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

PubMed

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

2018-06-01

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

Beyond drinking: differential effects of demographic and socioeconomic factors on alcohol-related adverse consequences across European countries.

PubMed

Kuendig, Hervé; Plant, Moira L; Plant, Martin A; Kuntsche, Sandra; Miller, Patrick; Gmel, Gerhard; Ahlström, Salme; Bergmark, Karin Helmersson; Olafsdóttir, Hildigunnur; Elekes, Zsuzsanna; Csemy, Ladislav; Knibbe, Ronald

2008-01-01

Evidence underlines the importance of drinking patterns and individual characteristics in experiencing adverse alcohol-related consequences; however, little research has been conducted to explore who does and who does not experience consequences with similar drinking patterns. Using data from seven European countries, this study assesses the association between demographic and socioeconomic characteristics and six adverse consequences. Conditional logistic regression models were estimated, cases (experiencing a consequence) being matched to controls (not experiencing the consequence) by drinking patterns. In general, protective effects with increasing age and being in a partnership were consistent. Gender effects were mixed, but mainly protective for women. Educational achievement and economic status showed consistent effects across countries, but different directions of effect across consequences. Consequences mostly associated with individual drinking pattern (injury, blackout, and loss of control over drinking) exhibited similar patterns of associations, but varying ones arose for consequences additionally influenced by societal reaction to drinking (guilt, role failure, and pressure to cut down drinking). Differences in strengths and directions of effects across consequences pointed to the possibility that the reporting of adverse consequences is not only influenced by alcohol consumption, but also by attributional processes related to demographic and socioeconomic statuses. Copyright 2008 S. Karger AG, Basel.

Biological Sensitivity to Context: The Interactive Effects of Stress Reactivity and Family Adversity on Socioemotional Behavior and School Readiness

ERIC Educational Resources Information Center

Obradovic, Jelena; Bush, Nicole R.; Stamperdahl, Juliet; Adler, Nancy E.; Boyce, W. Thomas

2010-01-01

This study examined the direct and interactive effects of stress reactivity and family adversity on socioemotional and cognitive development in three hundred and thirty-eight 5- to 6-year-old children. Neurobiological stress reactivity was measured as respiratory sinus arrhythmia and salivary cortisol responses to social, cognitive, sensory, and…

Efficacy and safety of oral ketamine for the relief of intractable chronic pain: A retrospective 5-year study of 51 patients.

PubMed

Marchetti, F; Coutaux, A; Bellanger, A; Magneux, C; Bourgeois, P; Mion, G

2015-08-01

This work summarizes the efficiency, failures and adverse effects of oral administration of ketamine at home for intractable pain. This 5-year retrospective study involved testing ketamine by intravenous in-hospital administration, then a conversion to an oral route, or oral treatment directly administered at home. The daily intravenous dose was increased by steps of 0.5 mg/kg to attain an effective daily dose of 1.5-3.0 mg/kg. Pain was evaluated on a numeric scale from 0 to 10, and evidence of adverse effects was collected every day. The effective daily dose was delivered orally (three to four intakes). If effective, ketamine was continued for 3 months. Short infusions or direct oral treatment began with a 0.5-mg/kg dose, then the daily ketamine dose was increased in 15- to 20-mg increments. Among 55 cases (51 patients, neuropathic pain 60%), the mean effective oral dose was 2 mg/kg. Ketamine was effective in 24 patients (44%, mean pain reduction 67 ± 17%), partially effective in 20% (mean pain reduction 30 ± 11%), with a mean opioid sparing of 63 ± 32%, and failure in 22%. Half of the patients experienced adverse effects, but only eight had to stop treatment. For patients with opioid therapy, failure of ketamine was less frequent (7% vs. 36%; p < 0.02), with fewer adverse effects (33% vs. 68%; p < 0.01). Pain was reduced or abolished in two-thirds of patients under ketamine therapy; ketamine was effective for patients taking opioids and resulted in few adverse effects. © 2014 European Pain Federation - EFIC®

Stress in 1st-year women teachers: the context of social support and coping.

PubMed

Schonfeld, I S

2001-05-01

The effects of adverse work environments were examined in the context of other risk/protective factors in this extension of a short-term longitudinal study involving 184 newly appointed women teachers. Regression analyses revealed that-adjusting for preemployment levels of the outcomes and negative affectivity-social support and adversity in the fall work environment were among the factors that affected spring depressive symptoms, self-esteem, job satisfaction, and motivation to teach. Support from nonwork sources was directly related to future improved symptom levels and self-esteem; supervisor and colleague support were directly related to future job satisfaction. Effects of occupational coping, professional efficacy, locus of control, and school factors (e.g., special vs. regular education) were largely nonsignificant. Structural equation analyses indicated that adverse working conditions began to seriously affect the women soon after they started teaching.

Direct His bundle pacing post AVN ablation.

PubMed

Lakshmanadoss, Umashankar; Aggarwal, Ashim; Huang, David T; Daubert, James P; Shah, Abrar

2009-08-01

Atrioventricular nodal (AVN) ablation with concomitant pacemaker implantation is one of the strategies that reduce symptoms in patients with atrial fibrillation (AF). However, the long-term adverse effects of right ventricular (RV) apical pacing have led to the search for alternating sites of pacing. Biventricular pacing produces a significant improvement in functional capacity over RV pacing in patients undergoing AVN ablation. Another alternative site for pacing is direct His bundle to reduce the adverse outcome of RV pacing. Here, we present a case of direct His bundle pacing using steerable lead delivery system in a patient with symptomatic paroxysmal AF with concurrent AVN ablation.

Exposure to socioeconomic adversity in early life and risk of depression at 18 years: The mediating role of locus of control.

PubMed

Culpin, Iryna; Stapinski, Lexine; Miles, Ömür Budanur; Araya, Ricardo; Joinson, Carol

2015-09-01

Previous studies have linked exposure to early socioeconomic adversity to depression, but the mechanisms of this association are not well understood. Locus of control (LoC), an individual's control-related beliefs, has been implicated as a possible mechanism, however, longitudinal evidence to support this is lacking. The study sample comprised 8803 participants from a UK cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Indicators of early socioeconomic adversity were collected from the antenatal period to 5 years and modelled as a latent factor. Depression was assessed using the Clinical Interview Schedule-Revised (CIS-R) at 18 years. LoC was assessed with the Nowicki-Strickland Internal-External (CNSIE) scale at 16 years. Using structural equation modelling, we found that 34% of the total estimated association between early socioeconomic adversity and depression at 18 years was explained by external LoC at 16 years. There was weak evidence of a direct pathway from early socioeconomic adversity to depression after accounting for the indirect effect via external locus of control. Socioeconomic adversity was associated with more external LoC, which, in turn, was associated with depression. Attrition may have led to an underestimation of the direct and indirect effect sizes in the complete case analysis. Results suggest that external LoC in adolescence is one of the factors mediating the link between early adversity and depression at 18 years. Cognitive interventions that seek to modify maladaptive control beliefs in adolescence may be effective in reducing risk of depression following early life adversity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Direct-to-consumer advertising for bleeding disorders: a content analysis and expert evaluation of advertising claims.

PubMed

Abel, G A; Neufeld, E J; Sorel, M; Weeks, J C

2008-10-01

In the United States, the Food and Drug Administration (FDA) requires that all direct-to-consumer advertising (DTCA) contain both an accurate statement of a medication's effects ('truth') and an even-handed discussion of its benefits and risks/adverse effects ('fair balance'). DTCA for medications to treat rare diseases such as bleeding disorders is unlikely to be given high priority for FDA review. We reviewed all DTCA for bleeding disorder products appearing in the patient-directed magazine HemeAware from January 2004 to June 2006. We categorized the information presented in each advertisement as benefit, risk/adverse effect, or neither, and assessed the amount of text and type size devoted to each. We also assessed the readability of each type of text using the Flesch Reading Ease Score (FRES, where a score of >or=65 is considered of average readability), and assessed the accuracy of the advertising claims utilizing a panel of five bleeding disorder experts. A total of 39 unique advertisements for 12 products were found. On average, approximately twice the amount of text was devoted to benefits as compared with risks/adverse effects, and the latter was more difficult to read [FRES of 32.0 for benefits vs. 20.5 for risks/adverse effects, a difference of 11.5 (95% CI: 4.5-18.5)]. Only about two-thirds of the advertising claims were considered by a majority of the experts to be based on at least low-quality evidence. As measured by our methods, print DTCA for bleeding disorders may not reach the FDA's standards of truth and fair balance.

Are adverse effects incorporated in economic models? An initial review of current practice.

PubMed

Craig, D; McDaid, C; Fonseca, T; Stock, C; Duffy, S; Woolacott, N

2009-12-01

To identify methodological research on the incorporation of adverse effects in economic models and to review current practice. Major electronic databases (Cochrane Methodology Register, Health Economic Evaluations Database, NHS Economic Evaluation Database, EconLit, EMBASE, Health Management Information Consortium, IDEAS, MEDLINE and Science Citation Index) were searched from inception to September 2007. Health technology assessment (HTA) reports commissioned by the National Institute for Health Research (NIHR) HTA programme and published between 2004 and 2007 were also reviewed. The reviews of methodological research on the inclusion of adverse effects in decision models and of current practice were carried out according to standard methods. Data were summarised in a narrative synthesis. Of the 719 potentially relevant references in the methodological research review, five met the inclusion criteria; however, they contained little information of direct relevance to the incorporation of adverse effects in models. Of the 194 HTA monographs published from 2004 to 2007, 80 were reviewed, covering a range of research and therapeutic areas. In total, 85% of the reports included adverse effects in the clinical effectiveness review and 54% of the decision models included adverse effects in the model; 49% included adverse effects in the clinical review and model. The link between adverse effects in the clinical review and model was generally weak; only 3/80 (< 4%) used the results of a meta-analysis from the systematic review of clinical effectiveness and none used only data from the review without further manipulation. Of the models including adverse effects, 67% used a clinical adverse effects parameter, 79% used a cost of adverse effects parameter, 86% used one of these and 60% used both. Most models (83%) used utilities, but only two (2.5%) used solely utilities to incorporate adverse effects and were explicit that the utility captured relevant adverse effects; 53% of those models that included utilities derived them from patients on treatment and could therefore be interpreted as capturing adverse effects. In total, 30% of the models that included adverse effects used withdrawals related to drug toxicity and therefore might be interpreted as using withdrawals to capture adverse effects, but this was explicitly stated in only three reports. Of the 37 models that did not include adverse effects, 18 provided justification for this omission, most commonly lack of data; 19 appeared to make no explicit consideration of adverse effects in the model. There is an implicit assumption within modelling guidance that adverse effects are very important but there is a lack of clarity regarding how they should be dealt with and considered in modelling. In many cases a lack of clear reporting in the HTAs made it extremely difficult to ascertain what had actually been carried out in consideration of adverse effects. The main recommendation is for much clearer and explicit reporting of adverse effects, or their exclusion, in decision models and for explicit recognition in future guidelines that 'all relevant outcomes' should include some consideration of adverse events.

Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011

PubMed Central

Nordanger, Dag Ø.; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

2014-01-01

Background Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care. PMID:24872862

Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011.

PubMed

Nordanger, Dag Ø; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

2014-01-01

Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents' proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care.

Biological Sensitivity to Context: The Interactive Effects of Stress Reactivity and Family Adversity on Socio-Emotional Behavior and School Readiness

PubMed Central

Obradović, Jelena; Bush, Nicole R.; Stamperdahl, Juliet; Adler, Nancy E.; Boyce, W. Thomas

2009-01-01

This study examined the direct and interactive effects of stress reactivity and family adversity on socio-emotional and cognitive development in 338 five-to-six-year-old children. Neurobiological stress reactivity was measured as respiratory sinus arrhythmia and salivary cortisol responses to social, cognitive, sensory, and emotional challenges. Adaptation was assessed using child, parent, and teacher reports of externalizing symptoms, prosocial behaviors, school engagement, and academic competence. Results revealed significant interactions between reactivity and adversity. High stress reactivity was associated with more maladaptive outcomes in the context of high adversity but with better adaption in the context of low adversity. The findings corroborate a reconceptualization of stress reactivity as biological sensitivity to context by showing that high reactivity can both hinder and promote adaptive functioning. PMID:20331667

49 CFR 106.40 - Direct final rule.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PHMSA Rulemaking Documents § 106.40 Direct final rule. A direct final rule makes regulatory changes and states that the regulatory changes will take effect on a specified date unless PHMSA receives an adverse... rule would be inappropriate, or would be ineffective or unacceptable without a change. It may challenge...

Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

PubMed

Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

2016-04-01

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. © The Author (2015). Published by Oxford University Press.

Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament

PubMed Central

Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A.; Münsterkötter, Anna L.; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter

2016-01-01

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations.

PubMed

Vilar, Santiago; Hripcsak, George

2016-01-01

Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.

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

PubMed

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

2018-02-01

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

Effects of Hurricane Katrina and Other Adverse Life Events on Adolescent Female Offenders: A Test of General Strain Theory

PubMed Central

Robertson, Angela R.; Stein, Judith A.; Schaefer-Rohleder, Lacey

2011-01-01

This study tested Agnew’s General Strain Theory (GST) by examining the roles of anger, anxiety, and maladaptive coping in mediating the relationship between strain and three outcomes (serious delinquency, minor delinquency, and continued involvement in the juvenile justice system) among adolescent female offenders (N = 261). Strains consisted of adverse life events and exposure to Hurricane Katrina. Greater exposure to Hurricane Katrina was directly related to serious delinquency and maladaptive coping. Hurricane Katrina also had an indirect effect on minor delinquency and Post–Katrina juvenile justice involvement mediated through maladaptive coping. Adverse life events were associated with increased anger, anxiety, and maladaptive coping. Anger mediated the relationship between adverse life events and serious delinquency. Anxiety mediated the relationship between adverse life events and minor delinquency. Maladaptive coping strategies were associated with minor delinquency and juvenile justice involvement. Findings lend support to GST. PMID:21572904

Cinnamon: A systematic review of adverse events.

PubMed

Hajimonfarednejad, Mahdie; Ostovar, Mohadeseh; Raee, Mohammad Javad; Hashempur, Mohammad Hashem; Mayer, Johannes Gottfried; Heydari, Mojtaba

2018-04-05

Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a popular spice for thousands of years around the world. Many studies have shown therapeutic effects of cinnamon including its antimicrobial, antiviral, antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic, gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon and several human reports on adverse events associated with short or long term use of cinnamon, we aimed to systematically review its human reports of adverse event. Databases including Medline, Scopus, Science Direct, Embase, PubMed Central and Google scholar were searched using the key words "cinnamon" or "cinnamomum" for clinical trials, case reports and case series. Also spontaneous reports about adverse effects of cinnamon were collected from five national and international spontaneous reporting schemes. Thirty eight clinical trials were found, five of them reported adverse events. Twenty case reports and seven case series, as well as, spontaneous reports including 160 adverse events were also included. The most frequent adverse events were gastrointestinal disorders and allergic reactions which were self-limiting in the majority of cases. The available data suggests that despite the safety of cinnamon use as a spice and/or flavoring agent, its use may be associated with significant adverse effects in medicinal uses with larger doses or longer duration of use and should be clinically monitored. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Effects of cumulative stress and impulsivity on smoking status.

PubMed

Ansell, Emily B; Gu, Peihua; Tuit, Keri; Sinha, Rajita

2012-03-01

The stress-vulnerability model of addiction predicts that environmental factors, such as cumulative stress, will result in individual adaptations that decrease self-control, increase impulsivity, and increase risk for addiction. Impulsivity and cumulative stress are risk factors for tobacco smoking that are rarely examined simultaneously in research. We examined the indirect and direct effects of cumulative adversity in a community sample consisting of 291 men and women who participated in an assessment of cumulative stress, self-reported impulsivity, and smoking history. Data were analyzed using bootstrapping techniques to estimate indirect effects of stress on smoking via impulsivity. Cumulative adversity is associated with smoking status via direct effects and indirect effects through impulsivity scores. Additional models examining specific types of stress indicate contributions of traumatic stress and recent life events as well as chronic relationship stressors. Overall, cumulative stress is associated with increased risk of smoking via increased impulsivity and via pathways independent of impulsivity. These findings support the stress-vulnerability model and highlight the utility of mediation models in assessing how, and for whom, cumulative stress increases risk of current cigarette smoking. Increasing self-control is a target for interventions with individuals who have experienced cumulative adversity. Copyright © 2012 John Wiley & Sons, Ltd.

Effects of cumulative stress and impulsivity on smoking status

PubMed Central

Ansell, Emily B.; Gu, Peihua; Tuit, Keri; Sinha, Rajita

2013-01-01

Objective The stress-vulnerability model of addiction predicts that environmental factors, such as cumulative stress, will result in individual adaptations that decrease self-control, increase impulsivity, and increase risk for addiction. Impulsivity and cumulative stress are risk factors for tobacco smoking that are rarely examined simultaneously in research. Methods We examined the indirect and direct effects of cumulative adversity in a community sample consisting of 291 men and women who participated in an assessment of cumulative stress, self-reported impulsivity, and smoking history. Data were analyzed using bootstrapping techniques to estimate indirect effects of stress on smoking via impulsivity. Results Cumulative adversity is associated with smoking status via direct effects and indirect effects through impulsivity scores. Additional models examining specific types of stress indicate contributions of traumatic stress and recent life events as well as chronic relationship stressors. Conclusions Overall, cumulative stress is associated with increased risk of smoking via increased impulsivity and via pathways independent of impulsivity. These findings support the stress-vulnerability model and highlight the utility of mediation models in assessing how, and for whom, cumulative stress increases risk of current cigarette smoking. Increasing self-control is a target for interventions with individuals who have experienced cumulative adversity. PMID:22389084

The effects of power, leadership and psychological safety on resident event reporting.

PubMed

Appelbaum, Nital P; Dow, Alan; Mazmanian, Paul E; Jundt, Dustin K; Appelbaum, Eric N

2016-03-01

Although the reporting of adverse events is a necessary first step in identifying and addressing lapses in patient safety, such events are under-reported, especially by frontline providers such as resident physicians. This study describes and tests relationships between power distance and leader inclusiveness on psychological safety and the willingness of residents to report adverse events. A total of 106 resident physicians from the departments of neurosurgery, orthopaedic surgery, emergency medicine, otolaryngology, neurology, obstetrics and gynaecology, paediatrics and general surgery in a mid-Atlantic teaching hospital were asked to complete a survey on psychological safety, perceived power distance, leader inclusiveness and intention to report adverse events. Perceived power distance (β = -0.26, standard error [SE] 0.06, 95% confidence interval [CI] -0.37 to 0.15; p < 0.001) and leader inclusiveness (β = 0.51; SE 0.07, 95% CI 0.38-0.65; p < 0.001) both significantly predicted psychological safety, which, in turn, significantly predicted intention to report adverse events (β = 0.34; SE 0.08, 95% CI 0.18-0.49; p < 0.001). Psychological safety significantly mediated the direct relationship between power distance and intention to report adverse events (indirect effect: -0.09; SE 0.02, 95% CI -0.13 to 0.04; p < 0.001). Psychological safety also significantly mediated the direct relationship between leader inclusiveness and intention to report adverse events (indirect effect: 0.17; SE 0.02, 95% CI 0.08-0.27; p = 0.001). Psychological safety was found to be a predictor of intention to report adverse events. Perceived power distance and leader inclusiveness both influenced the reporting of adverse events through the concept of psychological safety. Because adverse event reporting is shaped by relationships and culture external to the individual, it should be viewed as an organisational as much as a personal function. Supervisors and other leaders in health care should ensure that policies, procedures and leadership practices build psychological safety and minimise power distance between low- and high-status members in order to support greater reporting of adverse events. © 2016 John Wiley & Sons Ltd.

78 FR 43770 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-22

... elevator rear spar stiffener assembly, which could adversely affect elevator structural stiffness, which... aircraft in air commerce by prescribing regulations for practices, methods, and procedures the... 13132. This AD will not have a substantial direct effect on the States, on the relationship between the...

Adverse reactions to methylphenidate treatment for attention-deficit/hyperactivity disorder: structure and associations with clinical characteristics and symptom control.

PubMed

Sonuga-Barke, Edmund J S; Coghill, David; Wigal, Timothy; DeBacker, Marc; Swanson, James

2009-12-01

Methylphenidate (MPH)-related adverse events are well characterized. Their predictors and their relationship with therapeutic effects are less well understood. Here we examine these issues in relation to two long-acting formulations. Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Parents also completed the Barkley Stimulant Side Effect Rating Scale (BSSERS). The BSSERS had six factors: Emotionality, sleep/appetite, disengaged, dizzy, uninterested, and aches. Treatment effects were seen only for emotionality (which improved) and sleep and appetite (which worsened). Adverse events were not predictable from personal and clinical characteristics of patients. Sleep/appetite adverse events were not associated with therapeutic effects. Improvements in attention-deficit/hyperactivity disorder (ADHD) and emotionality were correlated. The results support a narrow conceptualization of MPH adverse events with problems restricted to appetite and sleep. These effects were not predictable on the basis of available information and may be due to an underlying mechanism rather distinct from those determining therapeutic effects.

40 CFR 227.18 - Factors considered.

Code of Federal Regulations, 2010 CFR

2010-07-01

... biochemical degradation during movement of the materials from a disposal site to an area of significant... humans directly; (g) Presence in the material of chemical constituents which may be bioaccumulated or persistent and may have an adverse effect on humans directly or through food chain interactions; (h) Presence...

Emotion dysregulation mediates the relationship between lifetime cumulative adversity and depressive symptomatology.

PubMed

Abravanel, Benjamin T; Sinha, Rajita

2015-02-01

Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and "at-risk" remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Emotion Dysregulation Mediates the Relationship between Lifetime Cumulative Adversity and Depressive Symptomatology

PubMed Central

Abravanel, Benjamin T.; Sinha, Rajita

2014-01-01

Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and “at-risk” remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. PMID:25528603

The cost of nurse-sensitive adverse events.

PubMed

Pappas, Sharon Holcombe

2008-05-01

The aim of this study was to describe the methodology for nursing leaders to determine the cost of adverse events and effective levels of nurse staffing. The growing transparency of quality and cost outcomes motivates healthcare leaders to optimize the effectiveness of nurse staffing. Most hospitals have robust cost accounting systems that provide actual patient-level direct costs. These systems allow an analysis of the cost consumed by patients during a hospital stay. By knowing the cost of complications, leaders have the ability to justify the cost of improved staffing when quality evidence shows that higher nurse staffing improves quality. An analysis was performed on financial and clinical data from hospital databases of 3,200 inpatients. The purpose was to establish a methodology to determine actual cost per case. Three diagnosis-related groups were the focus of the analysis. Five adverse events were analyzed along with the costs. A regression analysis reported that the actual direct cost of an adverse event was dollars 1,029 per case in the congestive heart failure cases and dollars 903 in the surgical cases. There was a significant increase in the cost per case in medical patients with urinary tract infection and pressure ulcers and in surgical patients with urinary tract infection and pneumonia. The odds of pneumonia occurring in surgical patients decreased with additional registered nurse hours per patient day. Hospital cost accounting systems are useful in determining the cost of adverse events and can aid in decision making about nurse staffing. Adverse events add costs to patient care and should be measured at the unit level to adjust staffing to reduce adverse events and avoid costs.

Stay Legal and Safe in Treating for Bed Bugs

EPA Pesticide Factsheets

Quick fix solutions may sound appealing, but they may not be legal, safe, or effective. To avoid adverse effects such as poisoning, buy EPA-registered pesticides labeled for bed bug control, and follow all label directions and precautions.

The Effect of Toxic Cyanobacteria on Human and Animal Health

EPA Science Inventory

The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

Gestational bisphenol A exposure and testis development.

PubMed

Williams, Cecilia; Bondesson, Maria; Krementsov, Dimitry N; Teuscher, Cory

Virtually all humans are exposed to bisphenol A (BPA). Since BPA can act as a ligand for estrogen receptors, potential hazardous effects of BPA should be evaluated in the context of endogenous estrogenic hormones. Because estrogen is metabolized in the placenta, developing fetuses are normally exposed to very low endogenous estrogen levels. BPA, on the other hand, passes through the placenta and might have distinct adverse consequences during the sensitive stages of fetal development. Testicular gametogenesis and steroidogenesis begin early during fetal development. These processes are sensitive to estrogens and play a role in determining the number of germ stem cells, sperm count, and male hormone levels in adulthood. Although studies have shown a correlation between BPA exposure and perturbed reproduction, a clear consensus has yet to be established as to whether current human gestational BPA exposure results in direct adverse effects on male genital development and reproduction. However, studies in animals and in vitro have provided direct evidence for the ability of BPA exposure to influence male reproductive development. This review discusses the current knowledge of potential effects of BPA exposure on male reproductive health and whether gestational exposure adversely affects testis development.

40 CFR 227.18 - Factors considered.

Code of Federal Regulations, 2012 CFR

2012-07-01

... persistent and may have an adverse effect on humans directly or through food chain interactions; (h) Presence... standards; (d) Visible characteristics of the materials (e.g., color, suspended particulates) which result...

40 CFR 227.18 - Factors considered.

Code of Federal Regulations, 2011 CFR

2011-07-01

... persistent and may have an adverse effect on humans directly or through food chain interactions; (h) Presence... standards; (d) Visible characteristics of the materials (e.g., color, suspended particulates) which result...

40 CFR 227.18 - Factors considered.

Code of Federal Regulations, 2013 CFR

2013-07-01

... persistent and may have an adverse effect on humans directly or through food chain interactions; (h) Presence... standards; (d) Visible characteristics of the materials (e.g., color, suspended particulates) which result...

40 CFR 227.18 - Factors considered.

Code of Federal Regulations, 2014 CFR

2014-07-01

... persistent and may have an adverse effect on humans directly or through food chain interactions; (h) Presence... standards; (d) Visible characteristics of the materials (e.g., color, suspended particulates) which result...

Maternal employment and the health of low-income young children.

PubMed

Gennetian, Lisa A; Hill, Heather D; London, Andrew S; Lopoo, Leonard M

2010-05-01

This study examines whether maternal employment affects the health status of low-income, elementary-school-aged children using instrumental variables estimation and experimental data from a welfare-to-work program implemented in the early 1990s. Maternal report of child health status is predicted as a function of exogenous variation in maternal employment associated with random assignment to the experimental group. IV estimates show a modest adverse effect of maternal employment on children's health. Making use of data from another welfare-to-work program we propose that any adverse effect on child health may be tempered by increased family income and access to public health insurance coverage, findings with direct relevance to a number of current policy discussions. In a secondary analysis using fixed effects techniques on longitudinal survey data collected in 1998 and 2001, we find a comparable adverse effect of maternal employment on child health that supports the external validity of our primary result.

User experience while viewing stereoscopic 3D television

PubMed Central

Read, Jenny C.A.; Bohr, Iwo

2014-01-01

3D display technologies have been linked to visual discomfort and fatigue. In a lab-based study with a between-subjects design, 433 viewers aged from 4 to 82 years watched the same movie in either 2D or stereo 3D (S3D), and subjectively reported on a range of aspects of their viewing experience. Our results suggest that a minority of viewers, around 14%, experience adverse effects due to viewing S3D, mainly headache and eyestrain. A control experiment where participants viewed 2D content through 3D glasses suggests that around 8% may report adverse effects which are not due directly to viewing S3D, but instead are due to the glasses or to negative preconceptions about S3D (the ‘nocebo effect'). Women were slightly more likely than men to report adverse effects with S3D. We could not detect any link between pre-existing eye conditions or low stereoacuity and the likelihood of experiencing adverse effects with S3D. Practitioner Summary: Stereoscopic 3D (S3D) has been linked to visual discomfort and fatigue. Viewers watched the same movie in either 2D or stereo 3D (between-subjects design). Around 14% reported effects such as headache and eyestrain linked to S3D itself, while 8% report adverse effects attributable to 3D glasses or negative expectations. PMID:24874550

14 CFR 11.13 - What is a direct final rule?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false What is a direct final rule? 11.13 Section 11.13 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL... adverse comment, we then withdraw the final rule before it becomes effective and may issue an NPRM. ...

14 CFR 11.13 - What is a direct final rule?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false What is a direct final rule? 11.13 Section 11.13 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL... adverse comment, we then withdraw the final rule before it becomes effective and may issue an NPRM. ...

Pharyngeal dysesthesia in refractory complex partial epilepsy: new seizure or adverse effect of vagal nerve stimulation?

PubMed

Akman, Cigdem; Riviello, James J; Madsen, Joseph R; Bergin, Ann M

2003-06-01

Sensory symptoms are commonly seen in association with focal epilepsy, but viscerosensory auras, such as pharyngeal dysesthesias, are rarely the main clinical manifestation. With the introduction of vagal nerve stimulation (VNS) for medically refractory epilepsy, viscerosensory symptoms commonly occur as an adverse effect of VNS. Voice alterations (hoarseness or tremulousness), local neck or throat pain, and cough are the most common adverse effects seen during active stimulation (on-time). Numbness of the throat, neck, or chin, as well as a tingling sensation of the neck and throat is directly related to stimulation intensity. We present a case in which recurrent pharyngeal sensations caused a diagnostic dilemma and in which monitoring the VNS artifact during video/EEG and correlating this with clinical symptoms helped determine the etiology of the recurrent sensory symptoms.

Completeness of serious adverse drug event reports received by the US Food and Drug Administration in 2014.

PubMed

Moore, Thomas J; Furberg, Curt D; Mattison, Donald R; Cohen, Michael R

2016-06-01

Adverse drug event reports to the US Food and Drug Administration (FDA) remain the primary tool for identifying serious drug adverse effects without adequate existing warnings. We assessed the completeness of reports the FDA received in 2014. Serious adverse drug event reports were evaluated for whether they included age, gender, event date, and at least one medical term describing the event in computer excerpts. Report sources were direct reports to the FDA, manufacturer expedited reports about events without adequate warnings, and manufacturer periodic reports about events with existing warnings. In 2014, the FDA received 528,192 new case reports indicating a serious or fatal outcome, 25,038 (4.7%) directly from health professionals and consumers, and 503,154 (95.3%) from drug manufacturers. Overall, 21,595 (86.2%) of serious reports submitted directly to the FDA provided data for all four completeness variables, compared with 271,022 (40.4%) of manufacturer expedited reports and 24,988 (51.3%) of periodic reports. Among manufacturer serious reports, 37.9% lacked age and 46.9% had no event date. Performance by 25 manufacturers submitting 5000 or more reports varied from 24.4% complete on all variables to 67% complete. Patient death cases had the lowest completeness scores in all categories. By these measures, report completeness from drug manufacturers was poor compared with direct submissions to the agency. The FDA needs to update reporting requirements and compliance policies to help industry capture better adverse event information from new forms of manufacturer interactions with health professionals and consumers. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

77 FR 72746 - Regulation of Fuels and Fuel Additives: Modifications to Renewable Fuel Standard and Diesel...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-06

...EPA published a direct final rule on October 9, 2012 to amend the definition of heating oil in 40 CFR 80.1401 in the Renewable Fuel Standard (``RFS'') program under section 211(o) of the Clean Air Act. The direct final rule also amended requirements under EPA's diesel sulfur program related to the sulfur content of locomotive and marine diesel fuel produced by transmix processors, and the fuel marker requirements for 500 ppm sulfur locomotive and marine (LM) diesel fuel to allow for solvent yellow 124 marker to transition out of the distribution system. Because EPA received adverse comments on the heating oil definition and transmix amendments, we are withdrawing those portions of the direct final rule. Because EPA did not receive adverse comments with respect to the yellow marker amendments, those amendments will become effective as indicated in the direct final rule.

Human Health Effects Associated with Exposure to Cyanobacteria and Cyanotoxins: What Do We Know?

EPA Science Inventory

The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

36 CFR 297.5 - Determination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... determined that: (1) The water resources project will not have a direct and adverse effect on the values for... the boundaries of said river, or; (2) The effects of the water resources project will neither invade...; (3) The effects of the water resources project will neither invade nor diminish the scenic...

36 CFR 297.5 - Determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... determined that: (1) The water resources project will not have a direct and adverse effect on the values for... the boundaries of said river, or; (2) The effects of the water resources project will neither invade...; (3) The effects of the water resources project will neither invade nor diminish the scenic...

36 CFR 297.5 - Determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... determined that: (1) The water resources project will not have a direct and adverse effect on the values for... the boundaries of said river, or; (2) The effects of the water resources project will neither invade...; (3) The effects of the water resources project will neither invade nor diminish the scenic...

36 CFR 297.5 - Determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... determined that: (1) The water resources project will not have a direct and adverse effect on the values for... the boundaries of said river, or; (2) The effects of the water resources project will neither invade...; (3) The effects of the water resources project will neither invade nor diminish the scenic...

36 CFR 297.5 - Determination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... determined that: (1) The water resources project will not have a direct and adverse effect on the values for... the boundaries of said river, or; (2) The effects of the water resources project will neither invade...; (3) The effects of the water resources project will neither invade nor diminish the scenic...

The long arm of community: the influence of childhood community contexts across the early life course.

PubMed

Wickrama, K A S; Noh, Samuel

2010-08-01

This study examines the longitudinal effects of childhood community contexts on young adult outcomes. The study uses a sample of 14,000 adolescents (52% female) derived from the 1990 US Census and the National Longitudinal Study of Adolescent Health (Addhealth). The study examines whether community and family environments exert separate and/or joint long-term influences on young adult achievement and depression. We found both direct and indirect long-term influences of childhood community adversity on young adult educational attainment. The indirect influences of childhood community adversity operated through family and individual-level factors. The long-term influence of childhood community adversity on young adult depression was only indirect. Overall, community influences on young adult achievement outcomes were mediated by family context and by the adolescents' adjustments and transitions, including adolescent depression, school adjustment, and disruptive transitional events. The moderating effect of childhood community adversity suggests that the protective effects of family resources on young adult outcomes dissipate significantly in extremely adverse neighborhoods. The findings demonstrate the importance of integrating multiple theoretical perspectives for longitudinal research to capture pathways of community influence on adolescent developmental and young adulthood outcomes.

Adverse Childhood Experiences and Suicide Attempts: The Mediating Influence of Personality Development and Problem Behaviors.

PubMed

Perez, Nicholas M; Jennings, Wesley G; Piquero, Alex R; Baglivio, Michael T

2016-08-01

Adverse childhood experiences, comprised of forms of maltreatment and certain dysfunctional household environments, can affect the development of a child in a variety of different ways. This multitude of developmental changes may subsequently produce compounding harmful effects on the child's life and increase acutely maladaptive outcomes, including adolescent suicidal behavior. This study uses data collected from 2007 to 2012 for 64,329 Florida Department of Juvenile Justice youth (21.67 % female, 42.88 % African American, and 15.37 % Hispanic) to examine the direct and indirect effects of adverse childhood experiences on suicide attempts. Using a generalized structural equation model, the effects of adverse childhood experience scores are estimated on suicidal behavior through pathways of certain aspects of a child's personality development (aggression and impulsivity), as well as adolescent problem behaviors (school difficulties and substance abuse). The results show that a large proportion of the relationship between childhood adversity and suicide is mediated by the aforementioned individual characteristics, specifically through the youth's maladaptive personality development. These results suggest that, if identified early enough, the developmental issues for these youth could potentially be addressed in order to thwart potential suicidal behavior.

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem.

PubMed

Kabiru, Caroline W; Elung'ata, Patricia; Mojola, Sanyu A; Beguy, Donatien

2014-01-01

Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? We used cross-sectional data from 3,064 males and females aged 12-19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries.

Adverse reactions from essential oil-containing natural flea products exempted from Environmental Protection Agency regulations in dogs and cats.

PubMed

Genovese, Allison G; McLean, Mary Kay; Khan, Safdar A

2012-08-01

To describe adverse effects in dogs and cats exposed to Environmental Protection Agency exempted plant-derived flea preventatives containing mixtures of essential oils. Retrospective study from 2006 to 2008. Records of dog and cat cases were reviewed from the American Society for the Prevention of Cruelty to Animals, Animal Poison Control Center database. Thirty-nine cats and 9 dogs with history of exposure to natural flea preventatives. The following information was retrieved from each incident: number of animals, species involved, frequency, types, onset time, duration of clinical signs, exposure appropriateness, final outcome, and treatment information. Ninety-two percent of animals (n = 44) showed presence of one or more adverse effects. The frequency of adverse effects in dogs (n = 8; 89%) and cats (n = 36; 92%) was similar. Onset time of adverse effects in 39 of 44 animals occurred within 24 hours. The duration of signs in 24 animals ranged from 30 minutes to 149 hours. The products were used as per label in 77% animals (n = 37). Of 28 animals with known outcome, 50% (n = 14) recovered with bathing alone while others received intravenous fluids, muscle relaxants, and anticonvulsive medications. Death (1 cat; n = 1/28; 4%) or euthanasia (1 cat and 1 dog; n = 2/28; 7%) was reported in 3 animals. Dogs and cats can experience significant adverse effects when exposed to plant-derived flea preventatives even when used according to label directions. The number of reports of exposure in cats was higher than dogs, but the frequency of reported adverse effects was similar between the 2 species. Agitation and hypersalivation were common in cats, whereas lethargy and vomiting were common in dogs. © Veterinary Emergency and Critical Care Society 2012.

Proximal muscular atrophy and weakness: An unusual adverse effect of deferasirox iron chelation therapy.

PubMed

Vill, K; Müller-Felber, W; Teusch, V; Blaschek, A; Gerstl, L; Huetker, S; Albert, M H

2016-01-01

Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of pesticides and contaminants on neotropical migrants

Treesearch

Nicholas W. Gard; Michael J. Hooper; Richard S. Bennett

1993-01-01

Many agricultural pesticides and industrial contaminants are capable of adversely affecting birds through direct effects such as elevated mortality rates and decreased reproductive success or indirectly by modifying habitat composition or food availability. Although neotropical migrants are potentially exposed to these contaminants on their breeding, migratory and...

COMPARATIVE IN VITRO CARDIAC TOXICITY OF PRIMARY COMBUSTION PARTICLES: IDENTIFICATION OF CAUSAL CONSTITUENTS AND MECHANISMS OF INJURY

EPA Science Inventory

Identification of causal particle characteristics and mechanisms of injury would allow linkage of particulate air pollution adverse health effects to sources. Research has examined the direct cardiovascular effects of air pollution particle constituents since previous studies dem...

77 FR 41716 - Amendment Relating to Reasonable Contract or Arrangement Under Section 408(b)(2)-Fee Disclosure...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-16

...This proposed rule is a companion to the Department of Labor (Department) Employee Benefits Security Administration's direct final rule (published today in the ``Rules and Regulations'' section of the Federal Register) amending the Department's fiduciary-level fee disclosure regulation under section 408(b)(2) of the Employee Retirement Income Security Act of 1974 (ERISA) to revise the mailing address and enhance the web-based submission procedure for notices filed under the regulation's fiduciary class exemption provision. The Department is publishing this amendment as a direct final rule without prior proposal because the Department views this as highly technical and anticipates no significant adverse comment. The Department has explained its reasons in the preamble to the direct final rule. If the Department receives no significant adverse comment during the comment period, no further action on this proposed rule will be taken. If, however, the Department receives significant adverse comment, the Department will withdraw the direct final rule and it will not take effect. In that case, the Department will address all public comments in a subsequent final rule based on this proposed rule. The Department will not institute a second comment period on this rule. Any parties interested in commenting must do so during this comment period.

Adverse effects of plant food supplements and botanical preparations: a systematic review with critical evaluation of causality

PubMed Central

Di Lorenzo, Chiara; Ceschi, Alessandro; Kupferschmidt, Hugo; Lüde, Saskia; De Souza Nascimento, Elizabeth; Dos Santos, Ariana; Colombo, Francesca; Frigerio, Gianfranco; Nørby, Karin; Plumb, Jenny; Finglas, Paul; Restani, Patrizia

2015-01-01

AIMS The objective of this review was to collect available data on the following: (i) adverse effects observed in humans from the intake of plant food supplements or botanical preparations; (ii) the misidentification of poisonous plants; and (iii) interactions between plant food supplements/botanicals and conventional drugs or nutrients. METHODS PubMed/MEDLINE and Embase were searched from database inception to June 2014, using the terms ‘adverse effect/s’, ‘poisoning/s’, ‘plant food supplement/s’, ‘misidentification/s’ and ‘interaction/s’ in combination with the relevant plant name. All papers were critically evaluated according to the World Health Organization Guidelines for causality assessment. RESULTS Data were obtained for 66 plants that are common ingredients of plant food supplements; of the 492 papers selected, 402 (81.7%) dealt with adverse effects directly associated with the botanical and 89 (18.1%) concerned interactions with conventional drugs. Only one case was associated with misidentification. Adverse effects were reported for 39 of the 66 botanical substances searched. Of the total references, 86.6% were associated with 14 plants, including Glycine max/soybean (19.3%), Glycyrrhiza glabra/liquorice (12.2%), Camellia sinensis/green tea ( 8.7%) and Ginkgo biloba/gingko (8.5%). CONCLUSIONS Considering the length of time examined and the number of plants included in the review, it is remarkable that: (i) the adverse effects due to botanical ingredients were relatively infrequent, if assessed for causality; and (ii) the number of severe clinical reactions was very limited, but some fatal cases have been described. Data presented in this review were assessed for quality in order to make the results maximally useful for clinicians in identifying or excluding deleterious effects of botanicals. PMID:25251944

75 FR 71559 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Withdrawal of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

...Mobil Refining and Supply Company-- Beaumont Refinery, published on October 1, 2010. DATES: Effective...: Because EPA received adverse comments, we are withdrawing the direct final exclusion for ExxonMobil...

One Health and the Environment: Toxic Cyanobacteria, a Case Study

EPA Science Inventory

The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants in ambient exposure situations. ...

The moderating role of decision authority and coworker- and supervisor support on the impact of job demands in nursing homes: a cross-sectional study.

PubMed

Willemse, Bernadette M; de Jonge, Jan; Smit, Dieneke; Depla, Marja F I A; Pot, Anne Margriet

2012-07-01

Healthcare workers in nursing homes are faced with high job demands that can have a detrimental impact on job-related outcomes, such as job satisfaction. Job resources may have a buffering role on this relationship. The Demand-Control-Support (DCS) Model offers a theoretical framework to study how specific job resources can buffer the adverse effects of high demands, and can even activate positive consequences of high demands. The present study tests the moderating (i.e. buffering and activating) effects of decision authority and coworker- and supervisor support that are assumed by the hypotheses of the DCS Model. A national cross-sectional survey was conducted with an anonymous questionnaire. One hundred and thirty six living arrangements that provide nursing home care for people with dementia in the Netherlands. Fifteen healthcare workers per living arrangement. In total, 1147 people filled out the questionnaires (59% response rate). Hierarchical multilevel regression analyses were conducted to test the assumption that the effect of job demands on the dependent variables is buffered or activated the most when both decision authority and social support are high. This moderation is statistically represented by three-way interactions (i.e. demands×authority×support), while lower-order effects are taken into account (i.e. two-way interactions). The hypotheses are supported when three-way interaction effects are found in the expected direction. The dependent variables studied are job satisfaction, emotional exhaustion, and personal accomplishment. The proposed buffering and activation hypotheses of the DCS Model were not supported in our study. Three-way interaction effects were found for emotional exhaustion and personal accomplishment, though not in the expected direction. In addition, two-way interaction effects were found for job satisfaction and emotional exhaustion. Decision authority was found to buffer the adverse effect of job demands and to activate healthcare staff. Supervisor support was found to buffer the adverse effect of job demands on emotional exhaustion in situations with low decision authority. Finally, coworker support was found to have an adverse effect on personal accomplishment in high strain situations. Findings reveal that decision authority in particular makes healthcare workers in nursing homes less vulnerable to adverse effects of high job demands, and promotes positive consequences of work. Copyright © 2012 Elsevier Ltd. All rights reserved.

Relationship between adverse childhood experiences and homelessness and the impact of axis I and II disorders.

PubMed

Roos, Leslie E; Mota, Natalie; Afifi, Tracie O; Katz, Laurence Y; Distasio, Jino; Sareen, Jitender

2013-12-01

We investigated the links between homelessness associated with serious mental and physical healthy disparities and adverse childhood experiences (ACEs) in nationally representative data, with Axis I and II disorders as potential mediators. We examined data from the National Epidemiologic Survey of Alcohol and Related Conditions in 2001-2002 and 2004-2005, and included 34,653 participants representative of the noninstitutionalized US population who were 20 years old or older. We studied the variables related to 4 classes of Axis I disorders, all 10 Axis II personality disorders, a wide range of ACEs, and a lifetime history of homelessness. Analyses revealed high prevalences of each ACE in individuals experiencing lifetime homelessness (17%-60%). A mediation model with Axis I and II disorders determined that childhood adversities were significantly related to homelessness through direct effects (adjusted odd ratios = 2.04, 4.24) and indirect effects, indicating partial mediation. Population attributable fractions were also reported. Although Axis I and II disorders partially mediated the relationship between ACEs and homelessness, a strong direct association remained. This novel finding has implications for interventions and policy. Additional research is needed to understand relevant causal pathways.

Mothers’ Employment and Health of Low-Income Children

PubMed Central

Gennetian, Lisa; Hill, Heather; Lopoo, Leonard; London, Andrew

2010-01-01

This study examines whether maternal employment affects the health status of low-income, elementary-school-aged children using instrumental variables estimation and experimental data from a welfare-to-work program implemented in the early 1990s. Mother’s report of child health status is predicted as a function of exogenous variation in maternal employment associated with random assignment to the program group. IV estimates show a modest adverse effect of maternal employment on children’s health. Making use of data from another welfare-to-work program we propose that any adverse effect on child health may be tempered by increased family income and access to public health insurance coverage, findings with direct relevance to a number of current policy discussions. In a secondary analysis using fixed effects techniques on longitudinal survey data collected in 1998 and 2001, we find a comparable adverse effect of maternal employment on child health that supports the external validity of our primary result. PMID:20356641

Bosutinib, dasatinib, imatinib, nilotinib, and ponatinib differentially affect the vascular molecular pathways and functionality of human endothelial cells.

PubMed

Gover-Proaktor, Ayala; Granot, Galit; Pasmanik-Chor, Metsada; Pasvolsky, Oren; Shapira, Saar; Raz, Oshrat; Raanani, Pia; Leader, Avi

2018-05-09

The tyrosine kinase inhibitors (TKIs), nilotinib, ponatinib, and dasatinib (but not bosutinib or imatinib), are associated with vascular adverse events (VAEs) in chronic myeloid leukemia (CML). Though the mechanism is inadequately understood, an effect on vascular cells has been suggested. We investigated the effect of imatinib, nilotinib, dasatinib, bosutinib, and ponatinib on tube formation, cell viability, and gene expression of human vascular endothelial cells (HUVECs). We found a distinct genetic profile in HUVECs treated with dasatinib, ponatinib, and nilotinib compared to bosutinib and imatinib, who resembled untreated samples. However, unique gene expression and molecular pathway alterations were detected between dasatinib, ponatinib, and nilotinib. Angiogenesis/blood vessel-related pathways and HUVEC function (tube formation/viability) were adversely affected by dasatinib, ponatinib, and nilotinib but not by imatinib or bosutinib. These results correspond to the differences in VAE profiles of these TKIs, support a direct effect on vascular cells, and provide direction for future research.

What magnitude are observed non-target impacts from weed biocontrol?

PubMed

Suckling, David Maxwell; Sforza, René François Henri

2014-01-01

A systematic review focused by plant on non-target impacts from agents deliberately introduced for the biological control of weeds found significant non-target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents on 140 non-target plants was retrospectively categorized using a risk management framework for ecological impacts of invasive species (minimal, minor, moderate, major, massive). The vast majority of agents introduced for classical biological control of weeds (>99% of 512 agents released) have had no known significant adverse effects on non-target plants thus far; major effects suppressing non-target plant populations could be expected to be detectable. Most direct non-target impacts on plants (91.6%) were categorized as minimal or minor in magnitude with no known adverse long-term impact on non-target plant populations, but a few cacti and thistles are affected at moderate (n = 3), major (n = 7) to massive (n = 1) scale. The largest direct impacts are from two agents (Cactoblastis cactorum on native cacti and Rhinocyllus conicus on native thistles), but these introductions would not be permitted today as more balanced attitudes exist to plant biodiversity, driven by both society and the scientific community. Our analysis shows (as far as is known), weed biological control agents have a biosafety track record of >99% of cases avoiding significant non-target impacts on plant populations. Some impacts could have been overlooked, but this seems unlikely to change the basic distribution of very limited adverse effects. Fewer non-target impacts can be expected in future because of improved science and incorporation of wider values. Failure to use biological control represents a significant opportunity cost from the certainty of ongoing adverse impacts from invasive weeds. It is recommended that a simple five-step scale be used to better communicate the risk of consequences from both action (classical biological control) and no action (ongoing impacts from invasive weeds).

What Magnitude Are Observed Non-Target Impacts from Weed Biocontrol?

PubMed Central

Suckling, David Maxwell; Sforza, René François Henri

2014-01-01

A systematic review focused by plant on non-target impacts from agents deliberately introduced for the biological control of weeds found significant non-target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents on 140 non-target plants was retrospectively categorized using a risk management framework for ecological impacts of invasive species (minimal, minor, moderate, major, massive). The vast majority of agents introduced for classical biological control of weeds (>99% of 512 agents released) have had no known significant adverse effects on non-target plants thus far; major effects suppressing non-target plant populations could be expected to be detectable. Most direct non-target impacts on plants (91.6%) were categorized as minimal or minor in magnitude with no known adverse long-term impact on non-target plant populations, but a few cacti and thistles are affected at moderate (n = 3), major (n = 7) to massive (n = 1) scale. The largest direct impacts are from two agents (Cactoblastis cactorum on native cacti and Rhinocyllus conicus on native thistles), but these introductions would not be permitted today as more balanced attitudes exist to plant biodiversity, driven by both society and the scientific community. Our analysis shows (as far as is known), weed biological control agents have a biosafety track record of >99% of cases avoiding significant non-target impacts on plant populations. Some impacts could have been overlooked, but this seems unlikely to change the basic distribution of very limited adverse effects. Fewer non-target impacts can be expected in future because of improved science and incorporation of wider values. Failure to use biological control represents a significant opportunity cost from the certainty of ongoing adverse impacts from invasive weeds. It is recommended that a simple five-step scale be used to better communicate the risk of consequences from both action (classical biological control) and no action (ongoing impacts from invasive weeds). PMID:24454755

Systematic review of pediatric health outcomes associated with childhood adversity.

PubMed

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

2018-02-23

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

75 FR 52316 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

..., electronic, mechanical, or other technological collection techniques or other forms of information technology... responsibilities. A Direct PLUS Loan borrower must not have an adverse credit history. If an applicant for a Direct PLUS Loan is determined to have an adverse credit history, the applicant may qualify for a Direct PLUS...

Adverse childhood experiences and adult smoking, Nebraska, 2011.

PubMed

Yeoman, Kristin; Safranek, Thomas; Buss, Bryan; Cadwell, Betsy L; Mannino, David

2013-09-19

Smoking is a public health risk; the prevalence of smoking among adults in Nebraska is 18.4%. Studies indicate that maltreatment of children alters their brain development, possibly increasing risk for tobacco use. Previous studies have documented associations between childhood maltreatment and adult health behaviors, demonstrating the influence of adverse experiences on tobacco use. We examined prevalence and associations between adverse childhood experiences and smoking among Nebraskans. We analyzed 2011 Nebraska Behavioral Risk Factor Surveillance System (Adverse Childhood Experience module) data, defining adverse childhood experience exposures as physical, sexual, and verbal abuse (ie, direct exposures), and household dysfunction associated with mental illness, substance abuse, divorce, domestic violence, and living with persons with incarceration histories (ie, environmental exposures). We estimated prevalence of exposures, taking into account the complex survey design. We used logistic regression with predicted margins to estimate adjusted relative risk for smoking by direct or environmental exposure. Approximately 51% of Nebraskans experienced 1 or more adverse childhood events; 7% experienced 5 or more. Prevalence of environmental exposures (42%) was significantly higher than that of direct exposures (31%). Prevalence of individual exposures ranged from 6% (incarceration of a household member) to 25% (verbal abuse). Adjusted relative risks of smoking for direct and environmental exposures were 1.5 and 1.8, respectively. We present a new method of evaluating adverse childhood experience data. Prevalence of adverse childhood experiences is high among Nebraskans, and these exposures are associated with smoking. State-specific strategies to monitor adverse events among children and provide interventions might help to decrease the smoking rate in this population.

78 FR 78770 - Fisheries of the Caribbean, Gulf of Mexico, and South Atlantic; Snapper-Grouper Fishery Off the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

..., to the extent practicable, the adverse effects on fishers, support industries, and associated... addition, the issue of disproportional effects on small versus large entities does not arise in the present... has no direct effects on the profits of commercial and for-hire vessels, because there are no...

Effectiveness and adverse effects of the use of apomorphine and 3% hydrogen peroxide solution to induce emesis in dogs.

PubMed

Khan, Safdar A; McLean, Mary Kay; Slater, Margaret; Hansen, Steven; Zawistowski, Stephen

2012-11-01

To determine the effectiveness and adverse effects of apomorphine and 3% hydrogen peroxide solution used for emesis in dogs. Prospective observational study. 147 dogs that received apomorphine (IV or placed in the conjunctival sac) or 3% hydrogen peroxide solution (PO) to induce emesis after exposure to toxic agents. Data regarding signalment; agent information; type, dose, route, and number of emetic administrations; whether emesis was successful; number of times emesis occurred; percentage of ingested agent recovered; and adverse effects were collected via telephone during American Society for the Prevention of Cruelty to Animals Animal Poison Control Center operations and stored in a database for analysis. Mann-Whitney and Fisher exact tests were used to evaluate emetic success rates. Apomorphine and 3% hydrogen peroxide solution successfully induced emesis in 59 of 63 (94%) and 76 of 84 (90%) of dogs, respectively. Mean time to onset of emesis after the first dose of emetic was 14.5 and 18.6 minutes when hydrogen peroxide (n = 37) and apomorphine (31) were used, respectively, with mean durations of 42 and 27 minutes, respectively. Mean estimates for recovery of ingested agents were 48% for hydrogen peroxide and 52% for apomorphine. Adverse effects were reported in 16 of 112 (14%) dogs for which information was available. 3% hydrogen peroxide solution and apomorphine effectively induced emesis in dogs when used as directed. Emesis occurred within minutes after administration and helped recover substantial amounts of ingested agents. Adverse effects of both emetics were considered mild and self-limiting.

