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Sample records for adverse developmental outcomes

  1. 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...

  2. A Review of Nitrates in Drinking Water: Maternal Exposure and Adverse Reproductive and Developmental Outcomes

    PubMed Central

    Manassaram, Deana M.; Backer, Lorraine C.; Moll, Deborah M.

    2006-01-01

    In this review we present an update on maternal exposure to nitrates in drinking water in relation to possible adverse reproductive and developmental effects, and also discuss nitrates in drinking water in the United States. The current standard for nitrates in drinking water is based on retrospective studies and approximates a level that protects infants from methemoglobinemia, but no safety factor is built into the standard. The current standard applies only to public water systems. Drinking water source was related to nitrate exposure (i.e., private systems water was more likely than community system water to have nitrate levels above the maximum contaminant limit). Animal studies have found adverse reproductive effects resulting from higher doses of nitrate or nitrite. The epidemiologic evidence of a direct exposure–response relationship between drinking water nitrate level and adverse reproductive effect is still not clear. However, some reports have suggested an association between exposure to nitrates in drinking water and spontaneous abortions, intrauterine growth restriction, and various birth defects. Uncertainties in epidemiologic studies include the lack of individual exposure assessment that would rule out confounding of the exposure with some other cause. Nitrates may be just one of the contaminants in drinking water contributing to adverse outcomes. We conclude that the current literature does not provide sufficient evidence of a causal relationship between exposure to nitrates in drinking water and adverse reproductive effects. Future studies incorporating individual exposure assessment about users of private wells—the population most at risk—should be considered. PMID:16507452

  3. The influence of heart developmental anatomy on cardiotoxicity-based adverse outcome pathways in fish.

    PubMed

    Incardona, John P; Scholz, Nathaniel L

    2016-08-01

    The developing fish heart is vulnerable to a diverse array of toxic chemical contaminants in freshwater, estuarine, and marine habitats. Globally occurring examples of cardiotoxic agents include dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The disruption of cardiac function during the process of heart morphogenesis can lead to adverse outcome pathways (AOPs) that can negatively affect fish survival at hatching as well as later life stages. Proximal impacts include cardiogenic fluid accumulation (edema) and defects of the body axis and jaw that preclude larval feeding. More subtle changes in heart development can produce permanent structural defects in the heart that reduce cardiac output and swimming performance in older fish. In recent decades, the presence of edema in fish embryos and larvae has been a very common bioindicator of cardiotoxicity. However, the different ways that edema forms in fish from different habitats (i.e., freshwater vs. marine, pelagic vs. demersal) has not been rigorously examined. Oil spills are an important source of PAHs in fish spawning areas worldwide, and research is revealing how patterns of cardiogenic edema are shaped by species-specific differences in developmental anatomy and ionoregulatory physiology. Here we review the visible evidence for circulatory disruption across nine freshwater and marine fish species, exposed to crude oils from different parts of the world. We focus on the close interconnectedness of the cardiovascular and osmoregulatory systems during early development, and corresponding implications for fish in hyperosmotic and hyposmotic habitats. Finally, we suggest there may be poorly understood adverse outcomes pathways related to osmotic gradients and water movement within embryos, the latter causing extreme shifts in tissue osmolality. PMID:27447099

  4. Adverse Reproductive and Developmental Health Outcomes Following Prenatal Exposure to a Hydraulic Fracturing Chemical Mixture in Female C57Bl/6 Mice.

    PubMed

    Kassotis, Christopher D; Bromfield, John J; Klemp, Kara C; Meng, Chun-Xia; Wolfe, Andrew; Zoeller, R Thomas; Balise, Victoria D; Isiguzo, Chiamaka J; Tillitt, Donald E; Nagel, Susan C

    2016-09-01

    Unconventional oil and gas operations using hydraulic fracturing can contaminate surface and groundwater with endocrine-disrupting chemicals. We have previously shown that 23 of 24 commonly used hydraulic fracturing chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors in a human endometrial cancer cell reporter gene assay and that mixtures can behave synergistically, additively, or antagonistically on these receptors. In the current study, pregnant female C57Bl/6 dams were exposed to a mixture of 23 commonly used unconventional oil and gas chemicals at approximately 3, 30, 300, and 3000 μg/kg·d, flutamide at 50 mg/kg·d, or a 0.2% ethanol control vehicle via their drinking water from gestational day 11 through birth. This prenatal exposure to oil and gas operation chemicals suppressed pituitary hormone concentrations across experimental groups (prolactin, LH, FSH, and others), increased body weights, altered uterine and ovary weights, increased heart weights and collagen deposition, disrupted folliculogenesis, and other adverse health effects. This work suggests potential adverse developmental and reproductive health outcomes in humans and animals exposed to these oil and gas operation chemicals, with adverse outcomes observed even in the lowest dose group tested, equivalent to concentrations reported in drinking water sources. These endpoints suggest potential impacts on fertility, as previously observed in the male siblings, which require careful assessment in future studies. PMID:27560547

  5. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  6. Developmental Outcome of Childhood Leukemia.

    ERIC Educational Resources Information Center

    Coniglio, Susan J.; Blackman, James A.

    1995-01-01

    Literature on developmental and psychosocial outcomes of childhood leukemia is reviewed, focusing on preschool-age children. Studies are categorized in terms of outcome measures: intelligence/achievement, neuropsychological, memory/attention, and psychosocial tests. Evidence suggests that preschool children with leukemia are at high risk for…

  7. The epidemiology of disasters and adverse reproductive outcomes: lessons learned.

    PubMed

    Cordero, J F

    1993-07-01

    A disaster has been defined as a disruption of human ecology that exceeds the capacity of the community to function normally. Little is known about the adverse effects of natural disasters on reproductive outcomes. Important lessons can be derived from several disasters caused by human factors, such as the Minamata Bay disaster. Adverse reproductive outcomes include infertility, early pregnancy loss, stillbirths, congenital malformations, and serious developmental disabilities such as cerebral palsy and mental retardation. Recent disasters like the Chernobyl and Bhopal explosions have provided important lessons on the need for accurate and sound information about the risk of prenatal exposures for adverse reproductive outcomes. To study questions of adverse reproductive outcomes and disasters requires a well-planned approach. It should include early development of surveillance for adverse reproductive outcomes, analytic studies on the risk of disasters from direct and indirect effects, sensitive methods to measure early pregnancy loss, and long-term follow-up programs to assess outcomes such as developmental disabilities. PMID:8243383

  8. The epidemiology of disasters and adverse reproductive outcomes: lessons learned.

    PubMed Central

    Cordero, J F

    1993-01-01

    A disaster has been defined as a disruption of human ecology that exceeds the capacity of the community to function normally. Little is known about the adverse effects of natural disasters on reproductive outcomes. Important lessons can be derived from several disasters caused by human factors, such as the Minamata Bay disaster. Adverse reproductive outcomes include infertility, early pregnancy loss, stillbirths, congenital malformations, and serious developmental disabilities such as cerebral palsy and mental retardation. Recent disasters like the Chernobyl and Bhopal explosions have provided important lessons on the need for accurate and sound information about the risk of prenatal exposures for adverse reproductive outcomes. To study questions of adverse reproductive outcomes and disasters requires a well-planned approach. It should include early development of surveillance for adverse reproductive outcomes, analytic studies on the risk of disasters from direct and indirect effects, sensitive methods to measure early pregnancy loss, and long-term follow-up programs to assess outcomes such as developmental disabilities. PMID:8243383

  9. 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...

  10. Translating Developmental Science to Address Childhood Adversity.

    PubMed

    Garner, Andrew S; Forkey, Heather; Szilagyi, Moira

    2015-01-01

    Demystifying child development is a defining element of pediatric care, and pediatricians have long appreciated the profound influences that families and communities have on both child development and life course trajectories. Dramatic advances in the basic sciences of development are beginning to reveal the biologic mechanisms underlying well-established associations between a spectrum of childhood adversities and less than optimal outcomes in health, education and economic productivity. Pediatricians are well positioned to translate this new knowledge into both practice and policy, but doing so will require unprecedented levels of collaboration with educators, social service providers, and policy makers. Pediatricians might recognize the negative impact of family-level adversities on child development, but developing an effective response will likely require the engagement of community partners. By developing collaborative, innovative ways to promote the safe, stable, and nurturing relationships that are biologic prerequisites for health, academic success, and economic productivity, family-centered pediatric medical homes will remain relevant in an era that increasingly values wellness and population health. PMID:26183002

  11. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  12. 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...

  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. The complement system and adverse pregnancy outcomes.

    PubMed

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

    2015-09-01

    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 fetal 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

  15. Practitioner Review: Early Adversity and Developmental Disorders

    ERIC Educational Resources Information Center

    Taylor, Eric; Rogers, Jody Warner

    2005-01-01

    Background: Knowledge of genetic influences, on developmental disorders such as autism spectrum, attention deficit/hyperactivity disorder and learning disabilities, has increased the opportunities for understanding the influences of the early environment. Methods: This paper provides a selective, narrative review for clinicians of the effects of…

  16. 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...

  17. 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...

  18. Prenatal Tobacco Exposure: Developmental Outcomes in the Neonatal Period

    ERIC Educational Resources Information Center

    Espy, Kimberly Andrews; Fang, Hua; Johnson, Craig; Stopp, Christian; Wiebe, Sandra A.; Respass, Jennifer

    2011-01-01

    Smoking during pregnancy is a persistent public health problem that has been linked to later adverse outcomes. The neonatal period--the first month of life--carries substantial developmental change in regulatory skills and is the period when tobacco metabolites are cleared physiologically. Studies to date mostly have used cross-sectional designs…

  19. A Review of Adversity, The Amygdala and the Hippocampus: A Consideration of Developmental Timing

    PubMed Central

    Tottenham, Nim; Sheridan, Margaret A.

    2009-01-01

    A review of the human developmental neuroimaging literature that investigates outcomes following exposure to psychosocial adversity is presented with a focus on two subcortical structures – the hippocampus and the amygdala. Throughout this review, we discuss how a consideration of developmental timing of adverse experiences and age at measurement might provide insight into the seemingly discrepant findings across studies. We use findings from animal studies to suggest some mechanisms through which timing of experiences may result in differences across time and studies. The literature suggests that early life may be a time of heightened susceptibility to environmental stressors, but that expression of these effects will vary by age at measurement. PMID:20161700

  20. Adverse Pregnancy Outcomes Following Motor Vehicle Crashes

    PubMed Central

    Vladutiu, Catherine J.; Marshall, Stephen W.; Poole, Charles; Casteel, Carri; Menard, M. Kathryn; Weiss, Harold B.

    2013-01-01

    Background Motor vehicle crashes are a leading cause of serious trauma during pregnancy, but little is known about their relationships with pregnancy outcomes. Purpose To estimate the association between motor vehicle crashes and adverse pregnancy outcomes. Methods A retrospective cohort study of 878,546 pregnant women, aged 16–46 years, who delivered a singleton infant in North Carolina (NC) from 2001 to 2008. Pregnant drivers in crashes were identified by probabilistic linkage of vital records and crash reports. Poisson regression modeled the association among crashes, vehicle safety features, and adverse pregnancy outcomes. Analyses were conducted in 2012. Results In 2001–2008, 2.9% of pregnant NC women were drivers in one or more crashes. After a single crash, compared to not being in a crash, pregnant drivers had slightly elevated rates of preterm birth (adjusted rate ratio, aRR=1.23, 95% CI=1.19, 1.28); placental abruption (aRR=1.34, 95% CI=1.15, 1.56); and premature rupture of the membranes (PROM; aRR=1.32, 95% CI=1.21, 1.43). Following a second or subsequent crash, pregnant drivers had more highly elevated rates of preterm birth (aRR=1.54, 95% CI=1.24, 1.90); stillbirth (aRR=4.82, 95% CI=2.85, 8.14); placental abruption (aRR=2.97, 95% CI=1.60, 5.53); and PROM (aRR=1.95, 95% CI=1.27, 2.99). Stillbirth rates were elevated following crashes involving unbelted pregnant drivers (aRR=2.77, 95% CI=1.22, 6.28) compared to belted pregnant drivers. Conclusions Crashes while driving during pregnancy were associated with elevated rates of adverse pregnancy outcomes, and multiple crashes were associated with even higher rates of adverse pregnancy outcomes. Crashes were especially harmful if drivers were unbelted. PMID:24139777

  1. Adverse blood transfusion outcomes: establishing causation.

    PubMed

    Isbister, James P; Shander, Aryeh; Spahn, Donat R; Erhard, Jochen; Farmer, Shannon L; Hofmann, Axel

    2011-04-01

    The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic. PMID:21345639

  2. 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,...

  3. 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...

  4. 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...

  5. Adverse Outcome Pathway Development II: Best Practices

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  6. Ouabain protects against adverse developmental programming of the kidney.

    PubMed

    Li, Juan; Khodus, Georgiy R; Kruusmägi, Markus; Kamali-Zare, Padideh; Liu, Xiao-Li; Eklöf, Ann-Christine; Zelenin, Sergey; Brismar, Hjalmar; Aperia, Anita

    2010-01-01

    The kidney is extraordinarily sensitive to adverse fetal programming. Malnutrition, the most common form of developmental challenge, retards the formation of functional units, the nephrons. The resulting low nephron endowment increases susceptibility to renal injury and disease. Using explanted rat embryonic kidneys, we found that ouabain, the Na,K-ATPase ligand, triggers a calcium-nuclear factor-κB signal, which protects kidney development from adverse effects of malnutrition. To mimic malnutrition, kidneys were serum deprived for 24 h. This resulted in severe retardation of nephron formation and a robust increase in apoptosis. In ouabain-exposed kidneys, no adverse effects of serum deprivation were observed. Proof of principle that ouabain rescues development of embryonic kidneys exposed to malnutrition was obtained from studies on pregnant rats given a low-protein diet and treated with ouabain or vehicle throughout pregnancy. Thus, we have identified a survival signal and a feasible therapeutic tool to prevent adverse programming of kidney development. PMID:20975704

  7. 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

  8. Early Childhood Adversity and Pregnancy Outcomes.

    PubMed

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

    2016-04-01

    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

  9. Sequential analysis of uncommon adverse outcomes.

    PubMed

    Morton, A; Mengersen, K; Waterhouse, M; Steiner, S; Looke, D

    2010-10-01

    Sequential analysis of uncommon adverse outcomes (AEs) such as surgical site infections (SSIs) is desirable. Short postoperative lengths of stay (LOS) result in many SSIs occurring after discharge and they are often superficial. Deep and organ space (complex) SSIs occur less frequently but are detected more reliably and are suitable for monitoring wound care. Those occurring post-discharge usually require readmissison and can be counted accurately. Sequential analysis of meticillin-resistant Staphylococcus aureus bacteraemia is also needed. The key to prevention is to implement systems based on evidence, e.g. using 'bundles' and checklists. Regular mortality and morbidity audit meetings are required and these may need to be followed by independent audits. Sequential statistical analysis is desirable for data presentation, to detect changes, and to discourage tampering with processes when occasional AEs occur in a reliable system. Tabulations and cumulative observed minus expected (O-E) charts and funnel plots are valuable, supplemented in the presence of apparent 'runs' of AEs by cumulative sum analysis. Used prospectively, they may enable staff to visualise and detect patterns or shifts in rates and counts that might not otherwise be apparent. PMID:20656377

  10. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

    PubMed Central

    2009-01-01

    OBJECTIVE—To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS—Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex. RESULTS—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. CONCLUSIONS—These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth. PMID:19011170

  11. 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...

  12. Intraventricular hemorrhage and developmental outcomes at 24 months of age in extremely preterm infants.

    PubMed

    O'Shea, T Michael; Allred, Elizabeth N; Kuban, Karl C K; Hirtz, Deborah; Specter, Barbara; Durfee, Sara; Paneth, Nigel; Leviton, Alan

    2012-01-01

    Whether intraventricular hemorrhage increases the risk of adverse developmental outcome among premature infants is controversial. Using brain ultrasound, we identified intraventricular hemorrhage and white matter abnormalities among 1064 infants born before 28 weeks' gestation. We identified adverse developmental outcomes at 24 months of age using a standardized neurologic examination and the Bayley Scales of Infant Development Mental and Motor Scales. In logistic regression models that adjusted for gestational age, sex, and public insurance, isolated intraventricular hemorrhage was associated with visual fixation difficulty but no other adverse outcome. Infants who had a white matter lesion unaccompanied by intraventricular hemorrhage were at increased risk of cerebral palsy, low Mental and Motor Scores, and visual and hearing impairments. Except when accompanied or followed by a white matter lesion, intraventricular hemorrhage is associated with no more than a modest increase (and possibly no increase) in the risk of adverse developmental outcome during infancy. PMID:22232137

  13. Developmental Toxicology##

    EPA Science Inventory

    Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

  14. 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...

  15. 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…

  16. 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...

  17. 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....

  18. 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...

  19. Developmental Outcomes of Very Preterm Infants with Tracheostomies

    PubMed Central

    DeMauro, Sara B.; D'Agostino, Jo Ann; Bann, Carla; Bernbaum, Judy; Gerdes, Marsha; Bell, Edward F.; Carlo, Waldemar A.; D'Angio, Carl; Das, Abhik; Higgins, Rosemary; Hintz, Susan R.; Laptook, Abbot R.; Natarajan, Girija; Nelin, Leif; Poindexter, Brenda B.; Sanchez, Pablo J.; Shankaran, Seetha; Stoll, Barbara J.; Truog, William; Van Meurs, Krisa P.; Vohr, Betty; Walsh, Michele C.; Kirpalani, Haresh

    2014-01-01

    Objectives To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. Study design Retrospective cohort study from 16 centers of the NICHD Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N=8,683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI, a composite of one or more of: developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed impact of timing, by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Results Tracheostomies were associated with all neonatal morbidities examined, and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without [odds ratio (OR) adjusted for center 7.0 (95%CI, 5.2-9.5)]. After adjustment for potential confounders, odds of death or NDI remained higher [OR 3.3 (95%CI, 2.4-4.6)], but odds of death alone were lower [OR 0.4 (95%CI, 0.3-0.7)], among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life [adjusted OR 0.5 (95%CI, 0.3-0.9)]. Conclusions Tracheostomy in preterm infants is associated with adverse developmental outcomes, and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population. PMID:24472229

  20. Placental Features of Late-Onset Adverse Pregnancy Outcome

    PubMed Central

    Higgins, Lucy E.; Wareing, Mark; Greenwood, Susan L.; Jones, Rebecca L.; Sibley, Colin P.; Johnstone, Edward D.; Heazell, Alexander E. P.

    2015-01-01

    Objective Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement. Methods Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium). Results Placentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10–12) vessels/mm2 vs. normal outcome 13 (12–15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19–50) nM vs. 12 (6–24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11–50) vs. 55 (24–102) mIU/mg, p = 0.007) and human placental lactogen (11 (6–14) vs. 27 (9–50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13–29) vs. 5 (2–15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue. Conclusion These data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may

  1. Developmental Outcomes of Extremely Preterm Infants Born to Adolescent Mothers

    PubMed Central

    Bann, Carla; Higgins, Rosemary; Vohr, Betty

    2015-01-01

    BACKGROUND AND OBJECTIVES: Extremely preterm infants and infants born to adolescent mothers are at risk for adverse developmental. The objectives were to evaluate development and behavior outcomes of extremely low birth weight (ELBW) infants born to adolescent mothers <20 compared with adult mothers ≥20 years and to identify socioeconomic risk factors that affect outcomes. METHODS: Retrospective cohort analysis of 211 infants >27 weeks of adolescent mothers and 1723 infants of adult mothers at Neonatal Research Network centers from 2008 to 2011. Groups were compared and regression models were run to predict 18- to 22-month adverse outcomes. Primary outcomes were Bayley-III scores, neurodevelopmental impairment, and Brief Infant Toddler Social Emotional Assessment problem scores (BITSEA/P) ≥75th percentile. RESULTS: Adolescent mothers were more often single, Hispanic, less educated, and had public insurance. By 18 to 22 months, their children had significantly increased rates of having lived ≥3 places (21% vs 9%), state supervision (7% vs 3%), rehospitalization (56% vs 46%), and BITSEA/P ≥75th percentile (50% vs 32%) and nonsignificant Bayley-III language scores <85 (56% vs 49%, P = .07). In regression analysis, children of adolescent mothers were more likely to have BITSEA/P ≥75th percentile (relative risk 1.50, 95% confidence interval 1.08–2.07). Living ≥3 places and nonwhite race were predictors of adverse behavior. State supervision was an independent predictor of each Bayley-III composite <70 and neurodevelopmental impairment. CONCLUSIONS: ELBW infants of adolescent mothers experience high social and environmental risks that are associated with adverse behavior outcomes. These findings inform the need for comprehensive follow-up, coordinated care services, and behavior interventions for ELBW infants of adolescent mothers. PMID:25963007

  2. 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...

  3. 1991 Gulf War Exposures and Adverse Birth Outcomes

    PubMed Central

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

    2014-01-01

    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. PMID:23584910

  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. Frailty as a predictor of short-term adverse outcomes

    PubMed Central

    Coelho, Tiago; Paúl, Constança; Gobbens, Robbert J.J.

    2015-01-01

    The objectives of this study were to compare how different frailty measures (Frailty Phenotype/FP, Groningen Frailty Indicator/GFI and Tilburg Frailty Indicator/TFI) predict short-term adverse outcomes. Secondarily, adopting a multidimensional approach to frailty (integral conceptual model–TFI), this study aims to compare how physical, psychological and social frailty predict the outcomes. A longitudinal study was carried out with 95 community-dwelling elderly. Participants were assessed at baseline for frailty, determinants of frailty, and adverse outcomes (healthcare utilization, quality of life, disability in basic and instrumental activities of daily living/ADL and IADL). Ten months later the outcomes were assessed again. Frailty was associated with specific healthcare utilization indicators: the FP with a greater utilization of informal care; GFI with an increased contact with healthcare professionals; and TFI with a higher amount of contacts with a general practitioner. After controlling for the effect of life-course determinants, comorbidity and adverse outcome at baseline, GFI predicted IADL disability and TFI predicted quality of life. The effect of the FP on the outcomes was not significant, when compared with the other measures. However, when comparing TFI’s domains, the physical domain was the most significant predictor of the outcomes, even explaining part of the variance of ADL disability. Frailty at baseline was associated with adverse outcomes at follow-up. However, the relationship of each frailty measure (FP, GFI and TFI) with the outcomes was different. In spite of the role of psychological frailty, TFI’s physical domain was the determinant factor for predicting disability and most of the quality of life. PMID:26246968

  6. Women, poverty and adverse maternal outcomes in Nairobi, Kenya

    PubMed Central

    2010-01-01

    Background The link between poverty and adverse maternal outcomes has been studied largely by means of quantitative data. We explore poor urban Kenyan women's views and lived experiences of the relationship between economic disadvantage and unpleasant maternal outcomes. Method Secondary analysis of focus group discussions and in-depth individual interviews data with women in two slums in Nairobi, Kenya. Results Urban poor women in Nairobi associate poverty with adverse maternal outcomes. However, their accounts and lived experiences of the impact of poverty on maternal outcomes underscore dynamics other than those typically stressed in the extant literature. To them, poverty primarily generates adverse maternal outcomes by exposing women to exceedingly hard and heavy workloads during pregnancy and the period surrounding it; to intimate partner violence; as well as to inhospitable and unpleasant treatment by service providers. Conclusions Poverty has wider and more intricate implications for maternal outcomes than are acknowledged in extant research. To deliver their expected impact, current efforts to promote better maternal outcomes must be guided by a more thorough perspective of the link between women's livelihoods and their health and wellbeing. PMID:21122118

  7. 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...

  8. Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

    PubMed Central

    Miller, Mark D.; Crofton, Kevin M.; Rice, Deborah C.; Zoeller, R. Thomas

    2009-01-01

    Background There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health. Objectives We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals. Data sources We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies. Data synthesis THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the “normal” range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms. Conclusions Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes. PMID:19654909

  9. 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...

  10. 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

  11. [Development and application of adverse outcome pathway in toxicology research].

    PubMed

    Wang, Yanhua; Duan, Huawei

    2015-12-01

    Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced. PMID:26887310

  12. Drinking water contaminants and adverse pregnancy outcomes: a review.

    PubMed Central

    Bove, Frank; Shim, Youn; Zeitz, Perri

    2002-01-01

    Concern for exposures to drinking water contaminants and their effects on adverse birth outcomes has prompted several studies evaluating chlorination disinfection by-products and chlorinated solvents. Some of these contaminants are found to be teratogenic in animal studies. This review evaluates 14 studies on chlorination disinfection by-products such as trihalomethanes (THMs) and five studies on chlorinated solvents such as trichloroethylene (TCE). The adverse birth outcomes discussed in this review include small for gestational age (SGA), low birth weight, preterm birth, birth defects, spontaneous abortions, and fetal deaths. Because of heterogeneities across the studies in the characterization of birth outcomes, the assessment and categorization of exposures, and the levels and mixtures of contaminants, a qualitative review was conducted. Generally, the chief bias in these studies was exposure misclassification that most likely underestimated the risk, as well as distorted exposure-response relationships. The general lack of confounding bias by risk factors resulted from these factors not being associated with drinking water exposures. The studies of THMs and adverse birth outcomes provide moderate evidence for associations with SGA, neural tube defects (NTDs), and spontaneous abortions. Because fewer studies have been conducted for the chlorinated solvents than for THMs, the evidence for associations is less clear. Nevertheless, the findings of excess NTDs, oral clefts, cardiac defects, and choanal atresia in studies that evaluated TCE-contaminated drinking water deserve follow-up. PMID:11834464

  13. 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...

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

    PubMed

    Vinken, Mathieu

    2013-10-01

    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. PMID:23978457

  16. 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

  17. Adverse Outcome Pathways and Drug-Induced Liver Injury Testing.

    PubMed

    Vinken, Mathieu

    2015-07-20

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis, and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This review evaluates these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  18. Adverse outcome pathways and drug-induced liver injury testing

    PubMed Central

    Vinken, Mathieu

    2015-01-01

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This paper reviews these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  19. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective

    PubMed Central

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  20. Adverse outcome pathways: From research to regulation scientific workshop report.

    PubMed

    Kleinstreuer, Nicole C; Sullivan, Kristie; Allen, David; Edwards, Stephen; Mendrick, Donna L; Embry, Michelle; Matheson, Joanna; Rowlands, J Craig; Munn, Sharon; Maull, Elizabeth; Casey, Warren

    2016-04-01

    An adverse outcome pathway (AOP) helps to organize 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 in Bethesda, Maryland 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. PMID:26774756

  1. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective.

    PubMed

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  2. Renal function trajectory over time and adverse clinical outcomes.

    PubMed

    Sohel, Badrul Munir; Rumana, Nahid; Ohsawa, Masaki; Turin, Tanvir Chowdhury; Kelly, Martina Ann; Al Mamun, Mohammad

    2016-06-01

    The growing burden of chronic kidney disease (CKD), with its associated morbidity and mortality, is recognized as a major public health problem globally and causing substantial load on health care systems. The current framework for the definition and staging of CKD, based on eGFR levels or presence of kidney damage, is useful for clinical classification of patients, but identifies a huge number of people as having CKD which is too many to target for intervention. The ability to identify a subset of patients, at high risk for adverse outcomes, would be useful to inform clinical management. The current staging system applies static definitions of kidney function that fail to capture the dynamic nature of the kidney disease over time. Now-a-days, it is possible to capture multiple measurements of different laboratory test results for an individual including eGFR values. A new possibility for identifying individuals at higher risk of adverse outcomes is being explored through assessment and consideration of the rate of change in kidney function over time, and this approach will be feasible in the current context of digitalization of health record keeping system. On the basis of the existing evidence, this paper summarizes important findings that support the concept of dynamic changes in kidney function over time, and discusses how the magnitude of these changes affect the future adverse outcomes of kidney disease, particularly the End Stage Renal Disease (ESRD), CVD and mortality. PMID:26728745

  3. Intraventricular Hemorrhage and Developmental Outcomes at 24 months of age in Extremely Preterm Infants

    PubMed Central

    O'Shea, T. Michael; Allred, Elizabeth N.; Kuban, Karl C. K.; Hirtz, Deborah; Specter, Barbara; Durfee, Sara; Paneth, Nigel; Leviton, Alan

    2013-01-01

    Whether intraventricular hemorrhage increases the risk of adverse developmental outcome among premature infants is controversial. Using brain ultrasound, we identified IVH and white matter abnormalities among 1064 infants born before 28 weeks gestation. We identified adverse developmental outcomes at 24 months of age using a standardized neurological examination and the Bayley Scales of Infant Development Mental and Motor Scales. In logistic regression models that adjusted for gestational age, sex, and public insurance, isolated intraventricular hemorrhage was associated with visual fixation difficulty (odds ratio: 2.5 (95% confidence limits: 1.2, 5.1)) but no other adverse outcome. Infants who had a white matter lesion unaccompanied by intraventricular hemorrhage were at increased risk of cerebral palsy, low Mental and Motor Scores, and visual and hearing impairments. Except when accompanied or followed by a white matter lesion, intraventricular hemorrhage is associated with no more than a mild increase (and possibly no increase) in the risk of adverse developmental outcome during infancy. PMID:22232137

  4. Are PRO discharge screens associated with postdischarge adverse outcomes?

    PubMed Central

    Wei, F.; Mark, D.; Hartz, A.; Campbell, C.

    1995-01-01

    OBJECTIVE. We evaluate whether patient outcomes may be affected by possible errors in care at discharge as assessed by Peer Review Organizations (PROs). DATA SOURCES/STUDY SETTING. The three data sources for the study were (1) the generic screen results of a 3 percent random sample of Medicare beneficiaries age 65 years or older who were admitted to California hospitals between 1 July 1987 and 30 June 1988 (n = 20,136 patients); (2) the 1987 and 1988 California Medicare Provided Analysis and Review (MEDPAR) data files; and (3) the American Hospital Association (AHA) 1988 Annual Survey of Hospitals. STUDY DESIGN. Multivariate logistic regression analysis was used to evaluate the association between the results of generic discharge administered by the PROs and two patient outcomes: mortality and readmission within 30 days. The analysis was adjusted for other patient characteristics recorded on the uniform discharge abstract. PRINCIPAL FINDINGS. Four discharge screens indicated an increased risk of an adverse outcome-absence of documentation of discharge planning, elevated temperature, abnormal pulse, and unaddressed abnormal test results at discharge. The other three discharge screens examined-abnormal blood pressure, IV fluids or drugs, and wound drainage before discharge-were unrelated to postdischarge adverse outcomes. CONCLUSIONS. Generic discharge screens based on inadequate discharge planning, abnormal pulse, increased temperature, or unaddressed abnormal tests may be important indicators of substandard care. Other discharge screens apparently do not detect errors in care associated with major consequences for patients. PMID:7649753

  5. 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

  6. 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

  7. 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. PMID:25454994

  8. 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

  9. Epileptic encephalopathies: Optimizing seizure control and developmental outcome.

    PubMed

    Jehi, Lara; Wyllie, Elaine; Devinsky, Orrin

    2015-10-01

    Cognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes. PMID:26293588

  10. Periodontal Disease and Adverse Birth Outcomes: A Study from Pakistan

    PubMed Central

    Mobeen, N; Jehan, I; Banjay, N; Moore, J; McClure, EM; Pasha, O; Wright, LL; Goldenberg, RL

    2013-01-01

    OBJECTIVES 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. METHODS Enrollment occurred at 20–26 wks. A study dentist performed the periodontal examination to assess probing depth (PD), clinical attachment level (CAL), gingivitis index (GI) and plaque index (PI). Outcomes included stillbirth, neonatal mortality, <32 wk preterm birth (PTB), 32–36 wk PTB, and low birthweight (LBW), and are presented for increasing periodontal disease severity by quartiles (Q1-4). RESULTS Dental examinations and outcome data were completed for 1152 women. 81% were multiparous with a mean age of 27 yrs. 33% had no education. Dental caries were present in 47%, missing teeth in 27%, and 92% had no dental care in the last year. Periodontal disease was common: 87% had ≥ 4 teeth with a PD of >3mm, 54% had ≥4 teeth with a PI = 3, and 58% had ≥ 4 teeth with a GI = 3. In general, as the measure of periodontal disease increased, stillbirth, PTB <32 wks and neonatal mortality also increased. Late PTB and LBW were not related to measures of periodontal disease. Adjustment for demographic characteristics did not significantly change the relationships. CONCLUSION Pregnant Pakistani women have high levels of moderate to severe dental disease. Both stillbirth and neonatal mortality increased with the severity of periodontal disease. PMID:18455527

  11. Paternal employment in solvent related occupations and adverse pregnancy outcomes.

    PubMed

    Daniell, W E; Vaughan, T L

    1988-03-01

    Washington State birth certificates were examined for associations between adverse pregnancy outcomes and paternal employment in solvent exposed occupations. Four cohorts defined by live, singleton births to fathers usually employed as auto body shop workers, painters (construction and maintenance), printers, or fibreglass workers were compared retrospectively with both a systematically selected control cohort and a low solvent exposed, occupationally defined control cohort (paternal electricians). The effects of maternal race and medical illness were controlled by sample restriction; maternal age and gravidity by stratified analysis. There was evidence of increased risk of low birth weight for infants born to fathers employed as body shop workers (relative risk = 1.6; 95% confidence interval = 1.1-2.4) or painters (RR = 1.4; CI = 0.9-2.1) when compared with the systematically selected controls but not with the electrician controls. The excess risk appeared stronger when only term infants were analysed suggesting a mechanism of growth retardation rather than prematurity. There was no evidence of increased risk among the other exposed cohorts or for other adverse pregnancy outcomes. Several design features limit the interpretation of the findings and confirmation by other studies is needed. PMID:3348995

  12. Spousal Military Deployment During Pregnancy and Adverse Birth Outcomes.

    PubMed

    Spieker, Amy; Schiff, Melissa A; Davis, Beth E

    2016-03-01

    Pregnant women with a military-deployed spouse have increased risk of depression and self-reported stress. In nonmilitary populations, depression and stress during pregnancy are associated with adverse birth outcomes. This study assesses the association between a spouse's military deployment and adverse birth outcomes. We conducted a retrospective cohort study at a large military medicine center in the Northwest and evaluated records of singleton deliveries to dependent Army spouses from September 2001 to September 2011. We used logistic regression to estimate relative risks and 95% confidence intervals (CI) of the associations between deployment and low birth weight (<2,500 g), preterm delivery (<37 weeks), small for gestational age (SGA, <10 percentile for gestational age), and cesarean delivery. We identified 10,536 births; 1,364 (12.9%) spouses were deployed at delivery. No associations were observed in the overall population. Among women with two or more children, we observed an 81% increased risk of SGA (95% CI 1.18-2.79). Women 30 to 34 years old had an 82% (95% CI 1.06-3.14) increased risk of low birth weight and an 84% increased risk of SGA (95% CI 1.13-2.98). Deployment's effects vary by maternal age and the number of children in the household. These findings may inform programs and practitioners to best serve women with military-deployed spouses. PMID:26926749

  13. Evaluating competing adverse and beneficial outcomes using a mixture model

    PubMed Central

    Lau, Bryan; Cole, Stephen R.; Moore, Richard D.; Gange, Stephen J.

    2008-01-01

    SUMMARY A competing risk framework occurs when individuals have the potential to experience only one of several mutually exclusive outcomes. Standard survival methods often overestimate the cumulative incidence of events when competing events are censored. Mixture distributions have been previously applied to the competing risk framework to obtain inferences regarding the subdistribution of an event of interest. Often the competing event is treated as a nuisance, but it may be of interest to compare adverse events against the beneficial outcome when dealing with an intervention. In this paper, methods for using a mixture model to estimate an adverse-benefit ratio curve (ratio of the cumulative incidence curves for the two competing events) and the ratio of the subhazards for the two competing events are presented. Both parametric and semi-parametric approaches are described with some remarks for extending the model to include uncertainty in the event type that occurred, left-truncation in order to allow for time-dependent analyses, and uncertainty in the timing of the event resulting in interval censoring. The methods are illustrated with data from a HIV clinical cohort examining whether individuals initiating effective antiretroviral therapy have a greater risk of antiretroviral discontinuation or switching compared to HIV RNA suppression. PMID:18416435

  14. The effects of air pollution on adverse birth outcomes

    PubMed Central

    Ha, Sandie; Hu, Hui; Roussos-Ross, Dikea; Haidong, Kan; Roth, Jeffrey; Xu, Xiaohui

    2014-01-01

    Background Air pollution has been shown to have adverse effects on many health outcomes including cardiorespiratory diseases and cancer. However, evidence on the effects of prenatal exposure is still limited. The purpose of this retrospective cohort study is to evaluate the effects of prenatal exposure to air pollutants including particulate matter with aerodynamic diameter less than 2.5 micrometer (PM2.5) and ozone (O3) on the risk of adverse birth outcomes (ABOs) including term low birth weight (LBW), preterm delivery (PTD) and very PTD (VPTD). Methods Singleton births from 2004–2005 in Florida were included in the study (N=423,719). Trimester-specific exposures to O3 and PM2.5 at maternal residence at delivery were estimated using the National Environmental Public Health Tracking Network data, which were interpolated using Hierarchical Bayesian models. Results After adjustment for potential confounders such as demographics, medical and lifestyle factors PM2.5 exposures in all trimesters were found to be significantly and positively associated with the risk of all ABOs. Second-trimester exposure had the strongest effects. For an interquartile range (IQR) increase in PM2.5 during the second trimester, the risk of term LBW, PTD and VPTD increased by 3% [95% confidence interval (CI): 1–6%)], 12% (11–14%) and 22% (18–25%), respectively. O3 was also found to be positively associated with PTD and VPTD with the strongest effects over the whole pregnancy period [3% (1–5%) for PTD and 13% (7–19%) for VPTD for each IQR increase]. However, O3 was observed to have protective effects on term LBW. Results were consistent for multi-pollutant models. Conclusion PM2.5 has consistent adverse effects on ABOs whereas O3 has inconsistent effects. These findings warrant further investigation. PMID:25173052

  15. 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

  16. Developmental Regression and Autism Reported to the Vaccine Adverse Event Reporting System

    ERIC Educational Resources Information Center

    Woo, Emily Jane; Ball, Robert; Landa, Rebecca; Zimmerman, Andrew W.; Braun, M. Miles

    2007-01-01

    We report demographic and clinical characteristics of children reported to the US Vaccine Adverse Event Reporting System (VAERS) as having autism or another developmental disorder after vaccination. We completed 124 interviews with parents and reviewed medical records for 31 children whose records contained sufficient information to evaluate the…

  17. Prenatal Tobacco Exposure: Developmental Outcomes in the Neonatal Period

    PubMed Central

    Espy, Kimberly Andrews; Fang, Hua; Johnson, Craig; Stopp, Christian; Wiebe, Sandra A.; Respass, Jennifer

    2010-01-01

    Smoking during pregnancy is a persistent public health problem that has been linked to later adverse outcomes. The neonatal period, the first month of life, carries substantial developmental change in regulatory skills, and is the period when tobacco metabolites are cleared physiologically. Studies to date mostly have used cross-sectional designs that limit characterizing potential impacts of prenatal tobacco exposure on the development of key self-regulatory processes and cannot disentangle short-term withdrawal effects from residual exposure-related impacts. In this study, pregnant participants (N = 304) were recruited prospectively during pregnancy and smoking was measured at multiple time points, using both self report and biochemical measures. Neonatal attention, irritable reactivity, and stress dysregulation were examined longitudinally at three time points during the first month of life, and physical growth indices were measured at birth. Tobacco-exposed infants showed significantly poorer attention skills after birth, and the magnitude of the difference between exposed and non-exposed groups attenuated across the neonatal period. In contrast, exposure-related differences in irritable reactivity were not evident and stable across the first month of life, but differed only marginally at 4-weeks of age. Third trimester smoking was associated with pervasive, deleterious, dose-response impacts on physical growth measured at birth, whereas nearly all smoking indicators throughout pregnancy predicted level and growth rates of early attention. The observed neonatal pattern is consistent with the neurobiology of tobacco on the developing nervous system and fits with developmental vulnerabilities observed later in life. PMID:21038943

  18. Perfluorinated Compounds in Umbilical Cord Blood and Adverse Birth Outcomes

    PubMed Central

    Chen, Mei-Huei; Ha, Eun-Hee; Wen, Ting-Wen; Su, Yi-Ning; Lien, Guang-Wen; Chen, Chia-Yang; Chen, Pau-Chung; Hsieh, Wu-Shiun

    2012-01-01

    Background Previous animal studies have shown that perfluorinated compounds (PFCs) have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) and birth outcomes. Methods In total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study (TBPS). Demographic data were obtained by interviewing mothers using a structured questionnaire and birth outcomes were extracted from medical records. Cord blood was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. Results The geometric mean (standard deviation) levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma were 1.84 (2.23), 5.94 (1.95), 2.36(4.74), and 10.26 (3.07) ng/mL, respectively. Only PFOS levels were found to be inversely associated with gestational age, birth weight, and head circumference [per ln unit: adjusted β (95% confidence interval, CI) = −0.37 (−0.60, −0.13) wks, −110.2 (−176.0, −44.5) gm and −0.25 (−0.46, −0.05) cm]. Additionally, the odds ratio of preterm birth, low birth weight, and small for gestational age increased with PFOS exposure [per ln unit: adjusted odds ratio (OR) (95%CI) = 2.45 (1.47, 4.08), 2.61(0.85, 8.03) and 2.27 (1.25, 4.15)]. When PFOS levels were divided into quartiles, a dose-response relation was observed. However, PFOA, PFNA, and PFUA were not observed to have any convincing impact on birth outcomes. Conclusions An adverse dose-dependent association was observed between prenatal PFOS exposure and birth outcomes. However, no associations were found for the other examined PFCs. PMID:22879996

  19. Adverse obstetric outcome for the vanishing twin syndrome.

    PubMed

    Almog, Benny; Levin, Ishai; Wagman, Israel; Kapustiansky, Rita; Lessing, Joseph B; Amit, Ami; Azem, Foad

    2010-02-01

    The aim was to compare obstetric outcomes of IVF singleton pregnancies diagnosed with vanishing twin (VT) syndrome with those pregnancies originating as singleton pregnancies and with twin pregnancies. In this case control study, 57 patients diagnosed with VT syndrome were matched and compared with 171 singleton controls and 171 twin controls. Mean gestational age was 35.1+/-3.7 versus 38.2+/-2.6 weeks (P=0.001) for patients and singleton controls respectively. Birth weights were 2834.4+/-821.2 versus 3036+/-489.3g (P=0.02), proportion of low birth weight (< 2500 g) was 33.3 versus 11.7% (P=0.0001) and very low birth weight (< 1500 g) 3.5 versus 0.6% for patients and singleton controls respectively. The proportion of deliveries before 28 weeks of gestation was 7.0 versus 1.2% (P=0.01) for patients and singleton controls respectively. When comparing the study group to twin control pregnancies, a similar gestational age at delivery (35 weeks) and rate of preterm birth (23%) were found. In conclusion, pregnancies diagnosed with the VT syndrome after IVF carry a higher rate of adverse obstetric outcomes in terms of preterm deliveries and lower birth weight, compared with IVF pregnancies that were originally singleton. Additionally, significant similarities were observed in the obstetrics outcome of vanishing twin pregnancies and twin pregnancies. PMID:20113963

  20. Excessive folic acid intake and relation to adverse health outcome.

    PubMed

    Selhub, Jacob; Rosenberg, Irwin H

    2016-07-01

    The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that "high folic acid intake has not reliably been shown to be associated with negative healeffects". In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999-2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young. Potential detrimental effects of high folic acid intake may not be limited to the elderly nor to those with B12 deficiency. A study from India linked maternal high RBC folate to increased insulin resistance in offspring. Our study suggested that excessive folic acid intake is associated with lower natural killer cells activity in elderly women. In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. In the elderly this polymorphism is associated with lower memory and executive scores, both being significantly worse in those with high plasma folate. These and other data strongly imply that

  1. Outcome Trajectories of Developmental Students in Community Colleges

    ERIC Educational Resources Information Center

    Bremer, Christine D.; Center, Bruce A.; Opsal, Christen L.; Medhanie, Amanuel; Jang, Yoo Jeong; Geise, Aaron C.

    2013-01-01

    This analysis explores student outcomes related to taking developmental English (i.e., reading and/or writing) and math classes in three community colleges in three different states, using institutional data from 7,898 students who began college in the fall of 2009 (Cohort 1) or fall 2010 (Cohort 2). We examine the outcome trajectories of students…

  2. Tracking Preschool Children with Developmental Delay: Third Grade Outcomes

    ERIC Educational Resources Information Center

    Delgado, Christine E. F.; Vagi, Sara J.; Scott, Keith G.

    2006-01-01

    Educational outcomes were evaluated for 2,046 preschool children identified with developmental delay. Results indicated that at third grade, 26% were in regular education and the remaining 74% were receiving special education services. The most common disability classifications at outcome were specific learning disabilities and educable mentally…

  3. Mycoplasma, Ureaplasma, and Adverse Pregnancy Outcomes: A Fresh Look

    PubMed Central

    Larsen, Bryan; Hwang, Joseph

    2010-01-01

    Recent work on the Molicutes that associate with genital tract tissues focuses on four species that may be of interest in potential maternal, fetal, and neonatal infection and in contributing to adverse pregnancy outcomes. Mycoplasma hominis and Ureaplasma urealyticum have historically been the subject of attention, but Mycoplasma genitalis which causes male urethritis in addition to colonizing the female genital tract and the division of Ureaplasma into two species, urealyticum and parvum, has also added new taxonomic clarity. The role of these genital tract inhabitants in infection during pregnancy and their ability to invade and infect placental and fetal tissue is discussed. In particular, the role of some of these organisms in prematurity may be mechanistically related to their ability to induce inflammatory cytokines, thereby triggering pathways leading to preterm labor. A review of this intensifying exploration of the mycoplasmas in relation to pregnancy yields several questions which will be important to examine in future research. PMID:20706675

  4. Developmental Outcomes after Early Prefrontal Cortex Damage

    ERIC Educational Resources Information Center

    Eslinger, Paul J.; Flaherty-Craig, Claire V.; Benton, Arthur L.

    2004-01-01

    The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical…

  5. Child Neglect: Developmental Issues and Outcomes.

    ERIC Educational Resources Information Center

    Hildyard, Kathryn L.; Wolfe, David A.

    2002-01-01

    This article reviews the effects of child neglect on three developmental periods: infancy/preschool, school-aged and younger adolescents, and older adolescents and adults. The severe cognitive and academic deficits, the social withdrawal and limited peer interactions, and the internalizing problems of neglected children relative to physically…

  6. Adverse Outcome Pathway (AOP) Development I: Strategies and Principles

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    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 organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components—notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development. PMID:25466378

  7. Adverse outcome pathway (AOP) development I: strategies and principles.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    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 organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components-notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development. PMID:25466378

  8. Adolescent Survivors of Sexual Abuse: Developmental Outcomes

    ERIC Educational Resources Information Center

    Banyard, Victoria L.; Williams, Linda M.

