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Sample records for adverse neurological outcomes

  1. Early neurological stability predicts adverse outcome after acute ischemic stroke.

    PubMed

    Irvine, Hannah J; Battey, Thomas Wk; Ostwaldt, Ann-Christin; Campbell, Bruce Cv; Davis, Stephen M; Donnan, Geoffrey A; Sheth, Kevin N; Kimberly, W Taylor

    2016-10-01

    Background Deterioration in the National Institutes of Health Stroke Scale (NIHSS) in the early days after stroke is associated with progressive infarction, brain edema, and/or hemorrhage, leading to worse outcome. Aims We sought to determine whether a stable NIHSS score represents an adverse or favorable course. Methods Brain magnetic resonance images from a research cohort of acute ischemic stroke patients were analyzed. Using NIHSS scores at baseline and follow-up (day 3-5), patients were categorized into early neurological deterioration (ΔNIHSS ≥ 4), early neurological recovery (ΔNIHSS ≤ -4) or early neurological stability (ΔNIHSS between -3 and 3). The association between these categories and volume of infarct growth, volume of swelling, parenchymal hemorrhage, and 3-month modified Rankin Scale score were evaluated. Results Patients with early neurological deterioration or early neurological stability were less likely to be independent (modified Rankin Scale = 0-2) at 3 months compared to those with early neurological recovery ( P < 0.001). Patients with early neurological deterioration or early neurological stability were observed to have significantly greater infarct growth and swelling volumes than those with early neurological recovery ( P = 0.03; P < 0.001, respectively). Brain edema was more common than the other imaging markers investigated and was independently associated with a stable or worsening NIHSS score after adjustment for age, baseline stroke volume, infarct growth volume, presence of parenchymal hemorrhage, and reperfusion ( P < 0.0001). Conclusions Stable NIHSS score in the subacute period after ischemic stroke may not be benign and is associated with tissue injury, including infarct growth and brain edema. Early improvement is considerably more likely to occur in the absence of these factors.

  2. Amniotic Fluid Infection, Cytokine Levels, and Mortality and Adverse Pulmonary, Intestinal, and Neurologic Outcomes in Infants at 32 Weeks' Gestation or Less

    PubMed Central

    2017-01-01

    To what extent the risks of neonatal morbidities are directly related to premature birth or to biological mechanisms of preterm birth remains uncertain. We aimed to examine the effect of exposure to amniotic fluid (AF) infection and elevated cytokine levels on the mortality and pulmonary, intestinal, and neurologic outcomes of preterm infants, and whether these associations persist after adjustment for gestational age at birth. This retrospective cohort study included 152 premature singleton infants who were born at ≤ 32 weeks. AF obtained by amniocentesis was cultured; and interleukin-6 (IL-6) and IL-8 levels in AF were determined. The primary outcome was adverse perinatal outcome defined as the presence of one or more of the followings: stillbirth, neonatal death, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and periventricular leukomalacia. Logistic regression analysis was adjusted for gestational age at birth and other potential confounders. In bivariate analyses, elevated AF IL-6 and IL-8 levels were significantly associated with adverse perinatal outcome. These results were not changed after adjusting for potential confounders, such as low Apgar scores, mechanical ventilation, and surfactant application. However, the independent effect of elevated cytokine levels in AF disappeared when additionally adjusted for low gestational age at birth; consequently, low gestational age remained strongly associated with the risk of adverse perinatal outcome. In conclusion, elevated levels of pro-inflammatory cytokines in AF are associated with increased risk of adverse perinatal outcomes, but this risk is not independent of low gestational age at birth. Culture-proven AF infection is not associated with this risk. PMID:28145652

  3. Serious adverse neonatal outcomes such as 5-minute Apgar score of zero and seizures or severe neurologic dysfunction are increased in planned home births after cesarean delivery.

    PubMed

    Grünebaum, Amos; McCullough, Laurence B; Arabin, Birgit; Chervenak, Frank A

    2017-01-01

    The United States is with 37,451 home births in 2014 the country with the largest absolute number of home births among all developed countries. The purpose of this study was to examine the occurrence and risks of a 5-minute Apgar score of zero and neonatal seizures or serious neurologic dysfunction in women with a history of prior cesarean delivery for planned home vaginal birth after cesarean (VBAC), compared to hospital VBAC and hospital birth cesarean deliveries for term normal weight infants in the United States from 2007-2014. We report in this study outcomes of women who had one or more prior cesarean deliveries and included women who had a successful vaginal birth after a trial of labor after cesarean (TOLAC) at home and in the hospital, and a repeat cesarean delivery in the hospital. We excluded preterm births (<37 weeks) and infants weighing under 2500 g. Hospital VBACS were the reference. Women with a planned home birth VBAC had an approximately 10-fold and higher increase in adverse neonatal outcomes when compared to hospital VBACS and hospital repeat cesarean deliveries, a significantly higher incidence and risk of a 5-minute Apgar score of 0 of 1 in 890 (11.24/10,000, relative risk 9.04, 95% confidence interval 4-20.39, p<.0001) and an incidence of neonatal seizures or severe neurologic dysfunction of 1 in 814 (Incidence: 12.27/10,000, relative risk 11.19, 95% confidence interval 5.13-24.29, p<.0001). Because of the significantly increased neonatal risks, obstetric providers should therefore not offer or perform planned home TOLACs and for those desiring a VBAC should strongly recommend a planned TOLAC in the appropriate hospital setting. We emphasize that this stance should be accompanied by effective efforts to make TOLAC available in the appropriate hospital setting.

  4. Serious adverse neonatal outcomes such as 5-minute Apgar score of zero and seizures or severe neurologic dysfunction are increased in planned home births after cesarean delivery

    PubMed Central

    McCullough, Laurence B.; Arabin, Birgit; Chervenak, Frank A.

    2017-01-01

    The United States is with 37,451 home births in 2014 the country with the largest absolute number of home births among all developed countries. The purpose of this study was to examine the occurrence and risks of a 5-minute Apgar score of zero and neonatal seizures or serious neurologic dysfunction in women with a history of prior cesarean delivery for planned home vaginal birth after cesarean (VBAC), compared to hospital VBAC and hospital birth cesarean deliveries for term normal weight infants in the United States from 2007–2014. We report in this study outcomes of women who had one or more prior cesarean deliveries and included women who had a successful vaginal birth after a trial of labor after cesarean (TOLAC) at home and in the hospital, and a repeat cesarean delivery in the hospital. We excluded preterm births (<37 weeks) and infants weighing under 2500 g. Hospital VBACS were the reference. Women with a planned home birth VBAC had an approximately 10-fold and higher increase in adverse neonatal outcomes when compared to hospital VBACS and hospital repeat cesarean deliveries, a significantly higher incidence and risk of a 5-minute Apgar score of 0 of 1 in 890 (11.24/10,000, relative risk 9.04, 95% confidence interval 4–20.39, p<.0001) and an incidence of neonatal seizures or severe neurologic dysfunction of 1 in 814 (Incidence: 12.27/10,000, relative risk 11.19, 95% confidence interval 5.13–24.29, p<.0001). Because of the significantly increased neonatal risks, obstetric providers should therefore not offer or perform planned home TOLACs and for those desiring a VBAC should strongly recommend a planned TOLAC in the appropriate hospital setting. We emphasize that this stance should be accompanied by effective efforts to make TOLAC available in the appropriate hospital setting. PMID:28319128

  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. Intimate Partner Violence, PTSD, and Adverse Health Outcomes

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  7. Reverse engineering adverse outcome pathways.

    PubMed

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

    2011-01-01

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.

  8. Neurological adverse effects of methylphenidate may be misdiagnosed as meningoencephalitis.

    PubMed

    Snell, Luke Blagdon; Bakshi, Dinkar

    2015-06-16

    We present a case of adverse neurological effects of methylphenidate therapy for attention deficit and hyperactivity disorder (ADHD). A 7-year-old boy presented to the emergency department (ED) having developed ataxic gait, orofacial dyskinesias and choreoathetosis of the limbs. The results of all blood investigations, EEG and CT scan of the head were unremarkable. Subsequently, a detailed history revealed he was being treated for ADHD, being started on methylphenidate in the past 3 months. Discontinuation of methylphenidate led to significant and rapid amelioration of neurological adverse effects.

  9. Adverse Outcomes in Group Psychotherapy

    PubMed Central

    Roback, Howard B.

    2000-01-01

    Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions. PMID:10896735

  10. Quinolones: review of psychiatric and neurological adverse reactions.

    PubMed

    Tomé, Ana M; Filipe, Augusto

    2011-06-01

    Quinolones are a class of antibacterial agents for the treatment of several infectious diseases (e.g. urinary and respiratory tract infections). They are used worldwide due to their broad spectrum of activity, high bioavailability and good safety profile. The safety profile varies from quinolone to quinolone. The aim of this article was to review the neurological and psychiatric adverse drug reaction (ADR) profile of quinolones, using a literature search strategy designed to identify case reports and case series. A literature search using PubMed/MEDLINE (from inception to 31 October 2010) was performed to identify case reports and case series related to quinolone-associated neurological and psychiatric ADRs. The search was conducted in two phases: the first phase was the literature search and in the second phase relevant articles were identified through review of the references of the selected articles. Relevant articles were defined as articles referring to adverse events/reactions associated with the use of any quinolone. Abstracts referring to animal studies, clinical trials and observational studies were excluded. Identified case reports were analysed by age group, sex, active substances, dosage, concomitant medication, ambulatory or hospital-based event and seriousness, after Medical Dictionary for Regulatory Activities (MedDRA®) coding. From a total of 828 articles, 83 were identified as referring to nervous system and/or psychiatric disorders induced by quinolones. 145 individual case reports were extracted from the 83 articles. 40.7% of the individual case reports belonged to psychiatric disorders only, whereas 46.9% related to neurological disorders only. Eight (5.5%) individual case reports presented both neurological and psychiatric ADRs. Ciprofloxacin, ofloxacin and pefloxacin were the quinolones with more neurological and psychiatric ADRs reported in the literature. Ciprofloxacin has been extensively used worldwide, which may explain the higher number

  11. 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...

  12. Recombinant human erythropoietin improves neurological outcomes in very preterm infants

    PubMed Central

    Song, Juan; Sun, Huiqing; Xu, Falin; Kang, Wenqing; Gao, Liang; Guo, Jiajia; Zhang, Yanhua; Xia, Lei; Wang, Xiaoyang

    2016-01-01

    Objective To evaluate the efficacy and safety of repeated low‐dose human recombinant erythropoietin (rhEPO) in the improvement of neurological outcomes in very preterm infants. Methods A total of 800 infants of ≤32‐week gestational age who had been in an intensive care unit within 72 hours after birth were included in the trial between January 2009 and June 2013. Preterm infants were randomly assigned to receive rhEPO (500IU/kg; n = 366) or placebo (n = 377) intravenously within 72 hours after birth and then once every other day for 2 weeks. The primary outcome was death or moderate to severe neurological disability assessed at 18 months of corrected age. Results Death and moderate/severe neurological disability occurred in 91 of 338 very preterm infants (26.9%) in the placebo group and in 43 of 330 very preterm infants (13.0%) in the rhEPO treatment group (relative risk [RR] = 0.40, 95% confidence interval [CI] = 0.27–0.59, p < 0.001) at 18 months of corrected age. The rate of moderate/severe neurological disability in the rhEPO group (22 of 309, 7.1%) was significantly lower compared to the placebo group (57 of 304, 18.8%; RR = 0.32, 95% CI = 0.19–0.55, p < 0.001), and no excess adverse events were observed. Interpretation Repeated low‐dose rhEPO treatment reduced the risk of long‐term neurological disability in very preterm infants with no obvious adverse effects. Ann Neurol 2016;80:24–34 PMID:27130143

  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. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

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

  15. Neurological outcome after experimental lung injury.

    PubMed

    Bickenbach, Johannes; Biener, Ingeborg; Czaplik, Michael; Nolte, Kay; Dembinski, Rolf; Marx, Gernot; Rossaint, Rolf; Fries, Michael

    2011-12-15

    We examined the influences of acute lung injury and hypoxia on neurological outcome. Functional performance was assessed using a neurocognitive test and a neurologic deficit score (NDS) five days before. On experimental day, mechanically ventilated pigs were randomized to hypoxia only (HO group, n=5) or to acute lung injury (ALI group, n=5). Hemodynamics, respiratory mechanics, systemic cytokines and further physiologic variables were obtained at baseline, at the time of ALI, 2, 4 and 8h thereafter. Subsequently, injured lungs were recruited and animals weaned from the ventilator. Neurocognitive testing was re-examined for five days. Then, brains were harvested for neurohistopathology. After the experiment, neurocognitive performance was significantly worsened and the NDS increased in the ALI group. Histopathology revealed no significant differences. Oxygenation was comparable between groups although significantly higher inspiratory pressures occured after ALI. Cytokines showed a trend towards higher levels after ALI. Neurocognitive compromise after ALI seems due to a more pronounced inflammatory response and complex mechanical ventilation.

  16. Putative adverse outcome pathways relevant to neurotoxicity

    PubMed Central

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

    2016-01-01

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

  17. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

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

    2015-01-01

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

  18. 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...

  19. 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...

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

    EPA Pesticide Factsheets

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

  1. Recurrent adverse pregnancy outcome and antiphospholipid antibodies.

    PubMed

    Reece, E A; Gabrielli, S; Cullen, M T; Zheng, X Z; Hobbins, J C; Harris, E N

    1990-07-01

    Antiphospholipid antibodies, which include lupus-like anticoagulant and anticardiolipin antibody, have been linked to a number of adverse pregnancy outcomes, although their exact pathogenic mechanisms remain poorly defined. The relative risk of complications such as intrauterine growth retardation, spontaneous abortions, and stillbirth in patients with antiphospholipid antibodies also remains undetermined. Heightened attention has been focused on the association, leading to investigations into the pathogenesis. Uncontrolled studies have also explored therapeutic regimens such as aspirin, steroids, and heparin, and clinical trials have used various treatment protocols. Although knowledge into the association of antiphospholipid antibodies and recurrent adverse pregnancy outcome is limited and continues to evolve, this association provides new insights into the disease and offers promise for pharmacologic prophylaxis. In this article, current concepts on pathogenesis, diagnosis, and therapy are reviewed and recommendations are made for clinical care of these patients.

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

    EPA Pesticide Factsheets

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

  3. Factors influencing neurologic outcome after neonatal cardiopulmonary bypass: what we can and cannot control.

    PubMed

    Hsia, Tain-Yen; Gruber, Peter J

    2006-06-01

    Advances in cardiopulmonary bypass and surgical techniques have led to progress in the early repair of congenital heart defects in children. However, as increasing numbers survive their initial cardiac operation, an awareness is emerging that significant early and late neurologic morbidities continue to complicate otherwise successful operative repairs. Adverse neurologic outcomes after neonatal cardiac surgery are multifactorial and relate to both fixed and modifiable mechanisms. The purpose of this review is to (1) review mechanisms of brain injury after neonatal cardiopulmonary bypass, (2) examine risk factors, and (3) speculate on how investigations may improve our understanding of neurologic injury.

  4. 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,...

  5. 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...

  6. 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...

  7. Adverse outcome pathway development II: best practices.

    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

    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.

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

    EPA Pesticide Factsheets

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

  9. PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON ...

    EPA Pesticide Factsheets

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

  10. D-Dimer elevation and adverse outcomes.

    PubMed

    Halaby, Rim; Popma, Christopher J; Cohen, Ander; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Goldhaber, Samuel Z; Hull, Russell; Hernandez, Adrian; Mentz, Robert; Harrington, Robert; Lip, Gregory; Peacock, Frank; Welker, James; Martin-Loeches, Ignacio; Daaboul, Yazan; Korjian, Serge; Gibson, C Michael

    2015-01-01

    D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

  11. Neurological Disorders Complicating Pregnancy - Focus on Obstetric Outcome

    PubMed Central

    Renukesh, Sandya

    2016-01-01

    Introduction Neurological disorders in pregnancy can be pregnancy related or can be caused by exacerbation of a pre-existing neurological condition or sometimes may even be detected for the first time during pregnancy in which it might be an incidental finding. The diagnosis and management of the neurological disorders in pregnancy is always a challenging task due to varied symptomatology and risks to the fetus. The evaluation and management should be performed in a stepwise fashion and requires multidisciplinary approach. Aim The present study was conducted with the aim to study the influence of neurological disorders on outcome of pregnancy. Material and Methods This was a prospective observational study conduted over a period of 1 year (2013-2014) including 54 pregnant women with neurological manifestations. The spectrum of neurological manifestations was divided into-pregnancy specific, incidental and pre-existing neurological disorders for analysis. Five unusual cases with varied manifestations were studied in detail. Any pregnant woman presenting with neurological manifestation, irrespective of gestational age were included in the present study. The neurological manifestation and the obstetric outcome were analysed in the present study. Results There were 54 women with varied neurological manifestations, majority (74%) of them being primigravida. Seizure was the most common (63%) manifestation. The incidence of pregnancy specific disorder (eclampsia), pre-existing disease (epilepsy) and incidental causes were 40.8%, 37% and 22.2% respectively. Of the 22 women with eclampsia, 15(68%) had seizure during antepartum period and 7(32%) in the postpartum period. Three patients out of 22 who had eclampsia had intrauterine fetal demise on arrival itself, whereas the perinatal outcome was good in the other 19 patients who had live born babies. The most common incidental cause in the present study was tubercular meningitis (44%). There was however a maternal and

  12. Peripartum cocaine use and adverse pregnancy outcome.

    PubMed

    Little, Bertis B.; Snell, Laura M.; Trimmer, Kenneth J.; Ramin, Susan M.; Ghali, Fred; Blakely, Craig A.; Garret, Andrea

    1999-09-01

    The objective of the study was to analyze possible adverse effects of peripartum cocaine use on maternal and fetal outcomes. Informed consent was given by 720 (97%) of 740 women who delivered consecutively at a large urban public hospital to test an umbilical cord blood sample for the presence of non-medically administered drugs of abuse and alcohol and to be interviewed for the study. Samples were tested for the presence of a cocaine metabolite (benzoylecgonine-BZE) by radioimmunoassay. The presence of other substances of abuse (alcohol, methamphetamine, opiates) resulted in exclusion from the sample of 143 subjects. Thus, in this cohort analysis, drug-free controls (N = 469) were compared to those positive for cocaine only (N = 108). Peripartum exposure to cocaine only, and no other substances of abuse, was associated with an increased frequency of abruptio placentae (1.9% vs 0% for control, P < 0.004), thick meconium stained amniotic fluid (3.9% vs 0.7% for controls, P < 0.006), premature rupture of membranes (P < 0.02), genitourinary anomalies (OR = 3.6, P < 0.05), abdominal wall defects (OR = 4.4, P < 0.01) and increased frequency of low birth weight (OR = 2.0, P < 0.02). These are important findings because previous studies have been complicated by the confounding effects of other substances of abuse. Am. J. Hum. Biol. 11:598-602, 1999. Copyright 1999 Wiley-Liss, Inc.

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

    EPA Pesticide Factsheets

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

  14. Adapting biomarker technologies to adverse outcome ...

    EPA Pesticide Factsheets

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

  15. Analyzing risks of adverse pregnancy outcomes.

    PubMed

    Kramer, Michael S; Zhang, Xun; Platt, Robert W

    2014-02-01

    Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

  16. Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil.

    PubMed

    Martins, Reinaldo de Menezes; Pavão, Ana Luiza Braz; de Oliveira, Patrícia Mouta Nunes; dos Santos, Paulo Roberto Gomes; Carvalho, Sandra Maria D; Mohrdieck, Renate; Fernandes, Alexandre Ribeiro; Sato, Helena Keico; de Figueiredo, Patricia Mandali; von Doellinger, Vanessa Dos Reis; Leal, Maria da Luz Fernandes; Homma, Akira; Maia, Maria de Lourdes S

    2014-11-20

    Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus.

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

    EPA Science Inventory

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

  18. 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...

  19. Neurological adverse events in patients receiving anti-TNF therapy: a prospective imaging and electrophysiological study

    PubMed Central

    2014-01-01

    Introduction The aim was to investigate the frequency of neurological adverse events in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) treated with tumor necrosis factor (TNF) α antagonists. Methods Seventy-seven patients eligible for anti-TNFα therapy were evaluated. There were 36 patients with RA, 41 with SpA [24 psoriatic arthritis (PsA) and 17 with ankylosing spondylitis (AS)]. All patients had a complete physical and neurological examination. Brain and cervical spine magnetic resonance imaging (MRI) and neurophysiological tests were performed in all patients before the initiation of anti-TNFα therapy and after a mean of 18 months or when clinical symptoms and signs indicated a neurological disease. Exclusion criteria included hypertension, diabetes mellitus, dyslipidemia, heart arrhythmias, atherothrombotic events, vitamin B12 and iron deficiency, head and neck trauma and neurological surgeries. Results Two patients did not receive anti-TNFα therapy because brain MRIs at baseline revealed lesions compatible with demyelinating diseases. Thus, 75 patients received anti-TNFα (38 infliximab, 19 adalimumab and 18 etanercept). Three patients developed neurological adverse events. A 35-year-old man with PsA after 8 months of infliximab therapy presented with paresis of the left facial nerve and brain MRI showed demyelinating lesions. Infliximab was discontinued and he was treated with pulses of corticosteroids recovering completely after two months. The second patient was a 45-year-old woman with RA who after 6 months of adalimumab therapy presented with optic neuritis. The third patient was a 50-year-old woman with AS, whom after 25 months of infliximab therapy, presented with tingling and numbness of the lower extremities and neurophysiological tests revealed peripheral neuropathy. In both patients anti-TNF were discontinued and they improved without treatment after 2 months. The rest of our patients showed no symptoms and MRIs

  20. Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole.

    PubMed

    Jakobsen, Klaus Damgaard; Bruhn, Christina Hedegaard; Pagsberg, Anne-Katrine; Fink-Jensen, Anders; Nielsen, Jimmi

    2016-10-01

    Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents. The ADR report database at Danish Medicines Agency was searched for all ADRs involving children and adolescents (<18 years) reported by the search term [aripiprazole] AND all spontaneous reports since the introduction of aripiprazole in 2003 until December 31, 2015. Nineteen case reports were included in the study and included both patients with psychotic disorders (PS group) and nonpsychotic disorders (non-PS group). The PS group consisted of 5 patients with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients.

  1. Neurologic Adverse Events Associated with Voriconazole Therapy: Report of Two Pediatric Cases

    PubMed Central

    Demir, Sevliya Öcal; Atici, Serkan; Akkoç, Gülşen; Yakut, Nurhayat; İkizoğlu, Nilay Baş; Eralp, Ela Erdem; Soysal, Ahmet; Bakir, Mustafa

    2016-01-01

    Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems. The first case was a 9-year-old boy with cystic fibrosis and invasive aspergillosis that developed photophobia, altered color sensation, and fearful visual hallucination. The second case was a 17-year-old girl with cystic fibrosis and allergic bronchopulmonary aspergillosis, and she experienced photophobia, fatigue, impaired concentration, and insomnia, when the dose of voriconazole therapy was increased from 12 mg/kg/day to 16 mg/kg/day. The complaints of the two patients disappeared after discontinuation of voriconazole therapy. Our experience in these patients reminded us of the importance of being aware of the neurologic adverse events associated with voriconazole therapy in establishing early diagnosis and initiating prompt treatment. In addition, although serum voriconazole concentration was not measured in the present cases, therapeutic drug monitoring for voriconazole seems to be critically important in preventing neurologic side effects in pediatric patients. PMID:27313918

  2. 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...

  3. 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...

  4. 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....

  5. Neurologic, Functional and Cognitive Stroke Outcomes in Mexican Americans

    PubMed Central

    Lisabeth, Lynda D; Sánchez, Brisa N; Baek, Jonggyu; Skolarus, Lesli E; Smith, Melinda A; Garcia, Nelda; Brown, Devin L; Morgenstern, Lewis B

    2014-01-01

    Background and Purpose: Our objective was to compare neurologic, functional, and cognitive stroke outcomes in Mexican Americans (MAs) and non-Hispanic whites (NHWs) using data from a population-based study. Methods: Ischemic strokes (2008-2012) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) Project. Data were collected from patient or proxy interviews (conducted at baseline and 90 days post-stroke) and medical records. Ethnic differences in neurologic (National Institutes of Health Stroke Scale (NIHSS), range 0-44, higher scores worse), functional (activities of daily living (ADL)/instrumental activities of daily living (IADL) score, range 1-4, higher scores worse), and cognitive (Modified Mini-Mental State Examination (3MSE), range 0-100, lower scores worse) outcomes were assessed with Tobit or linear regression adjusted for demographics and clinical factors. Results: 513, 510, and 415 subjects had complete data for neurologic, functional and cognitive outcomes and covariates, respectively. Median age was 66 (IQR: 57-78); 64% were MA. In MAs, median NIHSS, ADL/IADL and 3MSE score were 3 (IQR: 1-6), 2.5 (IQR: 1.6-3.5) and 88 (IQR: 76-94), respectively. MAs scored 48% worse (95% CI: 23%-78%) on NIHSS, 0.36 points worse (95% CI: 0.16-0.57) on ADL/IADL score, and 3.39 points worse (95% CI: 0.35-6.43) on 3MSE than NHWs after multivariable adjustment. Conclusions: MAs scored worse than NHWs on all outcomes after adjustment for confounding factors; differences were only partially explained by ethnic differences in survival. These findings in combination with the increased stroke risk in MAs suggest that the public health burden of stroke in this growing population is substantial. PMID:24627112

  6. 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...

  7. Risk of Adverse Pregnancy Outcomes in Women with CKD.

    PubMed

    Piccoli, Giorgina Barbara; Cabiddu, Gianfranca; Attini, Rossella; Vigotti, Federica Neve; Maxia, Stefania; Lepori, Nicola; Tuveri, Milena; Massidda, Marco; Marchi, Cecilia; Mura, Silvia; Coscia, Alessandra; Biolcati, Marilisa; Gaglioti, Pietro; Nichelatti, Michele; Pibiri, Luciana; Chessa, Giuseppe; Pani, Antonello; Todros, Tullia

    2015-08-01

    CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.

  8. Adverse birth outcomes in a malarious area.

    PubMed

    Kalanda, B F; Verhoeff, F H; Chimsuku, L; Harper, G; Brabin, B J

    2006-06-01

    To determine factors associated with fetal growth, preterm delivery and stillbirth in an area of high malaria transmission in Southern Malawi, a cross-sectional study of pregnant women attending and delivering at two study hospitals was undertaken. A total of 243 (17.3%) babies were preterm and 54 (3.7%) stillborn. Intra-uterine growth retardation (IUGR) occurred in 285 (20.3%), of whom 109 (38.2%) were low birthweight and 26 (9.1%) preterm. Factors associated with IUGR were maternal short stature [adjusted odds ratio (AOR) 1.6, 95% confidence interval (CI) 1.0-2.5]; primigravidae (AOR 1.9, 95% CI 1.4-2.7); placental or peripheral malaria at delivery (AOR 1.4, 95% CI 1.0-1.9) and maternal anaemia at recruitment (Hb<8 g/dl) (AOR 1.9, 95% CI 1.3-2.7). Increasing parasite density in the placenta was associated with both IUGR (P=0.008) and prematurity (P=0.02). Factors associated with disproportionate fetal growth were maternal malnutrition [mid-upper arm circumference (MUAC)<23 cm, AOR 1.9, 95% CI 1.0-3.7] and primigravidae (AOR 1.8, 95% CI 1.0-3.1). Preterm delivery and stillbirth were associated with <5 antenatal care visits (AOR 2.2, 95% CI 1.3-3.7 and AOR 3.1, 95% CI 1.4-7.0 respectively) and stillbirth with a positive Venereal Disease Research Laboratory (VDRL) test (AOR 4.7, 95% CI 1.5-14.8). Interventions to reduce poor pregnancy outcomes must reduce the burden of malaria in pregnancy, improve antenatal care and maternal malnutrition.

  9. MORTALITY AS AN ADVERSE OUTCOME OF SARCOPENIA

    PubMed Central

    ARANGO-LOPERA, V.E.; ARROYO, P.; GUTIERREZ-ROBLEDO, L.M.; PEREZ-ZEPEDA, M.U.; CESARI, M.

    2016-01-01

    Sarcopenia has an important impact in elderly. Recently the European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as the loss of muscle mass plus low muscle strength or low physical performance. Lack of clinical sounding outcomes (ie external validity), is one of the flaws of this algorithm. The aim of our study was to determine the association of sarcopenia and mortality in a group of Mexican elderly. A total of 345 elderly were recruited in Mexico City, and followed up for three years. The EWGSOP algorithm was integrated by: gait speed, grip strength and calf circumference. Other covariates were assessed in order to test the independent association of sarcopenia with mortality. Of the 345 subjects, 53.3% were women; with a mean age of 78.5 (SD 7) years. During the three year follow-up a total of 43 (12.4%) subjects died. Age, cognition, ADL, IADL, health self-perception, ischemic heart disease and sarcopenia were associated in the bivariate analysis with survival. Negative predictive value for sarcopenia regarding mortality was of 90%. Kaplan-Meier curves along with their respective log-rank test were significant for sarcopenia. The components of the final Cox-regression multivariate model were age, ischemic heart disease, ADL and sarcopenia. Adjusted HR for age was 3.24 (CI 95% 1.55-6.78 p 0.002), IHD 5.07 (CI 95% 1.89-13.59 p 0.001), health self-perception 5.07 (CI 95% 1.9-13.6 p 0.001), ADL 0.75 (CI 95% 0.56-0.99 p 0.048) and sarcopenia 2.39 (CI 95% 1.05-5.43 p 0.037). PMID:23459979

  10. 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). ...

  11. A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution

    PubMed Central

    Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

    2016-01-01

    There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology. PMID:27547751

  12. Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature.

    PubMed

    Cuzzubbo, S; Javeri, F; Tissier, M; Roumi, A; Barlog, C; Doridam, J; Lebbe, C; Belin, C; Ursu, R; Carpentier, A F

    2017-03-01

    Immune checkpoint inhibitors (ICIs) targeting CTLA4 and PD1 constitute a promising class of cancer treatment but are associated with several immune-related disorders. We here review the literature reporting neurological adverse events (nAEs) associated with ICIs. A systematic search of literature, up to February 2016, mentioning nAEs in patients treated with ICIs was conducted. Eligible studies included case reports and prospective trials. One case seen in our ward was also added. Within the 59 clinical trials (totalling 9208 patients) analysed, the overall incidence of nAEs was 3.8% with anti-CTLA4 antibodies, 6.1% with anti-PD1 antibodies, and 12.0% with the combination of both. The clinical spectrum of neurological disorders was highly heterogeneous. Most of these nAEs were grade 1-2 and consisted of non-specific symptoms such as headache (55%). The incidence of high grade nAEs was below 1% for all types of treatment. Headaches, encephalopathies and meningitis were the most commonly reported (21%, 19% and 15%, respectively). Among the 27 case reports, the most common nAEs were encephalopathies, meningoradiculoneuritis, Guillain-Barré like syndromes and myasthenic syndromes. The median time of nAEs onset was 6 weeks. In most cases, drug interruption and steroids led to neurological recovery, even in conditions where steroids are not usually recommended such as Guillain-Barré syndrome.

  13. 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

  14. Gastroschisis: Antenatal Sonographic Predictors of Adverse Neonatal Outcome

    PubMed Central

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

    2014-01-01

    Objectives. The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis. Methods. A quasi-systematic review was conducted in PubMed and Ovid using the key terms “gastroschisis,” “predictors,” “outcome,” and “ultrasound.” Results. A total of 18 papers were included. The most common sonographic predictors were intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR), and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were consistently found to be statistically insignificant with respect to predicting adverse outcome including abdominal circumference, stomach herniation and dilatation, and extra-abdominal bowel dilatation (EABD). Conclusions. Gastroschisis is associated with several comorbidities, yet there is much discrepancy in the literature regarding which specific ultrasound markers best predict adverse neonatal outcomes. Future research should include prospective trials with larger sample sizes and use well-defined and consistent definitions of the adverse outcomes investigated with consideration given to IABD. PMID:25587450

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. 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...

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. 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.

  4. The placenta and neurologic and psychiatric outcomes in the child: study design matters.

    PubMed

    Nelson, K B; Blair, E

    2011-09-01

    Much information exists about functions of the human placenta and about potential mechanisms by which the placenta may influence human health or disease, including developmental disorders of brain. Recent studies indicate a high frequency of placental pathology in infants with developmental brain disorders, or with risk factors for such disorders. However, most clinical studies of the association of placental features with adverse neurologic or psychiatric outcome have substantial methodologic limitations. We discuss issues of study design as they relate to studies of the placenta and human brain disorders. In addition to the need for further consensus on procedures and terminology for placental evaluation, there are a number of special features that make clinical studies of the association of placental features with neurologic and psychiatric disorders especially difficult: most such disorders are not diagnosed until months or years after the majority of placentas have been discarded; these disorders are individually uncommon, so that prospective studies - needed to provide denominator data to enable estimation of risks - will require very large sample sizes; the administrative structures required to relate features of the placenta with clinical outcome will be complicated and costly. We offer some suggestions concerning study design in the face of these practical difficulties. Systematic and methodologically rigorous exploration of the role of the placenta in human developmental brain disorders has scarcely begun. A new generation of studies, difficult but potentially enormously rewarding, will be needed for clinical investigations of the placenta and fetal brain development.

  5. Pulsatile reperfusion after cardiac arrest improves neurologic outcome.

    PubMed Central

    Anstadt, M P; Stonnington, M J; Tedder, M; Crain, B J; Brothers, M F; Hilleren, D J; Rahija, R J; Menius, J A; Lowe, J E

    1991-01-01

    Cardiopulmonary bypass (CPB) using nonpulsatile flow (NPF) is advocated for refractory cardiac arrest. This study examined cerebral outcome after resuscitation with pulsatile flow (PF) versus NPF. Dogs arrested for 12.5 minute were reperfused with NPF (n = 11) using roller pump CPB or PF (n = 11) using mechanical biventricular cardiac massage. Pump flows were similar between groups; however early arterial pressures were greater during PF versus NPF, *p less than 0.05. Circulatory support was weaned at 60 minutes' reperfusion. Neurologic recovery of survivors (n = 16) was significantly better after PF versus NPF, *p = 0.01. The presence of brain lesions on magnetic resonance images did not significantly differ between groups at 7 days. Brain then were removed and regions examined for ischemic changes. Loss of CA1 pyramidal neurons was more severe after NPF versus PF, +p = 0.009. Ischemic changes were more frequent after NPF in the caudate nucleus (+p = 0.009) and watershed regions of the cerebral cortex (+p = 0.062), compared with PF. These results demonstrate that PF improves cerebral resuscitation when treating cardiac arrest with mechanical circulatory support (* = MANOVA with repeated measures, + = categorical data analysis. Images Fig. 5. Fig. 7. PMID:1953100

  6. Neurologic outcomes of toxic oil syndrome patients 18 years after the epidemic.

    PubMed

    de la Paz, Manuel Posada; Philen, Rossanne M; Gerr, Fredric; Letz, Richard; Ferrari Arroyo, Maria José; Vela, Lydia; Izquierdo, Maravillas; Arribas, Concepción Martín; Borda, Ignacio Abaitua; Ramos, Alejandro; Mora, Cristina; Matesanz, Gloria; Roldán, Maria Teresa; Pareja, Juan

    2003-08-01

    Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women.

  7. Neurologic outcomes of toxic oil syndrome patients 18 years after the epidemic.

    PubMed Central

    de la Paz, Manuel Posada; Philen, Rossanne M; Gerr, Fredric; Letz, Richard; Ferrari Arroyo, Maria José; Vela, Lydia; Izquierdo, Maravillas; Arribas, Concepción Martín; Borda, Ignacio Abaitua; Ramos, Alejandro; Mora, Cristina; Matesanz, Gloria; Roldán, Maria Teresa; Pareja, Juan

    2003-01-01

    Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women. PMID:12896854

  8. Serum cortisol concentrations during induced hypothermia for perinatal asphyxia are associated with neurological outcome in human infants.

    PubMed

    Scaramuzzo, Rosa T; Giampietri, Matteo; Fiorentini, Erika; Bartalena, Laura; Fiori, Simona; Guzzetta, Andrea; Ciampi, Mariella; Boldrini, Antonio; Ghirri, Paolo

    2015-01-01

    Birth asphyxia is a cause of neonatal death or adverse neurological sequelae. Biomarkers can be useful to clinicians in order to optimize intensive care management and communication of prognosis to parents. During perinatal adverse events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis activation. We aimed to investigate if cortisol variations during therapeutic hypothermia are associated with neurodevelopmental outcome. We compared 18 cases (neonates with birth asphyxia) with 18 controls (healthy term newborns) and confirmed increased serum cortisol concentrations following the peri-partum adverse event. Among cases, we stratified patients according to neurological outcome at 18 months (group A - good; group B - adverse) and found that after 24 h of therapeutic hypothermia serum cortisol concentration was significantly lower in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum, cortisol concentration decreased more gradually during therapeutic hypothermia. We conclude that monitoring serum cortisol concentration during neonatal therapeutic hypothermia can add information to clinical evaluation of neonates with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a biomarker associated with neurodevelopmental outcome at 18 months of age.

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

    EPA Pesticide Factsheets

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

  10. 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.

  11. Early clinical prediction of neurological outcome following out of hospital cardiac arrest managed with therapeutic hypothermia

    PubMed Central

    Ruknuddeen, Mohammed Ishaq; Ramadoss, Rajaram; Rajajee, V.; Grzeskowiak, Luke E.; Rajagopalan, Ram E.

    2015-01-01

    Background: Therapeutic hypothermia (TH) may improve neurological outcome in comatose patients following out of hospital cardiac arrest (OHCA). The reliability of clinical prediction of neurological outcome following TH remains unclear. In particular, there is very limited data on survival and predictors of neurological outcome following TH for OHCA from resource-constrained settings in general and South Asia in specific. Objective: The objective was to identify factors predicting unfavorable neurological outcome at hospital discharge in comatose survivors of OHCA treated with hypothermia. Design: Retrospective chart review. Setting: Urban 200-bed hospital in Chennai, India. Methods: Predictors of unfavorable neurological outcome (cerebral performance category score [3–5]) at hospital discharge were evaluated among patients admitted between January 2006 and December 2012 following OHCA treated with TH. Hypothermia was induced with cold intravenous saline bolus, ice packs and cold-water spray with bedside fan. Predictors of unfavorable neurological outcome were examined through multivariate exact logistic regression analysis. Results: A total of 121 patients were included with 106/121 (87%) experiencing the unfavorable neurological outcome. Independent predictors of unfavorable neurological outcome included: Status myoclonus <24 h (odds ratio [OR] 21.79, 95% confidence interval [CI] 2.89-Infinite), absent brainstem reflexes (OR 50.09, 6.55-Infinite), and motor response worse than flexion on day 3 (OR 99.41, 12.21-Infinite). All 3 variables had 100% specificity and positive predictive value. Conclusion: Status myoclonus within 24 h, absence of brainstem reflexes and motor response worse than flexion on day 3 reliably predict unfavorable neurological outcome in comatose patients with OHCA treated with TH. PMID:26195855

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

    EPA Pesticide Factsheets

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

  13. Managing adverse birth outcomes: helping parents and families cope.

    PubMed

    Van Dinter, Maureen C; Graves, Lisa

    2012-05-01

    Unexpected adverse fetal and neonatal outcomes (e.g., stillbirth, birth trauma, congenital anomalies) present a crisis for the family and the medical care team. In cases of stillbirth, the family physician should be flexible in supporting the parents' choices, validate the loss, and work as a team with the nursing staff. Psychosocial support includes offering counseling services, assessing women for postpartum depression and anxiety, and considering the effect of the loss on the entire family. Although infants with birth asphyxia or major anomalies may require transfer to facilities with a neonatal intensive care unit, the physician will usually provide ongoing care for the mother in the postpartum period. A comprehensive assessment can determine the etiology of fetal demise in most cases, which may guide future preconception and maternity care. Women with a previous adverse pregnancy outcome may have increased psychological stress in a subsequent pregnancy. Knowledge of community resources will facilitate care for the mother and her partner or family. Physicians may need to seek peer support to cope with their own feelings of loss.