Childhood adversity, attachment and personality styles as predictors of anxiety among elderly caregivers.

PubMed

Prigerson, H G; Shear, M K; Bierhals, A J; Zonarich, D L; Reynolds, C F

1996-01-01

The purpose of this study was to examine the ways in which childhood adversity, attachment and personality styles influenced the likelihood of having an anxiety disorder among aged caregivers for terminally ill spouses. We also sought to determine how childhood adversity and attachment/personality styles jointly influenced the likelihood of developing an anxiety disorder among aged caregivers. Data were derived from semistructured interviews with 50 spouses (aged 60 and above) of terminally ill patients. The Childhood Experience of Care and Abuse (CECA) record provided retrospective, behaviorally based information on childhood adversity. Measures of attachment and personality styles were obtained from self-report questionnaires, and the Structured Clinical Interview for the DSM-III-R (SCID) was used to determine diagnoses for anxiety disorders. Logistic regression models estimated the effects of childhood adversity, attachment/personality disturbances, and the interaction between the two on the likelihood of having an anxiety disorder. Results indicated that childhood adversity and paranoid, histrionic and self-defeating styles all directly increase the odds of having an anxiety disorder as an elderly spousal caregiver. In addition, childhood adversity in conjunction with borderline, antisocial and excessively dependent styles increased the likelihood of having an anxiety disorder. The results indicate the need to investigate further the interaction between childhood experiences and current attachment/personality styles in their effects on the development of anxiety disorders.

Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

PubMed

Hurt, Hallam; Betancourt, Laura M

2016-01-01

It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem

PubMed Central

2014-01-01

Background Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? Methods We used cross-sectional data from 3,064 males and females aged 12–19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Results Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Conclusions Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries. PMID:25210535

One Health and the Environment: Toxic Cyanobacteria A Case Study

EPA Science Inventory

The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

The mediating effect of parental neglect on adolescent and young adult anti-sociality: a longitudinal study of twins and their parents.

PubMed

Eaves, Lindon J; Prom, Elizabeth C; Silberg, Judy L

2010-07-01

The causes of correlation between parental treatment and offspring behavior are ambiguous since genetic and social factors are correlated in typical family studies. The problem is complicated by the need to characterize the effects of genes and environment on both juvenile and adult behavioral outcomes. A model is developed for the resemblance between juvenile and adult twins and their parents that allows some of these effects to be resolved. Data on childhood adversity, parental anti-social behavior, and longitudinal adult and juvenile anti-social behavior were obtained from 1,412 families of adolescent and young adult twins. A structural model is fitted that allows for the effects of genetic and social transmission of information from parents to children. Environmental effects of parents may be mediated through measured features of the home environment. Parameters were estimated by diagonal weighted least squares applied to the 33 distinct polychoric correlations between relatives and between variables within and between ages. Sub-hypotheses were tested. Results confirmed that effects of genes and environment were both highly significant. Genetic effects were large in juveniles and largely age and sex-specific. Approximately 30% of the variation due to the shared environment was due to the effect of childhood adversity. The remaining shared environmental effects are unexplained. Adversity is affected significantly by maternal anti-social behavior. The correlation between paternal ASP and adversity may be explained by antisocial fathers selecting (or creating) antisocial mothers. All significant environmental effects of parental ASP are mediated through the measure of adversity. Though transmission of ASP is both genetic and social, passive genotype-environment correlation is very small. Assortative mating for ASP has barely detectable consequence for the genetic correlation between siblings. The longitudinal study of twins and their parents makes it possible to demonstrate there is a direct causal effect of childhood adversity on child conduct disorder over and above any indirect genetic correlation.

Early origins of inflammation: An examination of prenatal and childhood social adversity in a prospective cohort study.

PubMed

Slopen, Natalie; Loucks, Eric B; Appleton, Allison A; Kawachi, Ichiro; Kubzansky, Laura D; Non, Amy L; Buka, Stephen; Gilman, Stephen E

2015-01-01

Children exposed to social adversity carry a greater risk of poor physical and mental health into adulthood. This increased risk is thought to be due, in part, to inflammatory processes associated with early adversity that contribute to the etiology of many adult illnesses. The current study asks whether aspects of the prenatal social environment are associated with levels of inflammation in adulthood, and whether prenatal and childhood adversity both contribute to adult inflammation. We examined associations of prenatal and childhood adversity assessed through direct interviews of participants in the Collaborative Perinatal Project between 1959 and 1974 with blood levels of C-reactive protein in 355 offspring interviewed in adulthood (mean age=42.2 years). Linear and quantile regression models were used to estimate the effects of prenatal adversity and childhood adversity on adult inflammation, adjusting for age, sex, and race and other potential confounders. In separate linear regression models, high levels of prenatal and childhood adversity were associated with higher CRP in adulthood. When prenatal and childhood adversity were analyzed together, our results support the presence of an effect of prenatal adversity on (log) CRP level in adulthood (β=0.73, 95% CI: 0.26, 1.20) that is independent of childhood adversity and potential confounding factors including maternal health conditions reported during pregnancy. Supplemental analyses revealed similar findings using quantile regression models and logistic regression models that used a clinically-relevant CRP threshold (>3mg/L). In a fully-adjusted model that included childhood adversity, high prenatal adversity was associated with a 3-fold elevated odds (95% CI: 1.15, 8.02) of having a CRP level in adulthood that indicates high risk of cardiovascular disease. Social adversity during the prenatal period is a risk factor for elevated inflammation in adulthood independent of adversities during childhood. This evidence is consistent with studies demonstrating that adverse exposures in the maternal environment during gestation have lasting effects on development of the immune system. If these results reflect causal associations, they suggest that interventions to improve the social and environmental conditions of pregnancy would promote health over the life course. It remains necessary to identify the mechanisms that link maternal conditions during pregnancy to the development of fetal immune and other systems involved in adaptation to environmental stressors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Positive Parenting as a Protective Resource for Parentally Bereaved Children

ERIC Educational Resources Information Center

Haine, Rachel A.; Wolchik, Sharlene A.; Sandler, Irwin N.; Millsap, Roger E.; Ayers, Tim S.

2006-01-01

Positive parenting was examined as a protective resource against the adverse effects of negative life events on parentally bereaved children's mental health problems. The sample consisted of 313 recently bereaved children ages 8 to 16 and their current caregiver. Both the compensatory (direct effect independent of negative life events) and the…

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

Factors associated with adverse clinical outcomes among obstetric trainees

PubMed Central

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

2016-01-01

Objective To determine whether UK obstetric trainees transitioning from directly to indirectly-supervised practice have a higher likelihood of adverse patient outcomes from operative deliveries compared to other indirectly supervised trainees and to examine whether performing more procedures under direct supervision is associated with fewer adverse outcomes in initial indirect practice. Methods We examined all deliveries (13,861) conducted by obstetricians at a single centre over 5 years (2008-2013). Mixed-effects logistic regression models were used to compare estimated blood loss, maternal trauma, umbilical arterial pH, delayed neonatal respiration, failed instrumental delivery, and critical incidents for trainees in their first indirectly-supervised year with trainees in all other years of indirect practice. Outcomes for trainees in their first indirectly-supervised 3 months were compared to their outcomes for the remainder of the year. Linear regression was used to examine the relationship between number of procedures performed under direct supervision and initial outcomes under indirect supervision. Results Trainees in their first indirectly-supervised year had a higher likelihood of >2 litres estimated blood loss at any delivery (OR 1.32;CI(1.01-1.64) p<0.05) and of failed instrumental delivery (OR 2.33;CI(1.37-3.29) p<0.05) compared with other indirectly-supervised trainees. Other measured outcomes showed no significant differences. Within the first three months of indirect supervision, the likelihood of operative vaginal deliveries with >1litre estimated blood loss (OR 2.54;CI(1.88-3.20) p<0.05) was higher compared to the remainder of the first year. Performing more deliveries under direct supervision prior to beginning indirectly-supervised training was associated with decreased risk of >1litre estimated blood loss (p<0.05). Conclusions Obstetric trainees in their first year of indirectly-supervised practice have a higher likelihood of immediate adverse delivery outcomes, which are primarily maternal rather than neonatal. Undertaking more directly supervised procedures prior to transitioning to indirectly-supervised practice may reduce adverse outcomes, suggesting that experience is a key consideration in obstetric training programme design. PMID:26077215

DIESEL PARTICLE GENERATION, CHARACTERIZATION, AND DIRECT ANIMAL EXPOSURE STUDIES

EPA Science Inventory

Inhalation of diesel exhaust is associated with the development of asthma as well as other adverse health effects. Studies have also demonstrated that diesel exhaust induces pulmonary changes that worsen asthmatic responses to respiratory allergens. This paper describes the des...

75 FR 73972 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Removal of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... adverse comment by October 25, 2010, the direct final rule would not take effect and we would publish a.... Lists of Subjects in 40 CFR Part 261 Environmental Protection, Hazardous waste, Recycling, Reporting and...

Sodium Tetradecyl Sulphate Direct Intralesional Sclerotherapy of Venous Malformations of the Vulva and Vagina: Report of Five Cases

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

Krokidis, Miltiadis, E-mail: mkrokidis@hotmail.com; Venetucci, Pietro; Hatzidakis, Adam

2011-02-15

We report five cases of female patients affected by symptomatic focal external genital venous malformations treated with percutaneous direct intralesional injection of sodium tetradecyl sulphate (STS). All patients were referred because of discomfort and pain when sexual intercourse was attempted. Direct sclerotherapy with 3% STS was performed on a day-hospital basis with the patient under local anesthesia. Complete resolution of the symptoms was achieved in all cases. No major adverse effects were reported. Direct intralesional sclerotherapy with STS may be considered a safe and effective method for the treatment of female external genital malformation without the necessity of general anesthesiamore » for pain control.« less

Pharmacology of the Phosphate Binder, Lanthanum Carbonate

PubMed Central

Damment, Stephen JP

2011-01-01

Studies were conducted to compare the phosphate-binding efficacy of lanthanum carbonate directly with other clinically used phosphate binders and to evaluate any potential adverse pharmacology. To examine the phosphate-binding efficacy, rats with normal renal function and chronic renal failure received lanthanum carbonate, aluminum hydroxide, calcium carbonate, or sevelamer hydrochloride in several experimental models. Lanthanum carbonate and aluminum hydroxide markedly increased excretion of [32P]-phosphate in feces and reduced excretion in urine in rats with normal renal function (p < 0.05), indicating good dietary phosphate-binding efficacy. In rats with chronic renal failure, lanthanum carbonate and aluminum hydroxide reduced urinary phosphate excretion to a greater degree and more rapidly than calcium carbonate, which in turn was more effective than sevelamer hydrochloride. The potential to induce adverse pharmacological effects was assessed systematically in mice, rats, and dogs with normal renal function using standard in vivo models. There was no evidence of any adverse secondary pharmacological effects of lanthanum carbonate on the central nervous, cardiovascular, respiratory, or gastrointestinal systems. These studies indicate that lanthanum carbonate is the more potent of the currently available dietary phosphate binders. No adverse secondary pharmacological actions were observed in vivo in a systematic evaluation at high doses. PMID:21332344

Ecological risk assessment for DvSnf7 RNA: A plant-incorporated protectant with targeted activity against western corn rootworm.

PubMed

Bachman, Pamela M; Huizinga, Kristin M; Jensen, Peter D; Mueller, Geoffrey; Tan, Jianguo; Uffman, Joshua P; Levine, Steven L

2016-11-01

MON 87411 maize, which expresses DvSnf7 RNA, was developed to provide an additional mode of action to confer protection against corn rootworm (Diabrotica spp.). A critical step in the registration of a genetically engineered crop with an insecticidal trait is performing an ecological risk assessment to evaluate the potential for adverse ecological effects. For MON 87411, an assessment plan was developed that met specific protection goals by characterizing the routes and levels of exposure, and testing representative functional taxa that would be directly or indirectly exposed in the environment. The potential for toxicity of DvSnf7 RNA was evaluated with a harmonized battery of non-target organisms (NTOs) that included invertebrate predators, parasitoids, pollinators, soil biota as well as aquatic and terrestrial vertebrate species. Laboratory tests evaluated ecologically relevant endpoints such as survival, growth, development, and reproduction and were of sufficient duration to assess the potential for adverse effects. No adverse effects were observed with any species tested at, or above, the maximum expected environmental concentration (MEEC). All margins of exposure for NTOs were >10-fold the MEEC. Therefore, it is reasonable to conclude that exposure to DvSnf7 RNA, both directly and indirectly, is safe for NTOs at the expected field exposure levels. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

A review on cardiovascular diseases originated from subclinical hypothyroidism.

PubMed

Mansourian, Azad Reza

2012-01-15

Thyroid hormones play an important role on the cardiovascular systems and thyroid disorder ultimately have a profound adverse effects on myocardium and vascular functions. There are extensive reports on the role of overt thyroid dysfunction which adversely can modify the cardiovascular metabolism but even at the present of some controversial reports, the subclinical thyroid disorders are able also to manipulate cardiovascular system to some extent. The aim of this study is to review the cardiovascular disorders accompanied with subclinical hypothyroidism. It is concluded that adverse effect of thyroid malfunction on myocardium and vascular organs are through the direct role of thyroid hormone and dyslipidemia on heart muscle cells at nuclear level and vascular system, respectively. It seems many cardiovascular disorders initially would not have been occurred in the first place if the thyroid of affected person had functioned properly, therefore thyroid function tests should be one of a prior laboratory examinations in cardiovascular disorders.

Multiple lines of evidence risk assessment of American robins exposed to polychlorinated dibenzofurans (PCDFS) and polychlorinated dibenzo-P-dioxins (PCDDS) in the Tittabawassee River floodplain, Midland, Michigan, USA.

PubMed

Tazelaar, Dustin L; Fredricks, Timothy B; Seston, Rita M; Coefield, Sarah J; Bradley, Patrick W; Roark, Shaun A; Kay, Denise P; Newsted, John L; Giesy, John P; Bursian, Steven J; Zwiernik, Matthew J

2013-06-01

Concentrations of polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) in Tittabawassee River floodplain soils and biota downstream of Midland, Michigan, USA, are greater than regional background concentrations. From 2005 to 2008, a multiple lines of evidence approach was utilized to evaluate the potential for effects of PCDD/DFs on American robins (Turdus migratorius) breeding in the floodplains. A dietary-based assessment indicated there was potential for adverse effects for American robins predicted to have the greatest exposures. Conversely, a tissue-based risk assessment based on site-specific PCDD/DF concentrations in American robin eggs indicated minimal potential for adverse effects. An assessment based on reproductive endpoints indicated that measures of hatch success in study areas were significantly less than those of reference areas. However, there was no dose-response relationship between that endpoint and concentrations of PCDD/DF. Although dietary-based exposure and reproductive endpoint assessments predicted potential for adverse effects to resident American robins, the tissue-based assessment indicates minimal to no potential for adverse effects, which is reinforced by the fact the response was not dose related. It is likely that the dietary assessment is overly conservative given the inherent uncertainties of estimating dietary exposure relative to direct tissue-based assessment measures. Based on the available data, it can be concluded that exposure to PCDD/DFs in the Tittabawassee River floodplain would not likely result in adverse population-level effects to American robins. Copyright © 2013 SETAC.

You are not alone: relatedness reduces adverse effects of state orientation on well-being under stress.

PubMed

Chatterjee, Monischa B; Baumann, Nicola; Osborne, Danny

2013-04-01

A low ability to self-regulate emotions (state orientation) is associated with reduced well-being--especially under stress. Until now, research has approached this topic from an asocial perspective that views the self as devoid from relatedness concerns. However, people are social creatures who benefit from their relationships with others. As such, we expected that personally valuing (Study 1) and experimentally priming (Study 2) a sense of relatedness with others would act as a buffer against stress-related impairments in state-oriented individuals. In Study 1, high (vs. low) benevolence values removed the adverse effect of state orientation on well-being found under stressful life circumstances. In Study 2, focusing on similarities (vs. differences) while comparing oneself with a friend removed the adverse effect of state orientation on recovery from a negative mood induction. Our findings suggest that individuals with low self-regulatory competencies may profit from valuing and directing their attention toward their relatedness with others.

Gold standards in pharmacovigilance: the use of definitive anecdotal reports of adverse drug reactions as pure gold and high-grade ore.

PubMed

Hauben, Manfred; Aronson, Jeffrey K

2007-01-01

Anecdotal reports of adverse drug reactions are generally regarded as being of poor evidential quality. This is especially relevant for postmarketing drug safety surveillance, which relies heavily on spontaneous anecdotal reports. The numerous limitations of spontaneous reports cannot be overemphasised, but there is another side to the story: these datasets also contain anecdotal reports that can be considered to describe definitive adverse reactions, without the need for further formal verification. We have previously defined four categories of such adverse reactions: (i) extracellular or intracellular tissue deposition of the drug or a metabolite; (ii) a specific anatomical location or pattern of injury; (iii) physiological dysfunction or direct tissue damage demonstrable by physicochemical testing; and (iv) infection, as a result of the administration of an infective agent as the therapeutic substance or because of demonstrable contamination. In this article, we discuss the implications of these definitive ('between-the-eyes') adverse effects for pharmacovigilance.

78 FR 57280 - Chlorantraniliprole; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

... toxicity studies in rats, minimally increased microvesiculation of adrenal cortex was observed in males... cortex effects observed in rat studies were not considered adverse. Chlorantraniliprole does not exhibit.... 601 et seq.), do not apply. This final rule directly regulates growers, food processors, food handlers...

Impact of Wind Direction on Near-Road Pollutant Concentrations

EPA Science Inventory

Exposure to roadway emissions is an emerging area of research because of recent epidemiological studies reporting association between living within a few hundred meters of high-traffic roadways and adverse health effects. The air quality impact of roadway emissions has been studi...

Growing up with adversity: From juvenile justice involvement to criminal persistence and psychosocial problems in young adulthood.

PubMed

Basto-Pereira, Miguel; Miranda, Ana; Ribeiro, Sofia; Maia, Ângela

2016-12-01

Several studies have been carried out to investigate the effect of child maltreatment on juvenile justice involvement and future criminal life. However, little is known about the impact of other forms of adversity, beyond abuse and neglect, on juvenile delinquency and criminal persistence. The effect of early adversity on psychosocial problems is underexplored, particularly in juvenile delinquents. This study, using the Childhood Adverse Experiences (ACE) questionnaire, a tool accessing the exposure to different types of abuse, neglect and serious household dysfunction, explored the role of each adverse experience on juvenile justice involvement, persistence in crime and psychosocial problems during young adulthood. A Portuguese sample of 75 young adults with official records of juvenile delinquency in 2010/2011, and 240 young adults from a community sample completed ACE questionnaire and measures of psychosocial adjustment. Seven out of ten adverse experiences were significantly more prevalent in young adults with juvenile justice involvement than in the community sample, after matching the main demographic variables. The strongest predictor of juvenile justice involvement and criminal persistence during early adulthood was sexual abuse. Dimensions of child/adolescent emotional maltreatment and a mental illness in the household predicted a set of psychosocial problems in young adulthood. This study indicates that early adversity is significantly related to juvenile justice involvement, criminal persistence and psychosocial problems. This study also suggests that each experience has a different role in this process. There is an urgent need to screen, prevent and stop serious adversity. Future scientific directions and recommendations for policies are provided. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occupational exposure to ultrafine particles in police officers: no evidence for adverse respiratory effects.

PubMed

Jordakieva, G; Grabovac, I; Valic, E; Schmidt, K E; Graff, A; Schuster, A; Hoffmann-Sommergruber, K; Oberhuber, C; Scheiner, O; Goll, A; Godnic-Cvar, J

2018-01-01

Inhalation exposure to fine and ultrafine particles (UFPs) has been associated with respiratory diseases. However, little is known on the quality, threshold levels and concentration of these particles causing adverse health effects. The impact of occupational exposure to submicrometer and UFPs was assessed in 30 healthy police shooting instructors by clinical investigation, self-assessment questionnaire, sputum and spirometry and compared to a control group. General laboratory chemistry parameters, circulating cytokines (interleukin [IL]-2, IL-4, IL-5, IL-6, IL-8, interferon-gamma [IFN-γ]), and granulocyte macrophage colony-stimulating factor (GM-CSF) in serum were measured. UFP exposure was recorded by Scanning Mobility Particle Sizer. Concentrations of submicrometer sized airborne particles (< 700 nm) measured between 3.34 × 10 5 /cm 3 and 7.58 × 10 5 /cm 3 at shooting sites, with highest concentrations found in the UFP range (< 100 nm). The size of the monodispersed particles ranged from 54.74 ± 16.25 nm to 98.19 ± 22.83 nm. Short term exposure (4 h) to high levels of UFPs caused an increase of IFN-γ in exposed subjects ( p  = 0.022). 24 h after exposure a significant decrease of IgG, albumin fibrinogen and factor VII was found. Neither directly after 4 h of high levels UFPs exposure nor 24 h after exposure subjective complaints or objective measurements indicating adverse respiratory effects in exposed subjects were found. No consistent indications for adverse respiratory or inflammatory effects directly following exposure and 24 h after exposure to high levels of UFPs in our study group were detected. However we showed the assessment of short-term exposure effects at a genuine occupational setting, which might is relevant when a risk assessment of high level occupational exposures to UFPs is considered.

Relationship Between Adverse Childhood Experiences and Homelessness and the Impact of Axis I and II Disorders

PubMed Central

Roos, Leslie E.; Mota, Natalie; Afifi, Tracie O.; Katz, Laurence Y.; Distasio, Jino

2013-01-01

Objectives. We investigated the links between homelessness associated with serious mental and physical healthy disparities and adverse childhood experiences (ACEs) in nationally representative data, with Axis I and II disorders as potential mediators. Methods. We examined data from the National Epidemiologic Survey of Alcohol and Related Conditions in 2001–2002 and 2004–2005, and included 34 653 participants representative of the noninstitutionalized US population who were 20 years old or older. We studied the variables related to 4 classes of Axis I disorders, all 10 Axis II personality disorders, a wide range of ACEs, and a lifetime history of homelessness. Results. Analyses revealed high prevalences of each ACE in individuals experiencing lifetime homelessness (17%–60%). A mediation model with Axis I and II disorders determined that childhood adversities were significantly related to homelessness through direct effects (adjusted odd ratios = 2.04, 4.24) and indirect effects, indicating partial mediation. Population attributable fractions were also reported. Conclusions. Although Axis I and II disorders partially mediated the relationship between ACEs and homelessness, a strong direct association remained. This novel finding has implications for interventions and policy. Additional research is needed to understand relevant causal pathways. PMID:24148049

A structural model of racial discrimination, acculturative stress, and cultural resources among Arab American adolescents.

PubMed

Ahmed, Sawssan R; Kia-Keating, Maryam; Tsai, Katherine H

2011-12-01

Despite evidence towards the risk for discrimination and acculturative stress that Arab American adolescents may face, the link between socio-cultural adversities and psychological well-being in this population has not been established. This study examined the role of socio-cultural adversities (discrimination and acculturative stress) and cultural resources (ethnic identity, religious support and religious coping) in terms of their direct impact on psychological distress. Using structural equation modeling, the proposed model was tested with 240 Arab American adolescents. The results indicated a strong positive relationship between socio-cultural adversities and psychological distress. Furthermore, this study supported a promotive model of cultural resources, where a negative association between cultural resources and psychological distress was found. Understanding the manner in which socio-cultural adversities and resources are linked to psychological distress can inform the development of culturally appropriate interventions that can effectively mitigate mental health concerns for understudied and vulnerable populations.

Short-term efficacy and safety of new biological agents targeting the interleukin-23-T helper 17 pathway for moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis.

PubMed

Gómez-García, F; Epstein, D; Isla-Tejera, B; Lorente, A; Vélez García-Nieto, A; Ruano, J

2017-03-01

A new generation of biologics targeting the interleukin-23-T helper 17 pathway has been developed. This study aimed to assess the short-term effectiveness and safety of these new agents using a network meta-analysis. Twenty-seven randomized clinical trials (10 629 patients) were identified by a comprehensive systematic literature review (PROSPERO 2015: CRD42015025472). Quality of evidence was assessed following Cochrane-compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations approach. Efficacy and safety outcomes at weeks 10-16 were compared using a random-effects network meta-analysis within a frequentist framework to estimate pooled odds ratios (ORs) of direct and indirect comparisons among the therapeutic options. There were six direct drug-to-drug comparisons in the network, with a high degree of consistency between the direct and indirect evidence. From the available evidence, infliximab 5 mg kg -1 every 8 weeks [OR 118·89, 95% confidence interval (CI) 60·91-232·04] and secukinumab 300 mg every 4 weeks (OR 87·07, 95% CI 55·01-137·82) are shown to be among the most effective short-term treatments, but are ranked as the biologics most likely to produce any adverse event or an infectious adverse event, respectively. Ustekinumab 90 mg every 12 weeks, the third most efficacious treatment (OR 73·67, 95% CI 46·97-115·56), was the only agent that did not show increased risk of adverse events compared with placebo. Treatment recommendations should also consider long-term outcomes and costs. © 2016 British Association of Dermatologists.

Despite 2007 law requiring FDA hotline to be included in print drug ads, reporting of adverse events by consumers still low.

PubMed

Du, Dongyi; Goldsmith, John; Aikin, Kathryn J; Encinosa, William E; Nardinelli, Clark

2012-05-01

In 2007 the federal government began requiring drug makers to include in their print direct-to-consumer advertisements information for consumers on how to contact the Food and Drug Administration directly, either by phone or through the agency's website, to report any adverse events that they experienced after taking a prescription drug. Adverse events can range from minor skin problems like itching to serious injuries or illness that result in hospitalization, permanent disability, or even death. Even so, current rates of adverse event reporting are low. We studied adverse event reports about 123 drugs that came from patients before and after the enactment of the print advertising requirement and estimated that requirement's impact with model simulations. We found that if monthly spending on print direct-to-consumer advertising increased from zero to $7.7 million per drug, the presence of the Food and Drug Administration contact information tripled the increase in patient-reported adverse events, compared to what would have happened in the absence of the law. However, the absolute monthly increase was fewer than 0.24 reports per drug, suggesting that the public health impact of the increase was small and that the adverse event reporting rate would still be low. The study results suggest that additional measures, such as more publicity about the Adverse Event Reporting System or more consumer education, should be considered to promote patient reporting of adverse events.

Adverse breast cancer treatment effects: the economic case for making rehabilitative programs standard of care.

PubMed

Schmitz, Kathryn H; DiSipio, Tracey; Gordon, Louisa G; Hayes, Sandra C

2015-06-01

The purpose of this work was to evaluate the patient-borne financial cost of common, adverse breast cancer treatment-associated effects, comparing cost across women with or without these side effects. Two hundred eighty-seven Australian women diagnosed with early-stage breast cancer were prospectively followed starting at 6 months post-surgery for 12 months, with three monthly assessments of detailed treatment-related side effects and their direct and indirect patient costs attributable to breast cancer. Bootstrapping statistics were used to analyze cost data, and adjusted logistic regression was used to evaluate the association between costs and adverse events from breast cancer. Costs were inflated and converted from 2002 Australian to 2014 US dollars. More than 90 % of women experienced at least one adverse effect (i.e., post-surgical issue, reaction to radiotherapy, upper-body symptoms or reduced function, lymphedema, fatigue, or weight gain). On average, women paid $5,636 (95 % confidence interval (CI), $4,694, $6,577) in total costs. Women with any one of the following symptoms (fatigue, reduced upper-body function, upper-body symptoms) or women who report ≥4 adverse treatment-related effects, have 1.5 to nearly 4 times the odds of having higher healthcare costs than women who do not report these complaints (p < 0.05). Women face substantial economic burden due to a range of treatment-related health problems, which may persist beyond the treatment period. Improving breast cancer care by incorporating prospective surveillance of treatment-related side effects and strategies for prevention and treatment of concerns (e.g., exercise) has real potential for reducing patient-borne costs.

Proposed definition of environmental damage illustrated by the cases of genetically modified crops and invasive species.

PubMed

Bartz, Robert; Heink, Ulrich; Kowarik, Ingo

2010-06-01

The introduction of non-native plant species and the release of genetically modified (GM) crops can induce environmental changes at gene to ecosystem levels. Regulatory frameworks such as the Convention on Biological Diversity or the EU Deliberate Release Directive aim to prevent environmental damage but do not define the term. Although ecologists and conservationists often refer to environmental effects of GM crops or invasive species as damage, most authors do not disclose their normative assumptions or explain why some environmental impacts are regarded as detrimental and others are not. Thus far, a concise definition of environmental damage is missing and is necessary for a transparent assessment of environmental effects or risks. Therefore, we suggest defining environmental damage as a significant adverse effect on a biotic or abiotic conservation resource (i.e., a biotic or abiotic natural resource that is protected by conservational or environmental legislation) that has an impact on the value of the conservation resource, the conservation resource as an ecosystem component, or the sustainable use of the conservation resource. This definition relies on three normative assumptions: only concrete effects on a conservation resource can be damages; only adverse effects that lead to a decrease in the value of the conservation resource can be damages; and only significant adverse effects constitute damage to a conservation resource. Applying this definition within the framework of environmental risk assessment requires further normative determinations, for example, selection of a threshold to distinguish between adverse and significant adverse effects and approaches for assessing the environmental value of conservation resources. Such determinations, however, are not part of the definition of environmental damage. Rather they are part of the definition's operationalization through assessment procedures, which must be grounded in a comprehensible definition of environmental damage.

Quality of life at the retirement transition: Life course pathways in an early 'baby boom' birth cohort.

PubMed

Wildman, Josephine M; Moffatt, Suzanne; Pearce, Mark

2018-06-01

Promoting quality of life (QoL) in later life is an important policy goal. However, studies using prospective data to explore the mechanisms by which earlier events influence QoL in older age are lacking. This study is the first to use prospective data to investigate pathways by which a range of measures of life-course socioeconomic status contribute to later-life QoL. The study uses data from the Newcastle Thousand Families Study cohort (N = 1142), an early 'baby-boom' birth cohort born in 1947 in Newcastle upon Tyne, an industrial city in north-east England. Using prospective survey data collected between birth and later adulthood (N = 393), a path analysis investigated the effects and relative contributions of a range of life-course socioeconomic factors to QoL at age 62-64 measured using the CASP-19 scale. Strong positive effects on later-life QoL were found for advantaged occupational status in mid-life and better self-reported health, employment and mortgage-freedom in later adulthood. Significant positive indirect effects on QoL were found from social class at birth and achieved education level, mediated through later-life socioeconomic advantage. Experiencing no adverse events by age five had a large total positive effect on QoL at age 62-64, comprising a direct effect and indirect effects, mediated through education, mid-life social class and later-life self-reported health. Results support a pathway model with the effects of factors in earlier life acting via later-life factors, and an accumulation model with earlier-life factors having large total, cumulative effects on later-life QoL. The presence of a direct effect of adverse childhood events by age five on QoL suggests a 'critical period' and indicates that policies across the life-course are needed to promote later-life QoL, with policies directed towards older adults perhaps too late to 'undo the damage' of earlier adverse events. Copyright © 2018 Elsevier Ltd. All rights reserved.

Meta-analysis of the serotonin transporter promoter variant (5-HTTLPR) in relation to adverse environment and antisocial behavior.

PubMed

Tielbeek, Jorim J; Karlsson Linnér, Richard; Beers, Koko; Posthuma, Danielle; Popma, Arne; Polderman, Tinca J C

2016-07-01

Several studies have suggested an association between antisocial, aggressive, and delinquent behavior and the short variant of the serotonin transporter gene polymorphism (5-HTTLPR). Yet, genome wide and candidate gene studies in humans have not convincingly shown an association between these behaviors and 5-HTTLPR. Moreover, individual studies examining the effect of 5-HTTLPR in the presence or absence of adverse environmental factors revealed inconsistent results. We therefore performed a meta-analysis to test for the robustness of the potential interaction effect of the "long-short" variant of the 5-HTTLPR genotype and environmental adversities, on antisocial behavior. Eight studies, comprising of 12 reasonably independent samples, totaling 7,680 subjects with an effective sample size of 6,724, were included in the meta-analysis. Although our extensive meta-analysis resulted in a significant interaction effect between the 5-HTTLPR genotype and environmental adversities on antisocial behavior, the methodological constraints of the included studies hampered a confident interpretation of our results, and firm conclusions regarding the direction of effect. Future studies that aim to examine biosocial mechanisms that influence the etiology of antisocial behavior should make use of larger samples, extend to genome-wide genetic risk scores and properly control for covariate interaction terms, ensuring valid and well-powered research designs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Does age affect the stress and coping process? Implications of age differences in perceived control.

PubMed

Aldwin, C M

1991-07-01

The perceived controllability of situations is thought to influence the types of coping strategies used, and thus is important in adaptive processes. Elderly individuals are widely perceived to have less control over their environment than other adults. This lack of perceived control should have adverse affects on how they cope with stressful situations. However, most studies have shown that older adults differ little from younger adults in their approaches to coping with stress. This contradiction was investigated in a sample of 228 community-residing adults with a mean age of 42.16 (SD = 14.88). Path analysis revealed that appraisals and attributions do affect the use of coping strategies such as instrumental action and escapism in the expected directions, and age is negatively associated with perceived control. However, there was an independent and negative relationship between age and the reported use of escapist coping strategies, which mitigated the adverse effects of perceived lack of control. Neither age nor perceived controllability had direct effects on depression, but they had indirect effects through their influence on the use of coping strategies and perceived efficacy.

EADB: An Estrogenic Activity Database for Assessing Potential Endocrine Activity

EPA Science Inventory

Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body’s endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many ...

75 FR 65299 - Endangered and Threatened Species; Recovery Plans

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-22

.../quantity. Address direct impacts of Willamette hydropower and flood control dam/reservoir operations by... eastside tributaries of the Willamette River; adverse thermal effects downstream from operation of the dams... spawning is high. c. Downstream passage survival of juvenile offspring through the reservoir and dam...

Adverse Childhood Experiences among Direct Support Professionals

ERIC Educational Resources Information Center

Keesler, John M.

2018-01-01

Direct support professionals (DSPs) provide integral support to many individuals with intellectual and developmental disabilities (IDD). Yet, individuals' access to qualified DSPs is often compromised as organizations struggle to hire and retain DSPs. Despite a vast body of research exploring factors associated with turnover, adverse childhood…

Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure.

PubMed

Bender, Andreas; Scheiber, Josef; Glick, Meir; Davies, John W; Azzaoui, Kamal; Hamon, Jacques; Urban, Laszlo; Whitebread, Steven; Jenkins, Jeremy L

2007-06-01

Preclinical Safety Pharmacology (PSP) attempts to anticipate adverse drug reactions (ADRs) during early phases of drug discovery by testing compounds in simple, in vitro binding assays (that is, preclinical profiling). The selection of PSP targets is based largely on circumstantial evidence of their contribution to known clinical ADRs, inferred from findings in clinical trials, animal experiments, and molecular studies going back more than forty years. In this work we explore PSP chemical space and its relevance for the prediction of adverse drug reactions. Firstly, in silico (computational) Bayesian models for 70 PSP-related targets were built, which are able to detect 93% of the ligands binding at IC(50) < or = 10 microM at an overall correct classification rate of about 94%. Secondly, employing the World Drug Index (WDI), a model for adverse drug reactions was built directly based on normalized side-effect annotations in the WDI, which does not require any underlying functional knowledge. This is, to our knowledge, the first attempt to predict adverse drug reactions across hundreds of categories from chemical structure alone. On average 90% of the adverse drug reactions observed with known, clinically used compounds were detected, an overall correct classification rate of 92%. Drugs withdrawn from the market (Rapacuronium, Suprofen) were tested in the model and their predicted ADRs align well with known ADRs. The analysis was repeated for acetylsalicylic acid and Benperidol which are still on the market. Importantly, features of the models are interpretable and back-projectable to chemical structure, raising the possibility of rationally engineering out adverse effects. By combining PSP and ADR models new hypotheses linking targets and adverse effects can be proposed and examples for the opioid mu and the muscarinic M2 receptors, as well as for cyclooxygenase-1 are presented. It is hoped that the generation of predictive models for adverse drug reactions is able to help support early SAR to accelerate drug discovery and decrease late stage attrition in drug discovery projects. In addition, models such as the ones presented here can be used for compound profiling in all development stages.

Meta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological Overview

PubMed Central

Golder, Su; Loke, Yoon K.; Bland, Martin

2011-01-01

Background There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies. Methods and Findings Searches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93–1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance. Conclusions Empirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors' Summary PMID:21559325

Ketamine for Pain Management-Side Effects & Potential Adverse Events.

PubMed

Allen, Cheryl A; Ivester, Julius R

2017-12-01

An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

78 FR 39632 - Cotton Board Rules and Regulations: Adjusting Supplemental Assessment on Imports (2013 Amendment)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

...This proposed rule is a companion to the Agricultural Marketing Service's (AMS) direct final rule (published today in the ``Rules and Regulations'' section of the Federal Register), amending the Cotton Board Rules and Regulations by decreasing the value assigned to imported cotton for calculating supplemental assessments collected for use by the Cotton Research and Promotion Program. An amendment is required to adjust the value assigned to imported cotton and the cotton content of imported products so that it is the same as those paid on domestically produced cotton. In addition, AMS is updating two Harmonized Tariff Schedule (HTS) statistical reporting numbers that were amended since the last assessment adjustment. This proposed rule is a companion document to the direct final rule published elsewhere in this issue of the Federal Register. AMS is publishing this amendment as a direct final rule without prior proposal because the agency is contemplated by statute and required by regulation in 7 CFR 1205.510 and anticipates no significant adverse comment. AMS has explained its reasons in the preamble of the direct final rule. If AMS receives no significant adverse comment during the comment period, no further action on this proposed rule will be taken. If, however, AMS receives significant adverse comment, AMS will withdraw the direct final rule and it will not take effect. In that case, AMS will address all public comments in a subsequent final rule based on this proposed rule. AMS will not institute a second comment period on this rule. Any parties interested in commenting must do so during this comment period.

Serum from Diesel Exhaust-Exposed Rats with Cardiac Dysfunction Alters Aortic Endothelial Cell Function In Vitro: Circulating Mediators as Causative Factors?

EPA Science Inventory

Although circulating inflammatory mediators are strongly associated with adverse cardiovascular outcomes triggered by inhaled air pollution, direct cause-effect linkage has not been established. Given that endothelial toxicity often precedes and precipitates cardiac dysfunction, ...

Ocean Acidification Affects the Phyto-Zoo Plankton Trophic Transfer Efficiency

PubMed Central

Cripps, Gemma; Flynn, Kevin J.; Lindeque, Penelope K.

2016-01-01

The critical role played by copepods in ocean ecology and biogeochemistry warrants an understanding of how these animals may respond to ocean acidification (OA). Whilst an appreciation of the potential direct effects of OA, due to elevated pCO2, on copepods is improving, little is known about the indirect impacts acting via bottom-up (food quality) effects. We assessed, for the first time, the chronic effects of direct and/or indirect exposures to elevated pCO2 on the behaviour, vital rates, chemical and biochemical stoichiometry of the calanoid copepod Acartia tonsa. Bottom-up effects of elevated pCO2 caused species-specific biochemical changes to the phytoplanktonic feed, which adversely affected copepod population structure and decreased recruitment by 30%. The direct impact of elevated pCO2 caused gender-specific respiratory responses in A.tonsa adults, stimulating an enhanced respiration rate in males (> 2-fold), and a suppressed respiratory response in females when coupled with indirect elevated pCO2 exposures. Under the combined indirect+direct exposure, carbon trophic transfer efficiency from phytoplankton-to-zooplankton declined to < 50% of control populations, with a commensurate decrease in recruitment. For the first time an explicit role was demonstrated for biochemical stoichiometry in shaping copepod trophic dynamics. The altered biochemical composition of the CO2-exposed prey affected the biochemical stoichiometry of the copepods, which could have ramifications for production of higher tropic levels, notably fisheries. Our work indicates that the control of phytoplankton and the support of higher trophic levels involving copepods have clear potential to be adversely affected under future OA scenarios. PMID:27082737

Effect of Bar-code Technology on the Incidence of Medication Dispensing Errors and Potential Adverse Drug Events in a Hospital Pharmacy

PubMed Central

Poon, Eric G; Cina, Jennifer L; Churchill, William W; Mitton, Patricia; McCrea, Michelle L; Featherstone, Erica; Keohane, Carol A; Rothschild, Jeffrey M; Bates, David W; Gandhi, Tejal K

2005-01-01

We performed a direct observation pre-post study to evaluate the impact of barcode technology on medication dispensing errors and potential adverse drug events in the pharmacy of a tertiary-academic medical center. We found that barcode technology significantly reduced the rate of target dispensing errors leaving the pharmacy by 85%, from 0.37% to 0.06%. The rate of potential adverse drug events (ADEs) due to dispensing errors was also significantly reduced by 63%, from 0.19% to 0.069%. In a 735-bed hospital where 6 million doses of medications are dispensed per year, this technology is expected to prevent about 13,000 dispensing errors and 6,000 potential ADEs per year. PMID:16779372

The Potential Return on Public Investment in Detecting Adverse Drug Effects.

PubMed

Huybrechts, Krista F; Desai, Rishi J; Park, Moa; Gagne, Joshua J; Najafzadeh, Mehdi; Avorn, Jerry

2017-06-01

Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present. These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.

The Potential Return on Public Investment in Detecting Adverse Drug Effects

PubMed Central

Huybrechts, Krista F.; Desai, Rishi J.; Park, Moa; Gagne, Joshua J.; Najafzadeh, Mehdi; Avorn, Jerry

2017-01-01

Background Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Objective Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. Research Design We assessed three examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the healthcare system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. Results We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773 to $884 million for rofecoxib, $3 to $10 million for cerivastatin, and $38 to $63 million for troglitazone in the US through the prevention of adverse events. By contrast, the yearly public investment in FDA initiated population-based pharmacovigilance activities in the US is about $42.5 million at present. Conclusion These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public. PMID:28505041

Air pollution in India and related adverse respiratory health effects: past, present, and future directions.

PubMed

Khilnani, Gopi C; Tiwari, Pawan

2018-03-01

The review describes current status of air pollution in India, summarizes recent research on adverse health effects of ambient and household air pollution, and outlines the ongoing efforts and future actions required to improve air quality and reduce morbidity and mortality because of air pollution in India. Global burden of disease data analysis reveals more than one million premature deaths attributable to ambient air pollution in 2015 in India. More than one million additional deaths can be attributed to household air pollution. Particulate matter with diameter 2.5 μm or less has been causatively linked with most premature deaths. Acute respiratory tract infections, asthma, chronic obstructive pulmonary disease, exacerbations of preexisting obstructive airway disease and lung cancer are proven adverse respiratory effects of air pollution. Targeting air quality standards laid by WHO can significantly reduce morbidity and mortality because of air pollution in India. India is currently exposed to high levels of ambient and household air pollutants. Respiratory adverse effects of air pollution are significant contributors to morbidity and premature mortality in India. Substantial efforts are being made at legislative, administrative, and community levels to improve air quality. However, much more needs to be done to change the 'status quo' and attain the target air quality standards. VIDEO ABSTRACT: http://links.lww.com/COPM/A24.

Reasons for Energy Drink Use and Reported Adverse Effects Among Adolescent Emergency Department Patients.

PubMed

Nordt, Sean Patrick; Claudius, Ilene; Rangan, Cyrus; Armijo, Erick; Milano, Peter; Yanger, Sheryl; Tomaszsewski, Christian

2017-12-01

There is concern of energy drink use by adolescents. The objective of this study was to evaluate the energy drink consumption use, frequency, age of first use, reasons for use, influences of choice of brand, and adverse events recorded in a predominant Latino adolescent population. Subjects between the ages of 13 and 19 years utilizing emergency department services for any reason at a large county hospital answered a questionnaire about energy drink usage. There were 192 subjects, of which 49% were male and 51% were female. Latino adolescents were 85% of the participants, although other ethnic groups participated including African American, white, and Asian. Reasons for use include 61% to increase energy, 32% as study aide, 29% to improve sports performance, and 9% to lose weight. Twenty-four percent reported using energy drinks with ethanol or illicit drugs including marijuana, cocaine, and methamphetamine. Adverse reactions were reported in 40% of the subjects including insomnia (19%), feeling "jittery" (19%), palpitations (16%), gastrointestinal upset (11%), headache (8%), chest pain (5%), shortness of breath (4%), and seizures (1%). Both brand name and packaging influenced the choice of energy drink in most subjects. Forty percent reported at least 1 adverse effect. While most adverse effects were not severe, a small number are serious. In addition, we showed intentional ingestion with ethanol and illicit drugs. Of additional concern is that both brand and packaging seem to directly affect choice of energy drink consumed.

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

West, C.R.

This paper describes the way in which the Massachusetts Department of Environmental Protection uses risk assessment to implement the state`s environmental laws. It focuses on the Office of Research and Standards, which was created to provide information on adverse health effects of environmental contaminants, to recommend exposure levels, and to direct and manage research programs.

Direct and Indirect Effects of Childhood Adversity on Depressive Symptoms in Young Adults.

ERIC Educational Resources Information Center

Turner, Heather A.; Butler, Melissa J.

2003-01-01

Examined whether cumulative trauma in childhood and adolescence is related to depressive symptoms in young adults and explored mediating factors. Results for 649 college students indicate clear differences in cumulative trauma by sociodemographic characteristics, with high trauma associated with early onset of depression and later depressive…

36 CFR 800.7 - Failure to resolve adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... into account the Council's comments in reaching a final decision on the undertaking. Section 110(l) of the act directs that the head of the agency shall document this decision and may not delegate his or... comments. Upon request of the Council, the agency official shall provide additional existing information...

Fish population modeling approaches for assessing direct effects and recovery following mitigation of a pulp mill effluent in Jackfish Bay

EPA Science Inventory

We present an approach to link chemically-induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. A predictive population model was developed to translate changes in fecundity measures of white sucker (Catostomus commers...

12 CFR 310.6 - Special procedures: Medical records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Special procedures: Medical records. 310.6... PRIVACY ACT REGULATIONS § 310.6 Special procedures: Medical records. Medical records shall be disclosed on... transmission of the medical information directly to the requesting individual could have an adverse effect upon...

12 CFR 310.6 - Special procedures: Medical records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Special procedures: Medical records. 310.6... PRIVACY ACT REGULATIONS § 310.6 Special procedures: Medical records. Medical records shall be disclosed on... transmission of the medical information directly to the requesting individual could have an adverse effect upon...

INFLUENCE OF SUMMER STREAM TEMPERATURES ON BLACK SPOT INFESTATION OF JUVENILE COHO SALMON IN THE OREGON COAST RANGE

EPA Science Inventory

High summer water temperatures can adversely affect stream salmonids in numerous ways. The direct effects of temperature associated with increased metabolic demand can be exacerbated by other factors, including decreased resistance to disease and increased susceptibility to para...

Algal toxins and human health: A brief overview and notes on needed research directions

EPA Science Inventory

Marine and freshwater algae, both algae and cyanobacteria, are known to produce a wide variety of toxins that have caused severe adverse health effects in humans and other vertebrate species. There is general agreement that there is currently an increase in the incidence of hazar...

12 CFR 310.6 - Special procedures: Medical records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Special procedures: Medical records. 310.6... PRIVACY ACT REGULATIONS § 310.6 Special procedures: Medical records. Medical records shall be disclosed on... transmission of the medical information directly to the requesting individual could have an adverse effect upon...

Severe jaundice due to intrahepatic cholestasis after initiating anticoagulation with rivaroxaban.

PubMed

Aslan, Abdullah N; Sari, Cenk; Baştuğ, Serdal; Sari, Sevil Ö; Akçay, Murat; Durmaz, Tahir; Bozkurt, Engin

2016-03-01

Rivaroxaban, a highly selective direct factor Xa inhibitor, is a new oral anticoagulant approved by the US Food and Drug Administration in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation. Because of its efficacy and once-a-day dosing, it is commonly preferred in patients with nonvalvular atrial fibrillation and intolerance to warfarin in clinical practice. However, it can result in some adverse effects such as bleeding, rashes and liver injury. Here, we described a very rare adverse reaction of rivaroxaban, jaundice due to intrahepatic cholestasis, appeared in a 71-year-old male patient after taking rivaroxaban.

Childhood Adversities and Educational Attainment in Young Adulthood: The Role of Mental Health Problems in Adolescence.

PubMed

Veldman, Karin; Bültmann, Ute; Almansa, Josue; Reijneveld, Sijmen A

2015-11-01

The aims of this study were to examine whether the association between childhood adversities and educational attainment in young adulthood can be explained by mental health problems in adolescence and whether associations and pathways differ for boys and girls. Data were used of 2,230 participants from the Tracking Adolescents' Individual Lives Survey, a Dutch prospective cohort study with a 9-year follow-up. Childhood adversities were measured at age 11 years, mental health problems (i.e., externalizing, internalizing and attention problems with Youth Self-Report) at age 16 years, and educational attainment at age 19 years. Structural equation modeling was performed to analyze the data, overall and stratified by gender. Only among boys, childhood adversities were associated with low educational attainment in young adulthood. Externalizing problems in adolescence explained 5% of the association between childhood adversities and educational attainment. Furthermore, for both boys and girls, externalizing problems in adolescence had a direct effect on educational attainment in young adulthood. Among boys, childhood adversities are associated with poorer educational outcomes of young adults. A part of this association runs via adolescent externalizing problems. The results suggest that boys, compared with girls, are less capable to cope with childhood adversities. Monitoring of exposed boys to childhood adversities is of utmost importance. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Maltreatment, Child Welfare, and Recidivism in a Sample of Deep-End Crossover Youth.

PubMed

Baglivio, Michael T; Wolff, Kevin T; Piquero, Alex R; Bilchik, Shay; Jackowski, Katherine; Greenwald, Mark A; Epps, Nathan

2016-04-01

Although research has oft-documented a maltreatment-delinquency link, the effect of involvement in-and timing of-child welfare system involvement on offending has received less attention. We examine whether the timing of child welfare involvement has differential effects on recidivism of deep-end juvenile offenders (youth who have been adjudicated delinquent by the court and placed in juvenile justice residential programs). The current study uses a large, diverse sample of 12,955 youth completing juvenile justice residential programs between 1 January 2010 and 30 June 2013 in Florida (13 % female, 55 % Black, 11 % Hispanic). Additionally, we explore the direct effects of childhood traumatic events on delinquency, as well as their indirect effects through child welfare involvement using structural equation modeling. The findings indicate that adverse childhood experiences fail to exert a direct effect on recidivism, but do exhibit a significant indirect effect on recidivism through child welfare involvement, which is itself associated with recidivism. This means that while having exposures to more types of childhood traumatic events does not, in and of itself, increase the likelihood of re-offending, effects of such experiences operate through child welfare placement. Differences in the effects of maltreatment timing and of adverse childhood experiences are observed across sex and race/ethnicity subgroups. Across all racial subgroups, exposures to adverse childhood experiences have a significant effect on the likelihood of child welfare placement, yet child welfare placement exerts a significant effect on recidivism for White and Hispanic youth, but not for Black youth. Only Hispanic female and White male youth with overlapping child welfare and juvenile justice cases (open cases in both systems at the same time during the study period) were more likely to recidivate than their delinquent-only counterpart youth. Crossover status (child welfare and juvenile justice involvement, whether prior or open cases) was essentially irrelevant with respect to the re-offending of Black youth completing juvenile justice residential programs. The findings indicate the effects of exposure to adverse childhood experiences, and child welfare system and juvenile justice system involvement on re-offending are not uniform across subgroups of youth but that earlier child welfare involvement is more detrimental than concurrent child welfare system involvement when it does matter.

Approach for Assessing Direct Flood Damages

NASA Astrophysics Data System (ADS)

Gaňová, Lenka; Zeleňáková, Martina; Słyś, Daniel; Purcz, Pavol

2014-11-01

This article presents a methodological approach to flood direct tangible damage - damage to assets and direct intangible damage - environmental damage and loss of life assessment. The assessment of flood risk is an essential part of the risk management approach, which is the conceptual basis for the EU directive 2007/60/ES on the assessment and management of flood risk. The purpose of this directive is to establish a framework for the assessment and management of flood risk, aiming at the reduction of the adverse consequences for human health, the environment, cultural heritage and economic activity associated with flood in the community. Overall, an accurate estimation of negative effects on assets, environment and people is important in order to be able to determine the economy, environmental and social flood risk level in a system and the effects of risk mitigation measures.

The effect of brain based learning with contextual approach viewed from adversity quotient

NASA Astrophysics Data System (ADS)

Kartikaningtyas, V.; Kusmayadi, T. A.; Riyadi, R.

2018-05-01

The aim of this research was to find out the effect of Brain Based Learning (BBL) with contextual approach viewed from adversity quotient (AQ) on mathematics achievement. BBL-contextual is the model to optimize the brain in the new concept learning and real life problem solving by making the good environment. Adversity Quotient is the ability to response and faces the problems. In addition, it is also about how to turn the difficulties into chances. This AQ classified into quitters, campers, and climbers. The research method used in this research was quasi experiment by using 2x3 factorial designs. The sample was chosen by using stratified cluster random sampling. The instruments were test and questionnaire for the data of AQ. The results showed that (1) BBL-contextual is better than direct learning on mathematics achievement, (2) there is no significant difference between each types of AQ on mathematics achievement, and (3) there is no interaction between learning model and AQ on mathematics achievement.

