. Forty-seven percent of the women had dental caries; 27% of the women had missing teeth, and 91% of the women had had no dental care in the last year. Periodontal disease was common: 76% of the women had > or = 3 teeth with a probing depth of > or = 3 mm; 87% of the women had > or = 4 teeth with a clinical attachment level of > or = 3 mm; 56% of the women had > or = 4 teeth with a plaque index of 3; and 60% of the women had > or = 4 teeth with a gingival index of 3. As the measures of periodontal disease increased from the 1st to 4th quartile, stillbirth and neonatal and perinatal death also increased, with relative risks of approximately 1.3. Early preterm birth increased, but the results were not significant. Late preterm birth and low birthweight were not related to measures of periodontal disease. Pregnant Pakistani women have high levels of moderate-to-severe dental disease. Stillbirth and neonatal and perinatal deaths increased with the severity of periodontal disease.

  8. Placental Mitochondrial Toxicity, Oxidative Stress, Apoptosis, and Adverse Perinatal Outcomes in HIV Pregnancies Under Antiretroviral Treatment Containing Zidovudine.

    PubMed

    Hernández, Sandra; Catalán-García, Marc; Morén, Constanza; García-Otero, Laura; López, Marta; Guitart-Mampel, Mariona; Milisenda, José; Coll, Oriol; Cardellach, Francesc; Gratacós, Eduard; Miró, Òscar; Garrabou, Glòria

    2017-08-01

    To determine whether mitochondrial, oxidative, and apoptotic abnormalities in placenta derived from HIV and combined antiretroviral therapy (cART) containing zidovudine (AZT) could be associated with adverse perinatal outcome. Cross-sectional, controlled, observational study. We studied obstetric results and mitochondrial, oxidative, and apoptotic state in placenta of 24 treated HIV-infected and 32 -uninfected pregnant women. We measured mitochondrial DNA (mtDNA) content by quantitative reverse transcriptase-polymerase chain reaction (mtND2/n18SrRNA), oxidative stress by the spectrophotometric quantification of lipid peroxidation and apoptosis by Western blot analysis of active caspase-3 respect to β-actin content and analysis of the terminal deoxynucleotidyl transferase dUTP nick end labeling. Global adverse perinatal outcome (defined as preterm delivery or/and small newborns for gestational age) was significantly increased in HIV pregnancies [or 6.7 (1.3-33.2); P < 0.05]. mtDNA content in HIV-infected women was significantly depleted (39.20% ± 2.78%) with respect to controls (0.59 ± 0.03 vs. 0.97 ± 0.07; P < 0.001). A significant 29.50% ± 9.14% increase in oxidative stress was found in placentas of HIV-infected women (23.23 ± 1.64 vs. 17.94 ± 1.03; P < 0.01). A trend toward 41.18% ± 29.41% increased apoptosis active caspase-3/β-actin was found in HIV patients (0.48 ± 0.10 vs. 0.34 ± 0.05; P = not significant), confirmed by transferase dUTP nick end labeling assay. Adverse perinatal outcome did not correlate mitochondrial, oxidative, or apoptotic findings. Placentas of HIV-infected pregnant women under AZT cART showed evidence of mtDNA depletion, increased oxidative stress levels, and apoptosis suggestive of secondary mitochondrial failure, potential base of associated adverse perinatal outcome. Despite the fact that further demonstration of causality would need new approaches and bigger sample sizes, AZT-sparing cART should be considered in the context

  9. Perinatal mortality and adverse pregnancy outcomes in a low-income rural population of women who smoke.

    PubMed

    McElroy, Jane A; Bloom, Tina; Moore, Kelly; Geden, Beth; Everett, Kevin; Bullock, Linda F

    2012-04-01

    We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low-income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention. Copyright © 2012 Wiley Periodicals, Inc.

  10. Perioperative outcomes and adverse events of minimally invasive versus open posterior lumbar fusion: meta-analysis and systematic review.