  14. Innate immunity, coagulation and placenta-related adverse pregnancy outcomes.

    PubMed

    Li, Min; Huang, S Joseph

    2009-12-01

    Maternal immunity undergoes subtle adjustment in order to tolerate the semi-allogeneic embryo and maintain the host defense against potential pathogens. Concomitantly, coagulation systems change from an anti-coagulant state to a pro-coagulant state to meet the hemostatic challenge of placentation and delivery. Innate immunity and blood coagulation systems are the first line of defense to protect a host against exogenous challenges, including alloantigens and mechanical insults, and preserve the integrity of an organism. The interactions between coagulation and immune systems have been extensively studied. Immune cells play a pivotal role in the initiation of the coagulation cascade, whereas coagulation proteases display substantial immuno-modulatory effects. Upon exogenous challenges, the immune and coagulation systems are capable of potentiating each other leading to a vicious cycle. Natural killer (NK) cells, macrophages (Mphis) and dendritic cells (DCs) are three major innate immune cells that have been demonstrated to play essential roles in early pregnancy. However, immune maladaptation and hemostatic imbalance have been suggested to be responsible for adverse pregnant outcomes, such as preeclampsia (PE), miscarriage, recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR). In this review, we will summarize the mutual regulation between blood coagulation and innate immune systems as well as their roles in the maintenance of normal pregnancy and in the pathogenesis of adverse pregnancy outcomes.

  15. The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): I. Construct validity.

    PubMed

    Wilde, Elisabeth A; McCauley, Stephen R; Kelly, Tara M; Weyand, Annie M; Pedroza, Claudia; Levin, Harvey S; Clifton, Guy L; Schnelle, Kathleen P; Shah, Monika V; Moretti, Paolo

    2010-06-01

    The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure adapted from the National Institutes of Health Stroke Scale (NIHSS), and is intended to capture essential neurological deficits impacting individuals with traumatic brain injury (TBI) (see Wilde et al., 2010 ). In the present study we evaluate the measure's construct validity via comparison with a quantified neurological examination performed by a neurologist. Spearman rank-order correlation between the NOS-TBI and the neurological examination was rho = 0.76, p < 0.0001, suggesting a high degree of correspondence (construct validity) between these two measures of neurological function. Additionally, items from the NOS-TBI compared favorably to the neurological examination items, with correlations ranging from 0.60 to 0.99 (all p < 0.0001). On formal neurological examination, some degree of neurological impairment was observed in every participant in this cohort of individuals undergoing rehabilitation for TBI, and on the NOS-TBI neurological impairment was evident in all but one participant. This study documents the presence of measurable neurological sequelae in a sample of patients with TBI in a post-acute rehabilitation setting, underscoring the need for formal measurement of the frequency and severity of neurological deficits in this population. The results suggest that the NOS-TBI is a valid measure of neurological functioning in patients with TBI.

  16. Methylmercury exposure and neurological outcomes in Taiji residents accustomed to consuming whale meat.

    PubMed

    Nakamura, Masaaki; Hachiya, Noriyuki; Murata, Ken-ya; Nakanishi, Ichiro; Kondo, Tomoyoshi; Yasutake, Akira; Miyamoto, Ken-ichiro; Ser, Ping Han; Omi, Sanae; Furusawa, Hana; Watanabe, Chiho; Usuki, Fusako; Sakamoto, Mineshi

    2014-07-01

    Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to the central nervous system. In Japan, industrial emission of MeHg has resulted in MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans are exposed to MeHg derived from natural sources, primarily fish and fish predators. Therefore, MeHg continues to be an environmental risk to human health, particularly in susceptible populations that frequently consume substantial amounts of fish or fish predators such as whale. This study aimed to investigate the health effects of MeHg exposure in adults. The subjects were 194 residents (117 males, 77 females; age 20-85 years) who resided in the coastal town of Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for mercury content and performed detailed neurological examinations and dietary surveys. Audiometry, magnetic resonance imaging, and electromyography were performed to diagnose neurological defects. Whole blood mercury and selenium (Se) levels were measured in 23 subjects. The geometric mean of the hair mercury levels was 14.9 μg/g. Twelve subjects revealed hair mercury levels >50 μg/g (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale meat intake. These results suggested that residents in Taiji were highly exposed to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression analysis demonstrated no significant correlations between hair mercury levels and neurological outcomes, whereas some of the findings significantly correlated with age. A significantly positive correlation between whole blood mercury and Se levels was observed and the whole blood mercury/Se molar ratios of all subjects were <1. These findings suggested that sufficient Se intake might be one of causes of the absence of adverse effects of MeHg exposure in this study.

  17. 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...

  18. Adverse perinatal outcomes in borderline amniotic fluid index

    PubMed Central

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

    2016-01-01

    Background: Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. Objective: To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Materials and Methods: Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Results: Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. Conclusion: There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI. PMID:27981256

  19. Adverse Experiences in Early Childhood and Kindergarten Outcomes

    PubMed Central

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

    2016-01-01

    OBJECTIVE: To examine associations between adverse childhood experiences (ACEs) in early childhood and teacher-reported academic and behavioral problems in kindergarten. METHODS: We conducted a secondary analysis of data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort. Subjects with primary caregiver-reported information on ACE exposures ascertained at 5 years and teacher-reported outcomes at the end of the child’s kindergarten year were included. Outcomes included teacher ratings of academic skills, emergent literacy skills, and behavior. We included 8 ACE exposures on the basis of the original Centers for Disease Control and Prevention Kaiser study and created an ACE score by summing individual adversities. We examined the associations between teacher-reported academic and behavioral outcomes and ACE scores by using logistic regression. RESULTS: In the study sample, 1007 children were included. Fifty-five percent had experienced 1 ACE and 12% had experienced ≥ 3. Adjusting for potential confounders, experiencing ≥ 3 ACEs was associated with below-average language and literacy skills (adjusted odds ratio [AORs]: 1.8; 95% confidence interval [CI]: 1.1–2.9) and math skills (AOR: 1.8, 95% CI: 1.1–2.9), poor emergent literacy skills, attention problems (AOR: 3.5, 95% CI: 1.8–6.5), social problems (AOR: 2.7, 95% CI: 1.4–5.0), and aggression (AOR: 2.3, 95% CI: 1.2–4.6). CONCLUSIONS: In this study of urban children, experiencing ACEs in early childhood was associated with below-average, teacher-reported academic and literacy skills and behavior problems in kindergarten. These findings underscore the importance of integrated approaches that promote optimal development among vulnerable children. PMID:26768347

  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. Poverty in childhood and adverse health outcomes in adulthood.

    PubMed

    Raphael, Dennis

    2011-05-01

    The experience of poverty during childhood is a potent predictor of a variety of adverse health outcomes during middle and late adulthood. Children who live in poverty are more likely as adults than their peers to develop and die earlier from a range of diseases. These effects are especially strong for cardiovascular disease and type II diabetes. Most disturbingly, these effects appear in large part to be biologically embedded such that later improved life circumstances have only a modest ameliorative effect. Considering these findings and the relatively high rates of child poverty in nations such as Canada, UK, and USA, those concerned with improving the health of citizens should focus their attention on advocating for public policy that will reduce the incidence of child poverty.

  2. Risk Prediction for Adverse Pregnancy Outcomes in a Medicaid Population

    PubMed Central

    Hall, Eric S.; Greenberg, James M.; Kelly, Elizabeth A.

    2015-01-01

    Abstract Background: Despite prior efforts to develop pregnancy risk prediction models, there remains a lack of evidence to guide implementation in clinical practice. The current aim was to develop and validate a risk tool grounded in social determinants theory for use among at-risk Medicaid patients. Methods: This was a retrospective cohort study of 409 women across 17 Cincinnati health centers between September 2013 and April 2014. The primary outcomes included preterm birth, low birth weight, intrauterine fetal demise, and neonatal death. After random allocation into derivation and validation samples, a multivariable model was developed, and a risk scoring system was assessed and validated using area under the receiver operating characteristic curve (AUROC) values. Results: The derived multivariable model (n=263) included: prior preterm birth, interpregnancy interval, late prenatal care, comorbid conditions, history of childhood abuse, substance use, tobacco use, body mass index, race, twin gestation, and short cervical length. Using a weighted risk score, each additional point was associated with an odds ratio of 1.57 for adverse outcomes, p<0.001, AUROC=0.79. In the validation sample (n=146), each additional point conferred an odds ratio of 1.20, p=0.03, AUROC=0.63. Using a cutoff of 20% probability for the outcome, sensitivity was 29%, with specificity 82%. Positive and negative predictive values were 22% and 85%, respectively. Conclusions: Risk scoring based on social determinants can discriminate pregnancy risk within a Medicaid population; however, performance is modest and consistent with prior prediction models. Future research is needed to evaluate whether implementation of risk scoring in Medicaid prenatal care programs improves clinical outcomes. PMID:26102375

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Association between Body Temperature Patterns and Neurological Outcomes after Extracorporeal Cardiopulmonary Resuscitation.

    PubMed

    Ryu, Jeong-Am; Park, Taek Kyu; Chung, Chi Ryang; Cho, Yang Hyun; Sung, Kiick; Suh, Gee Young; Lee, Tae Rim; Sim, Min Seob; Yang, Jeong Hoon

    2017-01-01

    We evaluated the association of body temperature patterns with neurological outcomes after extracorporeal cardiopulmonary resuscitation (ECPR). Between December 2013 and December 2015, we enrolled 48 patients with cardiac arrest who survived for at least 24 hours after ECPR. Based on their body temperature patterns and the intention to control fever, we divided the patients into those in whom fever was actively controlled (N = 25), those with normothermia (N = 17), and those with unintended hypothermia (N = 6). The primary outcome was the Cerebral Performance Categories (CPC) scale at discharge. Of the 48 ECPR patients, 23 patients (47.9%) had good neurological outcomes (CPC 1 and 2) and 27 patients (56.3%) survived to discharge. The normothermia group showed a pattern of higher temperatures compared with the other groups during 48 hours after ECPR. Not only poor neurological outcomes but also intensive care unit (ICU) mortality occurred more often in the unintended hypothermia group than in the other two groups, regardless of the fever control strategy (p = 0.023 and p = 0.002, respectively). There were no differences in neurological outcomes and ICU mortality between the actively controlled fever group and the normothermia group (p = 0.845 and p = 0.616, respectively). Unintentionally sustained hypothermia may be associated with poor neurological outcomes after ECPR. These findings suggest that patients who are unable to generate a fever following ECPR may incur severe hypoxic brain injury.

  8. Association between Body Temperature Patterns and Neurological Outcomes after Extracorporeal Cardiopulmonary Resuscitation

    PubMed Central

    Ryu, Jeong-Am; Park, Taek Kyu; Chung, Chi Ryang; Cho, Yang Hyun; Sung, Kiick; Suh, Gee Young; Lee, Tae Rim; Sim, Min Seob; Yang, Jeong Hoon

    2017-01-01

    We evaluated the association of body temperature patterns with neurological outcomes after extracorporeal cardiopulmonary resuscitation (ECPR). Between December 2013 and December 2015, we enrolled 48 patients with cardiac arrest who survived for at least 24 hours after ECPR. Based on their body temperature patterns and the intention to control fever, we divided the patients into those in whom fever was actively controlled (N = 25), those with normothermia (N = 17), and those with unintended hypothermia (N = 6). The primary outcome was the Cerebral Performance Categories (CPC) scale at discharge. Of the 48 ECPR patients, 23 patients (47.9%) had good neurological outcomes (CPC 1 and 2) and 27 patients (56.3%) survived to discharge. The normothermia group showed a pattern of higher temperatures compared with the other groups during 48 hours after ECPR. Not only poor neurological outcomes but also intensive care unit (ICU) mortality occurred more often in the unintended hypothermia group than in the other two groups, regardless of the fever control strategy (p = 0.023 and p = 0.002, respectively). There were no differences in neurological outcomes and ICU mortality between the actively controlled fever group and the normothermia group (p = 0.845 and p = 0.616, respectively). Unintentionally sustained hypothermia may be associated with poor neurological outcomes after ECPR. These findings suggest that patients who are unable to generate a fever following ECPR may incur severe hypoxic brain injury. PMID:28114337

  9. Long-Term Neurological Outcomes in West Nile Virus–Infected Patients: An Observational Study

    PubMed Central

    Weatherhead, Jill E.; Miller, Vicki E.; Garcia, Melissa N.; Hasbun, Rodrigo; Salazar, Lucrecia; Dimachkie, Mazen M.; Murray, Kristy O.

    2015-01-01

    The Houston West Nile Cohort (HWNC) was founded in 2002 when West Nile virus (WNV) reached Houston, TX. The long-term outcomes following WNV infection are still mostly unknown, though neurological abnormalities up to 1 year postinfection have been documented. We report an observational study of neurological abnormalities at 1–3 and 8–11 years following WNV infection in the HWNC. We conducted standard neurological examinations at two separate time points to assess changes in neurological status over time. The majority of patients (86%, 30/35) with encephalitis had abnormal neurological exam findings at the time of the first assessment compared with uncomplicated fever (27%, 3/11) and meningitis (36%, 5/14) cases. At the time of the second assessment, 57% (4/7) of West Nile fever (WNF), 33% (2/6) of West Nile meningitis (WNM), and 36% (5/14) of West Nile encephalitis (WNE) had developed new neurological complications. The most common abnormalities noted were tandem gait, hearing loss, abnormal reflexes, and muscle weakness. Long-term neurological abnormalities were most commonly found in patients who experienced primary WNV encephalitis. New abnormalities may develop over time regardless of initial clinical infection. Future studies should aim to differentiate neurological consequences due to WNV neuroinvasive infection versus neurological decline related to comorbid conditions. PMID:25802426

  10. Impact of Early Vasopressor Administration on Neurological Outcomes after Prolonged Out-of-Hospital Cardiac Arrest.

    PubMed

    Hubble, Michael W; Tyson, Clark

    2017-02-22

    Introduction Vasopressors are associated with return of spontaneous circulation (ROSC), but no long-term benefit has been demonstrated in randomized trials. However, these trials did not control for the timing of vasopressor administration which may influence outcomes. Consequently, the objective of this study was to develop a model describing the likelihood of favorable neurological outcome (cerebral performance category [CPC] 1 or 2) as a function of the public safety answering point call receipt (PSAP)-to-pressor-interval (PPI) in prolonged out-of-hospital cardiac arrest. Hypothesis The likelihood of favorable neurological outcome declines with increasing PPI.

  11. Adverse outcome pathway development from protein alkylation to liver fibrosis.

    PubMed

    Horvat, Tomislav; Landesmann, Brigitte; Lostia, Alfonso; Vinken, Mathieu; Munn, Sharon; Whelan, Maurice

    2017-04-01

    In modern toxicology, substantial efforts are undertaken to develop alternative solutions for in vivo toxicity testing. The adverse outcome pathway (AOP) concept could facilitate knowledge-based safety assessment of chemicals that does not rely exclusively on in vivo toxicity testing. The construction of an AOP is based on understanding toxicological processes at different levels of biological organisation. Here, we present the developed AOP for liver fibrosis and demonstrate a linkage between hepatic injury caused by chemical protein alkylation and the formation of liver fibrosis, supported by coherent and consistent scientific data. This long-term process, in which inflammation, tissue destruction, and repair occur simultaneously, results from the complex interplay between various hepatic cell types, receptors, and signalling pathways. Due to the complexity of the process, an adequate liver fibrosis cell model for in vitro evaluation of a chemical's fibrogenic potential is not yet available. Liver fibrosis poses an important human health issue that is also relevant for regulatory purposes. An AOP described with enough mechanistic detail might support chemical risk assessment by indicating early markers for downstream events and thus facilitating the development of an in vitro testing strategy. With this work, we demonstrate how the AOP framework can support the assembly and coherent display of distributed mechanistic information from the literature to support the use of alternative approaches for prediction of toxicity. This AOP was developed according to the guidance document on developing and assessing AOPs and its supplement, the users' handbook, issued by the Organisation for Economic Co-operation and Development.

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

    EPA Pesticide Factsheets

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

  13. Application of adverse outcome pathway-based tools to ...

    EPA Pesticide Factsheets

    Increasing numbers and diversity of chemical contaminants are being detected in ambient surface waters. States, regions, and communities across the US are faced with the issue of understanding which chemicals may warrant concern and at what concentrations. Integrating new scientific data streams and predictive approaches into the process of numeric water aquatic life criteria development offers the potential to develop more criteria, for more chemicals, more rapidly. For example, well established models of non-polar narcosis provide an effective estimate of “baseline” toxicity. Emerging data streams from high throughput, pathway-based, toxicity testing programs provide broad spectrum screening for more specific modes of action that may result in deviations from “baseline” toxicity predictions (i.e., excess toxicity). The adverse outcome pathway (AOP) framework provides a scientifically credible basis for linking specific pathway-perturbations to predicted hazard and facilitates systematic consideration of taxa and life stages likely to be sensitive. Application of this information can facilitate more targeted and hypothesis-driven approaches to the collection of data for use in numeric criteria development. It can also support interim application of appropriate AOP-based prediction models in cases where empirical data are lacking. While these approaches will be subject to error and uncertainty, they offer the ability to provide a scientifically-based pre

  14. Sexually transmitted infections, adverse pregnancy outcome and neonatal infection.

    PubMed

    Moodley, P; Sturm, A W

    2000-08-01

    Prevention and treatment of sexually transmitted infections (STIs) in the sexually active population are the main steps to prevent perinatal infection. However, the spread of STIs continues at an astronomical pace despite various attempts at controlling the epidemic. An important reason for this lack of STI control is that a large percentage of infected people go untreated because they have asymptomatic or unrecognized infections. The microbial differential diagnosis of STIs implicated in adverse pregnancy outcome is broad and includes viral, bacterial and protozoal infections. Infertility, ectopic pregnancy, pelvic inflammatory disease, chorioamnionitis, premature rupture of membranes, preterm birth and puerperal sepsis are some of complications seen in women as a result of infection with sexually transmitted pathogens. In addition, STIs may facilitate the acquisition and transmission of HIV. In the fetus or neonate, complications include abnormalities of the major organ systems. Infections in the form of pneumonia or conjunctivitis may also occur. Due to the lack of simple, inexpensive and sensitive point-of-care tests, screening for STIs in pregnancy is not performed routinely.

  15. 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...

  16. Adverse perinatal outcome and later kidney biopsy in the mother.

    PubMed

    Vikse, Bjørn Egil; Irgens, Lorentz M; Bostad, Leif; Iversen, Bjarne M

    2006-03-01

    Strong associations of adverse perinatal outcomes have been identified with later cardiovascular disease in the mother. Few studies have addressed associations with kidney disease. This study investigated whether perinatal outcomes are associated with later clinical kidney disease as diagnosed by kidney biopsy. The Medical Birth Registry of Norway contains data on all childbirths in Norway since 1967. The Norwegian Kidney Biopsy Registry contains data on all kidney biopsies in Norway since 1988. All women with a first singleton delivery from 1967 to 1998 were included. Pregnancy-related predictors of later kidney biopsy were analyzed by Cox regression analyses. A total of 756,420 women were included, and after a mean period of 15.9+/-9.4 yr, 588 had a kidney biopsy. Compared with women without preeclampsia and with offspring with birth weight of >or=2.5 kg, women with no preeclampsia and with offspring with birth weight of 1.5 to 2.5 kg had a relative risk (RR) for a later kidney biopsy of 1.7, women with no preeclampsia and with offspring with birth weight of <1.5 kg had an RR of 2.9, women with preeclampsia and with offspring with a birth weight of >or=2.5 kg had an RR of 2.5, women with preeclampsia and with offspring with a birth weight of 1.5 to 2.5 kg had an RR of 4.5, and women with preeclampsia and with offspring with a birth weight of <1.5 kg had an RR of 17. Similar results were found in adjusted analyses and after exclusion of women with diabetes, kidney disease, or rheumatic disease before pregnancy. The same risk patterns applied to any of the specific categories of kidney disease as well as specific kidney diseases investigated. Women who have preeclampsia and give birth to offspring with low birth weight and short gestation have a substantially increased risk for having a later kidney biopsy.

  17. 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

  18. 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...

  19. Neurological outcome in a series of 58 patients operated for traumatic thoracolumbar spinal cord injuries

    PubMed Central

    Dobran, Mauro; Iacoangeli, Maurizio; Di Somma, Lucia Giovanna Maria; Di Rienzo, A.; Colasanti, Roberto; Nocchi, Niccolò; Alvaro, Lorenzo; Moriconi, Elisa; Nasi, Davide; Scerrati, Massimo

    2014-01-01

    Background: Traumatic thoracolumbar spinal fractures represent approximately 65% of all traumatic spinal fractures and are frequently associated to permanent disability with significant social and economic impact. These injuries create severe physical limitations depending on neurological status, level of fracture, severity of injury, patient age and comorbidities. Predicting neurological improvement in patients with traumatic spinal cord injuries (SCIs) is very difficult because it is related to different preoperative prognostic factors. We evaluated the neurological improvement related to the preoperative neurological conditions and the anatomic level of spinal cord injury. Methods: From January 2004 to June 2010, we operated 207 patients for unstable thoracolumbar spinal fractures. We carried out a retrospective analysis of 69 patients with traumatic SCIs operated on by a posterior fixation performed within 24 hours from the trauma. The preoperative neurological conditions (ASIA grade), the type of the fracture, the anatomic level of spinal cord injury and the postoperative neurological improvement were evaluated for each patient. Results: The ASIA grade at admission (P = 0,0005), the fracture type according to the AO spine classification (P = 0,0002), and the anatomic location of the injury (P = 0,0213) represented predictive factors of neurological improvement at univariate analysis. The preoperative neurological status (P = 0,0491) and the fracture type (P = 0,049) confirmed a positive predictive value also in the multivariate analysis. Conclusions: Our study confirms that the preoperative neurological status, the fracture type and the anatomic location of the fracture are predictive factors of the neurological outcome in patients with spinal cord injury. PMID:25289154

  20. Influence of early neurological complications on clinical outcome following lung transplant

    PubMed Central

    Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

    2017-01-01

    Background Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. Methods We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Results Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients’ survival. Conclusions The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors. PMID:28301586

  1. 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:…

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

    EPA Science Inventory

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

  3. 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...

  4. 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 ...

  5. 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...

  6. 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...

  7. Maternal Obesity in Early Pregnancy and Risk of Adverse Outcomes

    PubMed Central

    Bautista-Castaño, Inmaculada; Henriquez-Sanchez, Patricia; Alemán-Perez, Nestor; Garcia-Salvador, Jose J.; Gonzalez-Quesada, Alicia; García-Hernández, Jose A.; Serra-Majem, Luis

    2013-01-01

    Objectives To assess the role of the health consequences of maternal overweight and obesity at the start of pregnancy on gestational pathologies, delivery and newborn characteristics. Methods A cohort of pregnant women (n = 6.558) having delivered at the Maternal & Child University Hospital of Gran Canaria (HUMIGC) in 2008 has been studied. Outcomes were compared using multivariate analyses controlling for confounding variables. Results Compared to normoweight, overweight and obese women have greater risks of gestational diabetes mellitus (RR = 2.13 (95% CI: 1.52–2.98) and (RR = 2.85 (95% CI: 2.01–4.04), gestational hypertension (RR = 2.01 (95% CI: 1.27–3.19) and (RR = 4.79 (95% CI: 3.13–7.32) and preeclampsia (RR = 3.16 (95% CI: 1.12–8.91) and (RR = 8.80 (95% CI: 3.46–22.40). Obese women have also more frequently oligodramnios (RR = 2.02 (95% CI: 1.25–3.27), polyhydramnios. (RR = 1.76 (95% CI: 1.03–2.99), tearing (RR = 1.24 (95% CI: 1.05–1.46) and a lower risk of induced deliveries (RR = 0.83 (95% CI: 0.72–0.95). Both groups have more frequently caesarean section (RR = 1.36 (95% CI: 1.14–1.63) and (RR = 1.84 (95% CI: 1.53–2.22) and manual placenta extraction (RR = 1.65 (95% CI: 1.28–2.11) and (RR = 1.77 (95% CI: 1.35–2.33). Newborns from overweight and obese women have higher weight (p<0.001) and a greater risk of being macrosomic (RR = 2.00 (95% CI: 1.56–2.56) and (RR = 2.74 (95% CI: 2.12–3.54). Finally, neonates from obese mother have a higher risk of being admitted to special care units (RR = 1.34 (95% CI: 1.01–1.77). Apgar 1 min was significantly higher in newborns from normoweight mothers: 8.65 (95% CI: 8.62–8.69) than from overweight: 8.56 (95% CI: 8.50–8.61) or obese mothers: 8.48 (95% CI: 8.41–8.54). Conclusion Obesity and overweight status at the beginning of pregnancy increase the adverse outcomes of the pregnancy. It is important to promote

  8. Mitochondrial DNA haplogroups and short-term neurological outcomes of ischemic stroke

    PubMed Central

    Cai, Biyang; Zhang, Zhizhong; Liu, Keting; Fan, Wenping; Zhang, Yumeng; Xie, Xia; Dai, Minhui; Cao, Liping; Bai, Wen; Du, Juan; Dai, Qiliang; Zhou, Shuyu; Zhang, Hao; Zhu, Wusheng; Ma, Minmin; Liu, Wenhua; Liu, Xinfeng; Xu, Gelin

    2015-01-01

    Stroke is one of the leading causes of death and long-term disability worldwide. Mitochondrial DNA (mtDNA) is a potential contributor for the sex differences of ischemic stroke heritability. Although mtDNA haplogroups were associated with stroke onset, their impacts on stroke outcomes remain unclear. This study aimed to evaluate the impacts of mtDNA haplogroups on short-term outcomes of neurological functions in patients with ischemic stroke. A total of 303 patients were included, and their clinical data and mtDNA sequences were analyzed. Based on the changes between baseline and 14-day follow-up stroke severity, our results showed that haplogroup N9 was an independent protective factor against neurological worsening in acute ischemic stroke patients. These findings supported that mtDNA variants play a role in post-stroke neurological recovery, thus providing evidences for future pharmacological intervention in mitochondrial function. PMID:25993529

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

    PubMed Central

    2013-01-01

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

  10. 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...

  11. Adolescent Friendships Mediating Childhood Adversity and Adult Outcome.

    ERIC Educational Resources Information Center

    Pawlby, Susan J.; Mills, Alice; Taylor, Alan; Quinton, David

    1997-01-01

    Compares the friendships of girls (N=50) at risk for difficulties in early adult partnerships with those of 50 girls of the same age. Results indicate key differences in both romantic and non-romantic adolescent friendships between the two groups. Findings offer a clearer understanding of processes linking childhood adversity and poor adult…

  12. The Association Between Arterial Oxygen Tension and Neurological Outcome After Cardiac Arrest.

    PubMed

    Johnson, Nicholas J; Dodampahala, Kalani; Rosselot, Babette; Perman, Sarah M; Mikkelsen, Mark E; Goyal, Munish; Gaieski, David F; Grossestreuer, Anne V

    2017-03-01

    A number of observational studies have evaluated the association between arterial oxygen tensions and outcome after cardiac arrest with variable results. The objective of this study is to determine the association between arterial oxygen tension and neurological outcome after cardiac arrest. A retrospective cohort analysis was performed using the Penn Alliance for Therapeutic Hypothermia registry. Adult patients who experienced return of spontaneous circulation after in-hospital or out-of-hospital cardiac arrest (OHCA) and had a partial pressure of arterial oxygen (PaO2) recorded within 48 hours were included. Our primary exposure of interest was PaO2. Hyperoxemia was defined as PaO2 > 300 mmHg, hypoxemia as PaO2 < 60 mmHg, and optimal oxygenation as PaO2 60-300 mmHg. The primary outcome was neurological function at hospital discharge among survivors, as described by the cerebral performance category (CPC) score, dichotomized into "favorable" (CPCs 1-2) and "unfavorable" (CPCs 3-5). Secondary outcomes included in-hospital mortality. A total of 544 patients from 13 institutions were included. Average age was 61 years, 56% were male, and 51% were white. A total of 64% experienced OHCA, 81% of arrests were witnessed, and pulseless electrical activity was the most common initial rhythm (40%). More than 72% of the patients had cardiac etiology for their arrests, and 55% underwent targeted temperature management. A total of 38% of patients survived to hospital discharge. There was no significant association between PaO2 at any time interval and neurological outcome at hospital discharge. Hyperoxemia at 12 hours after cardiac arrest was associated with decreased odds of survival (OR 0.17 [0.03-0.89], p = 0.032). There was no significant association between arterial oxygen tension measured within the first 48 hours after cardiac arrest and neurological outcome.

  13. 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

  14. Responsiveness to therapy for increased intracranial pressure in traumatic brain injury is associated with neurological outcome.

    PubMed

    Colton, K; Yang, S; Hu, P F; Chen, H H; Stansbury, L G; Scalea, T M; Stein, D M

    2014-12-01

    In patients with severe traumatic brain injury, increased intracranial pressure (ICP) is associated with poor functional outcome or death. Hypertonic saline (HTS) is a hyperosmolar therapy commonly used to treat increased ICP; this study aimed to measure initial patient response to HTS and look for association with patient outcome. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a large urban tertiary care facility were retrospectively enrolled. The first dose of hypertonic saline administered after admission for ICP >19mmHg was recorded and correlated with vital signs recorded at the bedside. The absolute and relative change in ICP at 1 and 2h after HTS administration was calculated. Patients were stratified by mortality and long-term (≥6 months) functional neurological outcome. We identified 46 patients who received at least 1 dose of HTS for ICP>19, of whom 80% were male, mean age 34.4, with a median post-resuscitation GCS score of 6. All patients showed a significant decrease in ICP 1h after HTS administration. Two hours post-administration, survivors showed a further decrease in ICP (43% reduction from baseline), while ICP began to rebound in non-survivors (17% reduction from baseline). When patients were stratified for long-term neurological outcome, results were similar, with a significant difference in groups by 2h after HTS administration. In patients treated with HTS for intracranial hypertension, those who survived or had good neurological outcome, when compared to those who died or had poor outcomes, showed a significantly larger sustained decrease in ICP 2h after administration. This suggests that even early in a patient's treatment, treatment responsiveness is associated with mortality or poor functional outcome. While this work is preliminary, it suggests that early failure to obtain a sustainable response to hyperosmolar therapy may warrant greater treatment intensity or therapy escalation.

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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)...

  1. 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...

  2. Rosuvastatin improves myocardial and neurological outcomes after asphyxial cardiac arrest and cardiopulmonary resuscitation in rats.

    PubMed

    Qiu, Yun; Wu, Yichen; Meng, Min; Luo, Man; Zhao, Hongmei; Sun, Hong; Gao, Sumin

    2017-03-01

    Rosuvastatin, a potent HMG-CoA reductase inhibitor, is cholesterol-lowering drugs and reduce the risk of myocardial infarction and stroke. This study is to explore whether rosuvastatin improves outcomes after cardiac arrest in rats. Male Sprague-Dawley rats were subjected to 8min of cardiac arrest (CA) by asphyxia and randomly assigned to three experimental groups immediately following successful resuscitation: Sham; Control; and Rosuvastatin. The survival, hemodynamics, myocardial function, neurological outcomes and apoptosis were assessed. The 7-d survival rate was greater in the rosuvastatin treated group compared to the Control group (P=0.019 by log-rank test). Myocardial function, as measured by cardiac output and ejection fraction, was significantly impaired after CA and notably improved in the animals treated with rosuvastatin beginning at 60min after return of spontaneous circulation (ROSC) (P<0.05). Moreover, rosuvastatin treatment significantly ameliorated brain injury after ROSC, which was characterized by the increase of neurological function scores, and reduction of brain edema in cortex and hippocampus (P<0.05). Meanwhile, the levels of cardiac troponin T and neuron-specific enolase and the caspase-3 activity were significantly decreased in the Rosuvastatin group when compared with the Control group (P<0.05). In conclusion, rosuvastatin treatment substantially improves the 7-d survival rate as well as myocardial function and neurological outcomes after ROSC.

  3. 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

  4. Betel quid chewing and risk of adverse pregnancy outcomes among aborigines in southern Taiwan.

    PubMed

    Yang, M S; Chang, F T; Chen, S S; Lee, C H; Ko, Y C

    1999-07-01

    It is known that substance use is associated with increased risk of adverse pregnancy, outcomes. The aims of this study were to estimate the prevalence of alcohol, cigarette, betel quid and drug use during pregnancy and to assess the risk of adverse effects of betel quid chewing on pregnancy outcomes in aboriginal women in southern Taiwan. The study population included 62 women with adverse pregnancy outcomes and 124 age-matched women. Subjects were interviewed at their homes by trained interviewers using a structure questionnaire. Prevalences of various substance use in aborigines with adverse pregnancy outcomes were estimated as follows: alcohol, 43.6%; smoking, 14.5%; betel quid chewing, 43.6% and over-the-counter drug use, 8.1%; whereas in the comparison group it was alcohol, 38.7%; smoking, 8.1%; betel quid chewing, 28.2% and none used drugs. Univariate analysis revealed that adverse pregnancy outcomes were associated with maternal betel quid chewing, maternal illness during pregnancy, and the number of pregnancies (gravidity) experienced. After adjusting for maternal illness and number of previous pregnancies covariates, the prevalence of adverse pregnancy outcome was computed to be 2.8-fold higher among betel quid chewing women as compared to non-chewers (AOR=2.8, 95% CI=1.2-6.8). Among the aboriginal women, prenatal care is essential not only for routine care, but also to focus health education on the harmful effects of substance use, especially betel quid use during pregnancy.

  5. Prognostic factors of neurological outcomes in late-preterm and term infants with perinatal asphyxia

    PubMed Central

    Seo, Sun Young; Shim, Gyu Hong; Chey, Myoung Jae

    2016-01-01

    Purpose This study aimed to identify prognostic factors of neurological outcomes, including developmental delay, cerebral palsy and epilepsy in late-preterm and term infants with perinatal asphyxia. Methods All late-preterm and term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the neonatal intensive care unit of Inje University Sanggye Paik Hospital between 2006 and 2014 and were followed up for at least 2 years were included in this retrospective study. Abnormal neurological outcomes were defined as cerebral palsy, developmental delay and epilepsy. Results Of the 114 infants with perinatal asphyxia, 31 were lost to follow-up. Of the remaining 83 infants, 10 died, 56 had normal outcomes, and 17 had abnormal outcomes: 14 epilepsy (82.4%), 13 cerebral palsy (76.5%), 16 developmental delay (94.1%). Abnormal outcomes were significantly more frequent in infants with later onset seizure, clinical seizure, poor electroencephalography (EEG) background activity, lower Apgar score at 1 and 5 minutes and abnormal brain imaging (P<0.05). Infants with and without epilepsy showed significant differences in EEG background activity, clinical and electrographic seizures on EEG, Apgar score at 5 minutes and brain imaging findings. Conclusion We should apply with long-term video EEG or amplitude integrated EEG in order to detect and management subtle clinical or electrographic seizures in neonates with perinatal asphyxia. Also, long-term, prospective studies with large number of patients are needed to evaluate more exact prognostic factors in neonates with perinatal asphyxia. PMID:27895691

  6. [Relationship between lipid alterations during pregnancy and adverse pregnancy outcomes].

    PubMed

    Ferriols, Elena; Rueda, Carolina; Gamero, Rocío; Vidal, Mar; Payá, Antonio; Carreras, Ramón; Flores-le Roux, Juana A; Pedro-Botet, Juan

    Lipids play an important role during pregnancy, and in this period major changes occur in lipoprotein metabolism. During the third trimester plasma cholesterol and triglyceride levels are substantially increased, returning to normal after delivery. Described associations between increased morbidity during pregnancy and excessive increases in plasma cholesterol and triglycerides. For this reason we have reviewed the relationship between lipid alterations, preeclampsia, gestational diabetes and preterm birth. The overall metabolic control can improve pregnancy outcomes, and the assessment of supraphysiological changes in lipid profile will classify pregnancy risk at a higher level, which would entail a stricter control.

  7. 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

  8. 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...

  9. 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…

  10. 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...

  11. Remote Postconditioning Alone and Combined with Hypothermia Improved Postresuscitation Cardiac and Neurological Outcomes in Swine.

    PubMed

    Xu, Jiefeng; Huang, Zeng; Ye, Sen; Wang, Moli; Fang, Ya; Li, Zilong

    2016-01-01

    Objective. Previously, we demonstrated that remote ischemic postconditioning (RIpostC) improved postresuscitation myocardial and cerebral functions in rat. Here, we investigated the effects of RIpostC alone and combined with therapeutic hypothermia (TH) on cardiac and neurological outcomes after CPR in swine. Methods. Twenty-one pigs were subjected to 10 mins of VF and then 5 mins of CPR. The animals were randomized to receive RIpostC alone, or its combination with TH, or sham control. RIpostC was induced by 4 cycles of limb ischemia followed by reperfusion. TH was implemented by surface cooling to reach a temperature of 32-34°C. Results. During 72 hrs after resuscitation, lower level of cardiac troponin I and greater stroke volume and global ejection fraction were observed in animals that received RIpostC when compared to the control. RIpostC also decreased serum levels of neuron-specific enolase and S100B and increased neurologic alertness score after resuscitation. The combination of RIpostC and TH resulted in greater improvement in cardiac and neurological outcomes than RIpostC alone. Conclusion. RIpostC was conducive to improving postresuscitation myocardial and cerebral functions and reducing their organ injuries. Its combination with TH further enhanced its protective effects.