Impact on infants' cognitive development of antenatal exposure to iron deficiency disorder and common mental disorders.

PubMed

Tran, Thach Duc; Biggs, Beverley-Ann; Tran, Tuan; Simpson, Julie Anne; Hanieh, Sarah; Dwyer, Terence; Fisher, Jane

2013-01-01

The aim of this study was to examine the effects of antenatal exposure to iron deficiency anemia (IDA) and common mental disorders (CMD) on cognitive development of 6 months old infants in a developing country. A prospective population-based study in a rural province in Vietnam, which enrolled pregnant women at 12-20 weeks gestation and followed them up with their infants until six months postpartum. Criteria for IDA were Hb <11 g/dL and serum ferritin <15 ng/mL. CMD symptoms were assessed by the Edinburgh Postnatal Depression Scale-Vietnam validation. Infant cognitive development was assessed by Bayley Scales of Infant and Toddler Development, 3rd Ed. Path analyses were performed to determine the direct and indirect, partly or fully mediated, causal effects of the antenatal exposures. A total of 497 pregnant women were recruited, of those 378 women provided complete data which were included in the analyses. Statistically significant direct adverse effects of persistent antenatal IDA (estimated difference of -11.62 points; 95% CI -23.01 to -0.22) and antenatal CMD (-4.80 points; 95% CI: -9.40 to -0.20) on infant Bayley cognitive scores at six months were found. Higher birthweight, household wealth, and self-rated sufficient supply of breastmilk were associated with higher cognitive scores. Maternal age >30 years and primiparity had an indirect adverse effect on infants' Bayley cognitive scores. These findings suggest that antenatal IDA and CMD both have adverse effects on child cognitive development, which if unrecognized and unaddressed are likely to be lasting. It is crucial that both these risks are considered by policy makers, clinicians, and researchers seeking to improve child cognitive function in developing countries.

Impact on Infants’ Cognitive Development of Antenatal Exposure to Iron Deficiency Disorder and Common Mental Disorders

PubMed Central

Tran, Thach Duc; Biggs, Beverley-Ann; Tran, Tuan; Simpson, Julie Anne; Hanieh, Sarah; Dwyer, Terence; Fisher, Jane

2013-01-01

Objectives The aim of this study was to examine the effects of antenatal exposure to iron deficiency anemia (IDA) and common mental disorders (CMD) on cognitive development of 6 months old infants in a developing country. Methods A prospective population-based study in a rural province in Vietnam, which enrolled pregnant women at 12–20 weeks gestation and followed them up with their infants until six months postpartum. Criteria for IDA were Hb <11 g/dL and serum ferritin <15 ng/mL. CMD symptoms were assessed by the Edinburgh Postnatal Depression Scale-Vietnam validation. Infant cognitive development was assessed by Bayley Scales of Infant and Toddler Development, 3rd Ed. Path analyses were performed to determine the direct and indirect, partly or fully mediated, causal effects of the antenatal exposures. Results A total of 497 pregnant women were recruited, of those 378 women provided complete data which were included in the analyses. Statistically significant direct adverse effects of persistent antenatal IDA (estimated difference of −11.62 points; 95% CI −23.01 to −0.22) and antenatal CMD (−4.80 points; 95% CI: −9.40 to −0.20) on infant Bayley cognitive scores at six months were found. Higher birthweight, household wealth, and self-rated sufficient supply of breastmilk were associated with higher cognitive scores. Maternal age >30 years and primiparity had an indirect adverse effect on infants’ Bayley cognitive scores. Conclusions These findings suggest that antenatal IDA and CMD both have adverse effects on child cognitive development, which if unrecognized and unaddressed are likely to be lasting. It is crucial that both these risks are considered by policy makers, clinicians, and researchers seeking to improve child cognitive function in developing countries. PMID:24086390

Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study.

PubMed

Tabara, Yasuharu; Takahashi, Yoshimitsu; Setoh, Kazuya; Kawaguchi, Takahisa; Gotoh, Norimoto; Terao, Chikashi; Yamada, Ryo; Kosugi, Shinji; Sekine, Akihiro; Nakayama, Takeo; Matsuda, Fumihiko

2016-01-01

Previous studies have reported that artificial increases in circulating free fatty acid (FFA) levels might have adverse effects on the vasculature. However, whether or not this effect can be extrapolated to physiological variations in FFA levels has not been clarified. Given that FFAs exert a lipotoxic effect on pancreatic β-cells and might directly damage the arterial endothelium, we hypothesized that these adverse effects might synergize with hyperglycemia. A total of 9396 Japanese subjects were included in the study. Serum FFA levels were measured at baseline examination. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. As serum levels of FFA were markedly lower in subjects with higher insulin level, a significant association between FFA levels and baPWV was observed only in subjects with blood samples taken under fasting (≥12 h, P<0.001) or near-fasting (5-11 h, P<0.001) conditions, and not in those taken under non-fasting (<5 h, P=0.307) conditions. Although type 2 diabetes and HbA1c showed a strong association with baPWV, the association between FFA level and baPWV remained significant (β=0.052, P<0.001) after adjustment for glycemic levels. In addition to their direct relationship, FFA and glucose levels were synergistically associated with baPWV (FFA(⁎)glucose; β=0.036, P<0.001). Differences in baPWV between the lowest and highest subgroups divided by a combination of FFA and glucose reached approximately 300 cm/s. Physiological variations in FFA concentrations might be a risk factor for large arterial stiffness. FFA and hyperglycemia exert a synergistic adverse effect on the vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.

DITOP: drug-induced toxicity related protein database.

PubMed

Zhang, Jing-Xian; Huang, Wei-Juan; Zeng, Jing-Hua; Huang, Wen-Hui; Wang, Yi; Zhao, Rui; Han, Bu-Cong; Liu, Qing-Feng; Chen, Yu-Zong; Ji, Zhi-Liang

2007-07-01

Drug-induced toxicity related proteins (DITRPs) are proteins that mediate adverse drug reactions (ADRs) or toxicities through their binding to drugs or reactive metabolites. Collection of these proteins facilitates better understanding of the molecular mechanisms of drug-induced toxicity and the rational drug discovery. Drug-induced toxicity related protein database (DITOP) is such a database that is intending to provide comprehensive information of DITRPs. Currently, DITOP contains 1501 records, covering 618 distinct literature-reported DITRPs, 529 drugs/ligands and 418 distinct toxicity terms. These proteins were confirmed experimentally to interact with drugs or their reactive metabolites, thus directly or indirectly cause adverse effects or toxicities. Five major types of drug-induced toxicities or ADRs are included in DITOP, which are the idiosyncratic adverse drug reactions, the dose-dependent toxicities, the drug-drug interactions, the immune-mediated adverse drug effects (IMADEs) and the toxicities caused by genetic susceptibility. Molecular mechanisms underlying the toxicity and cross-links to related resources are also provided while available. Moreover, a series of user-friendly interfaces were designed for flexible retrieval of DITRPs-related information. The DITOP can be accessed freely at http://bioinf.xmu.edu.cn/databases/ADR/index.html. Supplementary data are available at Bioinformatics online.

Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly.

PubMed

Tritos, Nicholas A; Biller, Beverly M K

2017-02-01

To review published data on pegvisomant and its therapeutic role in acromegaly. Electronic searches of the published literature were conducted using the keywords: acromegaly, growth hormone (GH) receptor (antagonist), pegvisomant, therapy. Relevant articles (n = 141) were retrieved and considered for inclusion in this manuscript. Pegvisomant is a genetically engineered, recombinant growth hormone receptor antagonist, which is effective in normalizing serum insulin-like growth factor 1 (IGF-1) levels in the majority of patients with acromegaly and ameliorating symptoms and signs associated with GH excess. Pegvisomant does not have direct antiproliferative effects on the underlying somatotroph pituitary adenoma, which is the etiology of GH excess in the vast majority of patients with acromegaly. Therefore, patients receiving pegvisomant monotherapy require regular pituitary imaging in order to monitor for possible increase in tumor size. Adverse events in patients on pegvisomant therapy include skin rashes, lipohypertrophy at injection sites, and idiosyncratic liver toxicity (generally asymptomatic transaminitis that is reversible upon drug discontinuation), thus necessitating regular patient monitoring. Pegvisomant is an effective therapeutic agent in patients with acromegaly who are not in remission after undergoing pituitary surgery. It mitigates excess GH action, as demonstrated by IGF-1 normalization, but has no direct effects on pituitary tumors causing acromegaly. Regular surveillance for possible tumor growth and adverse effects (hepatotoxicity, skin manifestations) is warranted.

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

PubMed

Font, Sarah A; Maguire-Jack, Kathryn

2016-01-01

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

Environmental Impact Statement. Deactivation of the Minuteman II Missile Wing at Whiteman Air Force Base, Missouri

DTIC Science & Technology

1992-08-01

Hazardous Air Pollutants NHPA National Historic Preservation Act NIOSH National Institute for Occupational Safety and Health 1 NOEL no observed effect ...Pantex 3 document concluded that direct measurable effects to the health and safety of the general public or adverse impacts to the environment are likely...safety; and transportation accident potential. Solid wastes and underground storage tanks are also discussed in thic ection. Potential effects to health

Multivariate dependencies between difficult childhood, temperament and antisocial personality disorder in a population of French male prisoners.

PubMed

Pousset, M; Tremblay, R E; Falissard, B

2011-06-01

The aim of this study was to contribute to clarification of the relations between antisocial personality disorder (APD) and its potential risk factors in a population of 560 French male prisoners. Adverse childhood was assessed as a latent variable determined by several traumatic events. APD (MINI), character and temperament (Cloninger's model), WAIS®-III similarities subtest and psychosocial characteristics were assessed by two clinicians. The WAIS®-III subtest accounts for verbal and cognitive performance. We used a structural model to determine the weight of the different pathways between adverse childhood and APD. Study confirmed the major and direct role of adverse childhood (standardized coefficient=0.48). An intermediate effect mediated by character (considered as a global variable) and novelty-seeking was also shown, confirming previous results from the literature. This study emphasizes the role of adverse childhood in APD, suggesting the potential benefit of early intervention in the prevention of antisocial behaviours. Copyright © 2011. Published by Elsevier Masson SAS.

Protocol for evaluation of the cost-effectiveness of ePrescribing systems and candidate prototype for other related health information technologies

PubMed Central

2014-01-01

Background This protocol concerns the assessment of cost-effectiveness of hospital health information technology (HIT) in four hospitals. Two of these hospitals are acquiring ePrescribing systems incorporating extensive decision support, while the other two will implement systems incorporating more basic clinical algorithms. Implementation of an ePrescribing system will have diffuse effects over myriad clinical processes, so the protocol has to deal with a large amount of information collected at various ‘levels’ across the system. Methods/Design The method we propose is use of Bayesian ideas as a philosophical guide. Assessment of cost-effectiveness requires a number of parameters in order to measure incremental cost utility or benefit – the effectiveness of the intervention in reducing frequency of preventable adverse events; utilities for these adverse events; costs of HIT systems; and cost consequences of adverse events averted. There is no single end-point that adequately and unproblematically captures the effectiveness of the intervention; we therefore plan to observe changes in error rates and adverse events in four error categories (death, permanent disability, moderate disability, minimal effect). For each category we will elicit and pool subjective probability densities from experts for reductions in adverse events, resulting from deployment of the intervention in a hospital with extensive decision support. The experts will have been briefed with quantitative and qualitative data from the study and external data sources prior to elicitation. Following this, there will be a process of deliberative dialogues so that experts can “re-calibrate” their subjective probability estimates. The consolidated densities assembled from the repeat elicitation exercise will then be used to populate a health economic model, along with salient utilities. The credible limits from these densities can define thresholds for sensitivity analyses. Discussion The protocol we present here was designed for evaluation of ePrescribing systems. However, the methodology we propose could be used whenever research cannot provide a direct and unbiased measure of comparative effectiveness. PMID:25038609

The effects of early life adversity on the immune system.

PubMed

Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

2017-08-01

Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular Mechanisms Underlying the Cardiovascular Benefits of SGLT2i and GLP-1RA.

PubMed

Khat, Dorrin Zarrin; Husain, Mansoor

2018-06-09

In addition to their effects on glycemic control, two specific classes of relatively new anti-diabetic drugs, namely the sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated reduced rates of major adverse cardiovascular events (MACE) in subjects with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This review summarizes recent experimental results that inform putative molecular mechanisms underlying these benefits. SGLT2i and GLP-1RA exert cardiovascular effects by targeting in both common and distinctive ways (A) several mediators of macro- and microvascular pathophysiology: namely (A1) inflammation and atherogenesis, (A2) oxidative stress-induced endothelial dysfunction, (A3) vascular smooth muscle cell reactive oxygen species (ROS) production and proliferation, and (A4) thrombosis. These agents also exhibit (B) hemodynamic effects through modulation of (B1) natriuresis/diuresis and (B2) the renin-angiotensin-aldosterone system. This review highlights that while GLP-1RA exert direct effects on vascular (endothelial and smooth muscle) cells, the effects of SGLT2i appear to include the activation of signaling pathways that prevent adverse vascular remodeling. Both SGLT2i and GLP-1RA confer hemodynamic effects that counter adverse cardiac remodeling.

Parental childhood adversity, depressive symptoms, and parenting quality: Effects on toddler self-regulation in Child Welfare Services-involved families

PubMed Central

Spieker, Susan J.; Oxford, Monica L.; Fleming, Charles B.; Lohr, Mary Jane

2018-01-01

Parents who are child welfare services-involved (CWSI) often have a history of childhood adversity and depressive symptoms. Both affect parenting quality, which in turn influences child adaptive functioning. We tested a model of the relations between parental depression and child regulatory outcomes first proposed by Lyons-Ruth and colleagues (2002). We hypothesized that both parental depression and parenting quality mediate the effects of parental early adversity on offspring regulatory outcomes. Participants were 123 CWSI parents and their toddlers who were assessed three times over a period of six months. At T1, parents reported on their childhood adversity and current depressive symptoms. At T2, parents’ sensitivity to their child’s distress and non-distress cues were rated from a videotaped teaching task. At T3, observers rated children’s emotional regulation, orientation/engagement, and secure base behavior. The results of a path model partly supported hypotheses. Parent childhood adversity was associated with current depressive symptoms, which in turn was related to parent sensitivity to child distress but not non-distress. Sensitivity to distress also predicted secure base behavior. Depression directly predicted orientation/engagement, also predicted by sensitivity to non-distress. Sensitivity to distress predicted emotion regulation and orientation/engagement. Results are discussed in terms of intervention approaches for CWSI families. PMID:29266280

PARENTAL CHILDHOOD ADVERSITY, DEPRESSIVE SYMPTOMS, AND PARENTING QUALITY: EFFECTS ON TODDLER SELF-REGULATION IN CHILD WELFARE SERVICES INVOLVED FAMILIES.

PubMed

Spieker, Susan J; Oxford, Monica L; Fleming, Charles B; Lohr, Mary Jane

2018-01-01

Parents who are involved with child welfare services (CWSI) often have a history of childhood adversity and depressive symptoms. Both affect parenting quality, which in turn influences child adaptive functioning. We tested a model of the relations between parental depression and child regulatory outcomes first proposed by K. Lyons-Ruth, R. Wolfe, A. Lyubchik, and R. Steingard (2002). We hypothesized that both parental depression and parenting quality mediate the effects of parental early adversity on offspring regulatory outcomes. Participants were 123 CWSI parents and their toddlers assessed three times over a period of 6 months. At Time 1, parents reported on their childhood adversity and current depressive symptoms. At Time 2, parents' sensitivity to their child's distress and nondistress cues was rated from a videotaped teaching task. At Time 3, observers rated children's emotional regulation, orientation/engagement, and secure base behavior. The results of a path model partly supported the hypotheses. Parent childhood adversity was associated with current depressive symptoms, which in turn related to parent sensitivity to child distress, but not nondistress. Sensitivity to distress also predicted secure base behavior. Depression directly predicted orientation/engagement, also predicted by sensitivity to nondistress. Sensitivity to distress predicted emotion regulation and orientation/engagement. Results are discussed in terms of intervention approaches for CWSI families. © 2017 Michigan Association for Infant Mental Health.

Direct-acting Antiviral Agents for the Treatment of Chronic Hepatitis C Virus Infection

PubMed Central

Nakamoto, Shingo; Nakamura, Masato; Jiang, Xia; Miyamura, Tatsuo; Wu, Shuang; Yokosuka, Osamu

2014-01-01

Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the US and Japan. Therefore, eradication of HCV may reduce the occurrence of HCC in HCV-infected individuals. In 2011, the use of first-generation HCV NS3/4A protease inhibitors such as telaprevir and boceprevir was initiated for clinical treatment of HCV. Administration of telaprevir and boceprevir plus peginterferon and ribavirin increased rates of sustained virological response (SVR) in HCV genotype 1-infected patients. However, this treatment regimen also led to severe adverse events. Second-generation direct-acting antiviral agents (DAAs) for HCV, such as simeprevir plus peg-interferon and ribavirin also resulted in higher SVR rates, with similar adverse events to other peg-interferon and ribavirin treatments. Higher SVR rates in HCV genotype 1- and 2-infected patients were achieved with 12-16 weeks of sofosbuvir plus other class DAAs with/without ribavirin and 12 weeks of sofosbuvir plus ribavirin, respectively. For “difficult-to-treat” HCV-infected patients, more therapeutic options are needed. Further studies examining the efficacy and adverse effects of such therapies will be required for the development of additional treatments. PMID:26356295

Biopsychosocial determinants of pregnancy length and fetal growth.

PubMed

St-Laurent, Jennifer; De Wals, Philippe; Moutquin, Jean-Marie; Niyonsenga, Theophile; Noiseux, Manon; Czernis, Loretta

2008-05-01

The causes and mechanisms related to preterm delivery and intrauterine growth restriction are poorly understood. Our objective was to assess the direct and indirect effects of psychosocial and biomedical factors on the duration of pregnancy and fetal growth. A self-administered questionnaire was distributed to pregnant women attending prenatal ultrasound clinics in nine hospitals in the Montérégie region in the province of Quebec, Canada, from November 1997 to May 1998. Prenatal questionnaires were linked with birth certificates. Theoretical models explaining pregnancy length and fetal growth were developed and tested, using path analysis. In order to reduce the number of variables from the questionnaire, a principal component analysis was performed, and the three most important new dimensions were retained as explanatory variables in the final models. Data were available for 1602 singleton pregnancies. The biophysical score, covering both maternal age and the pre-pregnancy body mass index, was the only variable statistically associated with pregnancy length. Smoking, obstetric history, maternal health and biophysical indices were direct predictors of fetal growth. Perceived stress, social support and self-esteem were not directly related to pregnancy outcomes, but were determinants of smoking and the above-mentioned biomedical variables. More studies are needed to identify the mechanisms by which adverse psychosocial factors are translated into adverse biological effects.

38 CFR 1.577 - Access to records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... mental or physical health if they are disclosed to him or her. If, on review of the records, the... information directly to the individual could have an adverse effect on the physical or mental health of the... physician and where it is still the physician's professional medical opinion that physical access to the...

SOURCE SAMPLING FINE PARTICULATE MATTER--INSTITUTIONAL OIL-FIRED BOILER

EPA Science Inventory

EPA seeks to understand the correlation between ambient fine PM and adverse human health effects, and there are no reliable emission factors to use for estimating PM2.5 or NH3. The most common source of directly emitted PM2.5 is incomplete combustion of fossil or biomass fuels. M...

Cost and quality trends in direct contracting arrangements.

PubMed

Lyles, Alan; Weiner, Jonathan P; Shore, Andrew D; Christianson, Jon; Solberg, Leif I; Drury, Patricia

2002-01-01

This paper presents the first empirical analysis of a 1997 initiative of the Buyers Health Care Action Group (BHCAG) known as Choice Plus. This initiative entailed direct contracts with provider-controlled delivery systems; annual care system bidding; public reports of consumer satisfaction and quality; uniform benefits; and risk-adjusted payment. After case-mix adjustment, hospital costs decreased, ambulatory care costs rose modestly, and pharmacy costs increased substantially. Process-oriented quality indicators were stable or improved. The BHCAG employer-to-provider direct contracting and consumer choice model appeared to perform reasonably well in containing costs, without measurable adverse effects on quality.

Childhood adversity, parental vulnerability and disorder: examining inter-generational transmission of risk.

PubMed

Bifulco, A; Moran, P M; Ball, C; Jacobs, C; Baines, R; Bunn, A; Cavagin, J

2002-11-01

An investigation of intergenerational factors associated with psychiatric disorder in late adolescence/early adulthood was undertaken to differentiate influences from maternal disorder, maternal poor psychosocial functioning and poor parenting, on offspring. The sample comprised an intensively studied series of 276 mother-offspring pairs in a relatively deprived inner-city London area with high rates of lone parenthood and socio-economic disadvantage. The paired sample was collected over two time periods: first a consecutively screened series of mothers and offspring in 1985-90 (n = 172 pairs) and second a 'vulnerable' series of mothers and offspring in 1995-99 (n = 104 pairs). The vulnerable mothers were selected for poor interpersonal functioning and/or low self-esteem and the consecutive series were used for comparison. Rates of childhood adversity and disorder in the offspring were examined in the two groups. Maternal characteristics including psychosocial vulnerability and depression were then examined in relation to risk transmission. Offspring of vulnerable mothers had a fourfold higher rate of yearly disorder than those in the comparison series (43% vs. 11%, p < .001). They were twice as likely as those in the comparison series to have experienced childhood adversity comprising either severe neglect, physical or sexual abuse before age 17. Physical abuse, in particular, perpetrated either by mother or father/surrogate father was significantly raised in the vulnerable group. Analysis of the combined series showed that maternal vulnerability and neglect/abuse of offspring provided the best model for offspring disorder. Maternal history of depression had no direct effect on offspring disorder; its effects were entirely mediated by offspring neglect/abuse. Maternal childhood adversity also had no direct effect. Results are discussed in relation to psychosocial models of risk transmission for disorder. Maternal poor psychosocial functioning needs to be identified as a factor requiring intervention in order to stem escalation of risk across generations.

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Future water quality monitoring--adapting tools to deal with mixtures of pollutants in water resource management.

PubMed

Altenburger, Rolf; Ait-Aissa, Selim; Antczak, Philipp; Backhaus, Thomas; Barceló, Damià; Seiler, Thomas-Benjamin; Brion, Francois; Busch, Wibke; Chipman, Kevin; de Alda, Miren López; de Aragão Umbuzeiro, Gisela; Escher, Beate I; Falciani, Francesco; Faust, Michael; Focks, Andreas; Hilscherova, Klara; Hollender, Juliane; Hollert, Henner; Jäger, Felix; Jahnke, Annika; Kortenkamp, Andreas; Krauss, Martin; Lemkine, Gregory F; Munthe, John; Neumann, Steffen; Schymanski, Emma L; Scrimshaw, Mark; Segner, Helmut; Slobodnik, Jaroslav; Smedes, Foppe; Kughathas, Subramaniam; Teodorovic, Ivana; Tindall, Andrew J; Tollefsen, Knut Erik; Walz, Karl-Heinz; Williams, Tim D; Van den Brink, Paul J; van Gils, Jos; Vrana, Branislav; Zhang, Xiaowei; Brack, Werner

2015-04-15

Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy of antidepressive medication for depression in Parkinson disease: a network meta-analysis

PubMed Central

Zhuo, Chuanjun; Xue, Rong; Luo, Lanlan; Ji, Feng; Tian, Hongjun; Qu, Hongru; Lin, Xiaodong; Jiang, Ronghuan; Tao, Ran

2017-01-01

Abstract Background: Parkinson disease (PD) was considered as the 2nd most prevalent neurodegenerative disorder after Alzheimer disease, while depression is a prevailing nonmotor symptom of PD. Typically used antidepression medication includes tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), monoamine-oxidase inhibitors (MAOI), and dopamine agonists (DA). Our study aimed at evaluating the efficacy of antidepressive medications for depression of PD. Methods: Web of Science, PubMed, Embase, and the Cochrane library were searched for related articles. Traditional meta-analysis and network meta-analysis (NMA) were performed with outcomes including depression score, UPDRS-II, UPDRS-III, and adverse effects. Surface under the cumulative ranking curve (SUCRA) was also performed to illustrate the rank probabilities of different medications on various outcomes. The consistency of direct and indirect evidence was also assessed by node-splitting method. Results: Results of traditional pairwise meta-analysis were performed. Concerning depression score, significant improvement was observed in AD, MAOI, SSRI, and SNRI compared with placebo. NMA was performed and more information could be obtained. DA was illustrated to be effective over placebo concerning UPDRS-III, MAOI, and SNRI. DA demonstrated a better prognosis in UPDRS-II scores compared with placebo and MAOI. However, DA and SSRI demonstrated a significant increase in adverse effects compared with placebo. The SUCRA value was calculated to evaluate the ranking probabilities of all medications on investigated outcomes, and the consistency between direct and indirect evidences was assessed by node-splitting method. Conclusion: SSRI had a satisfying efficacy for the depression of PD patients and could improve activities of daily living and motor function of patient but the adverse effects are unneglectable. SNRI are the safest medication with high efficacy for depression as well while other outcomes are relatively poor. PMID:28562526

Ion channels in inflammation.

PubMed

Eisenhut, Michael; Wallace, Helen

2011-04-01

Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.

Videolaryngoscopy versus direct laryngoscopy for tracheal intubation in children (excluding neonates).

PubMed

Abdelgadir, Ibtihal S; Phillips, Robert S; Singh, Davinder; Moncreiff, Michael P; Lumsden, Joanne L

2017-05-24

Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta-analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers (www.clinicaltrials.gov and www.controlledtrials) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of 'Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta-analysis. We identified three studies that are awaiting classification and two ongoing studies.Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low-quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low-quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low-quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low-quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group.Two studies (n = 100) reported other haemodynamic responses to intubation (very low-quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low-quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group.Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low-quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome.

Gulf Coast Deep Water Port Facilities Study. Appendix D. Adverse Environmental Effects.

DTIC Science & Technology

1973-04-01

mds 2. Thigmotropic effect of submerged structures 3. Attachment or shelter for marine organisms 4. Gain of sheltered habitat (lee of islands) 5...marshplants Bay margin marine grass, clams, snails and blue crab Grass flats marine grass, clams, snails, black drum and t other fish Open bay with tidal...surrounding area. F. CONCLUSION The most direct and easily understood effects of dredging projects on marine biota are: I) the destruction and removal of

Epidemiologic study of Holstein dairy cow performance and reproduction near a high-voltage direct-current powerline.

PubMed

Martin, F B; Bender, A; Steuernagel, G; Robinson, R A; Revsbech, R; Sorensen, D K; Williamson, N; Williams, A

1986-01-01

The development and operation of a high-voltage direct-current (HVDC) transmission line in rural Minnesota generated public concern over potential adverse effects to nearby residents and their livestock. Electrical environmental parameters near an HVDC line decline rapidly with distance, but effects on ambient space charge have been detected out to 1 mile. Previous studies of powerline effects on livestock have involved the more common alternating-current (HVAC) lines, which create a different electrical environment. To identify potential adverse effects of HVDC line operation on livestock, case-control and cohort study methods were used to examine various indices of Holstein performance in relation to distance from the line and the onset of line operation. It was believed that these indices would reflect changes in physiologic function or overt health effects that might arise from the HVDC environment. High-quality performance data from existing Dairy Herd Improvement Association (DHIA) records were obtained for 97% of qualifying herds located within 10 miles of the line. The large number of animals and years of observation provided high statistical power to detect even small systematic changes in performance. No significant differences in milk production or reproductive capacity were associated with presumed exposure to the HVDC environment. The absence of measurable effects in a large "sentinel" animal population may have implications for the assessment of human health risks related to HVDC transmission lines.

Frequency and risk factors for donor reactions in an anonymous blood donor survey.

PubMed

Goldman, Mindy; Osmond, Lori; Yi, Qi-Long; Cameron-Choi, Keltie; O'Brien, Sheila F

2013-09-01

Adverse donor reactions can result in injury and decrease the likelihood of donor return. Reaction reports captured in the blood center's database provide an incomplete picture of reaction rates and risk factors. We performed an anonymous survey, mailed to 40,000 donors in 2008, including questions about symptoms, height, weight, sex, and donation status. Reaction rates were compared to those recorded in our database. Possible risk factors were assessed for various reactions. The response rate was 45.5%. A total of 32% of first-time and 14% of repeat donors reported having any adverse symptom, most frequently bruising (84.9 per 1000 donors) or feeling faint or weak (66.2 per 1000). Faint reactions were two to eight times higher than reported in our database, although direct comparison was difficult. Younger age, female sex, and first-time donation status were risk factors for systemic and arm symptoms. In females, low estimated blood volume (EBV) was a risk factor for systemic symptoms. Only 51% of donors who consulted an outside physician also called Canadian Blood Services. A total of 10% of first-time donors with reactions found adverse effects information inadequate. This study allowed us to collect more information about adverse reactions, including minor symptoms and delayed reactions. Based on our findings of the risk factors and frequency of adverse reactions, we are implementing more stringent EBV criteria for younger donors and providing more detailed information to donors about possible adverse effects and their management. © 2012 American Association of Blood Banks.

78 FR 66905 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... the use of information technology. Please note that written comments received in response to this... PLUS Loan borrower must not have an adverse credit history. If an applicant for a Direct PLUS Loan is determined to have an adverse credit history, the applicant may qualify for a Direct PLUS Loan by obtaining...

Role of polymorphic Fc receptor Fc gammaRIIa in cytokine release and adverse effects of murine IgG1 anti-CD3/T cell receptor antibody (WT31).

PubMed

Tax, W J; Tamboer, W P; Jacobs, C W; Frenken, L A; Koene, R A

1997-01-15

Anti-CD3 monoclonal antibody (mAb) OKT3 is immunosuppressive, but causes severe adverse effects during the first administration ("first-dose reaction"). These adverse effects are presumably caused by cytokine release that results from T-cell activation. In vitro, T-cell activation by anti-CD3 mAb requires interaction with monocyte Fc receptors. The Fc receptor for murine IgG1, Fc gammaRIIa, is polymorphic. In some individuals, murine IgG1 anti-CD3 mAb causes T-cell proliferation and cytokine release in vitro (high responders [HR]), whereas in individuals with the low-responder (LR) phenotype it does not. We have now investigated the role of this Fc gammaRIIa polymorphism in the release of cytokines in vivo and the occurrence of adverse effects after the administration of WT31, a murine IgG1 anti-CD3/T cell receptor mAb. WT31 caused an increase of plasma tumor necrosis factor-alpha in all four HR patients and none of the five LR patients. In all HR patients except one, plasma gamma-interferon and interleukin 6 also increased, and a first-dose response was observed, whereas no cytokine release or adverse effects occurred in any of the LR patients. WT31 caused lymphopenia in all HR and none of the LR patients. FACS analysis demonstrated that in HR patients, after the initial disappearance of CD3+ cells from peripheral blood, modulation of CD3 occurred, whereas in LR patients a high degree of coating of the lymphocytes was observed. Surprisingly, WT31 also induced a marked granulocytopenia, as well as a decrease of thrombocytes, in three of the four HR patients (and in none of the LR patients). These data provide direct clinical evidence that Fc receptor interaction determines the release of cytokines and the occurrence of adverse effects after administration of anti-CD3/T cell receptor mAb. Furthermore, these data suggest that tumor necrosis factor-alpha by itself is not sufficient to induce the first-dose reaction.

Benefit-risk assessment of levetiracetam in the treatment of partial seizures.

PubMed

Abou-Khalil, Bassel

2005-01-01

Levetiracetam is a novel antiepileptic drug that has been demonstrated as being effective in the management of partial seizures. It is rapidly and completely absorbed after oral administration and it is predominantly eliminated as unchanged drug in the urine. Its metabolism is independent of the cytochrome P450 enzyme system, nor does it induce cytochrome P450 enzymes. As a result of its pharmacokinetic features, levetiracetam has not been demonstrated to interact with other drugs in either direction. In double-blind, placebo-controlled trials, all the levetiracetam dosages tested were effective, including 1000 mg/day, 2000 mg/day and 3000 mg/day. The ineffective dose is not known. Efficacy seemed to be maintained in long-term studies, with no evidence of tolerance. In major double-blind, placebo-controlled trials discontinuation rates because of adverse events were 6.9-10.9% for levetiracetam-treated patients (all doses) compared with 5.3-8.6% for placebo-treated patients. The most common adverse events that differed between treatment groups and placebo control groups were somnolence, asthenia, dizziness and, in the US study, infection. Since levetiracetam was marketed, behavioural effects have been reported, namely irritability, agitation, anger and aggressive behaviour. These adverse effects are more likely in learning disabled individuals, those with prior psychiatric history and those with symptomatic generalised epilepsy. Overall, the risk has been estimated at 12-15%. Laboratory parameters overall seem to be not significantly affected by levetiracetam, although slight trends to lower white and red blood cell counts were detected in the studies. No organ toxicity has been described so far, with patient exposures exceeding 500,000. In summary, levetiracetam exhibits a very favourable safety profile in patients with partial onset seizures. Whereas somnolence, asthenia and dizziness were the most prominent adverse effects in clinical trials, behavioural adverse effects have generally been the most common reason for drug discontinuation in clinical practice.

Improving students’ creative mathematical reasoning ability students through adversity quotient and argument driven inquiry learning

NASA Astrophysics Data System (ADS)

Hidayat, W.; Wahyudin; Prabawanto, S.

2018-01-01

This study aimed to investigate the role factors of Adversity Quotient (AQ) and Argument-Driven Inquiry (ADI) instruction in improving mathematical creative reasoning ability from students’ who is a candidate for a math teacher. The study was designed in the form of experiments with a pretest-posttest control group design that aims to examine the role of Adversity Quotient (AQ) and Argument-Driven Inquiry (ADI) learning on improving students’ mathematical creative reasoning abilities. The population in this research was the student of mathematics teacher candidate in Cimahi City, while the sample of this research was 90 students of the candidate of the teacher of mathematics specified purposively then determined randomly which belong to experiment class and control class. Based on the results and discussion, it was concluded that: (1) Improvement the ability of mathematical creative reasoning of students’ who was a candidate for a math teacher who received Argument-Driven Inquiry (ADI) instruction is better than those who received direct instruction is reviewed based on the whole; (2) There was no different improvement the ability of mathematical creative reasoning of students’ who is a candidate for a math teacher who received Argument-Driven Inquiry (ADI) instruction and direct instruction was reviewed based on the type of Adversity Quotient (Quitter / AQ Low, Champer / AQ Medium, and the Climber / AQ High); (3) Learning factors and type of Adversity Quotient (AQ) affected the improvement of students’ mathematical creative reasoning ability. In addition, there was no interaction effect between learning and AQ together in developing of students’ mathematical creative reasoning ability; (4) mathematical creative reasoning ability of students’ who is a candidate for math teacher had not been achieved optimally on the indicators novelty.

Calcium and zinc DTPA administration for internal contamination with plutonium-238 and americium-241.

PubMed

Kazzi, Ziad N; Heyl, Alexander; Ruprecht, Johann

2012-08-01

The accidental or intentional release of plutonium or americium can cause acute and long term adverse health effects if they enter the human body by ingestion, inhalation, or injection. These effects can be prevented by rapid removal of these radionuclides by chelators such as calcium or zinc diethylenetriaminepentaacetate (calcium or zinc DTPA). These compounds have been shown to be efficacious in enhancing the elimination of members of the actinide family particularly plutonium and americium when administered intravenously or by nebulizer. The efficacy and adverse effects profile depend on several factors that include the route of internalization of the actinide, the type, and route time of administration of the chelator, and whether the calcium or zinc salt of DTPA is used. Current and future research efforts should be directed at overcoming limitations associated with the use of these complex drugs by using innovative methods that can enhance their structural and therapeutic properties.

Effects of kangaroo mother care on maternal mood and interaction patterns between parents and their preterm, low birth weight infants: a systematic review.

PubMed

Athanasopoulou, Eirini; Fox, John R E

2014-01-01

The birth of a premature infant can have adverse effects on the mood of mothers and on the interaction patterns between parents and their preterm babies. The aim of the present systematic review was to examine whether the Kangaroo Mother Care (KMC) intervention can attenuate these adverse psychological effects of a premature birth by ameliorating negative maternal mood and/or promoting more positive interactions between preterm infants and their parents. The results showed that although findings of studies were inconclusive, there is some evidence to suggest that KMC can make a positive difference on these areas. Specifically, it was found that KMC can improve negative maternal mood (e.g., anxiety or depression) and promote more positive parent-child interactions. Limitations and directions for future research are discussed. © 2014 Michigan Association for Infant Mental Health.

Pharmacotherapy of conduct disorder: Challenges, options and future directions.

PubMed

Hambly, Jessica L; Khan, Sohil; McDermott, Brett; Bor, William; Haywood, Alison

2016-10-01

There is a critical need for evaluation of the pharmacotherapies used in conduct disorder (CD), due to the high incidence of off-label prescribing. The aim of this review was to identify concerns associated with the safety, efficacy and impact on quality of life (QOL) that pharmacotherapy has in children and adolescents with CD. A systematic review was undertaken using pre-defined search criteria and four databases, including reference searches. We assessed these studies using the Strength of Recommendation Taxonomy, Grading of Recommendations Assessment, Development and Evaluation, and Review Manager Risk of Bias (RevMan®) tools. There were 12 randomised controlled trials that met our inclusion criteria. antipsychotics, atomoxetine, lithium, clonidine, divalproex sodium and psychostimulants. The antipsychotics demonstrated efficacy, but were associated with adverse effects. Other agents demonstrated mixed responses, highlighting the lack of clinical significance and increased incidence of adverse effects. The management of related adverse effects was addressed to assist with clinical gaps. Overall, there is limited evidence regarding the role of pharmacotherapy in CD. More research is needed that takes into account the heterogeneity of CD and analysis of pharmacotherapy in pure CD. © The Author(s) 2016.

ADVANCES IN CONTROL OF PM2..5 AND PM2..5 PRECURSORS GENERATED BY THE COMBUSTION OF PULVERIZED COAL

EPA Science Inventory

Particulate matter smaller than 2.5 micrometers in aerodynamic diameter (PM2.5) is of concern due to adverse health effects associated with elevated ambient mass concentrations of PM2.5. PM2.5 from coal-fired utility boilers is composed of directly emitted (primary) particles and...

[The concept of risk and its estimation].

PubMed

Zocchetti, C; Della Foglia, M; Colombi, A

1996-01-01

The concept of risk, in relation to human health, is a topic of primary interest for occupational health professionals. A new legislation recently established in Italy (626/94) according to European Community directives in the field of Preventive Medicine, called attention to this topic, and in particular to risk assessment and evaluation. Motivated by this context and by the impression that the concept of risk is frequently misunderstood, the present paper has two aims: the identification of the different meanings of the term "risk" in the new Italian legislation and the critical discussion of some commonly used definitions; and the proposal of a general definition, with the specification of a mathematical expression for quantitative risk estimation. The term risk (and risk estimation, assessment, or evaluation) has mainly referred to three different contexts: hazard identification, exposure assessment, and adverse health effects occurrence. Unfortunately, there are contexts in the legislation in which it is difficult to identify the true meaning of the term. This might cause equivocal interpretations and erroneous applications of the law because hazard evaluation, exposure assessment, and adverse health effects identification are completely different topics that require integrated but distinct approaches to risk management. As far as a quantitative definition of risk is of concern, we suggest an algorithm which connects the three basic risk elements (hazard, exposure, adverse health effects) by means of their probabilities of occurrence: the probability of being exposed (to a definite dose) given that a specific hazard is present (Pr(e[symbol: see text]p)), and the probability of occurrence of an adverse health effect as a consequence of that exposure (Pr(d[symbol: see text]e)). Using these quantitative components, risk can be defined as a sequence of measurable events that starts with hazard identification and terminates with disease occurrence; therefore, the following formal definition of risk is proposed: the probability of occurrence, in a given period of time, of an adverse health effect as a consequence of the existence of an hazard. In formula: R(d[symbol: see text]p) = Pr(e[symbol: see text]p) x Pr(d[symbol: see text]e). While Pr(e[symbol: see text]p) (exposure given hazard) must be evaluated in the situation under study, two alternatives exist for the estimation of the occurrence of adverse health effects (Pr(d[symbol: see text]e)): a "direct" estimation of the damage (Pr(d[symbol: see text]e) through formal epidemiologic studies conducted in the situation under observation; and an "indirect" estimation of Pr(d[symbol: see text]e) using information taken from the scientific literature (epidemiologic evaluations, dose-response relationships, extrapolations, ...). Both conditions are presented along with their respective advantages, disadvantages, and uncertainties. The usefulness of the proposed algorithm is discussed with respect to commonly used applications of risk assessment in occupational medicine; the relevance of time for risk estimation (both in the term of duration of observation, duration of exposure, and latency of effect) is briefly explained; and how the proposed algorithm takes into account (in terms of prevention and public health) both the etiologic relevance of the exposure and the consequences of exposure removal is highlighted. As a last comment, it is suggested that the diffuse application of good work practices (technical, behavioral, organizational, ...), or the exhaustive use of check lists, can be relevant in terms of improvement of prevention efficacy, but does not represent any quantitative procedure of risk assessment which, in any circumstance, must be considered the elective approach to adverse health effect prevention.

A path analysis of gender differences in adolescent onset of alcohol, tobacco and other drug use (ATOD), reported ATOD use and adverse consequences of ATOD use.

PubMed

Thomas, B S

1996-01-01

Gender differences in the ways a risk factor approach explains onset of using alcohol, tobacco and other drugs (ATOD), reported use of ATOD and adverse consequences from ATOD use were investigated by means of separate path analyses for male and female adolescents. A fully recursive model was specified in which alienation, trait anger, interaction anxiety and cognitive motivation for ATOD use comprised the first column variables which were used to predict earliness of onset. For the second step, column one variables plus onset were used to predict ATOD use. In the final step, column one variables plus onset and ATOD use were used to predict adverse consequences of ATOD use. An ex post facto design was used in surveying 796 high school students in a single Midwestern community. The data from this sample supported the predictive validity of the theoretical model. In addition to the expected indirect or mediated effects of the risk factors via onset of ATOD use on ATOD use and via onset and ATOD use on adverse consequences of ATOD use, there were direct effects of column on risk factors on both ATOD use and on adverse consequences of ATOD use for both males and females, lending support to the concept of multiple pathway risk factors. The three gender differences that emerged in the separate path analyses were entirely consistent with the gendered deviance model.

Integrating Passive Sampling Methods into Management of Contaminated Sediment Sites: A Guide for Department of Defense Remedial Project Managers

DTIC Science & Technology

2016-04-01

concentration and toxicity to invertebrates (Kreitinger et al. 2007). Bulk contaminant sediment measurements do not reveal the differences across...feed on fish and invertebrates , while others can affect wildlife through direct contact or ingestion; regardless, both effects are influenced by and...sediment management. PAHs are risk drivers primarily because of the potential for adverse effects on benthic invertebrates and sediment-associated fish

An observational study on the effects of aviation turbine fuel and lubricants on the skin of Indian Air Force ground crew in flying stations.

PubMed

Radhakrishnan, S; Chopra, Ajay; Mitra, Debdeep; Gnanasekaran, R; Kanagaraj, R

2017-07-01

Ground crew of the Air Force routinely handle aviation turbine fuel (ATF) and lubricants and a need was felt to study the adverse effects of these substances on their skin so that remedial measures could be taken to prevent these adverse effects. A multi-centric, cross-sectional, observational study was performed at three Air Force flying stations. 109 ground crew members of the Indian Air Force (IAF) who were in direct contact with ATF and lubricants were screened for dermatological manifestations on exposed areas. History of atopy was elicited, systemic and dermatological examination done and occlusive patch testing carried out where indicated. Fungal infections were excluded by a potassium hydroxide mount. 20 out of the 109 personnel (18.34%) were symptomatic in the form of mild irritant contact dermatitis. There was no case of allergic contact dermatitis. Only two cases showed an irritant reaction on patch testing. 65% of the symptomatic personnel were atopic. There was no predisposing trade or age group for adverse effects to ATF. This study revealed that contact with ATF is associated with only mild irritant contact dermatitis in exposed ground crew members of the IAF and atopy was a predisposing factor for susceptibility to the dermatitis.

Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

PubMed Central

Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

2016-01-01

Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

Update on Psychological Trauma, Other Severe Adverse Experiences and Eating Disorders: State of the Research and Future Research Directions.

PubMed

Trottier, Kathryn; MacDonald, Danielle E

2017-08-01

This paper provides an updated review of the literature on the relationship between psychological trauma exposure, other severe adverse experiences, and eating disorders. Trauma exposure and other severe adverse experiences (e.g., emotional abuse) in both childhood and adulthood are associated with eating disorders. The relationship between traumatic and other adverse experiences and eating disorders appears to be mediated by emotional and behavioral dysregulation, as well as by cognitive factors such as self-criticism. Biological vulnerabilities may also be relevant to this relationship. Overall, the literature is limited by predominantly cross-sectional designs. There is clear evidence of a correlational relationship between trauma exposure and other severe adverse events, and eating disorders. Both risk and maintenance factor hypotheses have been put forth; however, prospective research testing these hypotheses remains limited. Future research should use prospective designs and focus on trauma-related symptoms (rather than trauma exposure) in order to advance research on risk and maintaining factors for eating disorders and inform treatment directions.

The electrophysiologic properties of esmolol, a short acting beta-blocker.

PubMed

Greenspan, A M; Spielman, S R; Horowitz, L N; Laddu, A; Senior, S

1988-04-01

Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta-blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta-blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects.

Do shrubs reduce the adverse effects of grazing on soil properties?

USGS Publications Warehouse

Eldridge, David J.; Beecham, Genevieve; Grace, James B.

2015-01-01

Increases in the density of woody plants are a global phenomenon in drylands, and large aggregations of shrubs, in particular, are regarded as being indicative of dysfunctional ecosystems. There is increasing evidence that overgrazing by livestock reduces ecosystem functions in shrublands, but that shrubs may buffer the negative effects of increasing grazing. We examined changes in water infiltration and nutrient concentrations in soils under shrubs and in their interspaces in shrublands in eastern Australia that varied in the intensity of livestock grazing. We used structural equation modelling to test whether shrubs might reduce the negative effects of overgrazing on infiltration and soil carbon and nitrogen (henceforth ‘soil nutrients’). Soils under shrubs and subject to low levels of grazing were more stable and had greater levels of soil nutrients. Shrubs had a direct positive effect on soil nutrients; but, grazing negatively affected nutrients by increasing soil bulk density. Structural equation modelling showed that shrubs had a direct positive effect on water flow under ponded conditions but also enhanced water flow, indirectly, through increased litter cover. Any positive effects of shrubs on water flow under low levels of grazing waned at high levels of grazing. Our results indicate that shrubs may reduce the adverse effects of grazing on soil properties. Specifically, shrubs could restrict access to livestock and therefore protect soils and plants beneath their canopies. Low levels of grazing are likely to ensure the retention of soil water and soil carbon and nitrogen in shrubland soils.

Childhood memories of threatening experiences and submissiveness and its relationship to hallucination proneness and ideas of reference: The mediating role of dissociation.

PubMed

Bellido-Zanin, Gloria; Perona-Garcelán, Salvador; Senín-Calderón, Cristina; López-Jiménez, Ana María; Ruiz-Veguilla, Miguel; Rodríguez-Testal, Juan Francisco

2018-05-29

Recent studies have emphasized the importance of childhood memories of threatening experiences and submissiveness in a diversity of psychological disorders. The purpose of this work was to study their specific relationship with hallucination proneness and ideas of reference in healthy subjects. The ELES scale for measuring memory of adverse childhood experiences, the DES-II scale for measuring dissociation, the LSHS-R scale for measuring hallucination proneness, and the REF for ideas of reference were applied to a sample of 472 subjects. A positive association was found between childhood memories of adverse experiences and hallucination proneness and ideas of reference, on one hand, and dissociation on the other. A mediation analysis showed that dissociation was a mediator between the memory of adverse childhood experiences and hallucination proneness on one hand, and ideas of reference on the other. When the role of mediator of the types of dissociative experiences was studied, it was found that absorption and depersonalization mediated between adverse experiences and hallucination proneness. However, this mediating effect was not found between adverse experiences and ideas of reference. The relationship between these last two variables was direct. The results suggest that childhood memories of adverse experiences are a relevant factor in understanding hallucination proneness and ideas of reference. Similarly, dissociation is a specific mediator between adverse childhood experiences and hallucination proneness. © 2018 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Comparing new anticoagulants.

PubMed

Wooten, James M

2012-12-01

For years, the pharmaceutical industry has been trying to find a safe and effective drug to replace warfarin. Although warfarin is an effective anticoagulant, its pharmacology, adverse effects, and risk profiles dictate that patients taking this medication must be monitored judiciously. The US Food and Drug Administration has approved two drugs for commercial use, dabigatran and rivaroxaban, that will compete directly with warfarin for use in specific indications. Because of direct marketing to patients, physicians are being asked to comment on these new medications. This brief review illustrates the data available for the two new drugs when compared to warfarin for the specified indications. For some patients, these drugs may be highly beneficial and offer an excellent alternative to warfarin. For others, warfarin may still be the preferred drug.

Investigating Environmental Links Between Parent Depression and Child Depressive/Anxiety Symptoms Using an Assisted Conception Design

PubMed Central

Lewis, Gemma; Rice, Frances; Harold, Gordon T.; Collishaw, Stephan; Thapar, Anita

2011-01-01

Objective Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited effects, shared adversity, and child age and gender. Method Eight hundred fifty-two families with a child born by assisted conception provided questionnaire data. Mothers and fathers were genetically related or unrelated to the child depending on conception method. Parental depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Child depression/anxiety symptoms were assessed using the Short Mood and Feelings questionnaire and six items tapping generalized anxiety disorder symptoms. Associations between maternal and child symptoms were examined separately for genetically unrelated and related mother–child pairs, adjusting for three measurements of shared adversity: negative life events, family income, and socioeconomic status. Analyses were then run separately for boys and girls and for children and adolescents, and the role of paternal depression symptoms was also examined. Results Significant associations between parent and child symptoms were found for genetically unrelated mother–child (r = 0.32, p < .001) and father–child (r = 0.17, p < .05) pairs and genetically related mother–child (r = 0.31, p < .001) and father–child (r = 0.23, p < .001) pairs and were not explained by the shared adversity measurements. Environmental links were present for children and adolescents and were stronger for girls. Conclusions The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes. PMID:21515194

Neurodevelopmental consequences of pediatric cancer and its treatment: applying an early adversity framework to understanding cognitive, behavioral, and emotional outcomes.

PubMed

Marusak, Hilary A; Iadipaolo, Allesandra S; Harper, Felicity W; Elrahal, Farrah; Taub, Jeffrey W; Goldberg, Elimelech; Rabinak, Christine A

2018-06-01

Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine's true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent "cure" that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer - namely, the presence of a life-threatening disease and endurance of invasive medical procedures - has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for research.

Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

PubMed

Kim, M H; Lin, J; Hussein, M; Battleman, D

2009-12-01

Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). As a retrospective analysis, the study is subject to potential selection bias, while its reliance on diagnostic codes for identification of AF and suspected adverse events is a source of potential investigator error. A direct cause-effect relationship between suspected adverse events/function tests and AF therapy cannot be confirmed based on the claims data available. The incidence of suspected adverse events and adverse event monitoring during AF rhythm-control and/or rate-control therapy is high. Costs associated with adverse events and adverse event monitoring are likely to add considerably to the overall burden of AF management.

Testing a Theoretical Model of Perceived Self-Efficacy for Cancer-Related Fatigue Self-Management and Optimal Physical Functional Status

PubMed Central

Hoffman, Amy J.; von Eye, Alexander; Gift, Audrey G.; Given, Barbara A.; Given, Charles W.; Rothert, Marilyn

2009-01-01

Background Critical gaps exist in the understanding of cancer symptoms, particularly for cancer-related fatigue (CRF). Existing theories and models do not examine the key role perceived self-efficacy (PSE) plays in a person's ability to manage symptoms. Objectives To test the hypothesis that physical functional status (PFS) is predicted through patient characteristics, CRF, other symptoms, and PSE for fatigue self-management in persons with cancer. Methods This study is a secondary data analysis from the baseline observation of two randomized control trials. The combined data set includes 298 subjects who were undergoing a course of chemotherapy. Key variables included physiological and contextual patient characteristics, the severity from CRF and other symptoms, PSE, and PFS. Path analysis examined the relationships among the variables in the proposed theoretical model. Results Persons with cancer reported CRF as the most prevalent symptom among a mean of 7.4 other concurrent symptoms. The severity from CRF had a direct and indirect effect on PFS, with CRF having a direct adverse impact on PFS (t = -7.02) and an indirect adverse effect as part of the severity from the other symptoms (t = 9.69) which also adversely impacted PFS (t = -2.71). Consistent with the proposed theoretical model, PSE had a positive effect on the PFS (t = 2.87) of persons with cancer while serving as a mediator between CRF severity and PFS. Discussion Cancer-related fatigure is prevalent and related to the presence of other symptoms, and PSE for fatigue self-management is an important factor influencing CRF and PFS. A foundation is provided for future intervention studies to increase PSE to achieve optimal PFS in persons with cancer. PMID:19092553

Direct procurement of wound management products.