    PubMed

    Goldstein, Christina L; Macwan, Kevin; Sundararajan, Kala; Rampersaud, Y Raja

    2016-03-01

    The objective of this study was to determine the clinical comparative effectiveness and adverse event rates of posterior minimally invasive surgery (MIS) compared with open transforaminal or posterior lumbar interbody fusion (TLIF/PLIF). A systematic review of the Medline, EMBASE, PubMed, Web of Science, and Cochrane databases was performed. A hand search of reference lists was conducted. Studies were reviewed by 2 independent assessors to identify randomized controlled trials (RCTs) or comparative cohort studies including at least 10 patients undergoing MIS or open TLIF/PLIF for degenerative lumbar spinal disorders and reporting at least 1 of the following: clinical outcome measure, perioperative clinical or process measure, radiographic outcome, or adverse events. Study quality was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. When appropriate, a meta-analysis of outcomes data was conducted. The systematic review and reference list search identified 3301 articles, with 26 meeting study inclusion criteria. All studies, including 1 RCT, were of low or very low quality. No significant difference regarding age, sex, surgical levels, or diagnosis was identified between the 2 cohorts (856 patients in the MIS cohort, 806 patients in the open cohort). The meta-analysis revealed changes in the perioperative outcomes of mean estimated blood loss, time to ambulation, and length of stay favoring an MIS approach by 260 ml (p < 0.00001), 3.5 days (p = 0.0006), and 2.9 days (p < 0.00001), respectively. Operative time was not significantly different between the surgical techniques (p = 0.78). There was no significant difference in surgical adverse events (p = 0.97), but MIS cases were significantly less likely to experience medical adverse events (risk ratio [MIS vs open] = 0.39, 95% confidence interval 0.23-0.69, p = 0.001). No difference in nonunion (p = 0.97) or reoperation rates (p = 0.97) was observed. Mean Oswestry

  11. Glucose alert system improves health professional responses to adverse glycaemia and reduces the number of hyperglycaemic episodes in non-critical care inpatients.

    PubMed

    Kyi, M; Wraight, P R; Rowan, L M; Marley, K A; Colman, P G; Fourlanos, S

    2018-06-01

    To investigate the effect of a novel glucose alert system, comprising the Melbourne Glucose Alert Pathway and glucose-alert-capable networked blood glucose meters, on nursing and hospital medical officer responses to adverse glycaemia. A prospective, pre- and post-observational study was undertaken in non-critical care wards of a tertiary hospital over 4 months (n=148 or 660 patient-days). The intervention consisted of two components designed to promote a consistent staff response to blood glucose measurements: (1) a clinical escalation pathway, the Melbourne Glucose Alert Pathway, and (2) networked blood glucose meters, which provide a visual alert for out-of-range blood glucose measurement. All consecutive inpatients with diabetes were assessed for diabetes management and capillary blood glucose. The primary outcome was documented nursing and medical staff action in response to episodes of adverse glycaemia (blood glucose >15 mmol/l or <4 mmol/l). Secondary outcomes consisted of glycaemic measures. In response to episodes of adverse glycaemia, nursing action increased (proportion with nursing action: 45% to 73%; P<0.001), and medical action increased (proportion with medical action: 49% to 67%; P=0.011) with the glucose alert system in place. Patient-days with hyperglycaemia (any blood glucose value >15 mmol/l: 24% vs 16%; P=0.012) and patient-days with mean blood glucose >15 mmol/l (7.4% vs 2.6%; P=0.005) decreased. There was no difference in hypoglycaemia incidence. Use of a novel glucose alert system improved health professional responses to adverse glycaemia and decreased hyperglycaemia in the hospital setting. © 2018 Diabetes UK.

  12. Risks of adverse outcomes in the next birth after a first cesarean delivery.

    PubMed

    Kennare, Robyn; Tucker, Graeme; Heard, Adrian; Chan, Annabelle

    2007-02-01

    To estimate the risks of cesarean first birth, compared with vaginal first birth, for adverse obstetric and perinatal outcomes in the second birth. Population-based retrospective cohort study of all singleton, second births in the South Australian perinatal data collection 1998 to 2003 comparing outcomes for 8,725 women who underwent a cesarean delivery for their first birth with 27,313 women who underwent a vaginal first birth. Predictor variables include age, indigenous status, smoking, pregnancy interval, medical and obstetric complications, gestation, patient type, hospital category, and history of ectopic pregnancy, miscarriage, stillbirth or termination of pregnancy. The cesarean delivery cohort had increased risks for malpresentation (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.65-2.06), placenta previa (OR 1.66, 95% CI 1.30-2.11), antepartum hemorrhage (OR 1.23, 95% CI 1.08-1.41), placenta accreta (OR 18.79, 95% CI 2.28-864.6), prolonged labor (OR 5.89, 95% CI 3.91-8.89), emergency cesarean (relative risk 9.37, 95% CI 8.98-9.76) and uterine rupture (OR 84.42, 95% CI 14.64-infinity), preterm birth (OR 1.17, 95% CI 1.04-1.31), low birth weight (OR 1.30, 95% CI 1.14-1.48), small for gestational age (OR 1.12, 95% CI 1.02-1.23), stillbirth (OR 1.56, 95% CI 1.04-2.32), and unexplained stillbirth (OR 2.34, 95% CI 1.26-4.37). The range of the number of primary cesarean deliveries needed to harm included 134 for one additional preterm birth, up to 1,536 for one additional placenta accreta. Cesarean delivery is associated with increased risks for adverse obstetric and perinatal outcomes in the subsequent birth. However, some risks may be due to confounding factors related to the indication for the first cesarean. II.