  12. Remote Postconditioning Alone and Combined with Hypothermia Improved Postresuscitation Cardiac and Neurological Outcomes in Swine

    PubMed Central

    Xu, Jiefeng; Huang, Zeng; Ye, Sen; Wang, Moli; Fang, Ya

    2016-01-01

    Objective. Previously, we demonstrated that remote ischemic postconditioning (RIpostC) improved postresuscitation myocardial and cerebral functions in rat. Here, we investigated the effects of RIpostC alone and combined with therapeutic hypothermia (TH) on cardiac and neurological outcomes after CPR in swine. Methods. Twenty-one pigs were subjected to 10 mins of VF and then 5 mins of CPR. The animals were randomized to receive RIpostC alone, or its combination with TH, or sham control. RIpostC was induced by 4 cycles of limb ischemia followed by reperfusion. TH was implemented by surface cooling to reach a temperature of 32–34°C. Results. During 72 hrs after resuscitation, lower level of cardiac troponin I and greater stroke volume and global ejection fraction were observed in animals that received RIpostC when compared to the control. RIpostC also decreased serum levels of neuron-specific enolase and S100B and increased neurologic alertness score after resuscitation. The combination of RIpostC and TH resulted in greater improvement in cardiac and neurological outcomes than RIpostC alone. Conclusion. RIpostC was conducive to improving postresuscitation myocardial and cerebral functions and reducing their organ injuries. Its combination with TH further enhanced its protective effects. PMID:28097144

  13. Occupational and environmental exposure correlates of adverse live-birth outcomes among 1032 US Navy women.

    PubMed

    Hourani, L; Hilton, S

    2000-12-01

    The integration of women into non-traditional military occupations raises questions concerning the impact of such jobs on women's reproductive health. This study examines the extent to which US Navy women in their reproductive years report exposures to potential occupational and environmental hazards, and the degree to which such exposures are associated with self-reported adverse live-birth outcomes. Data from a survey of pregnant Navy women provided both maternal and paternal exposure information on more than 1000 active-duty women. Self-reported exposures to heavy metals, pesticides, petroleum products, and other chemicals were associated with adverse live-birth outcomes at the bivariate level. Only a father's exposure to pesticides at work predicted an adverse live-birth outcome (preterm delivery) in multivariate models. Maternal occupational exposures may exert their influence through maternal health and/or pregnancy complications and may act as mediators of health-reproductive outcome relationships.

  14. Urodynamic profile in acute transverse myelitis patients: Its correlation with neurological outcome

    PubMed Central

    Gupta, Anupam; Kumar, Sushruth Nagesh; Taly, Arun B.

    2017-01-01

    Objective: The objective of this study was to observe urodynamic profile of acute transverse myelitis (ATM) patients and its correlation with neurological outcome. Patients and Methods: This prospective study was conducted in the neurorehabilitation unit of a tertiary university research hospital from July 2012 to June 2014. Forty-three patients (19 men) with ATM with bladder dysfunction, admitted in the rehabilitation unit, were included in this study. Urodynamic study (UDS) was performed in all the patients. Their neurological status was assessed using ASIA impairment scale and functional status was assessed using spinal cord independence measure. Bladder management was based on UDS findings. Results: In total, 17 patients had tetraplegia and 26 had paraplegia. Thirty-six patients (83.7%) had complaints of increased frequency and urgency of urine with 26 patients reported at least one episode of urge incontinence. Seven patients reported obstructive urinary complaints in the form of straining to void with 13 patients reported both urgency and straining to void and 3 also had stress incontinence. Thirty-seven (86.1%) patients had neurogenic overactive detrusor with or without sphincter dyssynergia and five patients had acontractile detrusor on UDS. No definitive pattern was observed between neurological status and bladder characteristics. All patients showed significant neurological and functional recovery with inpatient rehabilitation (P < 0.05 and P < 0.001, respectively). Conclusions: The problem of neurogenic bladder dysfunction is integral to ATM. Bladder management in these patients should be based on UDS findings. Bladder characteristics have no definitive pattern consistent with the neurological status. PMID:28149080

  15. Magnetoencephalographic Imaging of Resting-State Functional Connectivity Predicts Postsurgical Neurological Outcome in Brain Gliomas

    PubMed Central

    Tarapore, Phiroz E.; Martino, Juan; Guggisberg, Adrian G.; Owen, Julia; Honma, Susanne M.; Findlay, Anne; Berger, Mitchel S.; Kirsch, Heidi E.; Nagarajan, Srikantan S.

    2013-01-01

    Background The removal of brain tumors in peri-eloquent or eloquent cortex risks causing new neurological deficits in patients. The assessment of the functionality of peri-lesional tissue is essential to avoidance of postoperative neurological morbidity. Objective To evaluate preoperative magnetoencephalography (MEG)-based functional connectivity as a predictor of short- and medium-term neurological outcome after removal of gliomas in peri-eloquent and eloquent areas. Methods Resting-state whole-brain MEG recordings were obtained from 79 consecutive subjects with focal brain gliomas near or within motor, sensory, or language areas. Neural activity was estimated using adaptive spatial filtering. The mean imaginary coherence between voxels in and around brain tumors was compared to contralesional voxels and used as an index of their functional connectivity with the rest of the brain. The connectivity values of the tissue resected during surgery were correlated to the early (one week post-operatively) and medium-term (six months post-operatively) neurological morbidity. Results Patients undergoing resection of tumors with decreased functional connectivity had a 29% rate of new neurological deficit 1 week after surgery and a 0% rate at 6-month follow-up. Patients undergoing resection of tumors with increased functional connectivity had a 60% rate of new deficit at 1 week and a 25% rate at 6 months. Conclusion MEG connectivity analysis gives a valuable preoperative evaluation of the functionality of the tissue surrounding tumors in peri-eloquent and eloquent areas. These data may be used to optimize pre-operative patient counseling and surgical strategy. PMID:22895403

  16. Frequency of changing enteral alimentation bags and tubing, and adverse clinical outcomes in patients in a long term care facility.

    PubMed

    Graham, S; McIntyre, M; Chicoine, J; Gerard, B; Laughren, R; Cowley, G; Morrison, J; Aoki, F Y; Nicolle, L E

    1993-01-01

    Enteral alimentation, given via nasogastric or gastrostomy tubes, is a well established practice to provide nutrition for patients with significant neurological injury. The frequency with which enteral feeding bags and tubes require change and potential adverse effects associated with bacterial contamination of tube feeds remain controversial. The authors studied different times between enteral feeding bag and tube changes, and the effect on adverse clinical outcomes in residents of a long term care facility. In the first study, residents were randomized to 24 h (n = 2), 48 h (n = 3) or 72 h (n = 6) tube feeding and bag changes with clinical status monitored in a standardized fashion for six months. In the second study, patients were randomized to 24 h (n = 6) or 72 h (n = 6) changes. Patient-days of follow-up were 382, 574 and 1000 for the three arms of the first study period and 556 and 496 for the two arms of the second study. No differences in potential clinical adverse events--including fever, gastrointestinal symptoms or pneumonia--were observed with different durations of tubing change. This study suggests it is appropriate to change alimentation tube and feeding bags every 72 h (rather than every 24 h). The less frequent changes will decrease supply costs and free nursing time for other activities.

  17. Comparison of neurological health outcomes between two adolescent cohorts exposed to pesticides in Egypt

    PubMed Central

    Bonner, Matthew R.; Hendy, Olfat; Abdel Rasoul, Gaafar; Wang, Kai; Olson, James R.; Rohlman, Diane S.

    2017-01-01

    Pesticide-exposed adolescents may have a higher risk of neurotoxic effects because of their developing brains and bodies. However, only a limited number of studies have addressed this risk among adolescents. The aim of this study was to compare neurological outcomes from two cohorts of Egyptian adolescents working as pesticide applicators. In 2005 and 2009, two cohorts of male adolescents working as pesticide applicators for the cotton crop were recruited from Menoufia Governorate, Egypt. The same application schedule and pesticides were used at both times, including both organophosphorus, and pyrethroid compounds. Participants in both cohorts completed three neurobehavioral tests, health and exposure questionnaires, and medical and neurological screening examinations. In addition, blood samples were collected to measure butyryl cholinesterase (BChE) activity. Pesticide applicators in both cohorts reported more neurological symptoms and signs than non-applicators, particularly among participants in the 2005 cohort (OR ranged from 1.18 to 15.3). Except for one test (Trail Making B), there were no significant differences between either applicators or non-applicators of both cohorts on the neurobehavioral outcome measures (p > 0.05). The 2005 cohort showed greater inhibition of serum BChE activity than the 2009 cohort (p < 0.05). In addition, participants with depressed BChE activity showed more symptoms and signs than others without BChE depression (p < 0.05). Our study is the first to examine the consistency of health outcomes associated with pesticide exposure across two cohorts tested at different times from the same geographical region in rural Egypt. This similar pattern of findings across the two cohorts provides strong evidence of the health impact of exposure of adolescents to pesticides. PMID:28231336

  18. Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

    PubMed Central

    Amiri-Nikpour, Mohammad Reza; Nazarbaghi, Surena; Ahmadi-Salmasi, Babak; Mokari, Tayebeh; Tahamtan, Urya; Rezaei, Yousef

    2014-01-01

    Background Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. Methods In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90. Results The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008) and day 90 (median 11, interquartile range 10–13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%). Conclusion Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke. PMID:25516711

  19. Comparison of neurological health outcomes between two adolescent cohorts exposed to pesticides in Egypt.

    PubMed

    Ismail, Ahmed A; Bonner, Matthew R; Hendy, Olfat; Abdel Rasoul, Gaafar; Wang, Kai; Olson, James R; Rohlman, Diane S

    2017-01-01

    Pesticide-exposed adolescents may have a higher risk of neurotoxic effects because of their developing brains and bodies. However, only a limited number of studies have addressed this risk among adolescents. The aim of this study was to compare neurological outcomes from two cohorts of Egyptian adolescents working as pesticide applicators. In 2005 and 2009, two cohorts of male adolescents working as pesticide applicators for the cotton crop were recruited from Menoufia Governorate, Egypt. The same application schedule and pesticides were used at both times, including both organophosphorus, and pyrethroid compounds. Participants in both cohorts completed three neurobehavioral tests, health and exposure questionnaires, and medical and neurological screening examinations. In addition, blood samples were collected to measure butyryl cholinesterase (BChE) activity. Pesticide applicators in both cohorts reported more neurological symptoms and signs than non-applicators, particularly among participants in the 2005 cohort (OR ranged from 1.18 to 15.3). Except for one test (Trail Making B), there were no significant differences between either applicators or non-applicators of both cohorts on the neurobehavioral outcome measures (p > 0.05). The 2005 cohort showed greater inhibition of serum BChE activity than the 2009 cohort (p < 0.05). In addition, participants with depressed BChE activity showed more symptoms and signs than others without BChE depression (p < 0.05). Our study is the first to examine the consistency of health outcomes associated with pesticide exposure across two cohorts tested at different times from the same geographical region in rural Egypt. This similar pattern of findings across the two cohorts provides strong evidence of the health impact of exposure of adolescents to pesticides.

  20. Increased incidence of adverse perinatal outcome with low maternal blood viscosity in preeclampsia.

    PubMed

    Pepple, D J; Mullings, A M; Reid, H L

    2004-01-01

    Hyperviscosity of the maternal blood has been reported to be associated with an increased incidence of adverse perinatal outcome in preeclampsia. We related the changes in maternal blood viscosity to perinatal outcome in 47 preeclamptic, nulliparous, black Jamaican women. A group of 49 non-preeclamptic, nulliparous, gestation-matched women acted as controls. Perinatal outcome was also compared between the women with high blood viscosity (> or = 5 mPa.s) and those with low blood viscosity (< 5 mPa.s) in both the preeclamptic and non-preeclamptic groups. Data was analysed by the comparison of two proportions, the chi-squared test, the Fisher's exact test and the Pearson's correlation method. The level of statistical significance was taken at p < 0.05. The incidence of adverse perinatal outcome was significantly (p < 0.001) higher in the preeclamptic women as compared with that of the non-preeclamptic controls. However, of interest, was the fact that within the preeclamptic group, the incidence of adverse perinatal outcome was significantly (p = 0.001, Fisher's exact test) higher in those with low blood viscosity as compared with those with high blood viscosity. These results suggest that low maternal blood viscosity may be related to increased incidence of adverse perinatal outcome in Jamaican women with preeclampsia.

  1. Time-Based Partitioning Model for Predicting Neurologically Favorable Outcome among Adults with Witnessed Bystander Out-of-Hospital CPA

    PubMed Central

    Abe, Toshikazu; Tokuda, Yasuharu; Cook, E. Francis

    2011-01-01

    Background Optimal acceptable time intervals from collapse to bystander cardiopulmonary resuscitation (CPR) for neurologically favorable outcome among adults with witnessed out-of-hospital cardiopulmonary arrest (CPA) have been unclear. Our aim was to assess the optimal acceptable thresholds of the time intervals of CPR for neurologically favorable outcome and survival using a recursive partitioning model. Methods and Findings From January 1, 2005 through December 31, 2009, we conducted a prospective population-based observational study across Japan involving consecutive out-of-hospital CPA patients (N = 69,648) who received a witnessed bystander CPR. Of 69,648 patients, 34,605 were assigned to the derivation data set and 35,043 to the validation data set. Time factors associated with better outcomes: the better outcomes were survival and neurologically favorable outcome at one month, defined as category one (good cerebral performance) or two (moderate cerebral disability) of the cerebral performance categories. Based on the recursive partitioning model from the derivation dataset (n = 34,605) to predict the neurologically favorable outcome at one month, 5 min threshold was the acceptable time interval from collapse to CPR initiation; 11 min from collapse to ambulance arrival; 18 min from collapse to return of spontaneous circulation (ROSC); and 19 min from collapse to hospital arrival. Among the validation dataset (n = 35,043), 209/2,292 (9.1%) in all patients with the acceptable time intervals and 1,388/2,706 (52.1%) in the subgroup with the acceptable time intervals and pre-hospital ROSC showed neurologically favorable outcome. Conclusions Initiation of CPR should be within 5 min for obtaining neurologically favorable outcome among adults with witnessed out-of-hospital CPA. Patients with the acceptable time intervals of bystander CPR and pre-hospital ROSC within 18 min could have 50% chance of neurologically favorable outcome. PMID:22194860

  2. Psychosocial outcomes among youth with spinal cord injury by neurological impairment

    PubMed Central

    Riordan, Anne; Kelly, Erin H.; Klaas, Sara J.; Vogel, Lawrence C.

    2015-01-01

    Objective Examine psychosocial outcomes of youth with spinal cord injury (SCI) as a function of neurological level (paraplegia/tetraplegia) and severity (American Spinal Injury Association (ASIA) Impairment Scale (AIS)). Design Survey research. Setting Three pediatric SCI specialty centers in the USA. Participants Youth with SCI ages 5–18 with neurological impairment classifications of: tetraplegia AIS ABC (tetraplegia ABC), paraplegia AIS ABC (paraplegia ABC), or AIS D. Outcome Measures Children's Assessment of Participation and Enjoyment, Pediatric Quality of Life Inventory, Revised Children's Manifest Anxiety Scale, and Children's Depression Inventory. Results Three hundred and forty youth participated; 57% were male; 60% were Caucasian, 21% Hispanic, 7% African-American, 2% Native American, and 3% reported “other”. Their mean age was 8.15 years (standard deviation (SD) = 5.84) at injury and 13.18 years (SD = 3.87) at interview. Ninety-six youth (28%) had tetraplegia ABC injuries, 191 (56%) paraplegia ABC injuries, and 53 (16%) AIS D injuries. Neurological impairment was significantly related to participation and quality of life (QOL). Specifically, youth with paraplegia ABC and AIS D injuries participated in more activities than youth with tetraplegia ABC (P = 0.002; P = 0.018, respectively) and youth with paraplegia ABC participated more often than youth with tetraplegia ABC (P = 0.006). Youth with paraplegia ABC reported higher social QOL than youth with tetraplegia ABC (P = 0.001) and AIS D injuries (P = 0.002). Groups did not differ regarding mental health. Conclusion Interventions should target youth with tetraplegia ABC, as they may need support in terms of participation, and both youth with tetraplegia ABC and AIS D injuries in terms of social integration. PMID:24621027

  3. The outcome of neurology outpatients with medically unexplained symptoms: a prospective cohort study

    PubMed Central

    Carson, A; Best, S; Postma, K; Stone, J; Warlow, C; Sharpe, M

    2003-01-01

    Background: In a previous cross sectional study of 300 consecutive new attenders at neurology outpatient clinics, 90 were detected with symptoms that were rated as "not at all" or only "somewhat" explained by organic disease. Objective: To report a follow up study of this cohort. Methods: Patients were reinterviewed by telephone eight months after their initial assessment. They were asked to rate their overall improvement on a clinical global improvement scale, and their health status on the medical outcome short form 36 item scale (SF-36). The PRIME MD interview was administered to determine psychiatric diagnoses. Neurological and primary care records were reviewed for any changes in diagnostic opinion during the follow up period. Results: Of the 90 eligible patients, 66 (73%) participated in follow up. Among these, five (8%) rated themselves as "much worse," four (6%) as "somewhat worse," 27 (40%) as "just the same," 15 (23%) as "somewhat better," and 15 (23%) as "much better." There were no cases in which an organic cause for the presenting complaint was uncovered during the follow up period. Poorer physical function at baseline was the only predictor of poorer outcome at follow up. Conclusions: Over half the patients who presented to neurologists with symptoms that were rated as largely or completely medically unexplained had not improved eight months later. In no case was a disease explanation for the original presenting symptoms subsequently identified. PMID:12810775

  4. Outcome measures in neurological physical therapy practice: part II. A patient-centered process.

    PubMed

    Sullivan, Jane E; Andrews, A Williams; Lanzino, Desiree; Perron, Aimee E; Peron, Aimee; Potter, Kirsten A

    2011-06-01

    Physical therapists working in neurological practice must make choices about which standardized outcome measures are most appropriate for each patient. Significant time constraints in the clinic limit the number of measures that one can reasonably administer. Therapists must choose measures that will provide results that guide the selection of appropriate interventions and are likely to show clinically meaningful change. Therefore, therapists must be able to compare the merits of available measures to identify those that are most relevant for each patient and setting. This article describes a process for selecting outcome measures and illustrates the use of that process with a patient who has had a stroke. The link between selecting objective outcome measures and tracking patient progress is emphasized. Comparisons are made between 2 motor function measures (the Fugl-Meyer Assessment [FMA] of Physical Performance vs the Stroke Rehabilitation Assessment of Movement), and 2 balance measures (Berg Balance Scale vs the Activities-specific Balance Confidence Scale). The use of objective outcome measures allows therapists to quantify information that previously had been described in subjective terms. This allows the tracking of progress, and the comparison of effectiveness and costs across interventions, settings, providers, and patient characteristics.

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

    PubMed Central

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

    2017-01-01

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

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

    EPA Science Inventory

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

  7. 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...

  8. 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)…

  9. 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...

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

    EPA Science Inventory

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

  11. 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

  12. 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.

  13. A Hospital-Based Retrospective Comparative Study of Complications, Outcomes, Clinical and Laboratory Parameters of Malaria with and without Neurological Involvement

    PubMed Central

    Ahmad, Sohaib; Shirazi, Nadia; Bhat, Nowneet K; Dhar, Minakshi; Mittal, Garima; Mittal, Manish; Kaeley, Nidhi; Kumar, Manoj

    2017-01-01

    Background & Objectives Classically associated with Plasmodium (P.) falciparum, neurological complications in severe malaria is associated with increased morbidity and mortality. However, reports implicate the long considered benign P. vivax for causing severe malaria as well. We aimed to analyse the cerebral complications in malaria, and study if there is a species-related difference in the presentation and outcomes. Methods We retrospectively compared patients with malaria hospitalised from 2009–15, with (n=105) and without (n=1155) neurological involvement regarding outcomes, complications, demographic attributes, clinical features, and laboratory parameters. Subsequently, the same parameters were studied in those with cerebral malaria due to mono-infections of P. vivax or P. falciparum and their co-infection. Results Cerebral malaria was observed in 8.3% (58/696), 7.4% (38/513) and 17.6% (6/51) of P. vivax, P. falciparum and combined plasmodial infections respectively. Those with cerebral malaria had significantly (p<0.05) longer hospitalisation, delayed defervescence, required mechanical ventilatory support and dialysis despite comparable levels of azotemia and renal insufficiency, and adverse outcomes compared to non-cerebral malaria. Severe thrombocytopenia, respiratory distress and mechanical ventilation were significantly (p<0.05) associated with P. vivax cerebral malaria. Conclusions The plasmodial species are comparable in clinical and laboratory parameters and outcomes in cerebral malaria in isolation and combination (p>0.05). P. vivax is emerging as the predominant cause of cerebral malaria, and its virulence is comparable to P. falciparum. PMID:28101311

  14. Periodontal treatment during pregnancy decreases the rate of adverse pregnancy outcome: a controlled clinical trial

    PubMed Central

    SANT’ANA, Adriana Campos Passanezi; de CAMPOS, Marinele R.; PASSANEZI, Selma Campos; de REZENDE, Maria Lúcia Rubo; GREGHI, Sebastião Luiz Aguiar; PASSANEZI, Euloir

    2011-01-01

    Objectives The aim of this study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes. Material and Methods Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups: NIG – "no intervention" (n=17) or IG- "intervention" (n=16). IG patients were submitted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning (SRP), professional prophylaxis (PROPH) and oral hygiene instruction (OHI). NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery. Periodontal evaluation was performed by a single trained examiner, blinded to periodontal treatment, according to probing depth (PD), clinical attachment level (CAL), plaque index (PI) and sulcular bleeding index (SBI) at baseline and 35 gestational weeks-28 days post-partum. Primary adverse pregnancy outcomes were preterm birth (<37 weeks), low birth weight (<2.5 kg), late abortion (14-24 weeks) or abortion (<14 weeks). The results obtained were statistically evaluated according to OR, unpaired t test and paired t test at 5% significance level. Results No significant differences were observed between groups at baseline examination. Periodontal treatment resulted in stabilization of CAL and PI (p>0.05) at IG and worsening of all periodontal parameters at NIG (p<0.0001), except for PI. Significant differences in periodontal conditions of IG and NIG were observed at 2nd examination (p<0.001). The rate of adverse pregnancy outcomes was 47.05% in NIG and 6.25% in IG. Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [OR=13.50; CI: 1.47-123.45; p=0.02]. Conclusions Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes. PMID:21552714

  15. Koumine exhibits anxiolytic properties without inducing adverse neurological effects on functional observation battery, open-field and Vogel conflict tests in rodents.

    PubMed

    Chen, Chao-Jie; Zhong, Zhi-Feng; Xin, Zhi-Ming; Hong, Long-Hui; Su, Yan-Ping; Yu, Chang-Xi

    2017-04-01

    Koumine, an active alkaloid of neurotoxic plant Gelsemium, has been focused on its therapeutic uses, especially in central nervous system. Nevertheless, less is known about the neurological effects of koumine, which hampers its potential therapeutic exploitation. Moreover, as the anxiolytic potential of Gelsemium has raised many critical issues, its active principles on the anxiolytic and other neurological effects need to be further investigated. Here, we used functional observation battery (FOB) of mice to systematically measure the neurological effects of koumine at the effective doses, and then further confirmed its anxiolytic properties in open-field test (OFT) of mice and Vogel conflict test (VCT) of rats. Koumine exhibited anxiolytic-like activities but did not affect other autonomic, neurological and physical functions in FOB. Furthermore, koumine released anxiolytic responses and anti-punishment action in a manner similar to diazepam in OFT and VCT, respectively. The results constitutes solid set of fundamental data further demonstrating anxiolytic properties of koumine at the therapeutic doses without inducing adverse neurological effects, which supports the perspectives for the development of safe and effective koumine medicine against pathological anxiety.

  16. 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

  17. Predictive value of sequential electroencephalogram (EEG) in neonates with seizures and its relation to neurological outcome.

    PubMed

    Khan, Richard Lester; Nunes, Magda Lahorgue; Garcias da Silva, Luis Fernando; da Costa, Jaderson Costa

    2008-02-01

    The aim of this study was to evaluate the relationship of sequential neonatal electroencephalography (EEG) and neurological outcome in neonates with seizures to identify polysomnographic features predictive of outcome. Sequential EEGs recordings of 58 neonates that belonged to 2 historical cohorts of newborns with seizures from the same neonatal intensive care unit and who had follow-up at the Neurodevelopment Clinic of the Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) in Porto Alegre, Brazil, were analyzed and classified into 4 groups: normal-normal, abnormal-normal, abnormal-abnormal, normal-abnormal. In patients with more than 2 recordings, during the neonatal period, the first EEG was compared with the following more abnormal. A total of 58 pairs of 2 sequential EEGs were analyzed. Considering the first EEG, a statistically significant difference was observed between the relationship of the result of this exam, if it was abnormal, with developmental delay (P = .030) and postnatal death (P = .030). Abnormal background activity was also related to neurodevelopment delay (P = .041). EEG sequences abnormal-abnormal and normal-abnormal significantly correlated to the outcome epilepsy ( P = .015). Abnormal sequential background activity was associated with neurodevelopment delay (P = .006) and epilepsy (P = .041). The burst suppression pattern when present in any EEG correlated with epilepsy (P = .013) and postnatal death (P = .034). Sequential abnormal background patterns in the first and second EEG increased the risk for epilepsy (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.03-3.0) and neurodevelopment delay (RR = 2.20; 95% CI = 1.3-3.0). Abnormal background activity only in the second electroencephalogram increased the risk for neurodevelopment delay (RR = 2.20; 95% CI = 1.3-3.0). All the neonates (n = 33) with seizures related to probable hypoxic ischemic encephalopathy had abnormalities in the first EEG (P

  18. Hypothermia and neurological outcome after cardiac arrest: state of the art.

    PubMed

    Polderman, K H

    2008-01-01

    Multi-centred studies in patients who remain comatose after cardiac arrest and also in newborn babies with perinatal asphyxia have clearly demonstrated that mild hypothermia (32-34 degrees C) can improve neurological outcome after post-anoxic injury. This represents a highly promising development in the field of neurocritical care. This review discusses the place of mild therapeutic hypothermia in the overall therapeutic strategy for cardiac arrest patients. Cooling should not be viewed in isolation but in the context of a 'treatment bundle,' which together can significantly improve outcome after cardiac arrest. Favourable outcomes of 50-60% are now routinely achieved in many centres in patients with witnessed arrest and an initial rhythm of ventricular fibrillation or ventricular tachycardia. These results have been achieved by combining a number of therapeutic strategies, including early and effective resuscitation with greater emphasis on continuing chest compressions throughout various procedures (including resumption of compressions immediately after defibrillation even if rhythm has been restored) as well as prevention of hypoxia and hypotension in all stages following restoration of spontaneous circulation. Regarding the use of hypothermia, early induction and proper management of side-effects are the key elements of successful implementation. Treatment should include the rapid infusion of 1500-3000 mL of cold fluids to induce hypothermia and prevent hypovolaemia and hypotension. Educational activities to increase awareness and acceptance of new therapeutic options and European Resuscitation Council guidelines are urgently required.

  19. 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...

  20. 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

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

    PubMed Central

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

    2015-01-01

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

  2. Low socioeconomic status, adverse gene expression profiles, and clinical outcomes in hematopoietic stem cell transplant recipients

    PubMed Central

    Knight, Jennifer M.; Rizzo, J. Douglas; Logan, Brent R.; Wang, Tao; Arevalo, Jesusa M.G.; Ma, Jeffrey; Cole, Steve W.

    2015-01-01

    Purpose Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biological mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I IFN response and antibody synthesis. Experimental Design We compared pre-transplant leukocyte CTRA gene expression between a group of 78 high vs. low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes. Results Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA up-regulation compared to matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival. Conclusions Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT. PMID:26286914

  3. 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.

  4. 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.

  5. 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

  6. 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...

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

    PubMed

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

    2016-10-01

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

  8. Population versus Customized Fetal Growth Norms and Adverse Outcomes in an Intrapartum Cohort

    PubMed Central

    Costantine, Maged M.; Lai, Yinglei; Bloom, Steven L.; Spong, Catherine Y.; Varner, Michael W.; Rouse, Dwight J.; Ramin, Susan M.; Caritis, Steve N.; Peaceman, Alan M.; Sorokin, Yoram; Sciscione, Anthony; Mercer, Brian M.; Thorp, John M.; Malone, Fergal D.; Harper, Margaret; Iams, Jay D.

    2013-01-01

    Objective To compare population versus customized fetal growth norms in identifying neonates at risk for adverse outcomes (APO) associated with small for gestational age (SGA). Study Design Secondary analysis of an intrapartum fetal pulse oximetry trial in nulliparous women at term. Birthweight percentiles were calculated using ethnicity- & gender-specific population norms and customized norms (Gardosi). Results 508 (9.9%) and 584 (11.3%) neonates were SGA by population (SGApop) and customized (SGAcust) norms. SGApop infants were significantly associated with a composite adverse neonatal outcome, neonatal intensive care admission, low fetal oxygen saturation and reduced risk of cesarean delivery; while both SGApop and SGAcust were associated with a 5-minute Apgar score < 4. The ability of customized and population birthweight percentiles in predicting APO was poor (12 out of 14 APOs had AUC <0.6). Conclusion In this intrapartum cohort, neither customized nor normalized-population norms adequately identify neonates at risk of APO related to SGA. PMID:22893556

  9. Decline in adverse outcomes and death in tuberculosis patients in Malawi: association with HIV interventions.

    PubMed

    Kanyerere, H; Mganga, A; Harries, A D; Tayler-Smith, K; Zachariah, R; Jahn, A; Chimbwandira, F M; Mpunga, J

    2015-06-21

    Between 2000 and 2012, the annual numbers of patients treated for tuberculosis (TB) in Malawi declined by 28%, from 28 234 to 20 463. During this time, the proportion of TB patients tested for the human immunodeficiency virus (HIV) increased from 6% to 87%. Most HIV-infected patients received cotrimoxazole preventive therapy, and the proportion receiving antiretroviral therapy increased to 88%. Between 2000 and 2008 there was a significant decline in all adverse outcomes (from 31% to 14%), and particularly in deaths (from 23% to 10%) and loss to follow-up (from 5.2% to 1.9%, P < 0.001). After 2008, there was no decrease in any adverse outcome. Ways to further reduce TB-associated mortality are discussed.

  10. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects.

    PubMed

    Streissguth, Ann P; Bookstein, Fred L; Barr, Helen M; Sampson, Paul D; O'Malley, Kieran; Young, Julia Kogan

    2004-08-01

    Clinical descriptions of patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) suggest major problems with adaptive behavior. Five operationally defined adverse outcomes and 18 associated risk/protective factors were examined using a Life History Interview with knowledgeable informants of 415 patients with FAS or FAE (median age 14 years, range 6-51; median IQ 86, range 29-126). Eighty percent of these patients were not raised by their biological mothers. For adolescents and adults, the life span prevalence was 61% for Disrupted School Experiences, 60% for Trouble with the Law, 50% for Confinement (in detention, jail, prison, or a psychiatric or alcohol/drug inpatient setting), 49% for Inappropriate Sexual Behaviors on repeated occasions, and 35% for Alcohol/Drug Problems. The odds of escaping these adverse life outcomes are increased 2- to 4-fold by receiving the diagnosis of FAS or FAE at an earlier age and by being reared in good stable environments.

  11. Acute disseminated encephalomyelitis with severe neurological outcomes following virosomal seasonal influenza vaccine.

    PubMed

    Alicino, Cristiano; Infante, Maria Teresa; Gandoglia, Ilaria; Miolo, Nadia; Mancardi, Gian Luigi; Zappettini, Simona; Capello, Elisabetta; Orsi, Andrea; Tamburini, Tiziano; Grandis, Marina

    2014-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory, usually monophasic, immune mediate, demyelinating disease of the central nervous system which involves the white matter. ADEM is more frequent in children and usually occurs after viral infections, but may follow vaccinations, bacterial infections, or may occur without previous events. Only 5% of cases of ADEM are preceded by vaccination within one month prior to symptoms onset. The diagnosis of ADEM requires both multifocal involvement and encephalopathy and specific demyelinating lesions of white matter. Overall prognosis of ADEM patients is often favorable, with full recovery reported in 23% to 100% of patients from pediatric cohorts, and more severe outcome in adult patients. We describe the first case of ADEM occurred few days after administration of virosomal seasonal influenza vaccine. The patient, a 59-year-old caucasic man with unremarkable past medical history presented at admission decreased alertness, 10 days after flu vaccination. During the 2 days following hospitalization, his clinical conditions deteriorated with drowsiness and fever until coma. The magnetic resonance imaging of the brain showed multiple and symmetrical white matter lesions in both cerebellar and cerebral hemispheres, suggesting demyelinating disease with inflammatory activity, compatible with ADEM. The patient was treated with high dose of steroids and intravenous immunoglobulin with relevant sequelae and severe neurological outcomes.

  12. Explaining the Association between Early Adversity and Young Adults' Diabetes Outcomes: Physiological, Psychological, and Behavioral Mechanisms.

    PubMed

    Wickrama, Kandauda A S; Bae, Dayoung; O'Neal, Catherine Walker

    2017-01-31

    Previous studies have documented that early adversity increases young adults' risk for diabetes resulting in morbidity and comorbidity with adverse health conditions. However, less is known about how inter-related physiological (e.g., body mass index [BMI]), psychological (e.g., depressive symptoms), and behavioral mechanisms (e.g., unhealthy eating and sedentary behavior) link early adversity to young adults' diabetes outcomes, although these mechanisms appear to stem from early stressful experiences. The current study tested the patterning of these longitudinal pathways leading to young adults' diabetes using a nationally representative sample of 13,286 adolescents (54% female) over a period of 13 years. The findings indicated that early adversity contributed to elevated BMI, depressive symptoms, and stress-related health behaviors. The impact of these linking mechanisms on hierarchical diabetes outcomes (i.e., prediabetes and diabetes) remained significant after taking their associations with each other into account, showing that these mechanisms operate concurrently. The findings emphasize the importance of early detection for risk factors of young adults' diabetes in order to minimize their detrimental health effects.

  13. Incident opioid drug use and adverse respiratory outcomes among older adults with COPD.

    PubMed

    Vozoris, Nicholas T; Wang, Xuesong; Fischer, Hadas D; Bell, Chaim M; O'Donnell, Denis E; Austin, Peter C; Stephenson, Anne L; Gill, Sudeep S; Rochon, Paula A

    2016-09-01

    We evaluated risk of adverse respiratory outcomes associated with incident opioid use among older adults with chronic obstructive pulmonary diseases (COPD).This was a retrospective population-based cohort study using a validated algorithm applied to health administrative data to identify adults aged 66 years and older with COPD. Inverse probability of treatment weighting using the propensity score was used to estimate hazard ratios comparing adverse respiratory outcomes within 30 days of incident opioid use compared to controls.Incident opioid use was associated with significantly increased emergency room visits for COPD or pneumonia (HR 1.14, 95% CI 1.00-1.29; p=0.04), COPD or pneumonia-related mortality (HR 2.16, 95% CI 1.61-2.88; p<0.0001) and all-cause mortality (HR 1.76, 95% CI 1.57-1.98; p<0.0001), but significantly decreased outpatient exacerbations (HR 0.88, 95% CI 0.83-0.94; p=0.0002). Use of more potent opioid-only agents was associated with significantly increased outpatient exacerbations, emergency room visits and hospitalisations for COPD or pneumonia, and COPD or pneumonia-related and all-cause mortality.Incident opioid use, and in particular use of the generally more potent opioid-only agents, was associated with increased risk for adverse respiratory outcomes, including respiratory-related mortality, among older adults with COPD. Potential adverse respiratory outcomes should be considered when prescribing new opioids in this population.

  14. Patient versus professional based psychosocial risk factor screening for adverse pregnancy outcomes.

    PubMed

    Quispel, Chantal; van Veen, Mieke J; Zuijderhoudt, Christianne; Steegers, Eric A P; Hoogendijk, Witte J G; Birnie, Erwin; Bonsel, Gouke J; Lambregtse-van den Berg, Mijke P

    2014-11-01

    To identify Psychopathology, Psychosocial problems and substance use (PPS) as predictors of adverse pregnancy outcomes, two screen-and-advice instruments were developed: Mind2Care (M2C, self-report) and Rotterdam Reproductive Risk Reduction (R4U, professional's checklist). To decide on the best clinical approach of these risks, the performance of both instruments was compared. Observational study of 164 pregnant women who booked at two midwifery practices in Rotterdam. Women were consecutively screened with M2C and R4U. For referral to tailored care based on specific PPS risks, inter-test agreement of single risks was performed in terms of overall accuracy and positive accuracy (risk present according to both instruments). With univariate regression analysis we explored determinants of poor agreement (<90 %). For triage based on risk accumulation and for detecting women-at-risk for adverse birth outcomes, M2C and R4U sum scores were compared. Overall accuracy of single risks was high (mean 93 %). Positive accuracy was lower (mean 46 %) with poorest accuracy for current psychiatric symptoms. Educational level and ethnicity partly explained poor accuracy (p < 0.05). Overall low PPS prevalence decreased the statistical power. For triage, M2C and R4U sum scores were interchangeable from sum scores of five or more (difference <1 %). The probability of adverse birth outcomes similarly increased with risk accumulation for both instruments, identifying 55-75 % of women-at-risk. The self-report M2C and the professional's R4U checklist seem interchangeable for triage of women-at-risk for PPS or adverse birth outcomes. However, the instruments seem to provide complementary information if used as a guidance to tailored risk-specific care.

  15. Optimal screening for increased risk for adverse outcomes in hospitalised older adults

    PubMed Central

    Heim, Noor; van Fenema, Ester M.; Weverling-Rijnsburger, Annelies W. E.; Tuijl, Jolien P.; Jue, Peter; Oleksik, Anna M.; Verschuur, Margot J.; Haverkamp, Jasper S.; Blauw, Gerard Jan; van der Mast, Roos C.; Westendorp, Rudi G. J.

    2015-01-01

    Background: screening for frailty might help to prevent adverse outcomes in hospitalised older adults. Objective: to identify the most predictive and efficient screening tool for frailty. Design and setting: two consecutive observational prospective cohorts in four hospitals in the Netherlands. Subjects: patients aged ≥70 years, electively or acutely hospitalised for ≥2 days. Methods: screening instruments included in the Dutch Safety Management Programme [VeiligheidsManagementSysteem (VMS)] on four geriatric domains (ADL, falls, undernutrition and delirium) were used and the Identification of Seniors At Risk, the 6-item Cognitive Impairment Test and the Mini-Mental State Examination were assessed. Three months later, adverse outcomes including functional decline, high-healthcare demand or death were determined. Correlation and regression tree analyses were performed and predictive capacities were assessed. Results: follow-up data were available of 883 patients. All screening instruments were similarly predictive for adverse outcome (predictive power 0.58–0.66), but the percentage of positively screened patients (13–72%), sensitivity (24–89%) and specificity (35–91%) highly differed. The strongest predictive model for frailty was scoring positive on ≥3 VMS domains if aged 70–80 years; or being aged ≥80 years and scoring positive on ≥1 VMS domains. This tool classified 34% of the patients as frail with a sensitivity of 68% and a specificity of 74%. Comparable results were found in the validation cohort. Conclusions: the VMS-tool plus age (VMS+) offers an efficient instrument to identify frail hospitalised older adults at risk for adverse outcome. In clinical practice, it is important to weigh costs and benefits of screening given the rather low-predictive power of screening instruments. PMID:25432981

  16. Significance of frailty for predicting adverse clinical outcomes in different patient groups with specific medical conditions.