PubMed

Jenkins, Trevor

2014-03-01

This article describes a collaborative project between Bedfordshire Community Health Services and Primary Care Trusts/Clinical Commissioning Groups to improve provision of dressings to nurses for the patients they treat. Commissioners have facilitated a transformational approach and encouraged development of efficient systems of increased cost-effectiveness rather than a transactional approach based on opportunistic cost improvement plans. Reconfiguration to direct procurement from GP prescribing has reduced wastage, released nurse time from processes to spend on clinical contact time with patients, increased efficiency, and reduced prescription workload for GPs, all without adverse effects on expenditure. Establishing a wound care products formulary placed control under the nurses treating patients and facilitated decision-making based on cost-effectiveness in clinical use. Nurses now manage 60% of expenditure in the local community health economy, and this is increasing. Relationships with the dressings manufacturing industry have also changed in a positive, constructive direction.

The Psychological Effects of Climate Change on Children.

PubMed

Burke, Susie E L; Sanson, Ann V; Van Hoorn, Judith

2018-04-11

We review recent evidence on the psychological effects of climate change on children, covering both direct and indirect impacts, and discuss children's psychological adaptation to climate change. Both the direct and flow-on effects of climate change place children at risk of mental health consequences including PTSD, depression, anxiety, phobias, sleep disorders, attachment disorders, and substance abuse. These in turn can lead to problems with emotion regulation, cognition, learning, behavior, language development, and academic performance. Together, these create predispositions to adverse adult mental health outcomes. Children also exhibit high levels of concern over climate change. Meaning-focused coping promotes well-being and environmental engagement. Both direct and indirect climate change impacts affect children's psychological well-being. Children in the developing world will suffer the worst impacts. Mental health professionals have important roles in helping mitigate climate change, and researching and implementing approaches to helping children cope with its impacts.

The effects of spatially displaced visual feedback on remote manipulator performance

NASA Technical Reports Server (NTRS)

Smith, Randy L.; Stuart, Mark A.

1993-01-01

The results of this evaluation have important implications for the arrangement of remote manipulation worksites and the design of workstations for telerobot operations. This study clearly illustrates the deleterious effects that can accompany the performance of remote manipulator tasks when viewing conditions are less than optimal. Future evaluations should emphasize telerobot camera locations and the use of image/graphical enhancement techniques in an attempt to lessen the adverse effects of displaced visual feedback. An important finding in this evaluation is the extent to which results from previously performed direct manipulation studies can be generalized to remote manipulation studies. Even though the results obtained were very similar to those of the direct manipulation evaluations, there were differences as well. This evaluation has demonstrated that generalizations to remote manipulation applications based upon the results of direct manipulation studies are quite useful, but they should be made cautiously.

Mental Health Effects of Stress over the Life Span of Refugees.

PubMed

Hollifield, Michael; Warner, Teddy D; Krakow, Barry; Westermeyer, Joseph

2018-02-06

Information about the relative impact of stressful events across the lifespan on the mental health of refugees is needed. Cross-sectional data from a community sample of 135 Kurdish and 117 Vietnamese refugees were fit to a path model about the effects of non-war stress, war-related stress, and post-migration stress on mental health. Kurdish and Vietnamese data were generally consistent with the model. However, war-related stress produced no direct but a large indirect effect through post-migration stress on mental health in Kurds. Vietnamese data indicated a modest direct war-related stress effect but no indirect influence through post-migration stress. Different types of stressful events lead to adverse mental health of displaced refugees in a somewhat group-dependent manner. Implications for prevention and treatment are discussed.

Effects of noise and electromagnetic fields on reproductive outcomes.

PubMed Central

Meyer, R E; Aldrich, T E; Easterly, C E

1989-01-01

Much public health research has been directed to studies of cancer risks due to chemical agents. Recently, increasing attention has been given to adverse reproductive outcomes as another, shorter-term biologic indicator of public health impact. Further, several low-level ubiquitous physical agents have been implicated recently as possibly affecting human health. These physical factors (noise and electromagnetic fields) represent difficult topics for research with epidemiologic study methods. This paper provides a brief review of the published data related to the risk of adverse reproductive outcomes and exposure to noise or electromagnetic fields. The discussion includes ideas for possible biologic mechanisms, considerations for exposure assessment, and suggestions for epidemiologic research. PMID:2667980

Are selective serotonin reuptake inhibitors safe for drivers? What is the evidence?

PubMed

Ravera, Silvia; Ramaekers, Johannes G; de Jong-van den Berg, Lolkje T W; de Gier, Johan J

2012-05-01

Selective serotonin reuptake inhibitors (SSRIs) are widely used medications to treat several psychiatric diseases and, above all, depression. They seem to be as effective as older antidepressants but have a different adverse effect profile. Despite their favorable safety profile, little is known about their influence on traffic safety. To conduct a literature review to summarize the current evidence on the role of SSRIs in traffic safety, particularly concerning undesirable effects that could potentially impair fitness to drive, experimental and pharmacoepidemiologic studies on driving impairment, 2 existing categorization systems for driving-impairing medications, and the European legislative procedures for assessing fitness to drive before issuing a driver's license and driving under the influence of medicines. The article search was performed in the following electronic databases: MEDLINE, PsycINFO, ScienceDirect, and SafetyLit. The English-language scientific literature was searched using key words such as SSRIs and psychomotor performance, car crash or traffic accident, and adverse effects. For inclusion in this review, papers had to be full-text articles, refer to possible driving-related adverse effects, and be experimental or pharmacoepidemiologic studies on SSRIs and traffic accident risks. No restrictions concerning publication year were applied. Ten articles were selected as background information on driving-related adverse effects, and 15 articles were selected regarding experimental and pharmacoepidemiologic work. Regarding SSRI adverse effects, the most reported undesirable effects referring to driving impairment were anxiety, agitation, sleep disturbances, headache, increased risk of suicidal behavior, and deliberate self-harm. Regarding the remaining issues addressed in this article, inconsistencies were found between the outcomes of the selected experimental and epidemiologic studies and between the 2 existing categorization systems under evaluation. Some pitfalls of the current legislative scenario were identified as well. Based on the current evidence, it was concluded that more experimental and epidemiologic research is needed to elucidate the relationship between SSRI use and traffic safety. Furthermore, a revision of the existing categorization systems and harmonized European legislation in the field of medication use and driving were highly recommended. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Life adversity in depressed and non-depressed older adults: A cross-sectional comparison of the brief LTE-Q questionnaire and life events and difficulties interview as part of the CASPER study.

PubMed

Donoghue, Hjördis M; Traviss-Turner, Gemma D; House, Allan O; Lewis, Helen; Gilbody, Simon

2016-03-15

There is a paucity of research on the nature of life adversity in depressed and non-depressed older adults. Early life events work used in-depth interviews; however, larger epidemiological trials investigate life adversity using brief questionnaires. This study investigates the type of life adversity experienced in later life and its association with depression and compares adversity captured using a brief (LTE-Q) and in-depth (LEDS) measure. 960 participants over 65 years were recruited in UK primary care to complete the PHQ-9 and LTE-Q. A sub-sample (n=19) completed the LEDS and a question exploring the subjective experience of the LTE-Q and LEDS. Important life adversity was reported on the LTE-Q in 48% of the sample. In the LTE-Q sample the prevalence of depression (PHQ-9≥10) was 12%. Exposure to recent adversity was associated with doubling of the odds of depression. The LTE-Q only captured a proportion of adversity measured by the LEDS (42% vs 84%). Both measures showed health, bereavement and relationship events were most common. The cross-sectional design limits the extent to which inferences can be drawn around the direction of causality between adversity and depression. Recall in older adults is questionable. UK older adults face adversity in areas of health, bereavement and relationships which are associated with depression. This has clinical relevance for psychological interventions for older adults to consider social context and social support. It helps identify the strengths and weaknesses of a brief adversity measure in large scale research. Further research is needed to explore the mechanisms of onset and direction of causality. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects.

PubMed

Dolder, Patrick C; Müller, Felix; Schmid, Yasmin; Borgwardt, Stefan J; Liechti, Matthias E

2018-02-01

3,4-Methylenedioxymethamphetamine (MDMA) is used recreationally and investigated as an adjunct to psychotherapy. Methylphenidate and modafinil are psychostimulants that are used to treat attention-deficit/hyperactivity disorder and narcolepsy, respectively, but they are also misused as cognitive enhancers. Little is known about differences in the acute effects of equally cardiostimulant doses of these stimulant-type substances compared directly within the same subjects. We investigated the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg), and placebo in a double-blind, cross-over study in 24 healthy participants. Acute drug effects were tested using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI). All active drugs produced comparable hemodynamic and adverse effects. MDMA produced greater increases in pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness than methylphenidate or modafinil. Only MDMA reduced subjective anxiety and impaired fear recognition and led to misclassifications of emotions as happy on the FERT. On the SADI, only MDMA produced sexual arousal-like effects. Only MDMA produced marked increases in cortisol, prolactin, and oxytocin. In contrast to MDMA, methylphenidate increased subjective anxiety, and methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT. Modafinil had no significant subjective drug effects but significant sympathomimetic and adverse effects. MDMA induced subjective, emotional, sexual, and endocrine effects that were clearly distinct from those of methylphenidate and modafinil at the doses used.

Effects of daily variation in outdoor particulates and ambient acid species in normal and asthmatic children

PubMed Central

Ward, D; Roberts, K; Jones, N; Harrison, R; Ayres, J; Hussain, S; Walters, S

2002-01-01

Background: Evidence suggests that the respiratory health of children may be adversely affected by daily variation in outdoor pollutants, particularly ozone and particulates. However, data from the UK are sparse and the contribution of different particulate fractions and acid species, together with the identification of those individuals most at risk, are not clear. Methods: One hundred and sixty two 9 year old children were enrolled from two inner city locations and recorded daily symptoms and twice daily peak expiratory flow (PEF) over 8 week periods in the winter and summer. Their results were analysed with daily pollutant levels at appropriate lags using regression models which corrected for trends, weather, pollen, and autocorrelation. Results: Pollutant levels were generally low, especially in the summer. Multiple statistically significant associations were noted between health outcomes and pollutant concentrations, but no consistent patterns in identified effects were apparent between pollutants, lags, direction of observed effect, or location. There was no evidence to suggest that subgroups with atopy or pre-existing wheeze are more sensitive to pollutant effects. Conclusion: These data do not suggest that adverse health outcomes are associated with daily variation in health effects. No evidence was found to indicate that particulates or individual acid and anion species are more closely related to adverse health outcomes than other pollutants. PMID:12037223

Comparing the Effectiveness and Safety of the Addition of and Switching to Aripiprazole for Resolving Antipsychotic-Induced Hyperprolactinemia: A Multicenter, Open-Label, Prospective Study.

PubMed

Yoon, Hui Woo; Lee, Jung Suk; Park, Sang Jin; Lee, Seon-Koo; Choi, Won-Jung; Kim, Tae Yong; Hong, Chang Hyung; Seok, Jeong-Ho; Park, Il-Ho; Son, Sang Joon; Roh, Daeyoung; Kim, Bo-Ra; Lee, Byung Ook

Hyperprolactinemia is an important but often overlooked adverse effect of antipsychotics. Several studies have shown that switching to or adding aripiprazole normalizes antipsychotic-induced hyperprolactinemia. However, no study has directly compared the effectiveness and safety of the 2 strategies. A total of 52 patients with antipsychotic-induced hyperprolactinemia were recruited. Aripiprazole was administered to patients with mild hyperprolactinemia (serum prolactin level < 50 ng/mL). Patients with severe hyperprolactinemia (serum prolactin level > 50 ng/mL) were randomized to an aripiprazole-addition group (adding aripiprazole to previous antipsychotics) or a switching group (switching previous antipsychotics to aripiprazole). Serum prolactin level, menstrual disturbances, sexual dysfunction, psychopathologies, and quality of life were measured at weeks 0, 1, 2, 4, 6, and 8. Both the addition and switching groups showed significantly reduced serum prolactin level and menstrual disturbances and improved sexual dysfunction. In patients with severe hyperprolactinemia, the numbers of patients with hyperprolactinemia and menstrual disturbance in the switching group were significantly lower than those in the addition group at week 8. Both the addition and switching strategies were effective in resolving antipsychotic-induced hyperprolactinemia and hyperprolactinemia-related adverse events, including menstrual disturbances and sexual dysfunction. In addition, these findings suggest that switching to aripiprazole may be more effective than addition of aripiprazole for normalizing hyperprolactinemia and improving hyperprolactinemia-related adverse events in patients with schizophrenia.

Exploring dispositional tendencies to seek online information about direct-to-consumer genetic testing.

PubMed

Paquin, Ryan S; Richards, Adam S; Koehly, Laura M; McBride, Colleen M

2012-12-01

Varying perspectives exist regarding the implications of genetic susceptibility testing for common disease, with some anticipating adverse effects and others expecting positive outcomes; however, little is known about the characteristics of people who are most likely to be interested in direct-to-consumer genetic testing. To that end, this study examines the association of individual dispositional differences with health risk perceptions and online information seeking related to a free genetic susceptibility test. Healthy adults enrolled in a large health maintenance organization were surveyed by telephone. Eligible participants (N = 1,959) were given access to a secure website that provided risk and benefit information about a genetic susceptibility test and given the option to be tested. Neuroticism was associated with increased perceptions of disease risk but not with logging on. Those scoring high in conscientiousness were more likely to log on. We found no evidence that neuroticism, a dispositional characteristic commonly linked to adverse emotional response, was predictive of online genetic information seeking in this sample of healthy adults.

Waste Management: DOD Has Generally Addressed Legislative Requirements on the Use of Burn Pits but Needs to Fully Assess Health Effects

DTIC Science & Technology

2016-09-01

without causing a nuisance through noise or odors , and without adversely affecting the countryside or places of special interest. Directive 2008/98/EC...by the body (for example, cotinine, a metabolite of nicotine), and it indicates the absorbed dose or allows an estimate of target-tissue dose for

DTC advertising harms patients and should be tightly regulated.

PubMed

Lurie, Peter

2009-01-01

Like all interventions in health care, direct-to-consumer (DTC) advertising should be evaluated by comparing its risks to its benefits, in the context of the available or potentially available alternatives. The objective, of course, is to realize any unique benefits while minimizing the risks. On balance, the adverse effects of DTC advertising outweigh the still-undemonstrated benefits of the advertising.

Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

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

Al-Salman, Fadheela; Plant, Nick, E-mail: N.Plant@Surrey.ac.uk

The polychlorinated biphenyl group possesses high environmental persistence, leading to bioaccumulation and a number of adverse effects in mammals. Whilst coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands for members of the nuclear receptor family of proteins. To better understand the biological actions of non-coplanar PCBs, we have undertaken a systematic analysis of their ability to activate PXR and CAR-mediated effects. Cells were exposed to a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77: Direct activation ofmore » PXR and CAR was measured using a mammalian receptor activation assay in human liver cells, with rifampicin and CITCO used as positive controls ligands for PXR and CAR, respectively; activation of target gene expression was examined using reporter gene plasmids for CYP3A4 and MDR1 transfected into liver, intestine and lung cell lines. Several of the non-coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not. Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a substitution- and tissue-specific manner. Non-coplanar PCBs act as direct activators for the nuclear receptors PXR and CAR, and are able to elicit transcriptional activation of target genes in a substitution- and tissue-dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and must be included in any risk assessment of PCBs. -- Highlights: ► Several Non-coplanar PCBs are able to directly activate both PXR and CAR in vitro. ► PCB153 is the most potent direct activator of PXR and CAR nuclear receptors. ► Non-coplanar PCB activation of CYP3A4/MDR1 reporter genes is structure-dependent. ► Non-coplanar PCB activate CYP3A4/MDR1 reporter genes in a tissue-dependent. ► PCB153 is the most potent activator of PXR/CAR target gene in all tissues.« less

Print Format Effects on ASVAB (Armed Services Vocational Aptitude Battery) Test Score Performance: Literature Review

DTIC Science & Technology

1989-08-01

1964), attention should be given to minimizing any adverse effects they may present in terms of test performance and possible distortion of test...was therefore reviewed to take this format difference into account in ASVAB norming. Boyle (1984) noted that the General Aptitude Test Batter , (GATE... cognitive paper-and-penci items such as those comprising the ASVAB. In one of the few articles directly concerned with test item format, Vanderplas and

Failure or success of search strategies to identify adverse effects of medical devices: a feasibility study using a systematic review.

PubMed

Golder, Su; Wright, Kath; Rodgers, Mark

2014-10-13

Research has indicated that adverse effects terms are increasingly prevalent in the title, abstract or indexing terms of articles that contain adverse drug effects data in MEDLINE and Embase. However, it is unknown whether adverse effects terms are present in the database records of articles that contain adverse effects data of medical devices, and thus, to what extent the development of an adverse effects search filter for medical devices may be feasible. A case study systematic review of a medical device was selected. The included studies from a systematic review of the safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) for spinal fusion were used in the analysis. For each included study, the corresponding database record on MEDLINE and Embase was assessed to measure the presence or absence of adverse effects terms in the title, abstract or indexing. The performance of each potential adverse effects search term was also measured and compared. There were 82 publications (49 studies) included in the systematic review with 51 of these indexed on MEDLINE and 55 on Embase. Ninety-four percent (48/51) of the records on MEDLINE and 95% (52/55) of the records on Embase contained at least one adverse effects related search term. The wide variety of adverse effects terms included in the title, abstract or indexing of bibliographic records, and the lack of any individual high-performing search terms suggests that a combination of terms in different fields is required to identify adverse effects of medical devices. In addition, the most successful search terms differed from the most successful terms for identifying adverse drug effects. The search filters currently available for adverse drug effects are not necessarily useful for searching adverse effects data of medical devices. The presence of adverse effects terms in the bibliographic records of articles on medical devices, however, indicates that combinations of adverse effects search terms may be useful in search strategies in MEDLINE and Embase. The results, therefore, suggest that not only a search filter for the adverse effects of medical devices is feasible, but also that it should be a research priority.

A Comparison of Clinical Outcomes for Diabetic and Nondiabetic Patients Following Directional Atherectomy in the DEFINITIVE LE Claudicant Cohort.

PubMed

Garcia, Lawrence A; Jaff, Michael R; Rocha-Singh, Krishna J; Zeller, Thomas; Bosarge, Christopher; Kamat, Suraj; McKinsey, James F

2015-10-01

To report a subset analysis that evaluated the hypothesis that directional atherectomy for peripheral artery disease in diabetic claudicants has noninferior primary patency at 12 months compared with nondiabetic claudicants. DEFINITIVE LE, a US/European multicenter study, assessed the effectiveness of directional atherectomy using SilverHawk/TurboHawk systems for treatment of peripheral artery disease in the superficial femoral, popliteal, and infrapopliteal arteries. Of the 800 patients enrolled in the study, only the 598 claudicant patients (mean age 69.5±10.4 years; 336 men) who were classified at baseline as Rutherford category 1-3 were eligible for this subset analysis. Of these, 46.8% (280/598) had diabetes. Follow-up to 12 months included duplex ultrasound examination, functional assessments, and adverse event evaluations. Independent angiographic and duplex ultrasound core laboratories assessed primary patency and secondary endpoints; a clinical events committee adjudicated adverse events. Although diabetics had significantly more baseline comorbidities, 12-month primary patency (77.0%) was no different than for nondiabetics (77.9%; superiority p=0.98; noninferiority p<0.001) across all anatomic territories treated. Freedom from clinically driven target lesion revascularization was no different between diabetics (83.8%) and nondiabetics (87.5%) overall (p=0.19) or by lesion locations. Secondary clinical outcomes (Rutherford category, ankle-brachial index, and walking impairment) improved at 12 months for both diabetics and nondiabetics. Noninferior 12-month patency rates demonstrate that directional atherectomy is an effective treatment in diabetic as well as nondiabetic claudicants. Directional atherectomy remains an attractive treatment option, improving luminal diameters without stents, which preserves future treatment options for both diabetic and nondiabetic patients with progressive, diffuse vascular disease. © The Author(s) 2015.

Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity.

PubMed

Taskinen, M-R; Söderlund, S; Bogl, L H; Hakkarainen, A; Matikainen, N; Pietiläinen, K H; Räsänen, S; Lundbom, N; Björnson, E; Eliasson, B; Mancina, R M; Romeo, S; Alméras, N; Pepa, G D; Vetrani, C; Prinster, A; Annuzzi, G; Rivellese, A; Després, J-P; Borén, J

2017-08-01

Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. To assess the effects of fructose (75 g day -1 ), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased β-hydroxybutyrate (a measure of β-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Adverse effects of aromatherapy: a systematic review of case reports and case series.

PubMed

Posadzki, Paul; Alotaibi, Amani; Ernst, Edzard

2012-01-01

This systematic review was aimed at critically evaluating the evidence regarding the adverse effects associated with aromatherapy. Five electronic databases were searched to identify all relevant case reports and case series. Forty two primary reports met our inclusion criteria. In total, 71 patients experienced adverse effects of aromatherapy. Adverse effects ranged from mild to severe and included one fatality. The most common adverse effect was dermatitis. Lavender, peppermint, tea tree oil and ylang-ylang were the most common essential oils responsible for adverse effects. Aromatherapy has the potential to cause adverse effects some of which are serious. Their frequency remains unknown. Lack of sufficiently convincing evidence regarding the effectiveness of aromatherapy combined with its potential to cause adverse effects questions the usefulness of this modality in any condition.

The toxicity study of functionalized CNT from fermented tapioca on neuroblastoma cell

NASA Astrophysics Data System (ADS)

Nurulhuda, I.; Mazatulikhma, M. Z.; Alrokayan, S.; Khan, H.; Rusop, M.

2018-05-01

Carbon nanotubes known as one of the most interesting types of nanomaterials, especially use in application directly to cells. Somehow the use should take into consideration regarding the potential adverse impact on human health. Current study, the carbon nanotube was synthesized from fermented tapioca and functionalized with polyethylene glycol and directly test on the neuroblastoma cells in vitro. The toxicity effect on cells was assessed by 3(4, 5-dimethylthiazol-2-yl)-2, 5-tetrazolium bromide assays. It showed a dose-and time-dependent less toxic effect on functionalized carbon nanotube compared to non-functionalized. This leads us to the conclusion that functionalized carbon nanotube can be use for drug delivery in future.

Sustained Virological Response after 8-Week Treatment of Simeprevir with Peginterferon α-2a plus Ribavirin in a Japanese Female with Hepatitis C Virus Genotype 1b and IL28B Minor Genotype

PubMed Central

Kanda, Tatsuo; Nakamura, Masato; Sasaki, Reina; Yasui, Shin; Nakamoto, Shingo; Haga, Yuki; Jiang, Xia; Wu, Shuang; Tawada, Akinobu; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

2015-01-01

Direct-acting antivirals with or without peginterferon α (PEG-IFN α) plus ribavirin are now available for the treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals are potent inhibitors of HCV replication, but some of them occasionally possess serious adverse events. We experienced a 64-year-old female with chronic HCV genotype 1b infection who showed elevated alanine aminotransferase of 528 IU/l at week 9 after the commencement of treatment of simeprevir with PEG-IFN α-2a plus ribavirin. However, she achieved sustained virological response at week 24 after the end of treatment. In Japan, we also have to treat elderly patients infected with HCV and/or advanced hepatic fibrosis. Until an effective interferon-free regimen is established, direct-acting antivirals with PEG-IFN plus ribavirin may still play a role in the treatment for certain patients. To avoid serious results from adverse events, careful attention and follow-up will be needed in the treatment course of simeprevir with PEG-IFN plus ribavirin for chronic HCV infection. PMID:26269697

Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events.

PubMed

Zhang, Patrick M; Sarkar, Indra Neil

2018-01-01

Recent technological advancements in genetic testing and the growing accessibility of public genomic data provide researchers with a unique avenue to approach personalized medicine. This feasibility study examined the potential of direct-to-consumer (DTC) genomic tests (focusing on 23andMe) in research and clinical applications. In particular, we combined population genetics information from the Personal Genome Project with adverse event reports from AEOLUS and pharmacogenetic information from PharmGKB. Primarily, associations between drugs based on co-occurring genetic variations and associations between variants and adverse events were used to assess the potential for leveraging single nucleotide polymorphism information from 23andMe. The results of this study suggest potential clinical uses of DTC tests in light of potential drug interactions. Furthermore, the results suggest great potential for analyzing associations at a population level to facilitate knowledge discovery in the realm of predicting adverse drug events.

Childhood Adversities and Traumata in Lebanon: A National Study

PubMed Central

Itani, Lynn; Haddad, Youmna C; Fayyad, John; Karam, Aimee; Karam, Elie

2014-01-01

Background: The goal of this paper is to map the total occurrence and evaluate the risk of co-occurrence of childhood adversities (CA) and a wide variety of childhood traumatic events (including war) in a national sample. Method: The nationally representative sample included 2,857 respondents and the instrument used was the Composite International Diagnostic Interview which screened for all CAs and traumatic events. Results: 27.9% experienced CAs; the most common were parental death and parental mental/substance use disorder. 70.6% experienced a war-related traumatic event during their lifetime, and around half of them (38.1%) experienced it below the age of 18 years. 51.3% of the subjects experienced a traumatic event not related to war during their lifetime, and 19.2% experienced it before the age of 18 years. Sexual abuse, being a refugee during war, and experiencing a natural disaster were associated with female gender. Having any CA was associated with active war exposure (OR: 4.2, CI: 2.0-8.6); war-related direct personal trauma (OR: 3.9, CI: 1.5-10.0); war-related trauma to others (OR: 2.4, CI: 1.3-4.4); non-war direct personal trauma (OR: 3.8, CI: 2.0-7.4); and any non-war childhood traumatic event (OR: 1.9, CI: 1.1-3.1). Conclusion:Childhood is awash with adversities and traumatic events that co-occur and should be measured simultaneously; otherwise, the effects of a subset of traumata or adversities could be wrongly thought to be the contributor to negative outcomes under study. PMID:25356085

Life Course Pathways of Adversities Linking Adolescent Socioeconomic Circumstances and Functional Somatic Symptoms in Mid-Adulthood: A Path Analysis Study

PubMed Central

Jonsson, Frida; San Sebastian, Miguel; Strömsten, Lotta M. J.; Hammarström, Anne; Gustafsson, Per E.

2016-01-01

While research examining the health impact of early socioeconomic conditions suggests that effects may exist independently of or jointly with adult socioeconomic position, studies exploring other potential pathways are few. Following a chain of risk life course model, this prospective study seeks to examine whether pathways of occupational class as well as material and social adversities across the life course link socioeconomic disadvantage in adolescent to functional somatic symptoms in mid-adulthood. Applying path analysis, a multiple mediator model was assessed using prospective data collected during 26 years through the Northern Swedish Cohort. The sample contained 987 individuals residing in the municipality of Luleå, Sweden, who participated in questionnaire surveys at age 16, 21, 30 and 42. Socioeconomic conditions (high/low) in adolescence (age 16) were operationalized using the occupation of the parents, while occupational class in adulthood (manual/non-manual) was measured using the participant’s own occupation at age 21 and 30. The adversity measurements were constructed as separate age specific parcels at age 21 and 30. Social adversity included items pertaining to stressful life events that could potentially harm salient relationships, while material adversity was operationalized using items concerning unfavorable financial and material circumstances. Functional somatic symptoms at age 42 was a summary measure of self-reported physical symptoms, palpitation and sleeping difficulties that had occurred during the last 12 months. An association between socioeconomic conditions at age 16 and functional somatic symptoms at age 42 (r = 0.068) which was partially explained by people’s own occupational class at age 21 and then material as well as social adversity at age 30 was revealed. Rather than proposing a direct and independent health effect of the socioeconomic conditions of the family, the present study suggests that growing up in an unfavorable socioeconomic environment might be a source for a chain of adverse material and social living situations, which in turn affects adult health. PMID:27214206

Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations

PubMed Central

Xie, Pingxing; Kranzler, Henry R.; Poling, James; Stein, Murray B.; Anton, Raymond F.; Brady, Kathleen; Weiss, Roger D.; Farrer, Lindsay; Gelernter, Joel

2010-01-01

Context: The 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) has been found to moderate several categories of emotional response after stressful life events. Previous studies generally focused on its effect on depressive symptoms; little is known about its moderation of the development of post-traumatic stress disorder (PTSD). Objective: To examine the effects of childhood adversity, adult traumatic events, 5-HTTLPR genotypes, and gene×environment interactions on the etiology of PTSD. Design: A cross-sectional study in which participants in several studies investigating the genetics of substance dependence were also screened for lifetime PTSD. The triallelic system of 5-HTTLPR was genotyped. Logistic regression modeling was used in the analyses. Setting: General community. Participants: Five hundred eighty-two European American and 670 African American individuals who reported experiences of childhood adversity, adult traumatic events, or both. Main Outcome Measure: Diagnosis of PTSD, defined by DSM-IV diagnostic criteria and assessed through the Semi-Structured Assessment for Drug Dependence and Alcoholism interview. Results: Childhood adversity and adult traumatic events both predicted PTSD. Although the 5-HTTLPR genotype alone did not predict the onset of PTSD, it interacted with adult traumatic events and childhood adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure (European American: odds ratio [OR], 2.86; 95% confidence interval [CI], 1.50-5.45; P=.002; African American: OR, 1.88; 95% CI, 1.04-3.40; P=.04; pooled: OR, 2.31; 95% CI, 1.50-3.56; P<.001). Conclusions: Participants who had both childhood adversity and adult traumatic events were more likely to develop lifetime PTSD compared with those who experienced either type of adverse event. The risk was increased in individuals with 1 or 2 copies of the S′ (S) allele compared with the L′ (L) homozygotes. Our study provides additional direct evidence that PTSD is influenced by the interactive effect of environmental and genetic factors. PMID:19884608

Improving the efficiency and directivity of THz photoconductive antennas by using a defective photonic crystal substrate

NASA Astrophysics Data System (ADS)

Rahmati, Ehsan; Ahmadi-Boroujeni, Mehdi

2018-04-01

One of the shortcomings of photoconductive (PC) antennas in terahertz (THz) generation is low effective radiated power in the desirable direction. In this paper, we propose a defective photonic crystal (DPC) substrate consisting of a customized 2D array of air holes drilled into a solid substrate in order to improve the radiation characteristics of THz PC antennas. The effect of the proposed structure on the performance of a conventional THz PC antenna has been examined from several aspects including radiation efficiency, directivity, and field distribution. By comparing the radiation performance of the THz antenna on the proposed DPC substrate to that of the conventional solid substrate, it is shown that the proposed technique can significantly improve the efficiency and directivity of the THz PC antenna over a wide frequency range. It is achieved by reducing the amount of power coupled to the substrate surface waves and limiting the radiation in undesirable directions. In addition, it is found that the sensitivity of directivity to the substrate thickness is considerably decreased and the adverse Fabry-Perot effects of the thick substrate are reduced by the application of the proposed DPC substrate.

A naturalistic cohort study on effectiveness, safety and usage pattern of an over-the-counter nicotine patch. Cohort study on smoking cessation.

PubMed

Hasford, Joerg; Fagerstrom, Karl Olov; Haustein, Knut-Olav

2003-09-01

INTRODUCTION. Nicotine replacement therapies (NRT) are effective for smoking cessation. After having received over-the-counter (OTC) status in Germany, concerns grew about effectiveness, increased risks, especially of adverse cardiovascular reactions, and inappropriate use of NRT. Thus, a pharmacy-based cohort study was launched. OBJECTIVES. To assess effectiveness, safety and appropriateness of use of an OTC nicotine patch (Nicotinell, Novartis Ltd.). Every customer who bought an OTC Nicotinell patch was eligible. All data were collected by self-administered questionnaires at weeks 2, 4, 8, 12 and 24 after inclusion. Six hundred and thirty-three customers were admitted, median duration of smoking was 19 years. Of the participants, 6% smoked up to 10 cigarettes per day, 43.6% between 11 and 20, 34.3% between 21 and 30, and 16.1% more than 30 cigarettes. Twenty-four weeks later, 351 participants replied: 28% (177 of 633) had quit smoking completely. Considering replies only the proportion of complete responders raised to 50.4%. There were no serious adverse events reported; 62.9% complied with the directions for use and did not use the patch for more than 3 months. About 45% smoked simultaneously with NRT. Pharmacy-based cohort studies are feasible. This study indicates that the nicotine patch is effective and safe in an OTC setting. There is still room to improve compliance with the directions for use.

Health implications of engineered nanomaterials

NASA Astrophysics Data System (ADS)

Pietroiusti, Antonio

2012-02-01

With the development of nanotechnology, a growing number of people are expected to be exposed to its products, the engineered nanomaterials (ENMs). Some physico-chemical properties of ENMs, linked to their size in the nanoscale (1-100 nm), make them potentially more reactive, and therefore raise concern about possible adverse effects in humans. In this article, I discuss human diseases which may be predicted after exposure to ENMs, and how their pathogenetic mechanisms may be linked to exposure; in this regard, special emphasis has been given to the triad of oxidative stress/inflammation/genotoxicity and to the interaction of ENMs/proteins in different biological compartments. The analysis of possible adverse effects has been made on an organ-by-organ basis, starting from the skin, respiratory system and gastrointestinal tract. These sites are in fact not only those exposed to the highest amounts of ENMs, but are also the portals of entry to internal organs for possible systemic effects. Although the list and the relevance of possible human disorders linked to ENM exposure are at least as impressive as that of their direct or indirect beneficial effects for human health, we must be clear that ENM-linked diseases belong to the realm of possible risk (i.e. cannot be excluded, but are unlikely), whereas ENMs with proven beneficial effects are on the market. Therefore, the mandatory awareness about possible adverse effects of ENMs should in no way be interpreted as a motivation to disregard the great opportunity represented by nanotechnology.

Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

PubMed

St Louis, Erik K; Louis, Erik K

2009-06-01

The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

Effect of the Entomogenous Nematode Nemplectana carpocapsae on the Tachinid Parasite Compsilura concinnata (Diptera: Tachinidae)

PubMed Central

Kaya, Harry K.

1984-01-01

The entomogenous nematode Neoaplectana carpocapsae and its associated bacterium, Xenorhabdus nematophilus, could not infect the pupal stage of the tachinid Compsilura concinnata through the puparium. N. carpocapsae had an adverse effect on 1-, 2- and 3-day-old C. concinnata larvae within the armyworm host in petri dish tests. All 1-day-old larvae treated with nematodes died in their hosts, whereas 61% and 69% of 2- and 3-day-old larvae treated with nematodes, respectively, died. However, the survivors developed to adults. Nine to thirty-seven percent of adult tachinids which emerged from nematode-treated soil (50 nematodes/cm²) were infected with N. carpocapsae. The nematode adversely affects C. concinnata directly by the frank infection of the tachinid and indirectly by causing the premature death of the host which results in tachinid death. PMID:19295866

Update in feline therapeutics: clinical use of 10 emerging therapies.

PubMed

Whitehouse, William; Viviano, Katrina

2015-03-01

The field of veterinary medicine is constantly evolving. New medications are being introduced into clinical practice, and novel uses for established medications are frequently being discovered as new information comes to light. Therapeutic options for our feline patients can be restricted based on inadequate clinical evidence, adverse effects and patient compliance concerns. Additionally, with the reduced availability of commonly used medications in some regions, clinicians are forced to utilize alternatives with which they may have limited experience. This review article is directed towards primary care veterinarians working with feline patients. The selection of medications discussed is based on many of the clinical challenges commonly encountered in practice. The evidence for use of some of these medications is limited due to their novelty. Known mechanisms of action, pharmacokinetic and pharmacodynamics data, adverse effects and clinical uses are reviewed where possible, with clinical recommendations made based on the evidence of data available. © ISFM and AAFP 2015.

Monitoring long-term oral corticosteroids

PubMed Central

Mundell, Lewis; Lindemann, Roberta; Douglas, James

2017-01-01

Corticosteroids are synthetic analogues of human hormones normally produced by the adrenal cortex. They have both glucocorticoid and mineralocorticoid properties. The glucocortoid components are anti-inflammatory, immunosuppressive, anti-proliferative and vasoconstrictive. They influence the metabolism of carbohydrate and protein, in addition to playing a key role in the body’s stress response. Mineralocorticoid’s main significance is in the balance of salt and water concentrations. Due to the combination of these effects, corticosteroids can cause many adverse effects. Oral corticosteroids are absorbed systemically and are therefore more likely to cause adverse effects than topical or inhaled corticosteroids. Furthermore, it is assumed that greater duration of treatment will lead to a greater number of adverse effects, and therefore the most at risk group are those taking high dose, long-term oral corticosteroids (LTOC). High dose is defined as a prescription of >5 mg oral prednisolone and long term as duration of treatment >1 month (based on National Institute for Health and Care Excellence guidance for patient’s ’at risk' of systemic side effects). Parameters to be monitored in primary care include weight, blood pressure, triglycerides, glucose and urea and electrolytes. From clinical experience within the general practice setting, the authors propose that these patients do not receive adequate baseline monitoring before starting corticosteroids nor are these markers monitored consistently thereafter. This project intended to evidence this claim, evaluate the adverse effect profile and improve monitoring in this patient group. The initial audit of 22 patients, within a single general practice, detected at least one documented adverse effect in 64% of patients, while 41% reported more than one adverse effect. 45% had recorded weight gain, 18% had recorded osteoporosis, 18% had at least one recorded cataract, 14% had recorded Hypertension, 14% had recorded diabetes mellitus, 9% had recorded dyspepsia and 5% had a recorded psychiatric complaint. All of these recorded conditions were either directly attributed to steroid medication or occurred since LTOC were prescribed. The aim of this project was to increase the percentage of patients on LTOC with complete baseline monitoring to 100%. ’Baseline monitoring' was defined as a measurement taken within the previous 5 years. Although somewhat arbitrary, 5 years was felt to be the maximum timeframe in which monitoring would still be relevant for comparison following introduction of LTOC. Quality improvement methodology was used throughout this project with multiple PDSA (Plan, Study, Do and Act) cycles. Through this, a monitoring system and protocol for patients taking LTOC was developed. As a result of this project, five adverse effects were detected in five different patients. These included two cases of secondary hypertension, one case of diabetes mellitus, one cataract and one case of adrenal insufficiency. 12 out of 20 patients achieved complete baseline monitoring. While this study did not fully achieve its aim, the aim was deliberately ambitious. As not all patients in this study attended for monitoring, a figure of 100% was impossible to achieve. The remaining ’incompletely monitored patients' had some but not all parameters measured. The creation of a staff protocol and increased clinical experience will ensure that complete monitoring takes place in the future. In conclusion, this project has shown that adverse effects from LTOC are prevalent in a single general practice population. It is also shown that monitoring for LTOC adverse effects is inadequate but can be improved relatively easily as skills and competencies from other medication monitoring systems already exist within healthcare settings and are immediately transferable. PMID:29450303

Monitoring long-term oral corticosteroids.

PubMed

Mundell, Lewis; Lindemann, Roberta; Douglas, James

2017-01-01

Corticosteroids are synthetic analogues of human hormones normally produced by the adrenal cortex. They have both glucocorticoid and mineralocorticoid properties. The glucocortoid components are anti-inflammatory, immunosuppressive, anti-proliferative and vasoconstrictive. They influence the metabolism of carbohydrate and protein, in addition to playing a key role in the body's stress response. Mineralocorticoid's main significance is in the balance of salt and water concentrations. Due to the combination of these effects, corticosteroids can cause many adverse effects. Oral corticosteroids are absorbed systemically and are therefore more likely to cause adverse effects than topical or inhaled corticosteroids. Furthermore, it is assumed that greater duration of treatment will lead to a greater number of adverse effects, and therefore the most at risk group are those taking high dose, long-term oral corticosteroids (LTOC). High dose is defined as a prescription of >5 mg oral prednisolone and long term as duration of treatment >1 month (based on National Institute for Health and Care Excellence guidance for patient's 'at risk' of systemic side effects). Parameters to be monitored in primary care include weight, blood pressure, triglycerides, glucose and urea and electrolytes. From clinical experience within the general practice setting, the authors propose that these patients do not receive adequate baseline monitoring before starting corticosteroids nor are these markers monitored consistently thereafter. This project intended to evidence this claim, evaluate the adverse effect profile and improve monitoring in this patient group. The initial audit of 22 patients, within a single general practice, detected at least one documented adverse effect in 64% of patients, while 41% reported more than one adverse effect. 45% had recorded weight gain, 18% had recorded osteoporosis, 18% had at least one recorded cataract, 14% had recorded Hypertension, 14% had recorded diabetes mellitus, 9% had recorded dyspepsia and 5% had a recorded psychiatric complaint. All of these recorded conditions were either directly attributed to steroid medication or occurred since LTOC were prescribed. The aim of this project was to increase the percentage of patients on LTOC with complete baseline monitoring to 100%. 'Baseline monitoring' was defined as a measurement taken within the previous 5 years. Although somewhat arbitrary, 5 years was felt to be the maximum timeframe in which monitoring would still be relevant for comparison following introduction of LTOC. Quality improvement methodology was used throughout this project with multiple PDSA (Plan, Study, Do and Act) cycles. Through this, a monitoring system and protocol for patients taking LTOC was developed. As a result of this project, five adverse effects were detected in five different patients. These included two cases of secondary hypertension, one case of diabetes mellitus, one cataract and one case of adrenal insufficiency. 12 out of 20 patients achieved complete baseline monitoring. While this study did not fully achieve its aim, the aim was deliberately ambitious. As not all patients in this study attended for monitoring, a figure of 100% was impossible to achieve. The remaining 'incompletely monitored patients' had some but not all parameters measured. The creation of a staff protocol and increased clinical experience will ensure that complete monitoring takes place in the future. In conclusion, this project has shown that adverse effects from LTOC are prevalent in a single general practice population. It is also shown that monitoring for LTOC adverse effects is inadequate but can be improved relatively easily as skills and competencies from other medication monitoring systems already exist within healthcare settings and are immediately transferable.

Whole-Organism Transcriptomic Analysis Provides Mechanistic Insight into the Acute Toxicity of Emamectin Benzoate in Daphnia magna.

PubMed

Song, You; Rundberget, Jan Thomas; Evenseth, Linn Mari; Xie, Li; Gomes, Tânia; Høgåsen, Tore; Iguchi, Taisen; Tollefsen, Knut Erik

2016-11-01

Emamectin benzoate (EMB) is an antisea lice chemical widely used in the aquaculture that may also unintentionally affect nontarget crustaceans in the environment. Although the adverse effects of this compound are well documented in various species, the full modes of action (MoAs) are still not well characterized. The current study was therefore conducted to characterize the MoAs of EMB and link perturbations of key toxicological pathways to adverse effects in the model freshwater crustacean Daphnia magna. Effects on molting and survival were determined after 48 h exposure to EMB, whereas global transcriptional changes and the ecdysone receptor (EcR) binding potency was determined to characterize the MoA. The results showed that the molting frequency and survival of D. magna decreased in a concentration-dependent manner, and the observed changes could not be attributed to direct interactions with the EcR. Major MoAs such as activation of glutamate-gated chloride channels and gamma-aminobutyric acid signaling, disruption of neuroendocrine regulation of molting, perturbation of energy homeostasis, suppression of DNA repair and induction of programmed cell death were observed by transcriptional analysis and successfully linked to the adverse effects. This study has demonstrated that acute exposure to intermediate and high pM levels of EMB may pose hazards to nontarget crustaceans in the aquatic environment.

Mental Health Effects of Stress over the Life Span of Refugees

PubMed Central

Hollifield, Michael; Krakow, Barry; Westermeyer, Joseph

2018-01-01

Information about the relative impact of stressful events across the lifespan on the mental health of refugees is needed. Cross-sectional data from a community sample of 135 Kurdish and 117 Vietnamese refugees were fit to a path model about the effects of non-war stress, war-related stress, and post-migration stress on mental health. Kurdish and Vietnamese data were generally consistent with the model. However, war-related stress produced no direct but a large indirect effect through post-migration stress on mental health in Kurds. Vietnamese data indicated a modest direct war-related stress effect but no indirect influence through post-migration stress. Different types of stressful events lead to adverse mental health of displaced refugees in a somewhat group-dependent manner. Implications for prevention and treatment are discussed. PMID:29415443

Can thinning slash cause a nitrogen deficiency in pumice soils of central Oregon?

Treesearch

P.H. Cochran

1968-01-01

Decomposition of thinning slash deposited on the soil surface should have no direct adverse effect on the soil nitrogen available to higher plants in the pumice soil region. Decomposition of roots of cut trees would immobilize nitrogen in the soil immediately adjacent to the root during the decomposition period, which appears to be short for the smaller roots. However...

Preliminary observations of organic gas-particle partitioning from biomass combustion smoke using an aerosol mass spectrometer

Treesearch

T. Lee; S. M. Kreidenweis; J. L. Collett; A. P. Sullivan; C. M. Carrico; J. L. Jimenez; M. Cubison; S. Saarikoski; D. R. Worsnop; T. B. Onasch; E. Fortner; W. C. Malm; E. Lincoln; Cyle Wold; WeiMin Hao

2010-01-01

Aerosols play important roles in adverse health effects, indirect and direct forcing of Earth’s climate, and visibility degradation. Biomass burning emissions from wild and prescribed fires can make a significant contribution to ambient aerosol mass in many locations and seasons. In order to better understand the chemical properties of particles produced by combustion...

Persistence of toxic and unethical leadership: how does the US Army improve leader development and selection

DTIC Science & Technology

2015-05-21

Source Assessment and Feedback OER Officer Evaluation Report PME Professional Military Education TRADOC Training and Doctrine Command...Toxic leadership is a combination of self-centered attitudes, motivations , and behaviors that have adverse effects on subordinates, the...process of influencing people by providing purpose, direction and motivation to accomplish the mission and improve the organization.”28 The ideal

78 FR 23149 - Air Quality: Revision to Definition of Volatile Organic Compounds-Exclusion of trans 1-chloro-3,3...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... contribution to tropospheric ozone formation. Because EPA received one adverse comment, we are withdrawing the... air quality standards (NAAQS) for ozone under title I of the Clean Air Act (CAA). The direct final... of preparing SIPs to attain the NAAQS for ozone under title I of the CAA. If it had become effective...

Strategic business planning linking strategy with financial reality.

PubMed

Bachrodt, Andrew K; Smyth, J Patrick

2004-11-01

To succeed in today's complex and often adverse business environment, a healthcare organization's strategic direction must be calculated, focused, and financially sustainable. Strategic business planning is an essential tool to help organizations focus strategic choices within the financial realities of their environment. An effective strategic business planning cycle includes conducting an assessment, identifying business objectives, developing strategy, conducting an impact analysis, and developing an implementation plan.

Drugs and Air Operations

DTIC Science & Technology

2001-06-01

in research alternative hypnotic free of such medico- legal establishments which directly support the military, restraints. In this context zolpidem is...1997) from the Reporto Medicina deprivation have been studied by the Walter Reed Aeronautica e Spatiale, Aeroporto Pratica di Mare, Army Institute of...the adverse effects of the compound at years, but in view of the constraint imposed by the appropriate dose rather than on the primary medico- legal

Anxiety symptoms mediate the relationship between exposure to stressful negative life events and depressive symptoms: A conditional process modelling of the protective effects of resilience.

PubMed

Anyan, Frederick; Worsley, Lyn; Hjemdal, Odin

2017-10-01

Resilience has provided a useful framework that elucidates the effects of protective factors to overcome psychological adversities but studies that address the potential contingencies of resilience to protect against direct and indirect negative effects are lacking. These obvious gaps have also resulted in oversimplification of complex processes that can be clarified by moderated mediation associations. This study examines a conditional process modelling of the protective effects of resilience against indirect effects. Two separate samples were recruited in a cross-sectional survey from Australia and Norway to complete the Patient Health Questionnaire -9, Generalized Anxiety Disorder, Stressful Negative Life Events Questionnaire and the Resilience Scale for Adults. The final sample sizes were 206 (females=114; males=91; other=1) and 210 (females=155; males=55) for Australia and Norway respectively. Moderated mediation analyses were conducted across the samples. Anxiety symptoms mediated the relationship between exposure to stressful negative life events and depressive symptoms in both samples. Conditional indirect effects of exposure to stressful negative life events on depressive symptoms mediated by anxiety symptoms showed that high subgroup of resilience was associated with less effect of exposure to stressful negative life events through anxiety symptoms on depressive symptoms than the low subgroup of resilience. As a cross-sectional survey, the present study does not answer questions about causal processes despite the use of a conditional process modelling. These findings support that, resilience protective resources can protect against both direct and indirect - through other channels - psychological adversities. Copyright © 2017 Elsevier B.V. All rights reserved.

Three-generation reproduction toxicity study of genetically modified rice with insect resistant genes.

PubMed

Hu, Yichun; Zhuo, Qin; Gong, Zhaolong; Piao, Jianhua; Yang, Xiaoguang

2017-01-01

In the present work, we evaluated the three generation reproductive toxicity of the genetically modified rice with insectresistant cry1Ac and sck genes. 120 Sprague-Dawley (SD) rats were divided into three groups which were fed with genetically modified rice diet (GM group), parental control rice diet (PR group) and AIN-93 control diet (both used as negative control) respectively. Bodyweight, food consumption, reproductive data, hematological parameters, serum chemistry, relative organ weights and histopathology for each generation were examined respectively. All the hematology and serum chemistry parameters, organ/body weight indicators were within the normal range or no change to the adverse direction was observed, although several differences in hematology and serum chemistry parameters (WBC, BUN, LDH of male rat, PLT, PCT, MPV of female rats), reproductive data (rate of morphologically abnormal sperm) were observed between GM rice group and two control groups. No macroscopic or histological adverse effects were found or considered as treatment-related, either. Overall, the three generation study of genetically modified rice with cry1Ac and sck genes at a high level showed no unintended adverse effects on rats's reproductive system. Copyright © 2016. Published by Elsevier Ltd.

Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects.

PubMed

Liu, Jingjing; Zhan, Xiudan; Wan, Jianbo; Wang, Yitao; Wang, Chunming

2015-05-05

Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Examination of Fluoxetine for the Treatment of Selective Mutism Using a Nonconcurrent Multiple-Baseline Single-Case Design Across 5 Cases.

PubMed

Barterian, Justin A; Sanchez, Joel M; Magen, Jed; Siroky, Allison K; Mash, Brittany L; Carlson, John S

2018-01-01

This study examined the utility of fluoxetine in the treatment of 5 children, aged 5 to 14 years, diagnosed with selective mutism who also demonstrated symptoms of social anxiety. A nonconcurrent, randomized, multiple-baseline, single-case design with a single-blind placebo-controlled procedure was used. Parents and the study psychiatrist completed multiple methods of assessment including Direct Behavior Ratings and questionnaires. Treatment outcomes were evaluated by calculating effect sizes for each participant as an individual and for the participants as a group. Information regarding adverse effects with an emphasis on behavioral disinhibition and ratings of parental acceptance of the intervention was gathered. All 5 children experienced improvement in social anxiety, responsive speech, and spontaneous speech with medium to large effect sizes; however, children still met criteria for selective mutism at the end of the study. Adverse events were minimal, with only 2 children experiencing brief occurrences of minor behavioral disinhibition. Parents found the treatment highly acceptable.

Tolerability of High-dose Baclofen in the Treatment of Patients with Alcohol Disorders: A Retrospective Study.

PubMed

Rigal, Laurent; Legay Hoang, Léa; Alexandre-Dubroeucq, Constance; Pinot, Juliette; Le Jeunne, Claire; Jaury, Philippe

2015-09-01

The aim of this study was to describe the tolerability of high-dose baclofen taken by patients with alcohol disorders during their first year of treatment. The medical records of all patients prescribed baclofen by one general practitioner were examined and all patients who could be contacted were retrospectively interviewed about adverse effects. Of the 146 eligible patients, 116 (79%) could be interviewed. Ninety (78%) reported at least one adverse effect (mean number per patient: 2.8 ± 2.7). The mean dosage of baclofen at the onset of the first adverse effect was 83 ± 57 mg/day. The most frequent group of adverse effects involved disruption of the wake-sleep cycle and affected 73 patients (63%). Persistent adverse effects occurred in 62 patients (53%). Eight patients (7%) had adverse effects that led them to stop taking baclofen. Their dosages were <90 mg/day at that time. Alertness disorders and depression were the adverse effects that most frequently led to stopping baclofen. Bouts of somnolence and hypomanic episodes were the most potentially dangerous adverse effects. Women reported significantly more adverse effects than men. High-dose baclofen exposes patients with alcohol disorders to many adverse effects. Generally persistent, some adverse effects appear at low doses and may be dangerous. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

The architecture of safety: hospital design.

PubMed

Joseph, Anjali; Rashid, Mahbub

2007-12-01

This paper reviews recent research literature reporting the effects of hospital design on patient safety. Features of hospital design that are linked to patient safety in the literature include noise, air quality, lighting conditions, patient room design, unit layout, and several other interior design features. Some of these features act as latent conditions for adverse events, and impact safety outcomes directly and indirectly by impacting staff working conditions. Others act as barriers to adverse events by providing hospital staff with opportunities for preventing accidents before they occur. Although the evidence linking hospital design to patient safety is growing, much is left to be done in this area of research. Nevertheless, the evidence reported in the literature may already be sufficient to have a positive impact on hospital design.

Tool to assess causality of direct and indirect adverse events associated with therapeutic interventions.