    2007-01-01

    Using an ecological model as a guiding framework, this article reviews key factors which put adolescent survivors of sexual abuse at risk for negative outcomes, as well as resources which might enhance positive outcomes and recovery. Throughout the article, quotes from women who experienced sexual abuse during their youth highlight opportunities…

  9. Adverse obstetric and neonatal outcomes in women with mental disorders.

    PubMed

    Hoirisch-Clapauch, Silvia; Brenner, Benjamin; Nardi, Antonio Egidio

    2015-02-01

    The brain and the placenta synthesize identical peptides and proteins, such as brain-derived neurotrophic factor, oxytocin, vascular endothelial growth factor, cortisol, and matrix metalloproteinases. Given the promiscuity between neurochemistry and the mechanism of placentation, it would be expected that mental disorders occurring during pregnancy would increase the risk of adverse obstetric and neonatal outcomes. Indeed, expectant mothers with anxiety disorders, post-traumatic stress disorder, schizophrenia, or depressive disorders are at higher risk of preterm birth, low-birth-weight and small-for-gestational-age infants than controls. These mental illnesses are accompanied by a procoagulant phenotype and low activity of tissue plasminogen activator, which may contribute to placental insufficiency. Another risk factor for pregnancy complications is hyperemesis gravidarum, more common among women with eating disorders or anxiety disorders than in controls. Severe hyperemesis gravidarum is associated with dehydration, electrolyte imbalance and malnutrition, all of which may increase the risk of miscarriages, of low-birth-weight babies and preterm birth. This paper reviews some aspects of mental disorders that may influence pregnancy and neonatal outcomes. PMID:25903540

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

    PubMed

    Oki, Noffisat O; Nelms, Mark D; Bell, Shannon M; Mortensen, Holly M; Edwards, Stephen W

    2016-03-01

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; 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 HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested. PMID:26809562

  11. 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

  12. Adverse health outcomes among cosmetologists and noncosmetologists in the Reproductive Outcomes of Salon Employees (ROSE) study.

    PubMed

    Gallicchio, Lisa; Miller, Susan R; Greene, Teresa; Zacur, Howard; Flaws, Jodi A

    2011-01-01

    The purpose of this study was to examine adverse health outcomes, including those related to cardiovascular and skin health as well as respiratory functions, among cosmetologists aged 21 to 55 yr and to compare data to women of the same age working in other occupations. Self-reported data were analyzed from 450 cosmetologists and 511 women in other occupations who participated in the Reproductive Outcomes of Salon Employees (ROSE) study in Maryland. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed using logistic regression to examine the associations between cosmetologist occupation and each adverse health outcome adjusted for age, education, and smoking status. Cosmetologists were at significantly increased risk of depression compared to noncosmetologists after adjustment for age, education, and smoking status (OR 1.49; 95% CI 1.10, 2.00). There were no statistically significant associations between cosmetology occupation and the other adverse health outcomes, including those related to allergies and skin disorders, in both the unadjusted and adjusted analyses. Cosmetologists may be exposed to chemicals in the salon that lead to depression. Future study needs to be conducted to examine specific chemical exposures in the salon. This will help to provide information required for the development of best occupational safety practices among salon workers. PMID:21120748

  13. 77 FR 48995 - Draft National Toxicology Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy; Request... Pregnancy Outcomes Associated with Cancer Chemotherapy Use during Pregnancy (available by August 14, 2012... NTP Monograph on Developmental Effects and Pregnancy Outcomes Associated with Cancer Chemotherapy...

  14. Infertility, Pregnancy Loss and Adverse Birth Outcomes in Relation to Maternal Secondhand Tobacco Smoke Exposure

    PubMed Central

    Meeker, John D.; Benedict, Merle D.

    2013-01-01

    A substantial proportion of the etiology involved in female infertility and adverse pregnancy outcomes remains idiopathic. Recent scientific research has suggested a role for environmental factors in these conditions. Secondhand tobacco smoke (STS) contains a number of known or suspected reproductive toxins, and human exposure to STS is prevalent worldwide. Robust evidence exists for the toxic effects of active smoking on fertility and pregnancy, but studies of passive exposure are much more limited in number. While the association between maternal STS exposure and declined birth weight has been fairly well-documented, only recently have epidemiologic studies begun to provide suggestive evidence for delayed conception, altered menstrual cycling, early pregnancy loss (e.g. spontaneous abortion), preterm delivery, and congenital malformations in relation to STS exposure. There is also new evidence that developmental exposures to tobacco smoke may be associated with reproductive effects in adulthood. To date, most studies have estimated maternal STS exposure through self-report even though exposure biomarkers are less prone to error and recall bias. In addition to utilizing biomarkers of STS exposure, future studies should aim to identify vital windows of STS exposure, important environmental co-exposures, individual susceptibility factors, and specific STS constituents associated with female infertility and adverse pregnancy outcomes. The role of paternal exposures/factors should also be investigated. PMID:23888128

  15. Developmental Outcomes of Internationally Adopted Children

    PubMed Central

    Welsh, Janet A.; Viana, Andres G.

    2013-01-01

    This study followed the development of a sample of 106 (67 girls) internationally adopted children over a period of 18 months. Children were adopted from five birth regions, including China, Korea, Latin America, Eastern Europe, and other Asian countries. Mean age at adoption was 11 months. Mothers completed the Ages and Stages Questionnaire (ASQ) at 6, 12, and 24 months post-adoption, assessing children's gross and fine motor, communicative, personal-social, and problem solving skills. Results revealed that the sample as a whole demonstrated linear improvement over time in most developmental domains, but children with initially low scores remained significantly lower than other children at the 18-month follow-up. At the first time point, communication was the domain where children most commonly experienced delays. Children with medical problems had significantly lower developmental scores than those without medical diagnoses. ASQ scores were unrelated to age at adoption, but significant differences by birth country region were found. Across most domains, children adopted from Eastern Europe showed generally lower scores than children adopted from other birth regions. PMID:23908583

  16. Antenatal psychosocial risk factors associated with adverse postpartum family outcomes.

    PubMed Central

    Wilson, L M; Reid, A J; Midmer, D K; Biringer, A; Carroll, J C; Stewart, D E

    1996-01-01

    OBJECTIVE: To determine the strength of the association between antenatal psychosocial risk factors and adverse postpartum outcomes in the family, such as assault of women by their partner, child abuse, postpartum depression, marital dysfunction and physical illness. DATA SOURCES: MEDLINE, Cinahl, Famli, Psych Abstracts and the Oxford Database of Perinatal Trials were searched from relevant articles published from Jan. 1, 1980, to Dec. 31, 1993, with the use of MeSH terms "depression, involutional," "child abuse," "child neglect," "domestic violence," "family," "marital adjustment," "family health," "newborn health," "child health," "physical illness," "social support," "psychosocial risk," "prediction," "risk factors," "obstetrics" and "prenatal care." Further articles were identified from bibliographies. STUDY SELECTION: Of the 370 articles identified through the search, 118 were included for review. Studies were included if they examined the association between psychosocial risk factors and the outcomes of interest. Articles were excluded if they were reviews of poor quality or they had one or more of the following features: insufficient description of the sample, a high attrition rate, a lack of standardized outcome measures, outcomes other than the ones of interest or results that had already been reported in a previous study. DATA EXTRACTION: The strength of evidence of each study was evaluated. On the basis of the evidence, each risk factor was assigned a rating of the strength of its association with each of the postpartum outcomes. The ratings were class A (good evidence of association), class B (fair evidence) and class C (no clear evidence). Of the 129 antenatal psychosocial risk factors studied, 15 were found to have a class A association with at least one of the postpartum outcomes. DATA SYNTHESIS: Child abuse and abuse of the mother by her partner were most strongly correlated (class A evidence) with a history of lack of social support, recent life

  17. 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...

  18. Adverse outcomes of frailty in the elderly: the Rotterdam Study.

    PubMed

    Lahousse, Lies; Maes, Bastiaan; Ziere, Gijsbertus; Loth, Daan W; Verlinden, Vincentius J A; Zillikens, M Carola; Uitterlinden, André G; Rivadeneira, Fernando; Tiemeier, Henning; Franco, Oscar H; Ikram, M Arfan; Hofman, Albert; Brusselle, Guy G; Stricker, Bruno H

    2014-06-01

    To investigate the prevalence of frailty in a Dutch elderly population and to identify adverse health outcomes associated with the frailty phenotype independent of the comorbidities. Cross-sectional and longitudinal analyses within the Rotterdam Study (the Netherlands), a prospective population-based cohort study in persons aged ≥55 years. Frailty was defined as meeting three or more of five established criteria for frailty, evaluating nutritional status, physical activity, mobility, grip strength and exhaustion. Intermediate frailty was defined as meeting one or two frailty criteria. Comorbidities were objectively measured. Health outcomes were assessed by means of questionnaires, physical examinations and continuous follow-up through general practitioners and municipal health authorities for mortality. Of 2,833 participants (median age 74.0 years, inter quartile range 9) with sufficiently evaluated frailty criteria, 163 (5.8 %) participants were frail and 1,454 (51.3 %) intermediate frail. Frail elderly were more likely to be older and female, to have an impaired quality of life and to have fallen or to have been hospitalized. 108 (72.0 %) frail participants had ≥2 comorbidities, compared to 777 (54.4 %) intermediate frail and 522 (44.8 %) non-frail participants. Adjusted for age, sex and comorbidities, frail elderly had a significantly increased risk of dying within 3 years (HR 3.4; 95 % CI 1.9-6.4), compared to the non-frail elderly. This study in a general Dutch population of community-dwelling elderly able to perform the frailty tests, demonstrates that frailty is common and that frail elderly are at increased risk of death independent of comorbidities. PMID:24935872

  19. Developmental Outcomes for Children of Young Mothers

    ERIC Educational Resources Information Center

    Pogarsky, Greg; Thornberry, Terence P.; Lizotte, Alan J.

    2006-01-01

    This study tested the association between mother's early age at first birth and various life outcomes for her children in later adolescence and early adulthood. Data were analyzed from the Rochester Youth Development Study, an ongoing panel study of adolescents enrolled in seventh or eighth grade in Rochester Public Schools in 1988 ("N"=729). Boys…

  20. Adverse pregnancy outcomes and cardiovascular risk factor management.

    PubMed

    Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel

    2015-06-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

  1. Adverse Pregnancy Outcomes and Cardiovascular Risk Factor Management

    PubMed Central

    Mehta, Puja K.; Minissian, Margo; Merz, C. Noel Bairey

    2015-01-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to established risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman’s risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia be evaluated for hypertension and other CVD risk factors within 6 months to 1 year post-partum. Given the burden and impact of CVD on women our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

  2. Identifying genomic and developmental causes of adverse drug reactions in children

    PubMed Central

    Becker, Mara L; Leeder, J Steven

    2011-01-01

    Adverse drug reactions are a concern for all clinicians who utilize medications to treat adults and children; however, the frequency of adult and pediatric adverse drug reactions is likely to be under-reported. In this age of genomics and personalized medicine, identifying genetic variation that results in differences in drug biotransformation and response has contributed to significant advances in the utilization of several commonly used medications in adults. In order to better understand the variability of drug response in children however, we must not only consider differences in genotype, but also variation in gene expression during growth and development, namely ontogeny. In this article, recommendations for systematically approaching pharmacogenomic studies in children are discussed, and several examples of studies that investigate the genomic and developmental contribution to adverse drug reactions in children are reviewed. PMID:21121777

  3. Trajectories of Physical Discipline: Early Childhood Antecedents and Developmental Outcomes

    ERIC Educational Resources Information Center

    Lansford, Jennifer E.; Criss, Michael M.; Dodge, Kenneth A.; Shaw, Daniel S.; Pettit, Gregory S.; Bates, John E.

    2009-01-01

    This study examined childhood antecedents and developmental outcomes associated with trajectories of mild and harsh parental physical discipline. Interview, questionnaire, and observational data were available from 499 children followed from ages 5 to 16 and from 258 children in an independent sample followed from ages 5 to 15. Analyses indicated…

  4. Developmental Outcome in a Tracheostomized Child: A Case Study.

    ERIC Educational Resources Information Center

    Vaivre-Douret, Laurence; And Others

    1995-01-01

    Reports developmental outcomes of a child who experienced a tracheostomy and had prolonged hospitalization and psychomotor therapy in an intensive care unit. Found a pattern of delay in speech and language production with no hearing loss, no cognitive impairment, an average level of fine motor disorders, no behavioral disorders, and normal…

  5. When Do Adaptive Developmental Mechanisms Yield Maladaptive Outcomes?

    ERIC Educational Resources Information Center

    Frankenhuis, Willem E.; Del Giudice, Marco

    2012-01-01

    This article discusses 3 ways in which adaptive developmental mechanisms may produce maladaptive outcomes. First, natural selection may favor risky strategies that enhance fitness on average but which have detrimental consequences for a subset of individuals. Second, mismatch may result when organisms experience environmental change during…

  6. Intimate Partner Violence During Pregnancy and Adverse Neonatal Outcomes in Low-Income Women

    PubMed Central

    Bullock, Linda; Sharps, Phyllis; Schminkey, Donna; Comstock, Emily; Campbell, Jacquelyn

    2014-01-01

    Abstract Background: Intimate partner violence (IPV) affects an estimated 1.5 million U.S. women annually. IPV impacts maternal and neonatal health with higher rates of depression and low birth weight (LBW). Less studied is experiencing IPV and delivering a small for gestational age (SGA) baby. SGA neonates are at increased risk of developmental and behavioral problems. The negative sequelae persist into adulthood with increased rates of diabetes mellitus and coronary heart disease. Methods: In a sample of 239 pregnant women experiencing IPV, in urban and rural settings, we examined cross-sectional associations of severity of IPV and neonatal outcomes (i.e., birth weight and gestational age). Severity of IPV was measured by the Conflict Tactics Scale 2 and neonatal outcomes were collected at the time of delivery. Results: Outcomes were collected on 194 neonates; 14.9% (n=29) were classified as LBW, 19.1% (n=37) classified as SGA, and 9.8% (n=19) as LBW and SGA. Women reporting higher severity of IPV during pregnancy had a greater likelihood of delivering an SGA neonate (odds ratio [OR] 4.81; 95% confidence interval [95% CI] 1.86–12.47), and LBW neonate (OR 4.20; 95% CI 1.46–12.10). Conclusions: In a sample of pregnant women experiencing perinatal IPV, women experiencing greater severities of IPV were more likely to deliver a neonate with an adverse outcome. Early recognition and intervention of IPV is essential to reduce disparities in birth outcomes and long-term health outcomes for these neonates. PMID:25290007

  7. 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...

  8. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  9. Risk-Adjusted Models for Adverse Obstetric Outcomes and Variation in Risk Adjusted Outcomes Across Hospitals

    PubMed Central

    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. N.; Saade, George; Sorokin, Yoram; Rouse, Dwight J.; Blackwell, Sean C.; Tolosa, Jorge E.; Van Dorsten, J. Peter

    2014-01-01

    Objective Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing 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 five obstetric outcomes and assess hospital performance across these outcomes. Study Design A cohort study of 115,502 women and their neonates born in 25 hospitals in the United States between March 2008 and 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. Results Venous thromboembolism occurred too infrequently (0.03%, 95% 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. Conclusions Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance. PMID:23891630

  10. A longitudinal study of maternal attachment and infant developmental outcomes

    PubMed Central

    Alhusen, Jeanne L.; Hayat, Matthew J.; Gross, Deborah

    2013-01-01

    Extant research has demonstrated that compared to adults with insecure attachment styles, more securely attached parents tend to be more responsive, sensitive, and involved parents resulting in improved outcomes for their children. Less studied is the influence of a mother's attachment style on her attachment to her unborn child during pregnancy and the consequent developmental outcomes of the child during early childhood. Thus, the aim of this prospective longitudinal study was to examine the relationship between maternal-fetal attachment (MFA) during pregnancy and infant and toddler outcomes and the role of mothers’ attachment style on early childhood developmental outcomes in an economically disadvantaged sample of women and their children. Gamma regression modeling demonstrated an avoidant maternal attachment style (b = .98, 95% CI [.97, .98], p < 0.001) and post-partum depressive symptomatology (b = .97, 95% CI [.96-.99], p = .03) were significant predictors of early childhood development. Women demonstrating higher avoidant attachment styles and greater depressive symptomatology were more likely to have children demonstrating early childhood developmental delays than those women with less avoidant attachment styles and less depressive symptomatology. Furthermore, women reporting higher MFA during pregnancy had more secure attachment styles and their children had more optimal early childhood development than those women reporting lower MFA and less secure attachment styles. Findings have implications for enhancing early intervention programs aimed at improving maternal and childhood outcomes. An earlier identification of disruptions in attachment may be beneficial in tailoring interventions focused on the mother-child dyad. PMID:23737011

  11. DOSE-RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY I. CHARACTERIZATION OF DATABASE AND DETERMINATION OF NO OBSERVED ADVERSE EFFECT LEVELS

    EPA Science Inventory

    Developmental toxicity risk assessment currently relies on the estimation of reference doses or reference concentrations based on no observed adverse effect levels (NOAELS) and uncertainty factors. he benchmark dose (BMD) has been proposed as an alternative basis for reference va...

  12. 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...

  13. 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:…

  14. 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 ...

  15. 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...

  16. 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...

  17. Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

    PubMed

    Tedeschi, Sara K; Guan, Hongshu; Fine, Alexander; Costenbader, Karen H; Bermas, Bonnie

    2016-07-01

    Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women's Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12-20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0-12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3-11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0-34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy. PMID:27166627

  18. A longitudinal study of maternal attachment and infant developmental outcomes.

    PubMed

    Alhusen, Jeanne L; Hayat, Matthew J; Gross, Deborah

    2013-12-01

    Extant research has demonstrated that compared to adults with insecure attachment styles, more securely attached parents tend to be more responsive, sensitive, and involved parents, resulting in improved outcomes for their children. Less studied is the influence of a mother's attachment style on her attachment to her unborn child during pregnancy and the consequent developmental outcomes of the child during early childhood. Thus, the aim of this prospective longitudinal study was to examine the relationship between maternal-fetal attachment (MFA) during pregnancy and infant and toddler outcomes and the role of mothers' attachment style on early childhood developmental outcomes in an economically disadvantaged sample of women and their children. Gamma regression modeling demonstrated that an avoidant maternal attachment style (b = .98, 95 % CI [.97, .98], p < 0.001) and post-partum depressive symptomatology (b = .97, 95 % CI [.96-.99], p = 0.03) were significant predictors of early childhood development. Women demonstrating higher avoidant attachment styles and greater depressive symptomatology were more likely to have children demonstrating early childhood developmental delays than those women with less avoidant attachment styles and less depressive symptomatology. Furthermore, women reporting higher MFA during pregnancy had more secure attachment styles, and their children had more optimal early childhood development than those women reporting lower MFA and less secure attachment styles. Findings have implications for enhancing early intervention programs aimed at improving maternal and childhood outcomes. An earlier identification of disruptions in attachment may be beneficial in tailoring interventions focused on the mother-child dyad. PMID:23737011

  19. 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...

  20. 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

  1. Calcium signaling triggered by ouabain protects the embryonic kidney from adverse developmental programming.

    PubMed

    Khodus, Georgiy R; Kruusmägi, Markus; Li, Juan; Liu, Xiao-Li; Aperia, Anita

    2011-09-01

    The kidney is extraordinarily sensitive to adverse fetal programming. Malnutrition, the most common form of developmental challenge, retards formation of the kidney's functional units, the nephrons. The resulting low nephron endowment increases susceptibility to renal injury and disease. Using explanted rat embryonic kidneys, we found that the sodium-potassium-adenosine triphosphatase (Na, K-ATPase) ligand ouabain triggers, via the Na, K-ATPase/ inositol 1,4,5-trisphosphate receptor signalosome, a calcium-nuclear factor-kappa B (NF-κB) signal that protects kidney development from adverse effects of malnutrition. Serum deprivation resulted in severe retardation of nephron formation and robust increase in apoptotic rate, but in ouabain-exposed kidneys, no adverse effects of serum deprivation were observed. Depletion of intracellular calcium stores and inhibition of NF-κB activity abolished the rescuing effect of ouabain. Proof of principle that ouabain rescues development of embryonic kidneys exposed to malnutrition was obtained from studies on pregnant rats given low-protein diets and treated with ouabain or vehicle throughout pregnancy. PMID:21424905

  2. When do adaptive developmental mechanisms yield maladaptive outcomes?

    PubMed

    Frankenhuis, Willem E; Del Giudice, Marco

    2012-05-01

    This article discusses 3 ways in which adaptive developmental mechanisms may produce maladaptive outcomes. First, natural selection may favor risky strategies that enhance fitness on average but which have detrimental consequences for a subset of individuals. Second, mismatch may result when organisms experience environmental change during ontogeny, for instance, because they move from one environment to another. Third, organisms may learn about their environment in order to develop an appropriate phenotype; when cues indicate the environmental state probabilistically, as opposed to deterministically, sampling processes may produce mismatch. For each source of maladaptation, we present a selection of the relevant empirical research and illustrate how models from evolutionary biology can be used to make predictions about maladaptation. We also discuss what data can be collected to test these models in humans. Our goal is to show that evolutionary approaches not only yield insights into adaptive outcomes but can also illuminate the conditions leading to maladaptation. This perspective provides additional nuance to the dialectic between the developmental psychopathology model and evolutionary developmental psychology. PMID:21967567

  3. Developmental Patterns of Adverse Childhood Experiences and Current Symptoms and Impairment in Youth Referred For Trauma-Specific Services.

    PubMed

    Grasso, Damion J; Dierkhising, Carly B; Branson, Christopher E; Ford, Julian D; Lee, Robert

    2016-07-01

    By the time children reach adolescence, most have experienced at least one type of severe adversity and many have been exposed to multiple types. However, whether patterns of adverse childhood experiences are consistent or change across developmental epochs in childhood is not known. Retrospective reports of adverse potentially traumatic childhood experiences in 3 distinct developmental epochs (early childhood, 0- to 5-years-old; middle childhood, 6- to 12-years-old; and adolescence, 13- to 18-years-old) were obtained from adolescents (N = 3485) referred to providers in the National Child Traumatic Stress Network (NCTSN) for trauma-focused assessment and treatment. Results from latent class analysis (LCA) revealed increasingly complex patterns of adverse/traumatic experiences in middle childhood and adolescence compared to early childhood. Depending upon the specific developmental epoch assessed, different patterns of adverse/traumatic experiences were associated with gender and with adolescent psychopathology (e.g., internalizing/externalizing behavior problems), and juvenile justice involvement. A multiply exposed subgroup that had severe problems in adolescence was evident in each of the 3 epochs, but their specific types of adverse/traumatic experiences differed depending upon the developmental epoch. Implications for research and clinical practice are identified. PMID:26438634

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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)...

  11. 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

  12. Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

    PubMed Central

    Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

    2012-01-01

    Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

  13. Biomedical risk, psychosocial influences, and developmental outcomes: lessons from the pediatric HIV population in Africa.

    PubMed

    Abubakar, Amina

    2014-01-01

    Sub-Saharan Africa is home to millions of HIV-affected children. These children are likely to experience multiple developmental delays. In this chapter, I present data highlighting compromised neurobehavioral, mental health, and scholastic outcomes for children affected by HIV. Furthermore, I discuss biomedical factors (e.g., disease severity and nutritional status) that may exacerbate the adverse effects of HIV on childhood outcomes. I also present evidence on how psychosocial risk factors such as poor maternal mental health, orphanhood, and poverty may aggravate the effects of HIV. The concluding section of the chapter highlights conceptual and methodological refinements in research on the impact of HIV on child development in Sub-Saharan Africa. PMID:25512044

  14. Alanine aminotransferase as a predictor of adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy

    PubMed Central

    Ekiz, Ali; Kaya, Basak; Avci, Muhittin Eftal; Polat, Ibrahim; Dikmen, Selin; Yildirim, Gokhan

    2016-01-01

    Objective: To evaluate the associations between adverse perinatal outcomes and serum transaminase levels at the time of diagnosis in patients with intrahepatic cholestasis of pregnancy. Methods: We performed a retrospective analysis of patients hospitalized for evaluation of intrahepatic cholestasis of pregnancy from January 2013 to June 2014 in a tertiary center. Seventy-one patients were divided into two groups according to the presence (Group I) or absence of adverse perinatal outcomes (Group II). Results: The mean aminotransferase levels and conjugated bilirubin levels at the time of diagnosis were significantly higher in Group I than in Group II. Receiver operating characteristic curve analysis revealed that the alanine aminotransferase level could predict adverse perinatal outcomes with 76.47% sensitivity and 78.38% specificity, and the cut-off value was 95 IU/L. Among patients with intrahepatic cholestasis of pregnancy, those with adverse perinatal outcomes were significantly older, had an earlier diagnosis, and had higher alanine aminotransferase levels. Using the 95-IU/L cut-off value, patients with intrahepatic cholestasis of pregnancy had a 3.54-fold increased risk for adverse perinatal outcomes. Conclusions: Patients with intrahepatic cholestasis of pregnancy and high alanineaminotransferase levels should be followed up for possible adverse perinatal outcomes.

  15. Candida Virulence Properties and Adverse Clinical Outcomes in Neonatal Candidiasis

    PubMed Central

    Bliss, Joseph M.; Wong, Angela Y.; Bhak, Grace; Laforce-Nesbitt, Sonia S.; Taylor, Sarah; Tan, Sylvia; Stoll, Barbara J.; Higgins, Rosemary D.; Shankaran, Seetha; Benjamin, Daniel K.

    2012-01-01

    Objective To determine if premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains. Study design Clinical isolates were studied from 2 populations; premature infants colonized with Candida (commensal, n=27), and those with invasive candidiasis (n=81). Individual isolates of C. albicans and C. parapsilosis were tested for virulence in each of 3 assays: phenotypic switching, adhesion, and cytotoxicity. Invasive isolates were considered to have enhanced virulence if they measured more than 1 SD above the mean for the commensal isolates in at least 1 assay. Outcomes of patients with invasive isolates with enhanced virulence were compared with those with invasive isolates lacking enhanced virulence characteristics. Results 61% of invasive isolates of C. albicans and 42% of invasive isolates of C. parapsilosis had enhanced virulence. All C. albicans cerebrospinal fluid (CSF) isolates (n=6) and 90% of urine isolates (n=10) had enhanced virulence, compared with 48% of blood isolates (n=40). Infants with more virulent isolates were younger at the time of positive culture and had higher serum creatinine. Conclusions Individual isolates of Candida species vary in their virulence properties. Strains with higher virulence are associated with certain clinical outcomes. PMID:22504098

  16. Predictive Models of Cognitive Outcomes of Developmental Insults

    NASA Astrophysics Data System (ADS)

    Chan, Yupo; Bouaynaya, Nidhal; Chowdhury, Parimal; Leszczynska, Danuta; Patterson, Tucker A.; Tarasenko, Olga

    2010-04-01

    Representatives of Arkansas medical, research and educational institutions have gathered over the past four years to discuss the relationship between functional developmental perturbations and their neurological consequences. We wish to track the effect on the nervous system by developmental perturbations over time and across species. Except for perturbations, the sequence of events that occur during neural development was found to be remarkably conserved across mammalian species. The tracking includes consequences on anatomical regions and behavioral changes. The ultimate goal is to develop a predictive model of long-term genotypic and phenotypic outcomes that includes developmental insults. Such a model can subsequently be fostered into an educated intervention for therapeutic purposes. Several datasets were identified to test plausible hypotheses, ranging from evoked potential datasets to sleep-disorder datasets. An initial model may be mathematical and conceptual. However, we expect to see rapid progress as large-scale gene expression studies in the mammalian brain permit genome-wide searches to discover genes that are uniquely expressed in brain circuits and regions. These genes ultimately control behavior. By using a validated model we endeavor to make useful predictions.

  17. Sexual Dimorphism in Adverse Pregnancy Outcomes - A Retrospective Australian Population Study 1981-2011

    PubMed Central

    Verburg, Petra E.; Tucker, Graeme; Scheil, Wendy; Erwich, Jan Jaap H. M.; Dekker, Gus A.; Roberts, Claire Trelford

    2016-01-01

    Objectives Sexual inequality starts in utero. The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult. Methods Retrospective population-based study of 574,358 South Australian singleton live births during 1981–2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches. Results The traditional approach showed male predominance for PTB [20–24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274–1.445], spontaneous PTB [25–29 weeks: RR M/F 1.118, 95%-CI 1.044–1.197%], GDM [RR M/F 1.042, 95%-CI 1.011–1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034–1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105]. The FAR approach showed that males were at increased risk for PTB [20–24 weeks: RR M/F 1.273, 95%-CI 1.087–1.490], for spontaneous PTB [25–29 weeks: RR M/F 1.269, 95%-CI 1.143–1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25–29 weeks: RR M/F 0.857, 95%-CI 0.780–0.941] and PIHD associated with PTB [25–29 weeks: RR M/F 0.686, 95%-CI 0.581–0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25–29 weeks: RR M/F 0.779, 95%-CI 0.648–0.937]. Conclusions This study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene

  18. 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...

  19. 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...

  20. 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…

  1. Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders

    PubMed Central

    Monari, Francesca; Pedrielli, Giulia; Vergani, Patrizia; Pozzi, Elisa; Mecacci, Federico; Serena, Caterina; Neri, Isabella; Facchinetti, Fabio

    2016-01-01

    Objective To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was “adverse neonatal outcome”, including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxic-ischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2–3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1–4.3). Conclusion When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor. PMID:27228078

  2. Adverse pregnancy outcome in a petrochemical polluted area in Taiwan.

    PubMed

    Lin, M C; Yu, H S; Tsai, S S; Cheng, B H; Hsu, T Y; Wu, T N; Yang, C Y

    2001-08-24

    The petrochemical industry is the main source of industrial air pollution in Taiwan. Reported here are the results from an ongoing study of outdoor air pollution and the health of individuals living in a community in close proximity to petrochemical industrial complexes. The prevalences of term low birth weight (LBW) in the petrochemical municipality and control municipality were 3.22%, and 1.84%, respectively. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, and infant sex), the adjusted odds ratio was 1.767 (1.002-3.116) for term LBW in the petrochemical municipality. Data provide further support for the hypothesis that air pollution can affect the outcome of pregnancy. PMID:11549116

  3. Attention-deficit/hyperactivity disorder and adverse health outcomes

    PubMed Central

    Nigg, Joel

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is defined by extreme levels of inattention–disorganization and/or hyperactivity–impulsivity. In DSM-IV, the diagnostic criteria required impairment in social, academic, or occupational functioning. With DSM-5 publication imminent in 2013, further evaluation of impairment in ADHD is timely. This article reviews the current state of knowledge on health-related impairments of ADHD, including smoking, drug abuse, accidental injury, sleep, obesity, hypertension, diabetes, and suicidal behavior. It concludes by suggesting the need for new avenues of research on mechanisms of association and the potential for ADHD to be an early warning sign for secondary prevention of some poor health outcomes. PMID:23298633

  4. Substantiation and adverse appeal outcomes: content analysis and testing of Drake's harm/evidence model.

    PubMed

    Fakunmoju, Sunday Bolanle

    2009-02-01

    Little is known about the influence of evidentiary and case characteristics on adverse appeal outcomes for substantiated cases of maltreatment. This article, therefore, reports on a sample of adverse appeal outcomes during a 2-year period. Using Drake's Harm/Evidence model to examine the adverse outcomes, the study describes differences between substantiated cases that were "modified" versus "overturned" during appeal, as well as differences in their evidentiary characteristics across different types of maltreatment. Content analysis and logistic regression analysis of administrative data were used to predict overturned versus modified outcome. Overall, child neglect, substantiated cases that did not meet basic evidentiary standards, and cases that were deemed as not credible were more likely to be overturned in comparison to being modified. A substantiation assessment framework (SAF) is developed and implications of Drake's Harm/Evidence model for investigating maltreatment as well as for understanding judicial decision making in appealed cases of maltreatment is highlighted. PMID:18612040

  5. Discriminating Characteristics of Families Watching Sesame Street. Early Developmental Adversity Program: Phase III, EDAP Technical Note 15.1.

    ERIC Educational Resources Information Center

    Jordan, Thomas E.

    "Sesame Street" is a television program aimed at stimulating young viewers. This study, a part of the Early Developmental Adversity Program, attempts to discover what demographic characteristics are associated with children who view or do not view "Sesame Street." The subjects of the study were 69 3-year-old children. Black and white, as well as…

  6. Long-Term Safety and Adverse Events of Risperidone in Children, Adolescents, and Adults with Pervasive Developmental Disorders

    ERIC Educational Resources Information Center

    Hellings, Jessica A.; Cardona, Alicia M.; Schroeder, Stephen R.

    2010-01-01

    The objective of this study was to examine long-term adverse events of risperidone in 19 children, adolescents, and adults with Pervasive Developmental Disorders and intellectual disability, continuing risperidone for a mean of 186.5 weeks, following a 46-week risperidone study. Nineteen individuals continued long-term follow-up after our…

  7. DOSE-RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY: I. CHARACTERIZATION OF DATA BASE AND DETERMINATION OF NO OBSERVED ADVERSE EFFECT LEVELS

    EPA Science Inventory

    Developmental toxicity risk assessment currently relies on the estimation of reference doses or references concentrations based on the use of no-observed-adverse-effect-levels (NOAELs) and uncertainty factors. The benchmark dose (BMD) has been proposed as an alternative basis for...

  8. An adverse outcome pathway framework for neural tube and axial defects mediated by modulation of retinoic acid homeostasis.

    PubMed

    Tonk, Elisa C M; Pennings, Jeroen L A; Piersma, Aldert H

    2015-08-01

    Developmental toxicity can be caused through a multitude of mechanisms and can therefore not be captured through a single simple mechanistic paradigm. However, it may be possible to define a selected group of overarching mechanisms that might allow detection of the vast majority of developmental toxicants. Against this background, we have explored the usefulness of retinoic acid mediated regulation of neural tube and axial patterning as a general mechanism that, when perturbed, may result in manifestations of developmental toxicity that may cover a large part of malformations known to occur in experimental animals and in man. Through a literature survey, we have identified key genes in the regulation of retinoic acid homeostasis, as well as marker genes of neural tube and axial patterning, that may be used to detect developmental toxicants in in vitro systems. A retinoic acid-neural tube/axial patterning adverse outcome pathway (RA-NTA AOP) framework was designed. The framework was tested against existing data of flusilazole exposure in the rat whole embryo culture, the zebrafish embryotoxicity test, and the embryonic stem cell test. Flusilazole is known to interact with retinoic acid homeostasis, and induced common and unique NTA marker gene changes in the three test systems. Flusilazole-induced changes were similar in directionality to gene expression responses after retinoic acid exposure. It is suggested that the RA-NTA framework may provide a general tool to define mechanistic pathways and biomarkers of developmental toxicity that may be used in alternative in vitro assays for the detection of embryotoxic compounds. PMID:25461899

  9. Late childbearing and changing risks of adverse birth outcomes in Korea.

    PubMed

    Cho, Youngtae; Hummer, Robert A; Choi, Yoon-Jung; Jung, Sung Won

    2011-05-01

    This study aimed to examine whether the relative importance of maternal age as a correlate of adverse birth outcomes has changed and to investigate if social inequalities in birth outcomes have widened during the past decade when the marriage and fertility related social environment has undergone tremendous change in Korea. Probabilities of adverse birth outcomes (prematurity and intrauterine growth retardation [IUGR]) were estimated with multinomial logistic regression models, utilizing the Korean birth registration data of 1995 and 2005. The main effects of maternal age and parental socioeconomic characteristics were compared between two study years, net of infant sex, birth order, and plurality. The association between maternal age and adverse birth outcomes, relative to the maternal and parental social characteristics, has clearly diminished between 1995 and 2005. During this period, differences in prematurity and IUGR by maternal age have also diminished, while those by parental social characteristics, particularly maternal education, have substantially widened. The intensified overall socioeconomic polarization since the economic crisis of the late 1990s is most likely responsible for the increased social inequality in adverse birth outcomes in Korea. A massive structural change in macro-economic conditions and culture during the study period may have modified the relationship between maternal age and birth outcomes. PMID:20432060

  10. Environmental factors and developmental outcomes in the lung.

    PubMed

    Kajekar, Radhika

    2007-05-01

    The developing lung is highly susceptible to damage from exposure to environmental toxicants particularly due to the protracted maturation of the respiratory system, extending from the embryonic phase of development in utero through to adolescence. The functional organization of the lungs requires a coordinated ontogeny of critical developmental processes that include branching morphogenesis, cellular differentiation and proliferation, alveolarization, and maturation of the pulmonary immune, vasculature, and neural systems. Therefore, exposure to environmental pollutants during crucial periods of prenatal and/or postnatal development may determine the course of lung morphogenesis and maturation. Depending on the timing of exposure and pathobiological response of the affected tissue, exposure to environmental pollutants can potentially result in long-term alterations that affect the structure and function of the respiratory system. Besides an immature respiratory system at birth, children possess unique differences in their physiology and behavioral characteristics compared to adults that are believed to augment the vulnerability of their developing lungs to perturbations by environmental toxins. Furthermore, an interaction between genetic predisposition and increased opportunity for exposure to chemical and infectious disease increase the hazards and risks for infants and children. In this article, the evidence for perturbations of lung developmental processes by key ambient pollutants (environmental tobacco smoke [ETS], ozone, and particulate matter [PM]) are discussed in terms of biological factors that are intrinsic to infants and children and that influence exposure-related lung development and respiratory outcomes. PMID:17408750

  11. Trajectories of Physical Discipline: Early Childhood Antecedents and Developmental Outcomes

    PubMed Central

    Lansford, Jennifer E.; Criss, Michael M.; Dodge, Kenneth A.; Shaw, Daniel S.; Pettit, Gregory S.; Bates, John E.

    2009-01-01

    This study examined childhood antecedents and developmental outcomes associated with trajectories of mild and harsh parental physical discipline. Interview, questionnaire, and observational data were available from 499 children followed from age 5 to 16 and from 258 children in an independent sample followed from age 5 to 15. Analyses indicated distinct physical discipline trajectory groups that varied in frequency of physical discipline and rate of change. In both samples, family ecological disadvantage differentiated the trajectory groups; in the first sample, early child externalizing also differentiated the groups. Controlling for early childhood externalizing, the minimal/ceasing trajectory groups were associated with the lowest levels of subsequent adolescent antisocial behavior in both samples and with parent-adolescent positive relationship quality in the second sample. PMID:19765007

  12. Developmental outcome of infants with grade III intraventricular hemorrhage

    SciTech Connect

    Naulty, C.M.; Gaiter, J.L.; Chang, C.S.; Eng, G.D.; Murray, S.L.; Reutter, S.; Horn, S.L.

    1983-02-01

    To determine the developmental outcome of premature infants weighing 1,750 gm or less at birth and who had grade III intraventricular hemorrhage (IVH), we followed up ten infants with IVH confirmed by computed tomography (CT) and ten CT-negative control infants until they were 12 months corrected age. The infants were evaluated at three-month intervals with neurologic examinations; hearing, speech, and language assessments; Bayley testing; and evoked response studies. Normal criteria were defined in each area. Eight of ten grade III IVH survivors had identifiable defects, with a predominance of motor deficits, as assessed by two or more parameters. Only three of the ten patients without IVH had two or more suspicious or abnormal assessments. Infants with grade III IVH may have widespread damage. Use of CT in these infants has permitted early diagnosis, with accurate assessment of the severity of the hemorrhage and prompt neurosurgical treatment.

  13. Developmental Disabilities and Socioeconomic Outcomes in Young Adulthood

    PubMed Central

    Wehby, George L.; Halpern, Carolyn T.

    2015-01-01

    Objective We assessed the associations between developmental disabilities and indicators of socioeconomic outcomes (i.e., educational attainment, employment status, occupation type, subjective perception of socioeconomic status [SES], income, and wage rate) among young U.S. adults aged 24–33 years. Methods We used data from the National Longitudinal Study of Adolescent Health (n=13,040), a nationally representative study of U.S. adolescents in grades 7–12 during the 1994–1995 school year. Young adult outcomes (i.e., educational attainment, employment status, income, occupation, and subjective SES) were measured in Wave IV (2008 for those aged 24–33 years). Multivariate methods controlled for sociodemographic characteristics and other relevant variables. Results Nearly 12% of this sample presented with a physical or cognitive disability. Respondents with physical disabilities had lower educational attainment (odds ratio [OR] = 0.69, 95% confidence interval [CI] 0.57, 0.85) and ranked themselves in lower positions on the subjective SES ladder (OR=0.71, 95% CI 0.57, 0.87) than those without a physical disability. Compared with individuals without disabilities, young adults with a cognitive disability also had lower educational attainment (OR=0.41, 95% CI 0.33, 0.52) and, when employed, were less likely to have a professional/managerial occupation (OR=0.50, 95% CI 0.39, 0.64). Young adults with disabilities also earned less annually (–$10,419.05, 95% CI –$4,954.79, –$5,883.37) and hourly (–$5.38, 95% CI –$7.64, –$3.12) than their non-disabled counterparts. Conclusion This study highlights the importance of considering multiple developmental experiences that may contribute to learning and work achievements through the transition from adolescence to young adulthood. PMID:25931625

  14. Emergency Department Discharge Diagnosis and Adverse Health Outcomes in Older Adults

    PubMed Central

    Hastings, S. Nicole; Whitson, Heather E.; Purser, Jama L.; Sloane, Richard J.; Johnson, Kimberly S.

    2010-01-01

    Objectives To determine the relationship between the reason for an emergency department (ED) visit and subsequent risk of adverse health outcomes in older adults discharged from the ED. Design Secondary analysis of data from the Medicare Current Beneficiary Survey. Setting ED. Participants One thousand eight hundred fifty-one community-dwelling Medicare fee-for-service enrollees aged 65 and older discharged from the ED between January 2000 and September 2002. Measurements Independent variables were ED discharge diagnosis groups: injury or musculoskeletal (MSK) (e.g., fracture, open wound), chronic condition (e.g., chronic obstructive pulmonary disorder, heart failure), infection, non-MSK symptom (e.g., chest pain, abdominal pain), and unclassified. Adverse health outcomes were hospitalization or death within 30 days of the index ED visit. Results Injury or MSK was the largest ED diagnosis group (31.4%), followed by non-MSK symptom (22.2%), chronic condition (20.9%), and infection (7.8%); 338 (17.8%) had ED discharge diagnoses that were unclassified. In adjusted analyses, a discharge diagnosis of injury or MSK condition was associated with lower risk of subsequent adverse health outcomes (hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.50–0.96) than for all other diagnosis groups. Patients seen in the ED for chronic conditions were at greater risk of adverse outcomes (HR = 1.86, 95% CI = 1.37–2.52) than all others. There were no significant differences in risk between patients with infections, those with non-MSK symptoms, and the unclassified group. Conclusion Adverse health outcomes were common in older patients with an ED discharge diagnosis classified as a chronic condition. ED discharge diagnosis may improve risk assessment and inform the development of targeted interventions to reduce adverse health outcomes in older adults discharged from the ED. PMID:19694872

  15. Developmental outcomes of newborn encephalopathy in the term infant.

    PubMed

    Badawi, N; Keogh, J M; Dixon, G; Kurinczuk, J J

    2001-06-01

    Newborn encephalopathy is a clinically defined condition of abnormal neurological behaviours in the newborn period. Though most cases have their origin in the preconceptional and antepartum period, newborn encephalopathy represents a crucial link between intrapartum events and permanent neurological problems in the child. The birth prevalence of newborn encephalopathy ranges from 1.8 to 7.7 per 1000 term live births according to the definition used and the population to which it is applied. Few studies have investigated the outcomes of newborn encephalopathy other than for cases solely attributed to intrapartum hypoxia. These adverse outcomes range from death to cerebral palsy, intellectual disability, and less severe neurological disabilities such as learning and behavioural problems. Outcomes following newborn encephalopathy may vary from country to country with 9.1% of affected babies dying in the newborn period in Western Australia and 10.1% manifesting cerebral palsy by the age of two. These compare to a case fatality of 30.5% in Kathmandu and a cerebral palsy rate of 14.5% by one year of age. The study by Robertson et al which followed children with hypoxic ischaemic encephalopathy found an incidence of impairment of 16% among survivors assessed at 8 years with 42% requiring school resource room help or special classes. This review emphasises the great need for comprehensive clinical and educational assessment as these infants approach school entry to enable appropriate educational provisions to be made. PMID:11450384

  16. Does Developmental Education Improve Labor Market Outcomes? Evidence from Two States. A CAPSEE Working Paper

    ERIC Educational Resources Information Center

    Hodara, Michelle; Xu, Di

    2014-01-01

    Nationally, about two thirds of community college students are referred to developmental education. Thus far, research on the effectiveness of developmental education has focused on students' academic outcomes; in this paper, we examine the economic consequences of developmental education for students. Using longitudinal student-unit record data…

  17. Behavior Problems in Toddlers with and without Developmental Delays: Comparison of Treatment Outcomes

    ERIC Educational Resources Information Center

    Holtz, Casey A.; Carrasco, Jennifer M.; Mattek, Ryan J.; Fox, Robert A.

    2009-01-01

    The purpose of this study is to examine the effectiveness of an in-home parent management program for toddlers with behavior problems and developmental delays by comparing outcomes for a group of toddlers with developmental delays (n = 27) and a group of toddlers without developmental delays (n = 27). The majority of children lived in single…

  18. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals. PMID:26465197

  19. Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

    USGS Publications Warehouse

    Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

    2015-01-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  20. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes.

    PubMed

    Dugoff, Lorraine

    2010-05-01

    Maternal serum levels of the first- and second-trimester markers for aneuploidy have been shown to be associated with adverse obstetric outcomes in the absence of aneuploidy or neural-tube defects. The likelihood of an adverse obstetric outcome increases as the values of the marker become more extreme, and as the number of abnormal markers increases. Although many of the associations between maternal serum markers for aneuploidy and adverse obstetric outcomes are statistically significant, the sensitivity and positive predictive values for the individual outcomes are too low for them to be clinically useful as screening tests. Currently in the United States there is not a uniformly accepted practice for the care of women with abnormal maternal serum markers regarding risk of future obstetric complications. There are no randomized trials assessing any type of intervention or treatment for patients with abnormal serum markers. Various strategies to manage patients with unexplained abnormal serum markers have been proposed. This article reviews the relationships between these markers and adverse obstetric outcomes. In addition, potential management strategies and future areas of research are discussed. PMID:20410782

  1. Virtual Tissue Models in Developmental Toxicity Research

    EPA Science Inventory

    Prenatal exposure to drugs and chemicals may perturb, directly or indirectly, core developmental processes in the embryo (patterning, morphogenesis, proliferation and apoptosis, and cell differentiation), leading to adverse developmental outcomes. Because embryogenesis entails a...

  2. 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...

  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. 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...

  5. 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...