    PubMed

    Ritt, Martin; Gaßmann, Karl-Günter; Sieber, Cornel Christian

    2016-10-01

    Frailty is a major health burden in an aging society. It constitutes a clinical state of reduced physiological reserves that is associated with a diminished ability to withstand internal and external stressors. Frail patients have an increased risk for adverse clinical outcomes, such as mortality, readmission to hospital, institutionalization and falls. Of further clinical interest, frailty might be at least in part reversible in some patients and subject to preventive strategies. In daily clinical practice older patients with a complex health status, who are mostly frail or at least at risk of developing frailty, are frequently cared for by geriatricians. Recently, clinicians and scientists from other medical disciplines, such as cardiology, pulmonology, gastroenterology, nephrology, endocrinology, rheumatology, surgery and critical care medicine also discovered frailty to be an interesting instrument for risk stratification of patients, including younger patients. In this review we highlight the results of recent studies that demonstrated the significance of frailty to predict adverse clinical outcomes in patients with specific medical conditions, such as cardiac, lung, liver and kidney diseases as well as diabetes mellitus, osteoarthritis, trauma patients, patients undergoing surgery and critically ill patients. Multiple studies in patients with the aforementioned specific medical conditions could be identified demonstrating a predictive role of frailty for several adverse clinical outcomes. The association between frailty and adverse clinical outcomes reported in these studies was in part independent of several major potential confounder factors, such as age, sex, race, comorbidities and disabilities and were also detected in younger patients.

  17. Iatrogenic neurology.

    PubMed

    Sposato, Luciano A; Fustinoni, Osvaldo

    2014-01-01

    Iatrogenic disease is one of the most frequent causes of hospital admissions and constitutes a growing public health problem. The most common type of iatrogenic neurologic disease is pharmacologic, and the central and peripheral nervous systems are particularly vulnerable. Despite this, iatrogenic disease is generally overlooked as a differential diagnosis among neurologic patients. The clinical picture of pharmacologically mediated iatrogenic neurologic disease can range from mild to fatal. Common and uncommon forms of drug toxicity are comprehensively addressed in this chapter. While the majority of neurologic adverse effects are listed and referenced in the tables, the most relevant issues are further discussed in the text.

  18. Neurologic complications of vaccinations.

    PubMed

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination.

  19. A review of nitrates in drinking water: maternal exposure and adverse reproductive and developmental outcomes.

    PubMed

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

    2006-03-01

    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.

  20. 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

  1. Urokinase-Type Plasminogen Activator Promotes Dendritic Spine Recovery and Improves Neurological Outcome Following Ischemic Stroke

    PubMed Central

    Wu, Fang; Catano, Marcela; Echeverry, Ramiro; Torre, Enrique; Haile, Woldeab B.; An, Jie; Chen, Changhua; Cheng, Lihong; Nicholson, Andrew; Tong, Frank C.; Park, Jaekeun

    2014-01-01

    Spines are dendritic protrusions that receive most of the excitatory input in the brain. Early after the onset of cerebral ischemia dendritic spines in the peri-infarct cortex are replaced by areas of focal swelling, and their re-emergence from these varicosities is associated with neurological recovery after acute ischemic stroke (AIS). Urokinase-type plasminogen activator (uPA) is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor (uPAR). We report that cerebral cortical neurons release uPA during the recovery phase from ischemic stroke in vivo or hypoxia in vitro. Although uPA does not have an effect on ischemia- or hypoxia-induced neuronal death, genetic deficiency of uPA (uPA−/−) or uPAR (uPAR−/−) abrogates functional recovery after AIS. Treatment with recombinant uPA after ischemic stroke induces neurological recovery in wild-type and uPA−/− but not in uPAR−/− mice. Diffusion tensor imaging studies indicate that uPA−/− mice have increased water diffusivity and decreased anisotropy associated with impaired dendritic spine recovery and decreased length of distal neurites in the peri-infarct cortex. We found that the excitotoxic injury induces the clustering of uPAR in dendritic varicosities, and that the binding of uPA to uPAR promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from uPAR-enriched varicosities. This effect is independent of uPA's proteolytic properties and instead is mediated by Rac-regulated profilin expression and cofilin phosphorylation. Our data indicate that binding of uPA to uPAR promotes dendritic spine recovery and improves functional outcome following AIS. PMID:25339736

  2. 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

  3. Maternal smoking during pregnancy and adverse outcomes in offspring: genetic and environmental sources of covariance.

    PubMed

    Kuja-Halkola, Ralf; D'Onofrio, Brian M; Larsson, Henrik; Lichtenstein, Paul

    2014-09-01

    Maternal smoking during pregnancy (SDP) has been associated with several psychiatric outcomes in the offspring; studies have questioned whether the associations are causal, however. We analyzed all children born in Sweden between 1983 and 2009 to investigate the effect of SDP on multiple indicators of adverse outcomes in three areas: pregnancy outcomes (birth weight, preterm birth and being born small for gestational age), long-term cognitive abilities (low academic achievement and general cognitive ability) and externalizing behaviors (criminal conviction, violent criminal conviction and drug misuse). SDP was associated with all outcomes. Within-family analyses of the pregnancy outcomes were consistent with a causal interpretation as the associations persisted when siblings discordant for SDP were compared. For the cognitive and externalizing outcomes, the results were not consistent with causal effects; when comparing differentially exposed siblings none of the associations remained significant. In quantitative genetic models genetic factors explained the majority of the associations between SDP and cognitive and externalizing outcomes. The results suggest that the associations between SDP in mothers and cognition and externalizing behaviors in their offspring is primarily due to genetic effects that influence the behaviors in both generations.

  4. Neurologic Functional and Quality of Life Outcomes after TBI: Clinic Attendees versus Non-Attendees.

    PubMed

    Patel, Mayur B; Wilson, Laura D; Bregman, Jana A; Leath, Taylor C; Humble, Stephen S; Davidson, Mario A; de Riesthal, Michael R; Guillamondegui, Oscar D

    2015-07-01

    This investigation describes the relationship between TBI patient demographics, quality of life outcome, and functional status outcome among clinic attendees and non-attendees. Of adult TBI survivors with intracranial hemorrhage, 63 attended our TBI clinic and 167 did not attend. All were telephone surveyed using the Extended-Glasgow Outcome Scale (GOSE), the Quality of Life after Brain Injury (QOLIBRI) scale, and a post-discharge therapy questionnaire. To determine risk factors for GOSE and QOLIBRI outcomes, we created multivariable regression models employing covariates of age, injury characteristics, clinic attendance, insurance status, post-discharge rehabilitation, and time from injury. Compared with those with severe TBI, higher GOSE scores were identified in individuals with both mild (odds ratio [OR]=2.0; 95% confidence interval [CI]: 1.1-3.6) and moderate (OR=4.7; 95% CI: 1.6-14.1) TBIs. In addition, survivors with private insurance had higher GOSE scores, compared with those with public insurance (OR=2.0; 95% CI: 1.1-3.6), workers' compensation (OR=8.4; 95% CI: 2.6-26.9), and no insurance (OR=3.1; 95% CI: 1.6-6.2). Compared with those with severe TBI, QOLIBRI scores were 11.7 points (95% CI: 3.7-19.7) higher in survivors with mild TBI and 17.3 points (95% CI: 3.2-31.5) higher in survivors with moderate TBI. In addition, survivors who received post-discharge rehabilitation had higher QOLIBRI scores by 11.4 points (95% CI: 3.7-19.1) than those who did not. Survivors with private insurance had QOLIBRI scores that were 25.5 points higher (95% CI: 11.3-39.7) than those with workers' compensation and 16.8 points higher (95% CI: 7.4-26.2) than those without insurance. Because neurologic injury severity, insurance status, and receipt of rehabilitation or therapy are independent risk factors for functional and quality of life outcomes, future directions will include improving earlier access to post-TBI rehabilitation, social work services, affordable insurance

  5. Neurologic Functional and Quality of Life Outcomes after TBI: Clinic Attendees versus Non-Attendees

    PubMed Central

    Wilson, Laura D.; Bregman, Jana A.; Leath, Taylor C.; Humble, Stephen S.; Davidson, Mario A.; de Riesthal, Michael R.; Guillamondegui, Oscar D.

    2015-01-01

    Abstract This investigation describes the relationship between TBI patient demographics, quality of life outcome, and functional status outcome among clinic attendees and non-attendees. Of adult TBI survivors with intracranial hemorrhage, 63 attended our TBI clinic and 167 did not attend. All were telephone surveyed using the Extended-Glasgow Outcome Scale (GOSE), the Quality of Life after Brain Injury (QOLIBRI) scale, and a post-discharge therapy questionnaire. To determine risk factors for GOSE and QOLIBRI outcomes, we created multivariable regression models employing covariates of age, injury characteristics, clinic attendance, insurance status, post-discharge rehabilitation, and time from injury. Compared with those with severe TBI, higher GOSE scores were identified in individuals with both mild (odds ratio [OR]=2.0; 95% confidence interval [CI]: 1.1–3.6) and moderate (OR=4.7; 95% CI: 1.6–14.1) TBIs. In addition, survivors with private insurance had higher GOSE scores, compared with those with public insurance (OR=2.0; 95% CI: 1.1–3.6), workers' compensation (OR=8.4; 95% CI: 2.6–26.9), and no insurance (OR=3.1; 95% CI: 1.6–6.2). Compared with those with severe TBI, QOLIBRI scores were 11.7 points (95% CI: 3.7–19.7) higher in survivors with mild TBI and 17.3 points (95% CI: 3.2–31.5) higher in survivors with moderate TBI. In addition, survivors who received post-discharge rehabilitation had higher QOLIBRI scores by 11.4 points (95% CI: 3.7–19.1) than those who did not. Survivors with private insurance had QOLIBRI scores that were 25.5 points higher (95% CI: 11.3–39.7) than those with workers' compensation and 16.8 points higher (95% CI: 7.4–26.2) than those without insurance. Because neurologic injury severity, insurance status, and receipt of rehabilitation or therapy are independent risk factors for functional and quality of life outcomes, future directions will include improving earlier access to post-TBI rehabilitation, social work

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

    PubMed

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

    2015-01-01

    Prenatal maternal stress is associated with pregnancy complications, poor fetal development and poor birth outcomes. Fetal sex has also been shown to affect the course of pregnancy and its outcomes. The aim of this study was to evaluate whether fetal sex modifies the association between continuous exposure to life-threatening rocket attack alarms and adverse pregnancy outcomes. A retrospective cohort study was conducted in which the exposed group was comprised of 1846 women exposed to rocket-attack alarms before and during pregnancy. The unexposed group, with similar sociodemographic characteristics, delivered during the same period of time at the same medical center, but resided out of rocket-attack range. Multivariable models for each gender separately, controlling for possible confounders, evaluated the risk associated with exposure for preterm births (PTB), low birthweight (LBW), small for gestational age and small head circumference (HC). In both univariable and multivariable analyses exposure status was a significant risk factor in female fetuses only: PTB (adj. OR = 1.43; 1.04-1.96), LBW (adj. OR = 1.41; 1.02-1.95) and HC < 31 cm (adj. OR = 1.78; 1.11-2.88). In addition, regarding all adverse outcomes, the male-to-female ratio was higher in the exposed group than in the unexposed group. The findings support the hypothesis that male and female fetuses respond differentially to chronic maternal stress.

  7. 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

  8. 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

  9. 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

  10. Vitamin D Deficiency Increases the Risk of Adverse Neonatal Outcomes in Gestational Diabetes

    PubMed Central

    Weinert, Letícia Schwerz; Reichelt, Angela Jacob; Schmitt, Leonardo Rauber; Boff, Roberta; Oppermann, Maria Lucia Rocha; Camargo, Joiza Lins; Silveiro, Sandra Pinho

    2016-01-01

    Background Gestational diabetes mellitus (GDM) and vitamin D deficiency have been associated with increased risk of adverse perinatal outcomes but the consequences of both conditions simultaneously present in pregnancy have not yet been evaluated. Our objective was to study the influence of vitamin D deficiency in neonatal outcomes of pregnancies with GDM. Methods 184 pregnant women with GDM referred to specialized prenatal monitoring were included in this cohort and had blood sampled for 25-hydroxyvitamin D measurement. Vitamin D was measured by chemiluminescence and deficiency was defined as < 20 ng/mL. Participants were followed until puerperium and adverse neonatal outcomes were evaluated. Results Newborns of women with vitamin D deficiency had higher incidences of hospitalization in intensive care units (ICU) (32 vs 19%, P = 0.048), of hypoglycemia (any, 17.3 vs 7.1%, P = 0.039requiring ICU, 15.3 vs 3.6%, P = 0.008), and were more frequently small for gestational age (SGA) (17.3 vs 5.9%, P = 0.017). After adjustment, relative risk (RR) for hypoglycemia requiring ICU was 3.63 (95%CI 1.09–12.11) and for SGA was 4.32 (95%CI 1.75–10.66). The incidence of prematurity, jaundice and shoulder dystocia was no statistically different between groups. Conclusions In this cohort of pregnant women with GDM, vitamin D deficiency was associated with a major increase in the incidence of adverse neonatal outcomes such as SGA newborns and neonatal hypoglycemia. PMID:27764194

  11. 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

  12. Intracerebral adenosine infusion improves neurological outcome after transient focal ischemia in rats.

    PubMed

    Kitagawa, Hisashi; Mori, Atsushi; Shimada, Jun; Mitsumoto, Yasuhide; Kikuchi, Tetsuro

    2002-04-01

    Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan In order to elucidate the role of adenosine in brain ischemia, the possible protective effects of adenosine on ischemic brain injury were investigated in a rat model of brain ischemia both in vitro and in vivo. Exogenous adenosine dose-dependently rescued cortical neuronal cells from injury after glucose deprivation in vitro. Adenosine (1 mM) also significantly reduced hypoglycemia/hypoxia-induced glutamate release from the hippocampal slice. In a rat model of transient middle cerebral artery occlusion (MCAO), extracellular adenosine concentration was increased immediately after occlusion, and then returned to the baseline by 30 min after reperfusion. Adenosine infusion through a microdialysis probe into the ipsilateral striatum (1 mM adenosine, 2 microl min(-1), total 4.5 h from the occlusion to 3 h after reperfusion) showed a significant improvement in the neurological outcome, and about 25% reduction of infarct volume, although the effect did not reach statistical significance, compared with the vehicle-treated group at 20 h after 90 min of MCAO. These results demonstrated the neuroprotective effect of adenosine against ischemic brain injury both in vitro and in vivo, suggesting the possible therapeutic application of adenosine regulating agents, which inhibit adenosine uptake or metabolism to enhance or maintain extracellular endogenous adenosine levels, for stroke treatment.

  13. Increased Blood Pressure Variability Is Associated with Worse Neurologic Outcome in Acute Anterior Circulation Ischemic Stroke

    PubMed Central

    Bennett, Alicia; Stoddard, Gregory J.; Smith, Gordon; Wang, Haimei; Wold, Jana; Chung, Lee; Tirschwell, David L.; Majersik, Jennifer J.

    2016-01-01

    Background. Although research suggests that blood pressure variability (BPV) is detrimental in the weeks to months after acute ischemic stroke, it has not been adequately studied in the acute setting. Methods. We reviewed acute ischemic stroke patients from 2007 to 2014 with anterior circulation stroke. Mean blood pressure and three BPV indices (standard deviation, coefficient of variation, and successive variation) for the intervals 0–24, 0–72, and 0–120 hours after admission were correlated with follow-up modified Rankin Scale (mRS) in ordinal logistic regression models. The correlation between BPV and mRS was further analyzed by terciles of clinically informative stratifications. Results. Two hundred and fifteen patients met inclusion criteria. At all time intervals, increased systolic BPV was associated with higher mRS, but the relationship was not significant for diastolic BPV or mean blood pressure. This association was strongest in patients with proximal stroke parent artery vessel occlusion and lower mean blood pressure. Conclusion. Increased early systolic BPV is associated with worse neurologic outcome after ischemic stroke. This association is strongest in patients with lower mean blood pressure and proximal vessel occlusion, often despite endovascular or thrombolytic therapy. This hypothesis-generating dataset suggests potential benefit for interventions aimed at reducing BPV in this patient population. PMID:27974991

  14. Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS)

    PubMed Central

    Chan, J; Ng, C; Chan, Y; Mok, T; Lee, S; Chu, S; Law, W; Lee, M; Li, P

    2003-01-01

    Background: Severe acute respiratory syndrome (SARS) was diagnosed in Hong Kong in over 1700 patients between March and early June 2003. Methods: 115 patients diagnosed with SARS were admitted to Queen Elizabeth Hospital, a large regional hospital in Hong Kong, from March 2003, of whom 100 were either discharged or were dead at 31 May. The patients were prospectively studied after admission to assess their short term outcomes and the risk factors associated with adverse outcomes, defined as death or the need for mechanical ventilation Results: At the time of writing 18 patients had died, with a crude mortality rate of 15.7% and a 21 day mortality of 10% (standard error 3%). Thirty nine patients (34%) were admitted to the intensive care unit, 30 of whom (26%) required mechanical ventilation. Multivariate analysis showed that age above 60 (hazards ratio (HR) 3.5, 95% CI 1.2 to 10.2; p=0.02), presence of diabetes mellitus or heart disease (HR 9.1, 95% CI 2.8 to 29.1; p<0.001), and the presence of other comorbid conditions (HR 5.2, 95% CI 1.4 to 19.7; p=0.01) were independently associated with mortality. However, only the presence of diabetes mellitus and/or cardiac disease (HR 7.3, 95% CI 3.1 to 17.4; p<0.001) was associated with adverse outcomes as a whole. Conclusion: SARS is a new disease entity that carries significant morbidity and mortality. Specific clinical and laboratory parameters predicting unfavourable outcomes have been identified. PMID:12885985

  15. B-type natriuretic peptide and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the Folic Acid for Vascular Outcome Reduction in...

  16. Television viewing associated with adverse dietary outcomes in children ages 2-6.

    PubMed

    Ford, C; Ward, D; White, M

    2012-12-01

    The aim of this paper was to systematically review the evidence for the association between television viewing and diet in children ages 2-6. Data sources included PubMed, PsycINFO, EMBASE, ERIC, SportDISCUS, Sociological Abstracts, Web of Science and hand searches of reference lists of relevant articles. Twelve studies were reviewed in which the relationship between television viewing and diet was assessed in children between the ages of 2 and 6. All but one study reported significant relationship between television viewing time and adverse dietary outcomes. Parent-reported television viewing time was used to assay child television viewing in all included studies. Food frequency survey was the most frequent method of dietary assessment, and parent served as proxies for children in all studies. Lower fruit and/or vegetable intake was the most frequently reported dietary outcome, followed by increased energy intake with increased television viewing. The majority of studies reported adverse dietary outcomes with as little as 1 h of daily television exposure. While these results are consistent with recommendations from child health advocates to limit television viewing in young children, they also suggest that further efforts to limit television viewing in young children may be needed to aid in obesity prevention.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Blood rheology at term in normal pregnancy and in patients with adverse outcome events.

    PubMed

    von Tempelhoff, Georg-Friedrich; Velten, Eva; Yilmaz, Asli; Hommel, Gerhard; Heilmann, Lothar; Koscielny, Jürgen

    2009-01-01

    Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05

  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. 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...

  4. 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...

  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. 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...

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

    EPA Pesticide Factsheets

    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 hierarch

  8. Photoselective vaporization of the prostate: outcomes and adverse events of 220 consecutive patients

    NASA Astrophysics Data System (ADS)

    Robson, C.; Mueller, E. J.

    2010-02-01

    Purpose: To evaluate the short term outcomes of 220 consecutive patients who underwent the 532 nm KTP photoselective vaporization of the prostate (PVP) procedure and to evaluate and categorize the complications of the procedure. Materials and Methods: A total of 220 patients with symptomatic benign prostatic obstruction were treated with KTP photoselective vaporization of the prostate. Evaluation measures included the AUA Symptom Score (AUASS)/Quality of Life Score (QOL), peak urinary flow rate (Qmax), post void residual urine (PVR) and adverse events. Results: Symptoms were evaluated at 3 months and adverse events at 1 and 3 months. 181 patients returned for their 1 month visit and 152 returned for their 3 month visit. The American Urological Association Symptom Score (AUASS) decreased from 21.8 to 6.7. The Quality of Life Score (QOL) decreased from 3.8 to 0.7. The peak urinary flow rate (Qmax) increased from 10.7 cc/sec to 22.7 cc/sec. And the post void residual urine (PVR) decreased from 262 cc to 105 cc. Most common adverse events lasting more than 10 days were mild hematuria in 45%, dysuria in 32%, and urgency/frequency in31%. Conclusion: These results confirm that photoselective vaporization of the prostate (PVP) is a safe and effective therapy for benign prostatic obstruction. However, there is frequent, but mild, hematuria and irritative voiding symptoms during the early postoperative period.

  9. 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

  10. Preventive Effects of Folic Acid Supplementation on Adverse Maternal and Fetal Outcomes

    PubMed Central

    Kim, Min Woo; Ahn, Ki Hoon; Ryu, Ki-Jin; Hong, Soon-Cheol; Lee, Ji Sung; Nava-Ocampo, Alejandro A.; Oh, Min-Jeong; Kim, Hai-Joong

    2014-01-01

    Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes. PMID:24842467

  11. 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

  12. From pathways to people: applying the adverse outcome pathway (AOP) for skin sensitization to risk assessment.

    PubMed

    MacKay, Cameron; Davies, Michael; Summerfield, Vicki; Maxwell, Gavin

    2013-01-01

    Consumer safety risk assessment of skin sensitization requires information on both consumer exposure to the ingredient through product use and the hazardous properties of the ingredient. Significant progress has been made in determining the hazard potential of ingredients without animal testing. However, hazard identification is insufficient for risk assessment, and an understanding of the dose-response is needed. Obtaining such knowledge without animal testing is challenging and requires applying available mechanistic knowledge to both assay development and the integration of these data. The recent OECD report "The Adverse Outcome Pathway for Skin Sensitization Initiated by Covalent Binding to Proteins" presents the available mechanistic knowledge of the sensitization response within an adverse outcome pathway (AOP). We propose to use this AOP as the mechanistic basis for physiologically- and mechanistically-based toxicokinetic-toxicodynamic models of the sensitization response. The approach would be informed by non-animal data, provide predictions of the dose-response required for risk assessment, and would be evaluated against human clinical data.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  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. 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.

  19. Biochemical markers and somatosensory evoked potentials in patients after cardiac arrest: the role of neurological outcome scores.

    PubMed

    Rana, Obaida R; Saygili, Erol; Schiefer, Johannes; Marx, Nikolaus; Schauerte, Patrick

    2011-06-15

    Biochemical markers, e.g. NSE or S100B, and somatosensory evoked potentials (SSEP) are considered promising candidates for neurological prognostic predictors in patients after cardiac arrest (CA). The Utstein Templates recommend the use of the Glasgow-Pittsburgh Cerebral Performance Categories (GP-CPC) to divide patients according to their neurological outcome. However, several studies investigating biochemical markers and SSEP are based on the Glasgow Outcome Score (GOS). We noticed that many studies failed to exclude patients who died without certified brain damage from patients classified as poor outcome, instead including all patients who died into this category. Therefore, we summarized the published NSE cut-off values and the derived sensitivity and specificity to predict poor outcome of those studies which only included patients with certified brain death in GOS-1 or GP-CPC-5 (group A) vs. those studies which did not differentiate between death from any cause or death due to primary brain damage (group B). On average, mean NSE cut-off values and sensitivity were higher (56 ± 35 ng/ml, 56 ± 18%) in group A than in group B (41 ± 17 ng/ml, 44 ± 25%), respectively. The specificity remained equally high in both groups. In analogy, the average sensitivity of SSEP to predict poor outcome was higher in group A (76 ± 11%) than in group B (50 ± 15%), while the specificity was similar in both groups. Conclusively, inclusion of deaths without certified brain damage after CA in neurological outcome studies will lead to underestimation of the prognostic power of biochemical or electrophysiological markers for brain damage. A modified GOS and GP-CPC score might help to avoid this bias.

  20. Early Diagnosis of Cerebral X-linked Adrenoleukodystrophy in Boys with Addison’s Disease Improves Survival and Neurological Outcomes

    PubMed Central

    Polgreen, LE; Chahla, S; Miller, W; Rothman, S.; Tolar, J; Kivisto, T; Nascene, D.; Orchard, PJ; Petryk, A

    2011-01-01

    Approximately one-third of boys with X-linked adrenoleukodystophy (X-ALD) develop an acute, progressive inflammatory process of the central nervous system, resulting in rapid neurologic deterioration and death. Hematopoietic cell transplantation (HCT) can halt the progression of neurologic disease if performed early in the course of the cerebral form of X-ALD. We describe a retrospective cohort study of 90 boys with X-ALD evaluated at our institution between 2000 and 2009, to determine if early diagnosis of X-ALD following the diagnosis of unexplained adrenal insufficiency (AI) improves outcomes. We describe 7 cases with a delay in the diagnosis of X-ALD, and compare their outcomes to 10 controls with the diagnosis of ALD made within 12 months following diagnosis of AI. At the time of evaluation for HCT, boys with a delay in the diagnosis of X-ALD had more extensive cerebral involvement and more limited functioning. These boys also were 3.9 times more likely to die, and had significant advancement of cerebral disease after HCT, compared to boys with a timely diagnosis of X-ALD. Conclusion Early diagnosis of cerebral X-ALD following the diagnosis of unexplained AI, and subsequent treatment with HCT, improves both neurological outcomes and survival in boys with cerebral X-ALD. PMID:21279382

  1. Adverse pregnancy outcome in women exposed to acyclovir during pregnancy: a population-based observational study.

    PubMed

    Ratanajamit, Chaveewan; Vinther Skriver, Mette; Jepsen, Peter; Chongsuvivatwong, Virasakdi; Olsen, Jørn; Sørensen, Henrik Toft

    2003-01-01

    This study aimed to examine the risk of adverse pregnancy outcomes in children born to mothers who redeemed a prescription for systemic or topical acyclovir during pregnancy. Data on prescriptions of acyclovir were obtained from the Danish North Jutland Prescription Database and data on pregnancy outcomes from the Danish Medical Birth Registry and the County Hospital Discharge Registry. The risk of malformations, low birth weight, preterm birth and stillbirth in users of acyclovir were compared with non-exposed women using a follow-up design, while the risk of spontaneous abortion was examined using a case-control design. 90 pregnant women had redeemed a prescription for systemic acyclovir, and 995 women for topical acyclovir, during 30 d before conception, or during their pregnancies from 1 January 1990 to 31 December 2001. The odds ratios (95% confidence intervals) of the exposed relative to the non-exposed for the systemic and topical acyclovir were: malformations, 0.69 (0.17-2.82) and 0.84 (0.51, 1.39); low birth weight, 2.03 (0.50-8.35) and 0.48 (0.21-1.07); preterm birth, 1.04 (0.38-2.85) and 0.95 (0.70-1.28); stillbirth (for topical acyclovir), 1.70 (0.80-3.60); and spontaneous abortion, 2.16 (0.60-7.80) and 1.29 (0.80-3.60). There is increasing evidence that the use of systemic acyclovir is not associated with an increased prevalence of malformations at birth and preterm delivery. The data for low birth weight and spontaneous abortion are still inconclusive, although the risk of spontaneous abortion is increased in women exposed to acyclovir during the first month of pregnancy. The use of topical acyclovir does not seem to be associated with any adverse pregnancy outcome, although data on stillbirth are inconclusive.

  2. 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

  3. The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease

    PubMed Central

    Chiu, Yi-Wen; Kuo, Hung-Tien; Lee, Jia-Jung; Lee, Su-Chu; Chen, Tzu-Hui; Lin, Ming-Yen; Hwang, Shang-Jyh; Kuo, Mei-Chuan; Hsu, Ya-Ling; Chen, Hung-Chun

    2017-01-01

    Background Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD. Methods This cohort study enrolled 290 patients with CKD stages 3–5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y). Results During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH≦1.1L and low circulating Angpt2 (2.14, 1.21–3.78, P = 0.009; 4.96, 1.45–16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02). Conclusions Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients. PMID:28333979

  4. Elevated Fecal Calprotectin Associates with Adverse Outcomes from Clostridium difficile Infection in Older Adults

    PubMed Central

    Rao, Krishna; Santhosh, Kavitha; Mogle, Jill A.; Higgins, Peter D. R.; Young, Vincent B.

    2016-01-01

    Background Clostridium difficile infection (CDI) causes a mild to moderate colitis in most patients, but some, especially older adults, develop severe, adverse outcomes. Biomarkers predicting outcomes are needed to optimize treatments. This study tested whether fecal calprotectin associated with a composite primary outcome of complicated CDI (intensive care unit admission, colectomy, or death due to CDI within 30 days of diagnosis) and/or 8-week recurrence. Methods Stool was collected in Cary-Blair media at the time of diagnosis from inpatients of age >60 years that tested positive for C. difficile (enzyme immunoassay [EIA] for toxin A/B or polymerase chain reaction for the tcdB gene). Fecal calprotectin was measured and normalized to solid stool weight. Analysis was performed using logistic regression. Variables were selected for the final model using likelihood ratio tests. Results Fifty patients were included with a mean age 72.8 (± 7.5), and 13 (26%) developed the primary outcome. Clinical variables such as age, gender, and comorbid disease did not associate with complicated CDI/recurrence, nor did traditional biomarkers such as serum albumin or white blood cell count. A high normalized fecal calprotectin (>2000 µg/g) associated with the primary outcome in the final model after adjustment for gender and detectable fecal toxin(s) by EIA (OR 24.9, 95% CI 2.4–257.9, P=.007) with a specificity of 91.9%. Conclusion This study provides evidence that fecal calprotectin level associates with complications from CDI in older adults. Further studies are required to validate these findings in larger cohorts and incorporate them into clinical prediction algorithms. PMID:27206404

  5. Antiepileptic drug teratogenesis: what are the risks for congenital malformations and adverse cognitive outcomes?

    PubMed

    Harden, Cynthia L

    2008-01-01

    Antiepileptic drug (AED) exposure in utero has been associated with major congenital malformations (MCMs) and adverse cognitive outcomes in the offspring of women with epilepsy (WWE). However, determining the exact risk and the relative risks of AEDs for these outcomes has been challenging, and only in recent years has improved study designs enabled us to get a clearer picture of the risks. Still, there is a startling lack of information for many of the newer and widely used AEDs. At this point of time, studies clearly show that valproate (VPA) as a part of polytherapy or when used as a monotherapy is associated with an increased risk of MCMs, and that it poses about threefold the risk of carbamazepine (CBZ). It is unclear if any other AEDs studied pose an increased risk of MCM occurrence; in the best available large study the absolute rates of MCMs with other several other AEDs were not different from untreated WWE. The absolute risks have been reported as CBZ 2.2%, lamotrigine (LTG) 3.2%, phenytoin (PHT) 3.7%, untreated WWE 3.5%, with VPA as the outlier at 6.2%. In utero VPA exposure is also associated with a risk of lower verbal intelligence quotient (IQ) in children, at approximately 10 points lower than controls. CBZ appears to pose no risk to cognitive outcome, and there is some evidence that PHT and phenobarbital (PB) may be associated with risk of reduced cognitive outcome. Polytherapy is associated with greater risk than monotherapy for both MCMs and cognitive outcome. Although more information is needed and hopefully will be obtained from ongoing prospective studies, it is clear that WWE taking VPA and planning pregnancy should have a discussion with their physician about considering changing to another AED before pregnancy, if possible.

  6. What outcomes are important to people with long-term neurological conditions using integrated health and social care?

    PubMed

    Spiers, Gemma; Aspinal, Fiona; Bernard, Sylvia; Parker, Gillian

    2015-09-01

    Measuring the outcomes that are meaningful to people with long-term neurological conditions (LTNCs) using integrated health and social care services may help to assess the effectiveness of integration. Conventional outcomes tend not to be derived from service user experiences, nor are they able to demonstrate the impact of integrated working. This paper reports findings about outcomes identified as being important to people with LTNCs using integrated services. We undertook qualitative work with five community neuro-rehabilitation teams that were integrated in different ways and to different degrees. In-depth, semi-structured interviews were conducted with 35 people with LTNCs using these teams. Data were collected between 2010 and 2011 and analysed using an adapted version of the Framework approach. We identified 20 outcomes across three domains: personal comfort outcomes, social and economic participation outcomes, and autonomy outcomes. Inter-relationships between outcomes, both within and across domains, were evident. The outcomes, and the inter-relationships between them, have implications for how individuals are assessed in practice.

  7. Racial Discrimination and the Black-White Gap in Adverse Birth Outcomes: A Review

    PubMed Central

    Giurgescu, Carmen; McFarlin, Barbara L.; Lomax, Jeneen; Craddock, Cindy; Albrecht, Amy

    2017-01-01

    Introduction The purpose of this integrative review was to evaluate what is known about the relationship between racial discrimination and adverse birth outcomes. Methods A search of the Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and PsycINFO was conducted. The keywords used were: preterm birth, premature birth, preterm delivery, preterm labor, low birth weight, very low birth weight, racism, racial discrimination, and prejudice. Ten research studies were reviewed. All of the studies included African American women in their samples, were conducted in the United States, and were written in English. We did not limit the year of publication for the studies. Data were extracted based on the birth outcomes of preterm birth, low birth weight, or very low birth weight. Results A consistent positive relationship existed between perceptions of racial discrimination and preterm birth, low birth weight, and very low birth weight. No relationship was found between racial discrimination and gestational age at birth. Discussion Future research should explore the effects of racial discrimination as a chronic stressor contributing to the persistent gap in birth outcomes between racial groups. PMID:21733107

  8. Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya

    PubMed Central

    Toko, Eunice N.; Sumba, Odada P.; Daud, Ibrahim I.; Ogolla, Sidney; Majiwa, Maxwel; Krisher, Jesse T.; Ouma, Collins; Dent, Arlene E.; Rochford, Rosemary; Mehta, Saurabh

    2016-01-01

    Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation. PMID:27941597

  9. Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya.

    PubMed

    Toko, Eunice N; Sumba, Odada P; Daud, Ibrahim I; Ogolla, Sidney; Majiwa, Maxwel; Krisher, Jesse T; Ouma, Collins; Dent, Arlene E; Rochford, Rosemary; Mehta, Saurabh

    2016-12-07

    Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation.

  10. Association of Chorioamnionitis with Aberrant Neonatal Gut Colonization and Adverse Clinical Outcomes

    PubMed Central

    Ambalavanan, Namasivayam; Schibler, Kurt R.; Morrow, Ardythe L.; Kallapur, Suhas G.

    2016-01-01

    Objective Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes. Study Design Preterm infants ≤ 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord). Results Of the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnionitis but no funisitis (AC), and 26 infants had chorioamnionitis with funisitis (ACF). The fecal samples from ACF infants collected by day of life 7 had higher relative abundance of family Mycoplasmataceae (phylum Tenericutes), genus Prevotella (phylum Bacteroidetes) and genus Sneathia (phylum Fusobacteria). Further, AC and ACF infants had higher incidence of late-onset sepsis/death as a combined outcome. Presence of specific clades in fecal samples, specifically, order Fusobacteria, genus Sneathia or family Mycoplasmataceae, were significantly associated with higher risk of sepsis or death. Conclusion The results support the hypothesis that specific alterations in the pioneering infant gastrointestinal microbiota induced by chorioamnionitis predispose to neonatal sepsis or death. PMID:27658190

  11. Serum Adiponectin is Associated with Adverse Outcomes of Asthma in Men but Not in Women

    PubMed Central

    Sood, Akshay; Dominic, Elizabeth; Qualls, Clifford; Steffes, Michael W.; Thyagarajan, Bharat; Smith, Lewis J.; Lewis, Cora E.; Jacobs, David R.

    2011-01-01

    Background: Murine studies suggest a beneficial effect of systemic adiponectin on asthma. Our objective was to determine the association between serum adiponectin concentrations and asthma control/severity outcomes in men and women separately. Methods: Cross-sectional and longitudinal analyses of data from years 10, 15, and 20 examinations of the prospective coronary artery risk development in young adults study in the United States were performed. Asthma was defined by self-reported provider diagnosis at or prior to year 15 examination. Outcomes included presence of active disease, number of respiratory symptoms, and number of asthma medications; as well as longitudinal decline in absolute FEV1. Year 15 serum adiponectin concentration was the predictor variable. Results: In a multivariable analysis of 411 eligible subjects, after adjusting for body mass index and covariates, higher serum adiponectin concentrations were associated with more frequent active disease (including more frequent use of any asthma medication), and greater number of respiratory symptoms and asthma medications among men but not among women with asthma (p for interactions between sex and adiponectin for all analyses < 0.05). Conclusions: Higher serum adiponectin concentrations may be independently associated with adverse clinical outcomes of asthma in men but not in women. If biological effect is confirmed in future studies, modification of systemic adiponectin concentrations may open up newer ways to treat asthma in men. PMID:22007173

  12. Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis

    PubMed Central

    Simmonds, Mark; Bryant, Maria; Sheldon, Trevor A; Tuffnell, Derek; Golder, Su; Dunne, Fidelma; Lawlor, Debbie A

    2016-01-01

    Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. Design Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials. Data sources Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts. Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome. Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools. Results 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of

  13. Factors influencing neurological outcome of children with bacterial meningitis at the emergency department.

    PubMed

    Bargui, Fatiha; D'Agostino, Irene; Mariani-Kurkdjian, Patricia; Alberti, Corinne; Doit, Catherine; Bellier, Nathalie; Morin, Laurence; Galli Gibertini, Giuliano; Smail, Assia; Zanin, Anna; Lorrot, Mathie; Dauger, Stéphane; Neve, Mathieu; Faye, Albert; Armoogum, Priscilla; Bourrillon, Antoine; Bingen, Edouard; Mercier, Jean-Christophe; Bonacorsi, Stéphane; Nigrovic, Lise E; Titomanlio, Luigi

    2012-09-01

    We performed a cohort study of children who survived bacterial meningitis after the neonatal period at a single pediatric center in France over a 10-year period (1995-2004) to identify predictors of death and long-term neurological deficits in children with bacterial meningitis. We performed multivariate regression to determine independent predictors of death and neurologic deficits. We identified 101 children with bacterial meningitis of which 19 died during initial hospitalization. Need for mechanical ventilation [hazard ratio (HR) 11.5, 95 % confidence interval (CI) 2.4-55.5)] and thrombocytopenia defined as a platelet count <150 × 10(9) per liter (HR 0.6, 95 % CI 0.4-0.9) at presentation were associated with death during initial hospitalization. At final assessment, 42 of the 70 survivors had no neurologic deficits identified; 20 had a single deficit, and eight had multiple deficits. A delay in initiation of antibiotics (HR 1.3, 95 % CI 1.1-1.7) and hydrocephalus on computed tomographic scan (HR 2.6, 95 % CI 1.1-6.0) were associated with having one or more long-term neurologic deficits. Identification of children at risk of death or long-term neurologic sequelae may allow therapeutic interventions to be directed to children at the highest risk.