PubMed

Zorzela, Liliane; Mior, Silvano; Boon, Heather; Gross, Anita; Yager, Jeromy; Carter, Rose; Vohra, Sunita

2018-03-01

To develop and test a tool to assess the causality of direct and indirect adverse events associated with therapeutic interventions. The intervention was one or more drugs and/or natural health products, a device, or practice (professional delivering the intervention). Through the assessment of causality of adverse events, we can learn about factors contributing to the harm and consider what modification may prevent its reoccurrence. Existing scales (WHO-UMC, Naranjo and Horn) were adapted to develop a tool (algorithm and table) to evaluate cases of serious harmful events reported through a national surveillance study. We also incorporated a novel approach that assesses indirect harm (caused by the delay in diagnosis/treatment) and the health provider delivering the intervention (practice). The tool was tested, revised and then implemented to assess all reported cases of serious events resulting from use of complementary therapies. The use of complementary therapies was the trigger to report the event. Each case was evaluated by two assessors, out of a panel of five, representing different health care professionals. The tool was used in assessment of eight serious adverse events. Each event was independently evaluated by two assessors. The algorithm facilitated assessment of a serious direct or indirect harm. Assessors agreed in the final score on seven of eight cases (weighted kappa coefficient of 0.75). A tool to support the assessment of causality of adverse events was developed and tested. We propose a novel method to assess direct and indirect harms related to product(s), device(s), practice or a combination of the previous. Further research will probably help evaluate this approach across different settings and interventions.

First grade classroom-level adversity: Associations with teaching practices, academic skills, and executive functioning.

PubMed

Abry, Tashia; Granger, Kristen L; Bryce, Crystal I; Taylor, Michelle; Swanson, Jodi; Bradley, Robert H

2018-05-24

Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development and a model-building approach, the authors examined direct and indirect associations between first-grade (G1) classroom-level adversity (CLA), G1 teaching practices, and student (N = 1,073; M = 6.64 years; 49% girls; 82% White) academic skills and executive functioning in G1 and third grades (G3). Teachers reported the prevalence of adversity among their students (e.g., poor home/family life, poor academic/social readiness). Observers rated G1 teaching practices: teachers' classroom management, controlling instruction, and amount of academic instruction (classroom observation system). Children completed literacy and math assessments at 54 months, G1, and G3 (Woodcock Johnson Letter-Word Identification and Applied Problems), and executive functioning at G1 and G3 (Tower of Hanoi). Direct associations emerged between CLA and controlling instruction (positive), classroom management, and academic instruction (both negative). In addition, CLA was related to G1 literacy (but not math) directly and indirectly via classroom management (negatively) and controlling instruction (positively). The addition of G3 outcomes revealed a negative direct longitudinal association between CLA and G3 executive functioning, and indirect associations with G3 literacy and math through G1 teaching practices and literacy. Results support the notion that collective student characteristics influence student outcomes in part through teaching practices and suggest that teachers and students may benefit from the diffusion of high-adversity classroom compositions when possible. Moreover, in high-adversity classrooms teachers and students may benefit from supports targeting classroom management and foundational student competencies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Toxicological Differences Between NMDA Receptor Antagonists and Cholinesterase Inhibitors.

PubMed

Shi, Xiaodong; Lin, Xiaotian; Hu, Rui; Sun, Nan; Hao, Jingru; Gao, Can

2016-08-01

Cholinesterase inhibitors (ChEIs), represented by donepezil, rivastigmine, and galantamine, used to be the only approved class of drugs for the treatment of Alzheimer's disease. After the approval of memantine by the Food and Drug Administration (FDA), N-methyl-d-aspartic acid (NMDA) receptor antagonists have been recognized by authorities and broadly used in the treatment of Alzheimer's disease. Along with complementary mechanisms of action, NMDA antagonists and ChEIs differ not only in therapeutic effects but also in adverse reactions, which is an important consideration in clinical drug use. And the number of patients using NMDA antagonists and ChEIs concomitantly has increased, making the matter more complicated. Here we used the FDA Adverse Event Reporting System for statistical analysis , in order to compare the adverse events of memantine and ChEIs. In general, the clinical evidence confirmed the safety advantages of memantine over ChEIs, reiterating the precautions of clinical drug use and the future direction of antidementia drug development. © The Author(s) 2016.

Drinking water disinfection by-products exposure and health effects on pregnancy outcomes: a systematic review.

PubMed

Mashau, Funanani; Ncube, Esper Jacobeth; Voyi, Kuku

2018-04-01

Epidemiological studies have found that maternal exposure to disinfection by-products (DBPs) may lead to adverse pregnancy outcomes although the findings tend to be inconsistent. The objective of this study was to systematically review the evidence in associated with drinking water DBP exposure in relation to adverse pregnancy outcomes. Peer-reviewed articles were identified using electronic databases searched for studies published in the English language. Studies selected for review were evaluated for exposure assessment, confounders, and analyses risks of bias in the selection, outcomes assessment, and attrition. A comprehensive search and screening yielded a total of 32 studies, of which 12 (38%) reported a statistical association between maternal exposure to DBPs and adverse pregnancy outcomes. A maternal exposure to trihalomethanes (THMs) shows an increased risk of small for gestational age (SGA) and slightly increased risk of pregnancy loss. Risks of bias were low among the studies included in the review. Evidence on association relating to adverse pregnancy outcomes to DBP exposure is still less significant. There is a need for future robust research in this field, with the use of urinary trichloroacetic acid (TCAA) biomarkers as a direct exposure assessment method for this field.

A Synthesis of the Effects of Pesticides on Microbial Persistence in Aquatic Ecosystems

PubMed Central

Staley, Zachery R.; Harwood, Valerie J.; Rohr, Jason R.

2016-01-01

Pesticides are a pervasive presence in aquatic ecosystems throughout the world. While pesticides are intended to control fungi, insects, and other pests, their mechanisms of action are often not specific enough to prevent unintended effects, such as on non-target microbial populations. Microorganisms, including algae and cyanobacteria, protozoa, aquatic fungi, and bacteria, form the basis of many food webs and are responsible for crucial aspects of biogeochemical cycling; therefore, the potential for pesticides to alter microbial community structures must be understood to preserve ecosystem services. This review examines studies that focused on direct population-level effects and indirect community-level effects of pesticides on microorganisms. Generally, insecticides, herbicides, and fungicides were found to have adverse direct effects on algal and fungal species. Insecticides and fungicides also had deleterious direct effects in the majority of studies examining protozoa species, although herbicides were found to have inconsistent direct effects on protozoans. Our synthesis revealed mixed or no direct effects on bacterial species among all pesticide categories, with results highly dependent on the target species, chemical, and concentration used in the study. Examination of community-level, indirect effects revealed that all pesticide categories had a tendency to reduce higher trophic levels, thereby diminishing top-down pressures and favoring lower trophic levels. Often, indirect effects exerted greater influence than direct effects. However, few studies have been conducted to specifically address community-level effects of pesticides on microorganisms and further research is necessary to better understand and predict the net effects of pesticides on ecosystem health. PMID:26565685

Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.

PubMed

Meaney, Calvin J; Arabi, Ziad; Venuto, Rocco C; Consiglio, Joseph D; Wilding, Gregory E; Tornatore, Kathleen M

2014-06-12

After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy. The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation. A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse effects (p=0.008) in renal transplant recipients receiving tacrolimus and mycophenolic acid compared to the cyclosporine regimen. This finding demonstrated construct validity. Intra-class correlation was 0.81 (95% confidence interval: 0.65-0.90) and Kappa statistic of 0.68 ± 0.25 for all 18 adverse effects and verified substantial inter-rater reliability. This immunosuppressive adverse effects scoring system in stable renal transplant recipients was evaluated and substantiated face, content and construct validity with inter-rater reliability. The scoring system may facilitate prospective, standardized clinical monitoring of immunosuppressive adverse drug effects in stable renal transplant recipients and improve medication adherence.

[Costs of serious adverse events in a community teaching hospital, in Mexico].

PubMed

Gutiérrez-Mendoza, Luis Meave; Torres-Montes, Abraham; Soria-Orozco, Manuel; Padrón-Salas, Aldanely; Ramírez-Hernández, María Elizabeth

2015-01-01

Serious adverse events during hospital care are a worldwide reality and threaten the safety of the hospitalised patient. To identify serious adverse events related to healthcare and direct hospital costs in a Teaching Hospital in México. A study was conducted in a 250-bed Teaching Hospital in San Luis Potosi, Mexico. Data were obtained from the Quality and Patient Safety Department based on 2012 incidents report. Every event was reviewed and analysed by an expert team using the "fish bone" tool. The costs were calculated since the event took place until discharge or death of the patient. A total of 34 serious adverse events were identified. The average cost was $117,440.89 Mexican pesos (approx. €7,000). The great majority (82.35%) were largely preventable and related to the process of care. Undergraduate medical staff were involved in 58.82%, and 14.7% of patients had suffered adverse events in other hospitals. Serious adverse events in a Teaching Hospital setting need to be analysed to learn and deploy interventions to prevent and improve patient safety. The direct costs of these events are similar to those reported in developed countries. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in Hepatitis C Monoinfection Compared to Hepatitis C/HIV Coinfection in a Community Care Setting.

PubMed

Vijay, Gayam; Rajib, Hossain Muhammad; Mazin, Khalid; Sandipan, Chakaraborty; Osama, Mukhtar; Sumit, Dahal; Amrendra Kumar, Mandal; Arshpal, Gill; Pavani, Garlapati; Ramakrishnaiah, Sreedevi; Khalid, Mowyad; Jagannath, Sherigar; Mohammed, Mansour; Smruti, Mohanty

2018-06-22

Limited data exist comparing the safety and efficacy of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human immunodeficiency virus (HIV) coinfected patients in the real-world clinic practice setting. All HCV monoinfected and HCV/HIV coinfected patients treated with DAAs between January 2014 and October 2017 in community clinic settings were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks (SVR 12) after treatment, and adverse reactions were compared between the groups. A total of 327 patients were included in the study, of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a statistically significant difference observed in SVR 12 when comparing HCV monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005). However, there were no significant factors identified as a predictor of a reduced response. The most common adverse effect was fatigue (27%). No significant drug interaction was observed between DAA and antiretroviral therapy. None of the patients discontinued the treatment due to adverse events. In a real-world setting, DAA regimens have lower SVR 12 in HCV/HIV coinfection than in HCV monoinfection. Further studies involving a higher number of HCV/HIV coinfected patients are needed to identify real predictors of a reduced response.

Being bullied during childhood and the prospective pathways to self-harm in late adolescence.

PubMed

Lereya, Suzet Tanya; Winsper, Catherine; Heron, Jon; Lewis, Glyn; Gunnell, David; Fisher, Helen L; Wolke, Dieter

2013-06-01

To assess whether being bullied between 7 and 10 years of age is directly associated with self-harm in late adolescence when controlling for previous exposure to an adverse family environment (domestic violence, maladaptive parenting); concurrent internalizing and externalizing behavior; and subsequent psychopathology (borderline personality disorder and depression symptoms). A total of 4,810 children and adolescents in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort were assessed to ascertain bullying exposure (between 7 and 10 years of age) and self-harm at 16 to 17 years. A total of 16.5% of 16- to 17-year-olds reported self-harm in the previous year. Being bullied was associated with an increased risk of self-harm directly, and indirectly via depression symptoms in early adolescence. The association between an adverse family environment (exposure to maladaptive parenting and domestic violence) and self-harm was partially mediated by being bullied. Being bullied during childhood increases the risk of self-harm in late adolescence via several distinct pathways, for example, by increasing the risk of depression and by exacerbating the effects of exposure to an adverse family environment; as well as in the absence of these risk exposures. Health practitioners evaluating self-harm should be aware that being bullied is an important potential risk factor. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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 ...

The influence of structural and institutional change on teaching and culture in clinical settings: an exploratory study.

PubMed

Goldie, J; Dowie, A; Goldie, Anne; Cotton, Phil; Morrison, Jill

2015-02-01

Learning in clinical settings is a function of activity, context and culture. Glasgow University's Medical School has undergone significant curricular change in recent years. This has coincided with change to National Health Service consultants' contracts, the introduction of the European Working Time Directive and the Modernising Medical Careers training initiative. We wished to explore teachers' and students' perspectives on the effects of change on our clinical teachers' capacity for teaching and on medical culture. A qualitative approach using individual interviews with educational supervisors and focus groups with senior clinical students was used. Data were analysed using a "framework" technique. Curricular change has led to shorter clinical attachments in the senior clinical rotation, which combined with more centralised teaching have had adverse effects on both formal and informal teaching during attachments. Consultants' NHS contract changes the implementation of the European Working Time Directive and changes to postgraduate training have adversely affected consultants' teaching capacity, which has had a detrimental effect on their relationships with students. Medical culture has also changed as a result of these and other societal influences. The apprenticeship model was still felt to be relevant in clinical settings. This has to be balanced against the need for systematic teaching. Structural and institutional change affects learning. Faculty needs to be aware of the socio-historical context of their institutions.

Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities

PubMed Central

Mangal, Sharad; Gao, Wei; Li, Tonglei; Zhou, Qi (Tony)

2017-01-01

Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects. Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects, including cough and bronchospasm. Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy. Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers. However, the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs. Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles. This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers. PMID:28504252

The Case for Including Adverse Childhood Experiences in Child Maltreatment Education: A Path Analysis

PubMed Central

Bachmann, Michael; Bachmann, Brittany A

2018-01-01

Context The lifelong, negative consequences of exposure to adverse childhood experiences (ACEs) for individuals and their families are well established. Objective To demonstrate the importance of including ACE information in child maltreatment education curricula using path analysis. Design Survey data examined the impact of child maltreatment education programs and knowledge about ACEs on medical practitioners’ reporting habits and ability to detect maltreatment. A path diagram distinguished between the direct impact of education programs on outcome measures and the indirect effect that is mediated through knowledge of ACEs. Main Outcome Measures Medical practitioners’ ability to detect child maltreatment and their number of referrals to Child Protective Services (CPS). Results The optimized path diagram (χ2SB(3) = 3.9, p = 0.27; RMSEA-SB = 0.017; R2 = 0.21, where SB is Satorra-Bentler coefficient and RMSEA is root-mean-square error of approximation) revealed the mediating variable “knowledge about ACEs” as the strongest structural effect (SB-β = 0.34) on the number of CPS referrals. It was almost twice as high as the second strongest effect of formal education programs (SB-β = 0.19). For workplace training programs, the total effect when including knowledge of ACEs was almost double as strong as the direct effect alone. Even when previous child maltreatment education was controlled for, practitioners familiar with the consequences of ACEs were significantly more likely to recognize and to report abuse to CPS. Conclusion This study documented the importance of specialized training programs on ACEs, and the essential role ACE knowledge plays in the effectiveness of provider education programs. PMID:29616910

The Case for Including Adverse Childhood Experiences in Child Maltreatment Education: A Path Analysis.

PubMed

Bachmann, Michael; Bachmann, Brittany A

2018-03-16

The lifelong, negative consequences of exposure to adverse childhood experiences (ACEs) for individuals and their families are well established. To demonstrate the importance of including ACE information in child maltreatment education curricula using path analysis. Survey data examined the impact of child maltreatment education programs and knowledge about ACEs on medical practitioners' reporting habits and ability to detect maltreatment. A path diagram distinguished between the direct impact of education programs on outcome measures and the indirect effect that is mediated through knowledge of ACEs. Medical practitioners' ability to detect child maltreatment and their number of referrals to Child Protective Services (CPS). The optimized path diagram (χ 2 SB(3) = 3.9, p = 0.27; RMSEA-SB = 0.017; R 2 = 0.21, where SB is Satorra-Bentler coefficient and RMSEA is root-mean-square error of approximation) revealed the mediating variable "knowledge about ACEs" as the strongest structural effect (SB-β = 0.34) on the number of CPS referrals. It was almost twice as high as the second strongest effect of formal education programs (SB-β = 0.19). For workplace training programs, the total effect when including knowledge of ACEs was almost double as strong as the direct effect alone. Even when previous child maltreatment education was controlled for, practitioners familiar with the consequences of ACEs were significantly more likely to recognize and to report abuse to CPS. This study documented the importance of specialized training programs on ACEs, and the essential role ACE knowledge plays in the effectiveness of provider education programs.

Which daily experiences can foster well-being at work? A diary study on the interplay between flow experiences, affective commitment, and self-control demands.

PubMed

Rivkin, Wladislaw; Diestel, Stefan; Schmidt, Klaus-Helmut

2018-01-01

Previous research has provided strong evidence for affective commitment as a direct predictor of employees' psychological well-being and as a resource that buffers the adverse effects of self-control demands as a stressor. However, the mechanisms that underlie the beneficial effects of affective commitment have not been examined yet. Drawing on the self-determination theory, we propose day-specific flow experiences as the mechanism that underlies the beneficial effects of affective commitment, because flow experiences as peaks of intrinsic motivation constitute manifestations of autonomous regulation. In a diary study covering 10 working days with N = 90 employees, we examine day-specific flow experiences as a mediator of the beneficial effects of interindividual affective commitment and a buffering moderator of the adverse day-specific effects of self-control demands on indicators of well-being (ego depletion, need for recovery, work engagement, and subjective vitality). Our results provide strong support for our predictions that day-specific flow experiences a) mediate the beneficial effects of affective commitment on employees' day-specific well-being and b) moderate (buffer) the adverse day-specific effects of self-control demands on well-being. That is, on days with high levels of flow experiences, employees were better able to cope with self-control demands whereas self-control demands translated into impaired well-being when employees experienced lower levels of day-specific flow experiences. We then discuss our findings and suggest practical implications. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

PubMed

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

2017-09-01

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

Multidimensional profiling platforms reveal metabolic dysregulation caused by organophosphorus pesticides.

PubMed

Medina-Cleghorn, Daniel; Heslin, Ann; Morris, Patrick J; Mulvihill, Melinda M; Nomura, Daniel K

2014-02-21

We are environmentally exposed to countless synthetic chemicals on a daily basis, with an increasing number of these chemical exposures linked to adverse health effects. However, our understanding of the (patho)physiological effects of these chemicals remains poorly understood, due in part to a general lack of effort to systematically and comprehensively identify the direct interactions of environmental chemicals with biological macromolecules in mammalian systems in vivo. Here, we have used functional chemoproteomic and metabolomic platforms to broadly identify direct enzyme targets that are inhibited by widely used organophosphorus (OP) pesticides in vivo in mice and to determine metabolic alterations that are caused by these chemicals. We find that these pesticides directly inhibit over 20 serine hydrolases in vivo leading to widespread disruptions in lipid metabolism. Through identifying direct biological targets of OP pesticides, we show heretofore unrecognized modes of toxicity that may be associated with these agents and underscore the utility of using multidimensional profiling approaches to obtain a more complete understanding of toxicities associated with environmental chemicals.

Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials

PubMed Central

Derry, Sheena; Kong Loke, Yoon; Aronson, Jeffrey K

2001-01-01

Background We would expect information on adverse drug reactions in randomised clinical trials to be easily retrievable from specific searches of electronic databases. However, complete retrieval of such information may not be straightforward, for two reasons. First, not all clinical drug trials provide data on the frequency of adverse effects. Secondly, not all electronic records of trials include terms in the abstract or indexing fields that enable us to select those with adverse effects data. We have determined how often automated search methods, using indexing terms and/or textwords in the title or abstract, would fail to retrieve trials with adverse effects data. Methods We used a sample set of 107 trials known to report frequencies of adverse drug effects, and measured the proportion that (i) were not assigned the appropriate adverse effects indexing terms in the electronic databases, and (ii) did not contain identifiable adverse effects textwords in the title or abstract. Results Of the 81 trials with records on both MEDLINE and EMBASE, 25 were not indexed for adverse effects in either database. Twenty-six trials were indexed in one database but not the other. Only 66 of the 107 trials reporting adverse effects data mentioned this in the abstract or title of the paper. Simultaneous use of textword and indexing terms retrieved only 82/107 (77%) papers. Conclusions Specific search strategies based on adverse effects textwords and indexing terms will fail to identify nearly a quarter of trials that report on the rate of drug adverse effects. PMID:11591220

Radiofrequency (RF) effects on blood cells, cardiac, endocrine, and immunological functions.

PubMed

Black, David R; Heynick, Louis N

2003-01-01

Effects of radiofrequency electromagnetic fields (RFEMF) on the pituitary adrenocortical (ACTH), growth (GH), and thyroid (TSH) hormones have been extensively studied, and there is coherent research on reproductive hormones (FSH and LH). Those effects which have been identified are clearly caused by heating. The exposure thresholds for these effects in living mammals, including primates, have been established. There is limited evidence that indicates no interaction between RFEMF and the pineal gland or an effect on prolactin from the pituitary gland. Studies of RFEMF exposed blood cells have shown that changes or damage do not occur unless the cells are heated. White cells (leukocytes) are much more sensitive than red cells (erythrocytes) but white cell effects remain consistent with normal physiological responses to systemic temperature fluctuation. Lifetime studies of RFEMF exposed animals show no cumulative adverse effects in their endocrine, hematological, or immune systems. Cardiovascular tissue is not directly affected adversely in the absence of significant RFEMF heating or electric currents. The regulation of blood pressure is not influenced by ultra high frequency (UHF) RFEMF at levels commonly encountered in the use of mobile communication devices. Copyright 2003 Wiley-Liss, Inc.

Command generator tracker based direct model reference adaptive tracking guidance for Mars atmospheric entry

NASA Astrophysics Data System (ADS)

Li, Shuang; Peng, Yuming

2012-01-01

In order to accurately deliver an entry vehicle through the Martian atmosphere to the prescribed parachute deployment point, active Mars entry guidance is essential. This paper addresses the issue of Mars atmospheric entry guidance using the command generator tracker (CGT) based direct model reference adaptive control to reduce the adverse effect of the bounded uncertainties on atmospheric density and aerodynamic coefficients. Firstly, the nominal drag acceleration profile meeting a variety of constraints is planned off-line in the longitudinal plane as the reference model to track. Then, the CGT based direct model reference adaptive controller and the feed-forward compensator are designed to robustly track the aforementioned reference drag acceleration profile and to effectively reduce the downrange error. Afterwards, the heading alignment logic is adopted in the lateral plane to reduce the crossrange error. Finally, the validity of the guidance algorithm proposed in this paper is confirmed by Monte Carlo simulation analysis.

Formation control of VTOL UAV vehicles under switching-directed interaction topologies with disturbance rejection

NASA Astrophysics Data System (ADS)

Kabiri, Meisam; Atrianfar, Hajar; Menhaj, Mohammad B.

2018-01-01

This paper addresses the adaptive formation control of a group of vertical take-off and landing (VTOL) unmanned aerial vehicles (UAV) with switching-directed interaction topologies. In addition, to tackle the adverse effect of disturbances, a couple of smooth bounded estimators are involved in the procedure design. Exploiting an extraction algorithm, we take advantage of the fully actuated rotational dynamics, to control the translational dynamics of each vehicle. We propose a distributed control scheme such that all vehicles track a desired reference velocity signal while keeping a desired prespecified formation. In this framework, the underlying topology of the agents may switch among several directed graphs, each having a spanning tree. The stability of the overall closed-loop system is proved through Lyapunov function. Finally, simulation results are given to better highlight the effectiveness of the proposed control scheme.

Clinical Pilot Study and Computational Modeling of Bitemporal Transcranial Direct Current Stimulation, and Safety of Repeated Courses of Treatment, in Major Depression.

PubMed

Ho, Kerrie-Anne; Bai, Siwei; Martin, Donel; Alonzo, Angelo; Dokos, Socrates; Loo, Colleen K

2015-12-01

This study aimed to examine a bitemporal (BT) transcranial direct current stimulation (tDCS) electrode montage for the treatment of depression through a clinical pilot study and computational modeling. The safety of repeated courses of stimulation was also examined. Four participants with depression who had previously received multiple courses of tDCS received a 4-week course of BT tDCS. Mood and neuropsychological function were assessed. The results were compared with previous courses of tDCS given to the same participants using different electrode montages. Computational modeling examined the electric field maps produced by the different montages. Three participants showed clinical improvement with BT tDCS (mean [SD] improvement, 49.6% [33.7%]). There were no adverse neuropsychological effects. Computational modeling showed that the BT montage activates the anterior cingulate cortices and brainstem, which are deep brain regions that are important for depression. However, a fronto-extracephalic montage stimulated these areas more effectively. No adverse effects were found in participants receiving up to 6 courses of tDCS. Bitemporal tDCS was safe and led to clinically meaningful efficacy in 3 of 4 participants. However, computational modeling suggests that the BT montage may not activate key brain regions in depression more effectively than another novel montage--fronto-extracephalic tDCS. There is also preliminary evidence to support the safety of up to 6 repeated courses of tDCS.

PM2.5 Exposure Suppresses Dendritic Maturation in Subgranular Zone in Aged Rats.

PubMed

Cheng, Lewis; Lau, Way K W; Fung, Timothy K H; Lau, Benson W M; Chau, Bolton K H; Liang, Yutong; Wang, Zhe; So, Kwok Fai; Wang, Tao; Chan, Chetwyn C H; Lee, Tatia M C

2017-07-01

Detrimental effects of long-term inhalation of fine particulate matter (PM 2.5 ) on the pulmonary and cardiovascular systems have been widely reported. Recent studies have shown that exposure to PM 2.5 also causes adverse neurocognitive effects. This study investigates the effects of inhaled ammonium sulfate, which is a major compound of inorganic air pollutants in PM 2.5 , on adult neurogenesis in aged Sprague-Dawley rats. A total of 20 rats were randomly assigned to experimental (n = 10) and control (n = 10) conditions, wherein they were exposed to either ammonium sulfate or sham air for 2 h per day and for 28 consecutive days. It was observed that ammonium sulfate inhibited the maturation process and diminished dendritic complexity of immature neurons in the subgranular zone (SGZ) of the hippocampus significantly, although the number of neural stem cells or the rates of differentiation were comparable between the two groups. Our findings provide clear evidence on the direct relationship between air quality and advantageous neurogenesis. Exposure to PM leads to specific adverse effects on the maturation process during neurogenesis.

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

Understanding older adults' medication decision making and behavior: A study on over-the-counter (OTC) anticholinergic medications.

PubMed

Holden, Richard J; Srinivas, Preethi; Campbell, Noll L; Clark, Daniel O; Bodke, Kunal S; Hong, Youngbok; Boustani, Malaz A; Ferguson, Denisha; Callahan, Christopher M

2018-03-06

Older adults purchase and use over-the-counter (OTC) medications with potentially significant adverse effects. Some OTC medications, such as those with anticholinergic effects, are relatively contraindicated for use by older adults due to evidence of impaired cognition and other adverse effects. To inform the design of future OTC medication safety interventions for older adults, this study investigated consumers' decision making and behavior related to OTC medication purchasing and use, with a focus on OTC anticholinergic medications. The study had a cross-sectional design with multiple methods. A total of 84 adults participated in qualitative research interviews (n = 24), in-store shopper observations (n = 39), and laboratory-based simulated OTC shopping tasks (n = 21). Simulated shopping participants also rank-ordered eight factors on their importance for OTC decision making. Findings revealed that many participants had concerns about medication adverse effects, generally, but were not aware of age-related risk associated with the use of anticholinergic medications. Analyses produced a map of the workflow of OTC-related behavior and decision making as well as related barriers such as difficulty locating medications or comparing them to an alternative. Participants reported effectiveness, adverse effects or health risks, and price as most important to their OTC medication purchase and use decisions. A persona analysis identified two types of consumers: the habit follower, who frequently purchased OTC medications and considered them safe; and the deliberator, who was more likely to weigh their options and consider alternatives to OTC medications. A conceptual model of OTC medication purchase and use is presented. Drawing on study findings and behavioral theories, the model depicts dual processes for OTC medication decision making - habit-based and deliberation-based - as well as the antecedents and consequences of decision making. This model suggests several design directions for consumer-oriented interventions to promote OTC medication safety. Copyright © 2018 Elsevier Inc. All rights reserved.

Possible directions of refining criteria of radiation safety of spaceflights

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

Kovalev, Y.Y.; Petrov, V.M.; Sakovich, V.A.

The possibility of characterizing space flight radiation safety is considered using a value which is integrated over the flight time, takes into account the radiation processes in an irradiated body and averages the probability of adverse radiobiological effects with respect to the distribution of solar proton flares of varying intensity. The proposed characteristic is compared with the current standards with reference to a hypothetic interplanetary flight.

The Effects of Using Direct Instruction and the Equal Additions Algorithm to Promote Subtraction with Regrouping Skills of Students with Emotional and Behavioral Disorders with Mathematics Difficulties

ERIC Educational Resources Information Center

Fain, Angela Christine

2013-01-01

Students with emotional and behavioral disorders (E/BD) display severe social and academic deficits that can adversely affect their academic performance in mathematics and result in higher rates of failure throughout their schooling compared to other students with disabilities (U.S. Department of Education, 2005; Webber & Plotts, 2008).…

Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination.

PubMed

Cagnoni, Francesca; Njwe, Christian Achiri Ngu; Zaninelli, Augusto; Ricci, Alessandra Rossi; Daffra, Diletta; D'Ospina, Antonio; Preti, Paola; Destro, Maurizio

2010-08-09

The renin-angiotensin-aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination.

Steam inhalation therapy: severe scalds as an adverse side effect

PubMed Central

Baartmans, Martin; Kerkhof, Evelien; Vloemans, Jos; Dokter, Jan; Nijman, Susanne; Tibboel, Dick; Nieuwenhuis, Marianne

2012-01-01

Background Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. Aim To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. Design and setting A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. Method Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. Results Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were €115 500 (£93 000), emotional costs are not reflected. Conclusion As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID:22781995

Effects of IL1B single nucleotide polymorphisms on depressive and anxiety symptoms are determined by severity and type of life stress.

PubMed

Kovacs, David; Eszlari, Nora; Petschner, Peter; Pap, Dorottya; Vas, Szilvia; Kovacs, Peter; Gonda, Xenia; Juhasz, Gabriella; Bagdy, Gyorgy

2016-08-01

Interleukin-1β is one of the main mediators in the cross-talk between the immune system and the central nervous system. Higher interleukin-1β levels are found in mood spectrum disorders, and the stress-induced expression rate of the interleukin-1β gene (IL1B) is altered by polymorphisms in the region. Therefore we examined the effects of rs16944 and rs1143643 single nucleotide polymorphisms (SNPs) within the IL1B gene on depressive and anxiety symptoms, as measured by the Brief Symptom Inventory, in a Hungarian population sample of 1053 persons. Distal and proximal environmental stress factors were also included in our analysis, namely childhood adversity and recent negative life-events. We found that rs16944 minor (A) allele specifically interacted with childhood adversity increasing depressive and anxiety symptoms, while rs1143643's minor (A) allele showed protective effect against depressive symptoms after recent life stress. The genetic main effects of the two SNPs were not significant in the main analysis, but the interaction effects remained significant after correction for multiple testing. In addition, the effect of rs16944 A allele was reversed in a subsample with low-exposure to life stress, suggesting a protective effect against depressive symptoms, in the post hoc analysis. In summary, both of the two IL1B SNPs showed specific environmental stressor-dependent effects on mood disorder symptoms. We also demonstrated that the presence of exposure to childhood adversity changed the direction of the rs16944 effect on depression phenotype. Therefore our results suggest that it is advisable to include environmental factors in genetic association studies when examining the effect of the IL1B gene. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

PubMed Central

Miyaoka, Tsuyoshi; Tsuji, Seiichi; Inami, Yasushi; Nishida, Akira; Horiguchi, Jun

2010-01-01

Objective: Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject. Data Sources: Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. Study Selection and Data Extraction: Publications relevant to the objective of this article were obtained (1992–2010), and some adverse neuropsychiatric reactions were summarized. Data Synthesis: Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem. Conclusions: Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem. PMID:21494350

Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial.

PubMed

Narita, Zui; Yokoi, Yuma

2017-06-19

Patients with Alzheimer's disease frequently elicit neuropsychiatric symptoms as well as cognitive deficits. Above all, depression is one of the most common neuropsychiatric symptoms in Alzheimer's disease but antidepressant drugs have not shown significant beneficial effects on it. Moreover, electroconvulsive therapy has not ensured its safety for potential severe adverse events although it does show beneficial clinical effect. Transcranial direct current stimulation can be the safe alternative of neuromodulation, which applies weak direct electrical current to the brain. Although transcranial direct current stimulation has plausible evidence for its effect on depression in young adult patients, no study has explored it in older subjects with depression in Alzheimer's disease. Therefore, we present a study protocol designed to evaluate the safety and clinical effect of transcranial direct current stimulation on depression in Alzheimer's disease in subjects aged over 65 years. This is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Subjects will be randomized to either an active or a sham transcranial direct current stimulation group. Participants in both groups will be evaluated at baseline, immediately, and 2 weeks after the intervention. This study investigates the safety and effect of transcranial direct current stimulation that may bring a significant impact on both depression and cognition in patients with Alzheimer's disease, and may be useful to enhance their quality of life. ClinicalTrials.gov, NCT02351388 . Registered on 27 January 2015. Last updated on 30 May 2016.

Molecular and clinical roles of incretin-based drugs in patients with heart failure.

PubMed

Orabi, Bassant; Kaddoura, Rasha; Omar, Amr S; Carr, Cornelia; Alkhulaifi, Abdulaziz

2018-05-01

Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors produce some beneficial and deleterious effects in diabetic patients not mediated by their glycemic lowering effects, and there is a need for better understanding of the molecular basis of these effects. They possess antioxidant and anti-inflammatory effects with some direct vasodilatory action (animal and human trial data) that may indirectly influence heart failure (HF). Unlike GLP-1R agonists, signaling for HF adverse effects was observed with two DPP-4 inhibitors, saxagliptin and alogliptin. Accordingly, these drugs should be used with caution in heart failure patients.

Work and its role in shaping the social gradient in health

PubMed Central

Clougherty, Jane E.; Souza, Kerry; Cullen, Mark R.

2013-01-01

Adults with better jobs enjoy better health: job title was, in fact, the social gradient metric first used to study the relationship between social class and chronic disease etiology, a core finding now replicated in most developed countries. What has been less well proved is whether this correlation is causal, and if so, through what mechanisms. During the past decade, much research has been directed at these issues.Best evidence in2009 suggests that occupation does affect health. Most recent research on the relationship has been directed at disentangling the pathways through which lower-status work leads to adverse health outcomes. This review focuses on six areas of recent progress: (1) the role of status in a hierarchical occupational system; (2) the roles of psychosocial job stressors; (3) effects of workplace physical and chemical hazard exposures; (4) evidence that work organization matters as a contextual factor; (5) implications for the gradient of new forms of nonstandard or “precarious” employment such as contract and shift work; and (6) emerging evidence that women may be impacted differently by adverse working conditions, and possibly more strongly, than men. PMID:20201870

Work and its role in shaping the social gradient in health.

PubMed

Clougherty, Jane E; Souza, Kerry; Cullen, Mark R

2010-02-01

Adults with better jobs enjoy better health: job title was, in fact, the social gradient metric first used to study the relationship between social class and chronic disease etiology, a core finding now replicated in most developed countries. What has been less well proved is whether this correlation is causal, and if so, through what mechanisms. During the past decade, much research has been directed at these issues. Best evidence in 2009 suggests that occupation does affect health. Most recent research on the relationship has been directed at disentangling the pathways through which lower-status work leads to adverse health outcomes. This review focuses on six areas of recent progress: (1) the role of status in a hierarchical occupational system; (2) the roles of psychosocial job stressors; (3) effects of workplace physical and chemical hazard exposures; (4) evidence that work organization matters as a contextual factor; (5) implications for the gradient of new forms of nonstandard or "precarious" employment such as contract and shift work; and (6) emerging evidence that women may be impacted differently by adverse working conditions, and possibly more strongly, than men.

Mental health and substance abuse insurance parity for federal employees: how did health plans respond?

PubMed

Barry, Colleen L; Ridgely, M Susan

2008-01-01

A fundamental concern with competitive health insurance markets is that they will not supply efficient levels of coverage for treatment of costly, chronic, and predictable illnesses, such as mental illness. Since the inception of employer-based health insurance, coverage for mental health services has been offered on a more limited basis than coverage for general medical services. While mental health advocates view insurance limits as evidence of discrimination, adverse selection and moral hazard can also explain these differences in coverage. The intent of parity regulation is to equalize private insurance coverage for mental and physical illness (an equity concern) and to eliminate wasteful forms of competition due to adverse selection (an efficiency concern). In 2001, a presidential directive requiring comprehensive parity was implemented in the Federal Employees Health Benefits (FEHB) Program. In this study, we examine how health plans responded to the parity directive. Results show that in comparison with a set of unaffected health plans, federal employee plans were significantly more likely to augment managed care through contracts with managed behavioral health "carve-out" firms after parity. This finding helps to explain the absence of an effect of the FEHB Program directive on total spending, and is relevant to the policy debate in Congress over federal parity.

36 CFR 800.6 - Resolution of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties. (1...

Investigating environmental links between parent depression and child depressive/anxiety symptoms using an assisted conception design.

PubMed

Lewis, Gemma; Rice, Frances; Harold, Gordon T; Collishaw, Stephan; Thapar, Anita

2011-05-01

Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited effects, shared adversity, and child age and gender. Eight hundred fifty-two families with a child born by assisted conception provided questionnaire data. Mothers and fathers were genetically related or unrelated to the child depending on conception method. Parental depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Child depression/anxiety symptoms were assessed using the Short Mood and Feelings questionnaire and six items tapping generalized anxiety disorder symptoms. Associations between maternal and child symptoms were examined separately for genetically unrelated and related mother-child pairs, adjusting for three measurements of shared adversity: negative life events, family income, and socioeconomic status. Analyses were then run separately for boys and girls and for children and adolescents, and the role of paternal depression symptoms was also examined. Significant associations between parent and child symptoms were found for genetically unrelated mother-child (r = 0.32, p < .001) and father-child (r = 0.17, p < .05) pairs and genetically related mother-child (r = 0.31, p < .001) and father-child (r = 0.23, p < .001) pairs and were not explained by the shared adversity measurements. Environmental links were present for children and adolescents and were stronger for girls. The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy.

PubMed

Eigentler, Thomas K; Hassel, Jessica C; Berking, Carola; Aberle, Jens; Bachmann, Oliver; Grünwald, Viktor; Kähler, Katharina C; Loquai, Carmen; Reinmuth, Niels; Steins, Martin; Zimmer, Lisa; Sendl, Anna; Gutzmer, Ralf

2016-04-01

PD-1 checkpoint inhibitors are associated with a specific spectrum of immune-related adverse events. This spectrum is different from toxicities known for kinase inhibitors or cytotoxic drugs. Since PD-1 directed therapies show effectivity in an increasing number of malignant diseases, their clinical usage will increase rapidly. Therefore clinicians from different specialities such as medical oncology, internal medicine, family doctors and emergency unit staff should be aware of the adverse effects of PD-1 checkpoint inhibitors to avoid delays in diagnosis and treatment. Based on pooled data from pivotal trials as reported by the European Medicines Agency, the present paper reviews incidences and kinetics of onset and resolution of immune-mediated "adverse events of specific interest" (AEOSI) of both approved PD-1 inhibitors nivolumab and pembrolizumab. In general, the severity of AEOSI is mild to moderate (grade 1-2); the frequency of immune-mediated but also idiopathic grade 3-4 adverse drug reactions is ⩽2% for any event term. Recommendations for the diagnosis, monitoring and management of the relevant dermatological, gastrointestinal, pulmonary, endocrine, renal and hepatic toxicities are convened by an expert panel that consolidated and clarified treatment recommendations after the onset of AEOSI. Although the time of onset is not predictable - the medians range from 1 to 6months - the huge majority of events is reversible, with no impact of the time of onset. By the systemic use of glucocorticoids, notably methylprednisolone or equivalents, most AEOSI are well manageable. Non-steroidal immunosuppressants may be used in certain cases of refractory/recalcitrant, long-lasting immune toxicities. With regard to the outstanding clinical activity of the anti-PD-1 antibodies, therapy restart is the principal therapeutic option after recovery of grade 2 AEOSI, or diminution of higher grade skin or endocrine events to mild severity. Early diagnosis and close clinical monitoring are essential for successful management of immune-related adverse events. Copyright © 2016 Elsevier Ltd. All rights reserved.

A realistic in vitro exposure revealed seasonal differences in (pro-)inflammatory effects from ambient air in Fribourg, Switzerland.

PubMed

Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

2018-01-01

Ambient air pollutant levels vary widely in space and time, therefore thorough local evaluation of possible effects is needed. In vitro approaches using lung cell cultures grown at the air-liquid interface and directly exposed to ambient air can offer a reliable addition to animal experimentations and epidemiological studies. To evaluate the adverse effects of ambient air in summer and winter a multi-cellular lung model (16HBE14o-, macrophages, and dendritic cells) was exposed in a mobile cell exposure system. Cells were exposed on up to three consecutive days each 12 h to ambient air from Fribourg, Switzerland, during summer and winter seasons. Higher particle number, particulate matter mass, and nitrogen oxide levels were observed in winter ambient air compared to summer. Good cell viability was seen in cells exposed to summer air and short-term winter air, but cells exposed three days to winter air were compromised. Exposure of summer ambient air revealed no significant upregulation of oxidative stress or pro-inflammatory genes. On the opposite, the winter ambient air exposure led to an increased oxidative stress after two exposure days, and an increase in three assessed pro-inflammatory genes already after 12 h of exposure. We found that even with a short exposure time of 12 h adverse effects in vitro were observed only during exposure to winter but not summer ambient air. With this work we have demonstrated that our simple, fast, and cost-effective approach can be used to assess (adverse) effects of ambient air.

Translational toxicology: a developmental focus for integrated research strategies.

PubMed

Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo

2013-09-30

Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.

Increased mortality risk among the visually impaired: the roles of mental well-being and preventive care practices.

PubMed

Zheng, D Diane; Christ, Sharon L; Lam, Byron L; Arheart, Kristopher L; Galor, Anat; Lee, David J

2012-05-14

Mechanisms by which visual impairment (VI) increases mortality risk are poorly understood. We estimated the direct and indirect effects of self-rated VI on risk of mortality through mental well-being and preventive care practice mechanisms. Using complete data from 12,987 adult participants of the 2000 Medical Expenditure Panel Survey with mortality linkage through 2006, we undertook structural equation modeling using two latent variables representing mental well-being and poor preventive care to examine multiple effect pathways of self-rated VI on all-cause mortality. Generalized linear structural equation modeling was used to simultaneously estimate pathways including the latent variables and Cox regression model, with adjustment for controls and the complex sample survey design. VI increased the risk of mortality directly after adjusting for mental well-being and other covariates (hazard ratio [HR] = 1.25 [95% confidence interval: 1.01, 1.55]). Poor preventive care practices were unrelated to VI and to mortality. Mental well-being decreased mortality risk (HR = 0.68 [0.64, 0.74], P < 0.001). VI adversely affected mental well-being (β = -0.54 [-0.65, -0.43]; P < 0.001). VI also increased mortality risk indirectly through mental well-being (HR = 1.23 [1.16, 1.30]). The total effect of VI on mortality including its influence through mental well-being was HR 1.53 [1.24, 1.90]. Similar but slightly stronger patterns of association were found when examining cardiovascular disease-related mortality, but not cancer-related mortality. VI increases the risk of mortality directly and indirectly through its adverse impact on mental well-being. Prevention of disabling ocular conditions remains a public health priority along with more aggressive diagnosis and treatment of depression and other mental health conditions in those living with VI.

Beyond Ether and Chloroform-A Major Breakthrough With Halothane.

PubMed

Huang, Lisa; Sang, Christine N; Desai, Manisha S

2017-07-01

The use of equipment powered by electricity in the operating room increased the risk of fires in the presence of flammable agents such as ether and cyclopropane. Chloroform was associated with cardiac arrhythmias and liver damage. The introduction of halothane in the late 1950s was heralded as a solution to many problems facing the specialty of anesthesia. We explore whether the manufacturer promptly reported halothane's adverse effects to regulatory agencies and practitioners. We consulted documents submitted by Ayerst Laboratories to federal authorities through the Freedom of Information Act, promotional advertisements, package inserts, published articles, and textbooks. Two major complications associated with the use of halothane, cardiac arrhythmias and the risk of hepatotoxicity, were disclosed by the manufacturer when the drug was first introduced to the US market. Reports appeared timely and complete; there was no apparent attempt to conceal or otherwise downplay these risks. The process of drug discovery and approval for clinical use has always been a lengthy, complex, and extremely expensive undertaking, with only a small minority of compounds receiving approval. The risk of adverse effects or drug interaction directly impacts commercial viability. In the case of halothane, the manufacturer disclosed major adverse effects, and the drug enjoyed decades of popularity until it was replaced by agents with a better drug profile. Copyright © 2017 Elsevier Inc. All rights reserved.

An Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Factor ADMA

PubMed Central

Ghebremariam, Yohannes T.; LePendu, Paea; Lee, Jerry C.; Erlanson, Daniel A.; Slaviero, Anna; Shah, Nigam H.; Leiper, James; Cooke, John P.

2013-01-01

Background Proton pump inhibitors (PPIs) are gastric acid suppressing agents widely prescribed for the treatment of gastro-esophageal reflux disease (GERD). Recently, several studies in patients with acute coronary syndrome (ACS) have raised the concern that use of PPIs in these patients may increase their risk of major adverse cardiovascular events (MACE). The mechanism of this possible adverse effect is not known. Whether the general population might also be at risk has not been addressed. Methods and Results Plasma ADMA is an endogenous inhibitor of nitric oxide synthase (NOS). Elevated plasma ADMA is associated with increased risk for cardiovascular disease, likely due to its attenuation of the vasoprotective effects of endothelial NOS. We find that PPIs elevate plasma asymmetric dimethylarginine (ADMA) level and reduce nitric oxide (NO) levels and endothelium-dependent vasodilation in a murine model and ex vivo human tissues. PPIs increase ADMA because they bind to, and inhibit dimethylarginine dimethylaminohydrolase (DDAH), the enzyme that degrades ADMA. Conclusions We present a plausible biological mechanism to explain the association of PPIs with increased MACE in patients with unstable coronary syndromes. Of concern, this adverse mechanism is also likely to extend to the general population using PPIs. This finding compels additional clinical investigations and pharmacovigilance directed toward understanding the cardiovascular risk associated with use of the PPIs in the general population. PMID:23825361

Wood combustion particles induce adverse effects to normal and diseased airway epithelia.

PubMed

Krapf, Manuel; Künzi, Lisa; Allenbach, Sandrine; Bruns, Emily A; Gavarini, Ilaria; El-Haddad, Imad; Slowik, Jay G; Prévôt, André S H; Drinovec, Luka; Močnik, Griša; Dümbgen, Lutz; Salathe, Matthias; Baumlin, Nathalie; Sioutas, Constantinos; Baltensperger, Urs; Dommen, Josef; Geiser, Marianne

2017-04-19

Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components.

Cardiomyopathy from 1,1-Difluoroethane Inhalation.

PubMed

Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

2016-10-01

Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

A rare adverse effect of metronidazole: nervous system symptoms.

PubMed

Kafadar, Ihsan; Moustafa, Fatma; Yalçın, Koray; Klç, Betül Aydn

2013-06-01

Metronidazole, as a 5-nitroimidazole compound, is effective on anaerobic bacteria and protozoon diseases. Mostly, metronidazole is a tolerable drug but rarely presents serious adverse effects on the nervous system. In case of these adverse effects, treatment must be stopped.In this report, a 3-year-old child hospitalized because of diarrhea is presented. During the metronidazole treatment, loss of sight, vertigo, ataxia, and headache occurred as the adverse effects. By this report, we want to express the rare adverse effects of drugs in the differential diagnoses of nervous system diseases.

Respiratory effects of air pollution on children.

PubMed

Goldizen, Fiona C; Sly, Peter D; Knibbs, Luke D

2016-01-01

A substantial proportion of the global burden of disease is directly or indirectly attributable to exposure to air pollution. Exposures occurring during the periods of organogenesis and rapid lung growth during fetal development and early post-natal life are especially damaging. In this State of the Art review, we discuss air toxicants impacting on children's respiratory health, routes of exposure with an emphasis on unique pathways relevant to young children, methods of exposure assessment and their limitations and the adverse health consequences of exposures. Finally, we point out gaps in knowledge and research needs in this area. A greater understanding of the adverse health consequences of exposure to air pollution in early life is required to encourage policy makers to reduce such exposures and improve human health. © 2015 Wiley Periodicals, Inc.

36 CFR 800.5 - Assessment of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply criteria of adverse effect. In consultation with the SHPO/THPO and any Indian tribe or Native Hawaiian...

Final Environmental Assessment Addressing Construction of a Fitness Center at Beale Air Force Base, California

DTIC Science & Technology

2009-10-01

adverse impacts on geology and soils would be anticipated due to construction and demolition activities, such as grading, excavation, and...2, during construction and demolition activities would limit adverse impacts on geology and soils. Therefore, no long-term, adverse, direct or...20 99 113 70 70 99 65 70 20 Live Oak Loma Rica Tierra Buena Wheatland Lincoln Linda Marysville Olivehurst South Yuba City Yuba City Source: ESRI

Comparison of search strategies in systematic reviews of adverse effects to other systematic reviews.

PubMed

Golder, Su; Loke, Yoon K; Zorzela, Liliane

2014-06-01

Research indicates that the methods used to identify data for systematic reviews of adverse effects may need to differ from other systematic reviews. To compare search methods in systematic reviews of adverse effects with other reviews. The search methodologies in 849 systematic reviews of adverse effects were compared with other reviews. Poor reporting of search strategies is apparent in both systematic reviews of adverse effects and other types of systematic reviews. Systematic reviews of adverse effects are less likely to restrict their searches to MEDLINE or include only randomised controlled trials (RCTs). The use of other databases is largely dependent on the topic area and the year the review was conducted, with more databases searched in more recent reviews. Adverse effects search terms are used by 72% of reviews and despite recommendations only two reviews report using floating subheadings. The poor reporting of search strategies in systematic reviews is universal, as is the dominance of searching MEDLINE. However, reviews of adverse effects are more likely to include a range of study designs (not just RCTs) and search beyond MEDLINE. © 2014 Crown Copyright.

The Efficacy of a Silicone Sheet in Postoperative Scar Management.

PubMed

Kim, Jin Sam; Hong, Joon Pio; Choi, Jong Woo; Seo, Dong Kyo; Lee, Eun Sook; Lee, Ho Seong

2016-09-01

Silicone gel sheeting has been introduced to prevent scarring, but objective evidence for its usefulness in scar healing is limited. Therefore, the authors' objective was to examine the effectiveness of silicone gel sheeting by randomly applying it to only unilateral scars from a bilateral hallux valgus surgery with symmetrical closure. In a prospective randomized, blinded, intraindividual comparison study, the silicone gel sheeting was applied to 1 foot of a hallux valgus incision scar (an experiment group) for 12 weeks upon removal of the stitches, whereas the symmetrical scar from the other foot was left untreated (a control group). The scars were evaluated at 4 and 12 weeks after the silicon sheet application. The Vancouver Scar Scale was used to measure the vascularity, pigmentation, pliability, height, and length of the scars. Adverse effects were also evaluated, and they included pain, itchiness, rash, erythema, and skin softening. At weeks 4 and 12, the experiment group scored significantly better on the Vancouver Scar Scale in all items, except length (P < .05 for all except the length of scar), compared with the control group. In all items, adverse effects of the experiment group were significantly lower than those of the control group at week 12, suggesting that direct attachment of the silicone sheet does not cause adverse effects (P < .05). To the authors' knowledge, this is one of the first models to minimize bias related to scar evaluation by using symmetrical scars. The early silicone sheet application did show a significant improvement in prevention of postoperative scarring.

Patients use an internet technology to report when things go wrong.

PubMed

Wasson, John H; MacKenzie, Todd A; Hall, Michael

2007-06-01

As patients directly experience harm from adverse events, investigators have proposed patient-report to complement professional reporting of adverse events. To investigate how an automated health assessment system can be used to identify adverse events. Internet survey responses from April 2003 to April 2005 involving communities and clinical practices across the USA. 44,860 adults aged 19-69 years. Patient perceptions of adverse events experienced during the previous year. Independent legal review was also used to estimate how many patient-reports were serious enough to be potentially compensable. Although patient reports of possible adverse events was low (1.4%), the percentage of adverse events was eight times higher for patients with the greatest burden of illness than for those with the least (3.4% vs 0.4%). Two expert malpractice attorneys agreed that 9% of the adverse events seemed to be serious. PATIENTS will use internet technology to report their perceptions of health-related adverse events. Some of the patient-reported events reported will be serious.

When it rains, it pours: future climate extremes and health.

PubMed

Patz, Jonathan A; Grabow, Maggie L; Limaye, Vijay S

2014-01-01

The accelerating accumulation of greenhouse gases in the Earth's atmosphere is changing global environmental conditions in unprecedented and potentially irreversible ways. Climate change poses a host of challenges to the health of populations through complex direct and indirect mechanisms. The direct effects include an increased frequency of heat waves, rising sea levels that threaten low-lying communities, anticipated extremes in the global hydrologic cycle (droughts, floods, and intense storms), and adverse effects on agricultural production and fisheries due to environmental stressors and changes in land use. Indirectly, climate change is anticipated to threaten health by worsening urban air pollution and increasing rates of infectious (particularly waterborne and vector-borne) disease transmission. To provide a state-of-the-science review on the health consequences of a changing climate. Environmental public health researchers have concluded that, on balance, adverse health outcomes will dominate under these changed climatic conditions. The number of pathways through which climate change can affect the health of populations makes this environmental health threat one of the largest and most formidable of the new century. Geographic location plays an influential role the potential for adverse health effects caused by climate change, and certain regions and populations are more vulnerable than others to expected health effects. Two kinds of strategies are available for responding to climate change: mitigation policies (which aim to reduce greenhouse gas emissions) and adaptation measures (relating to preparedness for anticipated impacts). To better understand and address the complex nature of health risks posed by climate change, interdisciplinary collaboration is critical. Efforts to move beyond our current reliance on fossil fuels to cleaner, more sustainable energy sources may offer some of the greatest health opportunities in more than a century and cobenefits beyond the health sector. Because the nations least responsible for climate change are most vulnerable to its effects, the challenge to reduce greenhouse gas emissions is not merely technical, but also moral. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Do indoor pollutants and thermal conditions in schools influence student performance? A critical review of the literature.