  6. Population Attributable Risk Fractions of Maternal Overweight and Obesity for Adverse Perinatal Outcomes.

    PubMed

    MacInnis, Natasha; Woolcott, Christy G; McDonald, Sarah; Kuhle, Stefan

    2016-01-01

    The objective of the current study was to determine the proportion of adverse perinatal outcomes that could be potentially prevented if maternal obesity were to be reduced or eliminated (population attributable risk fractions, PARF); and the number needed to treat (NNT) of overweight or obese women to prevent one case of adverse perinatal outcome. Data from the Atlee Perinatal Database on 66,689 singleton infants born in Nova Scotia, Canada, between 2004 and 2014, and their mothers were used. Multivariable-adjusted PARFs and NNTs of maternal pre-pregnancy weight status were determined for various perinatal outcomes under three scenarios: If all overweight and obese women were to i) become normal weight before pregnancy; ii) shift down one weight class; or iii) lose 10% of their body weight, significant relative reductions would be seen for gestational diabetes mellitus (GDM, 57/33/15%), hypertensive disorders of pregnancy (HDP, 26/16/6%), caesarean section (CS, 18/10/3%), and large for gestational age births (LGA, 24/14/3%). The NNT were lowest for the outcomes GDM, induction of labour, CS, and LGA, where they ranged from 13 to 73. The study suggests that a substantial proportion of adverse perinatal outcomes may be preventable through reductions in maternal pre-pregnancy weight. PMID:26961675

  7. Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

    PubMed Central

    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 from a prospective longitudinal study of prenatal substance exposure (N = 860). Cortisol reactivity was assessed at age 11. Among African-Americans, prenatal substance exposure exerted an indirect effect through early adversity and cortisol reactivity to predict externalizing behavior, delinquency, and a positive student-teacher relationship at age 11. Decreased cortisol reactivity was related to maladaptive outcomes, and increased cortisol reactivity predicted better executive functioning and a more positive student-teacher relationship. PMID:25376131

  8. Understanding the Association of Biomedical, Psychosocial and Behavioral Risks with Adverse Pregnancy Outcomes

    PubMed Central

    Kiely, Michele; El-Mohandes, Ayman A.E.; Gantz, Marie G.; Chowdhury, Dhuly; Thornberry, Jutta S.; El-Khorazaty, M. Nabil

    2011-01-01

    Objectives This study investigates the relationship between diabetes, hypertension, preeclampsia, and Body Mass Index (BMI) -- the most common and interrelated medical conditions occurring during pregnancy; sociodemographic and behavioral risk factors; and adverse pregnancy outcomes in high-risk urban African American women in Washington, DC. Methods Data are from a randomized controlled trial conducted in 6 prenatal clinics. Women in their 1st or 2nd trimester were screened for behavioral risks (smoking, environmental tobacco smoke exposure, depression, and intimate partner violence) and demographic eligibility. 1,044 were eligible, interviewed and followed through their pregnancies. Classification and Regression Trees (CART) methodology was used to: 1) explore the relationship between medical and behavioral risks (reported at enrollment), sociodemographic factors and pregnancy outcomes, 2) identify the relative importance of various predictors of adverse pregnancy outcomes, and 3) characterize women at the highest risk of poor pregnancy outcomes. Results Overall, the strongest predictors of poor outcomes were prepregnancy BMI, preconceptional diabetes, employment status, intimate partner violence, and depression. In CART analysis, preeclampsia was the first splitter for low birthweight; preconceptional diabetes was the first splitter for preterm birth (PTB) and neonatal intensive care admission; BMI was the first splitter for very PTB, large for gestational age, Cesarean section and perinatal death; and employment was the first splitter for miscarriage. Conclusions Preconceptional factors play a very important role in pregnancy outcomes. For many of these women, the risks that they bring into the pregnancy were more likely to impact their pregnancy outcome than events during pregnancy. PMID:21785892

  9. Use of harsh physical discipline and developmental outcomes in adolescence.

    PubMed

    Bender, Heather L; Allen, Joseph P; McElhaney, Kathleen Boykin; Antonishak, Jill; Moore, Cynthia M; Kelly, Heather O'Beirne; Davis, Steven M

    2007-01-01

    A history of exposure to harsh physical discipline has been linked to negative outcomes for children, ranging from conduct disorder to depression and low self-esteem. The present study extends this work into adolescence, and examines the relationship of lifetime histories of harsh discipline to adolescents' internalizing and externalizing symptoms and to their developing capacities for establishing autonomy and relatedness in family interactions. Adolescent and parent reports of harsh discipline, independently coded observations of conflictual interactions, and adolescent reports of symptoms were obtained for 141 adolescents at age 16. Both parents' use of harsh discipline was related to greater adolescent depression and externalizing behavior, even when these effects were examined over and above the effects of other parenting measures known to account for these symptoms. Adolescents exposed to harsh discipline from mothers were also less likely to appear warm and engaged during an interaction task with their mothers. It is suggested that a history of harsh discipline is associated not only with social and emotional functioning, but also with the developmental task of autonomy and relatedness. PMID:17241492

  10. Use of harsh physical discipline and developmental outcomes in adolescence

    PubMed Central

    BENDER, HEATHER L.; ALLEN, JOSEPH P.; McELHANEY, KATHLEEN BOYKIN; ANTONISHAK, JILL; MOORE, CYNTHIA M.; KELLY, HEATHER O’BEIRNE; DAVIS, STEVEN M.

    2012-01-01

    A history of exposure to harsh physical discipline has been linked to negative outcomes for children, ranging from conduct disorder to depression and low self-esteem. The present study extends this work into adolescence, and examines the relationship of lifetime histories of harsh discipline to adolescents’ internalizing and externalizing symptoms and to their developing capacities for establishing autonomy and relatedness in family interactions. Adolescent and parent reports of harsh discipline, independently coded observations of conflictual interactions, and adolescent reports of symptoms were obtained for 141 adolescents at age 16. Both parents’ use of harsh discipline was related to greater adolescent depression and externalizing behavior, even when these effects were examined over and above the effects of other parenting measures known to account for these symptoms. Adolescents exposed to harsh discipline from mothers were also less likely to appear warm and engaged during an interaction task with their mothers. It is suggested that a history of harsh discipline is associated not only with social and emotional functioning, but also with the developmental task of autonomy and relatedness. PMID:17241492

  11. 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...

  12. Are Women With Uterine Fibroids at Increased Risk for Adverse Pregnancy Outcome?

    PubMed

    Ezzedine, Dima; Norwitz, Errol R

    2016-03-01

    Uterine fibroids (leiomyomas) are common in reproductive age women. Most women with fibroids have uneventful pregnancies. The most common complication is painful degeneration. Are fibroids associated with adverse pregnancy outcomes? If so, can we predict which fibroids are most likely to cause complications? And is there anything that can be done to prevent these complications, such as performing a myomectomy before pregnancy? Here we review the published literature looking at the impact of uterine fibroids on adverse pregnancy events, such as miscarriage, preterm labor, placental abruption, fetal growth restriction, and fetal malpresentation. A series of clinical recommendations for the management of pregnancy in women with uterine fibroids are included. PMID:26670833

  13. Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis

    PubMed Central

    Awadzi, Kwablah

    2003-01-01

    Ivermectin (Mectizan®) is the only drug currently recommended for the treatment and control of onchocerciasis. Serious adverse events rarely occur during treatment, except in subjects heavily infected with Loa Loa. This review of drug-related serious adverse events in the treatment of onchocerciasis therefore revisited the pre-Mectizan® reference drugs, DEC and suramin, and other candidate drugs studied extensively for the treatment of human onchocerciasis. The benzimidazole carbamate derivatives and the antibiotic doxycycline were excluded, since no serious adverse events have been reported regarding their use. Using recommended definitions, serious adverse events reported or observed after the use of each drug were summarised, the level of attribution determined, and the results tabulated. Prominence was given to treatment-related deaths. The clinical picture of severe symptomatic postural hypotension is described and used to illustrate the difference between the severity and the seriousness of an adverse event. The epidemiology, management and outcome of serious adverse events are presented. The role of future research is discussed. PMID:14975063

  14. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  15. 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

  16. Risk for Gestational Diabetes Mellitus and Adverse Birth Outcomes in Chinese Women with Polycystic Ovary Syndrome

    PubMed Central

    Xiao, Qing; Cui, Yong-Yi; Lu, Jine; Zhang, Guo-Zheng

    2016-01-01

    Objective. To examine the association of polycystic ovary syndrome (PCOS) in early pregnancy with gestational diabetes mellitus (GDM) and adverse birth outcomes. Methods. In this retrospective cohort study including 2389 pregnant women, the medical records of 352 women diagnosed with PCOS were evaluated. Outcomes included GDM, preterm birth, low birth weight, macrosomia, and being small and large for gestational age. Multivariable logistic regression models were used to examine the association of the risk for GDM and adverse birth outcomes with PCOS after adjusting for confounders. Results. Women previously diagnosed with PCOS had a higher risk of GDM (adjusted odds ratio [OR] 1.55, 95% confidence interval [CI]: 1.14–2.09). A strong association was seen between PCOS and preterm birth (adjusted OR 1.69, 95% CI: 1.08–2.67). On stratified analysis, the adjusted OR for GDM among women with PCOS undergoing assisted reproductive technology was 1.44 (95% CI: 1.03–1.92) and among women with PCOS who conceived spontaneously was 1.60 (1.18–2.15). No increased risk for other adverse birth outcomes was observed. Conclusions. Women with PCOS were more likely to experience GDM and preterm birth. PMID:27066074

  17. 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. PMID:26229389

  18. 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...

  19. Adverse Pregnancy Outcomes: Opportunity for Analysis of Biospecimens and Co-development of Prognostics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pregnancy and Perinatology Branch seeks partners interested in collaborative research to: (i) evaluate data and samples taken from women for potential biomarkers indicative for adverse pregnancy outcomes and (ii) co-develop diagnostic kits useful as predictors of adverse pregnancy outcomes.

  20. Baby on board: do responses to stress in the maternal brain mediate adverse pregnancy outcome?

    PubMed

    Douglas, Alison J

    2010-07-01

    Stress and adverse environmental surroundings result in suboptimal conditions in a pregnant mother such that she may experience poor pregnancy outcome including complete pregnancy failure and preterm labor. Furthermore her developing baby is at risk of adverse programming, which confers susceptibility to long term ill health. While some mechanisms at the feto-maternal interface underlying these conditions are understood, the underlying cause for their adverse adaptation is often not clear. Progesterone plays a key role at many levels, including control of neuroendocrine responses to stress, procuring the required immune balance and controlling placental and decidual function, and lack of progesterone can explain many of the unwanted consequences of stress. How stress that is perceived by the mother inhibits progesterone secretion and action is beginning to be investigated. This overview of maternal neuroendocrine responses to stress throughout pregnancy analyses how they interact to compromise progesterone secretion and precipitate undesirable effects in mother and offspring. PMID:20546772

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

    SciTech Connect

    Peterson, David; Truong, Pauline T.; Parpia, Sameer; Olivotto, Ivo A.; Berrang, Tanya; Kim, Do-Hoon; Kong, Iwa; Germain, Isabelle; Nichol, Alan; Akra, Mohamed; Roy, Isabelle; Reed, Melanie; Fyles, Anthony; Trotter, Theresa; Perera, Francisco; Balkwill, Susan; Lavertu, Sophie; Elliott, Elizabeth; and others

    2015-04-01

    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 assess 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-dose treatment

  2. Regional White Matter Development in Very Preterm Infants: Perinatal Predictors and Early Developmental Outcomes

    PubMed Central

    Rogers, Cynthia E.; Smyser, Tara; Smyser, Christopher D.; Shimony, Joshua; Inder, Terrie E.; Neil, Jeffrey J.

    2015-01-01

    Background Preterm infants are at risk for white matter injury and adverse neurodevelopmental outcomes. Methods Serial diffusion tensor MRI data were obtained from very preterm infants (N=78) born <30 weeks gestation imaged up to four times from 26-42 weeks postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N=50). Sixty-five children underwent neurodevelopmental testing at age two years. Results FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with PDA had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At age 2 years, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent. Better social-emotional competence was related to lower FA in the left cingulum bundle. Conclusion This study demonstrates regional variability in the susceptibility/sensitivity of white matter maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates. PMID:26372513

  3. Adverse Outcome Pathways as Tools to Assess Drug-Induced Toxicity.

    PubMed

    Vinken, Mathieu

    2016-01-01

    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 toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of key events connected by key event relationships, and an adverse outcome. Development and evaluation of AOPs ideally complies with guidelines issued by the Organization for Economic Cooperation and Development. AOP frameworks have yet been proposed for major types of drug-induced injury, especially in the liver, including steatosis, fibrosis, and cholestasis. These newly postulated AOPs can serve a number of purposes pertinent to safety assessment of drugs, in particular the establishment of quantitative structure-activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies. PMID:27311472

  4. Adverse reproductive outcomes in families of atomic veterans: The feasibility of epidemiologic studies

    SciTech Connect

    1995-12-31

    This is an outstanding report from a distinguished academy committee, which in 71 pages of text provides the scientific basis for the carefully crafted 8-page executive summary. The principles and issues of the required epidemiological study are presented calmly and concisely, as are the ensuing short chapters on radiation biology, genetics and risk estimation, and all other adverse reproductive outcomes. The committee was mandated by Congress to determine the feasibility, cost and duration of a study on adverse reproductive outcomes in families of atomic veteran. The committee found that a scientifically adequate and epidemiologically valid study could not be mounted and the cost would be tens of millions of dollars lasting a decade. The Committee presents a number of well-discussed approaches in support of their position.

  5. Sleep and Developmental Disabilities: Assessment, Treatment, and Outcome Measures

    ERIC Educational Resources Information Center

    Doran, Scott M.; Harvey, Mark T.; Horner, Robert H.

    2006-01-01

    People with developmental disabilities sleep less and experience higher incidence of clinical sleep disorders than the general population. Exploring the neurophysiology linking sleep with daytime performance in patients with developmental disabilities is now possible using minimally sufficient sleep and sleep-sensitive behavioral assays. Although…

  6. Three Accelerated Developmental Education Programs: Features, Student Outcomes, and Implications

    ERIC Educational Resources Information Center

    Jaggars, Shanna Smith; Hodara, Michelle; Cho, Sung-Woo; Xu, Di

    2015-01-01

    To support the long-term success of underprepared students, many community colleges are experimenting with accelerated developmental education models, which allow students to complete remediation and enroll in college-level math and English within a shorter time frame. This study examines three developmental acceleration programs, including two in…

  7. What We Know about Developmental Education Outcomes. Research Overview

    ERIC Educational Resources Information Center

    Jaggars, Shanna Smith; Stacey, Georgia West

    2014-01-01

    Many recent high school graduates who enter community college are required to take remedial or developmental education courses before enrolling in college-level courses. Developmental courses essentially reteach high school- and junior high school-level content in reading, writing, and math. In some cases, students are referred to two or even…

  8. Transitioning Youth with Intellectual and Other Developmental Disabilities: Predicting Community Employment Outcomes

    ERIC Educational Resources Information Center

    Simonsen, Monica L.; Neubert, Debra A.

    2013-01-01

    Community employment outcomes were examined for 338 transitioning youth with intellectual and other developmental disabilities in one state 18 months after exiting public school. All transitioning youth received ongoing Developmental Disability agency funding. The majority of transitioning youth (57.1%) were engaged in sheltered or nonwork…

  9. Student Outcomes in Developmental Education, 1994-95 through 1999-2000. Preliminary Report.

    ERIC Educational Resources Information Center

    Germanna Community Coll., Locust Grove, VA.

    This report documents student outcomes in developmental English and mathematics courses at Germanna Community College (Virginia) for the academic years 1994-95 through 1999-2000. It provides data to answer three questions: What proportion of students enroll in developmental courses? What is the success rate for students enrolled in developmental…

  10. Microenterprise Options for People with Intellectual and Developmental Disabilities: An Outcome Evaluation

    ERIC Educational Resources Information Center

    Conroy, James W.; Ferris, Charles S.; Irvine, Ron

    2010-01-01

    Opportunities for community employment of people with intellectual and developmental disabilities are limited, and have not improved over the past quarter century of interest and effort. This report provides the findings from an outcome study of this issue. Twenty-seven people with intellectual and developmental disability, residents in Kent…

  11. Vitamin D Deficiency Strongly Predicts Adverse Medical Outcome Across Different Medical Inpatient Populations

    PubMed Central

    Graedel, Lena; Merker, Meret; Felder, Susan; Kutz, Alexander; Haubitz, Sebastian; Faessler, Lukas; Kaeslin, Martha; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

    2016-01-01

    Abstract Vitamin D deficiency has been associated with several adverse outcomes mainly in the outpatient setting. The objective of this study was to examine the prevalence of vitamin D deficiency and its association with risk of adverse clinical outcomes in a large prospective cohort of medical inpatients. We collected clinical data and measured 25(OH)D levels in adult medical patients upon hospital admission and followed them for 30 days. Regression analyses adjusted for age, gender, comorbidities, and main medical diagnosis were performed to study the effect of vitamin D deficiency on several hospital outcomes. Of 4257 included patients, 1510 (35.47%) had 25(OH)D levels of 25 to 50 nmol/L (vitamin D insufficiency) and 797 (18.72%) had levels of <25nmol/L (severe deficiency). Vitamin D insufficiency and severe deficiency were associated (OR/HR, 95%CI) with an increased risk of 30-day mortality (OR 1.70, 1.22–2.36 and 2.70, 1.22–2.36) and increased length of stay (HR 0.88, 0.81–0.97 and 0.72, 0.65–0.81). Severe deficiency was associated with risk of falls (OR 1.77, 1.18–2.63), impaired Barthel index (OR 1.80, 1.42–2.28), and impairment in quality of life. Most associations remained robust after multivariate adjustment and in subgroups stratified by gender, age, comorbidities, and main diagnoses (P for interaction >0.05). In this comprehensive and large medical inpatient cohort, vitamin D deficiency was highly prevalent and strongly associated with adverse clinical outcome. Interventional research is urgently needed to prove the effect of vitamin D supplementation on these outcomes. PMID:27175650

  12. Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia

    PubMed Central

    Palomaki, Glenn E; Haddow, James E; Haddow, Hamish R M; Salahuddin, Saira; Geahchan, Carl; Cerdeira, Ana Sofia; Verlohren, Stefan; Perschel, Frank H; Horowitz, Gary; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2015-01-01

    Introduction Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. Methods Women evaluated for suspected PE at a tertiary hospital (2009–2012) had pregnancy outcomes categorized as ‘referent’ or ‘severe’, based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered ‘unclassified’. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. Results Three hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2–58) and 15 (95% CI 5.8–40) fold, respectively. Conclusions This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:25641027

  13. Prediction of adverse outcomes of acute coronary syndrome using intelligent fusion of triage information with HUMINT

    NASA Astrophysics Data System (ADS)

    McCullough, Claire L.; Novobilski, Andrew J.; Fesmire, Francis M.

    2006-04-01

    Faculty from the University of Tennessee at Chattanooga and the University of Tennessee College of Medicine, Chattanooga Unit, have used data mining techniques and neural networks to examine a set of fourteen features, data items, and HUMINT assessments for 2,148 emergency room patients with symptoms possibly indicative of Acute Coronary Syndrome. Specifically, the authors have generated Bayesian networks describing linkages and causality in the data, and have compared them with neural networks. The data includes objective information routinely collected during triage and the physician's initial case assessment, a HUMINT appraisal. Both the neural network and the Bayesian network were used to fuse the disparate types of information with the goal of forecasting thirty-day adverse patient outcome. This paper presents details of the methods of data fusion including both the data mining techniques and the neural network. Results are compared using Receiver Operating Characteristic curves describing the outcomes of both methods, both using only objective features and including the subjective physician's assessment. While preliminary, the results of this continuing study are significant both from the perspective of potential use of the intelligent fusion of biomedical informatics to aid the physician in prescribing treatment necessary to prevent serious adverse outcome from ACS and as a model of fusion of objective data with subjective HUMINT assessment. Possible future work includes extension of successfully demonstrated intelligent fusion methods to other medical applications, and use of decision level fusion to combine results from data mining and neural net approaches for even more accurate outcome prediction.

  14. Maternal Ethnic Ancestry and Adverse Perinatal Outcomes in New York City

    PubMed Central

    Stein, Cheryl R.; Savitz, David A.; Janevic, Teresa; Ananth, Cande V.; Kaufman, Jay S.; Herring, Amy H.; Engel, Stephanie M.

    2009-01-01

    Objective To examine the association between narrowly defined subsets of maternal ethnicity and birth outcomes. Study Design Analysis of 1995-2003 New York City birth certificates linked to hospital discharge data for 949,210 singleton births to examine the multivariable associations between maternal ethnicity and preterm birth, subsets of spontaneous and medically indicated preterm birth, term small for gestational age (SGA), and term birthweight. Results Compared to non-Hispanic whites, Puerto Ricans had an elevated odds ratio (OR 1.9, 95% CI 1.9-2.0) for delivering at 32-36 weeks (adjusted for nativity, maternal age, parity, education, tobacco use, pre-pregnancy weight, birth year). We found an excess of adverse outcomes among most Latino groups. Outcomes also varied within regions, with North African infants nearly 100g (adjusted) heavier than sub-Saharan Africans. Conclusions The considerable heterogeneity in risk of adverse perinatal outcomes is obscured in broad categorizations of maternal race/ethnicity, and may help to formulate etiologic hypotheses. PMID:19729145

  15. The Violence Proneness Scale of the DUSI-R predicts adverse outcomes associated with substance abuse.

    PubMed

    Kirisci, Levent; Tarter, Ralph; Reynolds, Maureen

    2009-01-01

    Accuracy of the Violence Proneness Scale (VPS) of the Drug Use Screening Inventory (DUSI-R) was evaluated in 328 boys for predicting use of illegal drugs, DUI, selling drugs, sexually transmitted disease, car accident while under acute effects of drugs/alcohol, trading drugs for sex, injuries from a fight, and traumatic head injury. Boys were prospectively tracked from age 16 to 19 at which time these outcomes were documented in the interim period. The results demonstrated that the VPS score is a significant predictor of all outcomes. Prediction accuracy ranged between 62%-83%. These findings suggest that the VPS may be useful for identifying youths who are at high risk for using illicit drugs and commonly associated adverse outcomes. PMID:19283571

  16. Parental drinking and adverse outcomes in children: A scoping review of cohort studies

    PubMed Central

    Felix, Lambert; Keating, Patrick; McCambridge, Jim

    2015-01-01

    Abstract Introduction and Aims There is a growing interest in measuring alcohol's harms to people other than the drinker themselves. ‘Children of alcoholics’ and foetal alcohol spectrum disorder have received widespread attention. Less is known about how children are affected by post‐natal exposure to parental drinking other than alcohol abuse/dependence. In this scoping review, we aim to assemble and map existing evidence from cohort studies on the consequences of parental alcohol use for children, and to identify limitations and gaps in this literature. Design and Methods Systematic review methods were used. Electronic databases were searched (1980 to October 2013) and a total of 3215 abstracts were screened, 326 full text papers examined and 99 eligible for inclusion according to selection criteria including separation of exposure and outcome measurement in time and report of a quantitative effect size. Results The main finding is the large literature available. Adolescent drinking behaviour was the most common outcome measure and outcomes other than substance use were rarely analysed. In almost two of every three published associations, parental drinking was found to be statistically significantly associated with a child harm outcome measure. Several limitations in the literature are noted regarding its potential to address a possible causal role of parental drinking in children's adverse outcomes. Discussion and Conclusions This study identifies targets for further study and provides a platform for more targeted analytic investigations which ascertain risk of bias, and which are capable of considering the appropriateness of causal inferences for the observed associations. [Rossow I, Felix L, Keating P, McCambridge J. Parental drinking and adverse outcomes in children: A scoping review of cohort studies. Drug Alcohol Rev 2016;35:397–405] PMID:26332090

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

    PubMed Central

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

    2016-01-01

    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. PMID:26694041

  18. 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. PMID:26694041

  19. Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes

    PubMed Central

    Maccani, Jennifer Z.J.; Koestler, Devin C.; Lester, Barry; Houseman, E. Andrés; Armstrong, David A.; Kelsey, Karl T.

    2015-01-01

    Background Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly. Objectives We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes. Methods The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants. Results We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants’ placentas. Methylation at these loci was moderately correlated (correlation coefficients range, –0.33 to –0.45) with EMID2 expression. Conclusions EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes. Citation Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ. 2015. Placental DNA methylation related to both infant toenail mercury and adverse neurobehavioral outcomes. Environ Health Perspect 123:723–729; http://dx.doi.org/10.1289/ehp.1408561 PMID:25748564

  20. Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease

    PubMed Central

    Crispo, James A. G.; Willis, Allison W.; Thibault, Dylan P.; Fortin, Yannick; Hays, Harlen D.; McNair, Douglas S.; Bjerre, Lise M.; Kohen, Dafna E.; Perez-Lloret, Santiago; Mattison, Donald R.; Krewski, Daniel

    2016-01-01

    Background Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population. Methods Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits. Results Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge. Conclusions We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD. PMID:26939130

  1. Intimate partner violence, substance use, and adverse neonatal outcomes among urban women

    PubMed Central

    Alhusen, Jeanne L.; Lucea, Marguerite B.; Bullock, Linda; Sharps, Phyllis

    2013-01-01

    Objective To assess the prevalence of intimate partner violence, substance use, and their co-occurrence during pregnancy and examines their associations with adverse neonatal outcomes. Study design Between February 2009 and February 2010, pregnant women receiving obstetrical care at three urban clinics were screened for intimate partner violence and substance use between 24-28 weeks gestation. A chart review was conducted upon delivery to assess for adverse neonatal outcomes of low birth weight (LBW), preterm birth, and small for gestational age (SGA). Results Maternal and neonatal data were collected on 166 mothers and their neonates. Overall, 19% of the sample reported intimate partner violence during their pregnancies. Of the study's neonates 41% had at least one adverse neonatal outcome. Nearly half of the mothers reported using at least one substance during pregnancy. Women experiencing intimate partner violence had a higher prevalence of marijuana use than their non-abused counterparts (p < 0.01). Experiencing intimate partner violence was associated with a fourfold increase in having a SGA neonate (aOR = 4.00; 95% CI 1.58 – 9.97). Women who reported marijuana use had five times the odds of having a neonate classified as SGA (aOR = 5.16, 95% CI 2.24 – 11.89) or LBW (aOR 5.00; 95% CI 1.98 – 12.65). Conclusions The prevalence of intimate partner violence during pregnancy and substance use is high in urban mothers, the risks of which extend to their neonates. Pediatric providers are urged to routinely screen for both issues and recognize the impact of co-occurrence of these risk factors on poor neonatal and childhood outcomes. PMID:23485028

  2. Revolutionizing Toxicity Testing For Predicting Developmental Outcomes (DNT4)

    EPA Science Inventory

    Characterizing risk from environmental chemical exposure currently requires extensive animal testing; however, alternative approaches are being researched to increase throughput of chemicals screened, decrease reliance on animal testing, and improve accuracy in predicting adverse...

  3. How Does the Fast Track Intervention Prevent Adverse Outcomes in Young Adulthood?

    PubMed

    Sorensen, Lucy C; Dodge, Kenneth A

    2016-03-01

    Numerous studies have shown that childhood interventions can foster improved outcomes in adulthood. Less well understood is precisely how-that is, through which developmental pathways-these interventions work. This study assesses mechanisms by which the Fast Track project (n = 891), a randomized intervention in the early 1990s for high-risk children in four communities (Durham, NC; Nashville, TN; rural PA; and Seattle, WA), reduced delinquency, arrests, and general and mental health service utilization in adolescence through young adulthood (ages 12-20). A decomposition of treatment effects indicates that about a third of Fast Track's impact on later crime outcomes can be accounted for by improvements in social and self-regulation skills during childhood (ages 6-11), such as prosocial behavior, emotion regulation, and problem solving. These skills proved less valuable for the prevention of general and mental health problems. PMID:26670938

  4. A relational framework for understanding bullying: Developmental antecedents and outcomes.

    PubMed

    Rodkin, Philip C; Espelage, Dorothy L; Hanish, Laura D

    2015-01-01

    This article reviews current research on the relational processes involved in peer bullying, considering developmental antecedents and long-term consequences. The following themes are highlighted: (a) aggression can be both adaptive and maladaptive, and this distinction has implications for bullies' functioning within peer social ecologies; (b) developmental antecedents and long-term consequences of bullying have not been well-distinguished from the extant research on aggressive behavior; (c) bullying is aggression that operates within relationships of power and abuse. Power asymmetry and repetition elements of traditional bullying definitions have been hard to operationalize, but without these specifications and more dyadic measurement approaches there may be little rationale for a distinct literature on bullying--separate from aggression. Applications of a relational approach to bullying are provided using gender as an example. Implications for future research are drawn from the study of relationships and interpersonal theories of developmental psychopathology. PMID:25961312

  5. Pivmecillinam and adverse birth and neonatal outcomes: a population-based cohort study.

    PubMed

    Vinther Skriver, Mette; Nørgaard, Mette; Pedersen, Lars; Carl Schønheyder, Henrik; Sørensen, Henrik Toft

    2004-01-01

    A previous study unexpectedly showed an increased, statistically imprecise, risk of low Apgar score in children of women redeeming prescriptions for pivmecillinam in late pregnancy. To improve statistical precision we extended the previous dataset with data for 5 more y, and in addition added more neonatal outcomes. We thus examined the risk of adverse birth and neonatal outcomes among pregnant users of pivmecillinam based on population-based registries in North Jutland County, Denmark. We included 63,659 women with a live birth, or stillbirth after the 28th week of gestation. 2031 had redeemed prescriptions for pivmecillinam any time during pregnancy, 559 in the first trimester and 371 within 28 d before delivery. Adjusted odds ratios were: birth defects 0.83 (95% confidence interval (95% CI) 0.53-1.32) for exposure during first trimester, preterm delivery 0.96 (95% CI 0.79-1.18) and low birth weight 0.79 (95% CI 0.52-1.20) for exposure any time during pregnancy, and stillbirth 1.19 (95% CI 0.30-4.80), low Apgar score 1.17 (95% CI 0.37-3.66), hypoglycaemia 1.03 (95% CI 0.53-2.00), and respiratory distress syndrome 0.79 (95% CI 0.38-1.68) for exposure within 28 d before delivery. Use of pivmecillinam during pregnancy did not appear to increase the risk of adverse birth and neonatal outcomes; however, statistical precision is still low. PMID:15513399

  6. Adverse Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model: The Influence of Aging.

    PubMed

    Huizer-Pajkos, Aniko; Kane, Alice E; Howlett, Susan E; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Le Couteur, David G; Hilmer, Sarah N

    2016-05-01

    We aimed to develop a mouse model of polypharmacy, primarily to establish whether short-term exposure to polypharmacy causes adverse geriatric outcomes. We also investigated whether old age increased susceptibility to any adverse geriatric outcomes of polypharmacy. Young (n= 10) and old (n= 21) male C57BL/6 mice were administered control diet or polypharmacy diet containing therapeutic doses of five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, and citalopram). Mice were assessed before and after the 2- to 4-week intervention. Over the intervention period, we observed no mortality and no change in food intake, body weight, or serum biochemistry in any age or treatment group. In old mice, polypharmacy caused significant declines in locomotor activity (pre minus postintervention values in control 2 ± 13 counts, polypharmacy 32 ± 7 counts,p< .05) and front paw wire holding impulse (control -2.45 ± 1.02 N s, polypharmacy +1.99 ± 1.19 N s,p< .05), loss of improvement in rotarod latency (control -59 ± 11 s, polypharmacy -1.7 ± 17 s,p< .05), and lowered blood pressure (control -0.2 ± 3 mmHg, polypharmacy 11 ± 4 mmHg,p< .05). In young mice, changes in outcomes over the intervention period did not differ between control and polypharmacy groups. This novel model of polypharmacy is feasible. Even short-term polypharmacy impairs mobility, balance, and strength in old male mice. PMID:25940962

  7. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients.

    PubMed

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-02-01

    Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477-3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277-0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  8. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients

    PubMed Central

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-01-01

    Abstract Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477–3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277–0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  9. Adolescent Alcohol Abuse and Adverse Adult Outcomes: Evaluating Confounds with Drinking-Discordant Twins

    PubMed Central

    Rose, Richard J.; Winter, Torsten; Viken, Richard J.; Kaprio, Jaakko

    2014-01-01

    Background Adolescent alcohol abuse is associated with adverse outcomes in early adulthood, but differences in familial status and structure and household and community environments correlate with both adolescent drinking and adverse adult outcomes and may explain their association. We studied drinking-discordant twin pairs to evaluate such confounds to ask: Will between-family associations replicate in within-family comparisons? Methods With longitudinal data from > 3,000 Finnish twins, we associated drinking problems at age 18½ with 13 outcomes assessed at age 25; included were sustained substance abuse, poor health, physical symptoms, early coital debut, multiple sexual partners, life dissatisfaction, truncated education, and financial problems. We assessed associations among twins as individuals with linear regression adjusted for correlated observations; within-family analyses of discordant twin pairs followed, comparing paired means for adult outcomes among co-twins discordant for adolescent problem drinking. Defining discordance by extreme scores on self-reported problem drinking at age 18½ permitted parallel analyses of twins as individuals and discordant twin pairs. Alternate definitions of pair-wise discordance and difference score correlations across the entire twin sample yielded supplementary analyses. Results All individual associations were highly significant for all definitions of discordance we employed. Depending on definitions of discordance, 11 to 13 comparisons of all drinking-discordant twin pairs and 3 to 6 comparisons of discordant monozygotic twin pairs replicated between-family associations. For most outcomes, effect size attenuated from individual level analysis to that within discordant MZ twin pairs providing evidence of partial confounding in associations reported in earlier research. The exception was the General Health Questionnaire; at age 25, GHQ-12 had equivalent associations with age 18½ RAPI across all comparisons

  10. Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding

    PubMed Central

    Souk, Karina M; Tamim, Hani M; Abu Daya, Hussein A; Rockey, Don C; Barada, Kassem A

    2016-01-01

    AIM: To compare outcomes of patients with non-variceal upper gastrointestinal bleeding (NVUGIB) taking aspirin for primary prophylaxis to those not taking it. METHODS: Patients not known to have any vascular disease (coronary artery or cerebrovascular disease) who were admitted to the American University of Beirut Medical Center between 1993 and 2010 with NVUGIB were included. The frequencies of in-hospital mortality, re-bleeding, severe bleeding, need for surgery or embolization, and of a composite outcome defined as the occurrence of any of the 4 bleeding related adverse outcomes were compared between patients receiving aspirin and those on no antithrombotics. We also compared frequency of in hospital complications and length of hospital stay between the two groups. RESULTS: Of 357 eligible patients, 94 were on aspirin and 263 patients were on no antithrombotics (control group). Patients in the aspirin group were older, the mean age was 58 years in controls and 67 years in the aspirin group (P < 0.001). Patients in the aspirin group had significantly more co-morbidities, including diabetes mellitus and hypertension [25 (27%) vs 31 (112%) and 44 (47%) vs 74 (28%) respectively, (P = 0.001)], as well as dyslipidemia [21 (22%) vs 16 (6%), P < 0.0001). Smoking was more frequent in the aspirin group [34 (41%) vs 60 (27%), P = 0.02)]. The frequencies of endoscopic therapy and surgery were similar in both groups. Patients who were on aspirin had lower in-hospital mortality rates (2.1% vs 13.7%, P = 0.002), shorter hospital stay (4.9 d vs 7 d, P = 0.01), and fewer composite outcomes (10.6% vs 24%, P = 0.01). The frequencies of in-hospital complications and re-bleeding were similar in the two groups. CONCLUSION: Patients who present with NVUGIB while receiving aspirin for primary prophylaxis had fewer adverse outcomes. Thus aspirin may have a protective effect beyond its cardiovascular benefits. PMID:27462392

  11. Adverse inpatient outcomes during the transition to a new electronic health record system: observational study

    PubMed Central

    Barnett, Michael L; Mehrotra, Ateev

    2016-01-01

    Objective To assess the short term association of inpatient implementation of electronic health records (EHRs) with patient outcomes of mortality, readmissions, and adverse safety events. Design Observational study with difference-in-differences analysis. Setting Medicare, 2011-12. Participants Patients admitted to 17 study hospitals with a verifiable “go live” date for implementation of inpatient EHRs during 2011-12, and 399 control hospitals in the same hospital referral region. Main outcome measures All cause readmission within 30 days of discharge, all cause mortality within 30 days of admission, and adverse safety events as defined by the patient safety for selected indicators (PSI)-90 composite measure among Medicare beneficiaries admitted to one of these hospitals 90 days before and 90 days after implementation of the EHRs (n=28 235 and 26 453 admissions), compared with the control group of all contemporaneous admissions to hospitals in the same hospital referral region (n=284 632 and 276 513 admissions). Analyses were adjusted for beneficiaries’ sociodemographic and clinical characteristics. Results Before and after implementation, characteristics of admissions were similar in both study and control hospitals. Among study hospitals, unadjusted 30 day mortality (6.74% to 7.15%, P=0.06) and adverse safety event rates (10.5 to 11.4 events per 1000 admissions, P=0.34) did not significantly change after implementation of EHRs. There was an unadjusted decrease in 30 day readmission rates, from 19.9% to 19.0% post-implementation (P=0.02). In difference-in-differences analysis, however, there was no significant change in any outcome between pre-implementation and post-implementation periods (all P≥0.13). Conclusions Despite concerns that implementation of EHRs might adversely impact patient care during the acute transition period, we found no overall negative association of such implementation on short term inpatient mortality, adverse safety

  12. Fourth Grade Outcomes of Children with a Preschool History of Developmental Disability

    ERIC Educational Resources Information Center

    Delgado, Christine E. F.

    2009-01-01

    Special education outcomes were evaluated for 3,608 children (2,513 males) with a preschool history of developmental disability. Sixty-six percent of the children had an identified disability in fourth grade. The percentage of children with a disability at outcome varied across preschool disability categories from 54% to 96%. The consistency of…

  13. Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial

    PubMed Central

    Austin, Erin E.; Gersh, Bernard J.; Solak, Nusret; Rizvi, Syed A.; Bailey, Kent R.; Kullo, Iftikhar J.

    2016-01-01

    Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure. PMID:27284698

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

    SciTech Connect

    Watanabe, Karen H.; Andersen, Melvin E.; Basu, Nil; Carvan, Michael J.; Crofton, Kevin M.; King, Kerensa A.; Sunol, Cristina; Tiffany-Castiglioni, Evelyn; Schultz, Irvin R.

    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, 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.

  15. Hyperactive children as young adults: driving abilities, safe driving behavior, and adverse driving outcomes.

    PubMed

    Fischer, Mariellen; Barkley, Russell A; Smallish, Lori; Fletcher, Kenneth

    2007-01-01

    ADHD has been linked to poorer driving abilities and greater adverse outcomes (crashes, citations) in clinic-referred cases of teens and adults with ADHD. No study, however, has focused systematically on ADHD children followed into adulthood. The present paper does so while measuring driving-related cognitive abilities, driving behavior, and history of adverse driving outcomes. A multi-method, multi-source battery of driving measures was collected at the young adult follow-up on hyperactive (H; N=147; mean age=21.1) and community control children (CC; N=71; mean age=20.5) followed for more than 13 years. More of the H than CC groups had been ticketed for reckless driving, driving without a license, hit-and-run crashes, and had their licenses suspended or revoked. Official driving records found more of the H group having received traffic citations and a greater frequency of license suspensions. The cost of damage in their initial crashes was also significantly greater in the H than CC group. Both self-report and other ratings of actual driving behavior revealed less safe driving practices being used by the H group. Observations by driving instructors during a behind-the-wheel road test indicated significantly more impulsive errors. Performance on a simulator further revealed slower and more variable reaction times, greater errors of impulsiveness (false alarms, poor rule following), more steering variability, and more scrapes and crashes of the simulated vehicle against road boundaries in the H than in the CC group. These findings suggest that children growing up with ADHD may either have fewer driving risks or possibly under-report those risks relative to clinic-referred adults with this disorder. Deficits in simulator performance and safe driving behavior, however, are consistent with clinic-referred adults with ADHD suggesting ongoing risks for such adverse driving outcomes in children growing up with ADHD. PMID:16919226

  16. Physical Performance Characteristics of Assisted Living Residents and Risk for Adverse Health Outcomes

    PubMed Central

    Giuliani, Carol A.; Gruber-Baldini, Ann L.; Park, Nan S.; Schrodt, Lori A.; Rokoske, Franzi; Sloane, Philip D.; Zimmerman, Sheryl

    2013-01-01

    Purpose Little is known 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 paper are to: 1) describe the functional characteristics of RC/AL residents; 2) examine the relationships between resident- and facility-characteristics and physical performance; and 3) determine the predictive value of physical performance for adverse outcomes. Design and Methods Data were derived from 1791 residents in 189 RC/AL facilities, participating in the Collaborative Studies of Long-Term Care. At baseline, residents were tested on four performance measures (grip strength, chair rise, balance, and walking speed), and other resident- and facility-level information was collected. Adverse outcomes were measured over one year. Results Average grip strength was 14 ± 7 kg; 61% of residents walked < 0.6 m/second (average 0.41 m/second); 26% could perform five chair rises; and only 19% could perform a tandem stand for a least one second. Multivariable analyses showed that more cognitive and functional impairment, depressive symptoms and comorbid conditions, and for-profit ownership, were associated with poorer physical performance. Controlling for individual characteristics, better performance on the four physical performance measures was associated with a reduced risk of nursing home placement, fracture, and decline in function over one year. Implication Simple performance measures identify modifiable functional deficits, and suggest targeted interventions to prolong independent mobility and aging in place in RC/AL facilities. PMID:18483432

  17. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  18. 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...

  19. Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

    ERIC Educational Resources Information Center

    Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M. A.; Kobor, Michael S.

    2013-01-01

    Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal…

  20. 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...

  1. 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...

  2. 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...

  3. Characterization of the Risks of Adverse Outcomes Following Rubella Infection in Pregnancy.

    PubMed

    Thompson, Kimberly M; Simons, Emily A; Badizadegan, Kamran; Reef, Susan E; Cooper, Louis Z

    2016-07-01

    Although most infections with the rubella virus result in relatively minor sequelae, rubella infection in early pregnancy may lead to severe adverse outcomes for the fetus. First recognized in 1941, congenital rubella syndrome (CRS) can manifest with a diverse range of symptoms, including congenital cataracts, glaucoma, and cardiac defects, as well as hearing and intellectual disability. The gestational age of the fetus at the time of the maternal rubella infection impacts the probability and severity of outcomes, with infection in early pregnancy increasing the risks of spontaneous termination (miscarriage), fetal death (stillbirth), birth defects, and reduced survival for live-born infants. Rubella vaccination continues to change the epidemiology of rubella and CRS globally, but no models currently exist to evaluate the economic benefits of rubella management. This systematic review provides an overall assessment of the weight of the evidence for the outcomes associated with rubella infections in the first 20 weeks of pregnancy. We identified, evaluated, and graded 31 studies (all from developed countries) that reported on the pregnancy outcomes of at least 30 maternal rubella infections. We used the available evidence to estimate the increased risks of spontaneous termination, fetal death, infant death, and CRS as a function of the timing of rubella infection in pregnancy and decisions about induced termination. These data support the characterization of the disability-adjusted life years for outcomes associated with rubella infection in pregnancy. We find significant impacts associated with maternal rubella infections in early pregnancy, which economic analyses will miss if they only focus on live births of CRS cases. Our estimates of fetal loss from increased induced terminations due to maternal rubella infections provide context that may help to explain the relatively low numbers of observed CRS cases per year despite potentially large burdens of disease. Our

  4. Should we continue using amphotericin B deoxycholate for the treatment of fungal infections? Adverse events and clinical outcomes.

    PubMed

    Garbino, Jorge; Markham, Lydia; Matulionyte, Raimonda; Rives, Vincent; Lew, Daniel

    2006-01-01

    Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is associated with high adverse event and mortality rates. A retrospective review was undertaken to describe adverse events and clinical outcomes in adult patients with IFI treated with only AmBd as initial therapy. PMID:16449001

  5. 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

  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. PMID:26735528

  7. A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

    PubMed Central

    Chin, Calvin W.L.; Messika-Zeitoun, David; Shah, Anoop S.V.; Lefevre, Guillaume; Bailleul, Sophie; Yeung, Emily N.W.; Koo, Maria; Mirsadraee, Saeed; Mathieu, Tiffany; Semple, Scott I.; Mills, Nicholas L.; Vahanian, Alec; Newby, David E.; Dweck, Marc R.

    2016-01-01

    Aims Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis. Methods and results One hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001). Conclusion We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement. PMID:26491110

  8. Long-term developmental outcome of children with a fetal diagnosis of isolated inferior vermian hypoplasia

    PubMed Central

    Tarui, Tomo; Limperopoulos, Catherine; Sullivan, Nancy R; Robertson, Richard L; du Plessis, Adre J

    2015-01-01

    Objectives Isolated inferior vermian hypoplasia (iiVH) is one of the most common fetal cerebellar anomalies presenting for fetal neurological counselling with controversial postnatal neurodevelopmental outcome. In the present study, we characterised the long-term neurodevelopmental outcome of prenatally diagnosed iiVH at school age. Design and patients We prospectively followed 20 children with fetal MRI diagnosis of iiVH including their postnatal MRI result and developmental outcome at school age (mean 6.1 years±1.9 years SD) using a comprehensive age-appropriate developmental testing battery, which encompassed cognitive, language, social and behavioural domains. Parental stress level and socioeconomic status were also evaluated. Results All children with postnatally confirmed iiVH had a normal neurodevelopmental outcome. A subgroup of children (2/20) who demonstrated cognitive delays and behavioural impairments had more extensive cerebellar malformation. Despite a normal developmental outcome, the parents of children with postnatally confirmed iiVH had higher parental stress compared with those parents whose children had normal postnatal MRI. Conclusions Children with postnatally confirmed iiVH show age appropriate functioning at school age. Postnatal MRI is important to confirm the diagnosis of iiVH and to exclude associated anomalies that impact neurodevelopmental outcome. A diagnosis of iiVH is associated with persistent elevated parental stress despite normal developmental outcomes in these children suggesting the need for ongoing parental support. PMID:23964086

  9. Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models.