  13. Evidence for adverse reproductive outcomes among women microelectronic assembly workers.

    PubMed Central

    Huel, G; Mergler, D; Bowler, R

    1990-01-01

    Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents. PMID:2378817

  14. Estimating the Potential Impact of Tobacco Control Policies on Adverse Maternal and Child Health Outcomes in the United States Using the SimSmoke Tobacco Control Policy Simulation Model.

    PubMed

    Levy, David; Mohlman, Mary Katherine; Zhang, Yian

    2016-05-01

    Numerous studies document the causal relationship between prenatal smoking and adverse maternal and child health (MCH) outcomes. Studies also reveal the impact that tobacco control policies have on prenatal smoking. The purpose of this study is to estimate the effect of tobacco control policies on prenatal smoking prevalence and adverse MCH outcomes. The US SimSmoke simulation model was extended to consider adverse MCH outcomes. The model estimates prenatal smoking prevalence and, applying standard attribution methods, uses estimates of MCH prevalence and relative smoking risks to estimate smoking-attributable MCH outcomes over time. The model then estimates the effect of tobacco control policies on adverse birth outcomes averted. Different tobacco control policies have varying impacts on the number of smoking-attributable adverse MCH birth outcomes. Higher cigarette taxes and comprehensive marketing bans individually have the biggest impact with a 5% to 10% reduction across all outcomes for the period from 2015 to 2065. The policies with the lowest impact (2%-3% decrease) during this period are cessation treatment, health warnings, and complete smoke-free laws. Combinations of all policies with each tax level lead to 23% to 28% decreases across all outcomes. Our findings demonstrate the substantial impact of strong tobacco control policies for preventing adverse MCH outcomes, including long-term health implications for children exposed to low birth weight and preterm birth. These benefits are often overlooked in discussions of tobacco control. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Recent updates on recombinant human growth hormone outcomes and adverse events.

    PubMed

    Watson, Sara E; Rogol, Alan D

    2013-02-01

    To provide up-to-date information on outcomes and adverse events associated with the use of recombinant human growth hormone (rhGH). We will focus on patients with Prader Willi Syndrome and Idiopathic Short Stature. We will also discuss recent reports on long-term adverse events from the European database. Prader Willi Syndrome is associated with hypogonadism, which does not appear to be affected by treatment with rhGH. However, there is new evidence that treatment may improve cognition. For patients with Idiopathic Short Stature, the gain in near adult height with treatment with rhGH appears to be 3-4 cm. Although a recent analysis of this group shows that certain patient characteristics may help identify those most likely to have a good response to treatment. Additionally, the safety and appropriateness of growth hormone treatments in Europe study released preliminary data from patients treated in two separate locations that showed conflicting information on risk of mortality from treatment with rhGH. Although we will continue to receive new information regarding the safety and effects of treatment with rhGH, it is important to discuss the risks and benefits with our patients. Additionally, it is incumbent on us to help guide the treatment to those most likely to benefit.

  16. Excessive Daytime Sleepiness is Associated with Longer Culprit Lesion and Adverse Outcomes in Patients with Coronary Artery Disease

    PubMed Central

    Lee, Chi-Hang; Ng, Wai-Yee; Hau, William; Ho, Hee-Hwa; Tai, Bee-Choo; Chan, Mark Y.; Richards, A. Mark; Tan, Huay-Cheem