PubMed

Mendell, M J; Heath, G A

2005-02-01

To assess whether school environments can adversely affect academic performance, we review scientific evidence relating indoor pollutants and thermal conditions, in schools or other indoor environments, to human performance or attendance. We critically review evidence for direct associations between these aspects of indoor environmental quality (IEQ) and performance or attendance. Secondarily, we summarize, without critique, evidence on indirect connections potentially linking IEQ to performance or attendance. Regarding direct associations, little strongly designed research was available. Persuasive evidence links higher indoor concentrations of NO(2) to reduced school attendance, and suggestive evidence links low ventilation rates to reduced performance. Regarding indirect associations, many studies link indoor dampness and microbiologic pollutants (primarily in homes) to asthma exacerbations and respiratory infections, which in turn have been related to reduced performance and attendance. Also, much evidence links poor IEQ (e.g. low ventilation rate, excess moisture, or formaldehyde) with adverse health effects in children and adults and documents dampness problems and inadequate ventilation as common in schools. Overall, evidence suggests that poor IEQ in schools is common and adversely influences the performance and attendance of students, primarily through health effects from indoor pollutants. Evidence is available to justify (i) immediate actions to assess and improve IEQ in schools and (ii) focused research to guide IEQ improvements in schools. There is more justification now for improving IEQ in schools to reduce health risks to students than to reduce performance or attendance risks. However, as IEQ-performance links are likely to operate largely through effects of IEQ on health, IEQ improvements that benefit the health of students are likely to have performance and attendance benefits as well. Immediate actions are warranted in schools to prevent dampness problems, inadequate ventilation, and excess indoor exposures to substances such as NO(2) and formaldehyde. Also, siting of new schools in areas with lower outdoor pollutant levels is preferable.

The pathogenesis of constipation.

PubMed

Sykes, Nigel P

2006-05-01

The pathogenesis of the constipation that is commonly experienced by cancer patients, especially those with advanced disease, is the result of multiple influences on the control of intestinal motility and fluid handling. These factors include the direct effects of malignancy on gut structure, paraneoplastic neural impairment, biochemical disturbance, and adverse effects of cancer treatments. In addition, the debility and reduced oral intake associated with cancer also contribute, as, perhaps, might the older age of many cancer patients. A detailed understanding of the mechanisms of constipation, especially in association with illness, is lacking, and most treatments remain nonspecific.

Iatrogenic effects of psychosocial interventions: treatment, life context, and personal risk factors.

PubMed

Moos, Rudolf H

2012-01-01

Between 7% and 15% of individuals who participate in psychosocial interventions for substance use disorders may be worse off after treatment than before. Intervention-related predictors of iatrogenic effects include lack of bonding; lack of goal direction and monitoring; confrontation, criticism, and high emotional arousal; models and norms for substance use; and stigma and inaccurate expectations. Life context and personal predictors include lack of support, criticism, and more severe substance use and psychological problems. Ongoing monitoring and safety standards are needed to identify and counteract adverse consequences of intervention programs.

Neurobehavioral Manifestations of HIV/AIDS: Diagnosis and Treatment

PubMed Central

Singer, Elyse J.; Thames, April D.

2015-01-01

Synopsis Behavioral disorders are common in HIV-infected (HIV+) persons. The differential includes pre-existing psychiatric diseases, substance abuse, direct effects of HIV infection, opportunistic infection (OI), and the adverse effects of medical therapies. Many patients have more than one contributing or co-morbid problem to explain these behavioral changes. The differential should always include consideration of psychosocial, genetic, and medical causes of disease. Treatment strategies must take into account the co-administration of antiretroviral therapy and the specific neurological problems common in the HIV+ population. PMID:26613994

49 CFR 601.36 - Procedures for direct final rulemaking.

Code of Federal Regulations, 2010 CFR

2010-10-01

... non-controversial rules that: (1) Affect internal procedures of FTA, such as filing requirements and... by FTA within the specified time after the date of publication and that, if no written adverse... written notice of intent to submit adverse comment is received by FTA within the specified time of...

A Systematic Review Evaluating the Effect of Vitamin B6 on Semen Quality.

PubMed

Banihani, Saleem Ali

2017-12-30

This review systematically discusses and summarizes the effect of vitamin B6 on semen quality. To achieve this contribution, we searched the PubMed, Scopus, and Web of Science databases for English language papers from 1984 through 2017 using the key words "sperm" versus "Vitamin B6", "pyridoxine", and "pyridoxal". Also, the references from selected published papers were included, only if relevant. To date, as revealed by rodent studies, high doses of vitamin B6 impair semen quality and sperm parameters. While in humans, it is suggested, but not yet directly approved, that seminal vitamin B6 levels may alter sperm quality (i.e., sperm quantity and quality), and that vitamin B6 deficiency may trigger the chemical toxicity to sperm (i.e., hyperhomocysteinemia, oxidative injury). The adverse effect of vitamin B6, when used at high doses, has been revealed in experimental animals, but not yet directly approved in humans. Consequently, in vitro studies on human ejaculate as well as clinical studies that investigate the direct effect of vitamin B6 on semen quality seem very significant.

Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

PubMed Central

Mills, Nicholas L.; Miller, Mark R.; Lucking, Andrew J.; Beveridge, Jon; Flint, Laura; Boere, A. John F.; Fokkens, Paul H.; Boon, Nicholas A.; Sandstrom, Thomas; Blomberg, Anders; Duffin, Rodger; Donaldson, Ken; Hadoke, Patrick W.F.; Cassee, Flemming R.; Newby, David E.

2011-01-01

Aim Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions. PMID:21753226

The adverse health effects of chronic cannabis use.

PubMed

Hall, Wayne; Degenhardt, Louisa

2014-01-01

This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. Copyright © 2013 John Wiley & Sons, Ltd.

Increased behavioral output but intact goal-directed and habitual responding for food reward following early-life social deprivation in rats.

PubMed

Lomanowska, Anna M; Kraemer, Gary W

2014-09-01

Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity. Copyright © 2014 Elsevier B.V. All rights reserved.

Adverse events and treatment failure leading to discontinuation of recently approved antipsychotic drugs in schizophrenia: A network meta-analysis.

PubMed

Tonin, Fernanda S; Piazza, Thais; Wiens, Astrid; Fernandez-Llimos, Fernando; Pontarolo, Roberto

2015-12-01

Objective:We aimed to gather evidence of the discontinuation rates owing to adverse events or treatment failure for four recently approved antipsychotics (asenapine, blonanserin, iloperidone, and lurasidone).Methods: A systematic review followed by pairwise meta-analysis and mixed treatment comparison meta analysis(MTC) was performed, including randomized controlled trials (RCTs) that compared the use of the above-mentioned drugs versus placebo in patients with schizophrenia. An electronic search was conducted in PubMed, Scopus, Science Direct, Scielo, the Cochrane Library, and International Pharmaceutical Abstracts(January 2015). The included trials were at least single blinded. The main outcome measures extracted were discontinuation owing to adverse events and discontinuation owing to treatment failure.Results: Fifteen RCTs were identified (n = 5400 participants) and 13 of them were amenable for use in our meta-analyses. No significant differences were observed between any of the four drugs and placebo as regards discontinuation owing to adverse events, whether in pairwise meta-analysis or in MTC. All drugs presented a better profile than placebo on discontinuation owing to treatment failure, both in pairwise meta-analysis and MTC. Asenapine was found to be the best therapy in terms of tolerability owing to failure,while lurasidone was the worst treatment in terms of adverse events. The evidence around blonanserin is weak.Conclusion: MTCs allowed the creation of two different rank orders of these four antipsychotic drugs in two outcome measures. This evidence-generating method allows direct and indirect comparisons, supporting approval and pricing decisions when lacking sufficient, direct, head-to-head trials.

Identification and Characterization of Adverse Effects in 21st Century Toxicology

EPA Science Inventory

The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...

Clinical outcomes and adverse effect monitoring in allergic rhinitis.

PubMed

Juniper, Elizabeth F; Ståhl, Elisabeth; Doty, Richard L; Simons, F Estelle R; Allen, David B; Howarth, Peter H

2005-03-01

The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably reduced or absent CNS sedative effects. Therefore, the CNS effects are entirely avoidable, and the first-generation H 1 -antihistamines should no longer be used in the management of allergic rhinitis. The considerably rarer but potentially very serious cardiac arrhythmogenic effects of H 1 -antihistamines are appreciated to be molecule-specific rather than class-specific. The in vitro screening of new compounds to eliminate the further development of those with cardiotoxicity ideally will lead to this adverse effect being historic. The incorporation of electrocardiogram recording in clinical trials provides direct information relating to prolongation of QT interval corrected for heart rate. Although administered at low doses, intranasal steroids still have the potential for systemic absorption and adverse consequences. However, it is appreciated that meaningful differences exist in the bioavailability of different steroid molecules, and although a small but statistically significant effect on growth in children has been identified with the long-term use of intranasal beclomethasone when administered twice daily for 1 year, this is not evident with all intranasal steroids. In addition, twice-daily intranasal steroid administration may have more effect--from the endocrinologic perspective--than once-daily administration in the morning, which coincides better with the natural diurnal variation in cortisol. Thus, once-daily intranasal steroid administration is preferable, and when used in studies in children, measurement of height change during the study period is an important outcome variable together with other indices of systemic steroid bioavailability (eg, tests of hypothalamic-pituitary-adrenal axis function). These considerations have even greater relevance if children are concurrently also receiving inhaled steroids for asthma, because the total steroid load will be greater.

Seizures as a Potential Complication of Treatment With Simeprevir and Sofosbuvir.

PubMed

Syal, Gaurav; Heldenbrand, Seth D; Duarte-Rojo, Andres

2016-01-01

Newer direct-acting antiviral agents have revolutionized the medical management of chronic hepatitis C. In addition to being extremely efficacious, they report very mild adverse drug reactions from experience in clinical trials. However, because they are relatively new on the horizon, postmarketing surveillance studies refining the safety profile are not yet available. We present a case of seizures as a potential side effect of antiviral therapy with sofosbuvir and simeprevir.

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

Shvedova, Anna, E-mail: ats1@cdc.gov; Department of Physiology & Pharmacology, WVU, Morgantown, WV; Pietroiusti, Antonio

The mounting societal concerns about possible and maybe even likely adverse effects of nanomaterials are reflected in a large and growing number of publications in the field of nanotoxicology. Indeed, today's search in PubMed reveals > 3700 publications on the subject denoted by (toxic + nanomaterials) – quite a growth over the last decade that began with only two dozens of them up-to 2005. - Highlights: • Major factors of nanotoxicology • Key directions for research efforts • Global representation of the authorship.

Direct-to-physician and direct-to-consumer advertising: Time to have stringent regulations.

PubMed

Kannan, S; Gowri, S; Tyagi, V; Kohli, S; Jain, R; Kapil, P; Bhardwaj, A

2015-01-01

Direct to physician advertisements and direct to consumer advertisement (DTCA) is a well-known marketing strategy of pharmaceutical companies. Studies from the West and also from the Indian sub-continent revealed several lacunae in such advertisements. The present study was carried out to understand the international and national scenario regarding the lacunae in drug advertisements and the opinion of both physicians and patients regarding DTCA. The present study was conducted after obtaining approval from the institutional ethics committee. Warning letters (WLs) issued to pharmaceutical companies by United States Food and Drug Administration (USFDA) and Therapeutic Goods Administration (TGA) due to discrepancies in the advertisements were analyzed for reasons that were grouped into one of the following categories: overstatement of efficacy; unapproved indication; lack of adequate directions to use; omission of adverse effects; misleading claims; advertisement made for an unapproved drug (investigational new product). Drug advertisements in Current Index of Medical Specialties (CIMS) April-July 2014 issue was also analyzed for lacunae depending on categories as mentioned above. Physicians and patients in a tertiary care medical college and hospital were administered a validated questionnaire exploring their views about crucial aspects of DTCA. Descriptive statistics was used for each of the categories. A total of 93 WLs issued by USFDA and 36 by TGA were assessed. Majority of the WLs by USFDA were issued for omission of adverse effects (61/93, 65.6%) followed by misleading claims (54/93, 58.1%). Similarly, WLs by TGA were also mainly issued for the presence of misleading claims (35/36, 97.2%) followed by overstatement of efficacy (26/36, 72.2%) and CIMS evaluation had revealed that 78/92 (84.8%) advertisements omitted adverse effects, 20/92 (21.7%) had misleading claims, 9/92 (9.8%) had unapproved indications and 7/92 (7.6%) overstated the efficacy. With regard to the opinion regarding DTCA, 69.9% physicians had a patient discussing DTCA that was clinically inappropriate. One hundred (64.5%) out of 155 physicians opined that DTCA encourage patients to attend physicians regarding preventive healthcare. On the contrary, 82/155 (52.9%) physicians felt that DTCA would damage the same. Similarly, 69 out of the total 100 patients felt that drug advertisements aid them to have better discussions with their treating physicians. Surprisingly, a large majority (91/100) were of the opinion that only safe drugs are allowed to be advertised. To conclude, from the findings of this study both the physicians and patients should be cautious and not overzealous while dealing with drug advertisements or promotional literature. More stringent scrutiny and issue of WLs or blacklisting of indulging pharmaceutical companies are mandatory by the regulatory agency to contain the same.

[Euthanasia and the doctrine of double effect].

PubMed

Klein, Martin

2005-01-01

Direct active euthanasia is prohibited in most countries while passive and indirect is not. However, many arguments against the legalization of voluntary active euthanasia are flawed. Ethical differences between active and passive or indirect euthanasia are difficult to maintain especially when the passivity of the actor causes death. The crucial point is not activity or passivity but respect for the autonomy of individual human beings. In particular there appears to be little ethical difference between active and indirect euthanasia. Indirect euthanasia has often been justified by the principle of double effect, which traces back to Thomas Aquinas. But resorting to this rule contains a logical fallacy. The principle of double effect does not allow foreseen and unwanted adverse effects of an action to occur when they are avoidable. In terminal sedation, an example for indirect euthanasia, hypoxemia and dehydration can easily be prevented by respirator therapy and fluid administration. Therefore the rule of double effect is not applicable. Indirect and direct active euthanasia cannot be ethically distinguished by resorting to the principle of double effect.

The Effect of Marijuana Scenes in Anti-marijuana Public Service Announcements on Adolescents’ Evaluation of Ad Effectiveness

PubMed Central

Kang, Yahui; Cappella, Joseph N.; Fishbein, Martin

2014-01-01

This study explored the possible negative impact of a specific ad feature—marijuana scenes—on adolescents’ perception of ad effectiveness. A secondary data analysis was conducted on adolescents’ evaluations of 60 anti-marijuana public service announcements (PSAs) that were a part of national and state anti-drug campaigns directed at adolescents. The major finding of the study was that marijuana scenes in anti-marijuana PSAs negatively affected ad liking and thought valence toward the ads among adolescents who are at higher levels of risk for marijuana use. This negative impact was not reversed in the presence of strong anti-marijuana arguments. The results may be used to partially explain the lack of effectiveness of the anti-drug media campaign. It may also help us design more effective anti-marijuana PSAs by isolating adverse elements in the ads that may elicit boomerang effects in the target population. Limitations of the study and future directions were discussed. PMID:19735026

Neuropsychiatric Effects of Antimicrobial Agents.

PubMed

Zareifopoulos, Nicholas; Panayiotakopoulos, George

2017-05-01

Antimicrobial drugs used in clinical practice are selected on the basis of their selective toxicity against bacterial cells. However, all exhibit multiple offsite interactions with eukaryotic cell structures, resulting in adverse reactions during antimicrobial pharmacotherapy. A multitude of these side effects involve the nervous system as antimicrobials at clinically relevant concentrations seem to interact with many of the same molecules usually implicated in the action of psychotropic drugs. The importance of such events cannot be overstated, as the misdiagnosis of an adverse drug reaction as a symptom of a primary psychiatric or neurological disorder entails great suffering for the patient affected as well as significant costs for the healthcare system. The neuropsychiatric effects of antimicrobial drugs are extensively documented in the literature. A number of antimicrobial drugs have the potential to exert CNS effects and many are associated with stimulant, psychotomimetic and epileptogenic properties, mediated by GABA antagonism (beta-lactams, quinolones and clarithromycin), NMDA agonism (D-cycloserine, aminoglycosides, and perhaps quinolones), MAO inhibition (linezolid, metronidazole and isoniazid weakly) as well as more exotic mechanisms, as in the case of trimethoprim, isoniazid, ethambutol, rifampicin and the tetracyclines. While those effects are generally undesirable, they may also under certain circumstances be beneficial, and further research is warranted in that direction.

Effiectiveness and safety of transcranial direct current stimulation in fibromyalgia: A systematic review and meta-analysis.

PubMed

Zhu, Chang-E; Yu, Bo; Zhang, Wen; Chen, Wen-Hua; Qi, Qi; Miao, Yun

2017-01-19

To evaluate the effectiveness and safety of transcranial direct current stimulation for fibro-myalgia. Databases, conference records and registered trials were searched for articles published from the date of establishment of the database through to October 2015. Six randomized controlled trials (n=192) of transcranial direct current stimulation for fibromyalgia were included in the current study. Two researchers independently screened the literature, assessed methodological quality using the Cochrane Collaboration's tool, and extracted data. Studies were divided into 3 groups for meta-analysis according to stimulation site and polarity. Significant improvement in pain and general fibromyalgia-related function was seen with anodal transcranial direct current stimulation over the primary motor cortex (p<0.05). However, the pressure pain threshold did not improve (p>0.05). Anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex did not significantly reduce pain or improve general fibromyalgia-related function compared with sham stimulation (p>0.05). Cathodal transcranial direct current stimulation over the primary motor cortex did not improve the pressure pain threshold compared with sham stimulation (p>0.05). No significant adverse effects were seen. Anodal transcranial direct current stimulation over the primary motor cortex is more likely than sham transcranial direct current stimulation to relieve pain and improve general fibromyalgia-related function.

Adverse Effects of Electronic Cigarette Use: A Concept Mapping Approach

PubMed Central

Nasim, Aashir; Rosas, Scott

2016-01-01

Abstract Introduction: Electronic cigarette (ECIG) use has grown rapidly in popularity within a short period of time. As ECIG products continue to evolve and more individuals begin using ECIGs, it is important to understand the potential adverse effects that are associated with ECIG use. The purpose of this study was to examine and describe the acute adverse effects associated with ECIG use. Methods: This study used an integrated, mixed-method participatory approach called concept mapping (CM). Experienced ECIG users ( n = 85) provided statements that answered the focus prompt “A specific negative or unpleasant effect (ie, physical or psychological) that I have experienced either during or immediately after using an electronic cigarette device is…” in an online program. Participants sorted these statements into piles of common themes and rated each statement. Using multidimensional scaling and hierarchical cluster analysis, a concept map of the adverse effects statements was created. Results: Participants generated 79 statements that completed the focus prompt and were retained by researchers. Analysis generated a map containing five clusters that characterized perceived adverse effects of ECIG use: Stigma, Worry/Guilt, Addiction Signs, Physical Effects, and Device/Vapor Problems. Conclusions: ECIG use is associated with adverse effects that should be monitored as ECIGs continue to grow in popularity. If ECIGs are to be regulated, policies should be created that minimize the likelihood of user identified adverse effects. Implications: This article provides a list of adverse effects reported by experienced ECIG users. This article organizes these effects into a conceptual model that may be useful for better understanding the adverse outcomes associated with ECIG use. These identified adverse effects may be useful for health professionals and policy makers. Health professionals should be aware of potential negative health effects that may be associated with ECIG use and policy makers could design ECIG regulations that minimize the risk of the adverse effects reported by ECIG users in this study. PMID:26563262

Review of adverse reactions to injections of Chinese materia medica.

PubMed

Bian, Zhaoxiang; Shang, Hongcai; Cheng, Chungwah; Wu, Taixiang; Li, Youping; Zhang, Boli

2010-05-01

Using Chinese Materia Medica (CM) as injections is an innovation that is proving effective in extensive clinical use in Mainland China. However, recent reports have focused on adverse reactions, ignoring the considerable successes of these preparations. In order to achieve balance in the media and in the minds of the public, we suggest the first step is to clarify the concepts of and differences between adverse drug reactions (ADR) and adverse events (AE) for all concerned-the public, medical practitioners, government officials, and lawmakers. Second, the State Food and Drug Administration should raise the requirements for Chinese Materia Medica Injection (CMI) registration and license approval and emphasize the importance of evidence-based CMI development and evidence-based CMI license approval. Thirdly, drug companies and institutions should reinforce basic research about the quality control of herbs and CMI-drug interactions. Fourth, the Government should clarify the legal responsibilities for CMI approval agencies, CMI developers, medical doctors, and patients. Fifth, the medical association and Government should enhance training for health care professionals concerning the usage of CMIs. And finally sixth, State Food and Drug Administration should monitor the content and quality of the directions for use of CMI. © 2010 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Moving beyond a descriptive aquatic toxicology: the value of biological process and trait information.

PubMed

Segner, Helmut

2011-10-01

In order to improve the ability to link chemical exposure to toxicological and ecological effects, aquatic toxicology will have to move from observing what chemical concentrations induce adverse effects to more explanatory approaches, that are concepts which build on knowledge of biological processes and pathways leading from exposure to adverse effects, as well as on knowledge on stressor vulnerability as given by the genetic, physiological and ecological (e.g., life history) traits of biota. Developing aquatic toxicology in this direction faces a number of challenges, including (i) taking into account species differences in toxicant responses on the basis of the evolutionarily developed diversity of phenotypic vulnerability to environmental stressors, (ii) utilizing diversified biological response profiles to serve as biological read across for prioritizing chemicals, categorizing them according to modes of action, and for guiding targeted toxicity evaluation; (iii) prediction of ecological consequences of toxic exposure from knowledge of how biological processes and phenotypic traits lead to effect propagation across the levels of biological hierarchy; and (iv) the search for concepts to assess the cumulative impact of multiple stressors. An underlying theme in these challenges is that, in addition to the question of what the chemical does to the biological receptor, we should give increasing emphasis to the question how the biological receptor handles the chemicals, i.e., through which pathways the initial chemical-biological interaction extends to the adverse effects, how this extension is modulated by adaptive or compensatory processes as well as by phenotypic traits of the biological receptor. 2011 Elsevier B.V. All rights reserved.

The Role of Fructose, Sucrose and High-fructose Corn Syrup in Diabetes.

PubMed

Cozma, Adrian I; Sievenpiper, John L

2014-02-01

Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. High-fructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecological studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugar-sweetened beverages, these associations are small, do not hold at moderate levels of intake and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructose-containing sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycaemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research.

The Role of Fructose, Sucrose and High-fructose Corn Syrup in Diabetes

PubMed Central

Cozma, Adrian I

2014-01-01

Abstract Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. High-fructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecological studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugar-sweetened beverages, these associations are small, do not hold at moderate levels of intake and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructose-containing sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycaemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research. PMID:29872464

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.

PubMed

Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H; Hampstead, Benjamin M; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A; Reis, Janine; Richardson, Jessica D; Rotenberg, Alexander; Turkeltaub, Peter E; Woods, Adam J

2016-01-01

This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety of transcranial Direct Current Stimulation: Evidence Based Update 2016

PubMed Central

Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R.; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H.; Hampstead, Benjamin M.; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A.; Reis, Janine; Richardson, Jessica D.; Rotenberg, Alexander; Turkeltaub, Peter E.; Woods, Adam J.

2016-01-01

This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3–13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 mA, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1,000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. PMID:27372845

Workplace Bullying, Job Stress, Intent to Leave, and Nurses' Perceptions of Patient Safety in South Korean Hospitals.

PubMed

Oh, Hyunjin; Uhm, Dong-Choon; Yoon, Young Joo

2016-01-01

Negative work environments influence the ability of nurses to provide optimal patient care in a safe environment. The purpose of the study was to test a model linking workplace bullying (WPB) and lateral violence (LV) with job stress, intent to leave, and, subsequently, nurse-assessed patient adverse outcomes (safety issues). This descriptive-correlational study examined the relationships between study variables and used a structural equation model to test the validity of the proposed theoretical framework. A convenience sample of 508 clinical nurses working in eight general hospitals in Daejeon, South Korea, completed a questionnaire on measures of WPB, LV, job stress, intent to leave, and nurse-assessed patient safety. Analysis of moment structures was used to estimate a set of three models with competing measurement structures for WPB and LV and the same structural model. Akaike Information Criterion was used for model selection. Among the three proposed models, the model with complex factor loadings was selected (WPB and LV were both associated with verbal abuse and physical threat). WPB directly and indirectly influenced nurse-assessed patient safety. Job stress directly influenced intent to leave, and intent to leave directly influenced nurse-assessed patient safety. The results of the study support the proposition that WPB, job stress, and intent to leave may be associated with nurse-perceived adverse outcomes (patient safety issues) in hospitals. Nurse perceptions of WPB were associated with nurse-assessed patient safety outcomes (adverse events) directly and through mediating job stress and intent to leave. LV was not associated with the mediators or nurse-assessed adverse outcomes (safety).

FEMALE SEX AND DISCONTINUATION OF ISONIAZID DUE TO ADVERSE EFFECTS DURING THE TREATMENT OF LATENT TUBERCULOSIS

PubMed Central

Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.

2013-01-01

SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828

A case of fulminant Type 1 diabetes following anti-PD1 immunotherapy in a genetically susceptible patient.

PubMed

Araújo, Manuel; Ligeiro, Dário; Costa, Luís; Marques, Filipa; Trindade, Helder; Correia, José Manuel; Fonseca, Candida

2017-06-01

Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8). This finding supports that acute Type 1 diabetes can be an important adverse effect of immunotherapies targeting T-cell activation regulation. Because of the severity of this adverse effect, physicians should be aware of it, and studies directed to the detection of new biomarkers for early risk stratification (e.g., HLA) should be sought.

Nightmare and Abnormal Dreams: Rare Side Effects of Metformin?

PubMed Central

Yanto, Theo Audi; Kosasih, Felicia Nathania

2018-01-01

Background Metformin is widely known as an antidiabetic agent which has significant gastrointestinal side effects, but nightmares and abnormal dreams as its adverse reactions are not well reported. Case Presentation Herein we present a case of 56-year-old male patient with no known history of recurrent nightmares and sleep disorder, experiencing nightmare and abnormal dreams directly after consumption of 750 mg extended release metformin. He reported his dream as an unpleasant experience which awakened him at night with negative feelings. The nightmare only lasted for a night, but his dreams every night thereafter seemed abnormal. The dreams were vivid and indescribable. The disappearance and occurrence of abnormal dreams ensued soon after the drug was discontinued and rechallenged. The case was assessed using Naranjo Adverse Drug Reaction (ADR) probability scale and resulted as probable causality. Conclusion Metformin might be the underlying cause of nightmare and abnormal dreams in this patient. More studies are needed to confirm the association and causality of this findings. PMID:29581904

Effects of expiration of the Federal energy tax credit on the National Photovoltaics Program

NASA Technical Reports Server (NTRS)

Smith, J. L.

1984-01-01

Projected 1986 sales are significantly reduced as a direct result of system price increases following from expiration of the Federal energy tax credits. There would be greatly reduced emphasis on domestic electric utility applications. Indirect effects arising from unrealized economies of scale and reduced private investment in PV research and development (R&D) and in production facilities could have a very large cumulative adverse impact on the U.S. PV industry. The industry forecasts as much as fourfold reduction in 1990 sales if tax credits expire, compared with what sales would be with the credits. Because the National Photovoltaics Program is explicitly structured as a government partnership, large changes in the motivation or funding of either partner can affect Program success profoundly. Reduced industry participation implies that such industry tasks as industrialization and new product development would slow or halt. Those research areas receiving heavy R&D support from private PV manufacturers would be adversely affected.

Environmental impacts of modern agricultural technology diffusion in Bangladesh: an analysis of farmers' perceptions and their determinants.

PubMed

Rahman, Sanzidur

2003-06-01

Farmers' perception of the environmental impacts of modern agricultural technology diffusion and factors determining such awareness were examined using survey data from 21 villages in three agro-ecological regions of Bangladesh. Results reveal that farmers are well aware of the adverse environmental impacts of modern agricultural technology, although their awareness remains confined within visible impacts such as soil fertility, fish catches, and health effects. Their perception of intangible impacts such as, toxicity in water and soils is weak. Level and duration of modern agricultural technology adoption directly influence awareness of its adverse effects. Education and extension contacts also play an important role in raising awareness. Awareness is higher among farmers in developed regions, fertile locations and those with access to off-farm income sources. Promotion of education and strengthening extension services will boost farmers' environmental awareness. Infrastructure development and measures to replenish depleting soil fertility will also play a positive role in raising awareness.

A critical evaluation of Internet marketing of products that contain ephedra.

PubMed

Ashar, Bimal H; Miller, Redonda G; Getz, Kelly J; Pichard, Carmen P

2003-08-01

To evaluate information contained within Internet sites that advertise and market dietary supplements containing ephedra. We conducted an Internet search to identify Web sites advertising weight-loss supplements that contained ephedra. Between July 7 and July 18, 2002, 4 search engines were used by entering the term herbal weight loss. Outcome measures included disclosure of potential adverse effects of or contraindications to ephedra-containing supplements, disclosure of ephedra alkaloid dosage, and presence of misleading or incorrect information. Thirty-two products and advertisements were identified and systematically evaluated for deviance from truth-in-advertising standards. Of the 32 Web sites analyzed, 13 (41%) failed to disclose potential adverse effects or contraindications to supplement use. Seventeen (53%) did not reveal the dosage of ephedra alkaloids that was recommended. More importantly, 11 sites (34%) contained incorrect or misleading statements, some of which could directly result in serious harm to consumers. If dietary supplements containing ephedra are to continue to be marketed freely, substantial reform in advertising regulation and enforcement is warranted.

How can the study of physiological reactivity contribute to our understanding of adversity and resilience processes in development?

PubMed

Obradović, Jelena

2012-05-01

The focus of this article is to present current progress in understanding the interplay among adversity, physiological sensitivity to context, and adaptive functioning, with an emphasis on implications and future directions for resilience researchers. It includes a review of current literature that demonstrates (a) links between various levels of adversity exposure and variability in physiological reactivity, (b) how the interplay between children's physiological reactivity and different sources of risk and adversity relates to variability in adaptive functioning, and (c) various approaches for capturing a more dynamic nature of physiological reactivity and related processes. Throughout, important conceptual and empirical issues are highlighted.

The Microbiome in Mental Health: Potential Contribution of Gut Microbiota in Disease and Pharmacotherapy Management.

PubMed

Flowers, Stephanie A; Ellingrod, Vicki L

2015-10-01

The gut microbiome is composed of ~10(13) -10(14) microbial cells and viruses that exist in a symbiotic bidirectional communicative relationship with the host. Bacterial functions in the gut have an important role in healthy host metabolic function, and dysbiosis can contribute to the pathology of many medical conditions. Alterations in the relationship between gut microbiota and host have gained some attention in mental health because new evidence supports the association of gut bacteria to cognitive and emotional processes. Of interest, illnesses such as major depressive disorder are disproportionately prevalent in patients with gastrointestinal illnesses such as inflammatory bowel disease, which pathologically has been strongly linked to microbiome function. Not only is the microbiome associated with the disease itself, but it may also influence the effectiveness or adverse effects associated with pharmacologic agents used to treat these disorders. This field of study may also provide new insights on how dietary agents may help manage mental illness both directly as well as though their influence on the therapeutic and adverse effects of psychotropic agents. © 2015 Pharmacotherapy Publications, Inc.

18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

Code of Federal Regulations, 2013 CFR

2013-04-01

... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...

18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

Code of Federal Regulations, 2012 CFR

2012-04-01

... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...

18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

Code of Federal Regulations, 2011 CFR

2011-04-01

... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...

18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

Code of Federal Regulations, 2014 CFR

2014-04-01

... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...

18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

Code of Federal Regulations, 2010 CFR

2010-04-01

... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b) The...

Experimental Study of a Three-Dimensional Shear-Driven Turbulent Boundary Layer with Streamwise Adverse Pressure Gradient

NASA Technical Reports Server (NTRS)

Driver, David M.; Johnston, James P.

1990-01-01

The effects of a strong adverse pressure gradient on a three-dimensional turbulent boundary layer are studied in an axisymmetric spinning cylinder geometry. Velocity measurements made with a three-component laser Doppler velocimeter include all three mean flow components, all six Reynolds stress components, and all ten triple-product correlations. Reynolds stress diminishes as the flow becomes three-dimensional. Lower levels of shear stress were seen to persist under adverse pressure gradient conditions. This low level of stress was seen to roughly correlate with the magnitude of cross-flow (relative to free stream flow) for this experiment as well as most of the other experiments in the literature. Variations in pressure gradient do not appear to alter this correlation. For this reason, it is hypothesized that a three-dimensional boundary layer is more prone to separate than a two-dimensional boundary layer, although it could not be directly shown here. None of the computations performed with either a Prandtl mixing length, k-epsilon, or a Launder-Reece-Rodi full Reynolds-stress model were able to predict the reduction in Reynolds stress.

[Management of adverse drug effects].

PubMed

Schlienger, R G

2000-09-01

Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.

75 FR 21528 - Airworthiness Directives; McDonnell Douglas Corporation Model MD-90-30 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... subsequently damage the hydraulic system and adversely affect the airplane's ability to make a safe landing... cylinder support fitting for the MLG failing during gear extension and subsequently damaging the hydraulic... the retract cylinder support fitting for the MLG, which could adversely affect the airplane's safe...

Site-Specific Immunosuppression in Vascularized Composite Allotransplantation: Prospects and Potential

PubMed Central

Schnider, Jonas T.; Weinstock, Matthias; Plock, Jan A.; Solari, Mario G.; Venkataramanan, Raman; Zheng, Xin Xiao; Gorantla, Vijay S.

2013-01-01

Skin is the most immunogenic component of a vascularized composite allograft (VCA) and is the primary trigger and target of rejection. The skin is directly accessible for visual monitoring of acute rejection (AR) and for directed biopsy, timely therapeutic intervention, and management of AR. Logically, antirejection drugs, biologics, or other agents delivered locally to the VCA may reduce the need for systemic immunosuppression with its adverse effects. Topical FK 506 (tacrolimus) and steroids have been used in clinical VCA as an adjunct to systemic therapy with unclear beneficial effects. However, there are no commercially available topical formulations for other widely used systemic immunosuppressive drugs such as mycophenolic acid, sirolimus, and everolimus. Investigating the site-specific therapeutic effects and efficacy of systemically active agents may enable optimizing the dosing, frequency, and duration of overall immunosuppression in VCA with minimization or elimination of long-term drug-related toxicity. PMID:23476677

Frequency shift measurement in shock-compressed materials

DOEpatents

Moore, David S.; Schmidt, Stephen C.

1985-01-01

A method for determining molecular vibrational frequencies in shock-compressed transparent materials. A single laser beam pulse is directed into a sample material while the material is shock-compressed from a direction opposite that of the incident laser beam. A Stokes beam produced by stimulated Raman scattering is emitted back along the path of the incident laser beam, that is, in the opposite direction to that of the incident laser beam. The Stokes beam is separated from the incident beam and its frequency measured. The difference in frequency between the Stokes beam and the incident beam is representative of the characteristic frequency of the Raman active mode of the sample. Both the incident beam and the Stokes beam pass perpendicularly through the shock front advancing through the sample, thereby minimizing adverse effects of refraction.

Frequency shift measurement in shock-compressed materials

DOEpatents

Moore, D.S.; Schmidt, S.C.

1984-02-21

A method is disclosed for determining molecular vibrational frequencies in shock-compressed transparent materials. A single laser beam pulse is directed into a sample material while the material is shock-compressed from a direction opposite that of the incident laser beam. A Stokes beam produced by stimulated Raman scattering is emitted back along the path of the incident laser beam, that is, in the opposite direction to that of the incident laser beam. The Stokes beam is separated from the incident beam and its frequency measured. The difference in frequency between the Stokes beam and the incident beam is representative of the characteristic frequency of the Raman active mode of the sample. Both the incident beam and the Stokes beam pass perpendicularly through the stock front advancing through the sample, thereby minimizing adverse effects of refraction.

Using Integrated Assessment Models to Estimate the Economic Damages from Temperature Related Human Health Effects in the US

NASA Astrophysics Data System (ADS)

Gilmore, E.; Calvin, K. V.; Puett, R.; Sapkota, A.; Schwarber, A.

2014-12-01

Climate change is projected to increase risks to human health. One pathway that may be particularly difficult to manage is adverse human health impacts (e.g. premature mortality and morbidity) from increases in mean temperatures and changing patterns of temperature extremes. Modeling how these health risks evolve over decadal time-scales is challenging as the severity of the impacts depends on changes in climate as well as socioeconomic conditions. Here, we show estimates of health damages as well as both direct and indirect economic damages that span climate and socioeconomic dimensions for each US state to 2050. We achieve this objective by extending the integrated assessment model (IAM), Global Change Assessment Model (GCAM-USA). First, we quantify the change in premature mortality. We identify a range of exposure-response relationships for temperature related mortality through a critical review of the literature. We then implement these relationships in the GCAM by coupling them with projections of future temperature patterns and population estimates. Second, we monetize the effect of these adverse health effects, including both direct and indirect economic costs through labor force participation and productivity along a range of possible economic pathways. Finally, we evaluate how uncertainty in the parameters and assumptions affects the range of possible estimates. We conclude that the model is sensitive to assumptions regarding exposure-response relationship and population growth. The economic damages, however, are driven by the estimates of income and GDP growth as well as the potential for adaptation measures, namely the use and effectiveness of air conditioning.

Future Directions in Childhood Adversity and Youth Psychopathology.

PubMed

McLaughlin, Katie A

2016-01-01

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

Rare and very rare adverse effects of clozapine

PubMed Central

De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

2015-01-01

Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

Cholesterol embolisms as possible adverse drug reaction of direct oral anticoagulants.

PubMed

Muller-Hansma, A H G; Daemen-Gubbels, C R G M; Schut, N H

2018-04-01

The Netherlands Pharmacovigilance Centre Lareb has received two reports of cholesterol crystal embolisms associated with the use of a direct oral anticoagulant (DOAC). The European pharmacovigilance database contains several other cases concerning this association, and one report was published in the scientific literature. Cholesterol crystal embolisms were described in association with the use of several other antithrombotic drugs, although the role as an independent risk factor is not conclusive. The case series described in this article, indicates the possibility of an adverse drug reaction when a patient develops cholesterol crystal embolisms while using a DOAC.

Laboratory toxicity studies demonstrate no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design.

PubMed

Alvarez-Alfageme, Fernando; Bigler, Franz; Romeis, Jörg

2011-06-01

Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant.

Examining the Effects of Religious Attendance on Resilience for Older Adults.

PubMed

Manning, Lydia K; Miles, Andrew

2018-02-01

Growing older often brings hardship, adversity, and even trauma. Resilience is a broad term used to describe flourishing despite adversity. To date, resilience and the connections to religion have not been well studied, despite compelling evidence that religious practice can promote psychological health. This research examines the role that religion plays in promoting resilience among older adults. Research questions include: (a) What is the relationship between religion and trait resilience? and (b) Does religion promote resilient reintegration following traumatic life events? Results indicate that religious service attendance is tied to higher levels of trait resilience and that both service attendance and trait resilience directly predict lower levels of depression and higher rates of resilient reintegration following traumatic life events. Findings suggest that religious service attendance has protective properties that are worthy of consideration when investigating resilience.

Linking the response of endocrine regulated genes to adverse effects on sex differentiation improves comprehension of aromatase inhibition in a Fish Sexual Development Test.

PubMed

Muth-Köhne, Elke; Westphal-Settele, Kathi; Brückner, Jasmin; Konradi, Sabine; Schiller, Viktoria; Schäfers, Christoph; Teigeler, Matthias; Fenske, Martina

2016-07-01

The Fish Sexual Development Test (FSDT) is a non-reproductive test to assess adverse effects of endocrine disrupting chemicals. With the present study it was intended to evaluate whether gene expression endpoints would serve as predictive markers of endocrine disruption in a FSDT. For proof-of-concept, a FSDT according to the OECD TG 234 was conducted with the non-steroidal aromatase inhibitor fadrozole (test concentrations: 10μg/L, 32μg/L, 100μg/L) using zebrafish (Danio rerio). Gene expression analyses using quantitative RT-PCR were included at 48h, 96h, 28days and 63days post fertilization (hpf, dpf). The selection of genes aimed at finding molecular endpoints which could be directly linked to the adverse apical effects of aromatase inhibition. The most prominent effects of fadrozole exposure on the sexual development of zebrafish were a complete sex ratio shift towards males and an acceleration of gonad maturation already at low fadrozole concentrations (10μg/L). Due to the specific inhibition of the aromatase enzyme (Cyp19) by fadrozole and thus, the conversion of C19-androgens to C18-estrogens, the steroid hormone balance controlling the sex ratio of zebrafish was altered. The resulting key event is the regulation of directly estrogen-responsive genes. Subsequently, gene expression of vitellogenin 1 (vtg1) and of the aromatase cyp19a1b isoform (cyp19a1b), were down-regulated upon fadrozole treatment compared to controls. For example, mRNA levels of vtg1 were down-regulated compared to the controls as early as 48 hpf and 96 hpf. Further regulated genes cumulated in pathways suggested to be controlled by endocrine mechanisms, like the steroid and terpenoid synthesis pathway (e.g. mevalonate (diphospho) decarboxylase (mvd), lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase; lss), methylsterol monooxygenase 1 (sc4mol)) and in lipid transport/metabolic processes (steroidogenic acute regulatory protein (star), apolipoprotein Eb (apoEb)). Taken together, this study demonstrated that the existing Adverse Outcome Pathway (AOP) for aromatase inhibition in fish can be translated to the life-stage of sexual differentiation. We were further able to identify MoA-specific marker gene expression which can be instrumental in defining new measurable key events (KE) of existing or new AOPs related to endocrine disruption. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Adverse Effects Associated With Newer Diabetes Therapies.

PubMed

Akiyode, Oluwaranti F; Adesoye, Adebola A

2017-04-01

The increasing number of newer type 2 diabetes therapies has allowed providers an increased armamentarium for the optimal management of patients with diabetes. In fact, these newer agents have unique benefits in the management of type 2 diabetes. However, they are also associated with certain adverse effects. This review article aims to describe the notable adverse effects of these newer antidiabetic therapies including the glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter 2 inhibitors. The adverse effects reviewed herein include pancreatitis, medullary thyroid carcinoma, heart failure, gastrointestinal disturbances, renal impairment, and genitourinary infections. More clinical data are necessary to solidify the association of some of these adverse effects with the newer diabetes agents. However, it is important for health care practitioners to be well informed and prepared to properly monitor patients for these adverse effects.

Briefing Highlights Vulnerability of GPS to Adverse Space Weather

NASA Astrophysics Data System (ADS)

Balcerak, Ernie

2011-08-01

Through its effects on GPS and other technologies, space weather can affect a variety of industries, including agriculture, commercial air travel, and emergency response. Speakers focused on these topics at a 22 June briefing on Capitol Hill in Washington, D. C. Solar flares can produce radio bursts that directly interfere with GPS signals. Solar activity can also cause ionospheric disturbances that produce distortions and delays in GPS signals, degrading the accuracy of positioning and navigation systems.

Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

PubMed

Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

2017-05-01

Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patients use an internet technology to report when things go wrong

PubMed Central

Wasson, John H; MacKenzie, Todd A; Hall, Michael

2007-01-01

Background As patients directly experience harm from adverse events, investigators have proposed patient‐report to complement professional reporting of adverse events. Objective To investigate how an automated health assessment system can be used to identify adverse events. Design and setting Internet survey responses from April 2003 to April 2005 involving communities and clinical practices across the USA. Patients 44 860 adults aged 19–69 years. Outcome Patient perceptions of adverse events experienced during the previous year. Independent legal review was also used to estimate how many patient‐reports were serious enough to be potentially compensable. Results Although patient reports of possible adverse events was low (1.4%), the percentage of adverse events was eight times higher for patients with the greatest burden of illness than for those with the least (3.4% vs 0.4%). Two expert malpractice attorneys agreed that 9% of the adverse events seemed to be serious. Conclusions Patients will use internet technology to report their perceptions of health‐related adverse events. Some of the patient‐reported events reported will be serious. PMID:17545349

The use of existing environmental networks for the post-market monitoring of GM crop cultivation in the EU.

PubMed

Smets, G; Alcalde, E; Andres, D; Carron, D; Delzenne, P; Heise, A; Legris, G; Martinez Parrilla, M; Verhaert, J; Wandelt, C; Ilegems, M; Rüdelsheim, P

2014-07-01

The European Union (EU) Directive 2001/18/EC on the deliberate release of genetically modified organisms (GMOs) into the environment requires that both Case-Specific Monitoring (CSM) and General Surveillance (GS) are considered as post-market implementing measures. Whereas CSM is directed to monitor potential adverse effects of GMOs or their use identified in the environmental risk assessment, GS aims to detect un-intended adverse effects of GMOs or their use on human and animal health or the environment. Guidance documents on the monitoring of genetically modified (GM) plants from the Commission and EFSA clarify that, as appropriate, GS can make use of established routine surveillance practices. Networks involved in routine surveillance offer recognised expertise in a particular domain and are designed to collect information on important environmental aspects over a large geographical area. However, as the suitability of existing monitoring networks to provide relevant data for monitoring impacts of GMOs is not known, plant biotechnology companies developed an approach to describe the processes and criteria that will be used for selecting and evaluating existing monitoring systems. In this paper, the availability of existing monitoring networks for this purpose is evaluated. By cataloguing the existing environmental monitoring networks in the EU, it can be concluded that they can only be used, in the context of GMO cultivation monitoring, as secondary tools to collect baseline information.

Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study.

PubMed

Siddiqui, Ali Nasir; Khayyam, Khalid Umer; Sharma, Manju

2016-01-01

Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539-2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310-4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114-11.494, p = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence.

Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions: A Systematic Review

PubMed Central

Golder, Su; Wright, Kath

2016-01-01

Background We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events. Methods and Findings Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published. Conclusions There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events. PMID:27649528

Efficacy of preoperative biliary drainage in malignant obstructive jaundice: a meta-analysis and systematic review.

PubMed

Moole, Harsha; Bechtold, Matthew; Puli, Srinivas R

2016-07-11

In patients requiring surgical resection for malignant biliary jaundice, it is unclear if preoperative biliary drainage (PBD) would improve mortality and morbidity by restoration of biliary flow prior to operation. This is a meta-analysis to pool the evidence and assess the utility of PBD in patients with malignant obstructive jaundice. The primary outcome is comparing mortality outcomes in patients with malignant obstructive jaundice undergoing direct surgery (DS) versus PBD. The secondary outcomes include major adverse events and length of hospital stay in both the groups. Studies using PBD in patients with malignant obstructive jaundice were included in this study. For the data collection and extraction, articles were searched in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials & Database of Systematic Reviews, etc. Pooled proportions were calculated using both Mantel-Haenszel method (fixed effects model) and DerSimonian-Laird method (random effects model). Initial search identified 2230 reference articles, of which 204 were selected and reviewed. Twenty-six studies (N = 3532) for PBD in malignant obstructive jaundice which met the inclusion criteria were included in this analysis. The odds ratio for mortality in PBD group versus DS group was 0.96 (95 % CI = 0.71 to 1.29). Pooled number of major adverse effects was lower in the PBD group at 10.40 (95 % CI = 9.96 to 10.83) compared to 15.56 (95 % CI = 15.06 to 16.05) in the DS group. Subgroup analysis comparing internal PBD to DS group showed lower odds for major adverse events (odds ratio, 0.48 with 95 % CI = 0.32 to 0.74). In patients with malignant biliary jaundice requiring surgery, PBD group had significantly less major adverse effects than DS group. Length of hospital stay and mortality rate were comparable in both the groups.

Validation and Application of an Ultra High-Performance Liquid Chromatography Tandem Mass Spectrometry Method for Yuanhuacine Determination in Rat Plasma after Pulmonary Administration: Pharmacokinetic Evaluation of a New Drug Delivery System.

PubMed

Li, Man; Liu, Xiao; Cai, Hao; Shen, Zhichun; Xu, Liu; Li, Weidong; Wu, Li; Duan, Jinao; Chen, Zhipeng

2016-12-16

Yuanhuacine was found to have significant inhibitory activity against A-549 human lung cancer cells. However, there would be serious adverse toxicity effects after systemic administration of yuanhuacine, such as by oral and intravenous ways. In order to achieve better curative effect and to alleviate the adverse toxicity effects, we tried to deliver yuanhuacine directly into the lungs. Ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was used to detect the analyte and IS. After extraction (ether:dichloromethane = 8:1), the analyte and IS were separated on a Waters BEH-C 18 column (100 mm × 2.1 mm, 1.7 μm) under a 5 min gradient elution using a mixture of acetonitrile and 0.1% formic acid aqueous solution as mobile phase at a flow rate of 0.3 mL/min. ESI positive mode was chosen for detection. The method was fully validated for its selectivity, accuracy, precision, stability, matrix effect, and extraction recovery. This new method for yuanhuacine concentration determination in rat plasma was reliable and could be applied for its preclinical and clinical monitoring purpose.

Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork

PubMed Central

Barclay, Johanna L.; Husse, Jana; Bode, Brid; Naujokat, Nadine; Meyer-Kovac, Judit; Schmid, Sebastian M.; Lehnert, Hendrik; Oster, Henrik

2012-01-01

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers. PMID:22629359

Adverse effects of ketoconazole in dogs--a retrospective study.

PubMed

Mayer, Ursula K; Glos, Katharina; Schmid, Matthias; Power, Helen T; Bettenay, Sonya V; Mueller, Ralf S

2008-08-01

Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.

Adverse health effects of non-medical cannabis use.

PubMed

Hall, Wayne; Degenhardt, Louisa

2009-10-17

For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

Drug formulary review process for sargramostim and filgrastim: focus on analysis of adverse drug reactions.

PubMed

Kellihan, M J

1993-01-01

Selection of a drug for formulary inclusion involves evaluation of safety, efficacy, and cost. The colony-stimulating factors (CSFs) sargramostim and filgrastim have a broad range of potential indications and represent a costly formulary addition when acquisition price alone is considered; their comparative safety is unclear. These factors suggest that the CSFs should be closely scrutinized prior to formulary addition. In the absence of direct comparative studies, an assessment of the safety of CSFs involves evaluation of information provided in the product circular, official drug compendia, adverse biologic reports submitted to the United States Food and Drug Administration, and data from key clinical trials. Data in the product circulars report on adverse events in small numbers of patients treated for chemotherapy-induced neutropenia (filgrastim) or neutropenia subsequent to bone marrow transplantation (sargramostim). The official compendia and clinical trials include experience with CSFs produced in a variety of expression systems; these data are not limited to sargramostim and filgrastim. Importantly, there was a similar incidence of adverse events in patients who received sargramostim or filgrastim and in those who took placebo reported in the product circulars and the pivotal trials, suggesting that the underlying disease may have an important role in determining the side-effect profile of these agents. Adverse biologic reports represent experience with sargramostim and filgrastim obtained under actual clinical conditions and suggest that the same types of adverse events are seen with sargramostim as with filgrastim. This analysis suggests that a decision to select filgrastim over sargramostim for formulary inclusion based on the safety profile is not appropriate because currently available data are equivocal and that such decisions would more appropriately be based on efficacy and cost.

Medication safety knowledge, attitudes and practices among community pharmacists in Lebanon.

PubMed

Hajj, Aline; Hallit, Souheil; Ramia, Elsy; Salameh, Pascale

2018-01-01

The effectiveness of a national post-marketing surveillance program depends directly on the active participation of all health professionals. There is no current comprehensive and active pharmacovigilance program available in Lebanon. To assess the knowledge, attitudes, and practices (KAP) among community pharmacists in Lebanon with respect to potential pharmacovigilance and adverse-drug-reaction reporting in Lebanon. A cross-sectional descriptive study, using a self-administered KAP questionnaire and conducted between March and July 2016, included 1857 pharmacists practicing in community settings. Statistical analysis included χ 2 test for dichotomous or multinomial qualitative variables, and Wilcoxon test for quantitative variables with non-homogeneous variances or non-normal distribution. The majority of responders had good knowledge concerning the concept and purpose of pharmacovigilance as well as adverse drug reactions (how to report these/the importance of reporting adverse events/the definition of an adverse event and pharmacovigilance). Concerning community pharmacists' attitudes and practice towards pharmacovigilance, the majority described having a positive attitude towards their role in adverse drug reaction reporting and this activity was even seen as one of their core duties. The questionnaire revealed a lack of practice and training regarding pharmacovigilance. Nonetheless, the pharmacists agreed on the Order of Pharmacists in Lebanon and the Ministry of Health's role in promoting this practice and helping them be more involved in reporting adverse drug reactions (ADRs). The pharmacists thought that they are well positioned regarding patient-safety practice in their pharmacies and the results were not statistically different between pharmacy employers and employees. Lebanese pharmacists have the required knowledge and positive attitude to start reporting ADRs, were aware of ADRs occurring with various medicines post-marketing, yet were currently not able to disseminate this information widely or to record it centrally, emphasizing the importance of establishing a national ADR reporting system.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

PubMed

Chung, Wen-Hung; Chang, Wan-Chun; Lee, Yun-Shien; Wu, Ying-Ying; Yang, Chih-Hsun; Ho, Hsin-Chun; Chen, Ming-Jing; Lin, Jing-Yi; Hui, Rosaline Chung-Yee; Ho, Ji-Chen; Wu, Wei-Ming; Chen, Ting-Jui; Wu, Tony; Wu, Yih-Ru; Hsih, Mo-Song; Tu, Po-Hsun; Chang, Chen-Nen; Hsu, Chien-Ning; Wu, Tsu-Lan; Choon, Siew-Eng; Hsu, Chao-Kai; Chen, Der-Yuan; Liu, Chin-San; Lin, Ching-Yuang; Kaniwa, Nahoko; Saito, Yoshiro; Takahashi, Yukitoshi; Nakamura, Ryosuke; Azukizawa, Hiroaki; Shi, Yongyong; Wang, Tzu-Hao; Chuang, Shiow-Shuh; Tsai, Shih-Feng; Chang, Chee-Jen; Chang, Yu-Sun; Hung, Shuen-Iu

2014-08-06

The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state.