  14. Long-term neurological complications associated with surgery and peripheral nerve blockade: outcomes after 1065 consecutive blocks.

    PubMed

    Watts, S A; Sharma, D J

    2007-02-01

    Peripheral nerve blockade is gaining popularity as an analgesic option for both upper or lower limb surgery. Published evidence supports the improved efficacy of regional techniques when compared to conventional opioid analgesia. The incidence of neurological deficit after surgery associated with peripheral nerve block is unclear. This paper reports on neurological outcomes occurring after 1065 consecutive peripheral nerve blocks over a one-year period from a single institution. All patients receiving peripheral nerve blocks for surgery were prospectively followed for up to 12 months to determine the incidence and probable cause of any persistent neurological deficit. Formal independent neurological review and testing was undertaken as indicated. Thirteen patients reported symptoms that warranted further investigation. A variety of probable causes were identified, with peripheral nerve block being implicated in two cases (one resolved at nine months and one remaining persistent). Overall incidence of block-related neuropathy was 0.22%. Persistent postoperative neuropathy is a rare but serious complication of surgery associated with peripheral nerve block. Formal follow-up of all such blocks is recommended to assess causality and allow for early intervention.

  15. Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes

    PubMed Central

    Vermillion, Meghan S.; Lei, Jun; Shabi, Yahya; Baxter, Victoria K.; Crilly, Nathan P.; McLane, Michael; Griffin, Diane E.; Pekosz, Andrew; Klein, Sabra L.; Burd, Irina

    2017-01-01

    Zika virus (ZIKV) crosses the placenta and causes congenital disease. Here we develop an animal model utilizing direct ZIKV inoculation into the uterine wall of pregnant, immunocompetent mice to evaluate transplacental transmission. Intrauterine inoculation at embryonic day (E) 10, but not E14, with African, Asian or American strains of ZIKV reduces fetal viability and increases infection of placental and fetal tissues. ZIKV inoculation at E10 causes placental inflammation, placental dysfunction and reduces neonatal brain cortical thickness, which is associated with increased activation of microglia. Viral antigen localizes in trophoblast and endothelial cells in the placenta, and endothelial, microglial and neural progenitor cells in the fetal brain. ZIKV infection of the placenta increases production of IFNβ and expression of IFN-stimulated genes 48 h after infection. This mouse model provides a platform for identifying factors at the maternal–fetal interface that contribute to adverse perinatal outcomes in a host with an intact immune system. PMID:28220786

  16. Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development.

    PubMed

    Christian, Lisa M

    2012-01-01

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

  17. Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes.

    PubMed

    Vermillion, Meghan S; Lei, Jun; Shabi, Yahya; Baxter, Victoria K; Crilly, Nathan P; McLane, Michael; Griffin, Diane E; Pekosz, Andrew; Klein, Sabra L; Burd, Irina

    2017-02-21

    Zika virus (ZIKV) crosses the placenta and causes congenital disease. Here we develop an animal model utilizing direct ZIKV inoculation into the uterine wall of pregnant, immunocompetent mice to evaluate transplacental transmission. Intrauterine inoculation at embryonic day (E) 10, but not E14, with African, Asian or American strains of ZIKV reduces fetal viability and increases infection of placental and fetal tissues. ZIKV inoculation at E10 causes placental inflammation, placental dysfunction and reduces neonatal brain cortical thickness, which is associated with increased activation of microglia. Viral antigen localizes in trophoblast and endothelial cells in the placenta, and endothelial, microglial and neural progenitor cells in the fetal brain. ZIKV infection of the placenta increases production of IFNβ and expression of IFN-stimulated genes 48 h after infection. This mouse model provides a platform for identifying factors at the maternal-fetal interface that contribute to adverse perinatal outcomes in a host with an intact immune system.

  18. 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.

  19. Adverse obstetric outcome in women with a history of infertility: a retrospective study.

    PubMed

    Yasmin, H; Hassan, I; Vanga, P; Subramanium, M; Adeghe, J H

    2006-01-01

    Women with a history of infertility are associated with a higher incidence of adverse pregnancy outcome. This retrospective study reviewed 105 women with a known history of infertility; of these 105 women, 77 (73%) conceived spontaneously and 28 (27%) had assisted conception. Our finding confirms higher perinatal complications; relative ratios (RR) for pre-eclampsia was 4.6 (95% CI=2.1-9.9), intrauterine growth restriction 4.8 (95% CI=1.9-12.0), gestational diabetes 1.8 (95% CI=0.5-5.8), pre-term premature rupture of membrane 2.3 (95% CI=0.6-8.8) and pre-term labour 2.6 (95% CI=1.1-5.9). We postulate that women with a history of infertility are at high risk of such obstetric complications and may benefit from intensified antenatal care.

  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.

  1. Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice

    PubMed Central

    Zhang, Zhaobin; Hu, Ying; Guo, Jilong; Yu, Tong; Sun, Libei; Xiao, Xuan; Zhu, Desheng; Nakanishi, Tsuyoshi; Hiromori, Youhei; Li, Junyu; Fan, Xiaolin; Wan, Yi; Cheng, Siyu; Li, Jun; Guo, Xuan; Hu, Jianying

    2017-01-01

    Bisphenol A (BPA) is used in the production of plastic but has oestrogenic activity. Therefore, BPA substitutes, such as fluorene-9-bisphenol (BHPF), have been introduced for the production of so-called ‘BPA-free' plastics. Here we show that BHPF is released from commercial ‘BPA-free' plastic bottles into drinking water and has anti-oestrogenic effects in mice. We demonstrate that BHPF has anti-oestrogenic activity in vitro and, in an uterotrophic assay in mice, induces low uterine weight, atrophic endometria and causes adverse pregnancy outcomes, even at doses lower than those of BPA for which no observed adverse effect have been reported. Female mice given water containing BHPF released from plastic bottles, have detectable levels of BHPF in serum, low uterine weights and show decreased expressions of oestrogen-responsive genes. We also detect BHPF in the plasma of 7/100 individuals, who regularly drink water from plastic bottles. Our data suggest that BPA substitutes should be tested for anti-oestrogenic activity and call for further study of the toxicological effects of BHPF on human health. PMID:28248286

  2. 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.

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

    PubMed Central

    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

  4. 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.

  5. Interactive associations of depression and sleep apnea with adverse clinical outcomes after acute myocardial infarction

    PubMed Central

    Hayano, Junichiro; Carney, Robert M.; Watanabe, Eiichi; Kawai, Kiyohiro; Kodama, Itsuo; Stein, Phyllis K.; Watkins, Lana L.; Freedland, Kenneth E.; Blumenthal, James A.

    2012-01-01

    Objective Depression and sleep apnea (SA) are common among patients after acute myocardial infarction (AMI), and both are associated with increased risk for adverse outcomes. We tested the hypothesis that there is an interaction between depression and SA in relation to prognosis in post-AMI patients. Methods Participants were 337 depressed and 379 nondepressed post-AMI patients who participated in a substudy of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial. SA was identified from Holter ECG at the entry by an algorithm that detects cyclic variation of heart rate. Results During a median follow-up of 25 months, 43 (6.0%) of patients died and 83 (11.6%) either died or experienced a recurrent AMI. Among 94 patients with both depression and SA, these endpoints occurred in 20 (21.3%) and 25 (26.6%), the prevalence that was 6.9 and 3.9 times higher than predicted probabilities by ENRICHD clinical risk scores (P <.001 for both). In the patients with depression alone, SA alone, or neither, the frequencies did not differ significantly from the predicted probability. Although both depression and SA predicted death and the combined endpoint, we observed depression by SA interactions (P = .03 and .02). SA independently predicted these endpoints in depressed (P <.001 and P = .001), but not in nondepressed patients (P = .73 and .84). Similarly, depression independently predicted these endpoints in SA (P <.001 for both), but not in non-SA patients (P = .61 and .12). Conclusion The combination of depression and SA estimated by CVHR is associated with long-term adverse clinical outcomes after AMI. PMID:23023681

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

    PubMed

    Tollånes, Mette Christophersen; Aarsand, Aasne Karine; Sandberg, Sverre

    2011-02-01

    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.

  7. 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.

  8. Neurological Outcomes after Human Umbilical Cord Patch for In Utero Spina Bifida Repair in a Sheep Model

    PubMed Central

    Papanna, Ramesha; Mann, Lovepreet K.; Snowise, Saul; Morales, Yisel; Prabhu, Sanjay P.; Tseng, Scheffer C. G.; Grill, Raymond; Fletcher, Stephen; Moise, Kenneth J.

    2016-01-01

    Objectives The objective of our study was to test the hypothesis that in utero repair of surgically created spina bifida in a sheep model using cryopreserved human umbilical cord (HUC) patch improves neurological outcome. Methods Spina bifida with myelotomy was surgically created in timed pregnant ewes at gestational day (GD) 75. The fetuses were randomly assigned to unrepaired versus HUC and treated at GD 95 and then delivered at GD 140. Neurological evaluation was performed using the Texas Spinal Cord Injury Scale (TSCIS), bladder control using ultrasound, and the hindbrain herniation. Results Three lambs without the spina bifida creation served as controls. There were four lambs with spina bifida: two were unrepaired and two underwent HUC repair. The control lambs had normal function. Both unrepaired lambs had nonhealed skin lesions with leakage of cerebrospinal fluid, a 0/20 TSCIS score, no bladder control, and the hindbrain herniation. In contrast, both HUC lambs had a completely healed skin defect and survived to day 2 of life, a 3/20 and 4/20 TSCIS score (nociception), partial bladder control, and normal hindbrain anatomy. Conclusions Cryopreserved HUC patch appears to improve survival and neurological outcome in this severe form of the ovine model of spina bifida. PMID:27621952

  9. 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

  10. Neurological presentation and long-term outcome following operative intervention in patients with meningocele manqué.

    PubMed

    Tubbs, R S; McGirt, M J; Warder, D E; Oakes, W J

    2003-06-01

    We review and describe the neurological presentation and long-term outcome of patients with meningocele manqué, and describe the dysraphic features associated with this entity. Our series of patients was collected over a 25-year period with a mean follow-up of 11.5 years. The mean age of presentation was 10.4 years and 72% of the patients presented with an abnormal neurological examination. At most recent follow-up, symptoms were stable, improved, and progressed in 47, 37 and 16%, respectively. Meningocele manqué was associated with focal hirsutism in 37% of the cases. These bands were primarily found in the lumbar spine and involved two sequential vertebral levels in 42% of cases. Sectioning of meningocele manqué has good long-term results in the majority of patients. These bands should be sought in the evaluation of patients with spinal dysraphism and surgically transected.

  11. 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

  12. Early Growth and Neurologic Outcomes of Infants with Probable Congenital Zika Virus Syndrome

    PubMed Central

    Ganz, Jucelia Sousa Santos; Sousa, Patricia da Silva; Doriqui, Maria Juliana Rodvalho; Ribeiro, Marizelia Rodrigues Costa; Branco, Maria dos Remédios Freitas Carvalho; Queiroz, Rejane Christine de Sousa; Pacheco, Maria de Jesus Torres; Vieira da Costa, Flavia Regina; Silva, Francelena de Sousa; Simões, Vanda Maria Ferreira; Pacheco, Marcos Antonio Barbosa; Lamy-Filho, Fernando; Lamy, Zeni Carvalho; Soares de Britto e Alves, Maria Teresa Seabra

    2016-01-01

    We report the early growth and neurologic findings of 48 infants in Brazil diagnosed with probable congenital Zika virus syndrome and followed to age 1–8 months. Most of these infants had microcephaly (86.7%) and craniofacial disproportion (95.8%). The clinical pattern included poor head growth with increasingly negative z-scores, pyramidal/extrapyramidal symptoms, and epilepsy. PMID:27767931

  13. 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.

  14. 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

  15. 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.

  16. A lifetime experience of violence and adverse reproductive outcomes: findings from population surveys in India.

    PubMed

    Yoshikawa, K; Agrawal, N R; Poudel, K C; Jimba, M

    2012-06-01

    Intimate partner violence (IPV) is a global public health issue that threatens the reproductive health of women. Despite a growing demand for research on the potential threat of IPV in relation to adverse reproductive outcomes, there have been no population-based studies of India. The current study analyzed the National Family Health Survey 3, which contained detailed information on types of violence in relation to the single question of pregnancy outcomes. The dataset was used to assess the association between a lifetime experience of IPV and terminated pregnancies among married Indian women. Multiple logistic regression analysis was then used to assess the association between these variables, controlling for socio-demographic characteristics. Results showed that 39.6% of Indian women have experienced violence by their husbands, while 18.3% of women have terminated a pregnancy during their lifetimes. The odds ratio of a terminated pregnancy among women who had experienced any type of partner violence was 1.62 (95% CI (confidence interval) = 1.51-1.73). All combinations of violence except a combination of emotional and sexual violence were associated with an increased risk of a terminated pregnancy. These results suggest that prevention of IPV would reduce the high incidence of terminated pregnancies, thus improving maternal health in India.

  17. Adverse maternal and perinatal outcomes in women with previous preeclampsia: a prospective study

    PubMed Central

    Bramham, Kate; Briley, Annette L.; Seed, Paul; Poston, Lucilla; Shennan, Andrew H.; Chappell, Lucy C.

    2011-01-01

    Objective The purpose of this study was to assess recurrence rates of preeclampsia and neonatal outcomes in women with a history of preeclampsia that required preterm delivery. Study Design Five hundred women with previous preeclampsia that required delivery at <37 weeks' gestation were followed prospectively. Results Preeclampsia reoccurred in 117 women (23%). Predictive factors included black (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.16–4.53) or Asian (OR, 2.98; 95% CI, 1.33–6.59) ethnicity, enrollment systolic blood pressure of >130 mm Hg (OR, 2.89; 95% CI, 1.52–5.50), current antihypertensive use (OR, 6.39; 95% CI, 2.38–17.16), and proteinuria of ≥2+ on enrollment urinalysis (OR, 12.35; 95% CI, 3.45–44.21). Women who previously delivered at <34 weeks' gestation were more likely to deliver preterm again (29% vs 17%; relative risk, 1.69; 95% CI, 1.19–2.40) than were those women with previous delivery between 34 and 37 weeks' gestation. Conclusion Although this study confirms that women with previous preeclampsia that required early delivery are at high risk of the development of preeclampsia, the study identifies risk factors for recurrence and illustrates that women with previous preeclampsia are at greater risk of adverse neonatal outcome. PMID:21457915

  18. 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

  19. 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

  20. Food insecurity is associated with adverse health outcomes among human infants and toddlers.

    PubMed

    Cook, John T; Frank, Deborah A; Berkowitz, Carol; Black, Maureen M; Casey, Patrick H; Cutts, Diana B; Meyers, Alan F; Zaldivar, Nieves; Skalicky, Anne; Levenson, Suzette; Heeren, Tim; Nord, Mark

    2004-06-01

    The U.S. Household Food Security Scale, developed with federal support for use in national surveys, is an effective research tool. This study uses these new measures to examine associations between food insecurity and health outcomes in young children. The purpose of this study was to determine whether household food insecurity is associated with adverse health outcomes in a sentinel population ages < or = 36 mo. We conducted a multisite retrospective cohort study with cross-sectional surveys at urban medical centers in 5 states and Washington DC, August 1998-December 2001. Caregivers of 11,539 children ages < or = 36 mo were interviewed at hospital clinics and emergency departments (ED) in central cities. Outcome measures included child's health status, hospitalization history, whether child was admitted to hospital on day of ED visit (for subsample interviewed in EDs), and a composite growth-risk variable. In this sample, 21.4% of households were food insecure (6.8% with hunger). In a logistic regression, after adjusting for confounders, food-insecure children had odds of "fair or poor" health nearly twice as great [adjusted odds ratio (AOR) = 1.90, 95% CI = 1.66-2.18], and odds of being hospitalized since birth almost a third larger (AOR = 1.31, 95% CI = 1.16-1.48) than food-secure children. A dose-response relation appeared between fair/poor health status and severity of food insecurity. Effect modification occurred between Food Stamps and food insecurity; Food Stamps attenuated (but did not eliminate) associations between food insecurity and fair/poor health. Food insecurity is associated with health problems for young, low-income children. Ensuring food security may reduce health problems, including the need for hospitalizations.

  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. Predicting adverse outcomes after myocardial infarction among patients with diabetes mellitus

    PubMed Central

    Arnold, Suzanne V.; Spertus, John A.; Jones, Philip G.; McGuire, Darren K.; Lipska, Kasia J.; Xu, Yaping; Stolker, Joshua M.; Goyal, Abhinav; Kosiborod, Mikhail

    2017-01-01

    Background Although patients with diabetes mellitus experience high rates of adverse events after acute myocardial infarction (AMI), including death and recurrent ischemia, some diabetic patients are likely at low risk, while others are at very high risk. We sought to develop prediction models to stratify risk after AMI in patients with diabetes. Methods and Results We developed prediction models for long-term mortality and angina among 1613 patients with diabetes discharged alive after AMI from 24 US hospitals and then validated the models in a separate, multi-center registry of 786 patients with diabetes. Event rates in the derivation cohort were 27% for 5-year mortality and 27% for 1-year angina. Parsimonious prediction models demonstrated good discrimination (c-indices=0.78 and 0.69, respectively) and excellent calibration. Within the context of the predictors we estimated, the strongest predictors for mortality were higher creatinine, not working at the time of the AMI, older age, lower hemoglobin, left ventricular dysfunction, and chronic heart failure. The strongest predictors for angina were angina burden in the 4 weeks prior to the AMI, younger age, history of prior coronary bypass graft surgery, and non-Caucasian race. The lowest and highest deciles of predicted risk ranged from 4–80% for mortality and 12–59% for angina. The models also performed well in external validation (c-indices=0.78 and 0.73, respectively). Conclusion We found a wide range of risk for adverse outcomes after AMI in diabetic patients. Predictive models can identify patients with diabetes for whom closer follow-up and aggressive secondary prevention strategies should be considered. PMID:27220369

  3. Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

    PubMed Central

    XUE, LI-XIA; ZHANG, TING; ZHAO, YU-WU; GENG, ZHI; CHEN, JING-JIONG; CHEN, HAO

    2016-01-01

    Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875. PMID:27168844

  4. Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke.

    PubMed

    Xue, Li-Xia; Zhang, Ting; Zhao, Yu-Wu; Geng, Zhi; Chen, Jing-Jiong; Chen, Hao

    2016-05-01

    Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875.

  5. Correlation of EEG, CT, and MRI Brain with Neurological Outcome at 12 Months in Term Newborns with Hypoxic Ischemic Encephalopathy

    PubMed Central

    Jose, Annu; Matthai, John; Paul, Sarah

    2013-01-01

    Objective: To correlate electroencephalogram (EEG), computed tomography (CT), and magnetic resonance imaging (MRI) brain with neurological outcome at 12 months in term neonates with hypoxic ischemic encephalopathy. Design: Prospective observational study. Setting: Neonatal intensive care unit (NICU) in a tertiary care teaching hospital. Materials and Methods: The study was conducted between June 2010 and November 2011. Consecutive term neonates with perinatal asphyxia and hypoxic ischemic encephalopathy were the subjects. All babies were managed as per standard protocol. EEG was done as soon as the baby was stable and CT brain within 7 days. MRI was done at 3 months. Neurodevelpmental assessment was done at 12 months. Results: Of the 31 babies, four died and one was lost to follow-up. Neurodevelopmental at 12 months of age was normal in 15 babies. EEG was normal in six babies and all of them had a normal neurodevelopment. Thirteen of the 14 babies with burst suppression pattern were abnormal (P<0.001). CT brain was normal in 14 and all of them had normal neurodevelopment (P<0.001), while 11 of the 12 with cerebral edema had abnormal outcome (P<0.001). Of the 16 babies with normal MRI, 14 were normal, while all six babies with abnormal signals in the cortex and thalamus had abnormal outcome (P=0.002). Conclusions: A normal EEG and CT brain in a term newborn with hypoxic ischemic encephalopathy (HIE) is associated with good neurological outcome. Burst suppression pattern in EEG, bleeds, or hypodensities in the CT and involvement of basal ganglia/thalamus in the MRI are predictors of abnormal outcome. PMID:24251256

  6. North-South Gradients in Adverse Birth Outcomes for First Nations and Others in Manitoba, Canada.

    PubMed

    Martens, Patricia J; Heaman, Maureen; Hart, Lyna; Wilkins, Russell; Smylie, Janet; Wassimi, Spogmai; Simonet, Fabienne; Wu, Yuquan; Fraser, William D; Luo, Zhong-Cheng

    2010-01-01

    OBJECTIVE: to determine the relationship of north-south place of residence to adverse birth outcomes among First Nations and non-First Nations in Manitoba, Canada, a setting with universal health insurance. STUDY DESIGN: Live birth records (n=151,472) for the province of Manitoba, Canada 1991-2000 were analyzed, including 25,743 First Nations and 125,729 non-First Nations infants. North-south and rural-urban residence was determined for each birth through geocoding. RESULTS: Comparing First Nations to non-First Nations, crude rates in North (and South) were: 7.0% versus 8.4% (9.3% versus 7.5%) for preterm birth; 6.1% versus 8.4% (8.7% versus 10.0%) for small-for-gestational-age birth, 4.2% versus 6.5% (6.2% versus 5.7%) for low birth weight, and 20.6% versus 13.7% (17.0% versus 11.0%) for large-for-gestational-age birth; and mortality per 1000 - neonatal 3.2 versus 6.2 (3.8 versus 3.3), post-neonatal 6.4 versus 6.4 (5.8 versus 1.5), and infant 9.5 versus 12.6 (9.6 versus 4.8). Adjusting for observed maternal and infant characteristics and rural versus urban residence, the North was high risk for large-for-gestational-age birth for both First Nations and non-First Nations. First Nations' risk of preterm, small-for-gestational-age and low birth weight was lowest in the North, but for non-First Nations, the North was lower only for small-for-gestational-age. First Nations mortality indicators were similar North to South, but for non-First Nations, the North was high risk. CONCLUSION: North-South place of residence does matter for adverse birth outcomes, but the effects may differ by ethnicity and could require different intervention strategies.

  7. Advancing Age and 30-Day Adverse Outcomes Following Non-Emergent General Surgical Operations

    PubMed Central

    Gajdos, Csaba; Kile, Deidre; Hawn, Mary T.; Finlayson, Emily; Henderson, William G.; Robinson, Thomas N.

    2014-01-01

    Background While some single center studies have demonstrated that major surgical operations are safe to perform in older adults, most multicenter database studies find advancing age to independently predict adverse postoperative outcomes. We hypothesized that thirty-day postoperative mortality, complications, failure to rescue rates and postoperative length of stay will increase with advancing age. Design Retrospective cohort study. Setting Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participants Patients undergoing non-emergent major general surgical operations between 2005 and 2008 were studied. Measures Postoperative outcomes of interest were complications occurring within 30 days of the index operation, return to OR within 30 days, failure to rescue after a postoperative complication, post-surgical length of stay and 30 day mortality. Results A total of 165,600 patients were studied. The rates of postoperative mortality, overall morbidity, and each type of postoperative complication increased as age increased. The rates of failure to rescue after each type of postoperative complication also increased with age. Mortality rates in patients ≥80 following renal insufficiency (43.3%), stroke (36.5%), myocardial infarction (35.6%), and pulmonary complications (25-39%) were particularly high. Median postoperative length of stay increased with age following surgical site infection, UTI, pneumonia, return to OR, and overall morbidity, but not after venous thromboembolism, stroke, myocardial infarction, renal insufficiency, failure to wean from the ventilator or reintubations. Conclusion Thirty-day mortality, complications and failure to rescue rates increase with advancing age following non-emergent general surgical operations. Patients over 80 years of age have especially high mortality following renal, cardiovascular, and pulmonary complications. As patient age advances, surgeons need to be

  8. Serum Lactate Predicts Adverse Outcomes in Emergency Department Patients With and Without Infection

    PubMed Central

    Oedorf, Kimie; Day, Danielle E.; Lior, Yotam; Novack, Victor; Sanchez, Leon D.; Wolfe, Richard E.; Kirkegaard, Hans; Shapiro, Nathan I.; Henning, Daniel J.

    2017-01-01

    Introduction Lactate levels are increasingly used to risk stratify emergency department (ED) patients with and without infection. Whether a serum lactate provides similar prognostic value across diseases is not fully elucidated. This study assesses the prognostic value of serum lactate in ED patients with and without infection to both report and compare relative predictive value across etiologies. Methods We conducted a prospective, observational study of ED patients displaying abnormal vital signs (AVS) (heart rate ≥130 bpm, respiratory rate ≥24 bpm, shock index ≥1, and/or systolic blood pressure <90 mmHg). The primary outcome, deterioration, was a composite of acute renal failure, non-elective intubation, vasopressor administration or in-hospital mortality. Results Of the 1,152 patients with AVS who were screened, 488 patients met the current study criteria: 34% deteriorated and 12.5% died. The deterioration rate was 88/342 (26%, 95% CI: 21 – 30%) for lactate < 2.5 mmol/L, 47/90 (52%, 42 – 63%) for lactate 2.5 – 4.0 mmol/L, and 33/46 (72%, 59 – 85%) for lactate >4.0mmol/L. Trended stratified lactate levels were associated with deterioration for both infected (p<0.01) and non-infected (p<0.01) patients. In the logistic regression models, lactate > 4mmol/L was an independent predictor of deterioration for patients with infection (OR 4.8, 95% CI: 1.7 – 14.1) and without infection (OR 4.4, 1.7 – 11.5). Conclusion Lactate levels can risk stratify patients with AVS who have increased risk of adverse outcomes regardless of infection status. PMID:28210362

  9. Unplanned Intensive Care Unit Admission following Elective Surgical Adverse Events: Incidence, Patient Characteristics, Preventability, and Outcome

    PubMed Central

    Meziane, Mohammed; El Jaouhari, Sidi Driss; ElKoundi, Abdelghafour; Bensghir, Mustapha; Baba, Hicham; Ahtil, Redouane; Aboulaala, Khalil; Balkhi, Hicham; Haimeur, Charki

    2017-01-01

    Context: Adverse events (AEs) are a persistent and an important reason for Intensive Care Unit (ICU) admission. They lead to death, disability at the time of discharge, unplanned ICU admission (UIA), and prolonged hospital stay. They impose large financial costs on health-care systems. Aims: This study aimed to determine the incidence, patient characteristics, type, preventability, and outcome of UIA following elective surgical AE. Settings and Design: This is a single-center prospective study. Methods: Analysis of 15,372 elective surgical procedures was performed. We defined UIA as an ICU admission that was not anticipated preoperatively but was due to an AE occurring within 5 days after elective surgery. Statistical Analysis: Descriptive analysis using SPSS software version 18 was used for statistical analysis. Results: There were 75 UIA (0.48%) recorded during the 2-year study period. The average age of patients was 54.64 ± 18.02 years. There was no sex predominance, and the majority of our patients had an American Society of Anesthesiologist classes 1 and 2. Nearly 29% of the UIA occurred after abdominal surgery and 22% after a trauma surgery. Regarding the causes of UIA, we observed that 44 UIA (58.7%) were related to surgical AE, 24 (32%) to anesthetic AE, and 7 (9.3%) to postoperative AE caused by care defects. Twenty-three UIA were judged as potentially preventable (30.7%). UIA was associated with negative outcomes, including increased use of ICU-specific interventions and high mortality rate (20%). Conclusions: Our analysis of UIA is a quality control exercise that helps identify high-risk patient groups and patterns of anesthesia or surgical care requiring improvement.

  10. Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma.

    PubMed

    Gibson, Christopher J; Lindsley, R Coleman; Tchekmedyian, Vatche; Mar, Brenton G; Shi, Jiantao; Jaiswal, Siddhartha; Bosworth, Alysia; Francisco, Liton; He, Jianbo; Bansal, Anita; Morgan, Elizabeth A; Lacasce, Ann S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric; Armand, Philippe; Alyea, Edwin P; Koreth, John; Ho, Vincent; Soiffer, Robert J; Antin, Joseph H; Ritz, Jerome; Nikiforow, Sarah; Forman, Stephen J; Michor, Franziska; Neuberg, Donna; Bhatia, Ravi; Bhatia, Smita; Ebert, Benjamin L

    2017-01-09

    Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. Methods We performed whole-exome sequencing on pre- and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010. We assessed the effect of CHIP at the time of ASCT on subsequent outcomes, including TMN, cause-specific mortality, and overall survival. Results For six of 12 patients in the exome sequencing cohort, mutations found in the TMN specimen were also detectable in the pre-ASCT specimen. In the targeted sequencing cohort, 120 patients (29.9%) had CHIP at the time of ASCT, which was associated with an increased rate of TMN (10-year cumulative incidence, 14.1% v 4.3% for those with and without CHIP, respectively; P = .002). Patients with CHIP had significantly inferior overall survival compared with those without CHIP (10-year overall survival, 30.4% v 60.9%, respectively; P < .001), including increased risk of death from TMN and cardiovascular disease. Conclusion In patients undergoing ASCT for lymphoma, CHIP at the time of transplantation is associated with inferior survival and increased risk of TMN.

  11. 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

  12. 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...

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

    PubMed Central

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

    2017-01-01

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

  14. Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP).

    PubMed

    Vietti, Giulia; Lison, Dominique; van den Brule, Sybille

    2016-02-29

    Several experimental studies have shown that carbon nanotubes (CNT) can induce respiratory effects, including lung fibrosis. The cellular and molecular events through which these effects develop are, however, not clearly elucidated. The purpose of the present review was to analyze the key events involved in the lung fibrotic reaction induced by CNT and to assess their relationships. We thus address current knowledge and gaps with a view to draft an Adverse Outcome Pathway (AOP) concerning the fibrotic potential of CNT.As for many inhaled particles, CNT can indirectly activate fibroblasts through the release of pro-inflammatory (IL-1β) and pro-fibrotic (PDGF and TGF-β) mediators by inflammatory cells (macrophages and epithelial cells) via the induction of oxidative stress, inflammasome or NF-kB. We also highlight here direct effects of CNT on fibroblasts, which appear as a new mode of toxicity relatively specific for CNT. Direct effects of CNT on fibroblasts include the induction of fibroblast proliferation, differentiation and collagen production via ERK 1/2 or Smad signaling. We also point out the physico-chemical properties of CNT important for their toxicity and the relationship between in vitro and in vivo effects. This knowledge provides evidence to draft an AOP for the fibrogenic activity of CNT, which allows developing simple in vitro models contributing to predict the CNT effects in lung fibrosis, and risk assessment tools for regulatory decision.

  15. 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.

  16. 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.

  17. Meconium-Associated Umbilical Vascular Myonecrosis: Correlations with Adverse Outcome and Placental Pathology.

    PubMed

    Cimic, Adela; Baergen, Rebecca N

    2016-01-01

    Intrauterine passage of meconium is common, occurring in approximately 10-15% of term births. Uncommonly, long-standing meconium exposure is associated with umbilical vascular myonecrosis, but few studies have evaluated specific clinical and pathologic features. This is a retrospective study of 481 term placentas: 139 with meconium-associated myonecrosis, 139 with meconium in fetal membranes, only 62 with meconium in the cord without myonecrosis, and 139 controls without meconium. We studied clinical factors, including clinical evidence of meconium discharge, fetal distress, APGAR scores, intrauterine growth restriction (IUGR), and intrauterine fetal demise (IUFD), and histologic factors, including acute chorioamnionitis, umbilical cord complications, uteroplacental malperfusion, fetal thrombosis, chorangiosis, and fetal nucleated red blood cells. Meconium myonecrosis was significantly associated with clinical meconium, fetal distress, IUGR, IUFD, acute chorioamnionitis, cord complications, fetal thrombosis, chorangiosis, and nucleated red blood cells when compared to controls (P < 0.05). Compared to cases with meconium in the membranes only, clinical meconium, fetal distress, IUGR, chorioamnionitis, thrombosis, chorangiosis, and nucleated red blood cells remained significant. Compared to cases with meconium in the cord without myonecrosis, only chorioamnionitis retained significance. In conclusion, myonecrosis was associated with adverse clinical outcome and placental lesions associated with hypoxia. Chorioamnionitis was significantly more common in all meconium groups compared to controls. As myonecrosis is an important lesion, a clinical history of meconium should trigger a meticulous search for meconium and specifically myonecrosis.

  18. SOCIOECONOMIC STATUS AND ADVERSE BIRTH OUTCOMES: A POPULATION-BASED CANADIAN SAMPLE.

    PubMed

    Campbell, Emily E; Gilliland, Jason; Dworatzek, Paula D N; De Vrijer, Barbra; Penava, Debbie; Seabrook, Jamie A

    2017-03-08

    This study assessed the strength of the association between socioeconomic status (SES) and low birth weight (LBW) and preterm birth (PTB) in Southwestern Ontario. Utilizing perinatal and neonatal databases at the London Health Science Centre, maternal postal codes were entered into a Geographic Information System to determine home neighbourhoods. Neighbourhoods were defined by dissemination areas (DAs). Median household income for each DA was extracted from the latest Canadian Census and linked to each mother. All singleton infants born between February 2009 and February 2014 were included. Of 26,654 live singleton births, 6.4% were LBW and 9.7% were PTB. Top risk factors for LBW were: maternal amphetamine use, chronic hypertension and maternal marijuana use (OR respectively: 17.51, 3.18, 2.72); previously diagnosed diabetes, maternal narcotic use and insulin-controlled gestational diabetes predicted PTB (OR respectively: 17.95, 2.69, 2.42). Overall, SES had little impact on adverse birth outcomes, although low maternal education increased the likelihood of a LBW neonate (OR: 1.01).

  19. 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

  20. Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol.

    PubMed

    Cosme, Madelyne M; Lister, Andrea L; Van Der Kraak, Glen

    2015-08-01

    This study determined the effects of the estrogen receptor agonist ethinylestradiol (EE2) and the phospholipase A2 inhibitor quinacrine (QUIN) on the pathways controlling follicular development, steroidogenesis, oocyte maturation, ovulation and spawning success in adult zebrafish. Both EE2 and QUIN inhibited spawning but did so through different mechanisms. EE2 affected follicular development (reduced ovarian size and reduction in the proportion of cortical alveolus, vitellogenic and mature follicle stages), steroidogenesis (reduced expression of aromatase), maturation (reduced luteinizing hormone receptor expression) and ovulation (reduced expression of cytosolic phospholipase A2 and the nuclear progesterone receptor). Although EE2 alters the proportion of follicle stages within the ovary, the downregulation of gene expression as a consequence of EE2 exposure was primarily due to a decline in expression of the genes of interest in vitellogenic and mature ovarian follicles. QUIN targeted ovulation via a reduction of the steroid 17α,20β dihydroxy-4-prenen-3-one (17α,20β-P) and decreased expression of the prostaglandin metabolizing enzyme cyclooxygenase 2. This study demonstrates the usefulness in defining the impacts of toxicants at the molecular and cellular, organ and whole organism level and how connections between these impacts can be used to describe the adverse outcome pathways (AOPs) that mediate toxicant action. Histological analysis and gene expression were effective tools in defining the AOPs of QUIN and EE2 while the measurement of reproductive hormones level did not provide much valuable information regarding the toxicant's mode of action.

  1. Change in Motor Function and Adverse Health Outcomes in Older African Americas

    PubMed Central

    Buchman, Aron S.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.; Barnes, Lisa L.

    2015-01-01

    Objective We tested whether declining motor function accelerates with age in older African Americans. Methods Eleven motor performances were assessed annually in 513 older African Americans. Results During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/yr (Estimate, −0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p’s <0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. Conclusions The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African Americans. PMID:26209439

  2. Risk of adverse pregnancy and perinatal outcomes after high technology infertility treatment: a comprehensive systematic review.

    PubMed

    Palomba, Stefano; Homburg, Roy; Santagni, Susanna; La Sala, Giovanni Battista; Orvieto, Raoul

    2016-11-04

    In the literature, there is growing evidence that subfertile patients who conceived after infertility treatments have an increased risk of pregnancy and perinatal complications and this is particularly true for patients who conceived through use of high technology infertility treatments. Moreover, high technology infertility treatments include many concomitant clinical and biological risk factors. This review aims to summarize in a systematic fashion the current evidence regarding the relative effect of the different procedures for high technology infertility treatments on the risk of adverse pregnancy and perinatal outcome. A literature search up to August 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar and an evidence-based hierarchy was used to determine which articles to include and analyze. Data on prepregnancy maternal factors, low technology interventions, specific procedures for male factor, ovarian tissue/ovary and uterus transplantation, and chromosomal abnormalities and malformations of the offspring were excluded. The available evidences were analyzed assessing the level and the quality of evidence according to the Oxford Centre for Evidence-Based Medicine guidelines and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. Current review highlights that every single procedure of high technology infertility treatments can play a crucial role in increasing the risk of pregnancy and perinatal complications. Due to the suboptimal level and quality of the current evidence, further well-designed studies are needed.

  3. 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

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

    PubMed

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

    2014-01-01

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

  5. 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

  6. 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.

  7. 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.

  8. Systemic effects of periodontitis: Lessons learned from research on atherosclerotic vascular disease and adverse pregnancy outcomes

    PubMed Central

    Papapanou, Panos N.

    2015-01-01

    Studies conducted over the past 25 years have focused on the role of periodontitis, an inflammatory condition of microbial etiology that destroys the tooth supporting tissues, as a systemic inflammatory stressor that can act as an independent risk factor of atherosclerotic vascular disease (AVSD) and adverse pregnancy outcomes (APOs). It has been suggested that periodontitis-associated bacteremias and systemic dissemination of inflammatory mediators produced in the periodontal tissues may result in systemic inflammation and endothelial dysfunction, while bacteria of oral origin may translocate into the feto-placental unit. Epidemiologic studies largely support an association between periodontitis and ASVD / APOs independent of known confounders; indeed, periodontitis has been shown to confer statistically significantly elevated risk for clinical events associated with ASVD and APOs in multivariable adjustments. On the other hand, intervention studies demonstrate that although periodontal therapy reduces systemic inflammation and improves endothelial function, it has no positive effect on the incidence of APOs. Studies of the effects of periodontal interventions on ASVD-related clinical events are lacking. This review summarizes key findings from mechanistic, association and intervention studies and attempts to reconcile the seemingly contradictory evidence that originates from different lines of investigation. PMID:26388299

  9. Paternal military service in Vietnam and the risk of late adverse pregnancy outcomes.

    PubMed Central

    Aschengrau, A; Monson, R R

    1990-01-01

    To investigate the relationship between paternal military service in Vietnam and the risk of late adverse pregnancy outcomes, we conducted a case-control study of women who delivered infants from August 1977 until March 1980 at Boston Hospital for Women. Paternal military service history among 857 congenital anomaly cases, 61 stillbirth cases, and 48 neonatal death cases were compared with that of 998 normal controls. Military service veterans were identified by crossmatching identifying information from obstetric records with state and national military records. After controlling for confounding variables, we found that the Vietnam veterans' relative risk of fathering an infant with one or more major malformations was 1.7 (95% CI = 0.8, 3.5) compared to non-Vietnam veterans. The increased risk was present in several organ systems and did not seem to be related to a particular type of defect. No associations or highly unstable associations were found between paternal military service in Vietnam and the occurrence of congenital anomalies overall, minor malformations, normal variants, stillbirths, and neonatal deaths. These findings should be viewed with caution since maternal and delivery characteristics appear to have contributed to the etiology of several of the major malformations among the Vietnam veterans' children. PMID:2400033

  10. Polynitroxyl albumin and albumin therapy after pediatric asphyxial cardiac arrest: effects on cerebral blood flow and neurologic outcome.