    PubMed

    Sánchez, M M; Ladd, C O; Plotsky, P M

    2001-01-01

    Increasing evidence supports the view that the interaction of perinatal exposure to adversity with individual genetic liabilities may increase an individual's vulnerability to the expression of psycho- and physiopathology throughout life. The early environment appears to program some aspects of neurobiological development and, in turn, behavioral, emotional, cognitive, and physiological development. Several rodent and primate models of early adverse experience have been analyzed in this review, including those that "model" maternal separation or loss, abuse or neglect, and social deprivation. Accumulating evidence shows that these early traumatic experiences are associated with long-term alterations in coping style, emotional and behavioral regulation. neuroendocrine responsiveness to stress, social "fitness,' cognitive function, brain morphology, neurochemistry, and expression levels of central nervous system genes that have been related to anxiety and mood disorders. Studies are underway to identify important aspects of adverse early experience, such as (a) the existence of "sensitive periods" during development associated with alterations in particular output systems. (b) the presence of "windows of opportunity" during which targeted interventions (e.g., nurturant parenting or supportive-enriching environment) may prevent or reverse dysfunction, (c) the identity of gene polymorphisms contributing to the individual's variability in vulnerability, and (d) a means to translate the timing of these developmental "sensitive periods" across species. PMID:11523842

  10. Bisphenol A--Why an adverse outcome pathway framework needs to be applied.

    PubMed

    FitzGerald, R E; Wilks, M F

    2014-10-15

    Bisphenol A (BPA) is one of the most widely used and extensively studied chemicals. Numerous studies have reported in vitro effects or animal adverse findings at BPA doses lower than the no observed adverse effect levels (NOAELs) established in regulatory toxicity studies and used for human health risk assessment. Intensive discussions on the adequacy and relevance of test systems have not satisfactorily resolved whether positive or negative animal and/or in vitro findings are more relevant for human health risk assessment purposes. BPA imperfectly mimics endogenous estrogens at membrane-bound estrogen receptors in the fM-nM concentration range, and may have downstream pleiotropic effects such as human seminoma proliferation and mammary gland hyperplasia after in utero exposure which are not detectable in regulatory toxicology studies. We argue that a structured approach like the OECD Adverse Outcome Pathway (AOP) framework is needed to help researchers in designing relevant studies, and risk assessors in evaluating them. The huge amount of experimental data generated for BPA has highlighted data gaps in basic biology and the shortcomings of current approaches to hazard characterization and risk assessment. Establishing AOPs for BPA, and other endocrine active chemicals, will require major scientific as well as training investments by all responsible stakeholders. PMID:24831966

  11. Adverse neonatal outcomes in women with pre-eclampsia in Mulago Hospital, Kampala, Uganda: a cross-sectional study

    PubMed Central

    Kiondo, Paul; Tumwesigye, Nazarius Mbona; Wandabwa, Julius; Wamuyu-Maina, Gakenia; Bimenya, Gabriel S; Okong, Pius

    2014-01-01

    Introduction Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Methods Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Resuls Predictors of adverse neonatal outcomes were: preterm delivery (OR 5.97, 95% CI: 2.97-12.7) and severe pre-eclampsia (OR 5.17, 95% CI: 2.36-11.3). Conclusion Predictors of adverse neonatal outcomes among women with pre-eclampsia were preterm delivery and severe pre-eclampsia. Health workers need to identify women at risk, offer them counseling and, refer them if necessary to a hospital where they can be managed successfully. This may in turn reduce the neonatal morbidity and mortality associated with pre-eclampsia. PMID:24643210

  12. Common Sleep Disorders Increase Risk of Motor Vehicle Crashes and Adverse Health Outcomes in Firefighters

    PubMed Central

    Barger, Laura K.; Rajaratnam, Shantha M.W.; Wang, Wei; O'Brien, Conor S.; Sullivan, Jason P.; Qadri, Salim; Lockley, Steven W.; Czeisler, Charles A.

    2015-01-01

    Study Objectives: Heart attacks and motor vehicle crashes are the leading causes of death in US firefighters. Given that sleep disorders are an independent risk factor for both of these, we examined the prevalence of common sleep disorders in a national sample of firefighters and their association with adverse health and safety outcomes. Methods: Firefighters (n = 6,933) from 66 US fire departments were assessed for common sleep disorders using validated screening tools, as available. Firefighters were also surveyed about health and safety, and documentation was collected for reported motor vehicle crashes. Results: A total of 37.2% of firefighters screened positive for any sleep disorder including obstructive sleep apnea (OSA), 28.4%; insomnia, 6.0%; shift work disorder, 9.1%; and restless legs syndrome, 3.4%. Compared with those who did not screen positive, firefighters who screened positive for a sleep disorder were more likely to report a motor vehicle crash (adjusted odds ratio 2.00, 95% CI 1.29–3.12, p = 0.0021) and were more likely to self-report falling asleep while driving (2.41, 2.06–2.82, p < 0.0001). Firefighters who screened positive for a sleep disorder were more likely to report having cardiovascular disease (2.37, 1.54–3.66, p < 0.0001), diabetes (1.91, 1.31–2.81, p = 0.0009), depression (3.10, 2.49–3.85, p < 0.0001), and anxiety (3.81, 2.87–5.05, p < 0.0001), and to report poorer health status (p < 0.0001) than those who did not screen positive. Adverse health and safety associations persisted when OSA and non-OSA sleep disorders were examined separately. Conclusions: Sleep disorders are prevalent in firefighters and are associated with increased risk of adverse health and safety outcomes. Future research is needed to assess the efficacy of occupational sleep disorders prevention, screening, and treatment programs in fire departments to reduce these safety and health risks. Citation: Barger LK, Rajaratnam SM, Wang W, O'Brien CS

  13. The adverse effect of spasticity on 3-month poststroke outcome using a population-based model.

    PubMed

    Belagaje, S R; Lindsell, C; Moomaw, C J; Alwell, K; Flaherty, M L; Woo, D; Dunning, K; Khatri, P; Adeoye, O; Kleindorfer, D; Broderick, J; Kissela, B

    2014-01-01

    Several devices and medications have been used to address poststroke spasticity. Yet, spasticity's impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS) as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question "Did you have spasticity following your stroke?" on direct interview at 3 months from stroke onset. Patients who had expired by 90 days (n = 30) or did not have spasticity data available (n = 102) were excluded. Spasticity affected the 3-month functional status (β = 0.420, 95 CI = 0.194 to 0.645) after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model's R (2) changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors. PMID:25147752

  14. The Adverse Effect of Spasticity on 3-Month Poststroke Outcome Using a Population-Based Model

    PubMed Central

    Belagaje, S. R.; Lindsell, C.; Moomaw, C. J.; Alwell, K.; Flaherty, M. L.; Woo, D.; Dunning, K.; Khatri, P.; Adeoye, O.; Kleindorfer, D.; Broderick, J.; Kissela, B.

    2014-01-01

    Several devices and medications have been used to address poststroke spasticity. Yet, spasticity's impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS) as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question “Did you have spasticity following your stroke?” on direct interview at 3 months from stroke onset. Patients who had expired by 90 days (n = 30) or did not have spasticity data available (n = 102) were excluded. Spasticity affected the 3-month functional status (β = 0.420, 95 CI = 0.194 to 0.645) after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model's R2 changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors. PMID:25147752

  15. Management and outcome of Bacille Calmette-Guérin vaccine adverse reactions

    PubMed Central

    Venkataraman, Aishwarya; Yusuff, Michael; Liebeschuetz, Susan; Riddell, Anna; Prendergast, Andrew J.

    2015-01-01

    Background Bacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain. Aim To determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom. Methods All children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome. Results Sixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases. Conclusions Injection site reactions and non-suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain. PMID:26275478

  16. Common variants of the vitamin D binding protein gene and adverse health outcomes

    PubMed Central

    Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y. L.; Gozdzik, Agnes

    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. PMID:23427793

  17. Adverse Childhood Experiences and Adult Health Outcomes Among Veteran and Non-Veteran Women

    PubMed Central

    Blosnich, John R.; Dichter, Melissa E.

    2015-01-01

    Abstract Background: Women veterans represent a vulnerable population with unique health needs and disparities in access to care. One constellation of exposures related to subsequent poor health includes adverse childhood experiences (ACEs; e.g., physical and sexual child abuse), though research on impacts of ACEs among women veterans is limited. Methods: Data were drawn from the 2010 Behavioral Risk Factor Surveillance System for the 11 states that included the ACE module (n=36,485). Weighted chi-squared tests and multivariable logistic regression were used to assess the prevalence of ACEs among women veterans compared with women non-veterans and differences in the following outcomes, controlling for ACEs: social support, inadequate sleep, life satisfaction, mental distress, smoking, heavy alcohol use, obesity, diabetes, cardiovascular disease symptoms, asthma, and disability. Results: Women veterans (1.6% of the total sample) reported a higher prevalence of 7 out of 11 childhood adversities and higher mean ACE score than women non-veterans. Women veterans were more likely to be current smokers and report a disability, associations which were attenuated when controlling for ACE. Conclusions: Despite women veterans' higher prevalence of ACE, their health outcomes did not differ substantially from non-veterans. Further research is needed to understand the intersections of traumatic experiences and sources of resilience over the lifecourse among women veterans. PMID:26390379

  18. Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making.

    PubMed

    Edwards, Stephen W; Tan, Yu-Mei; Villeneuve, Daniel L; Meek, M E; McQueen, Charlene A

    2016-01-01

    The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High-throughput screening commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a framework for connecting high-throughput toxicity testing (HTT) and other results to potential impacts on human and wildlife populations. As a result of international efforts, the AOP development process is now well-defined and efforts are underway to broaden the participation through outreach and training. One key principle is that AOPs represent the chemical-agnostic portions of pathways to increase the generalizability of their application from early key events to overt toxicity. The closely related mode of action framework extends the AOP as needed when evaluating the potential risk of a specific chemical. This in turn enables integrated approaches to testing and assessment (IATA), which incorporate results of assays at various levels of biologic organization such as in silico; HTT; chemical-specific aspects including absorption, distribution, metabolism, and excretion (ADME); and an AOP describing the biologic basis of toxicity. Thus, it is envisaged that provision of limited information regarding both the AOP for critical effects and the ADME for any chemical associated with any adverse outcome would allow for the development of IATA and permit more detailed AOP and ADME research, where higher precision is needed based on the decision context. PMID:26537250

  19. The adverse outcome pathway (AOP) for chemical binding to tubulin in oocytes leading to aneuploid offspring.

    PubMed

    Marchetti, Francesco; Massarotti, Alberto; Yauk, Carole L; Pacchierotti, Francesca; Russo, Antonella

    2016-03-01

    The Organisation for Economic Co-operation and Development (OECD) has launched the Adverse Outcome Pathway (AOP) Programme to advance knowledge of pathways of toxicity and improve the use of mechanistic information in risk assessment. An AOP links a molecular initiating event (MIE) to an adverse outcome (AO) through intermediate key events (KE). Here, we present the scientific evidence in support of an AOP whereby chemicals that bind to tubulin cause microtubule depolymerization resulting in spindle disorganization followed by altered chromosome alignment and segregation and the generation of aneuploidy in female germ cells, ultimately leading to aneuploidy in the offspring. Aneuploidy, an abnormal number of chromosomes that is not an exact multiple of the haploid number, is a well-known cause of human disease and represents a major cause of infertility, pregnancy failure, and serious genetic disorders in the offspring. Among chemicals that induce aneuploidy in female germ cells, a large majority impairs microtubule dynamics and spindle function. Colchicine, a prototypical chemical that binds to tubulin and causes microtubule depolymerization, is used here to illustrate the AOP. This AOP is specific to female germ cells exposed during the periovulation period. Although the majority of the data come from rodent studies, the available evidence suggests that the MIE and KEs are conserved across species and would occur in human oocytes. The development of AOPs related to mutagenicity in germ cells is expected to aid the identification of potential hazards to germ cell genomic integrity and support regulatory efforts to protect population health. PMID:26581746

  20. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis. PMID:27149222

  1. 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. PMID:25261300

  2. Regression models and risk estimation for mixed discrete and continuous outcomes in developmental toxicology.

    PubMed

    Regan, M M; Catalano, P J

    2000-06-01

    Multivariate dose-response models have recently been proposed for developmental toxicity data to simultaneously model malformation incidence (a binary outcome), and reductions in fetal weight (a continuous outcome). In this and other applications, the binary outcome often represents a dichotomization of another outcome or a composite of outcomes, which facilitates analysis. For example, in Segment II developmental toxicology studies, multiple malformation types (i.e., external, visceral, skeletal) are evaluated on each fetus; malformation status may also be ordinally measured (e.g., normal, signs of variation, full malformation). A model is proposed is for fetal weight and multiple malformation variables measured on an ordinal scale, where the correlations between the outcomes and between the offspring within a litter are taken into account. Fully specifying the joint distribution of outcomes within a litter is avoided by specifying only the distribution of the multivariate outcome for each fetus and using generalized estimating equation methodology to account for correlations due to litter clustering. The correlations between the outcomes are required to characterize joint risk to the fetus, and are therefore a focus of inference. Dose-response models and their application to quantitative risk assessment are illustrated using data from a recent developmental toxicology experiment of ethylene oxide in mice. PMID:10949415

  3. Early life adversity alters the developmental profiles of addiction-related prefrontal cortex circuitry.

    PubMed

    Brenhouse, Heather C; Lukkes, Jodi L; Andersen, Susan L

    2013-01-01

    Early adverse experience is a well-known risk factor for addictive behaviors later in life. Drug addiction typically manifests during adolescence in parallel with the later-developing prefrontal cortex (PFC). While it has been shown that dopaminergic modulation within the PFC is involved in addiction-like behaviors, little is known about how early adversity modulates its development. Here, we report that maternal separation stress (4 h per day between postnatal days 2-20) alters the development of the prelimbic PFC. Immunofluorescence and confocal microscopy revealed differences between maternally-separated and control rats in dopamine D1 and D2 receptor expression during adolescence, and specifically the expression of these receptors on projection neurons. In control animals, D1 and D2 receptors were transiently increased on all glutamatergic projection neurons, as well as specifically on PFC→nucleus accumbens projection neurons (identified with retrograde tracer). Maternal separation exacerbated the adolescent peak in D1 expression and blunted the adolescent peak in D2 expression on projection neurons overall. However, neurons retrogradely traced from the accumbens expressed lower levels of D1 during adolescence after maternal separation, compared to controls. Our findings reveal microcircuitry-specific changes caused by early life adversity that could help explain heightened vulnerability to drug addiction during adolescence. PMID:24961311

  4. 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

  5. Integrating Publicly Available Data to Generate Computationally Predicted Adverse Outcome Pathways for Fatty Liver.

    PubMed

    Bell, Shannon M; Angrish, Michelle M; Wood, Charles E; Edwards, Stephen W

    2016-04-01

    Newin vitrotesting strategies make it possible to design testing batteries for large numbers of environmental chemicals. Full utilization of the results requires knowledge of the underlying biological networks and the adverse outcome pathways (AOPs) that describe the route from early molecular perturbations to an adverse outcome. Curation of a formal AOP is a time-intensive process and a rate-limiting step to designing these test batteries. Here, we describe a method for integrating publicly available data in order to generate computationally predicted AOP (cpAOP) scaffolds, which can be leveraged by domain experts to shorten the time for formal AOP development. A network-based workflow was used to facilitate the integration of multiple data types to generate cpAOPs. Edges between graph entities were identified through direct experimental or literature information, or computationally inferred using frequent itemset mining. Data from the TG-GATEs and ToxCast programs were used to channel large-scale toxicogenomics information into a cpAOP network (cpAOPnet) of over 20 000 relationships describing connections between chemical treatments, phenotypes, and perturbed pathways as measured by differential gene expression and high-throughput screening targets. The resulting fatty liver cpAOPnet is available as a resource to the community. Subnetworks of cpAOPs for a reference chemical (carbon tetrachloride, CCl4) and outcome (fatty liver) were compared with published mechanistic descriptions. In both cases, the computational approaches approximated the manually curated AOPs. The cpAOPnet can be used for accelerating expert-curated AOP development and to identify pathway targets that lack genomic markers or high-throughput screening tests. It can also facilitate identification of key events for designing test batteries and for classification and grouping of chemicals for follow up testing. PMID:26895641

  6. Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

    SciTech Connect

    Venkatramani, Rajkumar; Kamath, Sunil; Wong, Kenneth; Malvar, Jemily; Sposto, Richard; Goodarzian, Fariba; Freyer, David R.; Keens, Thomas G.; and others

    2013-08-01

    Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed

  7. Sex Differences in Device Therapy for Heart Failure: Utilization, Outcomes, and Adverse Events

    PubMed Central

    Herz, Naomi D.; Engeda, Joseph; Zusterzeel, Robbert; Sanders, William E.; O'Callaghan, Kathryn M.; Strauss, David G.; Jacobs, Samantha B.; Selzman, Kimberly A.; Piña, Ileana L.

    2015-01-01

    Abstract Background: Multiple studies of heart failure patients demonstrated significant improvement in exercise capacity, quality of life, cardiac left ventricular function, and survival from cardiac resynchronization therapy (CRT), but the underenrollment of women in these studies is notable. Etiological and pathophysiological differences may result in different outcomes in response to this treatment by sex. The observed disproportionate representation of women suggests that many women with heart failure either do not meet current clinical criteria to receive CRT in trials or are not properly recruited and maintained in these studies. Methods: We performed a systematic literature review through May 2014 of clinical trials and registries of CRT use that stratified outcomes by sex or reported percent women included. One-hundred eighty-three studies contained sex-specific information. Results: Ninety percent of the studies evaluated included ≤35% women. Fifty-six articles included effectiveness data that reported response with regard to specific outcome parameters. When compared with men, women exhibited more dramatic improvement in specific parameters. In the studies reporting hazard ratios for hospitalization or death, women generally had greater benefit from CRT. Conclusions: Our review confirms women are markedly underrepresented in CRT trials, and when a CRT device is implanted, women have a therapeutic response that is equivalent to or better than in men, while there is no difference in adverse events reported by sex. PMID:25793483

  8. Exposure to Mixtures of Metals and Neurodevelopmental Outcomes: A Multidisciplinary Review Using an Adverse Outcome Pathway Framework.

    PubMed

    von Stackelberg, Katherine; Guzy, Elizabeth; Chu, Tian; Claus Henn, Birgit

    2015-06-01

    Current risk assessment guidance calls for an individual chemical-by-chemical approach that fails to capture potential interactive effects of exposure to environmental mixtures and genetic variability. We conducted a review of the literature on relationships between prenatal and early life exposure to mixtures of lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn) with neurodevelopmental outcomes. We then used an adverse outcome pathway (AOP) framework to integrate lines of evidence from multiple disciplines based on evolving guidance developed by the Organization for Economic Cooperation and Development (OECD). Toxicological evidence suggests a greater than additive effect of combined exposures to As-Pb-Cd and to Mn with any other metal, and several epidemiologic studies also suggest synergistic effects from binary combinations of Pb-As, Pb-Cd, and Pb-Mn. The exposure levels reported in these epidemiologic studies largely fall at the high-end (e.g., 95th percentile) of biomonitoring data from the National Health and Nutrition Examination Survey (NHANES), suggesting a small but significant potential for high-end exposures. This review integrates multiple data sources using an AOP framework and provides an initial application of the OECD guidance in the context of potential neurodevelopmental toxicity of several metals, recognizing the evolving nature of regulatory interpretation and acceptance. PMID:26096925

  9. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

    PubMed

    Garner, Andrew S; Shonkoff, Jack P

    2012-01-01

    Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span. PMID:22201148

  10. Acidosis: A potential explanation for adverse fetal outcome in intrahepatic cholestasis of pregnancy. A case report

    PubMed Central

    Visser, W; Smit, LS; Cornette, J

    2014-01-01

    Background Intrahepatic cholestasis of pregnancy is a cholestatic disorder with an increased risk for adverse perinatal outcome. The mechanism underlying intrauterine demise is poorly understood. Case A nulliparous woman with gestational age of 36 plus 6 weeks presented with suspected intrahepatic cholestasis. Continuous CTG monitoring evolved from a normal pattern towards a non-reassuring pattern. A male neonate was delivered by caesarean section. Apgar scores 0, 1 and 4 at 1, 5 and 10 min. Fetal cord gas analysis showed pH 6.98, base deficit –15 mmol/L. Blood results showed maternal serum bile acid concentration of 220 µmol/L. Conclusion Our case suggests gradual evolution towards hypoxia and acidosis. It is unknown whether certain components in the bile acid concentrations might contribute to a fetal metabolic component of the acidosis.

  11. Identifying exposure disparities in air pollution epidemiology specific to adverse birth outcomes

    NASA Astrophysics Data System (ADS)

    Geer, Laura A.

    2014-10-01

    More than 147 million people in the US live in areas where pollutant levels are above regulatory limits and pose a risk to health. Most of the vast network of air pollutant monitors in the US are located in places with higher pollution levels and a higher density of pollutant sources (e.g., point sources from industrial pollution). Vulnerable populations are more likely to live closer to pollutant sources, and thus closer to pollutant monitors. These differential exposures have an impact on maternal and child health; maternal air pollutant exposures have been linked to adverse outcomes such as preterm birth and infant low birth weight. Several studies are highlighted that address methodological approaches in the study of air pollution and health disparities.

  12. Association of Increased Epicardial Adipose Tissue Thickness With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation

    PubMed Central

    Chu, Chun-Yuan; Lee, Wen-Hsien; Hsu, Po-Chao; Lee, Meng-Kuang; Lee, Hung-Hao; Chiu, Cheng-An; Lin, Tsung-Hsien; Lee, Chee-Siong; Yen, Hsueh-Wei; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Su, Ho-Ming

    2016-01-01

    Abstract The thickness of epicardial adipose tissue (EAT) was reported to be highly associated with the incidence and severity of atrial fibrillation (AF). This study was conducted to analyze the ability of EAT thickness in predicting adverse cardiovascular (CV) events in AF. In 190 persistent AF patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV mortality, hospitalization for heart failure, myocardial infarction, and stroke. There were 69 CV events including 19 CV deaths, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during a mean follow-up of 29 (25th–75th percentile: 17–36) months. The multivariable analysis demonstrates that chronic heart failure, increased left ventricular (LV) mass index and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity, decreased body mass index, and increased EAT thickness (per 1-mm increase, odds ratio 1.224, 95% confidence interval [CI] 1.096–1.368, P < 0.001) were associated with adverse CV events. Additionally, the addition of EAT thickness to a model containing CHA2DS2-VASc score, left atrial volume index, and LV systolic and diastolic function significantly improved the values in predicting CV events (global χ2 increase 14.65, P < 0.001 and integrated discrimination improvement 0.10, 95% CI 0.04–0.16, P < 0.001). In AF, EAT thickness was useful in predicting adverse CV events. Additionally, EAT thickness could provide incremental value for CV outcome prediction over traditional clinical and echocardiographic parameters in AF. PMID:26986099

  13. Association of Increased Epicardial Adipose Tissue Thickness With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation.

    PubMed

    Chu, Chun-Yuan; Lee, Wen-Hsien; Hsu, Po-Chao; Lee, Meng-Kuang; Lee, Hung-Hao; Chiu, Cheng-An; Lin, Tsung-Hsien; Lee, Chee-Siong; Yen, Hsueh-Wei; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Su, Ho-Ming

    2016-03-01

    The thickness of epicardial adipose tissue (EAT) was reported to be highly associated with the incidence and severity of atrial fibrillation (AF). This study was conducted to analyze the ability of EAT thickness in predicting adverse cardiovascular (CV) events in AF.In 190 persistent AF patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV mortality, hospitalization for heart failure, myocardial infarction, and stroke.There were 69 CV events including 19 CV deaths, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during a mean follow-up of 29 (25th-75th percentile: 17-36) months. The multivariable analysis demonstrates that chronic heart failure, increased left ventricular (LV) mass index and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity, decreased body mass index, and increased EAT thickness (per 1-mm increase, odds ratio 1.224, 95% confidence interval [CI] 1.096-1.368, P < 0.001) were associated with adverse CV events. Additionally, the addition of EAT thickness to a model containing CHA2DS2-VASc score, left atrial volume index, and LV systolic and diastolic function significantly improved the values in predicting CV events (global χ increase 14.65, P < 0.001 and integrated discrimination improvement 0.10, 95% CI 0.04-0.16, P < 0.001).In AF, EAT thickness was useful in predicting adverse CV events. Additionally, EAT thickness could provide incremental value for CV outcome prediction over traditional clinical and echocardiographic parameters in AF. PMID:26986099

  14. Children with Incarcerated Mothers: Developmental Outcomes, Special Challenges and Recommendations

    ERIC Educational Resources Information Center

    Dallaire, Danielle H.

    2007-01-01

    Incarcerated mothers represent a rapidly growing sector of the prison population. This review of the literature presents research examining the psychological and socio-emotional well-being of children with an incarcerated mother, highlighting risk and protective factors at different stages of children's development. Child outcomes are reviewed…

  15. School mobility and developmental outcomes in young adulthood.

    PubMed

    Herbers, Janette E; Reynolds, Arthur J; Chen, Chin-Chih

    2013-05-01

    School mobility has been shown to increase the risk of poor achievement, behavior problems, grade retention, and high school dropout. Using data over 25 years from the Chicago Longitudinal Study, we investigated the unique risk of school moves on a variety of young adult outcomes including educational attainment, occupational prestige, depression symptoms, and criminal arrests. We also investigated how the timing of school mobility, whether earlier or later in the academic career, may differentially predict these outcomes over and above associated risks. Results indicate that students who experience more school changes between kindergarten and 12th grade are less likely to complete high school on time, complete fewer years of school, attain lower levels of occupational prestige, experience more symptoms of depression, and are more likely to be arrested as adults. Furthermore, the number of school moves predicted outcomes above and beyond associated risks such as residential mobility and family poverty. When timing of school mobility was examined, results indicated more negative outcomes associated with moves later in the grade school career, particularly between 4th and 8th grades. PMID:23627959

  16. Exit Examinations, Peer Academic Climate, and Adolescents' Developmental Outcomes

    ERIC Educational Resources Information Center

    Benner, Aprile D.

    2013-01-01

    Implications of high school exit examination performance were examined with a sample of 672 racial/ethnic minority students. Exit examination failure in the 10th grade was negatively linked to subsequent grade point average, school engagement, and school belonging one year later, controlling for outcomes prior to taking the examination.…

  17. Diversity, Child Care Quality and Developmental Outcomes. FPG Snapshot, #21

    ERIC Educational Resources Information Center

    FPG Child Development Institute, University of North Carolina, 2004

    2004-01-01

    It is widely accepted that high quality child care enhances children's cognitive and social development, but some people question if what constitutes quality care depends on the child's ethnic and cultural background. To examine this issue, secondary analysis of the two largest U.S. studies of child care--the Cost, Quality, and Outcomes Study and…

  18. Enabling Outcomes for Students with Developmental Disabilities through Collaborative Consultation

    ERIC Educational Resources Information Center

    Villeneuve, Michelle; Hutchinson, Nancy L.

    2012-01-01

    Collaborative consultation has been widely adopted in school-based occupational therapy practice; however, limited research has examined how collaboration between educators and occupational therapists contributes to students' outcomes. The purpose of this study was to describe the nature of collaborative working in two cases of school-based…

  19. 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

  20. Chlorinated drinking water, cancers and adverse health outcomes in Gangtok, Sikkim, India.

    PubMed

    Sharma, Rabi N; Goel, Sudha

    2007-10-01

    Long-term impacts of drinking chlorinated water on the incidence of cancers and other adverse health outcomes were assessed in a population-based cross-sectional study. The study was conducted by comparing a group exposed to chlorinated drinking water for more than thirty years with control groups with less or no exposure to chlorine. A house-to-house survey was completed to gather information on residential history, age, education, income, source and extent of treatment of water and health characteristics. All residents below thirty years of age were excluded from the database used for analyses to ensure that the groups were comparable. Fourteen cancer cases were found in the long-term exposed groups of 1085 persons and 9 cancer cases in the two control populations of 725 persons. The odds ratio for cancers (OR) was 1.05 (95% CI = 0.43-2.65) and is not statistically significant. Reciprocal or inverse odds [corrected] ratios for gastrointestinal disorders, kidney problems and skin infections were statistically significant ranging from 2.06 (95% CI = 1.01-4.17) to 2.2 (95% CI = 1.45-3.33). These OR values indicate that there is no significant association between the incidence of cancer and exposure to chlorinated water while chlorinating drinking water significantly reduced the incidence of non-carcinogenic adverse health effects like gastrointestinal diseases, skin infections, and kidney diseases. PMID:18476370

  1. Is growth-discordance in twins a substantial risk factor in adverse neonatal outcomes?

    PubMed

    Frezza, Simonetta; Gallini, Francesca; Puopolo, Maria; De Carolis, Maria P; D'Andrea, Vito; Guidone, Paola I; Luciano, Rita; Zuppa, Antonio A; Romagnoli, Costantino

    2011-10-01

    To evaluate whether growth discordance is an independent risk factor in the neonatal outcome of the smaller twin, all medical records of twin pregnancies delivered between 26 and 41 weeks during a 5-year period (January 2004-December 2008) were reviewed. Among the 49 selected twins, weight discordance was 15-20% in 7 infants, 21-30% in 16 infants, 31-40% in 16 infants and > 40% in 10 infants. No significant differences between the four groups were found with regards to obstetric complications and neonatal disease. Occurrence of birthweight below the 10th percentile and rate of admission to the neonatal intensive care unit significantly increased as intra-pair birthweight difference increased (p = .03). The > 40% discordant group had a significantly lower gestational age (p = .03), lower birthweight (p = .007) and a significantly higher mortality rate (4/10 versus 3/39 p = .04) in comparison with the other discordant groups. Multiple logistic regression analysis showed that birthweight was the single independent and consistent factor associated with elevated risks of mortality. For every 250 g increase in birthweight, the risk for mortality decreased by about 84% [RR 0.16(CI 0.00-0.70)]. Gestational age was the most reliable predictor for major neonatal complications. For every 1-week increase in gestational age a significant decreased risk for all outcomes was found. Discordance alone should not be considered as a predictor for adverse neonatal outcome. Neonatal outcome in discordant twins appears to be related to gestational age and birthweight rather than to the degree of discordance. PMID:21962140

  2. Periodontal Treatment for Preventing Adverse Pregnancy Outcomes: A Meta- and Trial Sequential Analysis

    PubMed Central

    Schwendicke, Falk; Karimbux, Nadeem; Allareddy, Veerasathpurush; Gluud, Christian

    2015-01-01

    Objectives Periodontal treatment might reduce adverse pregnancy outcomes. The efficacy of periodontal treatment to prevent preterm birth, low birth weight, and perinatal mortality was evaluated using meta-analysis and trial sequential analysis. Methods An existing systematic review was updated and meta-analyses performed. Risk of bias, heterogeneity, and publication bias were evaluated, and meta-regression performed. Subgroup analysis was used to compare different studies with low and high risk of bias and different populations, i.e., risk groups. Trial sequential analysis was used to assess risk of random errors. Results Thirteen randomized clinical trials evaluating 6283 pregnant women were meta-analyzed. Four and nine trials had low and high risk of bias, respectively. Overall, periodontal treatment had no significant effect on preterm birth (odds ratio [95% confidence interval] 0.79 [0.57-1.10]) or low birth weight (0.69 [0.43-1.13]). Trial sequential analysis demonstrated that futility was not reached for any of the outcomes. For populations with moderate occurrence (<20%) of preterm birth or low birth weight, periodontal treatment was not efficacious for any of the outcomes, and trial sequential analyses indicated that further trials might be futile. For populations with high occurrence (≥20%) of preterm birth and low birth weight, periodontal treatment seemed to reduce the risk of preterm birth (0.42 [0.24-0.73]) and low birth weight (0.32 [0.15-0.67]), but trial sequential analyses showed that firm evidence was not reached. Periodontal treatment did not significantly affect perinatal mortality, and firm evidence was not reached. Risk of bias, but not publication bias or patients’ age modified the effect estimates. Conclusions Providing periodontal treatment to pregnant women could potentially reduce the risks of perinatal outcomes, especially in mothers with high risks. Conclusive evidence could not be reached due to risks of bias, risks of random

  3. Malnutrition in Hospitalized Pediatric Patients: Assessment, Prevalence, and Association to Adverse Outcomes.

    PubMed

    Daskalou, Efstratia; Galli-Tsinopoulou, Assimina; Karagiozoglou-Lampoudi, Thomais; Augoustides-Savvopoulou, Persefone

    2016-01-01

    Malnutrition is a frequent finding in pediatric health care settings in the form of undernutrition or excess body weight. Its increasing prevalence and impact on overall health status, which is reflected in the adverse outcomes, renders imperative the application of commonly accepted and evidence-based practices and tools by health care providers. Nutrition risk screening on admission and nutrition status evaluation are key points during clinical management of hospitalized pediatric patients, in order to prevent health deterioration that can lead to serious complications and growth consequences. In addition, anthropometric data based on commonly accepted universal growth standards can give accurate results for nutrition status. Both nutrition risk screening and nutrition status assessment are techniques that should be routinely implemented, based on commonly accepted growth standards and methodology, and linked to clinical outcomes. The aim of the present review was to address the issue of hospital malnutrition in pediatric settings in terms of prevalence, outline nutrition status evaluation and nutrition screening process using different criteria and available tools, and present its relationship with outcome measures. Key teaching points • Malnutrition-underweight or excess body weight-is a frequent imbalance in pediatric settings that affects physical growth and results in undesirable clinical outcomes. • Anthropometry interpretation through growth charts and nutrition screening are cornerstones for the assessment of malnutrition.To date no commonly accepted anthropometric criteria or nutrition screening tools are used in hospitalized pediatric patients. • Commonly accepted nutrition status and screening processes based on the World Health Organization's growth standards can contribute to the overall hospital nutrition care of pediatric patients. PMID:26709552

  4. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis.

    PubMed

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients' general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann-Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of disease

  5. Adverse events and outcomes of procedural sedation and analgesia in major trauma patients

    PubMed Central

    Green, Robert S.; Butler, Michael B.; Campbell, Samuel G.; Erdogan, Mete

    2015-01-01

    Context: Trauma patients requiring procedural sedation and analgesia (PSA) may have increased risk of adverse events (AEs) and poor outcomes. Aims: To determine the incidence of AEs in adult major trauma patients who received PSA and to evaluate their postprocedural outcomes. Settings and Design: Retrospective analysis of adult patients (age >16) who received PSA between 2006 and 2014 at a Canadian academic tertiary care center. Materials and Methods: We compared the incidence of PSA-related AEs in trauma patients with nontrauma patients. Postprocedural outcomes including Intensive Care Unit admission, length of hospital stay, and mortality were compared between trauma patients who did or did not receive PSA. Statistical Analysis Used: Descriptive statistics and multivariable logistic regression. Results: Overall, 4324 patients received PSA during their procedure, of which 101 were trauma patients (107 procedures). The majority (77%) of these 101 trauma patients were male, relatively healthy (78% with American Society of Anesthesiologists Physical Status [ASA-PS] 1), and most (85%) of the 107 procedures were orthopedic manipulations. PSA-related AEs were experienced by 45.5% of the trauma group and 45.9% of the nontrauma group. In the trauma group, the most common AEs were tachypnea (23%) and hypotension (20%). After controlling for age, gender, and ASA-PS, trauma patients were more likely than nontrauma patients to develop hypotension (odds ratio 1.79; 95% confidence interval 1.11-2.89). Conclusion: Although trauma patients were more likely than nontrauma patients to develop hypotension during PSA, their outcomes were not worse compared to trauma patients who did not have PSA. PMID:26604527

  6. 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

  7. Patient-reported outcomes and the evolution of adverse event reporting in oncology.

    PubMed

    Trotti, Andy; Colevas, A Dimitrios; Setser, Ann; Basch, Ethan

    2007-11-10

    Adverse event (AE) reporting in oncology has evolved from informal descriptions to a highly systematized process. The Common Terminology Criteria for Adverse Events (CTCAE) is the predominant system for describing the severity of AEs commonly encountered in oncology clinical trials. CTCAE clinical descriptors have been developed empirically during more than 30 years of use. The method of data collection is clinician based. Limitations of the CTC system include potential for incomplete reporting and limited guidance on data analysis and presentation methods. The Medical Dictionary for Regulatory Activities (MedDRA) is a comprehensive medical terminology system used for regulatory reporting and drug labeling. MedDRA does not provide for severity ranking of AEs. CTC-based data presentations are the primary method of AE data reporting used in scientific journals and oncology meetings. Patient-reported outcome instruments (PROs) cover the subjective domain of AEs. Exploratory work suggests PROs can be used with a high degree of patient engagement and compliance. Additional studies are needed to determine how PROs can be used to complement current AE reporting systems. Potential models for integrating PROs into AE reporting are described in this review. AE reporting methods will continue to evolve in response to changing therapies and growing interest in measuring the impact of cancer treatment on health status. Although integration of PROs into AE reporting may ultimately improve the comprehensiveness and quality of collected data, it may also increase the administrative burden and cost of conducting trials. Therefore, care must be used when developing health outcomes and safety data collection plans. PMID:17991931

  8. 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

  9. Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network.

    PubMed

    Yang, Lihua; Zhou, Bingsheng; Zha, Jinmiao; Wang, Zijian

    2016-10-01

    The adverse outcome pathway (AOP) framework could be helpful for chemical risk assessment and mechanistic research. The aim of the present study was to unravel the mechanism of chlordecone-induced endocrine disruption by illustrating the main molecular initiating event (MIE)/perturbations responsible for the observed effects. In silico simulations were performed to predict the MIE(s), and the results pointed to agonistic interaction with estrogen receptors (ERα, ERβ), androgen receptor (AR), cytochrome P450 (CYP19A) by chlordecone. In vivo endocrine disruptions were evaluated in rare minnow (Gobiocypris rarus) exposed to 0.01, 0.1, 1 and 10 μg L(-1) chlordecone from 2 h post-fertilization until sexually mature. In the females, increases of vitellogenin (vtg) mRNA levels in liver and gonad, plasma estradiol (E2), testosterone (T) and E2/T, and renalsomatic index confirmed the role of agonism of ER and CYP19A as MIEs, but the decreased gonadosomatic index, degenerated ovaries as well as the feed-forward response pointed to other potential but important MIEs and corresponding AOPs. In the males, increased E2/T ratio, increased testis vtg mRNA levels and occurrence of intersex confirmed the roles of agonism of ERα and CYP19A as main MIEs in chlordecone-induced endocrine disruptions. Our results also fetches out the limit of AOPs in predicting the adverse outcomes and explaining the mechanism of chemicals at present, thus reflected a critical need for expanding AOPs and AOP network before using it in chemical risk assessment. PMID:27448318

  10. Associations Between Residential Proximity to Power Plants and Adverse Birth Outcomes.

    PubMed

    Ha, Sandie; Hu, Hui; Roth, Jeffrey; Kan, Haidong; Xu, Xiaohui

    2015-08-01

    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

  11. Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study

    PubMed Central

    Aarsand, Aasne Karine; Sandberg, Sverre

    2010-01-01

    The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967–2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5–16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2–7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2–3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2–10.0) and premature delivery (3.5, 1.2–10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy. PMID:20978938

  12. Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer: Evaluation of Outcomes in the Regione Emilia-Romagna, Italy

    SciTech Connect

    Showalter, Timothy N.; Hegarty, Sarah E.; Rabinowitz, Carol; Maio, Vittorio; Hyslop, Terry; Dicker, Adam P.; Louis, Daniel Z.

    2015-03-15

    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 therapy 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. However

  13. Adverse psychosocial outcomes associated with drug use among US high school seniors: a comparison of alcohol and marijuana

    PubMed Central

    Palamar, Joseph J.; Fenstermaker, Michael; Kamboukos, Dimitra; Ompad, Danielle C.; Cleland, Charles M.; Weitzman, Michael

    2015-01-01

    Objectives There is debate about whether marijuana (cannabis) use is more dangerous than alcohol use. Although difficult to make objective comparisons, research is needed to compare relative dangers in order to help inform preventive efforts and policy. Methods Data were analyzed from a nationally representative sample of high school seniors in the Monitoring the Future study (2007–2011; Weighted n = 7437; modal age: 18) who reported lifetime use of alcohol or marijuana. Students were asked to indicate whether they experienced various adverse psychosocial outcomes resulting from use of each substance. We examined which outcomes were more prevalent for each substance. Results Compared to alcohol use, marijuana use was more commonly reported to compromise relationships with teachers or supervisors, result in less energy or interest, and result in lower school or job performance. Compared to marijuana use, alcohol was more commonly reported to compromise relationships with friends and significant others; it was also reported to lead to more regret (particularly among females), and driving unsafely. Marijuana users were more likely to report no adverse outcomes. Females and white students were more likely to report various adverse outcomes and higher frequency use of each substance also increased occurrences of reported adverse outcomes. Conclusions Marijuana and alcohol are associated with unique adverse psychosocial outcomes. Outcomes differ by sex and race/ethnicity, and perception or experience of outcomes may also be related to legal status and associated stigma. Public health interventions may be more effective by focusing on harm reduction strategies for these drug-specific outcomes. PMID:25169838

  14. 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

  15. School Mobility and Developmental Outcomes in Young Adulthood

    PubMed Central

    Herbers, Janette E.; Reynolds, Arthur J.; Chen, Chin-Chih

    2014-01-01

    School mobility has been shown to increase the risk of poor achievement, behavior problems, grade retention, and high school drop-out. Using data over 25 years from the Chicago Longitudinal Study, we investigated the unique risk of school moves on a variety of young adult outcomes including educational attainment, occupational prestige, depression symptoms, and criminal arrests. We also investigated how the timing of school mobility, whether earlier or later in the academic career, may differentially predict these outcomes over and above associated risks. Results indicate that students who experience more school changes between kindergarten and twelfth grade are less likely to complete high school on time, complete fewer years of school, attain lower levels of occupational prestige, are more likely to experience symptoms of depression, and are more likely to be arrested as adults. Furthermore, the number of school moves predicted above and beyond associated risks such as residential mobility and family poverty. When timing of school mobility was examined, results indicated more negative outcomes associated with moves later in the grade school career, particularly between fourth and eighth grade. PMID:23627959

  16. Family Context, Mexican-Origin Adolescent Mothers' Parenting Knowledge, and Children's Subsequent Developmental Outcomes

    PubMed Central

    Jahromi, Laudan B.; Guimond, Amy B.; Umaña-Taylor, Adriana J.; Updegraff, Kimberly A.; Toomey, Russell B.

    2014-01-01

    This study examined parenting knowledge among Mexican-origin adolescent mothers (N = 191; M age = 16.26 years), family contextual factors associated with adolescents' parenting knowledge, and toddlers' (M age = 2.01 years) subsequent developmental outcomes. Data came from home interviews and direct child assessments. Adolescents both under- and over-estimated children's developmental timing, and showed differences in their knowledge of specific developmental domains. Instrumental support from mother figures was positively linked to adolescents' knowledge accuracy, whereas emotional support was negatively related to adolescents' knowledge confidence. Furthermore, whereas mother figures' autonomy-granting was positively linked to knowledge confidence, psychological control was associated with less accurate adolescent parenting knowledge. Toddlers of adolescents with more accurate knowledge showed positive developmental functioning. Intervention implications are discussed. PMID:24004448

  17. Perceived Neighborhood Violence, Parenting Styles, and Developmental Outcomes among Spanish Adolescents

    ERIC Educational Resources Information Center

    Gracia, Enrique; Fuentes, Maria C.; Garcia, Fernando; Lila, Marisol

    2012-01-01

    This article analyzed perceptions of neighborhood violence of Spanish adolescents (N = 1,015) from authoritative, authoritarian, indulgent, and neglectful families, and its association with three sets of developmental outcomes (psychological, behavioral, and academic). Tests of main and interactive effects were conducted to answer research…

  18. Trends in Outcomes of the Vocational Rehabilitation Program for Adults with Developmental Disabilities: 1995-2005

    ERIC Educational Resources Information Center

    Migliore, Alberto; Butterworth, John

    2008-01-01

    This article describes national trends in outcomes of the vocational rehabilitation (VR) program, with a focus on adults with developmental disabilities during the period of 1995 to 2005. Findings show that the VR program has made substantial progress in excluding extended employment from the array of possible employment closures. Efforts are…

  19. Developmental Trajectories of Boys' and Girls' Delinquency: Sex Differences and Links to Later Adolescent Outcomes

    ERIC Educational Resources Information Center

    Miller, Shari; Malone, Patrick S.; Dodge, Kenneth A.

    2010-01-01

    This study examined gender differences in trajectories of delinquent behaviors over a 6-year period in adolescence and differential outcomes of these diverse developmental pathways. Participants were 754 children who were part of a longitudinal study of the development of early starting conduct problems. Four trajectory patterns were identified…

  20. Biomedical Risk, Psychosocial Influences, and Developmental Outcomes: Lessons from the Pediatric HIV Population in Africa

    ERIC Educational Resources Information Center

    Serpell, Robert; Marfo, Kofi; Abubakar, Amina

    2014-01-01

    Sub-Saharan Africa is home to millions of HIV-affected children. These children are likely to experience multiple developmental delays. In this chapter, I present data highlighting compromised neurobehavioral, mental health, and scholastic outcomes for children affected by HIV. Furthermore, I discuss biomedical factors (e.g., disease severity and…

  1. Social Outcomes in Childhood Brain Disorder: A Heuristic Integration of Social Neuroscience and Developmental Psychology

    ERIC Educational Resources Information Center

    Yeates, Keith Owen; Bigler, Erin D.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn

    2007-01-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer…

  2. Experiences and Outcomes of Preschool Physical Education: An Analysis of Developmental Discourses in Scottish Curricular Documentation

    ERIC Educational Resources Information Center

    McEvilly, Nollaig

    2014-01-01

    This article provides an analysis of developmental discourses underpinning preschool physical education in Scotland's Curriculum for Excellence. Implementing a post-structural perspective, the article examines the preschool experiences and outcomes related to physical education as presented in the Curriculum for Excellence "health and…

  3. Parental Factors Correlated with Developmental Outcome in the Migrant Head Start Child.

    ERIC Educational Resources Information Center

    Siantz, Mary Lou de Leon; Smith, M. Shelton

    1994-01-01

    Examined parental factors correlated with developmental outcomes among 60 Mexican American migrant farmworker children. Found that maternal parenting style accounted for a significant amount of the variance in child behavior problems reported by the mothers, whereas maternal social support helped to explain the variance in peer acceptance reported…

  4. Effects of a psychosocial couple-based prevention program on adverse birth outcomes.

    PubMed

    Feinberg, Mark E; Roettger, Michael E; Jones, Damon E; Paul, Ian M; Kan, Marni L

    2015-01-01

    Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)-a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression-on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects. PMID:24969352

  5. Adverse birth outcomes in the vicinity of industrial installations in Spain 2004-2008.

    PubMed

    Castelló, Adela; Río, Isabel; García-Pérez, Javier; Fernández-Navarro, Pablo; Waller, Lance A; Clennon, Julie A; Bolúmar, Francisco; López-Abente, Gonzalo

    2013-07-01

    Industrial activity is one of the main sources of ambient pollution in developed countries. However, research analyzing its effect on birth outcomes is inconclusive. We analyzed the association between proximity of mother's municipality of residence to industries from 24 different activity groups and risk of very (VPTB) and moderate (MPTB) preterm birth, very (VLBW) and moderate (MLBW) low birth weight, and small for gestational age (SGA) in Spain, 2004-2008. An ecological study was defined, and a "near vs. far" analysis (3.5 km threshold) was carried out using Hierarchical Bayesian models implemented via Integrated Nested Laplace Approximation. VPTB risk was higher for mothers living near pharmaceutical companies. Proximity to galvanization and hazardous waste management industries increased the risk of MPTB. Risk of VLBW was higher for mothers residing near pharmaceutical and non-hazardous or animal waste management industries. For MLBW many associations were found, being notable the proximity to mining, biocides and animal waste management plants. The strongest association for SGA was found with proximity to management animal waste plants. These results highlight the importance of further research on the relationship between proximity to industrial sites and the occurrence of adverse birth outcomes especially for the case of pharmaceutical and animal waste management activities. PMID:23322413

  6. Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection

    PubMed Central

    Micic, Dejan; Rao, Krishna; Trindade, Bruno Caetano; Walk, Seth T.; Chenoweth, Elizabeth; Jain, Ruchika; Trivedi, Itishree; Santhosh, Kavitha; Young, Vincent B.; Aronoff, David M.