PubMed

Martens, Géraldine; Lejeune, Nicolas; O'Brien, Anthony Terrence; Fregni, Felipe; Martial, Charlotte; Wannez, Sarah; Laureys, Steven; Thibaut, Aurore

2018-05-02

Patients with chronic disorders of consciousness face a significant lack of treatment options. We aimed at investigating the feasibility and the behavioral effects of home-based transcranial direct current stimulation (tDCS), applied by relatives or caregivers, in chronic patients in minimally conscious state (MCS). Each participant received, in a randomized order, 20 sessions of active and 20 sessions of sham tDCS applied over the prefrontal cortex for 4 weeks; separated by 8 weeks of washout. Level of consciousness was assessed using the Coma Recovery Scale-Revised before the first stimulation (baseline), at the end of the 20 tDCS sessions (direct effects) and 8 weeks after the end of each stimulation period (long-term effects). Reported adverse events and data relative to the adherence (i.e., amount of sessions effectively received) were collected as well. Twenty-seven patients completed the study and 22 patients received at least 80% of the stimulation sessions. All patients tolerated tDCS well, no severe adverse events were noticed after real stimulation and the overall adherence (i.e., total duration of stimulation) was good. A moderate effect size (0.47 and 0.53, for modified intention to treat and per protocol analysis, respectively) was observed at the end of the 4 weeks of tDCS in favor of the active treatment. We demonstrated that home-based tDCS can be used adequately outside a research facility or hospital by patients' relatives or caregivers. In addition, 4 weeks of tDCS moderately improved the recovery of signs of consciousness in chronic MCS patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of the mydriatic effects of topical administration of rocuronium bromide in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Petritz, Olivia A; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Wiggans, K Tomo; Kass, Philip H; Houck, Emma; Murphy, Christopher J; Paul-Murphy, Joanne

2016-01-01

OBJECTIVE :To determine the mydriatic effects of topical rocuronium bromide administration in Hispaniolan Amazon parrots (Amazona ventralis) and to identify any adverse effects associated with treatment. Randomized crossover study. 8 healthy adult Hispaniolan Amazon parrots. Rocuronium bromide (20 μL/eye; 10 mg/mL) or saline (20 μL/eye; 0.9% NaCl) solution was administered in both eyes of each bird with a 26-day washout period. The birds were manually restrained in lateral recumbency with the apex of the cornea positioned upward for 2 minutes following administration in each eye. Infrared pupillometry and direct pupillary light reflex measurements were used to evaluate the mydriatic effects. Pupillary measurements were recorded prior to administration and every 20 minutes for 2 hours after administration, then hourly for a total of 7 hours. A brief physical examination was performed, direct pupillary light reflex was tested, and fluorescein staining was performed on each eye of each bird 24 hours after administration. A significant difference in pupillary diameter for the active versus control treatment group was noted from 20 to 360 minutes after drug administration, but not at 420 minutes. Minimal adverse effects were noted. Three birds had transient inferior eyelid paresis noted in both eyes after receiving rocuronium; 24 hours after the treatment, no differences in ocular measurements existed between the active and control treatments. Results suggested that topical rocuronium bromide administration may be safely used for pupillary dilation in Hispaniolan Amazon parrots and could be used for clinical evaluation, fundus imaging, and surgical interventions involving the lens and posterior segment in this species.

Reconceptualizing synergism and antagonism among multiple stressors.

PubMed

Piggott, Jeremy J; Townsend, Colin R; Matthaei, Christoph D

2015-04-01

The potential for complex synergistic or antagonistic interactions between multiple stressors presents one of the largest uncertainties when predicting ecological change but, despite common use of the terms in the scientific literature, a consensus on their operational definition is still lacking. The identification of synergism or antagonism is generally straightforward when stressors operate in the same direction, but if individual stressor effects oppose each other, the definition of synergism is paradoxical because what is synergistic to one stressor's effect direction is antagonistic to the others. In their highly cited meta-analysis, Crain et al. (Ecology Letters, 11, 2008: 1304) assumed in situations with opposing individual effects that synergy only occurs when the cumulative effect is more negative than the additive sum of the opposing individual effects. We argue against this and propose a new systematic classification based on an additive effects model that combines the magnitude and response direction of the cumulative effect and the interaction effect. A new class of "mitigating synergism" is identified, where cumulative effects are reversed and enhanced. We applied our directional classification to the dataset compiled by Crain et al. (Ecology Letters, 11, 2008: 1304) to determine the prevalence of synergistic, antagonistic, and additive interactions. Compared to their original analysis, we report differences in the representation of interaction classes by interaction type and we document examples of mitigating synergism, highlighting the importance of incorporating individual stressor effect directions in the determination of synergisms and antagonisms. This is particularly pertinent given a general bias in ecology toward investigating and reporting adverse multiple stressor effects (double negative). We emphasize the need for reconsideration by the ecological community of the interpretation of synergism and antagonism in situations where individual stressor effects oppose each other or where cumulative effects are reversed and enhanced.

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 trials. Case reports supported an association between iatrogenic overdose of magnesium sulphate and life-threatening consequences. Conclusions Appropriate administration of antenatal magnesium sulphate was not shown to be associated with serious maternal adverse effects, though an increase in 'minor’ adverse effects and treatment cessation was shown. Larger trials are needed to determine optimal regimens, achieving maximal effectiveness with minimal adverse effects, for each antenatal indication for use. Vigilance in the use of magnesium sulphate is essential for women’s safety. PMID:24139447

Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.

PubMed

Kee, Kehkooi; Flores, Martha; Cedars, Marcelle I; Reijo Pera, Renee A

2010-09-01

Historically, effects of environmental toxicants on human development have been deduced via epidemiological studies because direct experimental analysis has not been possible. However, in recent years, the derivation of human pluripotent stem cells has provided a potential experimental system to directly probe human development. Here, we used human embryonic stem cells (hESCs) to study the effect of environmental toxicants on human germ cell development, with a focus on differentiation of the founding population of primordial germ cells (PGCs), which will go on to form the oocytes of the adult. We demonstrate that human PGC numbers are specifically reduced by exposure to polycyclic aromatic hydrocarbons (PAHs), a group of toxicants common in air pollutants released from gasoline combustion or tobacco smoke. Further, we demonstrate that the adverse effects of PAH exposure are mediated through the aromatic hydrocarbon receptor (AHR) and BAX pathway. This study demonstrates the utility of hESCs as a model system for direct examination of the molecular and genetic pathways of environmental toxicants on human germ cell development.

A Novel 3D Label-Free Monitoring System of hES-Derived Cardiomyocyte Clusters: A Step Forward to In Vitro Cardiotoxicity Testing

PubMed Central

Jahnke, Heinz-Georg; Steel, Daniella; Fleischer, Stephan; Seidel, Diana; Kurz, Randy; Vinz, Silvia; Dahlenborg, Kerstin; Sartipy, Peter; Robitzki, Andrea A.

2013-01-01

Unexpected adverse effects on the cardiovascular system remain a major challenge in the development of novel active pharmaceutical ingredients (API). To overcome the current limitations of animal-based in vitro and in vivo test systems, stem cell derived human cardiomyocyte clusters (hCMC) offer the opportunity for highly predictable pre-clinical testing. The three-dimensional structure of hCMC appears more representative of tissue milieu than traditional monolayer cell culture. However, there is a lack of long-term, real time monitoring systems for tissue-like cardiac material. To address this issue, we have developed a microcavity array (MCA)-based label-free monitoring system that eliminates the need for critical hCMC adhesion and outgrowth steps. In contrast, feasible field potential derived action potential recording is possible immediately after positioning within the microcavity. Moreover, this approach allows extended observation of adverse effects on hCMC. For the first time, we describe herein the monitoring of hCMC over 35 days while preserving the hCMC structure and electrophysiological characteristics. Furthermore, we demonstrated the sensitive detection and quantification of adverse API effects using E4031, doxorubicin, and noradrenaline directly on unaltered 3D cultures. The MCA system provides multi-parameter analysis capabilities incorporating field potential recording, impedance spectroscopy, and optical read-outs on individual clusters giving a comprehensive insight into induced cellular alterations within a complex cardiac culture over days or even weeks. PMID:23861955

Factors influencing antibiotic-prescribing decisions among inpatient physicians: a qualitative investigation

PubMed Central

Livorsi, D; Comer, AR; Matthias, MS; Perencevich, EN; Bair, MJ

2016-01-01

Objective To understand the professional and psychosocial factors that influence physicians' antibiotic-prescribing habits in the inpatient setting. Design We conducted semi-structured interviews with 30 inpatient physicians. Interviews consisted of open-ended questions and flexible probes based on participants' responses. Interviews were audio recorded, transcribed, de-identified, and reviewed for accuracy and completeness. Data were analyzed using emergent thematic analysis. Setting Two teaching hospitals in Indianapolis, IN Participants Thirty inpatient physicians (10 physicians-in-training, 20 supervising staff) Results Participants recognized that antibiotics are over-used, and many admitted to prescribing antibiotics even when the clinical evidence of infection was uncertain. Over-prescription was largely driven by anxiety about missing an infection while potential adverse effects of antibiotics did not strongly influence decision-making. Participants did not routinely disclose potential adverse effects of antibiotics to inpatients. Physicians-in-training were strongly influenced by the antibiotic prescribing behavior of their supervising staff physicians. Participants sometimes questioned their colleagues' antibiotic-prescribing decisions but frequently avoided providing direct feedback or critique, citing obstacles of hierarchy, infrequent face-to-face encounters, and the awkwardness of these conversations. Conclusion There is a physician-based culture of prescribing antibiotics, which involves over-using antibiotics and not challenging colleagues' decisions. The potential adverse effects of antibiotics do not strongly influence decision-making in this sample. A better understanding of these factors could be leveraged in future efforts to improve antibiotic-prescribing in the inpatient setting. PMID:26078017

The relationship between anatomically correct electric and magnetic field dosimetry and publishe delectric and magnetic field exposure limits.

PubMed

Kavet, Robert; Dovan, Thanh; Reilly, J Patrick

2012-12-01

Electric and magnetic field exposure limits published by International Commission for Non-Ionizing Radiation Protection and Institute of Electrical and Electronics Engineers are aimed at protection against adverse electrostimulation, which may occur by direct coupling to excitable tissue and, in the case of electric fields, through indirect means associated with surface charge effects (e.g. hair vibration, skin sensations), spark discharge and contact current. For direct coupling, the basic restriction (BR) specifies the not-to-be-exceeded induced electric field. The key results of anatomically based electric and magnetic field dosimetry studies and the relevant characteristics of excitable tissue were first identified. This permitted us to assess the electric and magnetic field exposure levels that induce dose in tissue equal to the basic restrictions, and the relationships of those exposure levels to the limits now in effect. We identify scenarios in which direct coupling of electric fields to peripheral nerve could be a determining factor for electric field limits.

Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

PubMed

DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H; Caudill, Jonathan W; Trulson, Chad R; Baglivio, Michael T

2017-03-22

Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered.

Life adversity is associated with smoking relapse after a quit attempt.

PubMed

Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

2016-09-01

Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pathways towards risk: syndemic conditions mediate the effect of adversity on HIV risk behaviors among young men who have sex with men (YMSM).

PubMed

Herrick, Amy; Stall, Ron; Egan, James; Schrager, Sheree; Kipke, Michele

2014-10-01

Research shows that young men who have sex with men (YMSM) engage in higher rates of health risk behaviors and experience higher rates of negative health outcomes than their peers. The purpose of this study is to determine if the effects of adversity on HIV risk are mediated by syndemics (co-occurring health problems). Participants were 470 ethnically diverse YMSM ages 18 to 24 recruited between 2005 and 2006 and surveyed every 6 months for 24 months. Regression analyses examined the impact of adversity on syndemics (emotional distress, substance use, and problematic alcohol use) and the effects of both adversity and syndemics on HIV risk behaviors over time. Gay-related discrimination and victimization-among other adversity variables-were significantly associated with syndemics and condomless sex (CS). Syndemics mediated the effects of adversity on CS in all models. Adverse events impact HIV risk taking among YMSM through syndemics. These findings suggest that prevention programs aimed at reducing adversity may reduce both the synergistic effect of multiple psychosocial health problems and HIV risk taking.

Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development

NASA Astrophysics Data System (ADS)

Wu-Smart, Judy; Spivak, Marla

2016-08-01

Many factors can negatively affect honey bee (Apis mellifera L.) health including the pervasive use of systemic neonicotinoid insecticides. Through direct consumption of contaminated nectar and pollen from treated plants, neonicotinoids can affect foraging, learning, and memory in worker bees. Less well studied are the potential effects of neonicotinoids on queen bees, which may be exposed indirectly through trophallaxis, or food-sharing. To assess effects on queen productivity, small colonies of different sizes (1500, 3000, and 7000 bees) were fed imidacloprid (0, 10, 20, 50, and 100 ppb) in syrup for three weeks. We found adverse effects of imidacloprid on queens (egg-laying and locomotor activity), worker bees (foraging and hygienic activities), and colony development (brood production and pollen stores) in all treated colonies. Some effects were less evident as colony size increased, suggesting that larger colony populations may act as a buffer to pesticide exposure. This study is the first to show adverse effects of imidacloprid on queen bee fecundity and behavior and improves our understanding of how neonicotinoids may impair short-term colony functioning. These data indicate that risk-mitigation efforts should focus on reducing neonicotinoid exposure in the early spring when colonies are smallest and queens are most vulnerable to exposure.

Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development

PubMed Central

Wu-Smart, Judy; Spivak, Marla

2016-01-01

Many factors can negatively affect honey bee (Apis mellifera L.) health including the pervasive use of systemic neonicotinoid insecticides. Through direct consumption of contaminated nectar and pollen from treated plants, neonicotinoids can affect foraging, learning, and memory in worker bees. Less well studied are the potential effects of neonicotinoids on queen bees, which may be exposed indirectly through trophallaxis, or food-sharing. To assess effects on queen productivity, small colonies of different sizes (1500, 3000, and 7000 bees) were fed imidacloprid (0, 10, 20, 50, and 100 ppb) in syrup for three weeks. We found adverse effects of imidacloprid on queens (egg-laying and locomotor activity), worker bees (foraging and hygienic activities), and colony development (brood production and pollen stores) in all treated colonies. Some effects were less evident as colony size increased, suggesting that larger colony populations may act as a buffer to pesticide exposure. This study is the first to show adverse effects of imidacloprid on queen bee fecundity and behavior and improves our understanding of how neonicotinoids may impair short-term colony functioning. These data indicate that risk-mitigation efforts should focus on reducing neonicotinoid exposure in the early spring when colonies are smallest and queens are most vulnerable to exposure. PMID:27562025

Alternative treatment strategies for neuropathic pain: Role of Indian medicinal plants and compounds of plant origin-A review.

PubMed

Singh, Hasandeep; Bhushan, Sakshi; Arora, Rohit; Singh Buttar, Harpal; Arora, Saroj; Singh, Balbir

2017-08-01

Neuropathic pain is a complex, chronic pain state accompanied by tissue injury and nerve damage. This important health issue constitutes a challenge for the modern medicine worldwide. The management of neuropathic pain remains a major clinical challenge, pertaining to an inadequate understanding of pathophysiological mechanisms of neuropathic pain. Various classes of drugs have been reported effective for the management of neuropathic pain viz. opiates, tricyclic antidepressants, and antiepileptic agents. However, association of adverse effects with these drugs hinders their confident prescription in people with neuropathic pain. Recently, various medicinal plants have been reported effective for the management of neuropathic pain. So, it may be prudent to look beyond synthetic drugs pertaining to their unprecedented pharmacotherapeutic effects with lesser adverse effects. The extensive literature review has been carried out from databases such as Science direct, Scifinder, Wiley online library, PubMed, Research gate, Google scholar and Chemical Abstracts. The list of Traditional Indian Medicinal plants (TIMPs) and isolated compounds have been compiled which have been reported effective as an alternative therapy for the management of neuropathic pain. This helps the researchers to discover some novel therapeutic agents against neuropathic pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development.

PubMed

Wu-Smart, Judy; Spivak, Marla

2016-08-26

Many factors can negatively affect honey bee (Apis mellifera L.) health including the pervasive use of systemic neonicotinoid insecticides. Through direct consumption of contaminated nectar and pollen from treated plants, neonicotinoids can affect foraging, learning, and memory in worker bees. Less well studied are the potential effects of neonicotinoids on queen bees, which may be exposed indirectly through trophallaxis, or food-sharing. To assess effects on queen productivity, small colonies of different sizes (1500, 3000, and 7000 bees) were fed imidacloprid (0, 10, 20, 50, and 100 ppb) in syrup for three weeks. We found adverse effects of imidacloprid on queens (egg-laying and locomotor activity), worker bees (foraging and hygienic activities), and colony development (brood production and pollen stores) in all treated colonies. Some effects were less evident as colony size increased, suggesting that larger colony populations may act as a buffer to pesticide exposure. This study is the first to show adverse effects of imidacloprid on queen bee fecundity and behavior and improves our understanding of how neonicotinoids may impair short-term colony functioning. These data indicate that risk-mitigation efforts should focus on reducing neonicotinoid exposure in the early spring when colonies are smallest and queens are most vulnerable to exposure.

Variations in Hematologic Responses to Increased Lead Absorption in Young Children

PubMed Central

Chisolm, J. Julian; Mellits, E. David; Keil, Julian E.; Barrett, Maureen B.

1974-01-01

In the study of human populations, much emphasis is placed on the concentration of lead in whole peripheral blood. There is a considerable body of evidence which indicates that this measurement reflects recent and current assimilation of lead. While broad ranges in blood lead concentration have been associated with differing risks of toxicity for groups, it is not a precise index of adverse effect per se, even at elevated levels. Within the red blood cell itself there is not a close association between the concentration of lead and such adverse metabolic effects as the increased loss of potassium caused by lead. Above the apparent “threshold zone” of approximately 30–50 μg Pb/100 ml whole blood, equivalent metabolic effects on heme synthesis may be seen over an interval of at least 20 μg Pb/100 ml whole blood. This variation will be examined with particular reference to the interrelationship between the concentrations of lead and protoporphyrin in peripheral blood. The data indicate that limitations in both precision and accuracy of measurement account for a relatively small fraction of the observed variations. Together with other experimental and clinical information, they suggest that concurrent dietary deficiency of iron may be one of the important modifying factors in the responses of subjects with increased lead absorption. It is suggested that suspected adverse effects upon the various organ systems associated with increased lead absorption be measured directly and that the CaEDTA mobilization test for lead should be more fully explored as a measure of the “metabolically active” fraction of the total body lead burden. PMID:4831151

A hierarchical modeling approach to estimate regional acute health effects of particulate matter sources

PubMed Central

Krall, J. R.; Hackstadt, A. J.; Peng, R. D.

2017-01-01

Exposure to particulate matter (PM) air pollution has been associated with a range of adverse health outcomes, including cardiovascular disease (CVD) hospitalizations and other clinical parameters. Determining which sources of PM, such as traffic or industry, are most associated with adverse health outcomes could help guide future recommendations aimed at reducing harmful pollution exposure for susceptible individuals. Information obtained from multisite studies, which is generally more precise than information from a single location, is critical to understanding how PM impacts health and to informing local strategies for reducing individual-level PM exposure. However, few methods exist to perform multisite studies of PM sources, which are not generally directly observed, and adverse health outcomes. We developed SHARE, a hierarchical modeling approach that facilitates reproducible, multisite epidemiologic studies of PM sources. SHARE is a two-stage approach that first summarizes information about PM sources across multiple sites. Then, this information is used to determine how community-level (i.e. county- or city-level) health effects of PM sources should be pooled to estimate regional-level health effects. SHARE is a type of population value decomposition that aims to separate out regional-level features from site-level data. Unlike previous approaches for multisite epidemiologic studies of PM sources, the SHARE approach allows the specific PM sources identified to vary by site. Using data from 2000–2010 for 63 northeastern US counties, we estimated regional-level health effects associated with short-term exposure to major types of PM sources. We found PM from secondary sulfate, traffic, and metals sources was most associated with CVD hospitalizations. PMID:28098412

A Cross-Cultural Longitudinal Examination of the Effect of Cumulative Adversity on the Mental and Physical Health of Older Adults

PubMed Central

Palgi, Yuval; Shrira, Amit

2015-01-01

Self-oriented adversity refers to traumatic events that primarily inflict the self, whereas other-oriented adversity refers to events that affect the self by primarily targeting others. The present study aimed to examine whether cultural background moderates the effects of self-oriented and other-oriented adversity on mental and physical health of older adults. Using longitudinal data from the Israeli component of the Survey of Health and Retirement, we focused on 370 Jews and 239 Arabs who reported their exposure to various adversities across the lifespan, and completed questionnaires regarding mental and physical health. Results showed that the effect of self-oriented adversity on health did not differ among Jews and Arabs. However, other-oriented adversity showed a stronger effect on Arabs’ mental and physical health than on Jews’ health. Our findings suggest that the accumulation of adverse events that affect the self by primarily targeting others may have a stronger impact in collectivist cultures than in individualist cultures. PMID:25961862

Neuroendocrine considerations in the treatment of men and women with epilepsy

PubMed Central

Harden, Cynthia L; Pennell, Page B

2016-01-01

Complex, multidirectional interactions between hormones, seizures, and the medications used to control them can present a challenge for clinicians treating patients with epilepsy. Many hormones act as neurosteroids, modulating brain excitability via direct binding sites. Thus, changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs. The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning. Knowledge of these complex interactions has increased and can now be incorporated in meaningful treatment approaches for men and women with epilepsy. PMID:23237902

Effects of risk disclosure prominence in direct-to-consumer advertising (DTCA) of prescription drugs: An integrative cognitive process model.

PubMed

Ju, Ilwoo; Park, Jin Seong

2018-01-01

The literature shows that the prominence of risk disclosure influences consumer responses to direct-to-consumer advertising of prescription drugs. However, little is known about the psychological process whereby disclosure prominence exerts its influences on health beliefs and behavior. Based on a review of the literature on health cognition and behavior, the current study proposed and tested a model to show that risk disclosure prominence affects consumers' drug choice intention through the mediating roles of awareness of drug adverse reactions (ARs), perceived control over ARs, and perceived risk of ARs. The findings were discussed in terms of their theoretical and managerial implications.

The Nrf2 pathway in the progression of renal disease.

PubMed

Zoja, Carlamaria; Benigni, Ariela; Remuzzi, Giuseppe

2014-02-01

The Nrf2/Keap1 system regulates the transcription of antioxidant and cytoprotective genes through direct Nrf2 binding to responsive elements in the promoter region of target genes or via Keap1-induced NF-kB inhibition. The association between oxidative stress and inflammation with progression of chronic kidney diseases (CKDs) directed attention towards bardoxolone methyl and its analogues, potent Nrf2/Keap1 inducers, as a potential modality of renoprotective intervention. In a phase II clinical trial (BEAM), bardoxolone methyl was shown to increase the estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes. The study generated great interest but raised concerns as well, on the adverse event profile of the drug. Experiments in rats with type 2 diabetic nephropathy treated with bardoxolone methyl analogues reproduced some drawbacks of bardoxolone methyl therapy in humans. Despite these warnings, a long-term phase III trial (BEACON) was started that was prematurely terminated because of an excess serious adverse events and mortality. Lessons from the above studies suggest that before jumping into use in clinical practice, adequately designed experiments in animal models are needed to provide insights into pathogenetic mechanisms as well as unexpected side effects.

Measures of fish behavior as indicators of sublethal toxicosis during standard toxicity tests

USGS Publications Warehouse

Little, E.E.; DeLonay, A.J.

1996-01-01

Behavioral functions essential for growth and survival can be dramatically altered by sublethal exposure to toxicants. Measures of these behavioral responses are effective in detecting adverse effects of sublethal contaminant exposure. Behavioral responses of fishes can be qualitatively and quantitatively evaluated during routine toxicity tests. At selected intervals of exposure, qualitative evaluations are accomplished through direct observations, whereas video recordings are used for quantitative evaluations. Standardized procedures for behavioral evaluation are readily applicable to different fish species and provide rapid, sensitive, and ecologically relevant assessments of sublethal exposure. The methods are readily applied to standardized test protocols.

Effect of winglets on performance and handling qualities of general aviation aircraft

NASA Technical Reports Server (NTRS)

Van Dam, C. P.; Holmes, B. J.; Pitts, C.

1980-01-01

Recent flight and wind tunnel evaluations of winglets mounted on general aviation airplanes have shown improvements in cruise fuel efficiency, and climbing and turning performance. Some of these analyses have also uncovered various effects of winglets on airplane handling qualities. Retrofitting an airplane with winglets can result in reduced cross wind take-off and landing capabilities. Also, winglets can have a detrimental effect on the lateral directional response characteristics of aircraft which have a moderate to high level of adverse yaw due to aileron. Introduction of an aileron-rudder-interconnect, and reduction of the effective dihedral by canting-in of the winglets, or addition of a lower winglet can eliminate these flying quality problems.

Adverse effects of cannabis.

PubMed

2011-01-01

Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.

Detailed assessments of childhood adversity enhance prediction of central obesity independent of gender, race, adult psychosocial risk and health behaviors.

PubMed

Davis, Cynthia R; Dearing, Eric; Usher, Nicole; Trifiletti, Sarah; Zaichenko, Lesya; Ollen, Elizabeth; Brinkoetter, Mary T; Crowell-Doom, Cindy; Joung, Kyoung; Park, Kyung Hee; Mantzoros, Christos S; Crowell, Judith A

2014-02-01

This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of "modifiable" risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities × severity × chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. 210 Black/African Americans and White/European Americans, mean age=45.8; ±3.3 years, were studied cross-sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist-hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. © 2013.

Implications of Middle School Behavior Problems for High School Graduation and Employment Outcomes of Young Adults: Estimation of a Recursive Model.

PubMed

Karakus, Mustafa C; Salkever, David S; Slade, Eric P; Ialongo, Nicholas; Stuart, Elizabeth

2012-01-01

The potentially serious adverse impacts of behavior problems during adolescence on employment outcomes in adulthood provide a key economic rationale for early intervention programs. However, the extent to which lower educational attainment accounts for the total impact of adolescent behavior problems on later employment remains unclear As an initial step in exploring this issue, we specify and estimate a recursive bivariate probit model that 1) relates middle school behavior problems to high school graduation and 2) models later employment in young adulthood as a function of these behavior problems and of high school graduation. Our model thus allows for both a direct effect of behavior problems on later employment as well as an indirect effect that operates via graduation from high school. Our empirical results, based on analysis of data from the NELS, suggest that the direct effects of externalizing behavior problems on later employment are not significant but that these problems have important indirect effects operating through high school graduation.

Parenting and Coregulation: Adaptive Systems for Competence in Children Experiencing Homelessness

PubMed Central

Herbers, Janette E.; Cutuli, J. J.; Supkoff, Laura M.; Narayan, Angela J.; Masten, Ann S.

2018-01-01

The role of effective parenting in promoting child executive functioning and school success was examined among 138 children (age 4 to 6 years) staying in family emergency shelters the summer before kindergarten or first grade. Parent-child coregulation, which refers to relationship processes wherein parents guide and respond to the behavior of their children, was observed during structured interaction tasks and quantified as a dyadic construct using state space grid methodology. Positive coregulation was related to children’s executive functioning and IQ, which in turn were related to teacher-reported outcomes once school began. Separate models considering parenting behavior demonstrated that EF carried indirect effects of parents’ directive control to school outcomes. Meanwhile, responsive parenting behaviors directly predicted children’s peer acceptance at school beyond effects of EF and IQ. Findings support theory and past research in developmental science indicating the importance of effective parenting in shaping positive adaptive skills among children who overcome adversity, in part through processes of coregulation. PMID:24999527

Adverse effects of methotrexate in three psoriatic arthritis patients.

PubMed

Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

2014-04-01

Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

77 FR 28785 - Revisions to Federal Implementation Plans To Reduce Interstate Transport of Fine Particulate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-16

... Ozone AGENCY: Environmental Protection Agency (EPA). ACTION: Withdrawal of direct final rule. SUMMARY... Particulate Matter and Ozone'' as a direct final rule on February 21, 2012. Because the EPA received adverse... Implementation Plans To Reduce Interstate Transport of Fine Particulate Matter and Ozone'' as a direct final rule...

Predictors of local adverse effects caused by topical tretinoin cream 0·1% in the Veterans Affairs Topical Tretinoin Chemoprevention trial.

PubMed

Pomerantz, H; Weinstock, M A

2014-09-01

Topical tretinoin is commonly prescribed, but its frequent adverse effects are barriers to use. Predictors of resistance or susceptibility to retinoid irritation are not known. To identify baseline patient characteristics associated with adverse effects of topical tretinoin. This cohort study used data collected from 324 participants in the Veterans Affairs Topical Tretinoin Chemoprevention trial who were randomized to apply tretinoin cream on the face and ears. Univariate and multivariate logistic regression models were used to examine the associations between baseline characteristics and local adverse effects. One hundred and ninety-seven patients (61% of those randomized to tretinoin) reported local adverse effects within 6 months. Clinical signs of severe photodamage at baseline [odds ratio (OR) 0·15, 95% confidence interval (CI) 0·04-0·54] and history of acne (OR 0·46, 95% CI 0·27-0·77) were associated with a decreased risk of adverse effects to tretinoin. The use of other topical medications at enrolment (OR 1·88, 95% CI 1·15-3·08) predicted an increase in adverse effects. In this study population, the common indications of topical tretinoin treatment were associated with lower risks of adverse effects. The concurrent use of other topical medications may worsen irritation caused by tretinoin. © 2014 British Association of Dermatologists.

Long-term mucocutaneous adverse effects of imatinib in Indian chronic myeloid leukemia patients.

PubMed

Vinay, Keshavamurthy; Yanamandra, Uday; Dogra, Sunil; Handa, Sanjeev; Suri, Vikas; Kumari, Savita; Khadwal, Alka; Prakash, Gaurav; Lad, Deepesh; Varma, Subhash; Malhotra, Pankaj

2018-03-01

Short-term mucocutaneous adverse effects are well documented with imatinib. However, studies on long-term adverse effects and in the ethnic population are lacking. To study the long-term mucocutaneous adverse effects of imatinib and factors predicting these adverse effects. In this cross-sectional study, consenting adult chronic myeloid leukemia patients on imatinib for more than 250 days were recruited. The details of imatinib treatment were retrieved from hematology clinic records. Four hundred and thirty-eight patients who were on imatinib for a mean duration of 1820 days were recruited. A mean number of 1.42 ± 0.98 cutaneous adverse effects were seen per patient. Melasma-like pigmentation, periorbital edema, oral lichenoid reaction, cutaneous hypopigmentation, and vesicobullous eruptions were seen in 236 (53.9%), 81 (18.5%), 70 (16%), 42 (9.6%), and 12 (2.7%) patients, respectively. Drug-induced cutaneous eruptions (9.1%) and cutaneous hypopigmentation (9.6%) were seen less frequently. Cutaneous hyperpigmentation was more likely seen in younger patients (P = 0.001) and females (P < 0.001). On multivariate analysis, female gender was a significant risk factor for developing cutaneous hyperpigmentation and periorbital edema. Cutaneous hyperpigmentation and periorbital edema are common long-term adverse effects of imatinib in Indian patients. Female gender is a significant risk factor for the development of both these adverse effects. © 2017 The International Society of Dermatology.

Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.

PubMed

Masip, Montserrat; Tuneu, Laura; Pagès, Neus; Torras, Xavier; Gallego, Adolfo; Guardiola, Josep Maria; Faus, María José; Mangues, Maria Antònia

2015-12-01

Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.

[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

PubMed

Eckhardt, K; Cremer-Schaeffer, P; König, J; Paeschke, N

2005-02-01

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member states.

Blood lead level and physical fitness of schoolchildren in the copper basin of south-western Poland: indirect effects through growth stunting.

PubMed

Ignasiak, Zosia; Sławinska, Teresa; Rozek, Krystyna; Malina, Robert; Little, B B

2007-01-01

The present study was set in the context of two questions. First, does blood lead level exert a direct effect on measures of physical fitness? And second, might blood lead influence physical fitness indirectly through growth stunting? Blood lead level is negatively associated with performances on a variety of fine motor tasks. Corresponding information on associations with measures of physical fitness and gross motor coordination are limited. Schoolchildren 7-15 years of age (463 males, 436 females) living in the vicinity of copper smelters and refineries were tested for blood lead. In addition to body size and blood lead, physical fitness was measured: right and left grip strength, timed sit-ups, flexed arm hang, plate tapping, shuttle run, standing long jump and medicine ball throw. Simple reaction time was also measured. The effect of blood lead level on physical fitness was indirect and small, and operated through anthropometric dimensions that more directly influenced the measures of fitness. Direct effects of blood lead level on indicators of physical fitness in school age youth are not evident. Blood lead level adversely affects physical fitness indirectly through growth stunting.

A Retrospective Case-Control Study, Factors Affecting Treatment Outcomes for Pulmonary Tuberculosis in İstanbul, Turkey

PubMed Central

Babalık, Aylin; Kılıçaslan, Zeki; Kızıltaş, Şule; Gencer, Serap; Öngen, Gül

2013-01-01

Background: Tuberculosis is a public health problem and its transmission is a threat to the community. Aims: The aim of this study was to determine the factors influencing the treatment outcomes and the effectiveness of the National Tuberculosis Program (NTP) in relation to the application of the directly observed treatment, short-course (DOTS) program in various sites in Istanbul, Turkey. Study Design: Case-Control Study Methods: A case-control study was used, where cases and controls were randomly selected from the Turkish Tuberculosis National Database, which includes complete data on treatment outcomes for patients recorded in the database from January 1, 2006 to December 31, 2009 and had one year follow-up. Results: The case group was composed of 464 patients with adverse outcome, while the control group was composed of 441 patients who had been cured of disease. Factors associated with adverse treatment outcome were >65 years of age (OR: 3.39 (1.99–5.76)) ; male gender (OR:2.11 (1.49–2.99)); born outside Turkey (OR: 5.48 (2.13–14.04)); co-morbidity (OR: 1.85 (1.29–2.65)); bilateral radiologic lesions (OR: 2.07 (1.41–3.00); previous treatment history (OR: 3.99 (2.78–5.74)); 3rd month positive microscopy (OR: 4.96 (3.04–8.09)) and any H&R +/− others multidrug resistant (MDR) resistance (OR: 22.64 (6.92–74.08)). There was no association between the adverse treatment outcome and the application site of direct observation treatment, short course (DOTS) delivery and the supervisors. Conclusion: Our findings indicate similar quality in DOTS application and supervision among patients with or without adverse treatment outcomes. However, patients with certain characteristics should be carefully monitored and aggressively treated. PMID:25207101

Detection of medication-related problems in hospital practice: a review

PubMed Central

Manias, Elizabeth

2013-01-01

This review examines the effectiveness of detection methods in terms of their ability to identify and accurately determine medication-related problems in hospitals. A search was conducted of databases from inception to June 2012. The following keywords were used in combination: medication error or adverse drug event or adverse drug reaction, comparison, detection, hospital and method. Seven detection methods were considered: chart review, claims data review, computer monitoring, direct care observation, interviews, prospective data collection and incident reporting. Forty relevant studies were located. Detection methods that were better able to identify medication-related problems compared with other methods tested in the same study included chart review, computer monitoring, direct care observation and prospective data collection. However, only small numbers of studies were involved in comparisons with direct care observation (n = 5) and prospective data collection (n = 6). There was little focus on detecting medication-related problems during various stages of the medication process, and comparisons associated with the seriousness of medication-related problems were examined in 19 studies. Only 17 studies involved appropriate comparisons with a gold standard, which provided details about sensitivities and specificities. In view of the relatively low identification of medication-related problems with incident reporting, use of this method in tracking trends over time should be met with some scepticism. Greater attention should be placed on combining methods, such as chart review and computer monitoring in examining trends. More research is needed on the use of claims data, direct care observation, interviews and prospective data collection as detection methods. PMID:23194349

Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

ERIC Educational Resources Information Center

Correll, Christoph U.; Carlson, Harold E.

2006-01-01

Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

Sugary beverages represent a threat to global health.

PubMed

Popkin, Barry M

2012-12-01

Sugary beverages represent a major global threat to the health of all populations. The shifts in distribution, marketing, and sales have made them the plague of the globe in terms of obesity, diabetes, and a host of other chronic health problems. The fructose-laden beverages have unique properties that lead to lack of dietary compensation and direct adverse effects on our health. Global efforts to limit marketing and sales are necessary to protect the health of the planet. Copyright © 2012 Elsevier Ltd. All rights reserved.

The classroom competence and attitudes towards pedagogical principles of beginning teachers.

PubMed

Preece, P F

1994-06-01

The relationship between preservice education students' (N = 135) attitudes towards general pedagogical principles and the quality of their classroom teaching was investigated. A weak negative relationship was obtained between students' attitudes and the assessment category 'relationships with children'. This suggests that fostering positive attitudes in preservice students towards general pedagogical principles, based on practices in themselves directly associated with enhancing pupil achievement, may result in lower quality teaching because of an adverse effect this has on pupil-teacher relationships.

Development of a Paradigm to Assess Nutritive and Biochemical Substances in Humans: A Preliminary Report on the Effects of Tyrosine upon Altitude- and Cold-Induced Stress Responses

DTIC Science & Technology

1987-03-01

3/4 hours. Performance tests evaluated simple and choice reaction time to visual stimuli, vigilance, and processing of symbolic, numerical, verbal...minimize the adverse consequences of these stressors. Tyrosine enhanced performance (e.g. complex information processing , vigilance, and reaction time... processes inherent in many real-world tasks. For example, Map Compass requires association of Wsi PL AFCm uA O-SV CHETCLtISS) direction and degree

The direct costs of drug-induced skin reactions.

PubMed

Kiepurska, Nina; Paluchowska, Elwira; Owczarek, Witold; Szkultecka-Dębek, Monika; Jahnz-Różyk, Karina

2017-05-11

[b] Abstract Objective.[/b] The aim of the study was an assessment of direct costs of patients hospitalised for for skin adverse drug reactions during 2002-2012 in the Department of Dermatology at the Military Institute of Medicine (Ministry of Defence) in Warsaw. The analysis was carried out from the perspectives of the public payer and service provider. [b]Materials and method. [/b]The retrospective study was carried out in a group of 164 adult patients due to skin adverse drug reactions. Analysis was based on data from patient medical records and medical orders which provided information on the used resources, including diagnostic tests, medical consultations, medicinal products, hospitalisation duration, together with cost estimation, regardless of the treatment being the cause of the skin reaction. [b]Results[/b]. According to the International Statistical Classification of Diseases and Related Health Problems(ICD) diagnosis and scores, assigned by the National Healthcare Fund, it has been estimated that patient hospitalisation at the Department of Dermatology for skin drug reaction incurred costs at the average amount of €717.00 per patient. The complex diagnostics and pharmacotherapy of the same group of patients generated costs for the hospital at the average amount of €680 per patient. [b]Conclusions[/b]. As a result of the analysis, the therapy for skin adverse drug effects generates significant costs, both for the payer and the service provider. Since the costs are comparable, it seems that the pricing of medical procedures by the public payer is adequate for the costs incurred by the medical service provider.

Particle number concentrations near the Rome-Ciampino city airport

NASA Astrophysics Data System (ADS)

Stafoggia, M.; Cattani, G.; Forastiere, F.; Di Menno di Bucchianico, A.; Gaeta, A.; Ancona, C.

2016-12-01

Human exposure to ultrafine particles (UFP) has been postulated to be associated with adverse health effects, and there is interest regarding possible measures to reduce primary emissions. One important source of UFP are airport activities, with aircraft take-offs being the most relevant one. We implemented two measurement campaigns of total particle number concentrations (PNC), a proxy for UFP, near a medium-size airport in central Italy. One-minute PNC averages were collected on June 2011 and January 2012 concurrently with 30-min average meteorological data on temperature and wind speed/direction. Data on minute-specific take-offs and landings were obtained by the airport authorities. We applied statistical regression models to relate PNC data to the presence of aircraft activities while adjusting for time trends and meteorology, and estimated the increases in PNC ±15 min before and after take-offs and landings. We repeated the analyses considering prevalent wind direction and by size of the aircraft. We estimated PNC increases of 5400 particles/cm3/minute during the 15 min before and after take-offs, with a peak of 19,000 particles/cm3/minute within 5 min after take-offs. Corresponding figures for landings were 1300 and 1000 particles, respectively. The highest PNC estimates were obtained when the prevailing wind came from the runway direction, and led to estimated PNC increases of 60,000 particles/cm3/minute within 5 min after take-offs. No main differences were noted from the exhaust of different types of aircrafts. The area surrounding Ciampino airport is densely inhabited, raising concerns about the potential adverse effects of long-term and short-term exposure to airport-borne UFP. A close monitoring of airport activities and emissions is mandatory to reduce the public health impact of the airport on the nearby population.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-04-01

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

Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

PubMed Central

DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H.; Caudill, Jonathan W.; Trulson, Chad R.; Baglivio, Michael T.

2017-01-01

Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered. PMID:28327508

Energy drink usage among university students in a Caribbean country: Patterns of use and adverse effects.

PubMed

Reid, Sandra D; Ramsarran, Jonathan; Brathwaite, Rachel; Lyman, Sarika; Baker, Ariane; Cornish, D'Andra C; Ganga, Stefan; Mohammed, Zahrid; Sookdeo, Avinash T; Thapelo, Cathrine K

2015-06-01

There has been little inquiry addressing whether or not concerns about adverse effects of energy drink usage are relevant in the Caribbean. This survey investigated energy drink usage and adverse consequences among tertiary level students in Trinidad and Tobago. A cross-sectional survey of 1994 students from eight institutions was conducted using a de novo questionnaire based on findings from a focus group of students. Chi-squared analyses and logistic regression were used to assess relationships between energy drink usage, adverse effects and other factors affecting energy drink use, and to verify predictors of energy drink use. Prevalence of use was 86%; 38% were current users. Males were more likely to use, used more frequently and at an earlier age. Energy drinks were used most commonly to increase energy (50%), combat sleepiness (45%) and enhance academic performance (40%), and occurred during sports (23%) and mixed with alcohol (22.2%). The majority (79.6%) consumed one energy drink per sitting; 62.2% experienced adverse effects, most commonly restlessness (22%), jolt and crash (17.1%) and tachycardia (16.6%). Awareness of adverse effects was associated with no use (p=0.004), but adverse effects were not a deterrent to continued use. Energy drink usage is prevalent among students. The use is not excessive, but associated with high rates of adverse effects and occurs in potentially dangerous situations like during exercise and with alcohol. There is a need to educate students about the potential adverse effects of energy drinks. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Stub, Trine; Musial, Frauke; Kristoffersen, Agnete A; Alræk, Terje; Liu, Jianping

2016-06-01

Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Utilization of Genomic Signatures to Direct Use of Primary Chemotherapy in Early Stage Breast Cancer

DTIC Science & Technology

2012-07-01

those seen with standard dose AC and TC  By chemotherapy:  AC: 11 of 19 with grade 3 or 4 adverse events (all neutropenia except one treatment...unrelated PE)  TC: 8 of 20 with grade 3 or 4 adverse events (all neutropenia except one docetaxel reaction)  By arm:  Genomically-guided: 14

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data.

PubMed

Moffa, Adriano H; Brunoni, André R; Fregni, Felipe; Palm, Ulrich; Padberg, Frank; Blumberger, Daniel M; Daskalakis, Zafiris J; Bennabi, Djamila; Haffen, Emmanuel; Alonzo, Angelo; Loo, Colleen K

2017-10-15

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that has been increasingly used for major depressive disorder (MDD) treatment. Although studies in healthy volunteers showed that the technique is well-tolerated, tDCS safety and acceptability have not been sufficiently explored in patients with MDD. We collected individual patient data from 6 randomized clinical trials that had been previously identified in a systematic review and meta-analysis. Primary outcomes were safety (rate of adverse events) and acceptability (rate of dropouts). Secondary outcomes were clinical, demographic and treatment predictors of the primary outcomes. Dropout rates between active (8.8%) and sham (12%) groups were not significantly different (OR= 0.7, p=0.38). Adverse event rates between active (73.5%) and sham (68.3%) groups were not significantly different (OR= 1.4, p= 0.23). Higher current densities were associated with lower adverse event rates. Dropout reasons were not systematically reported and adverse events were not collected using questionnaires standardized across studies. Active tDCS is as acceptable and safe as sham tDCS, as found in randomized clinical trials of MDD. Copyright © 2017. Published by Elsevier B.V.

Future Directions in Childhood Adversity and Youth Psychopathology

PubMed Central

McLaughlin, Katie A.

2016-01-01

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

Conduct Disorder and Neighborhood Effects.

PubMed

Jennings, Wesley G; Perez, Nicholas M; Reingle Gonzalez, Jennifer M

2018-05-07

There has been a considerable amount of scholarly attention to the relationship between neighborhood effects and conduct disorder, particularly in recent years. Having said this, it has been nearly two decades since a comprehensive synthesis of this literature has been conducted. Relying on a detailed and comprehensive search strategy and inclusion criteria, this article offers a systematic and interdisciplinary review of 47 empirical studies that have examined neighborhood effects and conduct disorder. Described results suggest that there are generally robust linkages between adverse neighborhood factors and conduct disorder and externalizing behavior problems, as 67 of the 93 (72.04%) effect sizes derived from these studies yielded statistically significant neighborhood effects. The review also identifies salient mediating and moderating influences. It discusses study limitations and directions for future research as well.

Effects of wingtip modifications on handling qualities of agricultural aircraft

NASA Technical Reports Server (NTRS)

Van Dam, C. P.

1981-01-01

The effect of wingtip modifications on the stability and control characteristics of an agricultural airplane has been studied by means of a nonplanar quasi-vortex-lattice method. The method is used to compute the changes in steady state and perturbed state lateral-directional stability and control derivatives produced by wingtip mounted winglets, vortex diffuser vanes, and tip extensions. The study shows that the combination of the excessive positive dihedral effect produced by the winglets and adverse yaw due to aileron deflection can have a detrimental effect on the roll control characteristics of the airplane. Introduction of an aileron-rudder-interconnect, and reduction of the effective dihedral by canting-in of the winglets, or addition of a lower winglet can eliminate the roll control problems.

21 CFR 812.46 - Monitoring investigations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Unanticipated adverse device effects. (1) A sponsor shall immediately conduct an evaluation of any unanticipated adverse device effect. (2) A sponsor who determines that an unanticipated adverse device effect presents...

Evidence for a neural dual-process account for adverse effects of cognitive control.

PubMed

Zink, Nicolas; Stock, Ann-Kathrin; Colzato, Lorenza; Beste, Christian

2018-06-09

Advantageous effects of cognitive control are well-known, but cognitive control may also have adverse effects, for example when it suppresses the implicit processing of stimulus-response (S-R) bindings that could benefit task performance. Yet, the neurophysiological and functional neuroanatomical structures associated with adverse effects of cognitive control are poorly understood. We used an extreme group approach to compare individuals who exhibit adverse effects of cognitive control to individuals who do not by combining event-related potentials (ERPs), source localization, time-frequency analysis and network analysis methods. While neurophysiological correlates of cognitive control (i.e. N2, N450, theta power and theta-mediated neuronal network efficiency) and task-set updating (P3) both reflect control demands and implicit information processing, differences in the degree of adverse cognitive control effects are associated with two independent neural mechanisms: Individuals, who show adverse behavioral effects of cognitive control, show reduced small-world properties and thus reduced efficiency in theta-modulated networks when they fail to effectively process implicit information. In contrast to this, individuals who do not display adverse control effects show enhanced task-set updating mechanism when effectively processing implicit information, which is reflected by the P3 ERP component and associated with the temporo-parietal junction (TPJ, BA 40) and medial frontal gyrus (MFG; BA 8). These findings suggest that implicit S-R contingencies, which benefit response selection without cognitive control, are always 'picked up', but may fail to be integrated with task representations to guide response selection. This provides evidence for a neurophysiological and functional neuroanatomical "dual-process" account of adverse cognitive control effects.

Potential application of ecological models in the European environmental risk assessment of chemicals. I. Review of protection goals in EU directives and regulations.

PubMed

Hommen, Udo; Baveco, J M Hans; Galic, Nika; van den Brink, Paul J

2010-07-01

Several European directives and regulations address the environmental risk assessment of chemicals. We used the protection of freshwater ecosystems against plant protection products, biocidal products, human and veterinary pharmaceuticals, and other chemicals and priority substances under the Water Framework Directive as examples to explore the potential of ecological effect models for a refined risk assessment. Our analysis of the directives, regulations, and related guidance documents lead us to distinguish the following 5 areas for the application of ecological models in chemical risk assessment: 1) Extrapolation of organism-level effects to the population level: The protection goals are formulated in general terms, e.g., avoiding "unacceptable effects" or "adverse impact" on the environment or the "viability of exposed species." In contrast, most of the standard ecotoxicological tests provide data only on organism-level endpoints and are thus not directly linked to the protection goals which focus on populations and communities. 2) Extrapolation of effects between different exposure profiles: Especially for plant protection products, exposure profiles can be very variable and impossible to cover in toxicological tests. 3) Extrapolation of recovery processes: As a consequence of the often short-term exposures to plant protection products, the risk assessment is based on the community recovery principle. On the other hand, assessments under the other directives assume a more or less constant exposure and are based on the ecosystem threshold principle. 4) Analysis and prediction of indirect effects: Because effects on 1 or a few taxa might have consequences on other taxa that are not directly affected by the chemical, such indirect effects on communities have to be considered. 5) Prediction of bioaccumulation within food chains: All directives take the possibility of bioaccumulation, and thus secondary poisoning within the food chain, into account. (c) 2010 SETAC.

Assessing Stress-Related Treatment Needs among Girls at Risk for Poor Functional Outcomes: The Impact of Cumulative Adversity, Criterion Traumas, and Non-Criterion Events

PubMed Central

Lansing, Amy E.; Plante, Wendy Y.; Beck, Audrey N.

2016-01-01

Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: 1) an average of 14 adverse Criterion-A and non-Criterion event exposures; 2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; 3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and 4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. PMID:27745922

A cross-cultural longitudinal examination of the effect of cumulative adversity on the mental and physical health of older adults.

PubMed

Palgi, Yuval; Shrira, Amit

2016-03-01

Self-oriented adversity refers to traumatic events that primarily inflict the self, whereas other-oriented adversity refers to events that affect the self by primarily targeting others. The present study aimed to examine whether cultural background moderates the effects of self-oriented and other-oriented adversity on mental and physical health of older adults. Using longitudinal data from the Israeli component of the Survey of Health and Retirement, we focused on 370 Jews and 239 Arabs who reported their exposure to various adversities across the life span, and completed questionnaires regarding mental and physical health. Results showed that the effect of self-oriented adversity on health did not differ among Jews and Arabs. However, other-oriented adversity showed a stronger effect on Arabs' mental and physical health than on Jews' health. Our findings suggest that the accumulation of adverse events that affect the self by primarily targeting others may have a stronger impact in collectivist cultures than in individualist cultures. (c) 2016 APA, all rights reserved).

Transfusion-Associated Circulatory Overload: Evidence-Based Strategies to Prevent, Identify, and Manage a Serious Adverse Event.

PubMed

Henneman, Elizabeth A; Andrzejewski, Chester; Gawlinski, Anna; McAfee, Kelley; Panaccione, Thomas; Dziel, Kimberly

2017-10-01

Transfusion-associated circulatory overload (TACO) is a potentially life-threatening complication of blood transfusion and is associated with increased morbidity, length of stay (hospital and intensive care unit), and hospital costs. Bedside nurses play a key role in the prevention, identification, and reporting of this complication. A common misperception is that the most frequently encountered serious adverse event during transfusion is a hemolytic reaction in a patient who receives ABO-incompatible blood. In fact, the incidence of TACO-related fatalities is higher than fatalities caused by ABO-related hemolytic reactions. Surveillance and evidence-based strategies such as clinical decision support systems have the potential to reduce the incidence of TACO and mitigate its effects. Practical suggestions for conducting bedside transfusion surveillance and future directions for improving transfusion care are presented. ©2017 American Association of Critical-Care Nurses.

[Changes of menstruation patterns and adverse effects during the treatment of LNG-IUS for symptomatic adenomyosis].

PubMed

Li, L; Leng, J H; Zhang, J J; Jia, S Z; Li, X Y; Shi, J H; Dai, Y; Zhang, J R; Li, T; Xu, X X; Liu, Z Z; You, S S; Chang, X Y; Lang, J H

2016-09-25

Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively( P <0.01). Total and subclassification of adverse effects decreased significantly( P <0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P > 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects.

Direct renal effects of a fructose-enriched diet: interaction with high salt intake

PubMed Central

Ares, Gustavo R.

2015-01-01

Consumption of fructose has increased during the last 50 years. Excessive fructose consumption has a detrimental effect on mammalian health but the mechanisms remain unclear. In humans, a direct relationship exists between dietary intake of added sugars and increased risk for cardiovascular disease mortality (52). While the causes for this are unclear, we recently showed that fructose provided in the drinking water induces a salt-dependent increase in blood pressure in Sprague-Dawley rats in a matter of days (6). However, little is known about the effects of fructose in renal salt handling and whether combined intake of high fructose and salt can lead to salt-sensitive hypertension before the development of metabolic abnormalities. The long-term (more than 4 wk) adverse effects of fructose intake on renal function are not just due to fructose but are also secondary to alterations in metabolism which may have an impact on renal function. This minireview focuses on the acute effect of fructose intake and its effect on salt regulation, as they affect blood pressure. PMID:26447210

Comparison of two spinal needle types to achieve a unilateral spinal block.

PubMed

Kuusniemi, Kristiina; Leino, Kari; Lertola, Kaarlo; Pihlajamäki, Kalevi; Pitkänen, Mikko

2013-04-01

Unilateral spinal anesthesia is beneficial in patients undergoing unilateral leg surgery. The direction and the shape of the spinal needle are thought to influence the unilateral distribution of the local anesthetic in the intrathecal space. Therefore, to study the effects of different spinal needles we compared the effects of the Whitacre and Quincke spinal needles. This was a prospective, randomized, double-blind study of 60 consecutive outpatients scheduled for unilateral lower-limb surgery. The patients were randomized to receive spinal anesthesia with 1.2 ml of 0.5 % plain bupivacaine using either a 27-G Whitacre or a Quincke needle. One half of the local anesthetic was injected towards the nondependent side and the other half was directed cranially. The spread of spinal anesthesia, both sensory and motor blocks, was defined as the primary endpoint and was recorded at 10, 20, and 30 min after the spinal injection, at the end of the operation, 2 h after the spinal injection, and every 30 min thereafter until there was no motor block. Secondary endpoints included patient satisfaction and adverse effects. There was no difference in the spread of sensory or motor blocks between the Whitacre and the Quincke groups. However, the sensory and motor blocks on the operated and the nonoperated sides were significantly different at all testing times, as expected. There was no difference in the incidence of adverse effects or patient satisfaction scores between the Whitacre and the Quincke groups. Unilateral spinal block for outpatient surgery can be achieved with both pencil-point (Whitacre) and Quincke needles using 6.0 mg of plain bupivacaine. Neither the spread of sensory and motor blocks nor the corresponding recovery times appeared to be different between the groups. Nor was there any difference in patient satisfaction.

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.

PubMed

Kunwar, Sandeep; Chang, Susan M; Prados, Michael D; Berger, Mitchel S; Sampson, John H; Croteau, David; Sherman, Jeffrey W; Grahn, Amy Y; Shu, Vince S; Dul, Jeanne L; Husain, Syed R; Joshi, Bharat H; Pedain, Christoph; Puri, Raj K

2006-04-15

Convection-enhanced delivery (CED) is an increasingly used novel local/regional delivery method targeted directly to tissue. It relies on a continuous pressure gradient for distribution of therapeutic agents into the interstitial space, with administration of the infusate over a few days. Cintredekin besudotox (also known as IL13- PE38QQR) is a recombinant chimeric cytotoxin consisting of interleukin-13 and a truncated exotoxin produced by the Pseudomonas aeruginosa bacterium, which targets malignant glioma cells. Cintredekin besudotox was administered via intraparenchymal CED after resection of supratentorial recurrent malignant glioma. The safety and toxicity profile was reviewed for 53 patients in whom infusion catheters had been placed; 51 of them received CED of the study drug. Adverse events were categorized based on time of onset in relation to CED, and the causal relationship with catheter placement or delivery of cintredekin besudotox. Catheters were placed in 53 patients, although only 51 of them received cintredekin besudotox. Most adverse events related to catheter placement or the study drug originated from the central nervous system. Three symptomatic windows were defined: the first one was between surgical procedure and CED; the second was during CED and up to 1 week after its completion; and the third window was 2 to 10 weeks after treatment. Those windows generally reflected adverse events related to surgical procedures, mass effect from infusate, and drug effect on tumor-infiltrated and normal brain parenchyma, respectively. The symptomatic windows identified in this study apply to any CED clinical trials, particularly those in which chimeric cytotoxins are used, and will help to determine the most likely underlying pathophysiological process causing symptoms. This information, in turn, will help to prevent adverse events or minimize their severity. Those events also have implications for dose escalation and outcome measures.

The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s).

PubMed

Dorato, Michael A; Engelhardt, Jeffery A

2005-08-01

The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what constitutes an adverse effect. Toxicologists, either investigating or reviewing, have not been consistent in defining an effect as either adverse or acceptable. The common definition of NOAEL, "the highest experimental point that is without adverse effect," serves us well in general discussions. It does not, however, address the interpretation of risk based on toxicologically relevant effects, nor does it consider the progression of effect with respect to duration and/or dose. This paper will discuss the issues and application of a functional definition of the NOAEL in toxicology evaluations.

The placebo effect and homeopathy.

PubMed

Teixeira, Marcus Z; Guedes, Cristina H F F; Barreto, Patrícia V; Martins, Mílton A

2010-04-01

Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations. We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline. Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum. Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed.

Detailed Assessments of Childhood AdversityEnhance Prediction of Central Obesity Independent of Gender, Race, Adult Psychosocial Risk and Health Behaviors

PubMed Central

Davis, Cynthia R.; Dearing, Eric; Usher, Nicole; Trifiletti, Sarah; Zaichenko, Lesya; Ollen, Elizabeth; Brinkoetter, Mary T.; Crowell-Doom, Cindy; Joung, Kyoung; Park, Kyung Hee; Mantzoros, Christos S.; Crowell, Judith A.

2017-01-01

Objective This study examined whether a novel indicator of overall childhood adversity, incorporating number of adversities, severity, and chronicity, predicted central obesity beyond contributions of “modifiable” risk factors including psychosocial characteristics and health behaviors in a diverse sample of midlife adults. The study also examined whether the overall adversity score (number of adversities X severity X chronicity) better predicted obesity compared to cumulative adversity (number of adversities), a more traditional assessment of childhood adversity. Materials/Methods 210 Black/African Americans and White/European Americans, mean age = 45.8; ±3.3 years, were studied cross-sectionally. Regression analysis examined overall childhood adversity as a direct, non-modifiable risk factor for central obesity (waist-hip ratio) and body mass index (BMI), with and without adjustment for established adult psychosocial risk factors (education, employment, social functioning) and heath behavior risk factors (smoking, drinking, diet, exercise). Results Overall childhood adversity was an independent significant predictor of central obesity, and the relations between psychosocial and health risk factors and central obesity were not significant when overall adversity was in the model. Overall adversity was not a statistically significant predictor of BMI. Conclusions Overall childhood adversity, incorporating severity and chronicity and cumulative scores, predicts central obesity beyond more contemporaneous risk factors often considered modifiable. This is consistent with early dysregulation of metabolic functioning. Findings can inform practitioners interested in the impact of childhood adversity and personalizing treatment approaches of obesity within high-risk populations. Prevention/intervention research is necessary to discover and address the underlying causes and impact of childhood adversity on metabolic functioning. PMID:24211017

Adverse mood effects of combined oral contraceptives in relation to personality traits.

PubMed

Borgström, Anna; Odlind, Viveca; Ekselius, Lisa; Sundström-Poromaa, Inger

2008-12-01

Mood symptoms, such as depressed mood, anxiety and increased irritability, remain one of the major reasons for discontinuation of combined oral contraceptive (COC) pills. The aim of this study was to compare personality traits in women with ongoing or previous use of COCs and different experiences from these compounds with respect to adverse mood symptoms. Thirty women currently on COCs with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 33 women who had discontinued COC use due to adverse mood effects were included. All participants were asked to fill out the Swedish universities Scales of Personality (SSP) to assess different personality traits. The women who were experiencing mood-related side effects on their current COC use exhibited higher scores on the somatic anxiety and stress susceptibility traits as compared to the women who did not experience any mood-related side effects from their current COCs. Women who had discontinued COC treatment because of adverse mood effects had higher scores of detachment and mistrust compared to women who had discontinued COC for reasons unrelated to mood effects. Higher scores on specific personality traits such as somatic anxiety and stress susceptibility are found in women with ongoing experience of adverse mood symptoms from COC. Higher scores of mistrust and detachment are more common among women who have discontinued COC treatment due to adverse mood effects.

Assessment of lung cell toxicity of various gasoline engine exhausts using a versatile in vitro exposure system.

PubMed

Bisig, Christoph; Comte, Pierre; Güdel, Martin; Czerwinski, Jan; Mayer, Andreas; Müller, Loretta; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

2018-04-01

Adverse effect studies of gasoline exhaust are scarce, even though gasoline direct injection (GDI) vehicles can emit a high number of particles. The aim of this study was to conduct an in vitro hazard assessment of different GDI exhausts using two different cell culture models mimicking the human airway. In addition to gasoline particle filters (GPF), the effects of two lubrication oils with low and high ash content were assessed, since it is known that oils are important contributors to exhaust emissions. Complete exhausts from two gasoline driven cars (GDI1 and GDI2) were applied for 6 h (acute exposure) to a multi-cellular human lung model (16HBE14o-cell line, macrophages, and dendritic cells) and a primary human airway model (MucilAir™). GDI1 vehicle was driven unfiltered and filtered with an uncoated and a coated GPF. GDI2 vehicle was driven under four settings with different fuels: normal unleaded gasoline, 2% high and low ash oil in gasoline, and 2% high ash oil in gasoline with a GPF. GDI1 unfiltered was also used for a repeated exposure (3 times 6 h) to assess possible adverse effects. After 6 h exposure, no genes or proteins for oxidative stress or pro-inflammation were upregulated compared to the filtered air control in both cell systems, neither in GDI1 with GPFs nor in GDI2 with the different fuels. However, the repeated exposure led to a significant increase in HMOX1 and TNFa gene expression in the multi-cellular model, showing the responsiveness of the system towards gasoline engine exhaust upon prolonged exposure. The reduction of particles by GPFs is significant and no adverse effects were observed in vitro during a short-term exposure. On the other hand, more data comparing different lubrication oils and their possible adverse effects are needed. Future experiments also should, as shown here, focus on repeated exposures. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Disclosing large scale adverse events in the US Veterans Health Administration: lessons from media responses.

PubMed

Maguire, E M; Bokhour, B G; Asch, S M; Wagner, T H; Gifford, A L; Gallagher, T H; Durfee, J M; Martinello, R A; Elwy, A R

2016-06-01

We examined print, broadcast and social media reports about health care systems' disclosures of large scale adverse events to develop future effective messaging. Directed content analysis. We systematically searched four communication databases, YouTube and Really Simple Syndication (RSS) feeds relating to six disclosures of lapses in infection control practices in the Department of Veterans Affairs occurring between 2009 and 2012. We assessed these with a coding frame derived from effective crisis and risk communication models. We identified 148 unique media reports. Some components of effective communication (discussion of cause, reassurance, self-efficacy) were more present than others (apology, lessons learned). Media about 'promoting secrecy' and 'slow response' appeared in reports when time from event discovery to patient notification was over 75 days. Elected officials' quotes (n = 115) were often negative (83%). Hospital officials' comments (n = 165) were predominantly neutral (92%), and focused on information sharing. Health care systems should work to ensure that they develop clear messages focused on what is not well covered by the media, including authentic apologies, remedial actions taken, and shorten the timeframe between event identification and disclosure to patients. Published by Elsevier Ltd.

Adverse effects of perinatal nicotine exposure on reproductive outcomes.

PubMed

Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

2015-12-01

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

Adversity, emotion recognition, and empathic concern in high-risk youth.

PubMed

Quas, Jodi A; Dickerson, Kelli L; Matthew, Richard; Harron, Connor; Quas, Catherine M

2017-01-01

Little is known about how emotion recognition and empathy jointly operate in youth growing up in contexts defined by persistent adversity. We investigated whether adversity exposure in two groups of youth was associated with reduced empathy and whether deficits in emotion recognition mediated this association. Foster, rural poor, and comparison youth from Swaziland, Africa identified emotional expressions and rated their empathic concern for characters depicted in images showing positive, ambiguous, and negative scenes. Rural and foster youth perceived greater anger and happiness in the main characters in ambiguous and negative images than did comparison youth. Rural children also perceived less sadness. Youth's perceptions of sadness in the negative and ambiguous expressions mediated the relation between adversity and empathic concern, but only for the rural youth, who perceived less sadness, which then predicted less empathy. Findings provide new insight into processes that underlie empathic tendencies in adversity-exposed youth and highlight potential directions for interventions to increase empathy.

Withdrawal of the Direct Final Revisions Rule (77 FR 28785)

EPA Pesticide Factsheets

EPA issued ‘‘Revisions to Federal Implementation Plans To Reduce Interstate Transport of Fine Particulate Matter and Ozone’’ as a direct final rule on February 21, 2012. Because EPA received adverse comments on this action, EPA withdrew the rule.

A UK scheme for reporting serious adverse events and reactions associated with ocular tissue transplantation.

PubMed

Kaye, Stephen; Baddon, Andrew; Jones, Mark; Armitage, W John; Fehily, Deirdre; Warwick, Ruth M

2010-02-01

Reporting and investigation of serious adverse events and reactions associated with tissue and cell transplantation is a fundamental aspect of ensuring adequate levels of safety and quality and is a requirement of the European Union Directives on tissues and cells. In the UK, a system for the reporting and analysis of events and reactions associated with ocular tissue transplantation is well established. It is operated by a network of individuals and organisations, each with clearly defined roles and responsibilities, following written procedures for reporting and investigation. Analysis of reports indicates that the most important adverse reactions associated with this type of tissue transplantation are endophthalmitis (0.58%) and primary graft failure (0.3%). This system allows the analysis of all types of events and reactions by the professionals involved so that trends can be identified and services improved. Tools to evaluate the severity and imputability of individual events or reactions, such as those developed by the EUSTITE project, can be utilised to facilitate the selection of those cases meeting the criteria for reporting to the Competent Authority. This vigilance model has been shown to be effective and could be applied in other fields of tissue or cell transplantation.

Microphysical properties of the Shuttle exhaust cloud

NASA Technical Reports Server (NTRS)

Keller, V. W.; Anderson, B. J.

1983-01-01

A data base describing the properties of the exhaust cloud produced by the launch of the STS has been developed based on data from a series of ground and aircraft based measurements made during the launches of STS 2, 3, and 4. Aircraft observations were performed during the STS-3 launch with a NOAA WP-3D Orion hurricane research aircraft which contained instrumentation for cloud condensation nucleus and ice nucleus counting, Aitken particle counting, and pH determination. Ground observations were conducted at 50 different sites, as well as in the direct exhaust from the solid rocket booster flame trench at all three launches. The data is analyzed in order to determine any possible adverse impacts of the exhaust products on human health and/or the environment. Analyses of the exhaust cloud measurements indicate that in the case of the ground cloud where plenty of large water drops are present and considerable scavenging and fallout of aerosol takes place, possible adverse impacts of the remaining aerosols (CCN and IN) on natural precipitation processes which may occur in the launch area hours after the launch are remote. However, it is determined that under certain atmospheric conditions there could be short term adverse effects on visibility.

Endothelial safety of radiological contrast media: why being concerned.

PubMed

Scoditti, Egeria; Massaro, Marika; Montinari, Maria Rosa

2013-01-01

Iodinated radiocontrast media have been the most widely used pharmaceuticals for intravascular administration in diagnostic and interventional angiographic procedures. Although they are regarded as relatively safe drugs and vascular biocompatibility of contrast media has been progressively improved, severe adverse reactions may occur, among which acute nephropathy is one of the most clinically significant complications after intravascular administration of contrast media and a powerful predictor of poor early and long-term outcomes. Since radiocontrast media are given through the arterial or the venous circulation in vascular procedures, morphological and functional changes of the microvascular and macrovascular endothelial cells substantially contribute to the pathogenesis of organ-specific and systemic adverse reactions of contrast media. Endothelial toxicity of contrast media seems to be the result of both direct proapoptotic effects and morphological derangements, as well as endothelial dysfunction and induction of inflammation, oxidative stress, thrombosis, and altered vasomotor balance, with predominant vasoconstrictive response in atherosclerotic coronary arteries and kidney microcirculation. Further understanding of pathogenetic mechanisms underlying contrast media-induced adverse reactions in cellular targets, including endothelial cells, will hopefully lead to the development of novel preventive strategies appropriately curbing the pathogenesis of contrast media vasotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Distinct contributions of adverse childhood experiences and resilience resources: a cohort analysis of adult physical and mental health.

PubMed

Logan-Greene, Patricia; Green, Sara; Nurius, Paula S; Longhi, Dario

2014-01-01

Although evidence is rapidly amassing as to the damaging potential of early life adversities on physical and mental health, as yet few investigations provide comparative snapshots of these patterns across adulthood. This population-based study addresses this gap, examining the relationship of adverse childhood experiences (ACEs) to physical and mental health within a representative sample (n = 19,333) of adults, comparing the prevalence and explanatory strength of ACEs among four birth cohorts spanning ages 18-79. This assessment accounts for demographic and socioeconomic factors, as well as both direct and moderating effects of resilience resources (social/emotional support, life satisfaction, and sleep quality). Findings demonstrate (1) increasing trends of reported ACEs across younger cohorts, including time period shifts such as more prevalent family incarceration, substance abuse, and divorce, (2) significant bivariate as well as independent associations of ACEs with poor health within every cohort, controlling for multiple covariates (increasing trends in older age for physical health), and (3) robust patterns wherein resilience resources moderated ACEs, indicating buffering pathways that sustained into old age. Theoretical and practice implications for health professionals are discussed.

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

30 CFR 875.15 - Reclamation priorities for noncoal program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...

30 CFR 875.15 - Reclamation priorities for noncoal program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...

30 CFR 875.15 - Reclamation priorities for noncoal program.

Code of Federal Regulations, 2012 CFR

2012-07-01

... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...

30 CFR 875.15 - Reclamation priorities for noncoal program.

Code of Federal Regulations, 2014 CFR

2014-07-01

... from the extreme danger of adverse effects of mineral mining and processing practices; (2) The protection of public health, safety, and general welfare from the adverse effects of mineral mining and... degraded by the adverse effects of mineral mining and processing practices. (c) Enhancement of facilities...

75 FR 38521 - Registration Review; Biopesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... perform its intended function without unreasonable adverse effects on human health or the environment...

75 FR 60117 - Registration Review; Biopesticides Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...

77 FR 74479 - Registration Review; Pesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-14

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... function without unreasonable adverse effects on human health or the environment. Registration review...

77 FR 59188 - Registration Review; Pesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... without unreasonable adverse effects on human health or the environment. Registration review dockets...

Light-Driven Contact Hearing Aid for Broad-Spectrum Amplification: Safety and Effectiveness Pivotal Study.

PubMed

Gantz, Bruce J; Perkins, Rodney; Murray, Michael; Levy, Suzanne Carr; Puria, Sunil

2017-03-01

Demonstrate safety and effectiveness of the light-driven contact hearing aid to support FDA clearance. A single-arm, open-label investigational-device clinical trial. Two private-practice and one hospital-based ENT clinics. Forty-three subjects (86 ears) with mild-to-severe bilateral sensorineural hearing impairment. Bilateral amplification delivered via a light-driven contact hearing aid comprising a Tympanic Lens (Lens) with a customized platform to directly drive the umbo and a behind-the-ear sound processor (Processor) that encodes sound into light pulses to wirelessly deliver signal and power to the Lens. The primary safety endpoint was a determination of "no change" (PTA4 < 10 dB) in residual unaided hearing at the 120-day measurement interval. The primary efficacy endpoint was improvement in word recognition using NU-6 at the 30-day measurement interval over the baseline unaided case. Secondary efficacy endpoints included functional gain from 2 to 10 kHz and speech-in-noise improvement over the baseline unaided case using both omnidirectional and directional microphones. The results for the 86 ears in the study determined a mean change of -0.40 dB in PTA4, indicating no change in residual hearing (p < 0.0001). There were no serious device- or procedure-related adverse events, or unanticipated adverse events. Word recognition aided with the Earlens improved significantly (p < 0.0001) over the unaided performance, by 35% rationalized arcsine units on average. Mean functional gain was 31 dB across 2 to 10 kHz. The average speech-recognition threshold improvement over the unaided case for the Hearing in Noise Test was 0.75 dB (p = 0.028) and 3.14 dB (p < 0.0001) for the omnidirectional and directional microphone modes, respectively. The safety and effectiveness data supported a de novo 510(k) submission that received clearance from the FDA.

Effect of Fertilizers and Neem Cake Amendment in Soil on Spore Germination of Arthrobotrys dactyloides

PubMed Central

Kumar, D.; Jaiswal, R. K.

2005-01-01

Application of fertilizers such as urea, diammonium phosphate (DAP) and muriate of potash in soil adversely affected the spore germination of Arthrobotrys dactyloides. Amendment of soil with urea at the concentrations of 1.0%, 0.5% and 0.1% completely inhibited spore germination and direct trap formation on the conidium, whereas muriate of potash delayed and reduced the spore germination even at the lowest concentration. DAP also inhibited spore germination at 1.0% concentration, while at lower concentration the percentage of spore germination was reduced. Application of neem cake at the concentration of 0.5% also inhibited spore germination after 24 h of amendment. The inhibitory effect of neem cake was reduced after 15 days of amendment, while after 30 days after amendment the inhibitory effect was completely lost and the spore germinated by direct trap as in unamended soil. Nematodes were not attracted to ungerminated spores after 24 h of amendment. After 15 days of amendment nematodes were attracted to agar blocks containing fewer germinated spores after 24 h of incubation but after 48 h of incubation large number of nematodes were attracted and trapped by the germinated spores with direct traps. After 30 days of amendment, larger number of nematodes were attracted and trapped by direct traps. PMID:24049500

Screening the Emission Sources of Volatile Organic Compounds (VOCs) in China Based on Multi-effect Evaluation

NASA Astrophysics Data System (ADS)

Niu, H., Jr.

2015-12-01

Volatile organic compounds (VOCs) in the atmosphere have adverse impacts via three main pathways: photochemical ozone formation, secondary organic aerosol production, and direct toxicity to humans. Few studies have integrated these effects to prioritize control measures for VOCs sources. In this study, we developed a multi-effect evaluation methodology based on updated emission inventories and source profiles, which was combined with ozone formation potential (OFP), secondary organic aerosol potential (SOAP), and VOC toxicity data to identify important emission sources and key species. We derived species-specific emission inventories for 152 sources. The OFPs, SOAPs, and toxicity of each source were determined, and the contribution and share of each source to each of these adverse effects was calculated. Weightings were given to the three adverse effects by expert scoring, and the integrated impact was determined. Using 2012 as the base year, solvent usage and industrial process were found to be the most important anthropogenic sources, accounting for 24.2 and 23.1% of the integrated environmental effect, respectively. This was followed by biomass burning, transportation, and fossil fuel combustion, all of which had a similar contribution ranging from 16.7 to 18.6%. The top five industrial sources, including plastic products, rubber products, chemical fiber products, the chemical industry, and oil refining, accounted for nearly 70.0% of industrial emissions. In China, emissions reductions are required for styrene, toluene, ethylene, benzene, and m/p-xylene. The 10 most abundant chemical species contributed 76.5% of the integrated impact. Beijing, Chongqing, Shanghai, Jiangsu, and Guangdong were the five leading provinces when considering the integrated effects. Besides, the chemical mass balance model (CMB) was used to verify the VOCs inventories of 47 cities in China, so as to optimize our evaluation results. We suggest that multi-effect evaluation is necessary to identify the need for abatement at the source type and substance levels.

Symmetrical and overloaded effect of diffusion in information filtering

NASA Astrophysics Data System (ADS)

Zhu, Xuzhen; Tian, Hui; Chen, Guilin; Cai, Shimin

2017-10-01

In physical dynamics, mass diffusion theory has been applied to design effective information filtering models on bipartite network. In previous works, researchers unilaterally believe objects' similarities are determined by single directional mass diffusion from the collected object to the uncollected, meanwhile, inadvertently ignore adverse influence of diffusion overload. It in some extent veils the essence of diffusion in physical dynamics and hurts the recommendation accuracy and diversity. After delicate investigation, we argue that symmetrical diffusion effectively discloses essence of mass diffusion, and high diffusion overload should be published. Accordingly, in this paper, we propose an symmetrical and overload penalized diffusion based model (SOPD), which shows excellent performances in extensive experiments on benchmark datasets Movielens and Netflix.

[The European Working Time Directive and surgical residents' expertise: no effect on the number of operations].

PubMed

Guicherit, Onno R

2015-01-01

Residents' working hours in the Netherlands were first capped in the early 1990 s. In 2003, European legislation consolidated restrictions to a 48-hour week. No adverse effects were seen on the number of surgical operations performed either in the first or the second decade following these measures. Either the effect on surgical training is minimal, or the number of operations carried out during a residency is not a meaningful indicator of its quality. Personalized modular rotations in both university and teaching hospitals are needed for residents with sub-specializations. Training activities, in combination with more supervision, have to focus on a broader set of competencies beyond simply mastering surgical procedures.

Arsenic exposure and adverse health effects: a review of recent findings from arsenic and health studies in Matlab, Bangladesh.

PubMed

Yunus, Mohammad; Sohel, Nazmul; Hore, Samar Kumar; Rahman, Mahfuzar

2011-09-01

The recent discovery of large-scale arsenic (As) contamination of groundwater has raised much concern in Bangladesh. Reliable estimates of the magnitude of As exposure and related health problems have not been comprehensively investigated in Bangladesh. A large population-based study on As and health consequences in Matlab (AsMat) was done in Matlab field site where International Centre for Diarrhoeal Disease Research, Bangladesh has maintained a health and demographic surveillance system registering prospectively all vital events. Taking advantage of the health and demographic surveillance system and collecting data on detailed individual level As exposure using water and urine samples, AsMat investigated the morbidity and mortality associated with As exposure. Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality. Future studies of clinical endpoints will enhance our knowledge gaps and will give directions for disease prevention and mitigations. Copyright © 2011. Published by Elsevier B.V.

Neuroendocrine disruption without direct endocrine mode of action: Polychloro-biphenyls (PCBs) and bisphenol A (BPA) as case studies.

PubMed

Pinson, Anneline; Franssen, Delphine; Gérard, Arlette; Parent, Anne-Simone; Bourguignon, Jean-Pierre

Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand. Consistent with the WHO definition of an endocrine disrupter, a key issue is the "altered function(s) of the endocrine system". Such altered functions can result from different chemical interactions, beyond agonistic or antagonistic effect at a given receptor. Based on neuroendocrine disruption by polychlorinated biphenyls and bisphenol A, this paper proposes different mechanistic paradigms that can result in adverse health effects. They are a consequence of altered endocrine function(s) secondary to chemical interaction with different steps in the physiological regulatory processes, thus accounting for a possibly indirect endocrine mode of action. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Spatially localized motion aftereffect disappears faster from awareness when selectively attended to according to its direction.

PubMed

Murd, Carolina; Bachmann, Talis

2011-05-25

In searching for the target-afterimage patch among spatially separate alternatives of color-afterimages the target fades from awareness before its competitors (Bachmann, T., & Murd, C. (2010). Covert spatial attention in search for the location of a color-afterimage patch speeds up its decay from awareness: Introducing a method useful for the study of neural correlates of visual awareness. Vision Research 50, 1048-1053). In an analogous study presented here we show that a similar effect is obtained when a target spatial location specified according to the direction of motion aftereffect within it is searched by covert top-down attention. The adverse effect of selective attention on the duration of awareness of sensory qualiae known earlier to be present for color and periodic spatial contrast is extended also to sensory channels carrying motion information. Copyright © 2011 Elsevier Ltd. All rights reserved.

Flight evaluation of the transonic stability and control characteristics of an airplane incorporating a supercritical wing

NASA Technical Reports Server (NTRS)

Matheny, N. W.; Gatlin, D. H.

1978-01-01

A TF-8A airplane was equipped with a transport type supercritical wing and fuselage fairings to evaluate predicted performance improvements for cruise at transonic speeds. A comparison of aerodynamic derivatives extracted from flight and wind tunnel data showed that static longitudinal stability, effective dihedral, and aileron effectiveness, were higher than predicted. The static directional stability derivative was slower than predicted. The airplane's handling qualities were acceptable with the stability augmentation system on. The unaugmented airplane exhibited some adverse lateral directional characteristics that involved low Dutch roll damping and low roll control power at high angles of attack and roll control power that was greater than satisfactory for transport aircraft at cruise conditions. Longitudinally, the aircraft exhibited a mild pitchup tendency. Leading edge vortex generators delayed the onset of flow separation, moving the pitchup point to a higher lift coefficient and reducing its severity.

Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

PubMed

Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P

2017-01-01

Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

Dabigatran for anticoagulation in atrial fibrillation - early clinical experience in a hospital population and comparison to trial data.

PubMed

Michel, Jonathan; Mundell, David; Boga, Tau; Sasse, Alexander

2013-01-01

Dabigatran is a recently introduced direct thrombin inhibitor licensed for use as an oral anticoagulant for stroke prevention in non-valvular atrial fibrillation. Our prospective observational study aimed to assess the adverse effects, tolerability and patient satisfaction of dabigatran therapy in a hospital-practice population. Patients starting dabigatran, after its release in June 2011, were identified from clinical practice at two Wellington hospitals, New Zealand. Baseline characteristics were recorded from the clinical record and a telephone interview was performed in January 2012. Primary outcomes included adverse events, adherence, and satisfaction with treatment. Data were available for 70 patients: median age 71.9 years (IQR 62.7-79.0), weight 80 kg (IQR 71-95), CHA(2)DS(2)-VASc score 3 (IQR 2-4). Seventy-one percent of patients reported adverse events although the majority were minor. Twenty-four percent (16/70) had discontinued treatment with dabigatran; four due to predominantly gastrointestinal side effects, three due to bleeding (one severe), one as a result of adverse media coverage with the remainder comprising planned treatment discontinuation and undetermined. In total, 29% reported bleeding events, predominantly minor bleeding and bruising. There were no cerebrovascular events. Nineteen percent reported some difficulty with twice daily dosing adherence with 13 of 70 reporting missed doses. Seventy-seven percent reported treatment satisfaction and 79% of those previously treated with warfarin preferred dabigatran. In this population our study demonstrates a discontinuation rate of 10% due to side effects of dabigatran, similar to the rate reported in RE-LY. The majority of patients are satisfied with their treatment and preferred dabigatran to warfarin, mainly due to the reduced requirement for blood testing. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

77 FR 40048 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...

77 FR 18810 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Docket Act

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...

75 FR 35810 - Registration Review; Pesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-23

... disproportionately high and adverse human health impacts or environmental effects from exposure to the pesticides... can still be used without unreasonable adverse effects on human health or the environment. A pesticide... function without unreasonable adverse effects on human health or the environment. Registration review...

75 FR 60119 - Registration Review; Antimicrobial Pesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

... disproportionately high and adverse human health impacts or environmental effects from exposure to the pesticides... can still be used without unreasonable adverse effects on human health or the environment. A pesticide... its intended function without unreasonable adverse effects on human health or the environment...

76 FR 79173 - Registration Review; Pesticide Dockets Opened for Review and Comment, and Notice of Availability...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... adverse effects on human health or the environment. Registration review dockets contain information that...

76 FR 38166 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Docket Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... perform its intended function without unreasonable adverse effects on human health or the environment...

The Neurobiology of Intervention and Prevention in Early Adversity.

PubMed

Fisher, Philip A; Beauchamp, Kate G; Roos, Leslie E; Noll, Laura K; Flannery, Jessica; Delker, Brianna C

2016-01-01

Early adverse experiences are well understood to affect development and well-being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy.

Mastering Resilience in Oncology: Learn to Thrive in the Face of Burnout.

PubMed

Hlubocky, Fay J; Rose, Miko; Epstein, Ronald M

2017-01-01

Oncology clinician burnout has become a noteworthy issue in medical oncology directly affecting the quality of patient care, patient satisfaction, and overall organizational success. Due to the increasing demands on clinical time, productivity, and the evolving medical landscape, the oncology clinician is at significant risk for burnout. Long hours in direct care with seriously ill patients/families, limited control over daily responsibilities, and endless electronic documentation, place considerable professional and personal demands on the oncologist. As a result, the oncology clinician's wellness is adversely impacted. Physical/emotional exhaustion, cynicism, and feelings of ineffectiveness evolve as core signs of burnout. Unaddressed burnout may affect cancer clinician relationships with their patients, the quality of care delivered, and the overall physical and emotional health of the clinician. Oncology clinicians should be encouraged to build upon their strengths, thrive in the face of adversity and stress, and learn to positively adapt to the changing cancer care system. Fostering individual resilience is a key protective factor against the development of and managing burnout. Empowering clinicians at both the individual and organizational level with tailored resilience strategies is crucial to ensuring clinician wellness. Resilience interventions may include: burnout education, work-life balance, adjustment of one's relationship to work, mindful practice, and acceptance of the clinical work environment. Health care organizations must act to provide institutional solutions through the implementation of: team-based oncology care, communication skills training, and effective resiliency training programs in order to mitigate the effects of stress and prevent burnout in oncology.

Safe Handling of Oral Antineoplastic Medications: Focus on Targeted Therapeutics in the Home Setting

PubMed Central

Cass, Yaakov; Connor, Thomas H.; Tabachnik, Alexander

2017-01-01

Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patient's waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-foetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject is warranted. PMID:27009803

The Academic Consequences of Marijuana Use during College

PubMed Central

Arria, Amelia M.; Caldeira, Kimberly M.; Bugbee, Brittany A.; Vincent, Kathryn B.; O’Grady, Kevin E.

2015-01-01

Although several studies have shown that marijuana use can adversely affect academic achievement among adolescents, less research has focused on its impact on post-secondary educational outcomes. This study utilized data from a large longitudinal cohort study of college students to test the direct and indirect effects of marijuana use on college GPA and time to graduation, with skipping class as a mediator of these outcomes. A structural equation model was evaluated taking into account a variety of baseline risk and protective factors (i.e., demographics, college engagement, psychological functioning, alcohol and other drug use) thought to contribute to college academic outcomes. The results showed a significant path from baseline marijuana use frequency to skipping more classes at baseline to lower first-semester GPA to longer time to graduation. Baseline measures of other drug use and alcohol quantity exhibited similar indirect effects on GPA and graduation time. Over time, the rate of change in marijuana use was negatively associated with rate of change in GPA, but did not account for any additional variance in graduation time. Percentage of classes skipped was negatively associated with GPA at baseline and over time. Thus, even accounting for demographics and other factors, marijuana use adversely affected college academic outcomes, both directly and indirectly through poorer class attendance. Results extend prior research by showing that marijuana use during college can be a barrier to academic achievement. Prevention and early intervention might be important components of a comprehensive strategy for promoting post-secondary academic achievement. PMID:26237288

Environmental projects. Volume 7: Environmental resources document

NASA Technical Reports Server (NTRS)

Kushner, Len; Kroll, Glenn

1988-01-01

The Goldstone Deep Space Communications Complex (GDSCC) in Barstow, California, is part of the NASA Deep Space Network, one of the world's largest and most sensitive scientific telecommunications and radio navigation networks. Goldstone is managed, directed and operated by the Jet Propulsion Laboratory of Pasadena, California. The GDSCC includes five distinct operational sites: Echo, Venus, Mars, Apollo, and Mojave Base. Within each site is a Deep Space Station (DPS), consisting of a large dish antenna and its support facilities. As required by NASA directives concerning the implementation of the National Environmental Policy Act, each NASA field installation is to publish an Environmental Resources Document describing the current environment at the installation, including any adverse effects that NASA operations may have on the local environment.

Surface smoothening of the inherent roughness of micro-lenses fabricated with 2-photon lithography

NASA Astrophysics Data System (ADS)

Schift, Helmut; Kirchner, Robert; Chidambaram, Nachiappan; Altana, Mirco

2018-01-01

Two-photon polymerization by direct laser writing enables to write refractive micro-optical elements with sub-μm precision. The trajectories and layering during the direct writing process often result in roughness in the range of the writing increment, which has adverse effects for optical applications. Instead of increasing overlap between adjacent voxels, roughness in the range of 100 nm can be smoothed out by post-processing. For this a method known as TASTE was developed, which allows polishing of surfaces without changing the structural details or the overall shape. It works particularly well with thermoplastic polymers and enables sub-10 nm roughness. The optical quality was confirmed for an array with several 100 microlenses.

Adverse effect of diesel engine produced particulate matter on various stone types and concrete: a laboratory exposure experiment

NASA Astrophysics Data System (ADS)

Farkas, Orsolya; Szabados, György; Antal, Ákos; Török, Ákos

2015-04-01

The effect of particulate matter on construction materials have been studied under laboratory conditions. For testing the adverse effects of diesel soot and particulate matter on stone and concrete a small scale laboratory exposure chamber was constructed. Blocks of 9 different stone types and concrete was placed in the chamber and an exhaust pipe of diesel engine was diverted into the system. Tested stones included: porous limestone, cemented non-porous limestone, travertine, marble, rhyolite tuff, andesite and granite. The engine was operated for 10 hours and the produced particulate matter was diverted directly to the surface of the material specimens of 3 cm in diameter each. Working parameters of the engine were controlled; the composition of the exhaust gas, smoke value and temperature were continuously measured during the test. Test specimens were documented and analysed prior to exposure and after the exposure test. Parameters such colorimetric values, weight, surface properties, mineralogical compositions of the test specimens were recorded. The working temperature was in the order of 300°C-320°C. The gas concentration was in ppm as follows: 157 CO; 5.98 CO2, 34.3 THC; 463 NOx; 408 NO; 12.88 O2. Our tests have demonstrated that significant amount of particulate matter was deposited on construction materials even at a short period of time; however the exposure was very intense. It also indicates that that the interaction of particulate matter and aerosol compounds with construction materials in urban areas causes rapid decay and has an adverse effect not only on human health but also on built structures.

Useful biomarkers for assessing the adverse health effects of PCBs in allergic children: pediatric molecular epidemiology.

PubMed

Tsuji, Mayumi

2015-01-01

The incidences of childhood allergies have been increasing in recent years in many parts of the world. The development of allergic disorders is attributed to a complex series of interactions between individuals' genetic backgrounds and their immune and psychoneurotic responses to environmental factors. Among the various possible environmental causes of childhood allergies, the early exposure of developing infants to air pollutants and the presence of persistent chemical pollutants such as pesticides have been suggested most frequently. Therefore, it is very important to obtain epidemiological evidence of direct associations between clearly defined adverse health effects and exposure to low levels of pollutants. However, there are no useful biomarkers for assessing such associations. Thus, we planned to establish reliable health-related biomarkers that could be used to investigate these relationships in children. The serum concentrations of several sub-types of polychlorinated biphenyl (PCB) congeners were found to be significantly correlated with interleukin (IL)-8 mRNA expression among asthmatic children. In addition, IL-22 mRNA expression was found to be particularly useful for detecting the effects of environmental pollutants, especially PCB congeners, in a sub-population of vulnerable children who exhibited positive immunoglobulin E (IgE) responses to milk or egg. Furthermore, we detected significant differences in IL-22 mRNA expression between the IgE-negative non-asthmatic subjects and the asthmatic children who exhibited positive IgE reactions toward egg or milk. In conclusion, IL-8 and IL-22 mRNA expressions could be useful biomarkers for detecting sub-populations of children who are particularly vulnerable to the adverse health effects of environmental pollutants, especially PCBs.

Responding to information about children in adversity: ten years of a differential response model in Western Australia.

PubMed

Harries, Maria; Cant, Rosemary L; Bilson, Andy; Thorpe, David

2015-01-01

This article uses a comprehensive database about children in adversity collected over the 16-year period from 1990 to 2005 in the state of Western Australia. The focus of this interrogation is the effect of major changes in responses to information about children brought to the attention of the Western Australian statutory authority in a 10-year period during this 16 years. The initiative for these changes was termed New Directions, and its associated policy and practice changes were aimed at differentiating information expressing concerns about children and families from allegations of child maltreatment. They emphasized the provision of supportive and empowering services to families experiencing difficulties - a form of differential response to children in adversity. The article covers the period leading up to the policy and practice change and the 10 years during which these changes were implemented. It examines some effects of the new policy and comments on whether the changes resulted in missed opportunities to protect children from harm, which in turn, might have led to higher rates of re-reporting. The authors present an overall picture of the nature of the information accepted by the statutory authority and how the interpretation of that information might have affected subsequent outcomes for children. In doing so, it shows that the policy and consequential practice changes associated with a differential response mechanism had long lasting positive effects that, despite dire warnings, did not compromise the protection of the small group of children identified as requiring protective interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD.

PubMed

Kortman, Guus A M; Reijnders, Dorien; Swinkels, Dorine W

2017-06-01

Patients with chronic kidney disease (CKD) and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to "uremia," an increased concentration of uremic retention solutes (toxins) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. There is a high prevalence of anemia in patients with CKD, for which patients are often treated with oral or intravenous iron. Recent in vivo and in vitro studies have reported adverse effects of oral iron supplementation on the gut microbiota composition, gut metabolome, and intestinal health, which in turn may result in an increased production of uremic toxins. It may also affect circulating levels of other microbe-derived molecules, that can act as mediators of immune regulation. Changes in body iron levels have also been reported to exert subtle effects on host immune function by modulating immune cell proliferation and differentiation, and by directly regulating cytokine formation and antimicrobial immune effector mechanisms. Based on the foregoing it is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection. Future studies are needed to confirm these hypotheses and to assess whether, compared to IV iron supplementation, oral iron supplementation negatively impacts on morbidity of CKD, and whether these adverse effects depend on the iron bioavailability of the iron formulation to the microbiota. © 2017 International Society for Hemodialysis.

Motor outcome and electrode location in deep brain stimulation in Parkinson's disease.

PubMed

Koivu, Maija; Huotarinen, Antti; Scheperjans, Filip; Laakso, Aki; Kivisaari, Riku; Pekkonen, Eero

2018-05-30

To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. STN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Testing an integral conceptual model of frailty.

PubMed

Gobbens, Robbert J; van Assen, Marcel A; Luijkx, Katrien G; Schols, Jos M

2012-09-01

This paper is a report of a study conducted to test three hypotheses derived from an integral conceptual model of frailty.   The integral model of frailty describes the pathway from life-course determinants to frailty to adverse outcomes. The model assumes that life-course determinants and the three domains of frailty (physical, psychological, social) affect adverse outcomes, the effect of disease(s) on adverse outcomes is mediated by frailty, and the effect of frailty on adverse outcomes depends on the life-course determinants. In June 2008 a questionnaire was sent to a sample of community-dwelling people, aged 75 years and older (n = 213). Life-course determinants and frailty were assessed using the Tilburg frailty indicator. Adverse outcomes were measured using the Groningen activity restriction scale, the WHOQOL-BREF and questions regarding healthcare utilization. The effect of seven self-reported chronic diseases was examined. Life-course determinants, chronic disease(s), and frailty together explain a moderate to large part of the variance of the seven continuous adverse outcomes (26-57%). All these predictors together explained a significant part of each of the five dichotomous adverse outcomes. The effect of chronic disease(s) on all 12 adverse outcomes was mediated at least partly by frailty. The effect of frailty domains on adverse outcomes did not depend on life-course determinants. Our finding that the adverse outcomes are differently and uniquely affected by the three domains of frailty (physical, psychological, social), and life-course determinants and disease(s), emphasizes the importance of an integral conceptual model of frailty. © 2011 Blackwell Publishing Ltd.

Goal-Directed Resilience in Training (GRIT): A Biopsychosocial Model of Self-Regulation, Executive Functions, and Personal Growth (Eudaimonia) in Evocative Contexts of PTSD, Obesity, and Chronic Pain

PubMed Central

Kent, Martha; Rivers, Crystal T.; Wrenn, Glenda

2015-01-01

This paper presents a biopsychosocial model of self-regulation, executive functions, and personal growth that we have applied to Goal-Directed Resilience in Training (GRIT) interventions for posttraumatic stress disorder (PTSD), obesity, and chronic pain. Implications of the training for the prevention of maladaptation, including psychological distress and health declines, and for promoting healthy development are addressed. Existing models of attention, cognition, and physiology were sourced in combination with qualitative study findings in developing this resilience skills intervention. We used qualitative methods to uncover life skills that are most salient in cases of extreme adversity, finding that goal-directed actions that reflected an individual’s values and common humanity with others created a context-independent domain that could compensate for the effects of adversity. The efficacy of the resilience skills intervention for promoting positive emotion, enhancing neurocognitive capacities, and reducing symptoms was investigated in a randomized controlled trial with a veteran population diagnosed with PTSD. The intervention had low attrition (8%) and demonstrated improvement on symptom and wellbeing outcomes, indicating that the intervention may be efficacious for PTSD and that it taps into those mechanisms which the intervention was designed to address. Feasibility studies for groups with comorbid diagnoses, such as chronic pain and PTSD, also showed positive results, leading to the application of the GRIT intervention to other evocative contexts such as obesity and chronic pain. PMID:26039013

Goal-Directed Resilience in Training (GRIT): A Biopsychosocial Model of Self-Regulation, Executive Functions, and Personal Growth (Eudaimonia) in Evocative Contexts of PTSD, Obesity, and Chronic Pain.

PubMed

Kent, Martha; Rivers, Crystal T; Wrenn, Glenda

2015-06-01

This paper presents a biopsychosocial model of self-regulation, executive functions, and personal growth that we have applied to Goal-Directed Resilience in Training (GRIT) interventions for posttraumatic stress disorder (PTSD), obesity, and chronic pain. Implications of the training for the prevention of maladaptation, including psychological distress and health declines, and for promoting healthy development are addressed. Existing models of attention, cognition, and physiology were sourced in combination with qualitative study findings in developing this resilience skills intervention. We used qualitative methods to uncover life skills that are most salient in cases of extreme adversity, finding that goal-directed actions that reflected an individual's values and common humanity with others created a context-independent domain that could compensate for the effects of adversity. The efficacy of the resilience skills intervention for promoting positive emotion, enhancing neurocognitive capacities, and reducing symptoms was investigated in a randomized controlled trial with a veteran population diagnosed with PTSD. The intervention had low attrition (8%) and demonstrated improvement on symptom and wellbeing outcomes, indicating that the intervention may be efficacious for PTSD and that it taps into those mechanisms which the intervention was designed to address. Feasibility studies for groups with comorbid diagnoses, such as chronic pain and PTSD, also showed positive results, leading to the application of the GRIT intervention to other evocative contexts such as obesity and chronic pain.

Positive Adjustment Among American Repatriated Prisoners of the Vietnam War: Modeling the Long-Term Effects of Captivity.

PubMed

King, Daniel W; King, Lynda A; Park, Crystal L; Lee, Lewina O; Kaiser, Anica Pless; Spiro, Avron; Moore, Jeffrey L; Kaloupek, Danny G; Keane, Terence M

2015-11-01

A longitudinal lifespan model of factors contributing to later-life positive adjustment was tested on 567 American repatriated prisoners from the Vietnam War. This model encompassed demographics at time of capture and attributes assessed after return to the U.S. (reports of torture and mental distress) and approximately 3 decades later (later-life stressors, perceived social support, positive appraisal of military experiences, and positive adjustment). Age and education at time of capture and physical torture were associated with repatriation mental distress, which directly predicted poorer adjustment 30 years later. Physical torture also had a salutary effect, enhancing later-life positive appraisals of military experiences. Later-life events were directly and indirectly (through concerns about retirement) associated with positive adjustment. Results suggest that the personal resources of older age and more education and early-life adverse experiences can have cascading effects over the lifespan to impact well-being in both positive and negative ways.

Positive Adjustment Among American Repatriated Prisoners of the Vietnam War: Modeling the Long-Term Effects of Captivity

PubMed Central

King, Daniel W.; King, Lynda A.; Park, Crystal L.; Lee, Lewina O.; Kaiser, Anica Pless; Spiro, Avron; Moore, Jeffrey L.; Kaloupek, Danny G.; Keane, Terence M.

2015-01-01

A longitudinal lifespan model of factors contributing to later-life positive adjustment was tested on 567 American repatriated prisoners from the Vietnam War. This model encompassed demographics at time of capture and attributes assessed after return to the U.S. (reports of torture and mental distress) and approximately 3 decades later (later-life stressors, perceived social support, positive appraisal of military experiences, and positive adjustment). Age and education at time of capture and physical torture were associated with repatriation mental distress, which directly predicted poorer adjustment 30 years later. Physical torture also had a salutary effect, enhancing later-life positive appraisals of military experiences. Later-life events were directly and indirectly (through concerns about retirement) associated with positive adjustment. Results suggest that the personal resources of older age and more education and early-life adverse experiences can have cascading effects over the lifespan to impact well-being in both positive and negative ways. PMID:26693100

Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs.

PubMed

Parmar, Jayesh R; Forrest, Benjamin D; Freeman, Robert A

2016-01-01

The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory related adverse effects. Finally, insufficient higher-order evidence to support the widespread use of medical marijuana was found, but a limited amount of moderate-level evidence supports its use in pain and seizure management. Published by Elsevier Inc.

Treatment of Functional Abdominal Pain With Antidepressants: Benefits, Adverse Effects, and the Gastroenterologist's Role.

PubMed

Zar-Kessler, Claire A M; Belkind-Gerson, Jaime; Bender, Suzanne; Kuo, Braden M

2017-07-01

Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians' prescribing patterns. Retrospective review (2005-2013) children (5-21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did. Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.

Cognitive control of familiarity: directed forgetting reduces proactive interference in working memory.

PubMed

Festini, Sara B; Reuter-Lorenz, Patricia A

2014-03-01

Proactive interference (PI) occurs when previously learned information interferes with new learning. In a working memory task, PI induces longer response times and more errors to recent negative probes than to new probes, presumably because the recent probe's familiarity invites a "yes" response. Warnings, longer intertrial intervals, and the increased contextual salience of the probes can reduce but not eliminate PI, suggesting that cognitive control over PI is limited. Here we tested whether control exerted in the form of intentional forgetting performed during working memory can reduce the magnitude of PI. In two experiments, participants performed a working memory task with directed-forgetting instructions and the occasional presentation of recent probes. Surprise long-term memory testing indicated better memory for to-be-remembered than for to-be-forgotten items, documenting the classic directed-forgetting effect. Critically, in working memory, PI was virtually eliminated for recent probes from prior to-be-forgotten lists, as compared to recent probes from prior to-be-remembered lists. Thus cognitive control, when executed via directed forgetting, can reduce the adverse and otherwise persistent interference from familiarity, an effect that we attribute to attenuated memory representations of the to-be-forgotten items.

Development of acute exposure guideline levels for airborne exposures to hazardous substances.

PubMed

Krewski, Daniel; Bakshi, Kulbir; Garrett, Roger; Falke, Ernest; Rusch, George; Gaylor, David

2004-04-01

Hazardous substances can be released into the atmosphere due to industrial and transportation accidents, fires, tornadoes, earthquakes, and terrorists, thereby exposing workers and the nearby public to potential adverse health effects. Various enforceable guidelines have been set by regulatory agencies for worker and ambient air quality. However, these exposure levels generally are not applicable to rare lifetime acute exposures, which possibly could occur at high concentrations. Acute exposure guideline levels (AEGLs) provide estimates of concentrations for airborne exposures for an array of short durations that possibly could cause mild (AEGL-1), severe, irreversible, potentially disabling adverse health effects (AEGL-2), or life threatening effects (AEGL-3). These levels can be useful for emergency responders and planners in reducing or eliminating potential risks to the public. Procedures and methodologies for deriving AEGLs are reviewed in this paper that have been developed in the United States, with direct input from international representatives of OECD member-countries, by the National Advisory Committee for Acute Exposure Guidelines for Hazardous Substances and reviewed by the National Research Council. Techniques are discussed for the extrapolation of effects across different exposure durations. AEGLs provide a viable approach for assisting in the prevention, planning, and response to acute airborne exposures to toxic agents.

Masculine Discrepancy Stress and Psychosocial Maladjustment: Implications for Behavioral and Mental Health of Adolescent Boys.

PubMed

Reidy, Dennis E; Smith-Darden, Joanne P; Vivolo-Kantor, Alana M; Malone, Carolyn A; Kernsmith, Poco D

2017-01-01

Gender role discrepancy (GRD), or nonconformity to socially prescribed gender roles, has been linked to a multitude of adverse mental and behavioral health outcomes. Masculine discrepancy stress (MDS), stress about being perceived not to conform to one's gender role, may explain the relationship between GRD and deleterious health outcomes. However, research on MDS has primarily been restricted to adult males. This leaves a critical gap pertaining to the potential effect of MDS on adolescent boys, who may be more malleable and susceptible to the influence and pressures of gender socialization. In the current study, data are drawn from a sample of adolescent male students ( N = 592) who completed self-report questionnaires. We employed structural equation modeling to test the effects of GRD and MDS on psychosocial maladjustment measured via sexual behavior, substance use, violence, mood disorder symptoms, and hopelessness. In addition, we controlled for critical risk factors including sociodemographic characteristics, adverse childhood experiences, trauma symptoms, and neighborhood disorganization. Findings indicate significant potentiating effects of MDS on maladjustment while there were direct protective effects of GRD. These data suggest that developing prevention strategies that incorporate social norms pertaining to gender socialization may have an impact on multiple behavioral and mental health problems.

[Adverse effects of oxcarbazepine].

PubMed

Fang, Shu; Gong, Zhi-Cheng

2015-04-01

Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

Efficiency and specificity of RAAS inhibitors in cardiovascular diseases: how to achieve better end-organ protection?

PubMed

Nehme, Ali; Zibara, Kazem

2017-11-01

RAAS, a major pharmacological target in cardiovascular medicine, is inhibited by pharmacological classes including angiotensin converting enzyme (ACE) inhibitors (ACEIs), angiotensin-II type 1 blockers (ARBs) and aldosterone receptors antagonists, in addition to the recently introduced direct renin inhibitors (DRIs). However, currently used RAAS inhibitors still cannot achieve their desired effects and are associated with certain drawbacks, such as adverse side effects, incomplete blockage of the system and poor end-organ protection. In this review, we discuss the efficiency and specificity of the current RAAS inhibitors and propose some recommendations for achieving better treatments with better end-organ protection.