    PubMed

    Manole, Mioara D; Kochanek, Patrick M; Foley, Lesley M; Hitchens, T Kevin; Bayır, Hülya; Alexander, Henry; Garman, Robert; Ma, Li; Hsia, Carleton J C; Ho, Chien; Clark, Robert S B

    2012-03-01

    Postresuscitation cerebral blood flow (CBF) disturbances and generation of reactive oxygen species likely contribute to impaired neurologic outcome after pediatric cardiac arrest (CA). Hence, we determined the effects of the antioxidant colloid polynitroxyl albumin (PNA) versus albumin or normal saline (NS) on CBF and neurologic outcome after asphyxial CA in immature rats. We induced asphyxia for 9 minutes in male and female postnatal day 16 to 18 rats randomized to receive PNA, albumin, or NS at resuscitation from CA or sham surgery. Regional CBF was measured serially from 5 to 150 minutes after resuscitation by arterial spin-labeled magnetic resonance imaging. We assessed motor function (beam balance and inclined plane), spatial memory retention (water maze), and hippocampal neuronal survival. Polynitroxyl albumin reduced early hyperemia seen 5 minutes after CA. In contrast, albumin markedly increased and prolonged hyperemia. In the delayed period after resuscitation (90 to 150 minutes), CBF was comparable among groups. Both PNA- and albumin-treated rats performed better in the water maze versus NS after CA. This benefit was observed only in males. Hippocampal neuron survival was similar between injury groups. Treatment of immature rats with PNA or albumin resulted in divergent acute changes in CBF, but both improved spatial memory retention in males after asphyxial CA.

  11. 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

  12. 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

  13. Impact of Dispatcher‐Assisted Bystander Cardiopulmonary Resuscitation on Neurological Outcomes in Children With Out‐of‐Hospital Cardiac Arrests: A Prospective, Nationwide, Population‐Based Cohort Study

    PubMed Central

    Goto, Yoshikazu; Maeda, Tetsuo; Goto, Yumiko

    2014-01-01

    Background The impact of dispatcher‐assisted bystander cardiopulmonary resuscitation (CPR) on neurological outcomes in children is unclear. We investigated whether dispatcher‐assisted bystander CPR shows favorable neurological outcomes (Cerebral Performance Category scale 1 or 2) in children with out‐of‐hospital cardiac arrest (OHCA). Methods and Results Children (n=5009, age<18 years) with OHCA were selected from a nationwide Utstein‐style Japanese database (2008–2010) and divided into 3 groups: no bystander CPR (n=2287); bystander CPR with dispatcher instruction (n=2019); and bystander CPR without dispatcher instruction (n=703) groups. The primary endpoint was favorable neurological outcome at 1 month post‐OHCA. Dispatcher CPR instruction was offered to 53.9% of patients, significantly increasing bystander CPR provision rate (adjusted odds ratio [aOR], 7.51; 95% confidence interval [CI], 6.60 to 8.57). Bystander CPR with and without dispatcher instruction were significantly associated with improved 1‐month favorable neurological outcomes (aOR, 1.81 and 1.68; 95% CI, 1.24 to 2.67 and 1.07 to 2.62, respectively), compared to no bystander CPR. Conventional CPR was associated with increased odds of 1‐month favorable neurological outcomes irrespective of etiology of cardiac arrest (aOR, 2.30; 95% CI, 1.56 to 3.41). However, chest‐compression‐only CPR was not associated with 1‐month meaningful outcomes (aOR, 1.05; 95% CI, 0.67 to 1.64). Conclusions In children with OHCA, dispatcher‐assisted bystander CPR increased bystander CPR provision rate and was associated with improved 1‐month favorable neurological outcomes, compared to no bystander CPR. Conventional bystander CPR was associated with greater likelihood of neurologically intact survival, compared to chest‐compression‐only CPR, irrespective of cardiac arrest etiology. PMID:24785780

  14. 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 ...

  15. 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 ...

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

    EPA Science Inventory

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

  17. 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...

  18. 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...

  19. 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 ...

  20. 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...

  1. 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

  2. Comparison of admission random glucose, fasting glucose, and glycated hemoglobin in predicting the neurological outcome of acute ischemic stroke: a retrospective study

    PubMed Central

    Sung, Jia-Ying; Chen, Chin-I; Hsieh, Yi-Chen; Chen, Yih-Ru; Wu, Hsin-Chiao; Chan, Lung; Hu, Chaur-Jong; Hu, Han-Hwa; Chiou, Hung-Yi

    2017-01-01

    Background Hyperglycemia is a known predictor of negative outcomes in stroke. Several glycemic measures, including admission random glucose, fasting glucose, and glycated hemoglobin (HbA1c), have been associated with bad neurological outcomes in acute ischemic stroke, particularly in nondiabetic patients. However, the predictive power of these glycemic measures is yet to be investigated. Methods This retrospective study enrolled 484 patients with acute ischemic stroke from January 2009 to March 2013, and complete records of initial stroke severity, neurological outcomes at three months, and glycemic measures were evaluated. We examined the predictive power of admission random glucose, fasting glucose, and HbA1c for neurological outcomes in acute ischemic stroke. Furthermore, subgroup analyses of nondiabetic patients and patients with diabetes were performed separately. Results Receiver operating characteristic (ROC) analysis revealed that admission random glucose and fasting glucose were significant predictors of poor neurological outcomes, whereas HbA1c was not (areas under the ROC curve (AUCs): admission random glucose = 0.564, p = 0.026; fasting glucose = 0.598, p = 0.001; HbA1c = 0.510, p = 0.742). Subgroup analyses of nondiabetic patients and those with diabetes revealed that only fasting glucose predicts neurological outcomes in patients with diabetes, and the AUCs of these three glycemic measures did not differ between the two groups. A multivariate logistic regression analysis of the study patients indicated that only age, initial stroke severity, and fasting glucose were independent predictors of poor neurological outcomes, whereas admission random glucose and HbA1c were not (adjusted odds ratio: admission random glucose = 1.002, p = 0.228; fasting glucose = 1.005, p = 0.039; HbA1c = 1.160, p = 0.076). Furthermore, subgroup multivariate logistic regression analyses of nondiabetic patients and those with diabetes indicated that none of the three glycemic

  3. 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.

  4. 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

  5. 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

  6. Applying the skin sensitisation adverse outcome pathway (AOP) to quantitative risk assessment.

    PubMed

    Maxwell, Gavin; MacKay, Cameron; Cubberley, Richard; Davies, Michael; Gellatly, Nichola; Glavin, Stephen; Gouin, Todd; Jacquoilleot, Sandrine; Moore, Craig; Pendlington, Ruth; Saib, Ouarda; Sheffield, David; Stark, Richard; Summerfield, Vicki

    2014-02-01

    As documented in the recent OECD report 'the adverse outcome pathway for skin sensitisation initiated by covalent binding to proteins' (OECD, 2012), the chemical and biological events driving the induction of human skin sensitisation have been investigated for many years and are now well understood. Several non-animal test methods have been developed to predict sensitiser potential by measuring the impact of chemical sensitisers on these key events (Adler et al., 2011; Maxwell et al., 2011); however our ability to use these non-animal datasets for risk assessment decision-making (i.e. to establish a safe level of human exposure for a sensitising chemical) remains limited and a more mechanistic approach to data integration is required to address this challenge. Informed by our previous efforts to model the induction of skin sensitisation (Maxwell and MacKay, 2008) we are now developing two mathematical models ('total haptenated protein' model and 'CD8(+) T cell response' model) that will be linked to provide predictions of the human CD8(+) T cell response for a defined skin exposure to a sensitising chemical. Mathematical model development is underpinned by focussed clinical or human-relevant research activities designed to inform/challenge model predictions whilst also increasing our fundamental understanding of human skin sensitisation. With this approach, we aim to quantify the relationship between the dose of sensitiser applied to the skin and the extent of the hapten-specific T cell response that would result. Furthermore, by benchmarking our mathematical model predictions against clinical datasets (e.g. human diagnostic patch test data), instead of animal test data, we propose that this approach could represent a new paradigm for mechanistic toxicology.

  7. The adverse outcome pathway concept: A basis for developing regulatory decision-making tools.

    PubMed

    Delrue, Nathalie; Sachana, Magdalini; Sakuratani, Yuki; Gourmelon, Anne; Leinala, Eeva; Diderich, Robert

    2016-10-01

    The Adverse Outcome Pathway (AOP) concept is expected to guide risk assessors in their work to use all existing information on the effects of chemicals on humans and wildlife, and to target the generation of additional information to the regulatory objective. AOPs will therefore be used in the Organisation for Economic Co-operation and Development (OECD) chemical safety programme, as underlying scientific rationales for the development of alternative methods for hazard assessment, such as read-across, in vitro test methods or the development of integrated testing strategies that have the potential to replace animal tests. As a proof-of-concept, the OECD has developed an AOP for skin sensitisation, and as a follow-up has: a) implemented the AOP into the OECD QSAR Toolbox, so that information related to the Key Events (KEs) in the AOP can be used to group chemicals that are expected to act by the same mechanism and hence have the same skin sensitisation potential; b) developed alternative test methods for the KEs, so that ultimately chemicals can be tested for skin sensitisation without the use of animal tests. The development of integrated testing strategies based on the AOP is ongoing. Building on this proof-of-concept, the OECD has launched an AOP development programme with a first batch of AOPs published in 2016. A number of IT tools, which together form an AOP Knowledge Base, are at various stages of development, and support the construction of AOPs and their use in the development of integrated approaches for testing and assessment. Following the publication of the first batch of AOPs, OECD member countries will decide on priorities for their use in supporting the development of tools for regulatory use.

  8. 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

  9. The mechanisms of nickel toxicity in aquatic environments: an adverse outcome pathway analysis.

    PubMed

    Brix, Kevin V; Schlekat, Christian E; Garman, Emily R

    2016-12-09

    Current ecological risk assessment and water quality regulations for nickel (Ni) use mechanistically based, predictive tools such as biotic ligand models (BLMs). However, despite many detailed studies, the precise mechanism(s) of Ni toxicity to aquatic organisms remains elusive. This uncertainty in the mechanism(s) of action for Ni has led to concern over the use of tools like the BLM in some regulatory settings. To address this knowledge gap, the authors used an adverse outcome pathway (AOP) analysis, the first AOP for a metal, to identify multiple potential mechanisms of Ni toxicity and their interactions with freshwater aquatic organisms. The analysis considered potential mechanisms of action based on data from a wide range of organisms in aquatic and terrestrial environments on the premise that molecular initiating events for an essential metal would potentially be conserved across taxa. Through this analysis the authors identified 5 potential molecular initiating events by which Ni may exert toxicity on aquatic organisms: disruption of Ca(2+) homeostasis, disruption of Mg(2+) homeostasis, disruption of Fe(2+/3+) homeostasis, reactive oxygen species-induced oxidative damage, and an allergic-type response of respiratory epithelia. At the organ level of biological organization, these 5 potential molecular initiating events collapse into 3 potential pathways: reduced Ca(2+) availability to support formation of exoskeleton, shell, and bone for growth; impaired respiration; and cytotoxicity and tumor formation. At the level of the whole organism, the organ-level responses contribute to potential reductions in growth and reproduction and/or alterations in energy metabolism, with several potential feedback loops between each of the pathways. Overall, the present AOP analysis provides a robust framework for future directed studies on the mechanisms of Ni toxicity and for developing AOPs for other metals. Environ Toxicol Chem 2017;9999:1-10. © 2016 SETAC.

  10. Adverse Outcomes of Tacrolimus Withdrawal in Immune-Quiescent Kidney Transplant Recipients.

    PubMed

    Hricik, Donald E; Formica, Richard N; Nickerson, Peter; Rush, David; Fairchild, Robert L; Poggio, Emilio D; Gibson, Ian W; Wiebe, Chris; Tinckam, Kathryn; Bunnapradist, Suphamai; Samaniego-Picota, Milagros; Brennan, Daniel C; Schröppel, Bernd; Gaber, Osama; Armstrong, Brian; Ikle, David; Diop, Helena; Bridges, Nancy D; Heeger, Peter S

    2015-12-01

    Concerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor-reactive IFN-γ ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria.

  11. 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.

  12. Metabolomics for informing adverse outcome pathways: Androgen receptor activation and the pharmaceutical spironolactone.

    PubMed

    Davis, J M; Ekman, D R; Skelton, D M; LaLone, C A; Ankley, G T; Cavallin, J E; Villeneuve, D L; Collette, T W

    2017-03-01

    One objective in developing adverse outcome pathways (AOPs) is to connect biological changes that are relevant to risk assessors (i.e., fecundity) to molecular and cellular-level alterations that might be detectable at earlier stages of a chemical exposure. Here, we examined biochemical responses of fathead minnows (Pimephales promelas) to inform an AOP relevant to spironolactone's activation of the androgen receptor, as well as explore other biological impacts possibly unrelated to this receptor. Liquid chromatography with high resolution mass spectrometry (LC-MS) was used to measure changes in endogenous polar metabolites in livers of male and female fish that were exposed to five water concentrations of spironolactone (0, 0.05, 0.5, 5, or 50μgL(-1)) for 21days. Metabolite profiles were affected at the two highest concentrations (5 and 50μgL(-1)), but not in the lower-level exposures, which agreed with earlier reported results of reduced female fecundity and plasma vitellogenin (VTG) levels. We then applied partial least squares regression to assess whether metabolite alterations covaried with changes in fecundity, VTG gene expression and protein concentrations, and plasma 17β-estradiol and testosterone concentrations. Metabolite profiles significantly covaried with all measured endpoints in females, but only with plasma testosterone in males. Fecundity reductions occurred in parallel with changes in metabolites important in osmoregulation (e.g., betaine), membrane transport (e.g., l-carnitine), and biosynthesis of carnitine (e.g., methionine) and VTG (e.g., glutamate). Based on a network analysis program (i.e., mummichog), spironolactone also affected amino acid, tryptophan, and fatty acid metabolism. Thus, by identifying possible key events related to changes in biochemical pathways, this approach built upon an established AOP describing spironolactone's androgenic properties and highlighted broader implications potentially unrelated to androgen receptor

  13. 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

  14. 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

  15. Chlorination by-products (CBPs) in drinking water and adverse pregnancy outcomes in Italy.

    PubMed

    Aggazzotti, Gabriella; Righi, Elena; Fantuzzi, Guglielmina; Biasotti, Barbara; Ravera, Gianbattista; Kanitz, Stefano; Barbone, Fabio; Sansebastiano, Giuliano; Battaglia, Mario Alberto; Leoni, Valerio; Fabiani, Leila; Triassi, Maria; Sciacca, Salvatore

    2004-12-01

    Chlorination by-products (CBPs) in drinking water have been associated with an increased risk of adverse pregnancy outcomes, including small for gestational age at term (term-SGA) and preterm delivery. Epidemiological evidence is weakened by a generally inaccurate exposure assessment, often at an ecological level. A case control study with incident cases was performed in nine Italian towns between October 1999 and September 2000. A total of 1,194 subjects were enrolled: 343 preterm births (26th-37th not completed week of pregnancy), 239 term-SGA (from 37th completed week, and weight less than the lowest 10th percentile) and 612 controls. Exposure was assessed both by applying a questionnaire on mothers' personal habits during pregnancy and by water sampling directly at mothers' homes. Levels of trihalomethanes (THMs) were low (median: 1.10 microg l(-1)), while chlorite and chlorate concentrations were relatively high (median: 216.5 microg l(-1) for chlorites and 76.5 microg l(-1) for chlorates). Preterm birth showed no association with CBPs, while term-SGA, when chlorite levels > or =200 microg l(-1) combined with low and high levels of inhalation exposure are considered, suggested a dose-response relationship (adjusted-Odds Ratios (ORs): 1.52, 95%CI: 0.91-2.54 and 1.70, 95%CI: 0.97-3.0, respectively). A weak association with high exposure levels of either THMs (> or =30 microg l(-1)), or chlorite or chlorate (> or =200 microg l(-1)) was also found (adjusted-OR: 1.38, 95%CI: 0.92-2.07). Chlorine dioxide treatment is widespread in Italy; therefore, chlorite levels should be regularly and carefully monitored and their potential effects on pregnancy further evaluated and better understood.

  16. Adverse School Context Moderates the Outcomes of Selective Interventions for Aggressive Children

    ERIC Educational Resources Information Center

    Hughes, Jan N.; Cavell, Timothy A.; Meehan, Barbara T.; Zhang, Duan; Collie, Claire

    2005-01-01

    Drawing on social ecological theory and empirical studies on the role of school context in aggression, the authors argue that school adversity is an important consideration in choosing selective interventions for aggressive children. The moderating role of school adversity on intervention effectiveness is illustrated with data from a randomized…

  17. Clinical islet isolation and transplantation outcomes with deceased cardiac death donors are similar to neurological determination of death donors.

    PubMed

    Andres, Axel; Kin, Tatsuya; O'Gorman, Doug; Livingstone, Scott; Bigam, David; Kneteman, Norman; Senior, Peter; Shapiro, A M James

    2016-01-01

    In islet transplantation, deceased cardiac death (DCD) donation has been identified as a potential extended source. There are currently no studies comparing outcomes between these categories, and our goal was to compare islet isolation success rates and transplantation outcomes between DCD and neurological determination of death (NDD) donors. Islet isolations from 15 DCD and 418 NDD were performed in our centre between September 2008 and September 2014. Donor variables, islet yields, metabolic function of isolated isled and insulin requirements at 1-month post-transplant were compared. Compared to NDD, pancreata from DCD were more often procured locally and donors required less vasopressive support (P < 0.001 and P = 0.023, respectively), but the other variables were similar between groups. Pre- and postpurification islet yields were similar between NDD and DCD (576 vs. 608 × 10(3) islet equivalent, P = 0.628 and 386 vs. 379, P = 0.881, respectively). The metabolic function was similar between NDD and DCD, as well as the mean decrease in insulin requirement at 1-month post-transplantation (NDD: 64.82%; DCD: 60.17% reduction, P = 0.517). These results support the broader use of DCD pancreata for islet isolation. A much larger DCD islet experience will be required to truly determine noninferiority of both short- and long-term outcomes.

  18. CD47 deficiency improves neurological outcomes of traumatic brain injury in mice.

    PubMed

    Zhao, Song; Yu, Zhanyang; Liu, Yu; Bai, Yang; Jiang, Yinghua; van Leyen, Klaus; Yang, Yong-Guang; Lok, Josephine M; Whalen, Michael J; Lo, Eng H; Wang, Xiaoying

    2017-03-16

    CD47 is a receptor for signal-regulatory protein alpha (SIRPα) in self-recognition by the innate immune system, and a receptor of thrombospondin-1 (TSP-1) contributing to vascular impairment in response to stress. However, the roles of CD47 in traumatic brain injury (TBI) have not been investigated. In this study we aimed to test our hypothesis that CD47 mediates early neutrophil brain infiltration and late brain vascular remodeling after TBI. Mice were subjected to TBI using a controlled cortical impact (CCI) device. We examined early phase neutrophil infiltration, and late phase brain vessel density, pro-angiogenic markers VEGF and Ang-1 protein expression, neurological function deficits and lesion volumes for up to three weeks after TBI. Our results show that mice deficient in CD47 (CD47 Knockout) had significantly less brain neutrophil infiltration at 24h, upregulated VEGF expression in peri-lesion cortex at 7 and 14days, and increased blood vessel density at 21days after TBI, compared to wild type (WT) mice. CD47 knockout also significantly decreased sensorimotor function deficits and reduced brain lesion volume at 21days after TBI. We conclude that CD47 may play pathological roles in brain neutrophil infiltration, progression of brain tissue damage, impairment of cerebrovascular remodeling and functional recovery after TBI.

  19. Predictive validity of parent- and self-rated ADHD symptoms in adolescence on adverse socioeconomic and health outcomes.

    PubMed

    Du Rietz, Ebba; Kuja-Halkola, Ralf; Brikell, Isabell; Jangmo, Andreas; Sariaslan, Amir; Lichtenstein, Paul; Kuntsi, Jonna; Larsson, Henrik

    2017-02-10

    There is scarcity of research investigating the validity of self-report of attention deficit hyperactivity disorder (ADHD) symptoms compared to other informants, such as parents. This study aimed to compare the predictive associations of ADHD symptoms rated by parents and their children across adolescence on a range of adverse socioeconomic and health outcomes in early adulthood. Parent- and self-rated ADHD symptoms were assessed in 2960 individuals in early (13-14 years) and late adolescence (16-17 years). Logistic regression analyses were used to compare the associations between parent- and self-rated ADHD symptoms at both time points and adverse life outcomes in young adulthood obtained from Swedish national registries. Both parent- and self-ratings of ADHD symptoms were associated with increased risk for adverse outcomes, although associations of parent-ratings were more often statistically significant and were generally stronger (OR = 1.12-1.49, p < 0.05) than self-ratings (OR = 1.07-1.17, p < 0.05). After controlling for the other informant, parent-ratings of ADHD symptoms in both early and late adolescence significantly predicted academic and occupational failure, criminal convictions and traffic-related injuries, while self-ratings of ADHD symptoms only in late adolescence predicted substance use disorder and academic failure. Our findings suggest that both parent- and self-ratings of ADHD symptoms in adolescence provides valuable information on risk of future adverse socioeconomic and health outcomes, however, self-ratings are not valuable once parent-ratings have been taken into account in predicting most outcomes. Thus, clinicians and researchers should prioritize parent-ratings over self-ratings.

  20. Can the Assessment of Spontaneous Oscillations by Near Infrared Spectrophotometry Predict Neurological Outcome of Preterm Infants?

    PubMed

    Stammwitz, André; von Siebenthal, Kurt; Bucher, Hans U; Wolf, Martin

    2016-01-01

    The aim was to assess the correlation between cerebral autoregulation and outcome. Included were 31 preterm infants, gestational age 26 1/7 to 32 2/7 and <24 h life. Coherence between cerebral total haemoglobin (tHb) or oxygenation index (OI) measured by near-infrared spectrophotometry (NIRS) and systemic heart rate (HR) or arterial blood pressure (MAP) was calculated as a measure of autoregulation. In contrast to previous studies, low coherences in the first 24 h were significantly associated with intraventricular haemorrhage, death or abnormal neurodevelopmental outcome at 18 months or later. We suggest that our results can be explained by the concept of a multi-oscillatory-functions-order.

  1. Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes.

    PubMed

    Shaw, C A; Li, Y; Tomljenovic, L

    2013-11-01

    Our previous ecological studies of autism spectrum disorder (ASD) has demonstrated a correlation between increasing ASD rates and aluminium (Al) adjuvants in common use in paediatric vaccines in several Western countries. The correlation between ASD rate and Al adjuvant amounts appears to be dose-dependent and satisfies 8 of 9 Hill criteria for causality. We have now sought to provide an animal model to explore potential behavioural phenotypes and central nervous system (CNS) alterations using s.c. injections of Al hydroxide in early postnatal CD-1 mice of both sexes. Injections of a "high" and "low" Al adjuvant levels were designed to correlate to either the U.S. or Scandinavian paediatric vaccine schedules vs. control saline-injected mice. Both male and female mice in the "high Al" group showed significant weight gains following treatment up to sacrifice at 6 months of age. Male mice in the "high Al" group showed significant changes in light-dark box tests and in various measures of behaviour in an open field. Female mice showed significant changes in the light-dark box at both doses, but no significant changes in open field behaviours. These current data implicate Al injected in early postnatal life in some CNS alterations that may be relevant for a better understanding of the aetiology of ASD.

  2. A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes

    PubMed Central

    Foo, K; Cooper, J; Deaner, A; Knight, C; Suliman, A; Ranjadayalan, K; Timmis, A D

    2003-01-01

    Objectives: To analyse the relation between serum glucose concentration and hospital outcome across the whole spectrum of acute coronary syndromes. Methods: This was a prospective cohort study of 2127 patients presenting with acute coronary syndromes. The patients were stratified into quartile groups (Q1 to Q4) defined by serum glucose concentrations of 5.8, 7.2, and 10.0 mmol/l. The relation between quartile group and major in-hospital complications was analysed. Results: The proportion of patients with acute myocardial infarction increased incrementally across the quartile groups, from 21.4% in Q1 to 47.9% in Q4 (p < 0.0001). The trend for frequency of in-hospital major complications was similar, particularly left ventricular failure (LVF) (Q1 6.4%, Q4 25.2%, p < 0.0001) and cardiac death (Q1 0.7%, Q4 6.1%, p < 0.0001). The relations were linear, each glucose quartile increment being associated with an odds ratio of 1.46 (95% confidence interval (CI) 1.27 to 1.70) for LVF and 1.52 (95% CI 1.17 to 1.97) for cardiac death. Although complication rates were higher for a discharge diagnosis of acute myocardial infarction than for unstable angina, there was no evidence that the effects of serum glucose concentration were different for the two groups, there being no significant interaction with discharge diagnosis in the associations between glucose quartile and LVF (p = 0.69) or cardiac death (p = 0.17). Similarly there was no significant interaction with diabetic status in the associations between glucose quartile and LVF (p = 0.08) or cardiac death (p = 0.09). Conclusion: Admission glycaemia stratified patients with acute coronary syndromes according to their risk of in-hospital LVF and cardiac mortality. There was no detectable glycaemic threshold for these adverse effects. The prognostic correlates of admission glycaemia were unaffected by diabetic status and did not differ significantly between patients with acute myocardial infarction and those with unstable

  3. 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...

  4. 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...

  5. 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.

  6. The effect of maternal pravastatin therapy on adverse sensorimotor outcomes of the offspring in a murine model of preeclampsia.

    PubMed

    Carver, Alissa R; Tamayo, Esther; Perez-Polo, J Regino; Saade, George R; Hankins, Gary D V; Costantine, Maged M

    2014-04-01

    Animal and human studies show that in-utero exposure to preeclampsia alters fetal programming and results in long-term adverse cardiovascular outcomes in the offspring. Human epidemiologic data also suggest that offspring born to preeclamptic mothers are also at risk of adverse long term neurodevelopmental outcomes. Pravastatin, a hydrophilic lipid-lowering drug with pleiotropic properties, was found to prevent the altered cardiovascular phenotype of preeclampsia and restore fetal growth in animal models, providing biological plausibility for its use as a preventive agent for preeclampsia. In this study, we used a murine model of preeclampsia based on adenovirus over-expression of the anti-angiogenic factor soluble Fms-like tyrosine kinase 1, and demonstrated that adult offspring born to preeclamptic dams perform poorly on assays testing vestibular function, balance, and coordination, and that prenatal pravastatin treatment prevents impairment of fetal programming.

  7. Renal systolic time intervals derived from intra-renal artery Doppler as a novel predictor of adverse cardiac outcomes

    PubMed Central

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

    2017-01-01

    The aim of this study was to evaluate the use of renal systolic time intervals measured by electrocardiographic gated Doppler ultrasonography for predicting adverse cardiac events. This longitudinal observation study enrolled 205 patients. Renal systolic time intervals, including pre-ejection period (PEP) and ejection time (ET), and ratio of renal PEP to ET, were measured by electrocardiographic gated Doppler ultrasound. The 14 adverse cardiac events identified in this population included 9 cardiac deaths and 5 hospitalizations for heart failure during an average follow up of 30.9 months (25th–75th percentile: 30–33 months). Renal PEP (hazard ratio = 1.023, P = 0.001), renal ET (hazard ratio = 0.975, P = 0.001) and renal PEP/ET (per 0.01 unit increase, hazard ratio = 1.060, P < 0.001) were associated with poor cardiac outcomes. The addition of renal PEP/ET to a Cox model containing important clinical variables and renal resistive index further improved the value in predicting adverse cardiac events (Chi-square increase, 9.996; P = 0.002). This study showed that parameters of intra-renal hemodynamics were potential predictors of adverse cardiac outcomes. However, the generalizability of these indicators need to be investigated in future large-scale studies. PMID:28266644

  8. Risk of adverse pregnancy outcome in women exposed to livestock: a study within the Danish National Birth Cohort.

    PubMed

    Nielsen, S Y; Henriksen, T B; Hjøllund, N H; Mølbak, K; Andersen, A M N

    2014-07-01

    Maternal infection in pregnancy is a known risk factor for adverse pregnancy outcome, and a number of zoonotic pathogens may constitute a risk to pregnant women and their fetuses. With animal contact as a proxy for the risk of zoonotic infection, this study aimed to evaluate pregnancy outcome in women with self-reported occupational or domestic contact with livestock compared to pregnant women without such contact. The Danish National Birth Cohort collected information on pregnancy outcome from 100 418 pregnant women (1996-2002) from which three study populations with occupational and/or domestic exposure to livestock and a reference group of women with no animal contact was sampled. Outcome measures were miscarriage, very preterm birth (before gestational week 32), preterm birth (before 37 gestational weeks), small for gestational age (SGA), and perinatal death. Adverse reproductive outcomes were assessed in four different exposure groups of women with occupational or domestic exposure to livestock with no association found between exposure to livestock and miscarriage, preterm birth, SGA or perinatal death. These findings should diminish general occupational health concerns for pregnant women with exposures to a range of different farm animals.

  9. Nutritional indicators of adverse pregnancy outcomes and mother-to-child transmission of HIV among HIV-infected women2

    PubMed Central

    Mehta, Saurabh; Manji, Karim P; Young, Alicia M; Brown, Elizabeth R; Chasela, Charles; Taha, Taha E; Read, Jennifer S; Goldenberg, Robert L; Fawzi, Wafaie W

    2008-01-01

    Background Poor nutrition may be associated with mother-to-child transmission (MTCT) of HIV and other adverse pregnancy outcomes. Objective The objective was to examine the relation of nutritional indicators with adverse pregnancy outcomes among HIV-infected women in Tanzania, Zambia, and Malawi. Design Body mass index (BMI; in kg/m2) and hemoglobin concentrations at enrollment and weight change during pregnancy were prospectively related to fetal loss, neonatal death, low birth weight, preterm birth, and MTCT of HIV. Results In a multivariate analysis, having a BMI < 21.8 was significantly associated with preterm birth [odds ratio (OR): 1.82; 95% CI: 1.34, 2.46] and low birth weight (OR: 2.09; 95% CI: 1.41, 3.08). A U-shaped relation between weight change during pregnancy and preterm birth was observed. Severe anemia was significantly associated with fetal loss or stillbirth (OR: 3.67; 95% CI: 1.16, 11.66), preterm birth (OR: 2.08; 95% CI: 1.39, 3.10), low birth weight (OR: 1.76; 95% CI: 1.07, 2.90), and MTCT of HIV by the time of birth (OR: 2.26; 95% CI: 1.18, 4.34) and by 4−6 wk among those negative at birth (OR: 2.33; 95% CI: 1.15, 4.73). Conclusions Anemia, poor weight gain during pregnancy, and low BMI in HIV-infected pregnant women are associated with increased risks of adverse infant outcomes and MTCT of HIV. Interventions that reduce the risk of wasting or anemia during pregnancy should be evaluated to determine their possible effect on the incidence of adverse pregnancy outcomes and MTCT of HIV. PMID:18541551

  10. Intersections of poverty, race/ethnicity, and sex: alcohol consumption and adverse outcomes in the United States.

    PubMed

    Glass, Joseph E; Rathouz, Paul J; Gattis, Maurice; Joo, Young Sun; Nelson, Jennifer C; Williams, Emily C

    2017-03-27

    We examine whether intersectionality theory-which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic-can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the US Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption.

  11. Clinical Predictors of Neurological Outcome within 72 h after Traumatic Cervical Spinal Cord Injury

    PubMed Central

    Qiu, Zhi; Wang, Fangyong; Hong, Yi; Zhang, Junwei; Tang, Hehu; Li, Xiang; Jiang, Shudong; Lv, Zhen; Liu, Shujia; Chen, Shizheng; Liu, Jiesheng

    2016-01-01

    To investigate the prognostic values of clinical factors 72 h within traumatic cervical spinal cord injury (TCSCI). Data were extracted from the medical materials of 57 TCSCI cases. AIS was used as the outcome measure and divided into dichotomous variables by two methods, i.e. “complete(AIS = A)/incomplete(AIS ≠ A) SCI” and “motor complete(AIS = A or B)/incomplete(AIS ≠ A and B) SCI”. Relationships between evaluated factors and outcomes were investigated by univariate and multivariate methods. MRI Cord transection (MCT) cases, most significantly related to complete SCIs by univariate analysis (P = 0.006), all showed complete SCIs when discharged, which makes it unsuitable for logistic regression. With MCT cases removed, univariate analysis was conducted again, then logistic regression. At last, only C5 spine injury (P = 0.024, OR = 0.241) was related to complete SCI. Cases with compression flexion injury mechanism (CFIM), most significantly related to motor complete SCIs by univariate analysis (P = 0.001), was also unsuitable for logistic regression for the same reason. At last, C3 spine injury (P = 0.033, OR = 0.068) and high energy injury (P = 0.033, OR = 14.763) were related to motor complete SCIs with CFIM cases removed. The results show that MCT and C5 spine injury are good predictors for complete/incomplete SCIs. CFIM, C3 spine injury and high energy injury are good predictors for motor complete/incomplete SCIs. PMID:27941855

  12. Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

    PubMed Central

    2012-01-01

    Background Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention. Methods Using a collection of reviews identified previously, 166 references including a meta-analysis were selected for review. At least one of the primary outcomes in each review was an adverse or unintended event. The nature of the intervention, source of funding, number of individual meta-analyses performed, number of primary studies included in the review, and use of meta-analytic methods were all recorded. Specific areas of interest relating to the methods used included the choice of outcome metric, methods of dealing with sparse events, heterogeneity, publication bias and use of individual patient data. Results The 166 included reviews were published between 1994 and 2006. Interventions included drugs and surgery among other interventions. Many of the references being reviewed included multiple meta-analyses with 44.6% (74/166) including more than ten. Randomised trials only were included in 42.2% of meta-analyses (70/166), observational studies only in 33.7% (56/166) and a mix of observational studies and trials in 15.7% (26/166). Sparse data, in the form of zero events in one or both arms where the outcome was a count of events, was found in 64 reviews of two-arm studies, of which 41 (64.1%) had zero events in both arms. Conclusions Meta-analyses of adverse events data are common and useful in terms of increasing the power to

  13. Circulating angiogenic factors are related to the severity of gestational hypertension and preeclampsia, and their adverse outcomes.

    PubMed

    Leaños-Miranda, Alfredo; Méndez-Aguilar, Francisco; Ramírez-Valenzuela, Karla Leticia; Serrano-Rodríguez, Marilyn; Berumen-Lechuga, Guadalupe; Molina-Pérez, Carlos José; Isordia-Salas, Irma; Campos-Galicia, Inova

    2017-01-01

    Gestational hypertension (GH) and preeclampsia (PE) are characterized by an imbalance in angiogenic factors. However, the relationship among these factors with the severity of hypertensive disorders of pregnancy (HDP) and adverse outcomes are not fully elucidated. We examined whether these biomarkers are related with the severity of HDP and adverse outcomes.Using a cross-sectional design, serum concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin were determined in 764 pregnant women: 75 healthy pregnant, 83 with mild GH (mGH), 105 with severe GH (sGH), 122 with mild PE (mPE), and 379 with severe PE (sPE).All angiogenic factors' concentrations were significantly different (P ≤ 0.041) in HDP than in healthy pregnancy. In addition, these factors were markedly different in sPE than in mPE, sGH, or mGH (P ≤ 0.027) and in patients with sGH that in those with mPE or mGH (P < 0.05). As compared to mGH and mPE, patients with sGH and sPE had higher rates of both preterm delivery at <34 weeks of gestation and small-for-gestational age infants. Moreover, patients with sPE had higher rates of adverse maternal outcomes (P < 0.001) when compared to patients with mGH, sGH, or mPE. In all cases, levels of sFlt-1/PlGF ratio were significantly higher in patients with sGH and sPE who had adverse perinatal and maternal outcomes than in those with sGH and sPE who did not (P ≤ 0.016).Circulating concentrations of angiogenic factors appear to be suitable markers to assess the severity of GH and PE, and adverse outcomes.

  14. Circulating angiogenic factors are related to the severity of gestational hypertension and preeclampsia, and their adverse outcomes

    PubMed Central

    Leaños-Miranda, Alfredo; Méndez-Aguilar, Francisco; Ramírez-Valenzuela, Karla Leticia; Serrano-Rodríguez, Marilyn; Berumen-Lechuga, Guadalupe; Molina-Pérez, Carlos José; Isordia-Salas, Irma; Campos-Galicia, Inova

    2017-01-01

    Abstract Gestational hypertension (GH) and preeclampsia (PE) are characterized by an imbalance in angiogenic factors. However, the relationship among these factors with the severity of hypertensive disorders of pregnancy (HDP) and adverse outcomes are not fully elucidated. We examined whether these biomarkers are related with the severity of HDP and adverse outcomes. Using a cross-sectional design, serum concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin were determined in 764 pregnant women: 75 healthy pregnant, 83 with mild GH (mGH), 105 with severe GH (sGH), 122 with mild PE (mPE), and 379 with severe PE (sPE). All angiogenic factors’ concentrations were significantly different (P ≤ 0.041) in HDP than in healthy pregnancy. In addition, these factors were markedly different in sPE than in mPE, sGH, or mGH (P ≤ 0.027) and in patients with sGH that in those with mPE or mGH (P < 0.05). As compared to mGH and mPE, patients with sGH and sPE had higher rates of both preterm delivery at <34 weeks of gestation and small-for-gestational age infants. Moreover, patients with sPE had higher rates of adverse maternal outcomes (P < 0.001) when compared to patients with mGH, sGH, or mPE. In all cases, levels of sFlt-1/PlGF ratio were significantly higher in patients with sGH and sPE who had adverse perinatal and maternal outcomes than in those with sGH and sPE who did not (P ≤ 0.016). Circulating concentrations of angiogenic factors appear to be suitable markers to assess the severity of GH and PE, and adverse outcomes. PMID:28121958

  15. Association between Intimate Partner Violence during Pregnancy and Adverse Pregnancy Outcomes in Vietnam: A Prospective Cohort Study

    PubMed Central

    Van, Toan Ngo; Gammeltoft, Tine; W. Meyrowitsch, Dan; Nguyen Thi Thuy, Hanh; Rasch, Vibeke

    2016-01-01

    Background Violence against pregnant women is an increasing public health concern particularly in low- and middle-income countries. The purpose of this study was to measure the association between intimate partner violence (IPV) during pregnancy and the risk of adverse birth outcomes. Methods Prospective cohort study of 1276 pregnant women in Dong Anh district, Vietnam. Women with gestational age less than 24 weeks were enrolled and interviewed. Repeated interviews were performed at 30–34 weeks gestation to assess experience of IPV during pregnancy and again 48 hours post-delivery to assess the birth outcome including birth weight and gestational age at delivery. Results There was a statistically significant association between exposure to physical violence during pregnancy and preterm birth (PTB) or low birth weight (LBW). After adjustment for age, education, occupation, body mass index (BMI), haemoglobin level, previous adverse pregnancy outcomes, the pregnant women who were exposed to physical violence during pregnancy were five times more likely to have PTB (AOR = 5.5; 95%CI: 2.1–14.1) and were nearly six times more likely to give birth to a child of LBW (AOR = 5.7; 95%CI: 2.2–14.9) as compared to those who were not exposed to physical violence. Conclusion Exposure to IPV during pregnancy increases the risk of PTB and LBW. Case-finding for violence in relation to antenatal care may help protect pregnant women and improve pregnancy outcomes. PMID:27631968

  16. 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.

  17. Early-Stage Hyperoxia Is Associated with Favorable Neurological Outcomes and Survival after Severe Traumatic Brain Injury: A Post-Hoc Analysis of the Brain Hypothermia Study.

    PubMed

    Fujita, Motoki; Oda, Yasutaka; Yamashita, Susumu; Kaneda, Kotaro; Kaneko, Tadashi; Suehiro, Eiichi; Dohi, Kenji; Kuroda, Yasuhiro; Kobata, Hitoshi; Tsuruta, Ryosuke; Maekawa, Tsuyoshi

    2017-01-19

    The effects of hyperoxia on the neurological outcomes of patients with severe traumatic brain injury (TBI) are still controversial. We examined whether the partial pressure of arterial oxygen (PaO2) and hyperoxia were associated with neurological outcomes and survival by conducting post-hoc analyses of the Brain Hypothermia (B-HYPO) study, a multi-center randomized controlled trial of mild therapeutic hypothermia for severe TBI. The differences in PaO2 and PaO2/fraction of inspiratory oxygen (P/F) ratio on the 1st day of admission were compared between patients with favorable (n = 64) and unfavorable (n = 65) neurological outcomes and between survivors (n = 90) and deceased patients (n = 39). PaO2 and the P/F ratio were significantly greater in patients with favorable outcomes than in patients with unfavorable neurological outcomes (PaO2: 252 ± 122 vs. 202 ± 87 mm Hg, respectively, p = 0.008; P/F ratio: 455 ± 171 vs. 389 ± 155, respectively, p = 0.022) and in survivors than in deceased patients (PaO2: 242 ± 117 vs. 193 ± 75 mm Hg, respectively, p = 0.005; P/F ratio: 445 ± 171 vs. 370 ± 141, respectively, p = 0.018). Similar tendencies were observed in subgroup analyses in patients with fever control and therapeutic hypothermia, and in patients with an evacuated mass or other lesions (unevacuated lesions). PaO2 was independently associated with survival (odds ratio 1.008, p = 0.037). These results suggested that early-stage hyperoxia might be associated with favorable neurological outcomes and survival following severe TBI.

  18. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    PubMed Central

    Wurst, Keele E.; Zedler, Barbara K.; Joyce, Andrew R.; Sasinowski, Maciek; Murrelle, E. Lenn

    2016-01-01

    BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment

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

    EPA Science Inventory

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

  20. Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results

    PubMed Central

    Starke, Robert M.; Wang, Tony; Ding, Dale; Durst, Christopher R.; Crowley, R. Webster; Chalouhi, Nohra; Hasan, David M.; Dumont, Aaron S.; Jabbour, Pascal; Liu, Kenneth C.

    2015-01-01

    Introduction. Idiopathic intracranial hypertension (IIH) may result in a chronic debilitating disease. Dural venous sinus stenosis with a physiologic venous pressure gradient has been identified as a potential etiology in a number of IIH patients. Intracranial venous stenting has emerged as a potential treatment alternative. Methods. A systematic review was carried out to identify studies employing venous stenting for IIH. Results. From 2002 to 2014, 17 studies comprising 185 patients who underwent 221 stenting procedures were reported. Mean prestent pressure gradient was 20.1 mmHg (95% CI 19.4–20.7 mmHg) with a mean poststent gradient of 4.4 mmHg (95% CI 3.5–5.2 mmHg). Complications occurred in 10 patients (5.4%; 95% CI 4.7–5.4%) but were major in only 3 (1.6%). At a mean clinical follow-up of 22 months, clinical improvement was noted in 130 of 166 patients with headaches (78.3%; 95% CI 75.8–80.8%), 84 of 89 patients with papilledema (94.4%; 95% CI 92.1–96.6%), and 64 of 74 patients with visual symptoms (86.5%; 95% CI 83.0–89.9%). In-stent stenosis was noted in six patients (3.4%; 95% CI 2.5–4.3%) and stent-adjacent stenosis occurred in 19 patients (11.4%; 95% CI 10.4–12.4), resulting in restenting in 10 patients. Conclusion. In IIH patients with venous sinus stenosis and a physiologic pressure gradient, venous stenting appears to be a safe and effective therapeutic option. Further studies are necessary to determine the long-term outcomes and the optimal management of medically refractory IIH. PMID:26146651

  1. 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…

  2. A review of nitrates in drinking water: maternal exposure and adverse reproductive and developmental outcomes.

    PubMed

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

    2007-01-01

    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 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. 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. 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.

  3. 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 ...

  4. 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...

  5. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    PubMed

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values < 0.05). For every reduction of 5% in left ventricular ejection fraction induced by mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  6. Associations between maternal serum free beta human chorionic gonadotropin (β-hCG) levels and adverse pregnancy outcomes.

    PubMed

    Sirikunalai, P; Wanapirak, C; Sirichotiyakul, S; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K; Tongsong, T

    2016-01-01

    The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low β-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

  7. Risks of adverse pregnancy outcomes among Inuit and North American Indian women in Quebec, 1985-97.

    PubMed

    Luo, Zhong-Cheng; Wilkins, Russell; Platt, Robert W; Kramer, Michael S

    2004-01-01

    We used Statistics Canada's linked stillbirth, live birth and infant death files to assess the risks of adverse pregnancy outcomes among Inuit and North American Indian vs. other ethnic women in Quebec, 1985-97 (1 125 462 singleton births). Mother tongue was used to define ethnicity, with the largest French language group as the reference. Main outcome measures are adjusted odds ratios (AOR) for preterm birth, small-for-gestational-age (SGA), stillbirth, neonatal and postneonatal death controlled for maternal age, education, marital status, parity, infant sex, community size, and community-level random effects using multilevel logit models. Inuit women had higher risks of preterm birth (AOR = 1.49, 95% CI [1.25, 1.78]) and immaturity-related infant mortality (AOR = 3.03 [1.36, 6.74]), while Indian women did not. Infants of Inuit (AOR = 0.39 [0.31, 0.49]) and Indian (AOR = 0.27 [0.24, 0.31]) women had substantially lower risks of SGA. Elevated risks of stillbirth were observed among Indian women [AOR = 1.53 (1.09, 2.15)], and of postneonatal death among both Inuit (AOR = 4.45 [2.74, 7.22]) and Indian (AOR = 1.86 [1.28, 2.70]) infants. Both Inuit and Indian infants had much higher risks of sudden infant death syndrome (SIDS) and infection-related mortality. Although the absolute risks of adverse outcomes declined from 1985-87 to 1995-97, the relative disparities between aboriginal and non-aboriginal women changed little over this period. We conclude that Inuit and Indian women have different risk profiles for adverse pregnancy outcomes, and that prevention of preterm birth among Inuit women, and of SIDS and infection-related infant mortality in both aboriginal groups, are important targets for future research and intervention.

  8. 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

  9. 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

  10. Toxins and adverse drug reactions affecting the equine nervous system.

    PubMed

    Dawson, Dominic R

    2011-12-01

    This article provides an overview of the more common toxins and adverse drug reactions, along with more rare toxins and reactions (Table 1), that result in neurologic dysfunction in horses. A wide variety of symptoms, treatments, and outcomes are seen with toxic neurologic disease in horses. An in-depth history and thorough physical examination are needed to determine if a toxin or adverse drug reaction is responsible for the clinical signs. Once a toxin or adverse drug reaction is identified, the specific antidote, if available, and supportive care should be administered promptly.

  11. Associations between maternal BMI as well as glucose tolerance and adverse pregnancy outcomes in women with polycystic ovary syndrome.

    PubMed

    Li, Ying-Ying; Ye, Su-Qi; Zhong, Zhuo-Hui; Xu, Qiong; Mai, Wei-Bi; Yin, Cai-Xin; Zhu, Zhi-Qin; He, Xiao-Qian; Xiao, Qing

    2017-04-01

    This retrospective, cohort study examined the association between maternal pre-pregnancy body mass index (BMI), independent of glucose tolerance and adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), for which there are few previous studies. Medical records from 2012 to 2015 at Guangzhou Women and Children's Medical Center, China were reviewed for women previously diagnosed with PCOS with normal 2-h 75-g oral glucose tolerance test (OGTT) results (n = 1249). The separate and joint effects of maternal BMI and glucose levels on pregnancy outcomes were assessed. Maternal pre-pregnancy BMI was associated with hypertensive disorders of pregnancy (HDP) (OR: 1.22, 95% CI: 1.02-1.45), preterm birth (OR: 1.49, 95% CI: 1.08-2.17), and large for gestational age (LGA) (OR: 1.69, 95% CI: 1.16-2.20). Elevated fasting glucose and maternal pre-pregnancy BMI were jointly associated with increased risks of HDP, preterm birth, and LGA. Therefore, among women with PCOS and normal glucose tolerance, maternal pre-pregnancy BMI is an independent risk factor of adverse pregnancy outcomes.

  12. Review of medicolegal cases for cauda equina syndrome: what factors lead to an adverse outcome for the provider?

    PubMed

    Daniels, Eldra W; Gordon, Zachary; French, Keisha; Ahn, Uri M; Ahn, Nicholas U

    2012-03-07

    Cauda equina syndrome is 1 of a few true surgical emergencies involving the lumbar spine. Although treatment within 48 hours has been found to correlate with improved outcomes, recovery of bowel and bladder control does not always occur, and loss of these functions can be distressing to patients. An understanding of factors affecting the legal outcome can aid the clinician in determining risk management for medicolegal cases of cauda equina syndrome. This study is a retrospective analysis of medicolegal cases involving cauda equina syndrome. The LexisNexis Academic legal search database was used to obtain medicolegal cases of cauda equina syndrome to determine risk factors for adverse decisions for the provider. Outcomes data on trial verdicts were collected, as were associated penalties. Case data were also compiled on age, sex, initial presentation site, initial diagnosis, whether a rectal examination was performed, time to consultation with a specialist, time to completion of advanced imaging study, time to surgery, and neurosurgical vs orthopedic consultation. Based on our study of court cases involving cauda equina syndrome, a positive association was found between time to surgery >48 hours and an adverse decision (P<.05). The actual degree of functional loss did not appear to affect the verdicts. Because 26.7% of the cases involved an initial presentation that included loss of bowel or bladder control, this study emphasizes the importance of cautioning all patients with spinal complaints of the potential risk for cauda equina syndrome.

  13. Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes.

    PubMed

    Panchaud, Alice; Stojanov, Miloš; Ammerdorffer, Anne; Vouga, Manon; Baud, David

    2016-07-01

    The rapid spread of the Zika virus (ZIKV) in the Americas and its potential association with thousands of suspected cases of microcephaly in Brazil and higher rates of Guillain-Barré syndrome meet the conditions for a Public Health Emergency of International Concern, as stated by the World Health Organization in February 2016. Two months later, the Centers for Disease Control and Prevention (CDC) announced that the current available evidence supports the existence of a causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Microcephaly can be caused by several factors, and its clinical course and prognosis are difficult to predict. Other pathogens with proven teratogenicity have been identified long before the current ZIKV epidemic. Despite the growing number of cases with maternal signs of infection and/or presence of ZIKV in tissues of affected newborns or fetuses, it is currently difficult to assess the magnitude of increase of microcephaly prevalence in Brazil, as well as the role of other factors in the development of congenital neurological conditions. Meanwhile, health agencies and medical organizations have issued cautious guidelines advising health care practitioners and expectant couples traveling to, returning from, or living in affected areas. Analogous to dengue virus (DENV) epidemics, ZIKV has the potential to become endemic in all countries infested by Aedes mosquitoes, while new mutations could impact viral replication in humans, leading to increased virulence and consequently heightened chances of viral transmission to additional naive mosquito vectors. Studies are urgently needed to answer the questions surrounding ZIKV and its role in congenital neurological conditions.

  14. 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

  15. Antibiotic Prevention for Maternal Group B Streptococcal Colonization on Neonatal GBS-Related Adverse Outcomes: A Meta-Analysis

    PubMed Central

    Li, Shunming; Huang, Jingya; Chen, Zhiyao; Guo, Dan; Yao, Zhenjiang; Ye, Xiaohua

    2017-01-01

    Maternal colonization with group B Streptococcus (GBS) during pregnancy increases the risk of neonatal infection by vertical transmission. However, it remains unclear whether treating all colonized women during labor exposes a large number of their neonates to possible adverse effects without benefit. We performed a meta-analysis to assess the effect of intrapartum antibiotic prophylaxis on neonatal adverse outcomes. We identified studies by searching several English and Chinese electronic databases and reviewing relevant articles. Data were pooled using fixed-effects or random-effects meta-analysis, and for each outcome both risk ratio (RR) and 95% confidence intervals (95% CIs) were calculated. Fourteen studies (2,051 pregnant women and 2,063 neonates) were included, comprising 13 randomized clinical trials and 1 cohort study. Antibiotic prophylaxis is associated with a significant reduced risk of all cause infections (RR = 0.28, 95% CI = 0.18–0.42), GBS infection (RR = 0.24, 95% CI = 0.13–0.44), early-onset GBS infection (RR = 0.24, 95% CI = 0.13–0.45), non-GBS infections (RR = 0.34, 95% CI = 0.20–0.59), and GBS colonization (RR = 0.10, 95% CI = 0.06–0.16). But no significant reduction was observed in late-onset GBS infection, mortality from early-onset GBS infection or from non-GBS infections. Notably, no significant differences were found between ampicillin and penicillin prevention for neonatal adverse outcomes. Our findings suggest that antibiotic prophylaxis is effective in reducing neonatal GBS colonization and infection. PMID:28367139

  16. In vitro testing of basal cytotoxicity: Establishment of an adverse outcome pathway from chemical insult to cell death.

    PubMed

    Vinken, Mathieu; Blaauboer, Bas J

    2017-03-01

    In this paper, an in vitro basal cytotoxicity testing strategy is described for new chemical entities that lack any pre-existing information on potential toxicity. Special attention is paid to the selection of the cellular system, cytotoxicity assay and exposure conditions. This approach is based on a newly proposed generic adverse outcome pathway from chemical insult to cell death that consists of 3 steps, including initial cell injury, mitochondrial dysfunction and cell demise. The suggested strategy to consider in vitro basal cytotoxicity as a first step in evaluating the toxicity of new chemical entities can be placed in a tiered strategy that could be continued by evaluating more specific types of toxicity.

  17. 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.

  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.

  19. Investigation of the relationship between idiopathic microscopic hematuria (in the first and second trimesters) and major adverse outcomes of pregnancy

    PubMed Central

    Shahraki, Azar Danesh; Bardeh, Mahboobeh Esteki; Najarzadegan, Mohammad Reza

    2016-01-01

    Background: The aim of this study was to investigate the relationship between idiopathic microscopic hematuria (in the first and second trimesters) and major adverse outcomes of pregnancy. Materials and Methods: Urinalysis was done for 700 pregnant women before 24 weeks of pregnancy. Those who had 3–5 red blood cells per milliliter in urinalysis were considered positive urinalysis. Then, all individuals were examined for blood pressure and other alarm signs of pregnancy complications in each visit. All mothers were followed for the incidence of preeclampsia, preterm delivery, and pregnancy outcome until the end of pregnancy. Results: The results of this study showed that no significant difference in terms of incident of pregnancy complications between the pregnant women with and without hematuria and the only abortions and neonatal deaths differed between the two groups. Conclusion: These results suggest that further studies are needed to determine whether idiopathic microscopic hematuria can be a predictive value for pregnancy complications or not. PMID:28028526

  20. 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…

  1. Human adverse reproductive outcomes and electromagnetic field exposures: review of epidemiologic studies.

    PubMed Central

    Shaw, G M; Croen, L A

    1993-01-01

    Concerns have been raised regarding a relation between residential and occupational electromagnetic (EM) field exposures and adverse reproductive effects. This paper reviews the epidemiologic evidence for this possible relation, including some pertinent methodologic issues, notes relevant findings from the experimental literature, and discusses areas for future research. Evidence is lacking for a strong association between a woman's use of a video display terminal (VDT) during pregnancy and spontaneous abortion. The evidence for a strong association between a women's use of a VDT and other adverse reproductive endpoints is also lacking, with some suggestive findings for congenital malformations and too few data to reach a conclusion about other endpoints. With respect to low-level EM field exposures other than VDTs, the paucity of data prevents one from determining whether there are reproductive health risks associated with such exposures. Therefore, this is an area that needs further investigation. Given that altered growth may be an underlying biologic effect of EM field exposures, endpoints that might be pursued in future studies include congenital malformations not associated with chromosomal anomalies, intrauterine growth retardation, and chromosomally normal spontaneous abortions. PMID:8206019

  2. Cognitive load imposed by ultrasound-facilitated teaching does not adversely affect gross anatomy learning outcomes.

    PubMed

    Jamniczky, Heather A; Cotton, Darrel; Paget, Michael; Ramji, Qahir; Lenz, Ryan; McLaughlin, Kevin; Coderre, Sylvain; Ma, Irene W Y

    2017-03-01

    Ultrasonography is increasingly used in medical education, but its impact on learning outcomes is unclear. Adding ultrasound may facilitate learning, but may also potentially overwhelm novice learners. Based upon the framework of cognitive load theory, this study seeks to evaluate the relationship between cognitive load associated with using ultrasound and learning outcomes. The use of ultrasound was hypothesized to facilitate learning in anatomy for 161 novice first-year medical students. Using linear regression analyses, the relationship between reported cognitive load on using ultrasound and learning outcomes as measured by anatomy laboratory examination scores four weeks after ultrasound-guided anatomy training was evaluated in consenting students. Second anatomy examination scores of students who were taught anatomy with ultrasound were compared with historical controls (those not taught with ultrasound). Ultrasound's perceived utility for learning was measured on a five-point scale. Cognitive load on using ultrasound was measured on a nine-point scale. Primary outcome was the laboratory examination score (60 questions). Learners found ultrasound useful for learning. Weighted factor score on "image interpretation" was negatively, but insignificantly, associated with examination scores [F (1,135) = 0.28, beta = -0.22; P = 0.61]. Weighted factor score on "basic knobology" was positively and insignificantly associated with scores; [F (1,138) = 0.27, beta = 0.42; P = 0.60]. Cohorts exposed to ultrasound had significantly higher scores than historical controls (82.4% ± SD 8.6% vs. 78.8% ± 8.5%, Cohen's d = 0.41, P < 0.001). Using ultrasound to teach anatomy does not negatively impact learning and may improve learning outcomes. Anat Sci Educ 10: 144-151. © 2016 American Association of Anatomists.

  3. Eating disorder behaviours amongst adolescents: investigating classification, persistence and prospective associations with adverse outcomes using latent class models.

    PubMed

    Micali, Nadia; Horton, N J; Crosby, R D; Swanson, S A; Sonneville, K R; Solmi, F; Calzo, J P; Eddy, K T; Field, A E

    2017-02-01

    Diagnostic criteria for eating disorders (ED) remain largely based on clinical presentations, but do not capture the full range of behaviours in the population. We aimed to derive an empirically based ED behaviour classification using behavioural and body mass index (BMI) indicators at three time-points in adolescence, and to validate classes investigating prospective associations with adverse outcomes. Adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) provided data on ED at age 14 (n = 6615), 16 (n = 5888), and 18 years (n = 5100), and had weight and height measured. Psychological and behavioural outcomes were assessed at 15.5/16 and 17.5/18 years. We fit gender- and age-stratified latent class models, and employed logistic regression to investigate associations between classes and later outcomes. One asymptomatic and two symptomatic (largely representing higher and lower frequency ED behaviours) classes were observed at each time-point, although their relative prevalence varied by age and gender. The majority of girls in symptomatic classes remained symptomatic at subsequent assessments. Girls in symptomatic classes had higher odds of subsequent anxiety and depressive disorders, binge drinking, drug use, and deliberate self-harm. Data analyses were underpowered amongst boys. The presence of two symptomatic classes (characterised by different ED behaviour frequency) and their prospective association with adverse outcomes suggest a need to refine diagnostic thresholds based on empirical data. Despite some instability of classes, particularly in mid-adolescence, evidence that half of girls in symptomatic classes remained symptomatic suggests persistence of ED behaviours in adolescence, and highlights a need for early identification to reduce chronicity.

  4. Gestational diabetes mellitus treatment reduces obesity-induced adverse pregnancy and neonatal outcomes: the St. Carlos gestational study

    PubMed Central

    Assaf-Balut, Carla; Familiar, Cristina; García de la Torre, Nuria; Rubio, Miguel A; Bordiú, Elena; del Valle, Laura; Lara, Miriam; Ruiz, Teresa; Ortolá, Ana; Crespo, Irene; Duran, Alejandra; Herraiz, Miguel A; Izquierdo, Nuria; Perez, Noelia; Torrejon, Maria J; Runkle, Isabelle; Montañez, Carmen; Calle-Pascual, Alfonso L

    2016-01-01

    Background Obesity and gestational diabetes mellitus (GDM) increase the morbidity of the mother and newborn, which could increase further should they coexist. We aimed to determine the risk of adverse pregnancy and neonatal outcomes associated with excess weight (EW), and within this group identify potential differences between those with and without GDM. Methods We carried out a post-hoc analysis of the St. Carlos Gestational Study which included 3312 pregnant women, arranged in 3 groups: normal-weight women (NWw) (2398/72.4%), overweight women (OWw) (649/19.6%) and obese women (OBw) (265/8%). OWw and OBw were grouped as EW women (EWw). We analyzed variables related to adverse pregnancy and neonatal outcomes. Results The relative risk (95% CI) for GDM was 1.82 (1.47 to 2.25; p<0.0001) for OWw, and 3.26 (2.45 to 4.35; p<0.0001) in OBw. Univariate analysis showed associations of EW to higher rates of prematurity, birth weight >90th centile, newborns admitted to neonatal intensive care unit (NICU), instrumental delivery and cesarean delivery (all p<0.005). Multivariate analysis, adjusted for parity and ethnicity, showed that EW increased the risk of prematurity, admission to NICU, cesarean and instrumental delivery, especially in EWw without GDM. NWw with GDM had a significantly lower risk of admission to NICU and cesarean delivery, compared with NWw without GDM. Conclusions EW is detrimental for pregnancy and neonatal outcomes, and treatment of GDM contributes to lowering the risk in EWw and NWw. Applying the same lifestyle changes to all pregnant women, independent of their weight or GDM condition, could improve these outcomes. PMID:28074143

  5. Associations of meteorology with adverse pregnancy outcomes: a systematic review of preeclampsia, preterm birth and birth weight.

    PubMed

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

    2013-12-20

    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.

  6. 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

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

    PubMed Central

    Sorensen, Lucy C.; Dodge, Kenneth A.

    2015-01-01

    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 health 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 mental and physical health problems. PMID:26670938

  8. 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.

  9. Proposing a scientific confidence framework to help support the application of adverse outcome pathways for regulatory purposes.

    PubMed

    Patlewicz, Grace; Simon, Ted W; Rowlands, J Craig; Budinsky, Robert A; Becker, Richard A

    2015-04-01

    An adverse outcome pathway (AOP) describes the causal linkage between initial molecular events and an adverse outcome at individual or population levels. Whilst there has been considerable momentum in AOP development, far less attention has been paid to how AOPs might be practically applied for different regulatory purposes. This paper proposes a scientific confidence framework (SCF) for evaluating and applying a given AOP for different regulatory purposes ranging from prioritizing chemicals for further evaluation, to hazard prediction, and ultimately, risk assessment. The framework is illustrated using three different AOPs for several typical regulatory applications. The AOPs chosen are ones that have been recently developed and/or published, namely those for estrogenic effects, skin sensitisation, and rodent liver tumor promotion. The examples confirm how critical the data-richness of an AOP is for driving its practical application. In terms of performing risk assessment, human dosimetry methods are necessary to inform meaningful comparisons with human exposures; dosimetry is applied to effect levels based on non-testing approaches and in vitro data. Such a comparison is presented in the form of an exposure:activity ratio (EAR) to interpret biological activity in the context of exposure and to provide a basis for product stewardship and regulatory decision making.

  10. Practical approaches to adverse outcome pathway (AOP) development and weight of evidence evaluation as illustrated by ecotoxicological case studies.

    PubMed

    Fay, Kellie A; Villeneuve, Daniel L; LaLone, Carlie A; Song, You; Tollefsen, Knut Erik; Ankley, Gerald T

    2017-02-15

    Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and depend largely on the intended use or motivation for development and data availability. Four ecotoxicological AOP case studies, developed for different purposes, are described herein. In each situation, creation of the AOP began in a manner determined by the initial motivation for its creation, and expanded either to include additional components of the pathway, or to address the domains of applicability in terms of chemical initiators, susceptible species, life stages, etc. From these case studies, some general strategies can be gleaned which a developer may find useful for supporting an existing AOP or creating a new one. Several web-based tools which can aid in AOP assembly and evaluation of weight of evidence for scientific robustness of AOP components are highlighted. This article is protected by copyright. All rights reserved.

  11. Maternal Influenza Immunization and Adverse Birth Outcomes: Using Data and Practice to Inform Theory and Research Design

    PubMed Central

    Phadke, Varun K.; Steinhoff, Mark C.; Omer, Saad B.; MacDonald, Noni E.

    2016-01-01

    Maternal influenza immunization can reduce influenza-attributable morbidity and mortality among pregnant women and infants who are too young to be vaccinated. Data from empirical studies also support the hypothesis that immunization can protect the fetus against adverse outcomes if the mother is exposed to influenza. In their theoretical analysis in the Journal, Hutcheon et al. (Am J Epidemiol. 2016;184(3):227–232) critiqued the existing evidence of the fetal benefits of maternal influenza immunization by calculating the sample sizes needed to demonstrate hypothetical reductions in risk and concluded that the benefits observed in empirical studies are likely implausible. However, in their analysis, they did not take into account multiple fundamental characteristics of influenza epidemiology, including the time-variable effects of influenza illness and vaccination during pregnancy, or well-known differences in disease epidemiology between seasons, populations, and geographic regions. Although these and other factors might affect the magnitude of fetal benefit conferred by maternal influenza immunization, studies in which investigators have accounted for influenza circulation have demonstrated a consistent protective effect against a variety of adverse birth outcomes; those studies include the only randomized controlled trial designed a priori and adequately powered to do so. Only a comprehensive and nuanced assessment of the evidence base will allow for effective translation of these data into a global immunization policy. PMID:27784657

  12. Cilostazol increases patency and reduces adverse outcomes in percutaneous femoropopliteal revascularisation: a meta-analysis of randomised controlled trials

    PubMed Central

    Benjo, Alexandre M; Garcia, Daniel C; Jenkins, J Stephen; Cardoso, Rhanderson M N; Molina, Taina P; El-Hayek, Georges E; Nadkarni, Girish N; Aziz, Emad F; Dinicolantonio, James J; Collins, Tyrone

    2014-01-01

    Background Cilostazol is an oral antiplatelet agent currently indicated for treatment of intermittent claudication. There is evidence that cilostazol may reduce femoropopliteal restenosis after percutaneous endovascular intervention. Methods We searched PubMed, Scopus and Cochrane databases from 1966 through September 2013 for randomised controlled trials (RCTs) evaluating the addition of cilostazol to standard care in patients receiving femoropopliteal endovascular treatment. Restenosis, target lesion revascularisation and combined adverse outcomes (death, revascularisation and amputation) within 1–2 years postprocedure were evaluated. Results Of 205 articles, three RCTs were included in the analysis. The pooled data provided a total of 396 patients, 195 of whom received cilostazol. When compared to standard medical therapy alone, cilostazol significantly reduced the risk of restenosis (risk difference −0.20; 95% CI −0.29 to −0.11; p<0.0001; number needed to treat 5), target lesion revascularisation (risk difference −0.17; 95% CI −0.25 to −0.09; p<0.0001; number needed to treat 6). Death and amputation were not different in between groups. Conclusions and limitation Cilostazol significantly increases femoropopliteal patency and decreases adverse outcomes in percutaneous endovascular intervention. However, further RCTs are needed because of limited sample size; this meta-analysis represents the best current evidence. PMID:25392738

  13. Platelet to lymphocyte ratio in the prediction of adverse outcomes after acute coronary syndrome: a meta-analysis

    PubMed Central

    Li, Wenzhang; Liu, Qianqian; Tang, Yin

    2017-01-01

    Recent studies have shown platelet to lymphocyte ratio (PLR) to be a potential inflammatory marker in cardiovascular diseases. We performed a meta-analysis to systematically evaluate the prognostic role of PLR in acute coronary syndrome (ACS). A comprehensive literature search up to May 18, 2016 was conducted from PUBMED, EMBASE and Web of science to identify related studies. The risk ratio (RR) with 95% confidence interval (CI) was extracted or calculated for effect estimates. Totally ten studies involving 8932 patients diagnosed with ACS were included in our research. We demonstrated that patients with higher PLR level had significantly higher risk of in-hospital adverse outcomes (RR = 2.24, 95%CI = 1.81–2.77) and long-term adverse outcomes (RR = 2.32, 95%CI = 1.64–3.28). Sensitivity analyses confirmed the stability of our results. We didn’t detect significant publication bias by Begg’s and Egger’s test (p > 0.05). In conclusion, our meta-analysis revealed that PLR is promising biomarker in predicting worse prognosis in ACS patients. The results should be validated by future large-scale, standard investigations. PMID:28071752

  14. 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.

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

    PubMed

    Leem, Jong-Han; Chung, Kyu Hyuck

    2016-01-01

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

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

    PubMed Central

    2017-01-01

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

  17. 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.

  18. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease.

    PubMed

    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

    2011-09-01

    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.

  19. 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

  20. The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD outcomes

    PubMed Central

    Bosnic-Anticevich, Sinthia; Chrystyn, Henry; Costello, Richard W; Dolovich, Myrna B; Fletcher, Monica J; Lavorini, Federico; Rodríguez-Roisin, Roberto; Ryan, Dermot; Wan Yau Ming, Simon; Price, David B

    2017-01-01

    Background Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known. Aims To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques. Methods A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database. Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”. COPD-related events were recorded during an outcome year of follow-up. The primary outcome measure was an incidence rate ratio (IRR) comparing the rate of exacerbations between study cohorts. A secondary outcome compared average daily use of short-acting beta agonist (SABA). Results The final study sample contained 8,225 patients in each cohort (mean age 67 [SD, 10], 57% males, 37% current smokers). Patients in the similar-devices cohort had a lower rate of exacerbations compared with those in the mixed-devices cohort (adjusted IRR 0.82, 95% confidence interval [CI] 0.80–0.84) and were less likely to be in a higher-dose SABA group (adjusted proportional odds ratio 0.54, 95% CI 0.51–0.57). Conclusion COPD patients who were prescribed one or more additional inhaler devices requiring similar inhalation techniques to their previous device(s) showed better outcomes than those who were prescribed devices requiring different techniques. PMID:28053517

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

    PubMed Central

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

    2013-01-01

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

  2. Effects of tissue plasminogen activator and annexin A2 combination therapy on long-term neurological outcomes of rat focal embolic stroke

    PubMed Central

    Wang, Xiaoshu; Fan, Xiang; Yu, Zhanyang; Liao, Zhengbu; Zhao, Jianhua; Mandeville, Emiri; Guo, Shuzhen; Lo, Eng H.; Wang, Xiaoying

    2014-01-01

    Background and Purpose Tissue type plasminogen activator (tPA) in combination with recombinant annexin A2 (rA2) is known to reduce acute brain damage after focal ischemia. Here, we ask whether tPA plus rA2 combination therapy can lead to sustained long term neurological improvements as well. Methods We compared the effects of intravenous high-dose tPA alone (10mg/kg) versus a combination of low-dose tPA (5mg/kg) plus 10 mg/kg rA2 in a model of focal embolic cerebral ischemia in rats. All rats were treated at 3 hours after embolization. Brain tissue and neurological outcomes were assessed at 1 month. Surrogate biomarkers for endogenous neurovascular remodeling in peri-infarct area were analyzed by immunohistochemistry. Results Compared to high-dose tPA alone, low-dose tPA plus rA2 significantly decreased infarction and improved neurological function at 1 month post-stroke. In peri-infarct areas, tPA-plus-rA2 combination therapy also significantly augmented microvessel density, VEGF and synaptophysin expression. Conclusions Compared to conventional high-dose tPA alone, combination low-dose tPA plus rA2 therapy may provide a safe and effective way to improve long term neurological outcomes after stroke. PMID:24368559

  3. Social deprivation and adverse perinatal outcomes among Western and non-Western pregnant women in a Dutch urban population.

    PubMed

    Poeran, Jashvant; Maas, Arno F G; Birnie, Erwin; Denktas, Semiha; Steegers, Eric A P; Bonsel, Gouke J

    2013-04-01

    Social deprivation is considered a key factor in adverse perinatal outcomes. Rotterdam, the second largest city in The Netherlands, has large inequalities in perinatal health and a high number of deprived neighbourhoods. Social deprivation is measured here through a composite variable: 'Social Index' (SI). We studied the impact of the SI (2008-2009; 5 categories) in terms of perinatal mortality, congenital anomalies, preterm birth, small for gestational age (SGA) and low 5-minute Apgar score as registered in The Netherlands Perinatal Registry (Rotterdam 2000-2007, n = 56,443 singleton pregnancies). We applied ethnic dichotomisation as Western (European/North-American/Australian) vs. Non-Western (all others) ethnicity was expected to interact with the impact of SI. Tests for trend and multilevel regression analysis were applied. Gradually decreasing prevalence of adverse perinatal outcomes was observed in Western women from the lowest SI category (low social quality) to the highest SI category (high social quality). In Western women the low-high SI gradient for prevalence of spontaneous preterm birth (per 1000) changed from 57.2 to 34.1, for iatrogenic preterm birth from 35.2 to 19.0, for SGA from 119.6 to 59.4, for low Apgar score from 10.9 to 8.2, and for perinatal mortality from 14.9 to 7.6. These trends were statistically confirmed by Chi2-tests for trend (p < 0.001). For non-Western women such trends were absent. These strong effects for Western women were confirmed by significant odds ratios for almost all adverse perinatal outcomes estimated from multilevel regression analysis. We conclude social deprivation to play a different role among Western vs. non-Western women. Our results suggest that improvements in social quality may improve perinatal outcomes in Western women, but alternative approaches may be necessary for non-Western groups. Suggested explanations for non-Western 'migrant' groups include the presence of 'protective' effects through knowledge

  4. Background Rates of Adverse Pregnancy Outcomes for Assessing the Safety of Maternal Vaccine Trials in Sub-Saharan Africa

    PubMed Central

    Orenstein, Lauren A. V.; Orenstein, Evan W.; Teguete, Ibrahima; Kodio, Mamoudou; Tapia, Milagritos; Sow, Samba O.; Levine, Myron M.

    2012-01-01

    Background Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa. Methods We developed a mathematical model that calculates a clinical trial's expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM), low birth weight (LBW), prematurity, and major congenital malformations (MCM) in Sub-Saharan African countries were also performed. Findings Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6–73.3) per 1,000 total births, and the most common causes were hemorrhage (34%), dystocia (22%), and severe hypertensive disorders of pregnancy (22%). Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9–16.4) or premature (median 15.4%, IQR: 10.6–19.1) were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5–17.6), with the musculoskeletal system comprising 30%. Interpretation Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that

  5. Impact of presenting rhythm on short- and long-term neurological outcome in comatose survivors of cardiac arrest treated with therapeutic hypothermia

    PubMed Central

    Terman, Samuel W; Hume, Benjamin; Meurer, William J; Silbergleit, Robert

    2014-01-01

    Objective To compare short- and long-term neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA) treated with mild therapeutic hypothermia (MTH) presenting with non-shockable (nSR) versus shockable (SR) initial rhythms. Design Retrospective cohort study. Setting ED and ICU of an academic hospital. Patients One hundred twenty-three consecutive post-OHCA adults (57 nSR, 67 SR) treated with therapeutic hypothermia between 2006 and 2012. Measurements and Main Results Data were collected from electronic health records. Neurological outcomes were dichotomized by Cerebral Performance Category at discharge and 6-12 month follow-up and analyzed via multivariable logistic regressions. Groups were similar, except nSR patients were more likely to have a history of diabetes mellitus (p = 0.01), be dialysis-dependent (p = 0.01), and not have bystander CPR (p = 0.05). At discharge, 3/57 (5%) patients with nSR versus 28/66 (42%) with SR had a favorable outcome (unadjusted OR 0.08, 95% CI 0.02-0.3; adjusted OR 0.1, 95% CI 0.03-0. 4). At follow-up, 4/55 (7%) versus 29/60 (48%) of patients with nSR and SR respectively had a favorable CPC (OR 0.08, 95% CI 0.03-0.3; adjusted OR 0.09, 95% CI 0.09-0.3). Among those surviving hospitalization, neurological outcome was more likely at long-term follow-up than at hospital discharge for both groups (OR 2.5, 95% CI 1.3-4.7; adjusted 2.9, 1.4-6.2). No significant interaction between changes in neurological status over time and presenting rhythm was seen (p=0.93). Conclusions These data indicate an association between initial nSR and significantly worse short- and long-term outcomes in patients treated with MTH. Among survivors, neurological status significantly improved over time for all patients and SR patients, and tended to improve over time for the small number of nSR patients who survived beyond hospitalization. No significant interaction between changes in neurological status over time and presenting rhythm

  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.

  7. Smallpox Vaccine and Adverse Reproductive Health Outcomes in Military Service Members

    DTIC Science & Technology

    2005-01-01

    disease to bioterrorist threat. Obstet Gynecol 2002;100(1):87-93 4. Levine MM. Live-virus vaccines in pregnancy: risks and recommendations. Lancet 1974;2...vaccination and outcome of pregnancy. AJPH Nations Health 1968;58(10)1910-21. 12. Luisi M. Smallpox vaccination and pregnancy. Am J Obstet Gynecol 1977;128...Valero J, Luna S, Dominguez-Rojas V. Risk factors in miscarriage: a review. Eur J Obstet Gynecol Reprod Biol 2002;102(2):111-9 14. Ellish NJ, Saboda K

  8. Multidimensional system biology: genetic markers and proteomic biomarkers of adverse pregnancy outcome in preterm birth.

    PubMed

    Buhimschi, Catalin S; Rosenberg, Victor A; Dulay, Antonette T; Thung, Stephen; Sfakianaki, Anna K; Bahtiyar, Mert-Ozan; Buhimschi, Irina A

    2008-03-01

    Premature birth before 37 weeks of gestation is a significant public health problem. Each year, 4.5 million premature infants are born worldwide. Despite extensive research and a variety of interventions, the rate of preterm birth has steadily increased over the past 20 years and reached a high of 12.8% in 2006. The etiology of most preterm births remains elusive and is likely multifactorial, with many pathophysiological pathways involved, such as excessive stretching, oxidative stress, decidual hemorrhage, and infection. Genomics and proteomics have emerged to provide a better comprehension of the pathophysiological conditions leading to preterm birth, thereby providing a perspective for improving neonatal outcome.

  9. Durations of second stage of labor and pushing, and adverse neonatal outcomes: a population-based cohort study

    PubMed Central

    Sandström, A; Altman, M; Cnattingius, S; Johansson, S; Ahlberg, M; Stephansson, O

    2017-01-01

    Objective: The associations between duration of second stage of labor, pushing time and risk of adverse neonatal outcomes are not fully established. Therefore, we aimed to examine such relationships. Study design: A population-based cohort study including 42 539 nulliparous women with singleton infants born in cephalic presentation at ⩾37 gestational weeks, using the Stockholm-Gotland Obstetric Cohort, Sweden, and the Swedish Neonatal Quality Register, 2008 to 2013. Poisson regression was used to analyze estimated adjusted relative risks (RRs), with 95% confidence intervals (CIs). Outcome measures were umbilical artery acidosis (pH <7.05 and base excess <−12), birth asphyxia-related complications (including any of the following conditions: hypoxic ischemic encephalopathy, hypothermia treatment, neonatal seizures, meconium aspiration syndrome or advanced resuscitation after birth) and admission to neonatal intensive care unit (NICU). Results: Overall rates of umbilical artery acidosis, birth asphyxia-related complications and admission to NICU were 1.08, 0.63 and 6.42%, respectively. Rate of birth asphyxia-related complications gradually increased with duration of second stage: from 0.42% at <1 h to 1.29% at ≥4 h (adjusted RR 2.46 (95% CI 1.66 to 3.66)). For admission to NICU, corresponding rates were 4.97 and 9.45%, and adjusted RR (95% CI) was 1.80 (95% CI 1.58 to 2.04). Compared with duration of pushing <15 min, a duration of pushing ⩾60 min increased rates of acidosis from 0.57 to 1.69% (adjusted RR 2.55 (95% CI 1.51 to 4.30)). Conclusion: Prolonged durations of second stage of labor and pushing are associated with increased RRs of adverse neonatal outcomes. Clinical assessment of fetal well-being is essential when durations of second stage and pushing increases. PMID:27929527

  10. 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

  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. Plasma glutathione peroxidase activity in kidney recipients with and without adverse outcome.

    PubMed

    Eftekhar, Ebrahim; Hajirahimkhan, Athie; Taghizadeh Afshari, Ali; Nourooz-Zadeh, Jaffar

    2012-01-01

    Kidney function is routinely monitored utilizing classic biochemical parameters including serum or plasma creatinine (Cr), and blood urea nitrogen (BUN) concentrations. This study demonstrates that the simultaneous assessment of plasma glutathione peroxidase (pGPx) and Cr levels provides a better strategy for the immediate follow-up of kidney function in organ recipients. Kidney recipients (Krs; n = 22) were recruited. Blood sampling schedule commenced at day 1 (pre-transplantation) and post-transplantation days (i.e., everyday from 1 until day 14, and thereafter on days 21, 28, 35, 42, 49, and 56). pGPx was measured spectrophotometrically. Candidates for transplantation exhibited lower pGPx than control subjects (42 ± 24 vs. 143 ± 31 U/L; p < 0.005). In Krs with a stable post-transplant outcome, pGPx increased to a maximum at day 28 (214 ± 61 U/L). In a Kr diagnosed with acute tubulonecrosis, pGPx provided a better predictive value (threefold increase) than Cr. In a Kr diagnosed with acute rejection, the increment in Cr values was found to be more pronounced than in pGPx values. The pGPx test is simple, inexpensive and automatable, and should be a valuable diagnostic tool of kidney function in organ recipients with and without troublesome outcome for the follow-up during hospitalization period.

  13. 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.

  14. Maternal characteristics, pregnancy complications and adverse birth outcomes among women with disabilities

    PubMed Central

    Clements, Karen M.; Zhang, Jianying; Iezzoni, Lisa I.; Smeltzer, Suzanne C.; Long-Bellil, Linda M.

    2015-01-01

    Objectives The objective of this study is to describe the maternal characteristics, pregnancy complications, and birth outcomes among a representative sample of Rhode Island women with disabilities who recently gave birth. Methods Data from the 2002–2011 Rhode Island Pregnancy Risk Assessment Monitoring System (PRAMS) survey were analyzed. Results Approximately 7% of women in Rhode Island reported a disability. Women with disabilities reported significant disparities in their health care utilization, health behaviors and health status before and during pregnancy and during the postpartum period. Compared to nondisabled women, they were significantly more likely to report stressful life events and medical complications during their most recent pregnancy, were less likely to receive prenatal care in the first trimester, and more likely to have preterm births (13.4%; 95% CI, 11.6–15.6 compared to 8.9%; 95% CI, 8.5–9.3 for women without disabilities) and low birth weight babies (10.3%; 95% CI, 9.4–11.2 compared to 6.8%; 95% CI, 6.8–6.9). There was no difference in the rates of cesarean section between women with and without disabilities. Conclusion These findings support the need for clinicians providing care to pregnant women with disabilities to be aware of the increased risk for medical problems during pregnancy and factors that increase the risk for poor infant outcomes. PMID:26492209

  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. Better management of out-of-hospital cardiac arrest increases survival rate and improves neurological outcome in the Swiss Canton Ticino

    PubMed Central

    Mauri, Romano; Burkart, Roman; Benvenuti, Claudio; Caputo, Maria Luce; Moccetti, Tiziano; Del Bufalo, Alessandro; Gallino, Augusto; Casso, Carlo; Anselmi, Luciano; Cassina, Tiziano; Klersy, Catherine; Auricchio, Angelo

    2016-01-01

    Aim To determine the incidence of out-of-hospital cardiac arrest (OHCA) fulfilling Utstein criteria in the Canton Ticino, Switzerland, the survival rate of OHCA patients and their neurological outcome. Methods and results All OHCAs treated in Canton Ticino between 1 January 2005 and 31 December 2014 were followed until either death or hospital discharge. The survival and neurological outcome of those OHCA fulfilling Utstein criteria are reported. A total of 3367 OHCAs occurred in the Canton Ticino over a 10-year period. Resuscitation was attempted in 2298 patients; of those 1492 (65%) were of presumed cardiac origin, 454 fulfilling the Utstein comparator criteria. About 69% [95% confidence interval (CI), 66.6–71.4%] of the patients had a bystander-witnessed arrest; a dispatched cardiopulmonary resuscitation (CPR) steadily and significantly increased from 2005 to 2014. Out-of-hospital cardiac arrest occurred prevalently home (67%), in men (71%) of a mean age of 71 ± 13 years. There were no statistically significant differences either in demographic characteristics of OHCA victims over these years or in presenting rhythm. There was a progressive increase in the survival at discharge from 15% in 2005 to 55% in 2014; overall 96% (95% CI, 93.3–99.9%) of the survivors had a good neurological outcome. Conclusion The significant increase in Utstein comparator survival rates and improved neurological outcome in OHCA victims in Canton Ticino are the result of an effective OHCA management programme which includes large-scale public education, a coordinated fast EMS response, high density of external defibrillators, and advances in clinical interventions for OHCAs. PMID:26346920

  17. 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.

  18. Adverse outcome analyses of observational data: assessing cardiovascular risk in HIV disease.

    PubMed

    Triant, V A; Josephson, F; Rochester, C G; Althoff, K N; Marcus, K; Munk, R; Cooper, C; D'Agostino, R B; Costagliola, D; Sabin, C A; Williams, P L; Hughes, S; Post, W S; Chandra-Strobos, N; Guaraldi, G; Young, S S; Obenchain, R; Bedimo, R; Miller, V; Strobos, J

    2012-02-01

    Clinical decisions are ideally based on randomized trials but must often rely on observational data analyses, which are less straightforward and more influenced by methodology. The authors, from a series of expert roundtables convened by the Forum for Collaborative HIV Research on the use of observational studies to assess cardiovascular disease risk in human immunodeficiency virus infection, recommend that clinicians who review or interpret epidemiological publications consider 7 key statistical issues: (1) clear explanation of confounding and adjustment; (2) handling and impact of missing data; (3) consistency and clinical relevance of outcome measurements and covariate risk factors; (4) multivariate modeling techniques including time-dependent variables; (5) how multiple testing is addressed; (6) distinction between statistical and clinical significance; and (7) need for confirmation from independent databases. Recommendations to permit better understanding of potential methodological limitations include both responsible public access to de-identified source data, where permitted, and exploration of novel statistical methods.

  19. Adverse impact of intermittent portal clamping on long-term postoperative outcomes in hepatocellular carcinoma.

    PubMed

    Hao, S; Chen, S; Yang, X; Wan, C

    2017-01-01

    Introduction To evaluate the impact of intermittent portal clamping (IPC) on long-term postoperative outcomes in patients with hepatocellular carcinoma (HCC). Methods Clinical records of 355 patients underwent curative liver resection for HCC in January 2007 to December 2010 were retrospectively reviewed. According to how portal clamping was performed, patients were grouped as: IPC, n=113; other portal clamping (OPC), n=190; and no portal clamping (NPC), n=52. Results Median recurrence-free survival (RFS) was statistically significantly shorter in the IPC (39.4 months) than OPC (47.3 months, p=0.010) and NPC groups (51.4 months, p=0.008). Median overall survival (OS) was also significantly shorter with IPC (46.3 months), versus 52.9 months with OPC (p=0.022) and 56.2 months with NPC (p=0.015). Kaplan-Meier survival analysis revealed that 5-year cumulative RFS was much lower in the IPC (42.5%) than OPC (50.9%, p=0.014) and NPC groups (49.6%, p=0.013). Five-year cumulative OS was also much lower in the IPC (44.9%) than OPC (58.0%, p=0.020) and NPC groups (57.7%, p=0.025). On univariate analysis, tumour grade, size and number, TNM stage, blood transfusion, vascular invasion and IPC were significantly inversely correlated with RFS and OS. On multivariate analysis, tumour size and number, blood transfusion, vascular invasion and IPC remained significant. Conclusions Our study suggests that IPC is an independent risk factor for poor long-term postoperative outcomes in patients with HCC.

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

    PubMed

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

    2017-02-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    SciTech Connect

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

    2016-12-19

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

  3. The effect of maternal betel quid exposure during pregnancy on adverse birth outcomes among aborigines in Taiwan.

    PubMed

    Yang, Mei-Sang; Lee, Chien-Hung; Chang, Shun-Jen; Chung, Tieh-Chi; Tsai, Eing-Mei; Ko, Allen Min-Jen; Ko, Ying-Chin

    2008-05-01

    In considering documented developmental toxicity and teratogenicity found in earlier research, maternal betel quid chewing may very well be linked to a higher risk of adverse birth outcomes. The aim of this study was to investigate the significance of betel quid chewing, together with the use of cigarettes or alcohol, either independently or combined, on birth-related outcomes. A total of 1264 aboriginal women who had just given birth in 10 hospitals in Southern and Eastern Taiwan were recruited. Information on their maternal and newborn characteristics was obtained from medical charts and by performing personal interviews using a validated questionnaire. Maternal areca nut chewing during pregnancy was found to be significantly associated with both birth weight loss (-89.54 g) and birth length reduction (-0.43 cm). A significantly lower male newborn rate (aOR=0.62) was observed among aboriginal women with a habit of betel quid chewing during pregnancy. The use of this substance conveyed a 2.40- and 3.67-fold independent risk of low birth weight and full-term low birth weight, respectively. An enhanced risk (aOR=3.26-5.99) of low birth weight was observed among women concomitantly using betel quid, cigarette and alcohol during gestation. Our findings suggest that betel quid chewing during pregnancy has a substantial effect on a number of birth outcomes, including sex ratio at birth, lower birth weight and reduced birth length.

  4. 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

  5. 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

  6. 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,...

  7. Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury.

    PubMed

    Magnoni, Sandra; Esparza, Thomas J; Conte, Valeria; Carbonara, Marco; Carrabba, Giorgio; Holtzman, David M; Zipfel, Greg J; Stocchetti, Nino; Brody, David L

    2012-04-01

    Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. To test this hypothesis, 100 kDa cut-off microdialysis catheters were placed in 16 patients with severe traumatic brain injury at two neurological/neurosurgical intensive care units. Tau levels in the microdialysis samples were highest early and fell over time in all patients. Initial tau levels were >3-fold higher in patients with microdialysis catheters placed in pericontusional regions than in patients in whom catheters were placed in normal-appearing right frontal lobe tissue (P = 0.005). Tau levels and neurofilament light-chain levels were positively correlated (r = 0.6, P = 0.013). Neurofilament light-chain levels were also higher in patients with pericontusional catheters (P = 0.04). Interestingly, initial tau levels were inversely correlated with initial amyloid-β levels measured in the same samples (r = -0.87, P = 0.000023). This could be due to reduced synaptic activity in areas with substantial axonal injury, as amyloid-β release is closely coupled with synaptic activity. Importantly, high initial tau levels correlated with worse clinical outcomes, as assessed using the Glasgow Outcome Scale 6 months after injury (r = -0.6, P = 0.018). Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of

  8. Planned Cesarean Delivery at Term and Adverse Outcomes in Childhood Health

    PubMed Central

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

    2016-01-01

    Importance Planned cesarean delivery comprises a significant proportion of births globally, with combined rates of planned and unscheduled cesarean delivery in a number of regions approaching 50%. Observational studies have shown that offspring born by cesarean delivery are at increased risk of ill health in childhood, but these studies have been unable to adjust for some key confounding variables. Additionally, risk of death beyond the neonatal period has not yet been reported for offspring born by planned cesarean delivery. Objective To investigate the relationship between planned cesarean delivery and offspring health problems or death in childhood. Design, Setting, and Participants Population-based data-linkage study of 321 287 term singleton first-born offspring born in Scotland, United Kingdom, between 1993 and 2007, with follow-up until February 2015. Exposures Offspring born by planned cesarean delivery in a first pregnancy were compared with offspring born by unscheduled cesarean delivery and with offspring delivered vaginally. Main Outcomes and Measures The primary outcome was asthma requiring hospital admission; secondary outcomes were salbutamol inhaler prescription at age 5 years, obesity at age 5 years, inflammatory bowel disease, type 1 diabetes, cancer, and death. Results Compared with offspring born by unscheduled cesarean delivery (n = 56 015 [17.4%]), those born by planned cesarean delivery (12 355 [3.8%]) were at no significantly different risk of asthma requiring hospital admission, salbutamol inhaler prescription at age 5 years, obesity at age 5 years, inflammatory bowel disease, cancer, or death but were at increased risk of type 1 diabetes (0.66% vs 0.44%; difference, 0.22% [95% CI, 0.13%-0.31%]; adjusted hazard ratio [HR], 1.35 [95% CI, 1.05-1.75]). In comparison with children born vaginally (n = 252 917 [78.7%]), offspring born by planned cesarean delivery were at increased risk of asthma requiring hospital admission (3.73% vs 3

  9. 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

  10. 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

  11. Linking prenatal maternal adversity to developmental outcomes in infants: the role of epigenetic pathways.

    PubMed

    Monk, Catherine; Spicer, Julie; Champagne, Frances A

    2012-11-01

    Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with risk of psychopathology. Although the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this article, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress.

  12. Linking Prenatal Maternal Adversity to Developmental Outcomes in Infants: The Role of Epigenetic Pathways

    PubMed Central

    Monk, Catherine; Spicer, Julie; Champagne, Frances A.

    2013-01-01

    Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with consequences for risk of psychopathology. Though the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally-induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this review, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and here we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress. PMID:23062303

  13. 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

  14. Mannose-binding lectin genotypes: potential role in tubal damage and adverse IVF outcome.

    PubMed

    Laisk, Triin; Peters, Maire; Salumets, Andres

    2011-12-01

    The innate immune system provides the first-line defence against genital tract pathogens and is also involved in establishing and maintaining a successful pregnancy. Genetic variation of factors regulating immune response can be associated with complications after genital tract infections and may lead to unfavourable pregnancy outcomes. This study focused on four polymorphisms in the mannose binding lectin gene (MBL2) and assessed their significance in tubal damage and female fertility by comparing genotype frequencies among 388 controls and women with tubal factor infertility (n=155) or previous ectopic pregnancy (n=178). The high-producing MBL2 genotype HYA/LYA was found to have a protective effect, while the hyper-producing MBL2 genotype HYA/HYA and low-producing MBL2 genotypes were associated with susceptibility to tubal factor infertility. Also, the low-producing genotypes showed association with early pregnancy loss in IVF treatment. In conclusion, these data suggest that certain MBL2 genotypes can be associated with tubal damage in patients with evidence of Chlamydia trachomatis infection and additionally may contribute to the pathogenesis of early pregnancy loss.

  15. Architectural heterogeneity and cribriform pattern predict adverse clinical outcome for Gleason grade 4 prostatic adenocarcinoma.

    PubMed

    Dong, Fei; Yang, Ping; Wang, Chaofu; Wu, Shulin; Xiao, Yu; McDougal, W Scott; Young, Robert H; Wu, Chin-Lee

    2013-12-01

    Gleason grade 4 defines a group of prostatic adenocarcinomas with a variety of architectural patterns, including poorly formed glands, fused glands, and cribriform pattern. To address the relative contribution to clinical prognosis by these distinct patterns, the histology of 241 consecutive radical prostatectomy specimens with the highest Gleason grade of 4 was reviewed. The presence of poorly formed glands, fused glands, and cribriform pattern was recorded for each case, and the types of architectural patterns present were associated with patient outcome. In this population, prostatic adenocarcinomas demonstrated architectural heterogeneity, with 17% of cases exhibiting a single Gleason grade 4 pattern, and 41% of cases exhibiting all 3 morphologic patterns. Patients exhibiting all 3 architectural patterns had lower rates of biochemical disease-free survival (66% vs. 76% at 5 y; log rank P=0.006). Twenty-two of 165 patients (13.3%) with cribriform pattern adenocarcinoma developed metastasis, whereas 2 of 76 patients (2.6%) without cribriform pattern developed metastasis at a median postoperative follow-up of 10.0 years. The presence of a cribriform pattern was an independent predictor for biochemical recurrence (hazard ratio 2.41; 95% confidence interval, 1.34-4.32; P=0.003) as well as metastasis after radical prostatectomy (hazard ratio 5.62; 95% confidence interval, 1.29-24.5; P=0.02). These results suggest that the morphologic subclassification of distinct Gleason grade 4 architectural patterns provides prognostic information beyond the current Gleason classification system.

  16. 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

  17. Which Anthropometric Indicators Identify a Pregnant Woman as Acutely Malnourished and Predict Adverse Birth Outcomes in the Humanitarian Context?

    PubMed Central

    Ververs, Mija-tesse; Antierens, Annick; Sackl, Anita; Staderini, Nelly; Captier, Valerie

    2013-01-01

    Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Médecins Sans Frontières Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts. PMID:23787989

  18. Adverse Pregnancy Outcomes after In Vitro Fertilization: Effect of Number of Embryos Transferred and Plurality at Conception

    PubMed Central

    Luke, Barbara; Stern, Judy E.; Kotelchuck, Milton; Declercq, Eugene R.; Hornstein, Mark D.; Gopal, Daksha; Hoang, Lan; Diop, Hafsatou

    2015-01-01

    Objective To evaluate risks for adverse pregnancy outcomes by number of embryos transferred (ET) and fetal heart beats (FHB) in ART conceived singleton live births. Design Longitudinal cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System between 2004 and 2008 among women who were treated and gave birth in Massachusetts. Setting Clinic-based data. Patients ART data on 6,073 births between 2004 and 2008 were linked to vital records and hospital data. Likelihood of ET ≥3 vs 1–2, FHB >1 vs 1, and risks of preterm birth (PTB, <37 weeks gestation), low birthweight (LBW, <2,500g), and small-for-gestational age birthweight (SGA, <10th%ile) with FHB >1 were modeled with binary logistic regression using a backward-stepping algorithm, and presented as adjusted odds ratios (AORs) and 95% confidence intervals. Interventions None Main Outcome Measures ET≥3, FHB >1, PTB, LBW, and SGA. Results Higher ET was significantly more likely with older maternal age, intracytoplasmic sperm injection, assisted hatching, cleavage-stage embryos, and thawed embryos. The likelihood of FHB>1 with ≥3 ET vs 1–2 ET was 2.04 (1.68–2.48). Risks of PTB and LBW with FHB>1 were 1.63 (1.27–2.09) and 1.81 (1.36– 2.39), respectively; the risk of SGA was not significant. Nulliparity was associated with higher risks of PTB (1.34, 1.12–1.59), LBW (1.48, 1.20–1.83), and SGA (2.17, 1.69–2.78). Conclusions Number of ETs were strongly associated with FHBs, with twice the risk of FHB>1 with ≥3 ET versus 1–2 ET. Increasing FHBs were associated with significantly greater risks for PTB and LBW outcomes. PMID:25956368

  19. 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.

  20. Women participating in a web-based preconception study have a high prevalence of risk factors for adverse pregnancy outcomes

    PubMed Central

    2014-01-01

    Background Adverse pregnancy outcomes (APOs) can be increased by preconception risk factors and lifestyles. We measured the prevalence of preconception risk factors for APOs in a population of Italian women of childbearing age enrolled in a web-based study. Methods Participants were enrolled through a web platform (http://www.mammainforma.it). After enrollment, participants filled in a questionnaire regarding socio-demographic characteristics, clinical data and preconception risk factors for adverse pregnancy outcomes. Through logistic regression, we explored how the prevalence of risk factors was affected by age, education level, employment, parity, physician’s recommendation and knowledge of the specific risk factor. Results We enrolled a total of 728 women. Sixty-two percent had a University degree, 84% were employed and 77% were planning their first pregnancy. Nearly 70% drank alcohol in any quantity; 16% were smokers; 6% was underweight; 21.4% was overweight; 51.6% did not assume folic acid; 22% was susceptible to rubella, 44.5% to hepatitis b and 13.2% to varicella. According to the multivariate analysis, compared to women who already had at least one pregnancy, nulliparous women had a higher BMI [OR 1.60 (CI 1.02;2.48)] and were less likely to be susceptible to rubella [OR 0.33 (CI 0.20;0.58)] and to be consuming alcohol [OR 0.47 (CI 0.31;0.70)] or cigarettes [OR 0.48 (CI 0.26;0.90)]. Appropriate knowledge was associated with a correct behavior regarding smoking, drinking alcohol and folic acid supplementation. Conclusions This study shows that the prevalence of risk factors for APOs in our population is high. Interventions aimed at reducing risk factors for APOs are needed and, to this purpose, a web intervention may represent a feasible tool to integrate tailored information and to inform preconception counseling targeting a specific group of women planning a pregnancy who are engaged on the web. PMID:24885235

  1. Inactive matrix Gla protein is causally related to adverse health outcomes: a Mendelian randomization study in a Flemish population.

    PubMed

    Liu, Yan-Ping; Gu, Yu-Mei; Thijs, Lutgarde; Knapen, Marjo H J; Salvi, Erika; Citterio, Lorena; Petit, Thibault; Carpini, Simona Delli; Zhang, Zhenyu; Jacobs, Lotte; Jin, Yu; Barlassina, Cristina; Manunta, Paolo; Kuznetsova, Tatiana; Verhamme, Peter; Struijker-Boudier, Harry A; Cusi, Daniele; Vermeer, Cees; Staessen, Jan A

    2015-02-01

    Matrix Gla-protein is a vitamin K-dependent protein that strongly inhibits arterial calcification. Vitamin K deficiency leads to production of inactive nonphosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP). The risk associated with dp-ucMGP in the population is unknown. In a Flemish population study, we measured circulating dp-ucMGP at baseline (1996-2011), genotyped MGP, recorded adverse health outcomes until December 31, 2012, and assessed the multivariable-adjusted associations of adverse health outcomes with dp-ucMGP. We applied a Mendelian randomization analysis using MGP genotypes as instrumental variables. Among 2318 participants, baseline dp-ucMGP averaged 3.61 μg/L. Over 14.1 years (median), 197 deaths occurred, 58 from cancer and 70 from cardiovascular disease; 85 participants experienced a coronary event. The risk of death and non-cancer mortality curvilinearly increased (P≤0.008) by 15.0% (95% confidence interval, 6.9-25.3) and by 21.5% (11.1-32.9) for a doubling of the nadir (1.43 and 0.97 μg/L, respectively). With higher dp-ucMGP, cardiovascular mortality log-linearly increased (hazard ratio for dp-ucMGP doubling, 1.14 [1.01-1.28]; P=0.027), but coronary events log-linearly decreased (0.93 [0.88-0.99]; P=0.021). dp-ucMGP levels were associated (P≤0.001) with MGP variants rs2098435, rs4236, and rs2430692. For non-cancer mortality and coronary events (P≤0.022), but not for total and cardiovascular mortality (P≥0.13), the Mendelian randomization analysis suggested causality. Higher dp-ucMGP predicts total, non-cancer and cardiovascular mortality, but lower coronary risk. For non-cancer mortality and coronary events, these associations are likely causal.

  2. Adverse pregnancy outcomes around incinerators and crematoriums in Cumbria, north west England, 1956–93

    PubMed Central

    Dummer, T; Dickinson, H; Parker, L

    2003-01-01

    Study objective: To investigate the risk of stillbirth, neonatal death, and lethal congenital anomaly among babies of mothers living close to incinerators and crematoriums in Cumbria, north west England, 1956–93. Design: Retrospective cohort study. Logistic regression was used to investigate the risk of each outcome in relation to proximity at birth to incinerators and crematoriums, adjusting for social class, year of birth, birth order, and multiple births. Continuous odds ratios for trend with proximity to sites were estimated. Setting: All 3234 stillbirths, 2663 neonatal deaths, and 1569 lethal congenital anomalies among the 244 758 births to mothers living in Cumbria, 1956–1993. Main results: After adjustment for social class, year of birth, birth order, and multiple births, there was an increased risk of lethal congenital anomaly, in particular spina bifida (odds ratio 1.17, 95% CI: 1.07 to 1.28) and heart defects (odds ratio 1.12, 95% CI: 1.03 to 1.22) around incinerators and an increased risk of stillbirth (odds ratio 1.04, 95% CI: 1.01 to 1.07) and anencephalus (odds ratio 1.05, 95% CI: 1.00 to 1.10) around crematoriums. Conclusions: The authors cannot infer a causal effect from the statistical associations reported in this study. However, as there are few published studies with which to compare our results, the risk of spina bifida, heart defects, stillbirth, and anencephalus in relation to proximity to incinerators and crematoriums should be investigated further, in particular because of the increased use of incineration as a method of waste disposal. PMID:12775795

  3. Residential proximity to traffic and adverse birth outcomes in Los Angeles county, California, 1994-1996.

    PubMed Central

    Wilhelm, Michelle; Ritz, Beate

    2003-01-01

    We reported previously that increases in ambient air pollution in the Los Angeles basin increased the risk of low weight and premature birth. However, ambient concentrations measured at monitoring stations may not take into account differential exposure to pollutants found in elevated concentrations near heavy-traffic roadways. Therefore, we used an epidemiologic case-control study design to examine whether residential proximity to heavy-traffic roadways influenced the occurrence of low birth weight (LBW) and/or preterm birth in Los Angeles County between 1994 and 1996. We mapped subject home locations at birth and estimated exposure to traffic-related air pollution using a distance-weighted traffic density (DWTD) measure. This measure takes into account residential proximity to and level of traffic on roadways surrounding homes. We calculated odds ratios (ORs) and risk ratios (RRs) for being LBW and/or preterm per quintile of DWTD. The clearest exposure-response pattern was observed for preterm birth, with an RR of 1.08 [95% confidence interval (CI), 1.01-1.15] for infants in the highest DWTD quintile. Although higher risks were observed for LBW infants, exposure-response relations were less consistent. Examining the influence of season, we found elevated risks primarily for women whose third trimester fell during fall/winter months (OR(term LBW) = 1.39; 95% CI, 1.16-1.67; OR(preterm and LBW) = 1.24; 95% CI = 1.03-1.48; RR(all preterm) = 1.15; 95% CI, 1.05-1.26), and exposure-response relations were stronger for all outcomes. This result is consistent with elevated pollution in proximity to sources during more stagnant air conditions present in winter months. Our previous research and these latest results suggest exposure to traffic-related pollutants may be important. PMID:12573907

  4. [The influence of locomotor treatment using robotic body-weight-supported treadmill training on rehabilitation outcome of patients suffering from neurological disorders].

    PubMed

    Schwartz, Isabella; Meiner, Zeev

    2013-03-01

    Regaining one's ability to walk is of great importance for neurological patients and is a major goal of all rehabilitation programs. Treating neurological patients in the acute phase after the event is technically difficult because of their motor weakness and balance disturbances. Based on studies in spinalized animals, a novel locomotor training that incorporates high repetitions of task-oriented practice by the use of body weight-supported treadmill training (BWSTT) was developed to overcome these obstacles. The use of BWSTT enables early initiation of gait training, integration of weightbearing activities, stepping and balance by the use of a task-specific approach, and a symmetrical gait pattern. However, despite the theoretical potential of BWSTT to become an invaluable therapeutic tool, its effect on walking outcomes was disappointing when compared with conventional training of the same duration. To facilitate the deLivery of BWSTT, a motorized robotic driven gait orthosis (RBWSTT) was recently developed. It has many advantages over the conventional method, including less effort for the physiotherapists, longer session duration, more physiological and reproducible gait patterns, and the possibility of measuring a patient's performances. Several studies have been conducted using RBWSTT in patients after stroke, spinal cord injury, multiple sclerosis and other neurological diseases. Although some of the results were encouraging, there is still uncertainty regarding proper patient selection, timing and protocol for RBWTT treatment following neurological diseases. More large randomized controlled studies are needed in order to answer these questions.

  5. Combined ureterorenoscopy for ureteral and renal calculi is not associated with adverse outcomes

    PubMed Central

    Turan, Mirac; Ozkanli, Oguz; Avci, Egemen; Basar, Mehmet Murad; Acar, Oguz; Balbay, Mevlana Derya

    2015-01-01

    Introduction We intended to evaluate the feasibility and effectiveness of the simultaneous rigid and flexible ureteroscopic treatment of symptomatic ureteral and ipsilateral small simultaneous calyceal stones. Outcomes of combined therapy were compared with monotherapy alone. Material and methods In this retrospective study, group 1 consisted of 45 patients with middle or lower ureteral and ipsilateral small simultaneous calyceal stones treated by combined therapy. Group 2 included 45 patients with middle or lower ureteral stones only and treated by monotherapy. Stone characteristics, operative time, hospital stay, stone free rates, and complications were compared between groups 1 and 2. Stone free status was defined as no fragments and/or the presence of asymptomatic fragments smaller than 4 mm. Results Mean BMI were 29.3 ±0.9 kg/m2 and 27.6 ±0.6 kg/m2 in groups 1 and 2, respectively. Mean ureteral stone size (7.6 ±0.4 mm vs. 8.0 ±0.4 mm, p = 0.261) and ureteral stone burden (56.0 ±5.5 mm2 vs. 54.8 ±6.1 mm2, p = 0.487) were similar between groups. Mean renal stone size and renal stone burden for group 1 were 7.1 ±0.8 mm and 83.7 ±11.3 mm2. The mean operative time was significantly longer (for a mean of 32.5±1.2 minutes) for group 1 (p = 0.001). Ureteral stents were left in 38 (84.4%) and 19 (42.2%) patients in group 1 and group 2 (p = 0.001). Hospital stay and complication rates were similar between groups. SFRs were 100% for ureteral stones in both groups and 88.9% for renal stones within group 1. Conclusions Simultaneous ureteroscopic treatment of the ureteral and ipsilateral small calyceal stones prolongs operative time and increases use of ureteral stent without leaving any residual renal stones. PMID:26251739

  6. Neurological outcomes in patients transported to hospital without a prehospital return of spontaneous circulation after cardiac arrest

    PubMed Central

    2013-01-01

    Introduction As emergency medical services (EMS) personnel in Japan are not allowed to perform termination of resuscitation in the field, most patients experiencing an out-of-hospital cardiac arrest (OHCA) are transported to hospitals without a prehospital return of spontaneous circulation (ROSC). As the crucial prehospital factors for outcomes are not clear in patients who had an OHCA without a prehospital ROSC, we aimed to determine the prehospital factors associated with 1-month favorable neurological outcomes (Cerebral Performance Category scale 1 or 2 (CPC 1–2)). Methods We analyzed the data of 398,121 adult OHCA patients without a prehospital ROSC from a prospectively recorded nationwide Utstein-style Japanese database from 2007 to 2010. The primary endpoint was 1-month CPC 1–2. Results The rate of 1-month CPC 1–2 was 0.49%. Multivariate logistic regression analysis indicated that the independent variables associated with CPC 1–2 were the following nine prehospital factors: (1) initial non-asystole rhythm (ventricular fibrillation (VF): adjusted odds ratio (aOR), 9.37; 95% confidence interval (CI), 7.71 to 11.4; pulseless ventricular tachycardia (VT): aOR, 8.50; 95% CI, 5.36 to 12.9; pulseless electrical activity (PEA): aOR, 2.75; 95% CI, 2.40 to 3.15), (2) age <65 years (aOR, 3.90; 95% CI, 3.28 to 4.67), (3) arrest witnessed by EMS personnel (aOR, 2.82; 95% CI, 2.48 to 3.19), (4) call-to-hospital arrival time <24 minutes (aOR, 2.58; 95% CI, 2.22 to 3.01), (5) arrest witnessed by any layperson, (6) physician-staffed ambulance, (7) call-to-response time <5 minutes, (8) prehospital shock delivery, and (9) presumed cardiac cause. When four crucial key factors (with an aOR >2.0 in the regression model: initial non-asystole rhythm, age <65 years, EMS-witnessed arrest, and call-to-hospital arrival time <24 minutes) were present, the rates of 1-month CPC 1–2 and 1-month survival were 16.1% and 23.2% in initial VF, 8.3% and 16.7% in pulseless VT, and 3

  7. The effect of childhood adversity on 4-year outcome in individuals at ultra high risk for psychosis in the Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial.

    PubMed

    Kraan, Tamar C; Ising, Helga K; Fokkema, Marjolein; Velthorst, Eva; van den Berg, David P G; Kerkhoven, Margot; Veling, Wim; Smit, Filip; Linszen, Don H; Nieman, Dorien H; Wunderink, Lex; Boonstra, Nynke; Klaassen, Rianne M C; Dragt, Sara; Rietdijk, Judith; de Haan, Lieuwe; van der Gaag, Mark

    2017-01-01

    Childhood adversity is associated with a range of mental disorders, functional impairment and higher health care costs in adulthood. In this study we evaluated if childhood adversity was predictive of adverse clinical and functional outcomes and health care costs in a sample of patients at ultra-high risk (UHR) for developing a psychosis. Structural Equation Modeling was used to examine the effect of childhood adversity on depression, anxiety, transition to psychosis and overall functioning at 4-year follow-up. In addition, we evaluated economic costs of childhood adversity in terms of health care use and productivity loss. Data pertain to 105 UHR participants of the Dutch Early Detection and Intervention Evaluation (EDIE-NL). Physical abuse was associated with higher depression rates (b=0.381, p=0.012) and lower social functional outcome (b=-0.219, p=0.017) at 4-year follow-up. In addition, emotional neglect was negatively associated with social functioning (b=-0.313, p=0.018). We did not find evidence that childhood adversity was associated with transition to psychosis, but the experience of childhood adversity was associated with excess health care costs at follow-up. The data indicate long-term negative effects of childhood adversity on depression, social functioning and health care costs at follow-up in a sample of UHR patients.

  8. Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study

    PubMed Central

    Di Bartolomeo, Aurélie; Chauleur, Céline; Gris, Jean-Christophe; Chapelle, Céline; Noblot, Edouard; Laporte, Silvy

    2017-01-01

    Objective The study aimed to evaluate if the rate of tissue factor pathway inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women. Methods This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor pathway inhibitor resistance (normalized ratio) and tissue factor pathway inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period. Results Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor pathway inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor pathway inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery. Conclusion Among high-risk women, the tissue factor pathway inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries. PMID:28328938

  9. 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.

  10. Increased alloreactivity and adverse outcomes in obese kidney transplant recipients are limited to those with diabetes mellitus.

    PubMed

    Schachtner, Thomas; Stein, Maik; Reinke, Petra

    2017-02-01

    Previous studies on patient and allograft outcomes of obese kidney transplant recipients (KTRs) remain controversial. To what extent obesity-related comorbidities contribute to adverse outcomes, however, hasn't been addressed. We studied all KTRs from 2005 to 2012. 29 (4%), 317 (48%), 217 (33%), 76 (12%), and 21 KTRs (4%) were identified as underweight, normal-weight, overweight, obese, and morbid obese, respectively. 33 of 97 obese KTRs (34%) had pre-existent diabetes. Samples were collected before transplantation and at +1, +2, +3months posttransplantation. Donor-reactive T-cells were measured using an interferon-γ Elispot assay. Obese KTRs showed an increased incidence pre-existent diabetes (p<0.001), but no differences for hypertension and coronary artery disease (p>0.05). Among obese KTRs, those with pre-existent diabetes showed inferior patient and allograft survival, worse allograft function, delayed graft function, and prolonged hospitalization (p<0.05). Interestingly, no differences were observed between obese non-diabetic, normal-weight diabetic, and normal-weight non-diabetic KTRs (p>0.05). Obese diabetic KTRs showed higher frequencies of donor-reactive T-cells pretransplantation (p<0.05). Our results suggest that the increased risk of mortality, allograft loss, delayed graft function, and prolonged hospitalization in obese KTRs is limited to those with diabetes. A state of obesity-related inflammation plus hyperglycemia may trigger increased alloreactivity and should call for adequate immunosuppression.

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

    USGS Publications Warehouse