    2015-01-01

    Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI. PMID:26500740

  7. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. PMID:25288430

  8. Effects of a Psychosocial Couple-Based Prevention Program on Adverse Birth Outcomes

    PubMed Central

    Roettger, Michael E.; Jones, Damon E.; Paul, Ian M.; Kan, Marni L.

    2015-01-01

    Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)—a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression—on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects. PMID:24969352

  9. Child marriage and its association with adverse reproductive outcomes for women in Bangladesh.

    PubMed

    Kamal, S M Mostafa; Hassan, Che Hashim

    2015-03-01

    This study examines the prevalence of child marriage and its effect on reproductive outcomes among women in Bangladesh using the most recent 2011 Bangladesh Demographic and Health Survey data. Both bivariate and multivariate statistical techniques used in the study yielded quantitatively important and reliable estimates of child marriage and its impact on adverse reproductive and health outcomes. Overall, 77% of the marriages among women aged 20 to 49 years old took place before the age of 18 years. Women's education is the most single significant determinant of child marriage. Findings revealed that after being adjusted for sociodemographic factors, child marriage significantly (P < .001) increases the likelihood of stillbirth/miscarriage (odds ratio [OR] = 1.80; 95% confidence interval [CI] = 1.45-2.24) and pregnancy termination (OR = 1.24; 95% CI = 1.12-1.38). Programs should aim to retain girls in school for longer periods not only to raise the age at first marriage but also for sound reproductive health and overall social development of Bangladesh. PMID:24097938

  10. Vitamins and neural and cognitive developmental outcomes in children.

    PubMed

    Benton, David

    2012-02-01

    The role of vitamin status in the development of the brain and the subsequent functioning of the brain was considered. There are data with a range of vitamins, from animal studies and human studies in developing countries, suggesting that a clinical deficiency during the critical period when the brain is developing causes permanent damage. To date there is, however, with the exception of cases of clinical deficiency such as those that might be associated with a vegan diet, little evidence that variations in the diet of those living in industrialised countries have a lasting developmental influence. Similarly, later in life clinical deficiencies of various vitamins disrupt cognition although there is to date limited evidence that variations in the intake of single vitamins in industrialised societies influence functioning. It may well be, however, unreasonable to expect that vitamins examined in isolation will be associated with differences in cognitive functioning. The output of the brain reflects millions of metabolic processes, each potentially susceptible to any of a range of vitamins. A diet poor in one respect is likely to be poor in other respects as well. As such, the preliminary reports in double-blind placebo-controlled trials that aspects of cognition and behaviour respond to supplementation with multi-micronutrients may indicate the way forward. PMID:22030620

  11. Developmental outcome after a single episode of status epilepticus.

    PubMed

    Roy, Hélène; Lippé, Sarah; Lussier, Francine; Sauerwein, Hannelore Catherine; Lortie, Anne; Lacroix, Jacques; Lassonde, Maryse

    2011-08-01

    Consequences of status epilepticus (SE) on psychomotor development and the specific impact of the convulsive event on emerging executive functions remain controversial. Infants treated for a single episode of SE, those treated for a single febrile seizure, and healthy infants were tested with respect to motor development, language, personal, and social skills and self-regulation. The children were divided into two age groups to investigate the impact of the convulsive event at different windows of brain maturation. We found that infants who had had SE were inferior to healthy controls on the development scales. Age differentiated SE impact on visuomotor development versus sociolinguistic development. Children who had been treated for SE had significantly more difficulties delaying a response to an attractive stimulus in one of the long-delay conditions. A single episode of SE can interfere with psychomotor and cognitive development in children without previous developmental delay, and it seems that the functions that are emerging at the time of insult are most vulnerable. PMID:21705280

  12. Vagal Regulation of Heart Rate in the Prediction of Developmental Outcome for Very Low Birth Weight Preterm Infants.

    ERIC Educational Resources Information Center

    Doussard-Roosevelt, Jane A.; And Others

    1997-01-01

    Used heart rate and respiratory sinus arrhythmia (RSA) assessed at 33 to 35 weeks gestational age to predict developmental outcome at 3 years for very low birth weight infants. Found that RSA measures predicted developmental outcome beyond effects of birth weight, medical risk, and socioeconomic status. For infants < 1,000 grams, RSA maturation…

  13. Planned Repeat Cesarean Section at Term and Adverse Childhood Health Outcomes: A Record-Linkage Study

    PubMed Central

    Black, Mairead; Bhattacharya, Siladitya; Philip, Sam; Norman, Jane E.; McLernon, David J.

    2016-01-01

    Background Global cesarean section (CS) rates range from 1% to 52%, with a previous CS being the commonest indication. Labour following a previous CS carries risk of scar rupture, with potential for offspring hypoxic brain injury, leading to high rates of repeat elective CS. However, the effect of delivery by CS on long-term outcomes in children is unclear. Increasing evidence suggests that in avoiding exposure to maternal bowel flora during labour or vaginal birth, offspring delivered by CS may be adversely affected in terms of energy uptake from the gut and immune development, increasing obesity and asthma risks, respectively. This study aimed to address the evidence gap on long-term childhood outcomes following repeat CS by comparing adverse childhood health outcomes after (1) planned repeat CS and (2) unscheduled repeat CS with those that follow vaginal birth after CS (VBAC). Methods and Findings A data-linkage cohort study was performed. All second-born, term, singleton offspring delivered between 1 January 1993 and 31 December 2007 in Scotland, UK, to women with a history of CS (n = 40,145) were followed up until 31 January 2015. Outcomes assessed included obesity at age 5 y, hospitalisation with asthma, learning disability, cerebral palsy, and death. Cox regression and binary logistic regression were used as appropriate to compare outcomes following planned repeat CS (n = 17,919) and unscheduled repeat CS (n = 8,847) with those following VBAC (n = 13,379). Risk of hospitalisation with asthma was greater following both unscheduled repeat CS (3.7% versus 3.3%, adjusted hazard ratio [HR] 1.18, 95% CI 1.05–1.33) and planned repeat CS (3.6% versus 3.3%, adjusted HR 1.24, 95% CI 1.09–1.42) compared with VBAC. Learning disability and death were more common following unscheduled repeat CS compared with VBAC (3.7% versus 2.3%, adjusted odds ratio 1.64, 95% CI 1.17–2.29, and 0.5% versus 0.4%, adjusted HR 1.50, 95% CI 1.00–2.25, respectively). Risk of obesity

  14. Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions.

    PubMed

    Stamoulis, Catherine; Vanderwert, Ross E; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A

    2015-12-01

    Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross-frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1-3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross-frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross

  15. Hypertension: An Unstudied Potential Risk Factor for Adverse Outcomes during Continuous Flow Ventricular Assist Device Support

    PubMed Central

    Wasson, Lauren T.; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P.; Demmer, Ryan T.; Colombo, Paolo C.

    2014-01-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device-implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device-implantation HTN as a potential predictor of adverse CF-LVAD outcomes. Hypertension among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard non-invasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-deflation cuff system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may i) consider potential mechanisms relating HTN to poor outcomes, ii) realize that HTN management is a stated goal despite scarce evidence, and iii) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  16. Hypertension: an unstudied potential risk factor for adverse outcomes during continuous flow ventricular assist device support.

    PubMed

    Wasson, Lauren T; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P; Demmer, Ryan T; Colombo, Paolo C

    2015-05-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device implantation HTN as a potential predictor of adverse CF-LVAD outcomes. HTN among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard noninvasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-cuff deflation system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may (1) consider potential mechanisms relating HTN to poor outcomes, (2) realize that HTN management is a stated goal despite scarce evidence, and (3) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  17. Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana

    PubMed Central

    Chen, Jennifer Y.; Ribaudo, Heather J.; Souda, Sajini; Parekh, Natasha; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen; Dryden-Peterson, Scott; Creek, Tracy; Jimbo, William; Madidimalo, Tebogo; Makhema, Joseph; Essex, Max; Shapiro, Roger L

    2012-01-01

    Background. It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings. Methods. We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)–infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4+ lymphocyte cell count. Results. Of 33 148 women, 32 113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4+ was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB. Conclusions. HAART receipt during pregnancy was associated with increased PTD, SGA, and SB. PMID:23066160

  18. A Meta Analysis on Risks of Adverse Pregnancy Outcomes in Toxoplasma gondii Infection

    PubMed Central

    Zhang, Hao; Peng, Hong-Juan; Lindsay, David S.

    2014-01-01

    Objective Quantified risks of congenital Toxoplasma gondii infection and abnormal pregnancy outcomes following primary maternal infection were evaluated with meta- analysis based on published studies. Methods The related literatures were searched in multiple literature databases regardless of languages. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risks of vertical transmission of Toxoplasma gondii and abnormal pregnancy outcomes following primary maternal infection with meta-analysis. Results 53 of the 2632 searched literatures were included in our analysis. The incidence of abnormal pregnancy outcomes in T. gondii infected pregnant women (infected group) was significantly higher than that in the uninfected pregnant women (control group) (OR = 5.10; 95% CI, 3.85–6.75). Toxoplasma gondii infection rate in the abnormal-pregnancy-outcome group was significantly higher than in the normal-pregnancy group (OR = 3.71; 95% CI, 3.31–4.15). The pooled rate of vertical transmission was 20% (95% CI, 15%–26%) in maternal infection of T. gondii. The incidences of vertical transmission in women who were infected in the first, second or third trimester of pregnancy were 5% (95%CI, 2%–16%), 13% (95%CI, 7%–23%), and 32% (95%CI, 24%–41%), respectively. The rates of vertical transmission in women who were treated with spiramycin-only, PSF (pyrimethamine + sulfadiazine + folinic acid) or PS (pyrimethamine + sulfadiazine) combined with spiramycin, or other untypical treatments were 13% (95%CI, 7%–22%), 13%(95%CI, 7%–25%), and 24%(95%CI, 18%–32%), respectively. Conclusions Toxoplasma gondii infection can result in adverse pregnancy outcomes in pregnant women. The pooled rate of vertical transmission was 20% in maternal infection and the incidences of vertical transmission increased in the first, second or third trimester of pregnancy. The pooled rates of transmission in groups treated with spiramycin-only, PSF or PS combined with

  19. Development of Children at Risk for Adverse Outcomes Participating in Early Intervention in Developing Countries: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Wallander, Jan L.; Bann, Carla M.; Biasini, Fred J.; Goudar, Shivaprasad S.; Pasha, Omrana; Chomba, Elwyn; McClure, Elizabeth; Carlo, Waldemar A.

    2014-01-01

    Background: Previous research has indicated positive effects of early developmental intervention (EDI) on the development of children in developing countries. Few studies, however, have examined longitudinally when differential treatment effects may be observed and whether differential outcomes are associated with exposure to different risk…

  20. The relationship of maternal and fetal toxicity in developmental toxicology bioassays with notes on the biological significance of the "no observed adverse effect level".

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects and include dose levels that induce maternal toxicity. The work reported here was undertaken to evaluate the relationship of maternal and fetal toxicity. It co...

  1. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA

    USGS Publications Warehouse

    Xun Shi; Ayotte, Joseph; Akikazu Onda; Stephanie Miller; Judy Rees; Diane Gilbert-Diamond; Onega, Tracy L; Gui, Jiang; Karagas, Margaret R.; Moeschler, John B

    2015-01-01

    There is increasing evidence of the role of arsenic in the etiology of adverse human reproductive outcomes. Because drinking water can be a major source of arsenic to pregnant women, the effect of arsenic exposure through drinking water on human birth may be revealed by a geospatial association between arsenic concentration in groundwater and birth problems, particularly in a region where private wells substantially account for water supply, like New Hampshire, USA. We calculated town-level rates of preterm birth and term low birth weight (term LBW) for New Hampshire, by using data for 1997–2009 stratified by maternal age. We smoothed the rates by using a locally weighted averaging method to increase the statistical stability. The town-level groundwater arsenic probability values are from three GIS data layers generated by the US Geological Survey: probability of local groundwater arsenic concentration >1 µg/L, probability >5 µg/L, and probability >10 µg/L. We calculated Pearson’s correlation coefficients (r) between the reproductive outcomes (preterm birth and term LBW) and the arsenic probability values, at both state and county levels. For preterm birth, younger mothers (maternal age <20) have a statewider = 0.70 between the rates smoothed with a threshold = 2,000 births and the town mean arsenic level based on the data of probability >10 µg/L; for older mothers, r = 0.19 when the smoothing threshold = 3,500; a majority of county level r values are positive based on the arsenic data of probability >10 µg/L. For term LBW, younger mothers (maternal age <25) have a statewide r = 0.44 between the rates smoothed with a threshold = 3,500 and town minimum arsenic concentration based on the data of probability >1 µg/L; for older mothers, r = 0.14 when the rates are smoothed with a threshold = 1,000 births and also adjusted by town median household income in 1999, and the arsenic values are the town minimum based on probability

  2. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA.

    PubMed

    Shi, Xun; Ayotte, Joseph D; Onda, Akikazu; Miller, Stephanie; Rees, Judy; Gilbert-Diamond, Diane; Onega, Tracy; Gui, Jiang; Karagas, Margaret; Moeschler, John

    2015-04-01

    There is increasing evidence of the role of arsenic in the etiology of adverse human reproductive outcomes. Because drinking water can be a major source of arsenic to pregnant women, the effect of arsenic exposure through drinking water on human birth may be revealed by a geospatial association between arsenic concentration in groundwater and birth problems, particularly in a region where private wells substantially account for water supply, like New Hampshire, USA. We calculated town-level rates of preterm birth and term low birth weight (term LBW) for New Hampshire, by using data for 1997-2009 stratified by maternal age. We smoothed the rates by using a locally weighted averaging method to increase the statistical stability. The town-level groundwater arsenic probability values are from three GIS data layers generated by the US Geological Survey: probability of local groundwater arsenic concentration >1 µg/L, probability >5 µg/L, and probability >10 µg/L. We calculated Pearson's correlation coefficients (r) between the reproductive outcomes (preterm birth and term LBW) and the arsenic probability values, at both state and county levels. For preterm birth, younger mothers (maternal age <20) have a statewide r = 0.70 between the rates smoothed with a threshold = 2,000 births and the town mean arsenic level based on the data of probability >10 µg/L; for older mothers, r = 0.19 when the smoothing threshold = 3,500; a majority of county level r values are positive based on the arsenic data of probability >10 µg/L. For term LBW, younger mothers (maternal age <25) have a statewide r = 0.44 between the rates smoothed with a threshold = 3,500 and town minimum arsenic concentration based on the data of probability >1 µg/L; for older mothers, r = 0.14 when the rates are smoothed with a threshold = 1,000 births and also adjusted by town median household income in 1999, and the arsenic values are the town minimum based on probability >10 µg/L. At the county level for

  3. Homeschooled adolescents in the United States: developmental outcomes.

    PubMed

    Green-Hennessy, Sharon

    2014-06-01

    The mission of schools has broadened beyond academics to address risk behaviors such as substance use, delinquency, and socialization problems. With an estimated 3.4% of all U.S. youth being homeschooled, this study examines how U.S. homeschoolers fare on these outcomes given their lack of access to these school services. Adolescents (ages 12-17) from the 2002 through 2011 National Surveys of Drug Use and Health (NSDUH) were divided based on school status (home vs. traditional schooling) and religious affiliation (stronger vs. weaker). Controlling for demographic differences, homeschoolers with weaker religious ties were three times more likely to report being behind their expected grade level and two and a half times more likely to report no extracurricular activities in the prior year than their traditionally schooled counterparts. This group was also more likely to report lax parental attitudes toward substance use. Findings suggest homeschoolers with weaker religious ties represent an at-risk group. PMID:24793392

  4. Retinal artery and vein thrombotic occlusion during pregnancy: markers for familial thrombophilia and adverse pregnancy outcomes

    PubMed Central

    Kurtz, Will S; Glueck, Charles J; Hutchins, Robert K; Sisk, Robert A; Wang, Ping

    2016-01-01

    Background Ocular vascular occlusion (OVO), first diagnosed during or immediately after giving birth, often reflects superposition of the physiologic thrombophilia of pregnancy on previously undiagnosed underlying familial or acquired thrombophilia associated with spontaneous abortion, eclampsia, or maternal thrombosis. Specific aim We describe OVO, first diagnosed during pregnancy or immediately postpartum, in three young females (ages 32, 35, 40) associated with previously undiagnosed familial thrombophilia. Results Branch retinal artery occlusion (BRAO) occurred at 9 and 13 weeks gestation in two females, aged 32 and 35. Central retinal vein occlusion occurred immediately postpartum in a 40-year-old. One of the two females with BRAO subsequently developed eclampsia, and one had a history of unexplained first trimester spontaneous abortion. All three females were found to have previously unexplained familial thrombophilia. The two females with BRAO had low first trimester free protein S 42 (41%), lower normal limit (50%), and one of these two had high factor VIII (165%, upper normal limit 150%). The woman with central retinal vein occlusion had high factor XI (169%, upper normal limit 150%). Enoxaparin (40–60 mg/day) was started and continued throughout pregnancy in both females with BRAO to prevent maternal–placental thrombosis, and of these two females, one had an uncomplicated pregnancy course and term delivery, and the second was at gestational week 22 without complications at the time of this manuscript. There were no further OVO events in the two females treated with enoxaparin or in the untreated patient with postpartum eclampsia. Conclusion OVO during pregnancy may be a marker for familial or acquired thrombophilia, which confers increased thrombotic risk to the mother and pregnancy, associated with spontaneous abortion or eclampsia. OVO during pregnancy, particularly when coupled with antecedent adverse pregnancy outcomes, should prompt urgent

  5. Mercury in fish and adverse reproductive outcomes: results from South Carolina

    PubMed Central

    2014-01-01

    Background Mercury is a metal with widespread distribution in aquatic ecosystems and significant neurodevelopmental toxicity in humans. Fish biomonitoring for total mercury has been conducted in South Carolina (SC) since 1976, and consumption advisories have been posted for many SC waterways. However, there is limited information on the potential reproductive impacts of mercury due to recreational or subsistence fish consumption. Methods To address this issue, geocoded residential locations for live births from the Vital Statistics Registry (1995–2005, N = 362,625) were linked with spatially interpolated total mercury concentrations in fish to estimate potential mercury exposure from consumption of locally caught fish. Generalized estimating equations were used to test the hypothesis that risk of low birth weight (LBW, <2,500 grams) or preterm birth (PTB, <37 weeks clinical gestation) was greater among women living in areas with elevated total mercury in fish, after adjustment for confounding. Separate analyses estimated term LBW and PTB risks using residential proximity to rivers with fish consumption advisories to characterize exposure. Results Term LBW was more likely among women residing in areas in the upper quartile of predicted total mercury in fish (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.00-1.09) or within 8 kilometers of a river with a ‘do not eat’ fish advisory (1.05; 1.00-1.11) compared to the lowest quartile, or rivers without fish consumption restrictions, respectively. When stratified by race, risks for term LBW or PTB were 10-18% more likely among African-American (AA) mothers living in areas with the highest total fish mercury concentrations. Conclusions To our knowledge, this is the first study to examine the relationship between fish total mercury concentrations and adverse reproductive outcomes in a large population-based sample that included AA women. The ecologic nature of exposure assessment in this study

  6. Human Cytomegalovirus-Induces Cytokine Changes in the Placenta with Implications for Adverse Pregnancy Outcomes

    PubMed Central

    Hamilton, Stuart T.; Scott, Gillian; Naing, Zin; Iwasenko, Jenna; Hall, Beverley; Graf, Nicole; Arbuckle, Susan; Craig, Maria E.; Rawlinson, William D.

    2012-01-01

    Human cytomegalovirus (CMV) infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2) and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (p = 0.001 and p = 0.007), which was not observed in placentae infected with other microorganisms (p = 0.62 and p = 0.71) (n = 7 per group). Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml) caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (p = 0.0003 and p<0.0001) (n = 25 per group). Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml), caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (p = 0.0001 and p = 0.017). Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury. PMID

  7. Counterfactual Evaluation of Outcomes in Social Risk Decision-Making Situations: The Cognitive Developmental Paradox Revisited

    PubMed Central

    Padrón, Iván; Rodrigo, María Jose; de Vega, Manuel

    2016-01-01

    We report a study that examined the existence of a cognitive developmental paradox in the counterfactual evaluation of decision-making outcomes. According to this paradox adolescents and young adults could be able to apply counterfactual reasoning and, yet, their counterfactual evaluation of outcomes could be biased in a salient socio-emotional context. To this aim, we analyzed the impact of health and social feedback on the counterfactual evaluation of outcomes in a laboratory decision-making task involving short narratives with the presence of peers. Forty risky (e.g., taking or refusing a drug), forty neutral decisions (e.g., eating a hamburger or a hotdog), and emotions felt following positive or negative outcomes were examined in 256 early, mid- and late adolescents, and young adults, evenly distributed. Results showed that emotional ratings to negative outcomes (regret and disappointment) but not to positive outcomes (relief and elation) were attenuated when feedback was provided. Evidence of development of cognitive decision-making capacities did also exist, as the capacity to perform faster emotional ratings and to differentially allocate more resources to the elaboration of emotional ratings when no feedback information was available increased with age. Overall, we interpret these findings as challenging the traditional cognitive developmental assumption that development necessarily proceeds from lesser to greater capacities, reflecting the impact of socio-emotional processes that could bias the counterfactual evaluation of social decision-making outcomes. PMID:27152127

  8. Counterfactual Evaluation of Outcomes in Social Risk Decision-Making Situations: The Cognitive Developmental Paradox Revisited.

    PubMed

    Padrón, Iván; Rodrigo, María Jose; de Vega, Manuel

    2016-01-01

    We report a study that examined the existence of a cognitive developmental paradox in the counterfactual evaluation of decision-making outcomes. According to this paradox adolescents and young adults could be able to apply counterfactual reasoning and, yet, their counterfactual evaluation of outcomes could be biased in a salient socio-emotional context. To this aim, we analyzed the impact of health and social feedback on the counterfactual evaluation of outcomes in a laboratory decision-making task involving short narratives with the presence of peers. Forty risky (e.g., taking or refusing a drug), forty neutral decisions (e.g., eating a hamburger or a hotdog), and emotions felt following positive or negative outcomes were examined in 256 early, mid- and late adolescents, and young adults, evenly distributed. Results showed that emotional ratings to negative outcomes (regret and disappointment) but not to positive outcomes (relief and elation) were attenuated when feedback was provided. Evidence of development of cognitive decision-making capacities did also exist, as the capacity to perform faster emotional ratings and to differentially allocate more resources to the elaboration of emotional ratings when no feedback information was available increased with age. Overall, we interpret these findings as challenging the traditional cognitive developmental assumption that development necessarily proceeds from lesser to greater capacities, reflecting the impact of socio-emotional processes that could bias the counterfactual evaluation of social decision-making outcomes. PMID:27152127

  9. 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...

  10. Oligohydramnios in Women with Preterm Prelabor Rupture of Membranes and Adverse Pregnancy and Neonatal Outcomes

    PubMed Central

    Kacerovsky, Marian; Musilova, Ivana; Andrys, Ctirad; Drahosova, Marcela; Hornychova, Helena; Rezac, Adam; Kostal, Milan; Jacobsson, Bo

    2014-01-01

    Objective To determine the association between the presence of oligohydramnios, determined as an amniotic fluid index ≤ 5 cm and the intra-amniotic inflammatory response, fetal inflammatory response and neonatal outcomes in actively managed preterm prelabor rupture of membranes (PPROM). Methods Women with singleton pregnancies complicated by PPROM at a gestational age of between 24+0 and 36+6 weeks were included in the study. Ultrasound assessments of the amniotic fluid index and evaluation of the amniotic fluid interleukin (IL)-6 levels were performed at admission. The umbilical cord blood IL-6 levels were evaluated after delivery. Results In total, 74 women were included. The women with oligohydramnios did not have different amniotic fluid IL-6 levels [with oligohydramnios: median 342 pg/mL, interquartile range (IQR) 110-1809 vs. without oligohydramnios: median 256 pg/mL, IQR 122–748; p = 0.71] or umbilical cord blood IL-6 levels (with oligohydramnios: median 8.2 pg/mL, IQR 3.8–146.9 vs. without oligohydramnios: median 5.9 pg/mL, IQR 2.1–27.9; p = 0.14) than those without oligohydramnios. No association between oligohydramnios and neonatal morbidity was found. A correlation between the amniotic fluid index and the interval from rupture of membranes to amniocentesis was observed (rho = −0.34; p = 0.003). Conclusion The presence of oligohydramnios is not associated with an adverse outcome in actively managed PPROM in singleton pregnancies in the absence of other complications. PMID:25171293

  11. Inadequate gestational weight gain and adverse pregnancy outcomes among normal weight women in China

    PubMed Central

    Wen, Tingyuan; Lv, Yanwei

    2015-01-01

    Objective: The objective of the paper is to find the association between inadequate gestational weight gain and pregnancy outcomes in normal weight women in China. Method: A retrospective study was conducted among 13,776 normal weight pregnant women who received antenatal care and delivered singleton infants at the participating hospital during August, 2009 to July, 2013. Adverse pregnancy outcomes like low birth weight (LBW), preterm birth, birth asphyxia, neonatal intensive care unit (NICU) admission and length of hospital stay were compared and analyzed between two groups with inadequate and adequate gestational weight gain. Results: According to the IOM recommendations, inadequate gestational weight gain was found to be 14.7% in this study. Women with inadequate gestational weight gain (GWG) were found to be at a higher risk for LBW (aOR = 2.13, 95% CI: 1.75, 2.86) and preterm birth (aOR = 1.44, 95% CI: 1.21, 1.67) than those in the adequate gestational weight gain group, after adjusting for monthly family income, maternal education, occupation, and whether they received any advice regarding benefits of gestational weight gain and residential area. However, inadequate GWG was not associated with longer hospital stay (aOR = 1.13, 95% CI: 0.91-1.43) in adjusted model. In addition, the rate of birth asphyxia and NICU admission were similar in both groups (P > 0.05). Conclusions: Normal weight pregnant women with GWG below the recommended AIOM 2009 guidelines were found to be at an increased risk of low birth weight and preterm birth. PMID:25932249

  12. Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Adverse Birth Outcomes

    PubMed Central

    Aschengrau, Ann; Weinberg, Janice; Rogers, Sarah; Gallagher, Lisa; Winter, Michael; Vieira, Veronica; Webster, Thomas; Ozonoff, David

    2008-01-01

    Background Prior studies of prenatal exposure to tetrachloroethylene (PCE) have shown mixed results regarding its effect on birth weight and gestational age. Objectives In this retrospective cohort study we examined whether PCE contamination of public drinking-water supplies in Massachusetts influenced the birth weight and gestational duration of children whose mothers were exposed before the child’s delivery. Methods The study included 1,353 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 772 children of unexposed mothers. Birth records were used to identify subjects and provide information on the outcomes. Mothers completed a questionnaire to gather information on residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. Results We found no meaningful associations between PCE exposure and birth weight or gestational duration. Compared with children whose mothers were unexposed during the year of the last menstrual period (LMP), adjusted mean differences in birth weight were 20.9, 6.2, 30.1, and 15.2 g for children whose mothers’ average monthly exposure during the LMP year ranged from the lowest to highest quartile. Similarly, compared with unexposed children, adjusted mean differences in gestational age were −0.2, 0.1, −0.1, and −0.2 weeks for children whose mothers’ average monthly exposure ranged from the lowest to highest quartile. Similar results were observed for two other measures of prenatal exposure. Conclusions These results suggest that prenatal PCE exposure does not have an adverse effect on these birth outcomes at the exposure levels experienced by this population. PMID:18560539

  13. Prevalence of Adverse Pregnancy Outcomes, by Maternal Diabetes Status at First and Second Deliveries, Massachusetts, 1998–2007

    PubMed Central

    Kotelchuck, Milton; Wilson, Hoyt G.; Diop, Hafsatou; Shapiro-Mendoza, Carrie K.; England, Lucinda J.

    2015-01-01

    Introduction Understanding patterns of diabetes prevalence and diabetes-related complications across pregnancies could inform chronic disease prevention efforts. We examined adverse birth outcomes by diabetes status among women with sequential, live singleton deliveries. Methods We used data from the 1998–2007 Massachusetts Pregnancy to Early Life Longitudinal Data System, a population-based cohort of deliveries. We restricted the sample to sets of parity 1 and 2 deliveries. We created 8 diabetes categories using gestational diabetes mellitus (GDM) and chronic diabetes mellitus (CDM) status for the 2 deliveries. Adverse outcomes included large for gestational age (LGA), macrosomia, preterm birth, and cesarean delivery. We computed prevalence estimates for each outcome by diabetes status. Results We identified 133,633 women with both parity 1 and 2 deliveries. Compared with women who had no diabetes in either pregnancy, women with GDM or CDM during any pregnancy had increased risk for adverse birth outcomes; the prevalence of adverse outcomes was higher in parity 1 deliveries among women with no diabetes in parity 1 and GDM in parity 2 (for LGA [8.5% vs 15.1%], macrosomia [9.7% vs. 14.9%], cesarean delivery [24.7% vs 31.3%], and preterm birth [7.7% vs 12.9%]); and higher in parity 2 deliveries among those with GDM in parity 1 and no diabetes in parity 2 (for LGA [12.3% vs 18.2%], macrosomia [12.3% vs 17.2%], and cesarean delivery [27.0% vs 37.9%]). Conclusions Women with GDM during one of 2 sequential pregnancies had elevated risk for adverse outcomes in the unaffected pregnancy, whether the diabetes-affected pregnancy preceded or followed it. PMID:26652218

  14. 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.

  15. Adverse Outcomes Among Homeless Adolescents and Young Adults Who Report a History of Traumatic Brain Injury

    PubMed Central

    Harpin, Scott B.; Grubenhoff, Joseph A.; Rivara, Frederick P.

    2014-01-01

    Objectives. We examined the prevalence of self-reported traumatic brain injury (TBI) among homeless young people and explored whether sociodemographic characteristics, mental health diagnoses, substance use, exposure to violence, or difficulties with activities of daily living (ADLs) were associated with TBI. Methods. We analyzed data from the Wilder Homelessness Study, in which participants were recruited in 2006 and 2009 from streets, shelters, and locations in Minnesota that provide services to homeless individuals. Participants completed 30-minute interviews to collect information about history of TBI, homelessness, health status, exposure to violence (e.g., childhood abuse, assault), and other aspects of functioning. Results. Of the 2732 participating adolescents and young adults, 43% reported a history of TBI. Participants with TBI became homeless at a younger age and were more likely to report mental health diagnoses, substance use, suicidality, victimization, and difficulties with ADLs. The majority of participants (51%) reported sustaining their first injury prior to becoming homeless or at the same age of their first homeless episode (10%). Conclusions. TBI occurs frequently among homeless young people and is a marker of adverse outcomes such as mental health difficulties, suicidal behavior, substance use, and victimization. PMID:25122029

  16. Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population-Level Effects

    SciTech Connect

    Kramer, Vincent J.; Etterson, Matthew A.; Hecker, Markus; Murphy, Cheryl A.; Roesijadi, Guritno; Spade, Daniel J.; Spromberg, Julann A.; Wang, Magnus; Ankley, Gerald T.

    2010-11-24

    The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitors, predators, prey, habitat and other biotic and abiotic factors. Models of population-level effects of contaminants can integrate information from lower levels of biological organization and feed that information into higher-level community and ecosystem models. As individual-level endpoints are utilized to predict population responses, this requires that biological responses at lower levels of organization be translated into a form that is useable by the population modeler. In this paper we describe how mechanistic data, as captured in adverse outcome pathways, can be translated into modeling focused on population-level risk assessments. First, we present a succinct overview of different approaches to population modeling, and discuss the types of data needed for these models. Then we discuss how toxicity data are used currently for population modeling, and provide recommendations as to how testing might be modified to better generate information to support modeling. From this we describe how different key processes measured at the level of the individual serve as the bridge between mechanistic toxicology data and predictions of population status, and provide case examples of how this linkage has been/can be achieved.

  17. Adverse pregnancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981

    SciTech Connect

    Deane, M.; Swan, S.H.; Harris, J.A.; Epstein, D.M.; Neutra, R.R.

    1989-05-01

    An epidemiologic study was conducted to investigate a suspected cluster of adverse outcomes of pregnancies conceived in 1980-1981 among women who resided in a census tract in Santa Clara County, California that was thought to be exposed to drinking water from a well contaminated by an organic solvent, trichloroethane. A comparison census tract that received water from a different source was selected on the basis of demographic comparability. The cluster was confirmed; the odds ratio for spontaneous abortion was 2.3 (95% confidence interval (Cl) 1.3-4.2) after adjustment by multiple logistic regression for maternal risk factors, including maternal age, alcohol consumption, smoking, and prior fetal loss. The relative risk for congenital malformations was 3.1 (95% Cl 1.1-10.4). Because of the lack of precise information on the timing and extent of contamination, the pattern of spontaneous abortion rates throughout the study period cannot be used to either support or refute a causal inference.

  18. Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

    PubMed Central

    2010-01-01

    Objective To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results PD was associated with a higher risk of PTB (RRadj. 3.47 95%CI 1.62-7.43), LBW (RRadj. 2.93 95%CI 1.36-6.34) and PROM (RRadj. 2.48 95%CI 1.35-4.56), but not with SGA neonates (RR 2.38 95%CI 0.93 - 6.10). Conclusions PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women. PMID:21047427

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

    PubMed Central

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

    2016-01-01

    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. PMID:26917256

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

    PubMed

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

    2016-01-01

    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. PMID:26917256

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

    USGS Publications Warehouse

    Rattner, Barnett A.; Lazarus, Rebecca; 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.

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

    PubMed

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

    2015-09-01

    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. PMID:25943792

  3. Quantitative Adverse Outcome Pathway Analysis of Hatching in Zebrafish with CuO Nanoparticles.

    PubMed

    Muller, Erik B; Lin, Sijie; Nisbet, Roger M

    2015-10-01

    This study develops and evaluates a mechanistic model of the hatching of zebrafish eggs that were exposed to CuO engineered nanoparticles (ENP) in a high-throughput screening system and places this model in an adverse outcome pathway (AOP) that also includes CuO ENP dissolution and Cu bioaccumulation. Cu(2+) inhibits the proteolytic activity of Zebrafish Hatching Enzyme 1 and thereby delay or impair hatching success. This study demonstrates that noncompetitive inhibition kinetics describe the impact of dissolved Cu on hatching; it is estimated that indefinitely long exposure to 1.88 μM dissolved Cu in the environment reduces hatching enzyme activity by 50%. The complexity arising from CuO ENP dissolution and CuO ENP assisted bioaccumulation of Cu has led to apparently contradictory findings about ion versus "nano" effects on hatching. Model-mediated data analyses indicate that, relative to copper salts, CuO ENPs increase the uptake rates of Cu into the perivitelline space up to 8 times. The toxicity assessment framework in this study can be adapted to accommodate other types of toxicant, environmental samples and other aquatic oviparous species. PMID:26378804

  4. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer

    PubMed Central

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-01-01

    Purpose Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. Materials and Methods This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. Results A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Conclusion Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer. PMID:26511801

  5. Correlates of functional status, self-management, and developmental competence outcomes in adolescents with spina bifida.

    PubMed

    Sawin, Kathleen J; Buran, Constance F; Brei, Timothy J; Fastenau, Philip S

    2003-01-01

    Adolescents with spina bifida (SB), a congenital spinal cord impairment, are at high risk for negative outcomes. Even those with favorable cognitive status often fail to achieve independence, exhibiting poor functional and psychosocial outcomes. The purpose of this study was to examine the relationship between adaptation outcomes (functional status, self-management, and developmental competence) and SB condition-specific, adolescent protective factors, and family protective factors in a sample of adolescents with SB. Individual, interpersonal, and social developmental competence were explored. Sixty-six adolescent/parent pairs were interviewed. Data analysis included descriptive statistics, Cronbach alpha coefficients, and partial correlations controlling for age. All instruments had acceptable reliabilities. Factors associated with outcomes generally fell into two patterns. SB condition-specific variables and adolescent activities (e.g., decision-making, household responsibilities) were related to functional status, self-management, and social competence. In contrast, adolescent beliefs (hope, attitude, and communication efficacy) were predominantly related to individual, interpersonal, and overall developmental competence. PMID:14626030

  6. Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol

    PubMed Central

    2014-01-01

    Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide. Most chronic diseases are associated with underlying preventable risk factors, such as elevated blood pressure, high blood glucose or glucose intolerance, high lipid levels, physical inactivity, excessive sedentary behaviours, and overweight/obesity. The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood. Sugar-sweetened beverages are known to be significant sources of additional caloric intake, and given recent attention to their contribution in the development of chronic diseases, a systematic review is warranted. We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are. Methods/Design Of interest are studies addressing sugar-sweetened beverage consumption, taking a broad perspective. Both direct consumption studies as well as those evaluating interventions that influence consumption (e.g. school policy, educational) will be relevant. Non-specific or multi-faceted behavioural, educational, or policy interventions may also be included subject to the level of evidence that exists for the other interventions/exposures. Comparisons of interest and endpoints of interest are pre-specified. We will include randomized controlled trials, controlled clinical trials, interrupted time series studies, controlled before-after studies, prospective and retrospective comparative cohort studies, case–control studies, and nested case–control designs. The MEDLINE®, Embase, The Cochrane Library, CINAHL, ERIC, and PsycINFO® databases and grey literature sources will be searched. The processes for selecting studies, abstracting data, and resolving conflicts are described. We will assess risk of bias using design-specific tools. To determine sets of

  7. 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 ...

  8. 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 ...

  9. 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...

  10. 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...

  11. 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 ...

  12. 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...

  13. 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...

  14. 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

  15. Risk of adverse birth outcomes in populations living near landfill sites

    PubMed Central

    Elliott, Paul; Briggs, David; Morris, Sara; de Hoogh, Cornelis; Hurt, Christopher; Jensen, Tina Kold; Maitland, Ian; Richardson, Sylvia; Wakefield, Jon; Jarup, Lars

    2001-01-01

    Objective To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. Design Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. Setting Great Britain. Subjects Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). Main outcome measures All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). Results For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. Conclusions We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various

  16. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study.

    PubMed

    Trotta, Antonella; Murray, Robin M; David, Anthony S; Kolliakou, Anna; O'Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L

    2016-03-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  17. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study

    PubMed Central

    Trotta, Antonella; Murray, Robin M.; David, Anthony S.; Kolliakou, Anna; O’Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L.

    2016-01-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  18. Legacy for ChildrenTM: a pair of randomized controlled trials of a public health model to improve developmental outcomes among children in poverty

    PubMed Central

    2012-01-01

    Background One in five Americans under age 18 lives in a family below the Federal poverty threshold. These more than 15 million children are at increased risk of a wide variety of adverse long-term health and developmental outcomes. The early years of life are critical to short- and long-term health and well-being. The Legacy for ChildrenTM model was developed in response to this need and marries the perspectives of epidemiology and public health to developmental psychology theory in order to better address the needs of children at environmental risk for poor developmental outcomes. Methods/design The Legacy for ChildrenTM group-based parenting intervention model was evaluated as a pair of randomized controlled trials among low-income families in Miami and Los Angeles. The study was designed to allow for site-stratified analysis in order to evaluate each model implementation separately. Evaluation domains include comprehensive assessments of family, maternal, and child characteristics, process outcomes, and prospective programmatic cost. Data collection began prenatally or at birth and continues into school-age. Discussion The societal costs of poor developmental outcomes are substantial. A concerted effort from multiple sectors and disciplines, including public health, is necessary to address these societal concerns. Legacy uses a public health model to engage parents and promote overall child well-being in families in poverty through rigorous evaluation methodologies and evidence-based intervention strategies. This study collects rich and modular information on maternal and child outcomes, process, and cost that will enable a detailed understanding of how Legacy works, how it can be refined and improved, and how it can be translated and disseminated. Taken together, these results will inform public policy and help to address issues of health disparities among at-risk populations. Trial registration NCT00164697 PMID:22917446

  19. DOSE RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY: II. COMPARISON OF GENERIC BENCHMARK DOSE ESTIMATES WITH NO OBSERVED ADVERSE EFFECT LEVELS

    EPA Science Inventory

    The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large data base of 246 developmental toxicity experiments compiled for use in comparing alternative approaches to developmental toxicity risk assessment. BMD estimates derived w...

  20. Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index

    PubMed Central

    El Ayadi, Alison M.; Nathan, Hannah L.; Seed, Paul T.; Butrick, Elizabeth A.; Hezelgrave, Natasha L.; Shennan, Andrew H.; Miller, Suellen

    2016-01-01

    Objective To determine the optimal vital sign predictor of adverse maternal outcomes in women with hypovolemic shock secondary to obstetric hemorrhage and to develop thresholds for referral/intensive monitoring and need for urgent intervention to inform a vital sign alert device for low-resource settings. Study Design We conducted secondary analyses of a dataset of pregnant/postpartum women with hypovolemic shock in low-resource settings (n = 958). Using receiver-operating curve analysis, we evaluated the predictive ability of pulse, systolic blood pressure, diastolic blood pressure, shock index, mean arterial pressure, and pulse pressure for three adverse maternal outcomes: (1) death, (2) severe maternal outcome (death or severe end organ dysfunction morbidity); and (3) a combined severe maternal and critical interventions outcome comprising death, severe end organ dysfunction morbidity, intensive care admission, blood transfusion ≥ 5 units, or emergency hysterectomy. Two threshold parameters with optimal rule-in and rule-out characteristics were selected based on sensitivities, specificities, and positive and negative predictive values. Results Shock index was consistently among the top two predictors across adverse maternal outcomes. Its discriminatory ability was significantly better than pulse and pulse pressure for maternal death (p<0.05 and p<0.01, respectively), diastolic blood pressure and pulse pressure for severe maternal outcome (p<0.01), and systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for severe maternal outcome and critical interventions (p<0.01). A shock index threshold of ≥ 0.9 maintained high sensitivity (100.0) with clinical practicality, ≥ 1.4 balanced specificity (range 70.0–74.8) with negative predictive value (range 93.2–99.2), and ≥ 1.7 further improved specificity (range 80.7–90.8) without compromising negative predictive value (range 88.8–98.5). Conclusions For women with hypovolemic

  1. A meta-analysis of exposure to particulate matter and adverse birth outcomes

    PubMed Central

    2015-01-01

    Objectives The objective of this study was to conduct a systematic review to provide summarized evidence on the association between maternal exposure to particulate air pollution and birth weight (BW) and preterm birth (PTB) after taking into consideration the potential confounding effect of maternal smoking. Methods We systematically searched all published cohort and case-control studies examining BW and PTB association with particulate matter (PM, less than or equal to 2.5μm and 10.0 μm in diameter, PM2.5 and PM10, respectively) from PubMed and Web of Science, from January 1980 to April 2015. We extracted coefficients for continuous BW and odds ratio (OR) for PTB from each individual study, and meta-analysis was used to combine the coefficient and OR of individual studies. The methodological quality of individual study was assessed using a standard protocol proposed by Downs and Black. Forty-four studies met the inclusion criteria. Results In random effects meta-analyses, BW as a continuous outcome was negativelyassociated with 10 μg/m3 increase in PM10 (-10.31 g; 95% confidence interval [CI], -13.57 to -3.13 g; I-squared=0%, p=0.947) and PM2.5 (-22.17 g; 95% CI, -37.93 to -6.41 g; I-squared=92.3%, p <0.001) exposure during entire pregnancy, adjusted for maternal smoking. A significantly increased risk of PTB per 10 μg/m3 increase in PM10 (OR, 1.23; 95% CI, 1.04 to 1.41; I-squared=0%, p =0.977) and PM2.5 (OR, 1.14; 95% CI, 1.06 to 1.22; I-squared=92.5%, p <0.001) exposure during entire pregnancy was observed. Effect size of change in BW per 10 μg/m3 increase in PM tended to report stronger associations after adjustment for maternal smoking. Conclusions While this systematic review supports an adverse impact of maternal exposure to particulate air pollution on birth outcomes, variation in effects by exposure period and sources of heterogeneity between studies should be further explored. PMID:26796890

  2. Do sugar-sweetened beverages cause adverse health outcomes in adults? A systematic review protocol

    PubMed Central

    2014-01-01

    Background Chronic diseases, such as cardiovascular disease and type 2 diabetes, impose significant burden to public health. Most chronic diseases are associated with underlying preventable risk factors, such as elevated blood pressure, blood glucose, and lipids, physical inactivity, excessive sedentary behaviours, overweight and obesity, and tobacco usage. Sugar-sweetened beverages are known to be significant sources of additional caloric intake, and given recent attention to their contribution in the development of chronic diseases, a systematic review is warranted. We will assess whether the consumption of sugar-sweetened beverages in adults is associated with adverse health outcomes and what the potential moderating factors are. Methods/Design Of interest are studies addressing sugar-sweetened beverage consumption, taking a broad perspective. Both direct consumption studies as well as those evaluating interventions that influence consumption (e.g. school policy, educational) will be relevant. Non-specific or multi-faceted behavioural, educational, or policy interventions may also be included subject to the level of evidence that exists for the other interventions/exposures. Comparisons of interest and endpoints of interest are pre-specified. We will include randomized controlled trials, controlled clinical trials, interrupted time series studies, controlled before-after studies, prospective and retrospective comparative cohort studies, case-control studies, and nested case-control designs. The MEDLINE®, Embase, The Cochrane Library, CINAHL, ERIC, and PsycINFO® databases and grey literature sources will be searched. The processes for selecting studies, abstracting data, and resolving conflicts are described. We will assess risk of bias using design-specific tools. To determine sets of confounding variables that should be adjusted for, we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessments. Meta-analysis will

  3. LUPUS ANTICOAGULANT, BUT NOT ANTICARDIOLIPIN ANTIBODY, PREDICTS ADVERSE PREGNANCY OUTCOME IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES

    PubMed Central

    Lockshin, Michael D.; Kim, Mimi; Laskin, Carl A.; Guerra, Marta; Branch, D. Ware; Merrill, Joan; Petri, Michelle; Porter, Flint; Sammaritano, Lisa; Stephenson, Mary D.; Buyon, Jill; Salmon, Jane E.

    2012-01-01

    BACKGROUND Which serologic and clinical findings predict adverse pregnancy outcome (APO) in patients with antiphospholipid antibody (aPL) is controversial. METHODS PROMISSE is a multicenter, prospective observational study of risk factors for APO in patients with aPL (lupus anticoagulant [LAC], anticardiolipin antibody [aCL] and/or antibody to β2 glycoprotein I [anti-β2-GP-I]). We tested the hypothesis that a pattern of clinical and serological variables can identify women at highest risk for APO. RESULTS Between 2003 and 2011 we enrolled 144 pregnant patients, of whom 28 had APO. Thirty-nine percent of patients with LAC had APO, compared to 3% who did not have LAC (p < 0.0001). Only 8% of women with IgG aCL ≥40 u/mL but not LAC suffered APO, compared to 43% of those with LAC (p = 0.002). IgM aCL or IgG or IgM anti-β2-GP-I did not predict APO. In bivariate analysis, APO occurred in 52% of patients with and 13% of patients without prior thrombosis (p = 0.00005), and in 23% with SLE compared to 17% without SLE (not significant); SLE was a predictor in multivariate analysis. Prior pregnancy loss did not predict APO, nor did maternal race. Simultaneous aCL, anti-β2-GP-I, and LAC did not predict APO better than did LAC alone. CONCLUSIONS LAC is the primary predictor of APO after 12 weeks gestation in aPL-associated pregnancies. ACL and anti-β2-GP-I, if LAC is not also present, do not predict APO. PMID:22275304

  4. Taxonomic applicability of inflammatory cytokines in adverse outcome pathway (AOP) development.

    PubMed

    Angrish, Michelle M; Pleil, Joachim D; Stiegel, Matthew A; Madden, Michael C; Moser, Virginia C; Herr, David W

    2016-01-01

    Cytokines, low-molecular-weight messenger proteins that act as intercellular immunomodulatory signals, have become a mainstream preclinical marker for assessing the systemic inflammatory response to external stressors. The challenge is to quantitate from healthy subjects cytokine levels that are below or at baseline and relate those dynamic and complex cytokine signatures of exposures with the inflammatory and repair pathways. Thus, highly sensitive, specific, and precise analytical and statistical methods are critically important. Investigators at the U.S. Environmental Protection Agency (EPA) have implemented advanced technologies and developed statistics for evaluating panels of inflammatory cytokines in human blood, exhaled breath condensate, urine samples, and murine biological media. Advanced multiplex, bead-based, and automated analytical platforms provided sufficient sensitivity, precision, and accuracy over the traditional enzyme-linked immunosorbent assay (ELISA). Thus, baseline cytokine levels can be quantified from healthy human subjects and animals and compared to an in vivo exposure response from an environmental chemical. Specifically, patterns of cytokine responses in humans exposed to environmental levels of ozone and diesel exhaust, and in rodents exposed to selected pesticides (such as fipronil and carbaryl), were used as case studies to generally assess the taxonomic applicability of cytokine responses. The findings in this study may aid in the application of measureable cytokine markers in future adverse outcome pathway (AOP)-based toxicity testing. Data from human and animal studies were coalesced and the possibility of using cytokines as key events (KE) to bridge species responses to external stressors in an AOP-based framework was explored. PMID:26914248

  5. Cannabis and Neuropsychiatry, 2: The Longitudinal Risk of Psychosis as an Adverse Outcome.

    PubMed

    Andrade, Chittaranjan

    2016-06-01

    Psychosis is one of the most serious among the adverse effects associated with cannabis use. The association between cannabis use and psychosis has been variously explored in a series of recent meta-analyses. The results of these meta-analyses show that persons who develop psychosis experience onset of psychosis about 2-3 years earlier if they are cannabis users; this effect is not observed with alcohol or other substance use. Higher levels of cannabis use are associated with greater risk of psychosis. Current cannabis abuse or dependence (but not past use or lower levels of current use) increases the risk of transition into psychosis in persons at ultrahigh risk of psychosis. About a third of patients with first-episode psychosis are cannabis users, and, at follow-up, about half of these users are found to continue their cannabis use. Continued cannabis use (in those who are treated after developing psychosis) is associated with higher risk of relapse into psychosis, and discontinuation of cannabis use reduces the risk of relapse to that in cannabis nonusers. Finally, persons with psychosis who continue to use cannabis have more severe positive symptoms and poorer levels of functioning. Because experimental studies in humans show that cannabinoids and cannabis can induce psychotic symptoms, it is reasonable to assume that the epidemiologic data indicate a causal effect of cannabis in anticipating, triggering, or exacerbating psychosis in vulnerable individuals and in worsening the course and outcome of the illness in those who continue to use the substance. Given the public health implications of these findings, the trend to legalize medical marijuana must be viewed with concern, and efforts are necessary to educate patients and the public about the serious mental and physical health risks associated with cannabis use and abuse. PMID:27337422

  6. 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. PMID:26614264

  7. Limitations of toxicity characterization in life cycle assessment: Can adverse outcome pathways provide a new foundation?

    PubMed

    Gust, Kurt A; Collier, Zachary A; Mayo, Michael L; Stanley, Jacob K; Gong, Ping; Chappell, Mark A

    2016-07-01

    Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, development, production, and disposal, with the inherent benefit of providing a forecast of potential health and environmental impacts. However, a technical review of current life cycle impact assessment (LCIA) methods revealed limitations within the biological effects assessment protocols, including: simplistic assessment approaches and models; an inability to integrate emerging types of toxicity data; a reliance on linear impact assessment models; a lack of methods to mitigate uncertainty; and no explicit consideration of effects in species of concern. The purpose of the current study is to demonstrate that a new concept in toxicological and regulatory assessment, the adverse outcome pathway (AOP), has many useful attributes of potential use to ameliorate many of these problems, to expand data utility and model robustness, and to enable more accurate and defensible biological effects assessments within LCIA. Background, context, and examples have been provided to demonstrate these potential benefits. We additionally propose that these benefits can be most effectively realized through development of quantitative AOPs (qAOPs) crafted to meet the needs of the LCIA framework. As a means to stimulate qAOP research and development in support of LCIA, we propose 3 conceptual classes of qAOP, each with unique inherent attributes for supporting LCIA: 1) mechanistic, including computational toxicology models; 2) probabilistic, including Bayesian networks and supervised machine learning models; and 3) weight of evidence, including models built using decision-analytic methods. Overall, we have highlighted a number of potential applications of qAOPs that can refine and add value to LCIA. As the AOP concept and support framework matures, we see the potential for qAOPs to serve a foundational role for next-generation effects characterization within LCIA. Integr Environ Assess Manag

  8. Quality of community drinking water and the occurrence of late adverse pregnancy outcomes.

    PubMed

    Aschengrau, A; Zierler, S; Cohen, A

    1993-01-01

    The relationship between community drinking water quality and the occurrence of late adverse pregnancy outcomes was investigated by conducting a case-control study among women who delivered infants during August 1977 through March 1980 at Brigham and Women's Hospital in Massachusetts. The water quality indices were compared among 1,039 congenital anomaly cases, 77 stillbirth cases, 55 neonatal death cases, and 1,177 controls. Trace element levels were gathered from routine analyses of public water supplies from the communities in which the women resided during pregnancy. It was observed that, after adjustment for confounding, the frequency of stillbirths was increased for women exposed to chlorinated surface water (OR 2.6 95% CI 0.9-7.5) and for women exposed to detectable lead levels (OR 2.1; 95% CI 0.6-7.2); the frequency of cardiovascular defects was increased relative to detectable lead levels (OR 2.2, 95% CI 0.9-5.7); and the frequency of central nervous system defects was increased relative to the highest tertile of potassium (OR 6.3, 95% CI 1.1-37.3). The frequency of ear, face, and neck anomalies was increased in relation to detectable silver levels (OR 3.3, 95% CI 0.9-12.2), but the frequency decreased relative to high potassium levels (OR 0.2, 95% CI 0.1-0.7). The frequency of neonatal deaths was decreased relative to detectable fluoride levels (OR 0.4, 95% CI 0.2-1.0), and the frequency of musculoskeletal defects was decreased relative to detectable chromium levels (OR 0.4, 95% CI 0.2-1.0). The majority of these associations were not stable statistically. Further research is needed to corroborate these findings. PMID:8476301

  9. Birth malformations and other adverse perinatal outcomes in four U.S. Wheat-producing states.

    PubMed Central

    Schreinemachers, Dina M

    2003-01-01

    Chlorophenoxy herbicides are widely used in the United States and Western Europe for broadleaf weed control in grain farming and park maintenance. Most of the spring and durum wheat produced in the United States is grown in Minnesota, Montana, North Dakota, and South Dakota, with more than 85% of the acreage treated with chlorophenoxy herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA). Rates of adverse birth outcomes in rural, agricultural counties of these states during 1995-1997 were studied by comparing counties with a high proportion of wheat acreage and those with a lower proportion. Information routinely collected and made available by federal agencies was used for this ecologic study. Significant increases in birth malformations were observed for the circulatory/respiratory category for combined sexes [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.07-2.55]. A stronger effect was observed for the subcategory, which excluded heart malformations (OR = 2.03; 95% CI, 1.14-3.59). In addition, infants conceived during April-June--the time of herbicide application--had an increased chance of being diagnosed with circulatory/respiratory (excluding heart) malformations compared with births conceived during other months of the year (OR = 1.75; 95% CI, 1.09-2.80). Musculoskeletal/integumental anomalies increased for combined sexes in the high-wheat counties (OR = 1.50; 95% CI, 1.06-2.12). Infant death from congenital anomalies significantly increased in high-wheat counties for males (OR = 2.66; 95% CI, 1.52-4.65) but not for females (OR = 0.48; 95% CI, 0.20-1.15). These results are especially of concern because of widespread use of chlorophenoxy herbicides. PMID:12842783

  10. Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome

    PubMed Central

    Vanterpool, Sizzle F.; Been, Jasper V.; Houben, Michiel L.; Nikkels, Peter G. J.; De Krijger, Ronald R.; Zimmermann, Luc J. I.; Kramer, Boris W.; Progulske-Fox, Ann; Reyes, Leticia

    2016-01-01

    Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48–0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15–14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31–36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy

  11. Maternal Factors and Adverse Perinatal Outcomes in Women with Preeclampsia in Maceió, Alagoas

    PubMed Central

    de Oliveira, Alane Cabral Menezes; Santos, Arianne Albuquerque; Bezerra, Alexandra Rodrigues; de Barros, Amanda Maria Rocha; Tavares, Myrian Cicyanne Machado

    2016-01-01

    Background Preeclampsia has been associated with several risk factors and events. However, it still deserves further investigation, considering the multitude of related factors that affect different populations. Objective To evaluate the maternal factors and adverse perinatal outcomes in a cohort of pregnant women with preeclampsia receiving care in the public health network of the city of Maceió. Methods Prospective cohort study carried out in 2014 in the public health network of the city with a sample of pregnant women calculated based on a prevalence of preeclampsia of 17%, confidence level of 90%, power of 80%, and ratio of 1:1. We applied a questionnaire to collect socioeconomic, personal, and anthropometric data, and retrieved perinatal variables from medical records and certificates of live birth. The analysis was performed with Poisson regression and chi-square test considering p values < 0.05 as significant. Results We evaluated 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP). A previous history of preeclampsia (prevalence ratio [PR] = 1.57, 95% confidence interval [95% CI] 1.47 - 1.67, p = 0.000) and black skin color (PR = 1.15, 95% CI 1.00 - 1.33, p = 0.040) were associated with the occurrence of preeclampsia. Among the newborns of PWP and PWoP, respectively, 12.5% and 13.1% (p = 0.907) were small for gestational age and 25.0% and 23.2% (p = 0.994) were large for gestational age. There was a predominance of cesarean delivery. Conclusion Personal history of preeclampsia and black skin color were associated with the occurrence of preeclampsia. There was a high frequency of birth weight deviations and cesarean deliveries. PMID:26761076

  12. Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam.

    PubMed

    Pawluski, Jodi L; Charlier, Thierry D; Fillet, Marianne; Houbart, Virginie; Crispin, Hilda T; Steinbusch, Harry W; van den Hove, Daniël L

    2012-03-01

    The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women. PMID:22173000

  13. Attention-deficit/hyperactivity disorder and adverse health outcomes in adults.

    PubMed

    Spencer, Thomas J; Faraone, Stephen V; Tarko, Laura; McDermott, Katie; Biederman, Joseph

    2014-10-01

    Whereas the adverse impact of attention-deficit/hyperactivity disorder (ADHD) on emotional and psychosocial well-being has been well investigated, its impact on physical health has not. The main aim of this study was to assess the impact of ADHD on lifestyle behaviors and measures of adverse health risk indicators. Subjects were 100 untreated adults with ADHD and 100 adults without ADHD of similar age and sex. Unhealthy lifestyle indicators included assessments of bad health habits, frequency of visits to healthcare providers, and follow through with recommended prophylactic tests. Assessments of adverse health risk indicators included measurements of cardiovascular and metabolic parameters, weight, body mass index, and waist circumference. No differences were identified in health habits between subjects with and without ADHD, but robust differences were found in a wide range of adverse health risk indicators. ADHD is associated with an adverse impact in health risk indicators well known to be associated with high morbidity and mortality. PMID:25211634

  14. Maternal pre-pregnancy BMI and adverse pregnancy outcomes among Chinese women: Results from the C-ABCS.

    PubMed

    Ding, X-X; Xu, S-J; Hao, J-H; Huang, K; Su, P-Y; Tao, F-B

    2016-04-01

    The aim of this study was to investigate associations between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among Chinese pregnant women. A prospective population-based cohort study was performed using data collected as part of the China-Anhui Birth Cohort Study or C-ABCS. A total of 13,121 pregnant women who received the first prenatal visit were enrolled from November 2008 to October 2010. Logistic regression analysis was used to calculate associations between pre-pregnancy BMI and pregnancy outcomes. Results indicated that the increased pre-pregnancy BMI was associated with a number of adverse pregnancy outcomes such as hypertensive disorder (adjusted relative risk (ARR) 2.3, 95% confidence interval [CI] 1.5-3.6), gestational diabetes (ARR 3.5, 95% CI 2.3-5.2), caesarean delivery (ARR 2.0, 95% CI 1.6-2.4), and medically indicated preterm delivery (ARR 1.8, 95% CI 1.1-2.9). Women with pre-pregnancy BMI above the normal range pose an increased risk of adverse pregnancy outcomes. PMID:26492517

  15. Birth Characteristics and Developmental Outcomes of Infants of Mexican-Origin Adolescent Mothers: Risk and Promotive Factors

    ERIC Educational Resources Information Center

    Jahromi, Laudan B.; Umana-Taylor, Adriana J.; Updegraff, Kimberly A.; Lara, Ethelyn E.

    2012-01-01

    Infants of adolescent mothers are at increased risk for negative developmental outcomes. Given the high rate of pregnancy among Mexican-origin adolescent females in the US, the present study examined health characteristics at birth and developmental functioning at 10 months of age in a sample of 205 infants of Mexican-origin adolescent mothers.…

  16. APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women

    PubMed Central

    2010-01-01

    Background Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women. Methods Blood samples collected from 907 pregnant women were tested using the Coatest® Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest® Classic and/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects. Results Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest® test only and at 45% in the group with APCR based on the Modified Coatest® test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%. Conclusions Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more frequent

  17. Resilient children: individual differences in developmental outcome of children born to drug abusers.

    PubMed

    Johnson, H L; Glassman, M B; Fiks, K B; Rosen, T S

    1990-12-01

    Since 1977, we have been following the neurobehavioral development of two groups of children: a group born to women on methadone maintenance and a drug-free comparison group. This study used the data on the children evaluated at 36 months of age to determine whether distinct patterns of developmental outcome can be identified, and which medical, familial, or environmental characteristics are associated with developmental differences. The children were clustered on four measures at 36 months: head circumference percentile, Merrill-Palmer Scale score, neurological evaluation, and referrals for developmental problems. Three distinct clusters emerged, with methadone children disproportionately frequent in Cluster 3, the group showing the poorest development. Comparisons of the clusters on a wide range of variables revealed consistent differences between Cluster 1 and Cluster 3 children in maternal responsiveness and incidence of neglect and family violence. These findings indicate that distinct developmental patterns do occur within this predominantly lower-class ghetto population; further, that children born to methadone-maintained women are more likely to show poor development. However, when the environment provides nurturance and stability, methadone children can show resilience and develop well. PMID:1705954

  18. Functional Outcome of School Children With History of Global Developmental Delay.

    PubMed

    Dornelas, Lílian F; Duarte, Neuza M C; Morales, Nívea M O; Pinto, Rogério M C; Araújo, Renata R H; Pereira, Sílvia A; Magalhães, Lívia C

    2016-07-01

    This study aimed to investigate the functional and developmental outcomes in school age children diagnosed with global developmental delay before 2 years old and to verify the association between their final diagnosis and environmental and biological factors. Forty-five Brazilian children (26 boys), mean age 95.84 (7.72) months, who attended regular school and were diagnosed with global developmental delay before they were 2 years old had their functions evaluated. Children with global developmental delay were diagnosed with several conditions at school age. Students with greater chances of receiving a diagnosis were those whose mothers were younger at the time their children were born (OR = 1.47, CI = 1.04-2.09, P = .03), who had impaired motor performance, specially balance (OR = 1.33, CI = 1.01-1.75, P = .04), and who needed help during cognitive and behavioral tasks at school (OR = 1.08, CI = 1.00-1.17, P = .048). Interdisciplinary evaluation contributed to defining the specific diagnosis and to identifying the necessity of specialized support. PMID:26936059

  19. Early neural disruption and auditory processing outcomes in rodent models: implications for developmental language disability

    PubMed Central

    Fitch, R. Holly; Alexander, Michelle L.; Threlkeld, Steven W.

    2013-01-01

    Most researchers in the field of neural plasticity are familiar with the “Kennard Principle,” which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood). As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents) aspects of human sensory processing that may correlate—both developmentally and functionally—with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic (HI) injuries (similar to those seen in premature infants and term infants with birth complications) led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human “term,” but only transient deficits (undetectable in adulthood) when induced in a “preterm” window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing (RAP) outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations). Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in

  20. Associations of prenatal exposure to five chlorophenols with adverse birth outcomes.

    PubMed

    Guo, Jianqiu; Wu, Chunhua; Lv, Shenliang; Lu, Dasheng; Feng, Chao; Qi, Xiaojuan; Liang, Weijiu; Chang, Xiuli; Xu, Hao; Wang, Guoquan; Zhou, Zhijun

    2016-07-01

    Exposures to chlorophenols (CPs) have been linked with adverse health effects on wildlife and humans. This study aimed to evaluate prenatal exposure to five CP compounds using maternal urinary concentrations during pregnancy and the potential associations with birth outcomes of their infants at birth. A total of 1100 mother-newborn pairs were recruited during June 2009 to January 2010 in an agricultural region, China. Urinary concentrations of five CPs from dichlorophenol (DCP) to pentachlorophenol (PCP), namely, 2,5-DCP, 2,4-DCP, 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-TCP and PCP, were measured using large-volume-injection gas chromatography-tandem mass spectrometry (LVI-GC-MS-MS), and associations between CP levels and weight, length as well as head circumference at birth were examined. Median urinary creatinine-adjusted concentrations of 2,5-DCP, 2,4-DCP, 2,4,5-TCP, 2,4,6-TCP and PCP were 3.34 μg/g, 1.03 μg/g, < LOD, 1.78 μg/g and 0.39 μg/g creatinine, respectively. We found lower birth weight 30 g [95% confidence interval (CI): -57, -3; p = 0.03] for per SD increase in log10-transformed concentrations of 2,4,6-TCP and lower birth weight 37 g (95% CI: -64, -10; p = 0.04) for PCP, respectively. Similarly, head circumference decrease in associations with creatinine-corrected 2,4,6-TCP and PCP concentrations were also achieved. Considering sex difference, the associations of lower birth weight were only found among male neonates, while head circumference was associated with 2,4-DCP and 2,5-DCP only found among female neonates. This study showed significant negative associations between CPs exposure and reduction in neonatal anthropometric measures. The biological mechanisms concerning CPs exposure on fetal growth deserved further investigations. PMID:27131805

  1. Socioeconomic Disparities in Ectopic Pregnancy: Predictors of Adverse Outcomes from Illinois Hospital-Based Care, 2000–2006

    PubMed Central

    Zhang, James X.; Lindau, Stacy Tessler

    2010-01-01

    This study aimed to identify the incidence of adverse outcomes from ectopic pregnancy hospital care in Illinois (2000–2006), and assess patient, neighborhood, hospital and time factors associated with these outcomes. Discharge data from Illinois hospitals were retrospectively analyzed and ectopic pregnancies were identified using DRG and ICD-9 diagnosis codes. The primary outcome was any complication identified by ICD-9 procedure codes. Secondary outcomes were length of stay and discharge status. Residential zip codes were linked to 2000 U.S. Census data to identify patients’ neighborhood demographics. Logistic regression was used to identify risk factors for adverse outcomes. Independent variables were insurance status, age, co-morbidities, neighborhood demographics, hospital type, hospital ectopic pregnancy service volume, and year of discharge. Of 13,007 ectopic pregnancy hospitalizations, 7.4% involved at least one complication identified by procedure codes. Hospitalizations covered by Medicare (for women with chronic disabilities) were more likely than those with other source or without insurance to result in surgical sterilization (OR 4.7, P = 0.012). Hospitalization longer than 2 days was more likely with Medicaid (OR 1.46, P<0.0005) or no insurance (OR 1.35, P<0.0005) versus other payers, and among church-operated versus secular hospitals (OR 1.21, P<0.0005). Compared to public hospitals, private hospitals had lower rates of complications (OR 0.39, P< 0.0005) and of hospitalization longer than 2 days (OR 0.57, P<0.0005). With time, hospitalizations became shorter (OR 0.53, P<0.0005) and complication rates higher (OR 1.33, P = 0.024). Ectopic pregnancy patients with Medicaid, Medicare or no insurance, and those admitted to public or religious hospitals, were more likely to experience adverse outcomes. PMID:20177756

  2. Socioeconomic disparities in ectopic pregnancy: predictors of adverse outcomes from Illinois hospital-based care, 2000-2006.

    PubMed

    Stulberg, Debra B; Zhang, James X; Lindau, Stacy Tessler

    2011-02-01

    This study aimed to identify the incidence of adverse outcomes from ectopic pregnancy hospital care in Illinois (2000-2006), and assess patient, neighborhood, hospital and time factors associated with these outcomes. Discharge data from Illinois hospitals were retrospectively analyzed and ectopic pregnancies were identified using DRG and ICD-9 diagnosis codes. The primary outcome was any complication identified by ICD-9 procedure codes. Secondary outcomes were length of stay and discharge status. Residential zip codes were linked to 2000 U.S. Census data to identify patients' neighborhood demographics. Logistic regression was used to identify risk factors for adverse outcomes. Independent variables were insurance status, age, co-morbidities, neighborhood demographics, hospital type, hospital ectopic pregnancy service volume, and year of discharge. Of 13,007 ectopic pregnancy hospitalizations, 7.4% involved at least one complication identified by procedure codes. Hospitalizations covered by Medicare (for women with chronic disabilities) were more likely than those with other source or without insurance to result in surgical sterilization (OR 4.7, P = 0.012). Hospitalization longer than 2 days was more likely with Medicaid (OR 1.46, P < 0.0005) or no insurance (OR 1.35, P < 0.0005) versus other payers, and among church-operated versus secular hospitals (OR 1.21, P < 0.0005). Compared to public hospitals, private hospitals had lower rates of complications (OR 0.39, P < 0.0005) and of hospitalization longer than 2 days (OR 0.57, P < 0.0005). With time, hospitalizations became shorter (OR 0.53, P < 0.0005) and complication rates higher (OR 1.33, P = 0.024). Ectopic pregnancy patients with Medicaid, Medicare or no insurance, and those admitted to public or religious hospitals, were more likely to experience adverse outcomes. PMID:20177756

  3. 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.

  4. TOXICOLOGY OF MALE REPRODUCTIVE DEVELOPMENT: PROFILING 774 CHEMICALS FOR MOLECULAR TARGETS AND ADVERSE OUTCOMES (SOT)

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

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

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

  6. Early augmented language intervention for children with developmental delays: potential secondary motor outcomes.

    PubMed

    Whitmore, Ani S; Romski, Mary Ann; Sevcik, Rose A

    2014-09-01

    This exploratory study examined the potential secondary outcome of an early augmented language intervention that incorporates speech-generating devices (SGD) on motor skill use for children with developmental delays. The data presented are from a longitudinal study by Romski and colleagues. Toddlers in the augmented language interventions were either required (Augmented Communication-Output; AC-O) or not required (Augmented Communication-Input; AC-I) to use the SGD to produce an augmented word. Three standardized assessments and five event-based coding schemes measured the participants' language abilities and motor skills. Toddlers in the AC-O intervention used more developmentally appropriate motor movements and became more accurate when using the SGD to communicate than toddlers in the AC-I intervention. AAC strategies, interventionist/parent support, motor learning opportunities, and physical feedback may all contribute to this secondary benefit of AAC interventions that use devices. PMID:25109299

  7. Effect of Increased Immunosuppression on Developmental Outcome of Opsoclonus Myoclonus Syndrome (OMS).

    PubMed

    Mitchell, Wendy G; Wooten, Amelia A; O'Neil, Sharon H; Rodriguez, Jenny G; Cruz, Rosa E; Wittern, Rachael

    2015-07-01

    Opsoclonus myoclonus syndrome (OMS) produces long-term cognitive, behavioral, and motor deficits. Objective was to see if more aggressive treatment improved outcome. Assessment included opsoclonus myoclonus syndrome rating, developmental/cognitive and motor assessment, and adaptive behavior. Fourteen subjects completed testing. Nine had neuroblastoma. Onset was at 10 to 35 months; onset to diagnosis: 2 days to 14 months, and onset to first treatment: 5 days to 15 months. Initial treatment was corticotropin (12), oral steroids (3), plus intravenous immunoglobulin in all. Ten received rituximab, 5 cyclophosphamide. Age at testing ranged from 2.5 to 10.3 years. Adaptive Behavior Score (11 subjects), mean 93.5; estimated Intelligence Quotient/Developmental Quotient mean 93.5; Motor: mean 92.8. Residual opsoclonus myoclonus syndrome symptoms at the time of the evaluation were generally minor; opsoclonus myoclonus syndrome scores ranged from 0 to 6. Comparison to previously reported opsoclonus myoclonus syndrome subjects showed improved outcomes: Adaptive behavior, cognitive and motor scores were significantly higher (P < .001) in new subjects. Outcomes have improved with more aggressive immunosuppression, with most opsoclonus myoclonus syndrome survivors now functioning at or near normal. PMID:25342308

  8. 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

  9. A short-term in vivo screen using fetal testosterone production, a key event in the phthalate adverse outcome pathway, to predict disruption of sexual differentiation.

    PubMed

    Furr, Johnathan R; Lambright, Christy S; Wilson, Vickie S; Foster, Paul M; Gray, Leon E

    2014-08-01

    This study was designed to develop and validate a short-term in vivo protocol termed the Fetal Phthalate Screen (FPS) to detect phthalate esters (PEs) and other chemicals that disrupt fetal testosterone synthesis and testis gene expression in rats. We propose that the FPS can be used to screen chemicals that produce adverse developmental outcomes via disruption of the androgen synthesis pathway more rapidly and efficiently, and with fewer animals than a postnatal one-generation study. Pregnant rats were dosed from gestational day (GD) 14 to 18 at one dose level with one of 27 chemicals including PEs, PE alternatives, pesticides known to inhibit steroidogenesis, an estrogen and a potent PPARα agonist and ex vivo testis testosterone production (T Prod) was measured on GD 18. We also included some chemicals with "unknown" activity including DMEP, DHeP, DHEH, DPHCH, DAP, TOTM, tetrabromo-diethyl hexyl phthalate (BrDEHP), and a relatively potent environmental estrogen BPAF. Dose-response studies also were conducted with this protocol with 11 of the above chemicals to determine their relative potencies. CD-1 mice also were exposed to varying dose levels of DPeP from GD 13 to 17 to determine if DPeP reduced T Prod in this species since there is a discrepancy among the results of in utero studies of PEs in mice. Compared to the known male reproductive effects of the PEs in rats the FPS correctly identified all known "positives" and "negatives" tested. Seven of eight "unknowns" tested were "negatives", they did not reduce T Prod, whereas DAP produced an "equivocal" response. Finally, a dose-response study with DPeP in CD-1 mice revealed that fetal T Prod can be inhibited by exposure to a PE in utero in this species, but at a higher dose level than required in rats.Key words. Phthalate Syndrome, Fetal endocrine biomarkers, Phthalate adverse outcome pathway, testosterone production, fetal rat testis. PMID:24798384

  10. Research Note: Are Life-Course-Persistent Offenders at Risk for Adverse Health Outcomes?

    ERIC Educational Resources Information Center

    Piquero, Alex R.; Daigle, Leah E.; Gibson, Chris; Piquero, Nicole Leeper; Tibbetts, Stephen G.

    2007-01-01

    Moffitt's developmental taxonomy of adolescence-limited and life-course-persistent offenders has received much empirical attention, with researchers focusing on the etiology and trajectory of offending between the two groups. Recently, Moffitt articulated a new hypothesis that has yet to be empirically assessed--that life-course-persistent…

  11. 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

    OBJECT 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). METHODS 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. RESULTS 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

  12. Developmental neurotoxicity of persistent organic pollutants: an update on childhood outcome.

    PubMed

    Berghuis, Sietske A; Bos, Arend F; Sauer, Pieter J J; Roze, Elise

    2015-05-01

    Organohalogens are persistent organic pollutants that have a wide range of chemical application. There is growing evidence that several of these chemical compounds interfere with human development in various ways. The aim of this review is to provide an update on the relationship between various persistent organic pollutants and childhood neurodevelopmental outcome from studies from the past 10 years. This review focuses on exposure to polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs) and dichlorodiphenyldichloroethylene (DDE), and in addition on exposure to phthalates, bisphenol A, and perfluorinated compounds and their associations with neurodevelopmental outcome in childhood, up to 18 years of age. This review shows that exposure to environmental chemicals affects neurodevelopmental outcome in children. Regarding exposure to PCBs and OH-PCBs, most studies report no or inverse associations with neurodevelopmental outcomes. Regarding exposure to PBDEs, lower mental development, psychomotor development and IQ were found at preschool age, and poorer attention at school age. Regarding exposure to DDE, most studies reported inverse associations with outcome, while others found no associations. Significant relations were particularly found at early infancy on psychomotor development, on attention and ADHD, whereas at school age, no adverse relationships were described. Additionally, several studies report gender-related vulnerability. Future research should focus on the long-term effects of prenatal and childhood exposure to these environmental chemicals, on sex-specific and combined exposure effects of environmental chemicals, and on possible mechanisms by which these chemicals have their effects on neurodevelopmental and behavioral outcomes. PMID:25618547

  13. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

    PubMed Central

    Kumbhani, Dharam J.; Steg, Ph. Gabriel; Cannon, Christopher P.; Eagle, Kim A.; Smith, Sidney C.; Goto, Shinya; Ohman, E. Magnus; Elbez, Yedid; Sritara, Piyamitr; Baumgartner, Iris; Banerjee, Subhash; Creager, Mark A.; Bhatt, Deepak L.

    2014-01-01

    Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72–0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73–0.96; P = 0.01). Conclusion Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD. PMID:24585266

  14. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series.

    PubMed

    Buchan, Sarah; Muldoon, Katherine A; Spaans, Johanna N; Balfour, Louise; Samson, Lindy; Walker, Mark; Cameron, D William

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990-2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990-2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03-1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12-6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04-1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30-40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  15. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series

    PubMed Central

    Buchan, Sarah; Spaans, Johanna N.; Balfour, Louise

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990–2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990–2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03–1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12–6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04–1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30–40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  16. 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...

  17. Childhood adversity and behavioral health outcomes for youth: An investigation using state administrative data.

    PubMed

    Lucenko, Barbara A; Sharkova, Irina V; Huber, Alice; Jemelka, Ron; Mancuso, David

    2015-09-01

    This study aimed to measure the relative contribution of adverse experiences to adolescent behavioral health problems using administrative data. Specifically, we sought to understand the predictive value of adverse experiences on the presence of mental health and substance abuse problems for youth receiving publicly funded social and health services. Medicaid claims and other service records were analyzed for 125,123 youth age 12-17 and their biological parents. Measures from administrative records reflected presence of parental domestic violence, mental illness, substance abuse, criminal justice involvement, child abuse and/or neglect, homelessness, and death of a biological parent. Mental health and substance abuse status of adolescents were analyzed as functions of adverse experiences and other youth characteristics using logistic regression. In multivariate analyses, all predictors except parental domestic violence were statistically significant for substance abuse; parental death, parental mental illness, child abuse or neglect and homelessness were statistically significant for mental illness. Odds ratios for child abuse/neglect were particularly high in both models. The ability to identify risks during childhood using administrative data suggests the potential to target prevention and early intervention efforts for children with specific family risk factors who are at increased risk for developing behavioral health problems during adolescence. This study illustrates the utility of administrative data in understanding adverse experiences on children and the advantages and disadvantages of this approach. PMID:26234784

  18. 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 ...

  19. Childhood Adverse Events and Health Outcomes among Methamphetamine-Dependent Men and Women

    ERIC Educational Resources Information Center

    Messina, Nena P.; Marinelli-Casey, Patricia; Hillhouse, Maureen; Ang, Alfonso; Hunter, Jeremy; Rawson, Richard

    2008-01-01

    To describe the prevalence of childhood adverse events (CAEs) among methamphetamine-dependent men and women, and assess the relationship of cumulative CAEs to health problems. Data for 236 men and 351 women were analyzed assessing CAEs. Dependent variables included 14 self-reported health problems or psychiatric symptom domains. Mental health was…

  20. Adolescent-Onset Depression: Are Obesity and Inflammation Developmental Mechanisms or Outcomes?

    PubMed

    Byrne, Michelle L; O'Brien-Simpson, Neil M; Mitchell, Sarah A; Allen, Nicholas B

    2015-12-01

    Depression often has its first onset during adolescence and is associated with obesity. Furthermore, inflammatory processes have been implicated in both depression and obesity, although research amongst adolescents is limited. This review explores associations between depression and obesity, depression and inflammation, and obesity and inflammation from a developmental perspective. The temporal relations between these factors are examined to explore whether obesity and elevated inflammation act as either risk factors for, or outcomes of, adolescent-onset depression. Sex differences in these processes are also summarized. We propose a model whereby increases in sex hormones during puberty increase risk for depression for females, which can lead to obesity, which in turn increases levels of inflammation. Importantly, this model suggests that inflammation and obesity are outcomes of adolescent depression, rather than initial contributing causes. Further research on biological and psychosocial effects of sex hormones is needed, as is longitudinal research with children and adolescents. PMID:25666100

  1. Adverse Outcomes after Major Surgery in Patients with Pressure Ulcer: A Nationwide Population-Based Retrospective Cohort Study

    PubMed Central

    Chou, Chia-Lun; Lee, Woan-Ruoh; Yeh, Chun-Chieh; Shih, Chun-Chuan

    2015-01-01

    Background Postoperative adverse outcomes in patients with pressure ulcer are not completely understood. This study evaluated the association between preoperative pressure ulcer and adverse events after major surgeries. Methods Using reimbursement claims from Taiwan’s National Health Insurance Research Database, we conducted a nationwide retrospective cohort study of 17391 patients with preoperative pressure ulcer receiving major surgery in 2008-2010. With a propensity score matching procedure, 17391 surgical patients without pressure ulcer were selected for comparison. Eight major surgical postoperative complications and 30-day postoperative mortality were evaluated among patients with pressure ulcer of varying severity. Results Patients with preoperative pressure ulcer had significantly higher risk than controls for postoperative adverse outcomes, including septicemia, pneumonia, stroke, urinary tract infection, and acute renal failure. Surgical patients with pressure ulcer had approximately 1.83-fold risk (95% confidence interval 1.54-2.18) of 30-day postoperative mortality compared with control group. The most significant postoperative mortality was found in those with serious pressure ulcer, such as pressure ulcer with local infection, cellulitis, wound or treatment by change dressing, hospitalized care, debridement or antibiotics. Prolonged hospital or intensive care unit stay and increased medical expenditures were also associated with preoperative pressure ulcer. Conclusion This nationwide propensity score-matched retrospective cohort study showed increased postoperative complications and mortality in patients with preoperative pressure ulcer. Our findings suggest the urgency of preventing and managing preoperative pressure ulcer by a multidisciplinary medical team for this specific population. PMID:26000606

  2. High level amplification of N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours

    PubMed Central

    Lillington, D M; Goff, L K; Kingston, J E; Onadim, Z; Price, E; Domizio, P; Young, B D

    2002-01-01

    Twenty-five primary retinoblastoma tumours were analysed by real-time quantitative polymerase chain reaction to determine the genomic copy number of the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization to contain variable copy number increases of chromosomal material mapping to 2p. High level amplification (>30-fold) of N-MYC was found in three tumours, none of which showed adverse histological features and all patients are surviving at between 54 and 108 months post enucleation. Furthermore, the three tumours associated with metastasis and adverse patient outcome showed normal N-MYC copy number. Although high level amplification of N-MYC is an unfavourable prognostic indicator in neuroblastoma, these data show no evidence of a correlation between amplification of N-MYC and adverse outcome in retinoblastoma. British Journal of Cancer (2002) 87, 779–782. doi:10.1038/sj.bjc.6600532 www.bjcancer.com © 2002 Cancer Research UK PMID:12232763

  3. BIOLOGICALLY-BASED DOSE-RESPONSE MODELING IN DEVELOPMENTAL TOXICOLOGY: BIOCHEMICAL AND CELLULAR SEQUELAE OF 5-FLUOROURACIL EXPOSURE IN THE DEVELOPING RAT

    EPA Science Inventory

    Mechanistically-based dose-response models for developmental toxicity require elucidation of biological events that intervene between maternal exposure and adverse developmental outcome. We examined some of the major events in the rat embryo following subcutaneous injection of 5-...

  4. Parent-Adolescent Discrepancies in Perceived Parenting Characteristics and Adolescent Developmental Outcomes in Poor Chinese Families.

    PubMed

    Leung, Janet T Y; Shek, Daniel T L

    2014-01-01

    We examined the relationships between parent-adolescent discrepancies in perceived parenting characteristics (indexed by parental responsiveness, parental demandingness, and parental control) and adolescent developmental outcomes (indexed by achievement motivation and psychological competence) in poor families in Hong Kong. A sample of 275 intact families having at least one child aged 11-16 experiencing economic disadvantage were invited to participate in the study. Fathers and mothers completed the Parenting Style Scale and Chinese Parental Control Scale, and adolescents completed the Social-Oriented Achievement Motivation Scale and Chinese Positive Youth Development Scale in addition to paternal and maternal Parenting Style Scale and Chinese Parental Control Scale. Results indicated that parents and adolescents had different perceptions of parental responsiveness, parental demandingness, and paternal control, with adolescents generally perceived lower levels of parenting behaviors than did their parents. While father-adolescent discrepancy in perceived paternal responsiveness and mother-adolescent discrepancy in perceived maternal control negatively predicted adolescent achievement motivation, mother-adolescent discrepancy in perceptions of maternal responsiveness negatively predicted psychological competence in adolescents experiencing economic disadvantage. The present findings provided support that parent-child discrepancies in perceived parenting characteristics have negative impacts on the developmental outcomes of adolescents experiencing economic disadvantage. The present study addresses parent-child discrepancies in perceived parental behaviors as "legitimate" constructs, and explores their links with adolescent psychosocial development, which sheds light for researchers and clinical practitioners in helping the Chinese families experiencing economic disadvantage. PMID:24482569

  5. Does “Tiger Parenting” Exist? Parenting Profiles of Chinese Americans and Adolescent Developmental Outcomes

    PubMed Central

    Kim, Su Yeong; Wang, Yijie; Orozco-Lapray, Diana; Shen, Yishan; Murtuza, Mohammed

    2013-01-01

    “Tiger parenting,” as described by Chua (2011), has put parenting in Asian American families in the spotlight. The current study identified parenting profiles in Chinese American families and explored their effects on adolescent adjustment. In a three-wave longitudinal design spanning eight years, from early adolescence to emerging adulthood, adolescents (54% female), fathers and mothers from 444 Chinese American families reported on eight parenting dimensions (e.g., warmth and shaming) and six developmental outcomes (e.g., GPA and academic pressure). Latent profile analyses on the eight parenting dimensions demonstrated four parenting profiles: supportive, tiger, easygoing, and harsh parenting. Over time, the percentage of parents classified as tiger parents decreased among mothers but increased among fathers. Path analyses showed that the supportive parenting profile, which was the most common, was associated with the best developmental outcomes, followed by easygoing parenting, tiger parenting, and harsh parenting. Compared with the supportive parenting profile, a tiger parenting profile was associated with lower GPA and educational attainment, as well as less of a sense of family obligation; it was also associated with more academic pressure, more depressive symptoms and a greater sense of alienation. The current study suggests that, contrary to the common perception, tiger parenting is not the most typical parenting profile in Chinese American families, nor does it lead to optimal adjustment among Chinese American adolescents. PMID:23646228

  6. Does "Tiger Parenting" Exist? Parenting Profiles of Chinese Americans and Adolescent Developmental Outcomes.

    PubMed

    Kim, Su Yeong; Wang, Yijie; Orozco-Lapray, Diana; Shen, Yishan; Murtuza, Mohammed

    2013-03-01

    "Tiger parenting," as described by Chua (2011), has put parenting in Asian American families in the spotlight. The current study identified parenting profiles in Chinese American families and explored their effects on adolescent adjustment. In a three-wave longitudinal design spanning eight years, from early adolescence to emerging adulthood, adolescents (54% female), fathers and mothers from 444 Chinese American families reported on eight parenting dimensions (e.g., warmth and shaming) and six developmental outcomes (e.g., GPA and academic pressure). Latent profile analyses on the eight parenting dimensions demonstrated four parenting profiles: supportive, tiger, easygoing, and harsh parenting. Over time, the percentage of parents classified as tiger parents decreased among mothers but increased among fathers. Path analyses showed that the supportive parenting profile, which was the most common, was associated with the best developmental outcomes, followed by easygoing parenting, tiger parenting, and harsh parenting. Compared with the supportive parenting profile, a tiger parenting profile was associated with lower GPA and educational attainment, as well as less of a sense of family obligation; it was also associated with more academic pressure, more depressive symptoms and a greater sense of alienation. The current study suggests that, contrary to the common perception, tiger parenting is not the most typical parenting profile in Chinese American families, nor does it lead to optimal adjustment among Chinese American adolescents. PMID:23646228

  7. Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study

    PubMed Central

    Wynn, Julia; Aspelund, Gudrun; Zygmunt, Annette; Stolar, Charles JH.; Mychaliska, George; Butcher, Jennifer; Lim, Foong-Yen; Gratton, Teresa; Potoka, Douglas; Brennan, Kate; Azarow, Ken; Jackson, Barbara; Needelman, Howard; Crombleholme, Timothy; Zhang, Yuan; Duong, Jimmy; Arkovitz, Marc S.; Chung, Wendy K.; Farkouh, Christiana

    2013-01-01

    Purpose To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at two years of age. Methods This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at two years of age. Results BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 +/− 15, 95 +/−16, and 95 +/− 11. Ten percent (5/47) scored more than two standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 +/−14, 94+/−16, 93 +/− 13, 97+/− 10, and 94 +/− 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At two years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. Conclusion CDH patients on average have lower developmental scores at two years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays. PMID:24094947

  8. The developmental basis of epigenetic regulation of HTR2A and psychiatric outcomes.

    PubMed

    Paquette, Alison G; Marsit, Carmen J

    2014-12-01

    The serotonin receptor 5-HT2A (encoded by HTR2A) is an important regulator of fetal brain development and adult cognitive function. Environmental signals that induce epigenetic changes of serotonin response genes, including HTR2A, have been implicated in adverse mental health outcomes. The objective of this perspective article is to address the medical implications of HTR2A epigenetic regulation, which has been associated with both infant neurobehavioral outcomes and adult mental health. Ongoing research has identified a region of the HTR2A promoter that has been associated with a number of medical outcomes in adults and infants, including bipolar disorder, schizophrenia, chronic fatigue syndrome, borderline personality disorder, suicidality, and neurobehavioral outcomes. Epigenetic regulation of HTR2A has been studied in several different types of tissues, including the placenta. The placenta is an important source of serotonin during fetal neurodevelopment, and placental epigenetic variation of HTR2A has been associated with infant neurobehavioral outcomes, which may represent the basis of adult mental health disorders. Further analysis is needed to identify intrinsic and extrinsic factors that modulate HTR2A methylation, and the mechanism by which this epigenetic variation influences fetal growth and leads to altered brain development, manifesting in psychiatric disorders. PMID:25043477

  9. Developmental Outcomes of School-Age Children with Duarte Galactosemia: A Pilot Study.

    PubMed

    Lynch, Mary Ellen; Potter, Nancy L; Coles, Claire D; Fridovich-Keil, Judith L

    2015-01-01

    Duarte galactosemia (DG) is a mild allelic variant of classic galactosemia that results from partial impairment of galactose-1P uridylyltransferase (GALT). Although infants with DG are detected by newborn screening in some US states at close to 1/4,000 live births, most are discharged from follow-up very early in life and there is no consensus on whether these children are at increased risk for any of the long-term developmental delays seen in classic galactosemia. There is also no consensus on whether infants with DG benefit from dietary restriction of galactose. Reflecting the current uncertainty, some states choose to identify infants with DG by newborn screening and others do not. As a first step toward characterizing the developmental outcomes of school-age children with DG, we conducted a pilot study, testing 10 children with DG and 5 unaffected siblings from the same group of families. All children tested were between 6 and 11 years old. We used standardized direct assessments and parent-response surveys to collect information regarding cognition, communication, socio-emotional, adaptive behavior, and physical development for each child. Despite the small sample size, our data demonstrated some notable differences between cases and controls in socio-emotional development, in delayed recall, and in auditory processing speed. These results confirm that direct assessment of school-age children with DG can detect subtle but potentially problematic developmental deficits, and underscore the need for a larger study which has sufficient power to evaluate these outcomes while controlling for potentially confounding factors. PMID:25681083

  10. Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife

    PubMed Central

    Madden, Judith C.; Rogiers, Vera; Vinken, Mathieu

    2014-01-01

    There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called ‘adverse outcome pathway’ (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife. PMID:25405971

  11. The Effects of Chewing Betel Nut with Tobacco and Pre-pregnancy Obesity on Adverse Birth Outcomes Among Palauan Women.

    PubMed

    Berger, Katherine E; Masterson, James; Mascardo, Joy; Grapa, Jayvee; Appanaitis, Inger; Temengil, Everlynn; Watson, Berry Moon; Cash, Haley L

    2016-08-01

    The small Pacific Island nation of Palau has alarmingly high rates of betel nut with tobacco use and obesity among the entire population including pregnant women. This study aimed to determine the effects of betel nut with tobacco use and pre-pregnancy obesity on adverse birth outcomes. This study used retrospective cohort data on 1171 Palauan women who gave birth in Belau National Hospital in Meyuns, Republic of Palau between 2007 and 2013. The exposures of interest were pre-pregnancy obesity and reported betel nut with tobacco use during pregnancy. The primary outcomes measured were preterm birth and low birth weight among full-term infants. A significantly increased risk for low birth weight among full-term infants was demonstrated among those women who chewed betel nut with tobacco during pregnancy when other known risk factors were controlled for. Additionally, pre-pregnancy obesity was associated with a significantly increased risk for preterm birth when other known risk factors were controlled for. Both betel nut with tobacco use and pre-pregnancy obesity were associated with higher risks for adverse birth outcomes. These findings should be used to drive public health efforts in Palau, as well as in other Pacific Island nations where these studies are currently lacking. PMID:26994610

  12. Perinatal Mortality and Adverse Pregnancy Outcomes in a Low-Income Rural Population of Women who Smoke

    PubMed Central

    McElroy, Jane A.; Bloom, Tina; Moore, Kelly; Geden, Beth; Everett, Kevin; Bullock, Linda F.

    2012-01-01

    SUMMARY 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 re-recruited into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population, perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n=79), 29% were spontaneous abortions of <20 weeks gestation, 23% were premature births and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1,000 births (BB study) compared to 8.6 per 1,000 births (state of MO) and 8.5 per 1,000 births (U.S.) The postneonatal infant mortality rate was 13.4 per 1,000 live births (BBK) compared to 2.1 per 1,000 live births (U.S.). The health disparity in this population of impoverished rural pregnant women who smoke, particular with regard to perinatal and infant deaths, warrants attention. PMID:22371350

  13. Young adolescent girls are at high risk for adverse pregnancy outcomes in sub-Saharan Africa: an observational multicountry study

    PubMed Central

    Mombo-Ngoma, Ghyslain; Mackanga, Jean Rodolphe; González, Raquel; Ouedraogo, Smaila; Kakolwa, Mwaka A; Manego, Rella Zoleko; Basra, Arti; Rupérez, María; Cot, Michel; Kabanywany, Abdunoor M; Matsiegui, Pierre-Blaise; Agnandji, Seldiji T; Vala, Anifa; Massougbodji, Achille; Abdulla, Salim; Adegnika, Ayôla A; Sevene, Esperança; Macete, Eusebio; Yazdanbakhsh, Maria; Kremsner, Peter G; Aponte, John J; Menéndez, Clara; Ramharter, Michael

    2016-01-01

    Objectives One of Africa's most important challenges is to improve maternal and neonatal health. The identification of groups at highest risk for adverse pregnancy outcomes is important for developing and implementing targeted prevention programmes. This study assessed whether young adolescent girls constitute a group at increased risk for adverse birth outcomes among pregnant women in sub-Saharan Africa. Setting Data were collected prospectively as part of a large randomised controlled clinical trial evaluating intermittent preventive treatment of malaria in pregnancy (NCT00811421—Clinical Trials.gov), conducted between September 2009 and December 2013 in Benin, Gabon, Mozambique and Tanzania. Participants Of 4749 participants, pregnancy outcomes were collected for 4388 deliveries with 4183 live births including 83 multiple gestations. Of 4100 mothers with a singleton live birth delivery, 24% (975/4100) were adolescents (≤19 years of age) and 6% (248/4100) were aged ≤16 years. Primary and secondary outcome measures Primary outcomes of this predefined analysis were preterm delivery and low birth weight. Results The overall prevalence of low birthweight infants and preterm delivery was 10% (371/3851) and 4% (159/3862), respectively. Mothers aged ≤16 years showed higher risk for the delivery of a low birthweight infant (OR: 1.96; 95% CI 1.35 to 2.83). Similarly, preterm delivery was associated with young maternal age (≤16 years; OR: 2.62; 95% CI 1.59 to 4.30). In a subanalysis restricted to primiparous women: preterm delivery, OR 4.28; 95% CI 2.05 to 8.93; low birth weight, OR: 1.29; 95% CI 0.82 to 2.01. Conclusions Young maternal age increases the risk for adverse pregnancy outcomes and it is a stronger predictor for low birth weight and preterm delivery than other established risk factors in sub-Saharan Africa. This finding highlights the need to improve adolescent reproductive health in sub-Saharan Africa. Trial registration number NCT00811421

  14. Adverse maternal and perinatal outcomes in adolescent pregnancies: The Global Network’s Maternal Newborn Health Registry study

    PubMed Central

    2015-01-01

    Background Adolescent girls between 15 and 19 years give birth to around 16 million babies each year, around 11% of births worldwide. We sought to determine whether adolescent mothers are at higher risk of maternal and perinatal adverse outcomes compared with mothers aged 20–24 years in a prospective, population-based observational study of newborn outcomes in low resource settings. Methods We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in six low-middle income countries (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). The study population for this analysis was restricted to women aged 24 years or less, who gave birth to infants of at least 20 weeks’ gestation and 500g or more. We compared adverse pregnancy maternal and perinatal outcomes among pregnant adolescents 15-19 years, <15 years, and adults 20-24 years. Results A total of 269,273 women were enrolled from January 2010 to December 2013. Of all pregnancies 11.9% (32,097/269,273) were in adolescents 15-19 years, while 0.14% (370/269,273) occurred among girls <15 years. Pregnancy among adolescents 15-19 years ranged from 2% in Pakistan to 26% in Argentina, and adolescent pregnancies <15 year were only observed in sub-Saharan Africa and Latin America. Compared to adults, adolescents did not show increased risk of maternal adverse outcomes. Risks of preterm birth and LBW were significantly higher among both early and older adolescents, with the highest risks observed in the <15 years group. Neonatal and perinatal mortality followed a similar trend in sub-Saharan Africa and Latin America, with the highest risk in early adolescents, although the differences in this age group were not significant. However, in South Asia the risks of neonatal and perinatal death were not different among adolescents 15-19 years compared to adults. Conclusions This study suggests that pregnancy among adolescents is not associated

  15. Developmental exposure to a mixture of two mechanistically distinct antiandrogens results in cumulative adverse reproductive effects in adult male rats

    EPA Science Inventory

    Typically, toxicological studies have focused on the adverse effects from exposure to single chemicals. However, endocrine disrupting chemicals (EDCs) are detected in the environment as mixtures. Empirical evidence suggests that mixtures of EDCs with the same mechanism of action...

  16. Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload

    NASA Technical Reports Server (NTRS)

    Evans-Flynn, Erin; Gregory, Kevin; Arsintescu, Lucia; Whitmire, Alexandra; Leveton, Lauren B.; Vessey, William

    2015-01-01

    Sleep loss, circadian desynchronization, and work overload occur to some extent for ground and flight crews, prior to and during spaceflight missions. Ground evidence indicates that such risk factors may lead to performance decrements and adverse health outcomes, which could potentially compromise mission objectives. Efforts are needed to identify the environmental and mission conditions that interfere with sleep and circadian alignment, as well as individual differences in vulnerability and resiliency to sleep loss and circadian desynchronization. Specifically, this report highlights a collection of new evidence to better characterize the risk and reveals new gaps in this risk.

  17. Association of Arsenic with Adverse Pregnancy Outcomes/Infant Mortality: A Systematic Review and Meta-Analysis

    PubMed Central

    Armah, Frederick Ato; Essumang, David Kofi; Luginaah, Isaac; Clarke, Edith; Marfoh, Kissinger; Cobbina, Samuel Jerry; Nketiah-Amponsah, Edward; Namujju, Proscovia Bazanya; Obiri, Samuel; Dzodzomenyo, Mawuli

    2015-01-01

    Background Exposure to arsenic is one of the major global health problems, affecting > 300 million people worldwide, but arsenic’s effects on human reproduction are uncertain. Objectives We conducted a systematic review and meta-analysis to examine the association between arsenic and adverse pregnancy outcomes/infant mortality. Methods We searched PubMed and Ovid MEDLINE (from 1946 through July 2013) and EMBASE (from 1988 through July 2013) databases and the reference lists of reviews and relevant articles. Studies satisfying our a priori eligibility criteria were evaluated independently by two authors. Results Our systematic search yielded 888 articles; of these, 23 were included in the systematic review. Sixteen provided sufficient data for our quantitative analysis. Arsenic in groundwater (≥ 50 μg/L) was associated with increased risk of spontaneous abortion (6 studies: OR = 1.98; 95% CI: 1.27, 3.10), stillbirth (9 studies: OR = 1.77; 95% CI: 1.32, 2.36), moderate risk of neonatal mortality (5 studies: OR = 1.51; 95% CI: 1.28, 1.78), and infant mortality (7 studies: OR = 1.35; 95% CI: 1.12, 1.62). Exposure to environmental arsenic was associated with a significant reduction in birth weight (4 studies: β = –53.2 g; 95% CI: –94.9, –11.4). There was paucity of evidence for low-to-moderate arsenic dose. Conclusions Arsenic is associated with adverse pregnancy outcomes and infant mortality. The interpretation of the causal association is hampered by methodological challenges and limited number of studies on dose response. Exposure to arsenic continues to be a major global health issue, and we therefore advocate for high-quality prospective studies that include individual-level data to quantify the impact of arsenic on adverse pregnancy outcomes/infant mortality. Citation Quansah R, Armah FA, Essumang DK, Luginaah I, Clarke E, Marfoh K, Cobbina SJ, Nketiah-Amponsah E, Namujju PB, Obiri S, Dzodzomenyo M. 2015. Association of arsenic with adverse pregnancy

  18. Using patient safety indicators to estimate the impact of potential adverse events on outcomes.

    PubMed

    Rivard, Peter E; Luther, Stephen L; Christiansen, Cindy L; Shibei Zhao; Loveland, Susan; Elixhauser, Anne; Romano, Patrick S; Rosen, Amy K

    2008-02-01

    The authors estimated the impact of potentially preventable patient safety events, identified by Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs), on patient outcomes: mortality, length of stay (LOS), and cost. The PSIs were applied to all acute inpatient hospitalizations at Veterans Health Administration (VA) facilities in fiscal 2001. Two methods-regression analysis and multivariable case matching- were used independently to control for patient and facility characteristics while predicting the effect of the PSI on each outcome. The authors found statistically significant (p < .0001) excess mortality, LOS, and cost in all groups with PSIs. The magnitude of the excess varied considerably across the PSIs. These VA findings are similar to those from a previously published study of nonfederal hospitals, despite differences between VA and non-VA systems. This study contributes to the literature measuring outcomes of medical errors and provides evidence that AHRQ PSIs may be useful indicators for comparison across delivery systems. PMID:18184870

  19. Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States.

    PubMed

    Fejzo, Marlena S; MacGibbon, Kimber W; Mullin, Patrick M

    2016-07-01

    This is an analysis of fetal outcome in pregnancies exposed to ondansetron to treat Hyperemesis Gravidarum (HG). In this retrospective cohort study, U.S. data on outcome were collected on 1070 pregnancies exposed to ondansetron and compared to outcomes in two control groups: 771 pregnancies in women with a history of HG with no ondansetron exposure and 1555 pregnancies with neither a history of HG nor ondansetron exposure. Ventricular septal defects were reported in 2/952 of infants in the HG/Ondansetron-exposure group and 4/1286 in the No HG/No Ondansetron-exposure group. Cleft palate was reported in 1/952 live births in the HG/Ondansetron and 2/1286 in the No HG/No Ondansetron-exposure groups. Women with a history of HG who took ondansetron reported less miscarriages and terminations, and higher live birth rates. The overall results do not support evidence of teratogenicity of ondansetron. PMID:27151373

  20. Household and community-level Adverse Childhood Experiences and adult health outcomes in a diverse urban population.

    PubMed

    Wade, Roy; Cronholm, Peter F; Fein, Joel A; Forke, Christine M; Davis, Martha B; Harkins-Schwarz, Mary; Pachter, Lee M; Bair-Merritt, Megan H

    2016-02-01

    Adverse Childhood Experiences (ACEs), which include family dysfunction and community-level stressors, negatively impact the health and well being of children throughout the life course. While several studies have examined the impact of these childhood exposures amongst racially and socially diverse populations, the contribution of ACEs in the persistence of socioeconomic disparities in health is poorly understood. To determine the association between ACEs and health outcomes amongst a sample of adults living in Philadelphia and examine the moderating effect of Socioeconomic Status (SES) on this association, we conducted a cross-sectional survey of 1,784 Philadelphia adults, ages 18 and older, using random digit dialing methodology to assess Conventional ACEs (experiences related to family dysfunction), Expanded ACEs (community-level stressors), and health outcomes. Using weighted, multivariable logistic regression analyses along with SES stratified models, we examined the relationship between ACEs and health outcomes as well as the modifying effect of current SES. High Conventional ACE scores were significantly associated with health risk behaviors, physical and mental illness, while elevated Expanded ACE scores were associated only with substance abuse history and sexually transmitted infections. ACEs did have some differential impacts on health outcomes based on SES. Given the robust impact of Conventional ACEs on health, our results support prior research highlighting the primacy of family relationships on a child's life course trajectory and the importance of interventions designed to support families. Our findings related to the modifying effect of SES may provide additional insight into the complex relationship between poverty and childhood adversity. PMID:26726759

  1. Women with Intellectual Disability at Risk of Adverse Pregnancy and Birth Outcomes

    ERIC Educational Resources Information Center

    Mcconnell, D.; Mayes, R.; Llewellyn, G.

    2008-01-01

    Background: An increasing number of women with intellectual disability (ID) have children. Cross-sectional, clinical population data suggest that these women face an increased risk of delivering preterm and/or low birthweight babies. The aim of this study was to explore the prevalence of poor pregnancy and birth outcomes in women with ID and/or…

  2. Associations of Meteorology with Adverse Pregnancy Outcomes: A Systematic Review of Preeclampsia, Preterm Birth and Birth Weight

    PubMed Central

    Beltran, Alyssa J.; Wu, Jun; Laurent, Olivier

    2013-01-01

    The relationships between meteorology and pregnancy outcomes are not well known. This article reviews available evidence on the relationships between seasonality or meteorology and three major pregnancy outcomes: the hypertensive disorders of pregnancy (including preeclampsia, eclampsia and gestational hypertension), gestational length and birth weight. In total 35, 28 and 27 studies were identified for each of these outcomes. The risks of preeclampsia appear higher for women with conception during the warmest months, and delivery in the coldest months of the year. Delivery in the coldest months is also associated with a higher eclampsia risk. Patterns of decreased gestational lengths have been observed for births in winter, as well as summer months. Most analytical studies also report decreases in gestational lengths associated with heat. Birth weights are lower for deliveries occurring in winter and in summer months. Only a limited number of studies have investigated the effects of barometric pressure on gestational length or the effects of temperature and sunshine exposure on birth weight, but these questions appear worth investigating further. Available results should encourage further etiological research aiming at enhancing our understanding of the relationships between meteorology and adverse pregnancy outcomes, ideally via harmonized multicentric studies. PMID:24362545

  3. Management of patients with chronic lymphocytic leukemia with a high risk of adverse outcome: the Mayo Clinic approach

    PubMed Central

    ZENT, CLIVE S.; KAY, NEIL E.

    2012-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually an incidental diagnosis in patients with early–intermediate stage disease. However, most patients with a diagnosis of CLL will subsequently have significant morbidity and die from their disease and its complications. For these patients, CLL is not the ‘good leukemia’ with a predictably ‘benign’ outcome. Indeed, we can now identify a cohort of patients with high-risk CLL at diagnosis who will have rapid disease progression, poor response to treatment, and poor survival based on prognostic methods developed from an improved understanding of the biology of CLL. The concomitant development of improved treatments has led to risk-adjusted management approaches that could improve outcomes. We discuss the clinical and laboratory components of comprehensive risk evaluation of patients with CLL and our approach to the management of patients with a high to very high risk of disease progression and poor outcome. In addition, we review the challenges and prospects for improving prognostic precision and the development of new drugs to improve the treatment of patients with CLL with a high risk of adverse outcome. PMID:21649549

  4. Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.

    PubMed

    Steelman, Samantha M; Johnson, Philip; Jackson, Amy; Schulze, James; Chowdhary, Bhanu P

    2014-05-15

    Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis. PMID:24619519

  5. 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. PMID:26500288

  6. Developmental Exposure to TCDD Reduces Fertility and Negatively Affects Pregnancy Outcomes across Multiple Generations

    PubMed Central

    Bruner-Tran, Kaylon L.; Osteen, Kevin G.

    2010-01-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Since humans and animals are most sensitive to toxicant exposure during development, we previously developed a mouse model of in utero TCDD exposure in order to examine the impact of this toxicant on adult reproductive function. Our initial in utero toxicant-exposure study revealed a dose-dependent reduction in uterine sensitivity to progesterone; however, we did not previously explore establishment or maintenance of pregnancy. Thus, in the current study, we examined pregnancy outcomes in adult C57BL/6 mice with a history of developmental TCDD exposure. Herein we demonstrate reduced fertility and an increased incidence of premature birth (PTB) in F1 mice exposed in utero to TCDD as well as in three subsequent generations. Finally, our studies revealed that mice with a history of developmental TCDD exposure exhibit an increased sensitivity to inflammation which further negatively impacted gestation length in all generations examined. PMID:20955784

  7. Social Outcomes in Childhood Brain Disorder: A Heuristic Integration of Social Neuroscience and Developmental Psychology

    PubMed Central

    Yeates, Keith Owen; Bigler, Erin D.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn

    2010-01-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer interactions and relationships, social problem solving and communication, social-affective and cognitive-executive processes, and their neural substrates. The model is illustrated by research on a specific form of childhood brain disorder, traumatic brain injury. The heuristic model may promote research regarding the neural and cognitive-affective substrates of children’s social development. It also may engender more precise methods of measuring impairments and disabilities in children with brain disorder and suggest ways to promote their social adaptation. PMID:17469991

  8. A spatial bivariate probit model for correlated binary data with application to adverse birth outcomes.

    PubMed

    Neelon, Brian; Anthopolos, Rebecca; Miranda, Marie Lynn

    2014-04-01

    Motivated by a study examining geographic variation in birth outcomes, we develop a spatial bivariate probit model for the joint analysis of preterm birth and low birth weight. The model uses a hierarchical structure to incorporate individual and areal-level information, as well as spatially dependent random effects for each spatial unit. Because rates of preterm birth and low birth weight are likely to be correlated within geographic regions, we model the spatial random effects via a bivariate conditionally autoregressive prior, which induces regional dependence between the outcomes and provides spatial smoothing and sharing of information across neighboring areas. Under this general framework, one can obtain region-specific joint, conditional, and marginal inferences of interest. We adopt a Bayesian modeling approach and develop a practical Markov chain Monte Carlo computational algorithm that relies primarily on easily sampled Gibbs steps. We illustrate the model using data from the 2007-2008 North Carolina Detailed Birth Record. PMID:22599322

  9. Current Perspectives on Arthroplasty in Systemic Lupus Erythematosus: Rates, Outcomes, and Adverse Events.

    PubMed

    Kasturi, Shanthini; Goodman, Susan

    2016-09-01

    Systemic lupus erythematosus (SLE) is a chronic debilitating condition with significant impact on the musculoskeletal system. Arthroplasty may be indicated for damage related to active lupus or its treatment. As therapies for SLE have advanced, morbidity and mortality have declined, while the rate of joint replacement has increased. The age of SLE patients undergoing arthroplasty is increasing, and the indication for surgery is evolving-while avascular necrosis was previously the predominant indication for arthroplasty, osteoarthritis now accounts for a larger proportion of surgeries. Pain and functional outcomes of arthroplasty in SLE patients are comparable to those of the general population with osteoarthritis, but lupus remains an independent risk factor for post-hip arthroplasty complications and mortality. Further research is needed to characterize the impact of lupus disease activity and severity on arthroplasty outcomes. PMID:27443850

  10. Adverse Symptom Event Reporting by Patients vs Clinicians: Relationships With Clinical Outcomes

    PubMed Central

    Jia, Xiaoyu; Heller, Glenn; Barz, Allison; Sit, Laura; Fruscione, Michael; Appawu, Mark; Iasonos, Alexia; Atkinson, Thomas; Goldfarb, Shari; Culkin, Ann; Kris, Mark G.; Schrag, Deborah

    2009-01-01

    Background In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood. Methods Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patient's vs clinician's reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided. Results A total of 163 patients were enrolled for an average of 12 months (range = 1–28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue (P < .001), nausea (P = .01), constipation (P = .038), and Karnofsky Performance Status (P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms. Conclusions Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are

  11. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  12. Circulating Influenza Virus and Adverse Pregnancy Outcomes: A Time-Series Study.

    PubMed

    Fell, Deshayne B; Buckeridge, David L; Platt, Robert W; Kaufman, Jay S; Basso, Olga; Wilson, Kumanan

    2016-08-01

    Individual-level epidemiologic studies of pregnancy outcomes after maternal influenza are limited in number and quality and have produced inconsistent results. We used a time-series design to investigate whether fluctuation in influenza virus circulation was associated with short-term variation in population-level rates of preterm birth, stillbirth, and perinatal death in Ontario between 2003 and 2012. Using Poisson regression, we assessed the association between weekly levels of circulating influenza virus and counts of outcomes offset by the number of at-risk gestations during 3 gestational exposure windows. The rate of preterm birth was not associated with circulating influenza level in the week preceding birth (adjusted rate ratio = 1.01, 95% confidence interval: 1.00, 1.02) or in any other exposure window. These findings were robust to alternate specifications of the model and adjustment for potential confounding. Stillbirth and perinatal death rates were similarly not associated with gestational exposure to influenza circulation during late pregnancy. We could not assess mortality outcomes relative to early gestational exposure because of missing dates of conception for many stillbirths. In this time-series study, population-level influenza circulation was not associated with short-term variation in rates of preterm birth, stillbirth, or perinatal death. PMID:27449415

  13. Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study

    PubMed Central

    Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang

    2015-01-01

    Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ≥ 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153

  14. No adverse effects were identified on the perinatal outcomes after laser-assisted hatching treatment.

    PubMed

    Zhou, Hanying; Zao, Wanqiu; Zhang, Wei; Shi, Juanzi; Shi, Wenhao

    2014-12-01

    The aim of this study was to evaluate the safety of laser-assisted hatching (LAH) by comparing obstetric and neonatal outcomes between assisted hatching and control groups in cryopreserved embryo transfer cycles. A retrospective cohort analysis was carried out. A total of 699 women with 392 infants delivered were included. Laser- assisted hatching was carried out on D-3 thawed and warmed embryos before transfer in 480 cryopreserved embryos transfer cycles. Obstetric outcomes, neonatal outcomes, and congenital birth defects were recorded. A total of 815 cryopreserved embryo transfer cycles (480 in LAH group and 335 in control group) in 699 patients were analysed. Statistically significantly higher implantation (31.85% versus 16.95%), clinical pregnancy (53.96% versus 33.43%) and live delivery (44.58% versus 23.88%) rates were observed in the LAH group (all P < 0.001). For either singleton or multiple gestations, no statistically significant differences were found in mean gestational age, mean birth weight and mean Apgar score. Four major malformations occurred in the assisted hatching group and three malformations (one major and two minor) in the control group. This study did not identify any harmful effect of LAH on neonates, which suggested that LAH may be a safe treatment in cryopreserved embryo transfer cycles. PMID:25444502

  15. Trauma patient adverse outcomes are independently associated with rib cage fracture burden and severity of lung, head, and abdominal injuries

    PubMed Central

    Dunham, C Michael; Hileman, Barbara M; Ransom, Kenneth J; Malik, Rema J

    2015-01-01

    Objective: We hypothesized that lung injury and rib cage fracture quantification would be associated with adverse outcomes. Subjects and methods: Consecutive admissions to a trauma center with Injury Severity Score ≥ 9, age 18-75, and blunt trauma. CT scans were reviewed to score rib and sternal fractures and lung infiltrates. Sternum and each anterior, lateral, and posterior rib fracture was scored 1 = non-displaced and 2 = displaced. Rib cage fracture score (RCFS) = total rib fracture score + sternal fracture score + thoracic spine Abbreviated Injury Score (AIS). Four lung regions (right upper/middle, right lower, left upper, and left lower lobes) were each scored for % of infiltrate: 0% = 0; ≤ 20% = 1, ≤ 50% = 2, > 50% = 3; total of 4 scores = lung infiltrate score (LIS). Results: Of 599 patients, 193 (32%) had 854 rib fractures. Rib fracture patients had more abdominal injuries (p < 0.001), hemo/pneumothorax (p < 0.001), lung infiltrates (p < 0.001), thoracic spine injuries (p = 0.001), sternal fractures (p = 0.0028) and death or need for mechanical ventilation ≥ 3 days (Death/Vdays ≥ 3) (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p < 0.001), LIS (p < 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Of the 193 rib fracture patients, Glasgow Coma Score 3-12 or head AIS ≥ 2 occurred in 43%. A lung infiltrate or hemo/pneumothorax occurred in 55%. Thoracic spine injury occurred in 23%. RCFS was 6.3 ± 4.4 and Death/Vdays ≥ 3 occurred in 31%. Death/Vdays ≥ 3 rates correlated with RCFS values: 19% for 1-3; 24% for 4-6; 42% for 7-12 and 65% for ≥ 13 (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p = 0.02), LIS (p = 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Death/Vdays ≥ 3 association was better for RCFS (p = 0.005) than rib fracture score (p = 0.08) or number of fractured ribs (p = 0.80). Conclusion: Rib fracture patients have increased risk for truncal injuries and

  16. Not all developmental assets are related to positive health outcomes in college students

    PubMed Central

    2011-01-01

    Background The purpose of this investigation was to model the relationships between developmental assets, life satisfaction, and health-related quality of life (HRQOL) among a stratified, random sample (n = 765, 56% response rate) of college students. Methods Structural equation modeling techniques were employed to test the relationships using Mplus v4.21; Model evaluations were based on 1) theoretical salience, 2) global fit indices (chi-square goodness of fit, comparative fit index: CFI and Tucker-Lewis Index: TLI), 3) microfit indices (parameter estimates, root mean squared error of approximation: RMSEA and residuals) and 4) parsimony. Results The model fit the data well: χ2(n = 581, 515) = 1252.23, CFI = .94, TLI = .93 and RMSEA = .05. First, participants who reported increased Family Communication also reported higher levels of life satisfaction. Second, as participants reported having more Non-Parental Role Models, life satisfaction decreased and poor mental HRQOL days increased. Finally increased Future Aspirations was related to increased poor mental HRQOL days. Results were variant across gender. Conclusions Preliminary results suggest not all developmental assets are related to positive health outcomes among college students, particularly mental health outcomes. While the findings for Family Communication were expected, the findings for Non-Parental Role Models suggest interactions with potential role models in college settings may be naturally less supportive. Future Aspirations findings suggest college students may harbor a greater temporal urgency for the rigors of an increasingly competitive work world. In both cases, these assets appear associated with increased poor mental HRQOL days. PMID:21752293

  17. Surgery for sight: outcomes of congenital and developmental cataracts operated in Durban, South Africa.

    PubMed

    Gogate, P; Parbhoo, D; Ramson, P; Budhoo, R; Øverland, L; Mkhize, N; Naidoo, K; Levine, S; du Bryn, A; Benjamin, L

    2016-03-01

    PurposeTo study the visual outcomes of congenital and developmental cataract surgery and determine variables for presentation for pediatric cataract surgery in KwaZulu Natal province of South Africa.MethodsCare-givers of children presenting with cataract to a quaternary centre were asked when they first detected the condition. The reasons for delay between detection and surgery were studied. The children underwent a comprehensive eye examination and then appropriate surgery. They were prospectively followed up for 3 months and visual acuity and stereopsis were noted. Delay in presentation for surgery and visual outcomes were co-related with demographic and clinical factors.ResultsEighty-three non-traumatic cataract surgeries in 50 children were studied. Twenty-six (52%) were males, mean age was 3 years 10 months (SD 3yrs 4 months). The mean delay between identification and surgery was 20.7 months (SD 18 months). Twenty-six (52%) children had >15 months interval between diagnosis and surgery. Only mother's occupation was significantly associated with delay (P=0.017). Post-surgery 17/69 (24.7%) had visual acuity ≥6/18, 20/69 (29.0%) had vision between 6/24-6/60, whereas 32/69 (46.3%) had visual acuity ≤6/60. The final vision was associated with age (P=0.031), delay between diagnosis and surgery (P<0.001), type of surgery (P=0.046) and preoperative vision (P<0.001).ConclusionAlthough the children's vision improved substantially, a longer follow-up and amblyopia treatment would be necessary to optimize the visual outcome, which depended on age and preoperative vision. Health promotion activities aimed at mothers are important in improving visual outcomes. PMID:26611841

  18. Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

    PubMed

    Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

    2014-12-01

    In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development. PMID:24595754

  19. Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

    SciTech Connect

    Lam, Tai-Chung; Krishnan, Monica; Groff, Michael; Cheney, Matthew; Balboni, Tracy

    2015-10-01

    Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥11 and SF RT were associated with a higher rate of SAEs.

  20. Association between Environmental Dioxin-Related Toxicants Exposure and Adverse Pregnancy Outcome: Systematic Review and Meta-Analysis

    PubMed Central

    Pan, Xinjuan; Liu, Xiaozhuan; Li, Xing; Niu, Nannan; Yin, Xinjuan; Li, Ning; Yu, Zengli

    2015-01-01

    Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity (I2) were used to evaluate heterogeneity. In either cohort studies (I2=0.89, p<0.0001) or case control studies (I2=0.69, p=0.02), significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95% CI:0.85–1.16), no significant increased risk of spontaneous abortion (SAB) with exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80–1.37), higher significant risks of low birth weight (LBW) with exposure to food dioxin-related compounds (RR=1.55, 95% CI:1.24–1.94), and higher significant risks of birth defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19–1.29). In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome. PMID:25780516

  1. Clinical Characteristics and Predictors of Adverse Outcome in Adult and Pediatric Patients With Healthcare-Associated Ventriculitis and Meningitis

    PubMed Central

    Srihawan, Chanunya; Castelblanco, Rodrigo Lopez; Salazar, Lucrecia; Wootton, Susan H.; Aguilera, Elizabeth; Ostrosky-Zeichner, Luis; Sandberg, David I.; Choi, HuiMahn A.; Lee, Kiwon; Kitigawa, Ryan; Tandon, Nitin; Hasbun, Rodrigo

    2016-01-01

    Background. Healthcare-associated meningitis or ventriculitis is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Methods. We performed a retrospective study of adults and children with the diagnosis of healthcare-associated meningitis or ventriculitis, as defined by the 2015 Centers of Disease Control and Prevention case definition, at 2 large tertiary care hospitals in Houston, Texas from July 2003 to November 2014. Patients were identified by infection control practitioners and by screening cerebrospinal fluid samples sent to the central laboratory. We collected data on demographics, clinical presentations, laboratory results, imaging studies, treatments, and outcomes. Results. A total of 215 patients were included (166 adults and 49 children). A positive cerebrospinal fluid culture was seen in 106 (49%) patients, with the majority of the etiologies being Staphylococcus and Gram-negative rods. An adverse clinical outcome was seen in 167 patients (77.7%) and was defined as death in 20 patients (9.3%), persistent vegetative state in 31 patients (14.4%), severe disability in 77 patients (35.8%), or moderate disability in 39 patients (18.1%). On logistic regression analysis, age >45 years (adjusted odds ratio [OR], 6.47; 95% confidence interval [CI], 2.31–18.11; P ≤ .001), abnormal neurological exam (adjusted OR, 3.04; 95% CI, 1.27–7.29; P = .013), and mechanical ventilation (adjusted OR, 5.34; 95% CI, 1.51–18.92; P = .01) were associated with an adverse outcome. Conclusions. Healthcare-associated meningitis or ventriculitis is associated with significant morbidity and mortality. PMID:27419154

  2. Adverse Birth Outcomes and Maternal Exposure to Trichloroethylene and Tetrachloroethylene through Soil Vapor Intrusion in New York State

    PubMed Central

    Lewis-Michl, Elizabeth L.; Gomez, Marta I.

    2011-01-01

    Background: Industrial spills of volatile organic compounds (VOCs) in Endicott, New York (USA), have led to contamination of groundwater, soil, and soil gas. Previous studies have reported an increase in adverse birth outcomes among women exposed to VOCs in drinking water. Objective: We investigated the prevalence of adverse birth outcomes among mothers exposed to trichloroethylene (TCE) and tetrachloroethylene [or perchloroethylene (PCE)] in indoor air contaminated through soil vapor intrusion. Methods: We examined low birth weight (LBW), preterm birth, fetal growth restriction, and birth defects among births to women in Endicott who were exposed to VOCs, compared with births statewide. We used Poisson regression to analyze births and malformations to estimate the association between maternal exposure to VOCs adjusting for sex, mother’s age, race, education, parity, and prenatal care. Two exposure areas were identified based on environmental sampling data: one area was primarily contaminated with TCE, and the other with PCE. Results: In the TCE-contaminated area, adjusted rate ratios (RRs) were significantly elevated for LBW [RR = 1.36; 95% confidence interval (CI): 1.07, 1.73; n = 76], small for gestational age (RR = 1.23; 95% CI: 1.03, 1.48; n = 117), term LBW (RR = 1.68; 95% CI: 1.20, 2.34; n = 37), cardiac defects (RR = 2.15; 95% CI: 1.27, 3.62; n = 15), and conotruncal defects (RR = 4.91; 95% CI: 1.58, 15.24; n = 3). In the PCE-contaminated area, RRs for cardiac defects (five births) were elevated but not significantly. Residual socioeconomic confounding may have contributed to elevations of LBW outcomes. Conclusions: Maternal residence in both areas was associated with cardiac defects. Residence in the TCE area, but not the PCE area, was associated with LBW and fetal growth restriction. PMID:22142966

  3. Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

    PubMed Central

    Fidler, M M; Frobisher, C; Guha, J; Wong, K; Kelly, J; Winter, D L; Sugden, E; Duncan, R; Whelan, J; Reulen, R C; Hawkins, M M

    2015-01-01

    Background: With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study. Methods: Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire. Results: Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likely to develop a SPN than expected, where the excess was restricted to 5–24 years post diagnosis. Increased health-care usage and poor health status were also found. Nonetheless, for some psychosocial outcomes survivors were better off than expected. Conclusions: Up to 25 years after 5-year survival, bone sarcoma survivors are at substantial risk of death and SPNs, but this is greatly reduced thereafter. As 95% of all excess deaths before 25 years follow-up were due to recurrences and SPNs, increased monitoring of survivors could prevent mortality. Furthermore, bone and breast SPNs should be a particular concern. Since there are variations in the magnitude of excess risk depending on the specific adverse outcome under investigation and whether the survivors were initially diagnosed with osteosarcoma or Ewing sarcoma, risks need to be assessed in relation to these factors. These findings should provide useful evidence for risk stratification and updating

  4. Promoting equal developmental opportunity and outcomes among America's children and youth: results from the National Promises Study.

    PubMed

    Scales, Peter C; Benson, Peter L; Moore, Kristin A; Lippman, Laura; Brown, Brett; Zaff, Jonathan F

    2008-03-01

    Building on a developmental framework positing five types of assets or inputs needed for children's development, referred to as promises, we investigated the extent to which American children and youth experience the five Promises articulated by the America's Promise Alliance. These are: (1) Caring Adults, (2) Safe Places and Constructive Use of Time, (3) A Healthy Start, (4) Effective Education, and (5) Opportunities to Make a Difference. Data came from a nationally representative poll designed to assess these five resources and involved more than 4,000 teenagers and their parents. Results showed that only a minority of young people experienced rich developmental nourishment (having 4-5 of the Promises). Males, older adolescents, adolescents of color, and adolescents from families with less education and lower parental annual incomes were significantly less likely to experience sufficient developmental opportunities and were also less likely to experience desirable developmental outcomes. However, among those young people who reported experiencing 4-5 Promises, the great majority of demographic differences in developmental outcomes were either eliminated or significantly reduced. The results suggest that increasing children's experience of these Promises would reduce developmental inequalities among America's young people. EDITORS' STRATEGIC IMPLICATIONS: Longitudinal studies with representative samples will be necessary to further validate this approach and study causal contributions of assets, but this integration of Positive Youth Development frameworks holds great promise for theory, practice, and policy. PMID:18373201

  5. Do adult men with untreated ventral penile curvature have adverse outcomes?

    PubMed Central

    Menon, Vani; Breyer, Benjamin; Copp, Hillary L.; Baskin, Laurence; Disandro, Michael; Schlomer, Bruce J.

    2016-01-01

    Summary Introduction Congenital ventral penile curvature without hypospadias is often treated surgically in childhood. The history of untreated ventral curvature is unknown. Objective This study’s aim was to examine the association of untreated ventral penile curvature with various sexual and psychosexual outcomes. Study design An electronic survey was advertised to men older than 18 years on Facebook. Men with possible ventral penile curvature identified themselves by choosing sketches that most closely represented their anatomy. Outcomes assessed included: Sexual Health Inventory for Men, difficulty of intercourse because of curvature, International Prostate Symptom Score, Penile Perception Score, psychosexual milestones, paternity, infertility, sitting to urinate, and the CDC HRQOL-4 module. Results Among participants, 81 out of 684 men (11.8%) reported untreated ventral penile curvature. Participants with self-reported curvature noted more difficulty with intercourse because of curvature (4.5 vs 4.9, p < 0.001), more unhealthy mental days (8.6 vs 6.2, p = 0.02), and increased dissatisfaction with penile self-perception compared with men without reported curvature (8.6 vs 9.5, p < 0.001). Discussion Men with possible untreated ventral curvature reported worse penile perception scores, more mentally unhealthy days, and increased difficulty with intercourse secondary to curvature compared with men without curvature. A limitation to this study is selection bias; responses collected were self-reported from survey volunteers. Additionally, the question identifying ventral penile curvature is not validated but performed well in pretesting. Most questions were from validated surveys, but some were modeled after validated surveys and/or contained high face validity types of questions. Conclusion Men with possible untreated ventral penile curvature reported more dissatisfaction with penile appearance, increased difficulty with intercourse, and more unhealthy mental

  6. Recent immigration and adverse pregnancy outcomes in an urban setting in Spain.

    PubMed

    Garcia-Subirats, Irene; Pérez, Glòria; Rodríguez-Sanz, Maica; Salvador, Joaquín; Jané, Mireia

    2011-07-01

    To describe social and economic inequalities in non-fatal pregnancy outcomes (low birth weight, preterm birth and small for gestational age births) in the neighbourhoods of the city of Barcelona (Spain), according to maternal age and maternal country of origin, between 1991 and 2005. A cross-sectional ecological study was carried out using the 38 neighbourhoods of Barcelona as the unit of analysis. The study population comprises the 192,921 live births to resident women aged 12-49 residing from 1991 to 2005. Information was gathered from births registry. Prevalence of low birth-weight, preterm birth and small for gestational age, was calculated for each of the 38 neighbourhoods of mothers' residence, stratifying results by maternal age and country of origin. The indicator of neighbourhood socio-economic level was the unemployment rate. Quartile maps along with Spearman correlation coefficients and linear regression were performed between indicators. The present study reports socio-economic inequalities in pregnancy outcomes among neighbourhoods in Barcelona (Spain): the more disadvantaged neighbourhoods have worse pregnancy outcomes (low birth weight, preterm birth and small for gestational age births) in all women age groups. These inequalities do not exist among immigrant women, and some groups of foreign mothers even have lower rates of low birth weight, preterm birth, and small for gestational age births than autochthonous women. The existing inequalities suggest that policy efforts to reduce these inequalities are not entirely successful and should focus on improving pregnancy and delivery care in less privileged women in a country with universal access to health care. PMID:20440546

  7. Long-Term Maternal Stress and Post-traumatic Stress Symptoms Related to Developmental Outcome of Extremely Premature Infants.

    PubMed

    Zerach, Gadi; Elsayag, Adi; Shefer, Shahar; Gabis, Lidia

    2015-08-01

    In this study, we examined the relations between the severity of developmental outcomes of extremely low birth weight (ELBW) children and their mothers' stress and post-traumatic stress disorder (PTSD) symptoms, 4-16 years after birth. Israeli mothers (N = 78) of a cohort of extremely premature infants (24-27 weeks) born 4-16 years earlier were asked to report about the medical and developmental condition of their child and their current perceived stress and PTSD symptoms. Results show that mothers of ELBW children with normal development reported the lowest perceived stress compared with mothers of ELBW children with developmental difficulties. We also found that 25.6% of the mothers had the potential to suffer from PTSD following the birth of an ELBW child. Furthermore, the severity of prematurity developmental outcomes made a significant contribution to mothers' perceived stress. To sum, mothers of ELBW infants' perceived stress is related to their children's severity of prematurity developmental outcomes, 4-16 years after birth. Clinical implications of these findings are discussed. PMID:26252160

  8. Family factors and social support in the developmental outcomes of very low-birth weight children.

    PubMed

    Hogan, D P; Park, J M

    2000-06-01

    This study used data that were representative of the normative population of all infants born in 1988 and were followed during the first 3 years of life. Large developmental delays and limitations in function were common among children weighing less than 1500 g at birth. Among very low-birth weight infants, minority status and living in a household headed by a single mother further worsen the disadvantages associated with a very low birth weight. Nor could the disadvantages associated with very low birth weight be accounted for by controls for other risk factors or buffering statuses and behaviors. Among all children (including those of very low birth weight) poverty, reliance on Medicaid and other government sources for health insurance, a history of risky behaviors, and inadequate prenatal care are the major risk factors for developmental delays, limitations in function, and impairment at birth. State program benefit levels have no obvious effects on child outcomes, taking into account participation in individual programs. An important finding in light of TANF is that maternal work, the use of child care, and the form and cost of child care did not influence developmental delay, limitation in function, or impairment, the outcomes that we were able to measure during the first 3 years of life. TANF eligibility requirements, however, may increase difficulty in obtaining prenatal and other medical services for mothers and children in need--factors shown here to be related strongly to increased risk of low birth weight and developmental delays, limitations, and impairments. Race and ethnicity, poverty status, and family structure are fundamental factors in early child development and function. Minority status, poverty, and single-parent households greatly increase the likelihood that a mother will engage in risky behaviors (smoking, alcohol use, illegal drug use) during pregnancy and receive inadequate prenatal care. Risky behaviors and inadequate prenatal care are

  9. Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers.

    PubMed

    Wang, Zhenghe; Li, Li; Guda, Kishore; Chen, Zhengyi; Barnholtz-Sloan, Jill; Park, Young Soo; Markowitz, Sanford D; Willis, Joseph

    2016-12-01

    African Americans have the highest incidence and mortality from colorectal cancer (CRC) of any US racial group. We recently described a panel of 15 genes that are statistically significantly more likely to be mutated in CRCs from African Americans than in Caucasians (AA-CRC genes). The current study investigated the outcomes associated with these mutations in African American CRCs (AA-CRCs). In a cohort of 66 patients with stage I-III CRCs, eight of 27 CRCs with AA-CRC gene mutations (Mut+) developed metastatic disease vs only four of 39 mutation-negative (Mut-) cases (P = .03, Cox regression model with two-sided Wald test). Moreover, among stage III cases (n = 33), Mut+ cancers were nearly three times more likely to relapse as Mut- cases (7 of 15 Mut+ vs 3 of 18 Mut-; P = .03, Cox regression model with two-sided Wald test). AA-CRC mutations may thus define a high-risk subset of CRCs that contributes to the overall disparity in CRC outcomes observed in African Americans. PMID:27582379

  10. 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. PMID:26333919

  11. Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion

    PubMed Central

    Stundner, O.; Chiu, Y-L.; Sun, X.; Ramachandran, S-K.; Gerner, P.; Vougioukas, V.; Mazumdar, M.; Memtsoudis, S. G.

    2014-01-01

    Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84 655 patients undergoing posterior lumbar fusion were identified and 7.28% also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood transfusion, and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (Odds Ratio (OR) 1.50, Confidence Interval (CI) 1.38;1.62), blood transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians. PMID:24493191

  12. Role of genetic susceptibility in development of treatment-related adverse outcomes in cancer survivors.

    PubMed

    Bhatia, Smita

    2011-10-01

    Clear and unambiguous associations have been established between therapeutic exposures and specific complications. However, considerable interindividual variability is observed in the risk of developing an outcome for a given therapeutic exposure. Genetic predisposition and especially its interaction with therapeutic exposures can potentially exacerbate the toxic effect of treatment on normal tissues and organ systems, and can possibly explain the interindividual variability. This article provides a brief overview of the current knowledge about the role of genomic variation in the development of therapy-related complications. Relatively common outcomes with strong associations with therapeutic exposures, including cardiomyopathy, obesity, osteonecrosis, ototoxicity, and subsequent malignancies are discussed here. To develop a deeper understanding of the molecular underpinnings of therapy-related complications, comprehensive and near-complete collection of clinically annotated samples is critical. Methodologic issues such as study design, definition of the endpoints or phenotypes, identification of appropriate and adequately sized study population together with a reliable plan for collecting and maintaining high-quality DNA, and selection of an appropriate approach or platform for genotyping are also discussed. Understanding the etiopathogenetic pathways that lead to the morbidity is critical to developing targeted prevention and intervention strategies, optimizing risk-based health care of cancer survivors, thus minimizing chronic morbidities and improving quality of life. PMID:21980013

  13. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction.

    PubMed

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients' medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  14. Periodontal bacteria in the genital tract: are they related to adverse pregnancy outcome?

    PubMed

    Cassini, M A; Pilloni, A; Condò, S G; Vitali, L A; Pasquantonio, G; Cerroni, L

    2013-01-01

    One of the most important factors implicated in preterm birth (PTB) is acute genitourinary tract infection. The bacteria causing chronic periodontal inflammation include Gram-negative rods and anaerobes similar to those found in women with bacterial vaginosis. The aim of this prospective study is to investigate the relationship between oral and vaginal microflora and preterm low birth weight. Real-time polymerase chain reaction was used to detect both the presence and level of six periodontitis-related species: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Fusobacterium nucleatum ssp(Fn), and Prevotella intermedia (Pi) for both oral samples of subgingival plaque and cervical samples, obtained from 80 patients, during gynaecological examinations. The more representative oral pathogen (less than 60 percent) species in oral samples of preterm and term group were Tf, Td, and Fn. 24.4 percent of pregnant women presented periodontal pathogens in vaginal swab; the most representative species with a percentage over 0.1 percent of total bacteria in genital tract of preterm group were Tf, Td, and Piwith a positive correlation (less than 0.5). The presence of the bacterium T. denticolain the vagina, regardless of the amount, adversely affects preterm delivery. PMID:24355228

  15. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction

    PubMed Central

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients’ medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  16. 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,...

  17. DEVELOPMENTAL TRAJECTORIES OF MARIJUANA USE FROM ADOLESCENCE TO ADULTHOOD: PERSONALITY AND SOCIAL ROLE OUTCOMES1,2

    PubMed Central

    BROOK, JUDITH S.; LEE, JUNG YEON; BROWN, ELAINE N.; FINCH, STEPHEN J.; BROOK, DAVID W.

    2011-01-01

    Summary Longitudinal trajectories of marijuana use from adolescence into adulthood were examined for adverse life-course outcomes among African-Americans and Puerto Ricans. Data for marijuana use were analyzed at four points in time and on participants’ personality attributes, work functioning, and partner relations in adulthood using growth mixture modeling. Each of the three marijuana-use trajectory groups (maturing-out, late-onset, and chronic marijuana-users) had greater adverse life-course outcomes than a non or low-use trajectory group. The chronic marijuana-use trajectory group was highly associated with criminal behavior and partners’ marijuana use in adulthood. Treatment programs for marijuana use should also directly address common adverse life-course outcomes which users may already be experiencing. PMID:21675549

  18. Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Kluetz, Paul G; Chingos, Diana T; Basch, Ethan M; Mitchell, Sandra A

    2016-01-01

    Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials. PMID:27249687

  19. Conduct Problems in Childhood and Adolescence: Developmental Trajectories, Predictors and Outcomes in a Six-Year Follow Up.

    PubMed

    López-Romero, Laura; Romero, Estrella; Andershed, Henrik

    2015-10-01

    Understanding youth conduct problems requires examination from a developmental perspective, analyzing distinctive pathways across childhood and adolescence, and identifying early predictors which will lead to specific adolescent outcomes. Bearing this in mind, developmental trajectories of conduct problems were identified from a person-oriented perspective, and using data collected from three waves over a six-year period, in a sample of Spanish children aged 6-11 at the onset of the study. Conduct problems showed five distinctive trajectories which were grouped into three major pathways in further analyses: Stable low, Stable high, and Decreasing. Associations with early personality and psychopathic traits, as well as with a wide range of adolescent behavioral and psychosocial outcomes were examined, revealing the Stable high group as exhibiting the highest risk profile. These results contribute to improving our knowledge about one of the most relevant problems in youth populations, and will help in refining interventions strategies by recognizing the developmental heterogeneity of the construct. PMID:25354563

  20. A Short-term In Vivo Screen Using Fetal Testosterone Production, a Key Event in the Phthalate Adverse Outcome Pathway, to Predict Disruption of Sexual Differentiation

    PubMed Central

    Wilson, Vickie S.; Foster, Paul M.; Gray, Leon E.

    2014-01-01

    This study was designed to develop and validate a short-term in vivo protocol termed the Fetal Phthalate Screen (FPS) to detect phthalate esters (PEs) and other chemicals that disrupt fetal testosterone synthesis and testis gene expression in rats. We propose that the FPS can be used to screen chemicals that produce adverse developmental outcomes via disruption of the androgen synthesis pathway more rapidly and efficiently, and with fewer animals than a postnatal one-generation study. Pregnant rats were dosed from gestational day (GD) 14 to 18 at one dose level with one of 27 chemicals including PEs, PE alternatives, pesticides known to inhibit steroidogenesis, an estrogen and a potent PPARα agonist and ex vivo testis testosterone production (T Prod) was measured on GD 18. We also included some chemicals with “unknown” activity including DMEP, DHeP, DHEH, DPHCH, DAP, TOTM, tetrabromo-diethyl hexyl phthalate (BrDEHP), and a relatively potent environmental estrogen BPAF. Dose-response studies also were conducted with this protocol with 11 of the above chemicals to determine their relative potencies. CD-1 mice also were exposed to varying dose levels of DPeP from GD 13 to 17 to determine if DPeP reduced T Prod in this species since there is a discrepancy among the results of in utero studies of PEs in mice. Compared to the known male reproductive effects of the PEs in rats the FPS correctly identified all known “positives” and “negatives” tested. Seven of eight “unknowns” tested were “negatives”, they did not reduce T Prod, whereas DAP produced an “equivocal” response. Finally, a dose-response study with DPeP in CD-1 mice revealed that fetal T Prod can be inhibited by exposure to a PE in utero in this species, but at a higher dose level than required in rats.Key words. Phthalate Syndrome, Fetal endocrine biomarkers, Phthalate adverse outcome pathway, testosterone production, fetal rat testis. PMID:24798384

  1. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

    PubMed

    Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

    2015-07-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  2. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

    PubMed Central

    Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

    2016-01-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  3. Prenatal Diagnosis and Evaluation of Sonographic Predictors for Intervention and Adverse Outcome in Congenital Pulmonary Airway Malformation

    PubMed Central

    Hellmund, Astrid; Berg, Christoph; Geipel, Annegret; Bludau, Meike; Heydweiller, Andreas; Bachour, Haitham; Müller, Andreas; Müller, Annette; Gembruch, Ulrich

    2016-01-01

    Objective To describe antenatal findings and evaluate prenatal risk parameters for adverse outcome or need for intervention in fetuses with congenital pulmonary airway malformation (CPAM). Methods In our retrospective study all fetuses with a prenatal diagnosis of CPAM detected in our tertiary referral center between 2002 and 2013 were analyzed. Sonographic findings were noted and measurements of mass-to-thorax-ratio (MTR), congenital pulmonary airway malformation volume-ratio (CVR) and observed to expected lung-to head-ratio (o/e LHR) were conducted and correlated to fetal or neonatal morbidity and mortality and/or need for prenatal intervention. Results 67 fetuses with CPAM were included in the study. Hydropic fetuses were observed in 16.4% (11/67) of cases, prenatal intervention was undertaken in 9 cases; 7 pregnancies were terminated. The survival rate of non-hydropic fetuses with conservatively managed CPAM was 98.0% (50/51), the survival rate for hydropic fetuses with intention to treat was 42.9% (3/7). 10 (18.2%) children needed respiratory assistance. Fetuses with a CVR of <0.91 were significantly less likely to experience adverse outcome or need for prenatal intervention with sensitivity, specificity and positive/negative predictive value of 0.89, 0.71, 0.62 and 0.93, respectively. A MTR (mass-to-thorax-ratio) of < 0.51 had a positive predictive value of 0.54 and a negative predictive value of 0.96 of adverse events with a sensitivity of 0.95 and a specificity of 0.63. The negative predictive value for o/e LHR of 45% was 0.84 with sensitivity, specificity and positive predictive value of 0.73, 0.68 and 0.52, respectively. Conclusions The majority of cases with CPAM have a favorable outcome. MTR and CVR are able to identify fetuses at risk, the o/e LHR is less sensitive. PMID:26978067

  4. Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of adverse renal outcomes in immunoglobulin A nephropathy

    PubMed Central

    Park, Ga-Young; Yu, Chung-Hoon; Kim, Jun-Seop; Kang, Yun-Jeong; Kwon, Owen; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Kim, Yong-Lim

    2015-01-01

    Background/Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). Methods In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. Results The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. Conclusions pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value. PMID:25995665

  5. The adverse outcome pathway for rodent liver tumor promotion by sustained activation of the aryl hydrocarbon receptor.

    PubMed

    Becker, Richard A; Patlewicz, Grace; Simon, Ted W; Rowlands, J Craig; Budinsky, Robert A

    2015-10-01

    An Adverse Outcome Pathway (AOP) represents the existing knowledge of a biological pathway leading from initial molecular interactions of a toxicant and progressing through a series of key events (KEs), culminating with an apical adverse outcome (AO) that has to be of regulatory relevance. An AOP based on the mode of action (MOA) of rodent liver tumor promotion by dioxin-like compounds (DLCs) has been developed and the weight of evidence (WoE) of key event relationships (KERs) evaluated using evolved Bradford Hill considerations. Dioxins and DLCs are potent aryl hydrocarbon receptor (AHR) ligands that cause a range of species-specific adverse outcomes. The occurrence of KEs is necessary for inducing downstream biological responses and KEs may occur at the molecular, cellular, tissue and organ levels. The common convention is that an AOP begins with the toxicant interaction with a biological response element; for this AOP, this initial event is binding of a DLC ligand to the AHR. Data from mechanistic studies, lifetime bioassays and approximately thirty initiation-promotion studies have established dioxin and DLCs as rat liver tumor promoters. Such studies clearly show that sustained AHR activation, weeks or months in duration, is necessary to induce rodent liver tumor promotion--hence, sustained AHR activation is deemed the molecular initiating event (MIE). After this MIE, subsequent KEs are 1) changes in cellular growth homeostasis likely associated with expression changes in a number of genes and observed as development of hepatic foci and decreases in apoptosis within foci; 2) extensive liver toxicity observed as the constellation of effects called toxic hepatopathy; 3) cellular proliferation and hyperplasia in several hepatic cell types. This progression of KEs culminates in the AO, the development of hepatocellular adenomas and carcinomas and cholangiolar carcinomas. A rich data set provides both qualitative and quantitative knowledge of the progression of

  6. What Factors Are Related to a Negative Outcome of Self-Injurious Behaviour during Childhood in Pervasive Developmental Disorders?

    ERIC Educational Resources Information Center

    Baghdadli, A.; Picot, M. C.; Pry, R.; Michelon, C.; Burzstejn, C.; Lazartigues, A.; Aussilloux, C.

    2008-01-01

    Aim: To explore the factors related to the outcome of self-injurious behaviour (SIB) in children with pervasive developmental disorders (PDD). Method: Children with PDD were assessed on individual and environmental variables at time 1 and 3 years later. A questionnaire about the presence or absence of SIB was also administered at both times in…

  7. The Interest-Driven Pursuits of 15 Year Olds: "Sparks" and Their Association with Caring Relationships and Developmental Outcomes

    ERIC Educational Resources Information Center

    Ben-Eliyahu, Adar; Rhodes, Jean E.; Scales, Peter

    2014-01-01

    In this study, we examined the characteristics of adolescents' deep interests or "sparks," the role of relationships in supporting the development of sparks, and whether having a spark was associated with positive developmental outcomes. Participants included 1,860 15 years olds from across the United States who participated in the…

  8. Familism as a Predictor of Parent-Adolescent Relationships and Developmental Outcomes for Adolescents in Armenian American Immigrant Families

    ERIC Educational Resources Information Center

    Ghazarian, Sharon R.; Supple, Andrew J.; Plunkett, Scott W.

    2008-01-01

    We investigated associations between familism, parent-adolescent relationships, and developmental outcomes for a sample of 97 Armenian adolescents in immigrant families. Our results suggested that adolescents emphasizing family needs over their own were more likely to report conformity to parents' wishes, respect for parental authority, and…

  9. Maternal Schooling and Children's Relative Inequalities in Developmental Outcomes: Evidence from the 1947 School Leaving Age Reform in Britain

    ERIC Educational Resources Information Center

    Sabates, Ricardo; Duckworth, Kathryn

    2010-01-01

    This paper investigates whether mothers' participation in post-compulsory education impacts on children's relative inequalities across four developmental outcomes. The empirical analysis uses information from children born in 1958 in Britain. Mothers of the 1958 British cohort were affected by the 1947 school leaving age reform, which increased…

  10. Effects of School Counselor Supervised Peer Tutoring in Inclusive Settings on Meeting IEP Outcomes of Students with Developmental Disabilities

    ERIC Educational Resources Information Center

    Odluyurt, Serhat; Tekin-Iftar, Elif; Ersoy, Gulhan

    2014-01-01

    The purpose of this study was to investigate the effects of school counselor supervised peer tutoring intervention on meeting IEP outcomes of six inclusion students with developmental disabilities in a public elementary and secondary school. The effectiveness of this intervention was evaluated by using multiple probe design across students.…

  11. Observed Ecological Assets in Families, Schools, and Neighborhoods: Conceptualization, Measurement, and Relations with Positive and Negative Developmental Outcomes

    ERIC Educational Resources Information Center

    Theokas, Christina; Lerner, Richard M.

    2006-01-01

    The relations among observed ecological assets in youth's families, schools, and neighborhoods with positive and negative developmental outcomes were assessed with a sample of 646 fifth-grade youth. The majority of participants were Latino (37.5%) or European American (35.5%) and lived in 2-parent families. Ecological asset indicators were…

  12. Family Caregivers of Adults with Intellectual and Developmental Disabilities: Outcomes Associated with U.S. Services and Supports

    ERIC Educational Resources Information Center

    Williamson, Heather J.; Perkins, Elizabeth A.

    2014-01-01

    Individuals with intellectual and developmental disabilities (IDD) in the U.S. predominantly live with their family caregivers. As care delivery and support systems vary widely globally, consideration of caregiver outcomes specifically in the U.S. context is needed. A systematic literature review was conducted to identify U.S. family caregiver…

  13. Developmental Language Disorders--A Follow-Up in Later Adult Life. Cognitive, Language and Psychosocial Outcomes

    ERIC Educational Resources Information Center

    Clegg, J.; Hollis, C.; Mawhood, L.; Rutter, M.

    2005-01-01

    Background: Little is known on the adult outcome and longitudinal trajectory of childhood developmental language disorders (DLD) and on the prognostic predictors. Method: Seventeen men with a severe receptive DLD in childhood, reassessed in middle childhood and early adult life, were studied again in their mid-thirties with tests of intelligence…

  14. Interaction Pattern and Developmental Outcome of Infants with Severe Asphyxia: A Longitudinal Study of the First Years of Life.

    ERIC Educational Resources Information Center

    Campbell, Philippa H.; And Others

    1989-01-01

    Seven full-term infants with severe encephalopathy following perinatal asphyxia were followed longitudinally to two years of age to determine health and developmental outcome and to investigate mother-infant interaction patterns over time. Six infants demonstrated delayed development; five were diagnosed with cerebral palsy. Mother-infant…

  15. Oxygen desaturation in 6-min walk test is a risk factor for adverse outcomes in COPD.

    PubMed

    Waatevik, Marie; Johannessen, Ane; Gomez Real, Francisco; Aanerud, Marianne; Hardie, Jon Andrew; Bakke, Per Sigvald; Lind Eagan, Tomas Mikal

    2016-07-01

    The 6-min walk test (6MWT) is an exercise test that measures functional status in chronic obstructive pulmonary disease (COPD) patients and provides information on oxygen desaturation. We investigated oxygen desaturation during 6MWT as a risk factor for important COPD outcomes: mortality, frequency of exacerbations, decline in lung function and decline in lean body mass.433 COPD patients were included in the Bergen COPD Cohort Study 2006-2009, and followed-up for 3 years. Patients were characterised using spirometry, bioelectrical impedance measurements, Charlson comorbidity score, exacerbation history, smoking and arterial blood gases. 370 patients completed the 6MWT at the baseline of the study. Information on all-cause mortality was collected in 2011.Patients who experienced oxygen desaturation during the 6MWT had an approximately twofold increased risk of death (hazard ratio 2.4, 95% CI 1.2-5.1), a 50% increased risk for experiencing later COPD exacerbations (incidence rate ratio 1.6, 95% CI 1.1-2.2), double the yearly rate of decline in both forced vital capacity and forced expiratory volume in 1 s (3.2% and 1.7% versus 1.7% and 0.9%, respectively) and manifold increased yearly rate of loss of lean body mass (0.18 kg·m(-2) versus 0.03 kg·m(-2) among those who did not desaturate).Desaturating COPD patients had a significantly worse prognosis than non-desaturating COPD patients, for multiple important disease outcomes. PMID:27076586

  16. Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

    PubMed Central

    Espe, Katharina M.; Raila, Jens; Henze, Andrea; Blouin, Katja; Schneider, Andreas; Schmiedeke, Daniel; Krane, Vera; Pilz, Stefan; Schweigert, Florian J.; Hocher, Berthold; Wanner, Christoph

    2013-01-01

    Summary Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of α-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), α-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma α-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66±8 years, and mean plasma α-tocopherol level was 22.8±9.6 µmol/L. Levels of α-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest α-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratiostroke=1.56, 95% confidence interval=0.75–3.25; hazard ratiomortality=1.22, 95% confidence interval=0.89–1.69, respectively). There was no association between α-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma α-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients. PMID:23335039

  17. Adverse health outcomes, perpetrator characteristics, and sexual violence victimization among U.S. adult males.

    PubMed

    Choudhary, Ekta; Coben, Jeffrey; Bossarte, Robert M

    2010-08-01

    In the United States, an estimated three million men are victims of sexual violence each year, yet the majority of existing studies have evaluated the consequences and characteristics of victimization among women alone. The result has been a gap in the existing literature examining the physical and psychological consequences of sexual assault among men. The main objective of this study was to identify health outcomes, risk behaviors, and perpetrator/victim relationship characteristics among men who have experienced an attempted or completed sexual assault using data from the sexual violence module of the Behavioral Risk Factor Surveillance System survey. A total of 59,511 male respondents participated in the sexual violence module, and the majority of participants were White (73.7%), between the ages of 35 to 44 years (19.8%), married (69.0%), graduated from college (34.6%), and had an annual household income of more than US$50,000 (49.9%). Stratified multivariate logistic regression models were conducted to test the associations between victimization and health outcomes and risk behaviors controlling for age, marital status, race/ethnicity, income, education, and other potential confounders. Results of these analyses suggest important associations between health and sexual violence victimization. Specifically, men who reported unwanted attempted intercourse and attempted and completed intercourse were more likely to report poor mental health, poor life satisfaction, activity limitations, and lower emotional and social support. The current study extends knowledge of consequences of male sexual violence by considering characteristics of sexual assault and by identifying associations between victimization and a broad range of health indicators. PMID:19940163

  18. Outcomes and Adverse Events of Enlarged Tracheoesophageal Puncture after Total Laryngectomy

    PubMed Central

    Hutcheson, Katherine A.; Lewin, Jan S.; Sturgis, Erich M.; Risser, Jan

    2014-01-01

    Objective Enlargement of the tracheoesophageal puncture (TEP) results in aspiration around the voice prosthesis (VP) and may lead to pneumonia. The primary objective was to summarize control of leakage around the VP after conservative management of enlarged TEP. Study Design Retrospective cohort study. Methods This 5-year cohort included 194 patients who underwent total laryngectomy (± pharyngectomy) and TEP at the University of Texas MD Anderson Cancer Center. Control of leakage around the VP was analyzed at last follow-up after enlarged TEP. Adverse events were compared in patients with and without enlarged TEP. Results The incidence of enlarged TEP was 18.6% (36/194, 95% CI: 13.0%-24.1%). Conservative methods commonly attempted in lieu of complete TEP closure included placement of an enlarged-flange VP (34/36, 94%), temporary VP removal (14/36, 39%), and TEP-site injection (8/36, 22%). At last follow-up, conservative methods controlled leakage around the VP in 81% (29/36) of patients. Only 2 patients required complete TEP closure due to persistent leakage after enlarged TEP. Unresolved leakage was more common in patients with recurrent cancer after laryngectomy (p=0.081) and irregular TEP contour (p=0.003). Relative to controls without TEP enlargement, patients with enlarged TEP had 3-fold higher risk of pneumonia (RR: 3.4, 95% CI: 1.9-6.2) and aspiration of the prosthesis (RR: 3.3, 95% CI: 0.8-14.1). Conclusions Although the rate of enlarged TEP is relatively low, the complication significantly elevates risk of pneumonia. Prosthetic leakage related to TEP enlargement can often be managed conservatively to avoid complete closure of the TEP. Level of evidence: 2b PMID:21647906

  19. Predictors of severity and outcome of global developmental delay without definitive etiologic yield: a prospective observational study

    PubMed Central

    2014-01-01

    Background Although several determinants of global developmental delay (GDD) have been recognized, a significant number of children remain without definitive etiologic diagnosis. The objective of this study was to assess the effect of various prenatal and perinatal factors on the severity and outcome of developmental delay without definitive etiologic yield. Methods From March 2008 to February 2010, 142 children with developmental quotient (DQ) <70 and without definitive etiologic diagnosis, were included. Prenatal and perinatal risk factors known to be associated with disordered neonatal brain function were identified. Participants underwent a thorough investigation, an individualized habilitation plan was recommended, and the children were followed-up regularly for a period of 2 < years. The effect of prenatal and perinatal risk factors on the severity and outcome of GDD was assessed by regression analysis. Results The mean age at enrolment was 31 ± 12 < months, and the mean DQ 52.2 ± 11.4. Prematurity and intrauterine growth restriction (IUGR) were found to be independently associated with lower DQ values. The mean DQ after the 2-year follow-up was 62.5 ± 12.7, and the DQ difference from the enrollment 10.4 ± 8.9 (median 10; range-10 to 42). DQ improvement (defined as a DQ difference?≥?median) was noted in 52.8% of the children. IUGR, low socio-economic status, and poor compliance to habilitation plan were found to be independently associated with poorer developmental outcomes. Conclusions Prematurity and IUGR were found to be significantly and independently related to the severity of GDD in cases without definitive etiologic yield. Poorer 2-year developmental outcome was associated with IUGR, low socioeconomic status and non compliance to habilitation plan. Prematurity was a significant determinant of the outcome only in association with the above mentioned factors. PMID:24521451

  20. Left Atrial Volume and Adverse Cardiovascular Outcomes in Unselected Patients with and without CKD

    PubMed Central

    Hee, Leia; Nguyen, Tuan; Whatmough, Melinda; Descallar, Joseph; Chen, Jack; Kapila, Shruti; French, John K.

    2014-01-01

    Background and objectives Patients with CKD have increased cardiovascular morbidity and mortality. This study investigated the prognostic value of common clinical echocardiographic parameters. Design, setting, participants, & measurements There were 289 unselected consecutive patients who had a transthoracic echocardiogram between January and June 2003. Patients with stage 3 or 4 CKD (n=49) were compared with those with eGFR≥60 ml/min per 1.73 m2, n=240). Left ventricular volume, ejection fraction and mass, left atrial volume, and function parameters were measured. The primary endpoint, determined a priori, was a composite of cardiac death, myocardial infarction, and congestive cardiac failure. Results Patients were followed for a median 5.6 years. The incidence of the primary endpoint was higher in patients with CKD (29% versus 12%, P=0.001), who were older and had a higher prevalence of hypertension and ischemic heart disease. Indexed left ventricular mass (LVMI) and left atrial volume (LAVI) were higher in patients with CKD. Furthermore, patients with LAVI>32 ml/m2 had significantly lower event-free survival than patients with normal (<28 ml/m2) or mildly dilated LAVI (28–32 ml/m2) (P<0.001). Multivariate analysis showed that age (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.08 to 1.31; P=0.001) and LVMI (OR, 3.66; 95% CI, 2.47 to 5.41; P<0.001) were independently associated with LAVI>32 ml/m2. Multivariate Cox regression analysis demonstrated that CKD (hazard ratio [HR], 1.13; 95% CI, 1.01 to 1.26; P=0.04), hypertension (HR, 2.18; 95% CI, 1.05 to 4.54; P=0.04), and a larger LAVI (HR, 1.35; 95% CI, 1.02 to 1.77; P=0.04) were independent predictors of the primary endpoint. Conclusions Patients with CKD were at higher risk for cardiovascular events. LAVI was significantly larger in the CKD group and was a predictor of adverse cardiac events. PMID:24923578

  1. Acquired Activated Protein C Resistance, Thrombophilia and Adverse Pregnancy Outcomes: A Study Performed in an Irish Cohort of Pregnant Women

    PubMed Central

    Sedano-Balbás, Sara; Lyons, Mark; Cleary, Brendan; Murray, Margaret; Gaffney, Geraldine; Maher, Majella

    2011-01-01

    The combination of thrombophilia and pregnancy increases the risk of thrombosis and the potential for adverse outcomes during pregnancy. The most significant common inherited risk factor for thrombophilia is activated protein C resistance (APCR), a poor anticoagulant response of APC in haemostasis, which is mainly caused by an inherited single-nucleotide polymorphism (SNP), factor V G1691A (FV Leiden) (FVL), referred as inherited APCR. Changes in the levels of coagulation factors: FV, FVIII, and FIX, and anticoagulant factors: protein S (PS) and protein C (PC) can alter APC function causing acquired APCR. Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T are prothrombotic SNPs which in association with APCR can also increase the risk of thrombosis amongst Caucasians. In this study, a correlation between an acquired APCR phenotype and increased levels of factors V, VIII, and IX was demonstrated. Thrombophilic mutations amongst our acquired APCR pregnant women cohort are relatively common but do not appear to exert a severe undue adverse effect on pregnancy. PMID:21869933

  2. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis.

    PubMed

    Roberge, Stéphanie; Demers, Suzanne; Berghella, Vincenzo; Chaillet, Nils; Moore, Lynne; Bujold, Emmanuel

    2014-11-01

    A systematic review and metaanalysis were performed through electronic database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, which compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy, and uterine scar evaluation by ultrasound. Twenty of 1278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-layer closure, which had shorter operative time (-6.1 minutes; 95% confidence interval [CI], -8.7 to -3.4; P < .001) than double-layer closure. Single layer (-2.6 mm; 95% CI, -3.1 to -2.1; P < .001) and locked first layer (mean difference, -2.5 mm; 95% CI, -3.2 to -1.8; P < .001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between single- vs double-layer closure for uterine dehiscence (relative risk, 1.86; 95% CI, 0.44-7.90; P = .40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness. PMID:24912096

  3. Driving in young adults with attention deficit hyperactivity disorder: knowledge, performance, adverse outcomes, and the role of executive functioning.

    PubMed

    Barkley, Russell A; Murphy, Kevin R; Dupaul, George I; Bush, Tracie

    2002-07-01

    Past studies find that attention deficit hyperactivity disorder (ADHD) creates a higher risk for adverse driving outcomes. This study comprehensively evaluated driving in adults with ADHD by comparing 105 young adults with the disorder (age 17-28) to 64 community control (CC) adults on five domains of driving ability and a battery of executive function tasks. The ADHD group self-reported significantly more traffic citations, particularly for speeding, vehicular crashes, and license suspensions than the CC group, with most of these differences corroborated in the official DMV records. Cognitively, the ADHD group was less attentive and made more errors during a visual reaction task under rule-reversed conditions than the CC group. The ADHD group also obtained lower sceres on a test of driving rules and decision-making but not on a simple driving simulator. Both self- and other-ratings showed the CC group employed safer routine driving habits than the ADHD group. Relationships between the cognitive and driving measures and the adverse outcomes were limited or absent, calling into question their use in screening ADHD adults for driving risks. Several executive functions also were significantly yet modestly related to accident frequency and total traffic violations after controlling for severity of ADHD. These results are consistent with earlier studies showing significant driving problems are associated with ADHD. This study found that these driving difficulties were not a function of comorbid oppositional defiant disorder, depression, anxiety, or frequency of alcohol or illegal drug use. Findings to date argue for the development of interventions to reduce driving risks among adults with ADHD. PMID:12164675

  4. Sexual Hookups and Adverse Health Outcomes: A Longitudinal Study of First-Year College Women

    PubMed Central

    Fielder, Robyn L.; Walsh, Jennifer L.; Carey, Kate B.; Carey, Michael P.

    2013-01-01

    “Hookups” are sexual encounters between partners who are not in a romantic relationship and do not expect commitment. We examined the associations between sexual hookup behavior and depression, sexual victimization (SV), and sexually transmitted infections (STIs) among first-year college women. In this longitudinal study, 483 women completed 13 monthly surveys assessing oral and vaginal sex with hookup and romantic partners, depression, SV, and self-reported STIs. Participants also provided biological specimens that were tested for STIs. During the study, 50% of participants reported hookup sex, and 62% reported romantic sex. Covariates included previous levels of the outcome, alcohol use, impulsivity, sensation-seeking, and romantic sex. Autoregressive cross-lagged models showed that controlling for covariates, hookup behavior during college was correlated with depression, Bs = .21, ps < .05, and SV, Bs = .19, ps < .05. Additionally, pre-college hookup behavior predicted SV early in college, B = .62, p < .05. Hookup sex, OR 1.32, p < .05, and romantic sex, OR 1.19, p < .05, were associated with STIs. Overall, sexual hookup behavior among college women was positively correlated with experiencing depression, SV, and STIs, but the nature of these associations remains unclear, and hooking up did not predict future depression. PMID:24350600

  5. Preeclampsia-Eclampsia Adverse Outcomes Reduction: The Preeclampsia-Eclampsia Checklist

    PubMed Central

    Nwanodi, Oroma B.

    2016-01-01

    Globally, preeclampsia-eclampsia (PE-E) is a major cause of puerperal intensive care unit admission, accounting for up to 10% of maternal deaths. PE-E primary prevention is possible. Antepartum low-dose aspirin prophylaxis, costing USD $10–24 can cut the incidence of PE-E in half. Antepartum low molecular weight heparin combined with low-dose aspirin prophylaxis can cut the incidence of early onset PE-E and fetuses that are small for their gestational age in half. Despite predictive antepartum models for PE-E prophylaxis, said prophylaxis is not routinely provided. Therefore, magnesium sulfate secondary prevention of eclampsia remains the globally recommended intervention. Implementation of a PE-E checklist is a continuous quality improvement (CQI) tool facilitating appropriate antepartum PE-E prophylaxis and maternal care from the first trimester through the postpartum fourth trimester inter-partum interval. A novel clinical PE-E checklist and implementation strategy are presented below. CQI PE-E checklist implementation and appropriate PE-E prophylaxis provides clinicians and healthcare systems an opportunity to achieve Millennium Development Goals 4 and 5, reducing child mortality and improving maternal health. While CQI checklist implementation may be a tedious ongoing process requiring healthcare team resiliency, improved healthcare outcomes are well worth the effort. PMID:27417614

  6. Is ABO blood group truly a risk factor for thrombosis and adverse outcomes?

    PubMed Central

    Zhou, Shan; Welsby, Ian

    2014-01-01

    ABO blood type is one of the most readily available laboratory tests, and serves as a vital determinant in blood transfusion and organ transplantation. The ABO antigens are expressed not only on red blood cell membranes, determining the compatibility of transfusion, but also on the surface of other human cells, including epithelium, platelet and vascular endothelium, therefore extending the research into other involvements of cardiovascular disease and postoperative outcomes. ABO blood group has been recognized as a risk factor of venous thrombosis embolism since the 1960’s, effects now understood to be related to ABO dependent variations are procoagulant factor VIII (FVIII) and von Willebrand factor (vWF) levels. Levels of vWF, mostly genetically determined, are strongly associated with venous thromboembolism (VTE). It mediates platelet adhesion aggregation and stabilizes FVIII in plasma. Moreover, many studies have tried to identify the relationship between ABO blood types and ischemic heart disease. Unlike the clear and convincing associations between VTE and ABO blood type, the link between ABO blood type and ischemic heart disease is less consistent and may be confusing. Other than genetic factors, ischemic heart disease is strongly related to diet, race, lipid metabolism and economic status. In this review, we’ll summarize the data relating race and genetics, including ABO blood type, to VTE, ischemic heart disease and postoperative bleeding after cardiac surgery. PMID:25276299

  7. Regulation of Calcitriol Biosynthesis and Activity: Focus on Gestational Vitamin D Deficiency and Adverse Pregnancy Outcomes

    PubMed Central

    Olmos-Ortiz, Andrea; Avila, Euclides; Durand-Carbajal, Marta; Díaz, Lorenza

    2015-01-01

    Vitamin D has garnered a great deal of attention in recent years due to a global prevalence of vitamin D deficiency associated with an increased risk of a variety of human diseases. Specifically, hypovitaminosis D in pregnant women is highly common and has important implications for the mother and lifelong health of the child, since it has been linked to maternal and child infections, small-for-gestational age, preterm delivery, preeclampsia, gestational diabetes, as well as imprinting on the infant for life chronic diseases. Therefore, factors that regulate vitamin D metabolism are of main importance, especially during pregnancy. The hormonal form and most active metabolite of vitamin D is calcitriol. This hormone mediates its biological effects through a specific nuclear receptor, which is found in many tissues including the placenta. Calcitriol synthesis and degradation depend on the expression and activity of CYP27B1 and CYP24A1 cytochromes, respectively, for which regulation is tissue specific. Among the factors that modify these cytochromes expression and/or activity are calcitriol itself, parathyroid hormone, fibroblast growth factor 23, cytokines, calcium and phosphate. This review provides a current overview on the regulation of vitamin D metabolism, focusing on vitamin D deficiency during gestation and its impact on pregnancy outcomes. PMID:25584965

  8. ASSOCIATION BETWEEN CHILDHOOD SEXUAL ABUSE (CSA) AND ADVERSE PSYCHOLOGICAL OUTCOMES AMONG YOUTH IN TAIPEI

    PubMed Central

    Li, Nan; Ahmed, Saifuddin; Zabin, Laurie S.

    2014-01-01

    Purpose The objective of this study is to examine the relationship between a history of CSA and negative psychological consequences in adulthood controlling for family environments and Confucian values. Methods The data used in this study was collected from Taipei. 4084 participants aged 15-24 composed the final analysis sample. Three sets of logistic regression models were fitted to verify the association between CSA and negative psychological outcomes. Socio-demographic variables, household instability and parenting variables, as well as Confucian value variables were controlled in models step by step. The overall prevalence of CSA in our analysis sample was 5.2 %. Results The overall prevalence of depression, anxiety and suicidal ideation among Taipei respondents were 11.8 %, 16.4 % and 16.7 %, respectively, but young people who experienced CSA had significantly higher rates of all three than young adults who had not experienced CSA. After controlled for other covariates, the odds ratios of depression, anxiety and suicidal ideation associated with a history of CSA were 1.78 (95% CI: 1.25-2.54), 1.77 (95% CI: 1.28-2.44) and 2.56 (95% CI: 1.56-4.29), respectively. Conclusion Our findings suggested that CSA is an independent predictor of negative psychological consequences in adulthood. In our analysis, we controlled for household, parenting and Confucian culture factors which provides a better understanding of how they work together to affect adult psychological status. PMID:22340856

  9. Late Enteral Feedings Are Associated with Intestinal Inflammation and Adverse Neonatal Outcomes

    PubMed Central

    Konnikova, Yelizaveta; Zaman, Munir M.; Makda, Meher; D’Onofrio, Danila; Freedman, Steven D.; Martin, Camilia R.

    2015-01-01

    Background Morbidities of impaired immunity and dysregulated inflammation are common in preterm infants. Postnatal Intestinal development plays a critical role in the maturation of the immune system and is, in part, driven by exposure to an enteral diet. Objective The aim of this study was to evaluate the influence of the timing of the first enteral feeding on intestinal inflammation and risk of disease. Methods 130 infants <33 weeks’ gestation were studied. Maternal and infant data were abstracted from the medical record. Single and multiplex ELISA assays quantified cytokines from fecal and serum samples at two weeks postnatal age. Results A delay in enteral feedings after the third postnatal day is associated with a 4.5 (95% CI 1.8-11.5, p=0.002) fold increase in chronic lung disease, 2.9 (1.1-7.8, p=0.03) fold increase in retinopathy of prematurity, and 3.4 (1.2-9.8, p=0.02) fold increase in multiple comorbidities compared to infants fed on or before the third day. Additionally, a delay in the initiation of feedings is associated with increased fecal IL-8 levels and a decreased IL-10:IL-8 ratio. Conclusions A delay in enteral feeding is associated with intestinal inflammation and increased risks of morbidities. To improve neonatal outcomes, early nutritional practices need to be reevaluated. PMID:26172126

  10. Regulation of calcitriol biosynthesis and activity: focus on gestational vitamin D deficiency and adverse pregnancy outcomes.

    PubMed

    Olmos-Ortiz, Andrea; Avila, Euclides; Durand-Carbajal, Marta; Díaz, Lorenza

    2015-01-01

    Vitamin D has garnered a great deal of attention in recent years due to a global prevalence of vitamin D deficiency associated with an increased risk of a variety of human diseases. Specifically, hypovitaminosis D in pregnant women is highly common and has important implications for the mother and lifelong health of the child, since it has been linked to maternal and child infections, small-for-gestational age, preterm delivery, preeclampsia, gestational diabetes, as well as imprinting on the infant for life chronic diseases. Therefore, factors that regulate vitamin D metabolism are of main importance, especially during pregnancy. The hormonal form and most active metabolite of vitamin D is calcitriol. This hormone mediates its biological effects through a specific nuclear receptor, which is found in many tissues including the placenta. Calcitriol synthesis and degradation depend on the expression and activity of CYP27B1 and CYP24A1 cytochromes, respectively, for which regulation is tissue specific. Among the factors that modify these cytochromes expression and/or activity are calcitriol itself, parathyroid hormone, fibroblast growth factor 23, cytokines, calcium and phosphate. This review provides a current overview on the regulation of vitamin D metabolism, focusing on vitamin D deficiency during gestation and its impact on pregnancy outcomes. PMID:25584965

  11. Association between maternal HBsAg carrier status and neonatal adverse outcomes: meta-analysis.

    PubMed

    Luo, Lili; Wu, Jinlin; Qu, Yi; Li, Jiao; Pan, Lingli; Li, Deyuan; Wang, Huiqing; Mu, Dezhi

    2014-09-18

    Abstract Objective: We conducted a meta-analysis to evaluate whether maternal hepatitis B virus (HBV) carrier status increases the risk of neonatal complications. Methods: Publications addressing the association between maternal HBV carrier status and neonatal outcomes were selected from the PubMed, EMBASE, Web of Science, Cochrane Library and China National Knowledge Infrastructure. Publication bias and heterogeneity across studies were evaluated and summary odds ratios, weighted mean difference or standardized mean difference and 95% confidence intervals were calculated and compared between groups. Results: Eighteen studies and 7600 pregnant HBV carriers were selected for analyses. A statistically association with maternal HBV carrier status was demonstrated for premature birth and asphyxia, with no difference found among perinatal mortality, gestational age, small for gestational age, large for gestational age, birth weight, low birth weight, macrosomia, Apgar sore at 1 min, jaundice and congenital anomaly. Heterogeneity across studies was found, and no publication bias was detected. Conclusion: Our analysis suggests that maternal hepatitis B carrier status is significantly associated with premature birth and asphyxia. Large-scale prospective studies are still warranted. PMID:25231370

  12. Preeclampsia-Eclampsia Adverse Outcomes Reduction: The Preeclampsia-Eclampsia Checklist.

    PubMed

    Nwanodi, Oroma B

    2016-01-01

    Globally, preeclampsia-eclampsia (PE-E) is a major cause of puerperal intensive care unit admission, accounting for up to 10% of maternal deaths. PE-E primary prevention is possible. Antepartum low-dose aspirin prophylaxis, costing USD $10-24 can cut the incidence of PE-E in half. Antepartum low molecular weight heparin combined with low-dose aspirin prophylaxis can cut the incidence of early onset PE-E and fetuses that are small for their gestational age in half. Despite predictive antepartum models for PE-E prophylaxis, said prophylaxis is not routinely provided. Therefore, magnesium sulfate secondary prevention of eclampsia remains the globally recommended intervention. Implementation of a PE-E checklist is a continuous quality improvement (CQI) tool facilitating appropriate antepartum PE-E prophylaxis and maternal care from the first trimester through the postpartum fourth trimester inter-partum interval. A novel clinical PE-E checklist and implementation strategy are presented below. CQI PE-E checklist implementation and appropriate PE-E prophylaxis provides clinicians and healthcare systems an opportunity to achieve Millennium Development Goals 4 and 5, reducing child mortality and improving maternal health. While CQI checklist implementation may be a tedious ongoing process requiring healthcare team resiliency, improved healthcare outcomes are well worth the effort. PMID:27417614

  13. Sexual hookups and adverse health outcomes: a longitudinal study of first-year college women.

    PubMed

    Fielder, Robyn L; Walsh, Jennifer L; Carey, Kate B; Carey, Michael P

    2014-01-01

    "Hookups" are sexual encounters between partners who are not in a romantic relationship and do not expect commitment. We examined the associations between sexual hookup behavior and depression, sexual victimization (SV), and sexually transmitted infections (STIs) among first-year college women. In this longitudinal study, 483 women completed 13 monthly surveys assessing oral and vaginal sex with hookup and romantic partners, depression, SV, and self-reported STIs. Participants also provided biological specimens that were tested for STIs. During the study, 50% of participants reported hookup sex and 62% reported romantic sex. Covariates included previous levels of the outcome, alcohol use, impulsivity, sensation seeking, and romantic sex. Autoregressive cross-lagged models showed that, controlling for covariates, hookup behavior during college was correlated with depression, Bs = .21, ps < .05, and SV, Bs = .19, ps < .05. In addition, precollege hookup behavior predicted SV early in college, B = .62, p < .05. Hookup sex, OR 1.32, p < .05, and romantic sex, OR 1.19, p < .05, were associated with STIs. Overall, sexual hookup behavior among college women was positively correlated with experiencing depression, SV, and STIs, but the nature of these associations remains unclear, and hooking up did not predict future depression. PMID:24350600

  14. Gender-Specific Developmental Trajectories of Anxiety during Adolescence: Determinants and Outcomes. The TRAILS Study

    PubMed Central

    Legerstee, Jeroen S.; Verhulst, Frank C.; Robbers, Sylvana C. C.; Ormel, Johan; Oldehinkel, Albertine J.; van Oort, Floor V. A.

    2013-01-01

    Objective To identify developmental trajectories of anxiety symptoms for adolescent girls and boys. Trajectories were compared with regard to early-adolescent risk factors and psychiatric outcomes during adolescence and in young adulthood. Method A community sample of 2,230 adolescents was assessed three times across a six-year interval (10–17 years). Symptom scores of anxiety were analyzed with growth mixture models, stratified by gender. Results Three gender-specific anxiety trajectories were identified for both girls (93.3% low, 4.1% mid-adolescence limited, 2.6% mid-adolescence increasing) and boys (84.4% low, 9.5% mid-adolescence limited, 6.1% early-adolescence decreasing). Child, family and peer factors at baseline predicted group membership of the mid-adolescence limited anxiety trajectory and the early-adolescence decreasing anxiety trajectory in boys. Parental emotional problems predicted the early-adolescence anxiety increase trajectory in girls. Prevalence of anxiety disorders and depression during adolescence and in early adulthood was higher in both the mid-adolescence limited and the mid-adolescence anxiety increase trajectory. Conclusions The longitudinal course of anxiety symptoms during adolescence was characterized by three distinct gender-specific developmental trajectories. The most at-risk trajectory in girls was the mid-adolescence anxiety increase trajectory, and in boys the mid-adolescence limited trajectory. None of the environmental (i.e., child, family and peer) factors distinguished the at-risk trajectories from the other trajectories. PMID:23390430

  15. The effect of obesity on adverse outcomes and metabolism in pediatric burn patients

    PubMed Central

    Kraft, Robert; Herndon, David N.; Williams, Felicia N.; Al-Mousawi, Ahmed M; Finnerty, Celeste C.; Jeschke, Marc G

    2011-01-01

    Hypothesis Obesity influences metabolism and increases the incidence of clinical complications and worsens outcomes in pediatric burn patients. Design Retrospective, single-center study. Subjects Five hundred ninety-two severely burned pediatric patients who had burns covering more than 30% of the total body surface area and who were treated between 2001 and 2008 were enrolled in this study. Patients were divided into ≥ 85th percentile (n = 277) and normal (n = 315) weight groups based on body mass index percentiles. Results Patients stratified below (normal) and ≥ 85th percentile had similar age, gender distribution, and total burn size. No significant differences were detected in the incidence of sepsis (11% for obese vs. 10% for normal), the incidence of multiple organ failure (21% for obese and 16% for normal), or mortality (11% for obese vs. 8% for normal). Compared to the normal group, the ≥ 85th percentile group had low levels of constitutive proteins (α2macroglobulin and Apolipoprotein A-1) (p < 0.05 for both) as well as high levels of triglycerides and the acute-phase protein, C-reactive protein (p < 0.05 for both) up to 60 days after injury. Patients ≥ 85th percentile showed a significant higher loss of bone mineral density and lipolysis compared to normal individuals. Stepwise logistic regression analysis revealed that body mass index had a positive predictive value towards the maximum DENVER2 score, an index of organ failure (p < 0.001). Conclusions BMI ≥ 85th percentile altered the post-burn acute phase and catabolic response but did not increase the incidence of sepsis, multiple organ failure, or mortality in pediatric burn patients. Our results suggest that impaired metabolism and an altered inflammatory response occurs already in patients starting at the 85th percentile BMI. PMID:22143622

  16. The alternative complement pathway is longitudinally associated with adverse cardiovascular outcomes. The CODAM study.

    PubMed

    Hertle, Elisabeth; Arts, Ilja C W; van der Kallen, Carla J H; Feskens, Edith J M; Schalkwijk, Casper G; Stehouwer, Coen D A; van Greevenbroek, Marleen M J

    2016-01-01

    The alternative pathway of complement activation is highly reactive and can be activated spontaneously in the vasculature. Activation may contribute to vascular damage and development of cardiovascular disease (CVD). We aimed to investigate functional components of the alternative pathway in cardiovascular risk. We studied 573 individuals who were followed-up for seven years. At baseline, we measured the enhancer properdin; the rate-limiting protease factor D (FD); and a marker of systemic activation, Bb. Using generalised estimating equations, we investigated their longitudinal associations with cardiovascular events (CVE, N=89), CVD (N=159), low-grade inflammation (LGI), endothelial dysfunction (ED) and carotid intima-media thickness (cIMT). Furthermore, we investigated associations with incident CVE (N=39) and CVD (N=73) in 342 participants free of CVD at baseline. CVE included myocardial infarction, stroke, cardiac angioplasty and/or cardiac bypass. CVD additionally included ischaemia on an electrocardiogram and/or ankle-brachial index < 0.9. In adjusted analyses, properdin was positively associated with CVE (per 1SD, longitudinal OR=1.36 [1.07; 1.74], OR for incident CVE=1.53 [1.06; 2.20]), but not with CVD. Properdin was also positively associated with ED (β=0.13 [95%CI 0.06; 0.20]), but not with LGI or cIMT. FD and Bb were positively associated with LGI (per 1SD, FD: β=0.21 [0.12; 0.29], Bb: β=0.14 [0.07; 0.21]), and ED (FD: β=0.20 [0.11; 0.29], Bb: β=0.10 [0.03; 0.18]), but not with cIMT, CVE or CVD. Taken together, this suggests that the alternative complement pathway contributes to processes of vascular damage, and that in particular a high potential to enhance alternative pathway activation may promote unfavourable cardiovascular outcomes in humans. PMID:26446431

  17. Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial.

    PubMed

    Bansal, Nisha; Carpenter, Myra A; Weiner, Daniel E; Levey, Andrew S; Pfeffer, Marc; Kusek, John W; Cai, Jianwen; Hunsicker, Lawrence G; Park, Meyeon; Bennett, Michael; Liu, Kathleen D; Hsu, Chi-Yuan

    2016-07-01

    Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes. PMID:26538631

  18. Developmental toxicity of PAH mixtures in fish early life stages. Part I: adverse effects in rainbow trout.

    PubMed

    Le Bihanic, Florane; Morin, Bénédicte; Cousin, Xavier; Le Menach, Karyn; Budzinski, Hélène; Cachot, Jérôme

    2014-12-01

    A new gravel-contact assay using rainbow trout, Oncorhynchus mykiss, embryos was developed to assess the toxicity of polycyclic aromatic hydrocarbons (PAHs) and other hydrophobic compounds. Environmentally realistic exposure conditions were mimicked with a direct exposure of eyed rainbow trout embryos incubated onto chemical-spiked gravels until hatching at 10 °C. Several endpoints were recorded including survival, hatching delay, hatching success, biometry, developmental abnormalities, and DNA damage (comet and micronucleus assays). This bioassay was firstly tested with two model PAHs, fluoranthene and benzo[a]pyrene. Then, the method was applied to compare the toxicity of three PAH complex mixtures characterized by different PAH compositions: a pyrolytic extract from a PAH-contaminated sediment (Seine estuary, France) and two petrogenic extracts from Arabian Light and Erika oils, at two environmental concentrations, 3 and 10 μg g(-1) sum of PAHs. The degree and spectrum of toxicity were different according to the extract considered. Acute effects including embryo mortality and decreased hatching success were observed only for Erika oil extract. Arabian Light and pyrolytic extracts induced mainly sublethal effects including reduced larvae size and hemorrhages. Arabian Light and Erika extracts both induced repairable DNA damage as revealed by the comet assay versus the micronucleus assay. The conc