    2013-01-01

    Study Objectives: We assessed whether excessive daytime sleepiness was associated with coronary plaque phenotype and subsequent adverse cardiovascular events. Methods: Prospective cohort study. Intravascular ultrasound (IVUS) examination of the culprit coronary stenosis was performed. The Epworth Sleepiness Scale (ESS) questionnaire was administered, and the patients were divided into 2 groups—(1) sleepier and (2) less sleepy—based on the ESS score. Adverse cardiovascular outcomes were defined as cardiac death, myocardial infarction, stroke, unplanned revascularization, or heart failure admission. Results: One hundred seventeen patients undergoing urgent or non-urgent coronary angiography were recruited. Compared with the less sleepy group (ESS ≤ 10, n = 87), the sleepier group (ESS > 10, n = 30) had higher serum levels of total cholesterol and of low-density-lipoprotein cholesterols (p < 0.05 for both). The IVUS examinations indicated coronary stenoses were longer in the sleepier group than in the less sleepy group (p = 0.011). The cumulative incidence of adverse cardiovascular events at 16-month follow-up was higher in the sleepier than the less sleepy group (12.5% versus 6.9%, p = 0.03). Cox regression analysis adjusting for age and smoking showed increased hazard of adverse cardiovascular events in sleepier group as compared to less sleepy group (HR = 3.44, 95% CI 1.01-11.72). Conclusion: In patients presenting with coronary artery disease, excessive daytime sleepiness based on ESS > 10 was associated with longer culprit lesions and future adverse cardiovascular events. Citation: Lee CH; Ng WY; Hau W; Ho HH; Tai BC; Chan MY; Richards AM; Tan HC. Excessive daytime sleepiness is associated with longer culprit lesion and adverse outcomes in patients with coronary artery disease. J Clin Sleep Med 2013;9(12):1267-1272. PMID:24340288

  17. Aggregated adverse-events outcomes in oncology phase III reports: A systematic review.

    PubMed

    Maillet, Denis; Gan, Hui K; Blay, Jean-Yves; You, Benoit; Péron, Julien

    2016-01-01

    Randomised controlled trials (RCTs) represent a major source of information on treatment-related adverse events (AEs). In this study, we reviewed the use and the reporting methods of aggregated-AEs (A-AEs) outcomes in RCTs reports published in oncology and compared that to the expectations of European Organisation for Research and Treatment of Cancer (EORTC) membership. RCTs reports published between 2007 and 2011 were reviewed regarding the reporting of A-AEs-outcomes. A-AEs were defined as summary outcome combining several related AEs, usually grouped by organ system e.g. cardiac-AEs, dermatologic-AEs. Trial characteristics associated with the use of A-AEs outcomes were investigated. The expectation of EORTC members concerning A-AEs utilisation was queried through a survey. Among 325 RCTs published between 2007 and 2011, 94 (29%) included one or more A-AE outcomes. A clear description of the nature of AEs included in such aggregations was provided in 19 articles (20%). No description of A-AEs was conversely provided in the other 75 articles (80%). The most commonly used A-AEs-outcomes were dermatologic-AEs (45%) and cardiac-AEs (33%). In multivariate analysis, the use of A-AEs outcomes was more frequent when trials were conducted in Europe (p = 0.038) and in trials performed on colon/rectal cancers (p = 0.016). Finally, there is no consensus of EORTC members regarding the utilisation of A-AEs but a majority of them (88%) felt that a clear description of A-AEs should systematically be reported. The use of A-AEs is infrequent in oncology RCT manuscripts although their use is accepted by most clinicians. However, a clear definition of A-AEs is strongly recommended if they are to be used in order to avoid a loss of important details about drug toxicities that is useful to clinicians. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Stress, Behavior and Health: Developing a Model for Predicting Post-Deployment Morbidity, Mortality and Other Adverse Outcomes

    DTIC Science & Technology

    1999-07-01

    related health outcomes and risk factors for adverse health events. A secondary effort is to link self-reports of stress and subsequent increases in...Gulf War era veterans, information critical to the interpretation of postwar differences between these two groups . We have identified potential

  19. Reflection on Lessons Learned: An Analysis of the Adverse Outcomes Observed During the Hurricane Rita Evacuation.

    PubMed

    Baker, Karen

    2018-02-01

    In September 2005, nearly 3.7 million people evacuated the Texas coastline in advance of Hurricane Rita's landfall, making the event the largest emergency evacuation in US history. The Rita evacuation underscored the importance of planning for domestic mass-evacuation events, as the evacuation itself led to over 100 of the at least 119 deaths attributed to the storm. In the days preceding Rita's landfall, several cascading, interrelated circumstances precipitated such adverse outcomes. This article explores the series of events leading up to the evacuation's poor outcomes, the response following Rita to amend evacuation plans, and how Texas successfully implemented these changes during later storms to achieve better outcomes. (Disaster Med Public Health Preparedness. 2018;12:115-120).

  20. Common variants of the vitamin D binding protein gene and adverse health outcomes.

    PubMed

    Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y L; Gozdzik, Agnes; Cole, David E C

    2013-01-01

    The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene - rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys - change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged.